HK1054030A - Method for producing asymmetrical 4,6-bis(aryloxy)pyrimidine derivatives - Google Patents

Description

Process for preparing unsymmetrical 4, 6-bis (aryloxy) pyrimidine derivatives

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The present invention relates to a novel process for the preparation of known asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives.

Asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives are known and are used, for example, as pesticides in the field of crop protection (cf. WO94/02470, WO97/27189, WO98/21189, WO 99/57116).

The preparation of asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives is more difficult than the preparation of symmetric 4, 6-bis (aryloxy) pyrimidine compounds, because different aryloxy groups have to be introduced into the respective reactions.

Many methods for the preparation of asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives have been disclosed.

WO94/02470 discloses the preparation of asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives by a two-step process. 4, 6-dichloropyrimidine (A) is reacted with 1 equivalent of a phenol derivative (B) under basic reaction conditions, followed by reaction with a second phenol derivative (D) to obtain an asymmetric 4, 6-bis (aryloxy) pyrimidine derivative (E) (see reaction scheme 1).

Reaction scheme 1

The disadvantage of this process is that in the second reaction stage an aryloxy exchange takes place, giving a mixture of the unsymmetrical 4, 6-bis (aryloxy) pyrimidine derivative (E) and the symmetrical 4, 6-bis (aryloxy) pyrimidine derivatives (F) and (G).

Therefore, the asymmetric 4, 6-bis (aryloxy) pyrimidine derivative (E) is low in yield and can be isolated only by a complicated isolation method.

To avoid the problem of exchange of aryloxy groups in the second reaction stage, the starting 4, 6-difluoropyrimidine can be used (cf. scheme 2 and WO94/02470, EP-A1-794177).

Reaction scheme 2

However, a disadvantage of this process is that 4, 6-difluoropyrimidine is prepared starting from 4, 6-dichloropyrimidine by chlorine/fluorine exchange. Thus, the preparation of asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives requires additional reaction steps. Preferred starting materials are therefore 4, 6-dichloropyrimidine and 4, 6-dichloropyrimidine derivatives.

A process for the preparation of asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives starting from 4, 6-dichloro-5-halo-pyrimidines in analogy to the process disclosed in WO94/02470 is disclosed in WO 98/41513.

Another preparation process for the preparation of unsymmetrical 4, 6-bis (aryloxy) pyrimidine derivatives (E) starting from 4, 6-dichloropyrimidine (A) is disclosed in EP-A1-794177, U.S. Pat. No. 3, 5,849,910 and U.S. Pat. No. 5,977,363 (see scheme 3).

Reaction scheme 3

In this process, the aryloxy-chloropyrimidine derivative (C) obtained after the first reaction stage is treated with at least one molar equivalent of a tertiary amine.

The intermediate formed is a pyrimidinyl-ammonium derivative (J) which is reacted with a phenol derivative (D) to give an asymmetric 4, 6-bis (aryloxy) pyrimidine derivative (E).

The disadvantage of this process is that at least equimolar amounts of tertiary amine are required, which have to be recovered in a complicated manner. Moreover, only moderate yields of asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives were obtained. Therefore, the process is not suitable for large-scale industrial preparation, especially if expensive amines are used.

It has now been found that asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives of general formula (I) can be prepared by the following process

Wherein

Ar¹Represents a substituted or unsubstituted aryl or heterocyclic group,

x represents hydrogen, fluorine, chlorine or bromine,

L¹，L²，L³，L⁴and L⁵Are identical or different and each independently represent hydrogen, halogen, cyano, nitro, alkylcarbonyl, formyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl which is in each case optionally substituted by halogen, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl,

or

L¹，L²，L³And L⁴Are identical or different and each independently represent hydrogen, halogen, cyano, nitro, alkylcarbonyl, formyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl which is in each case optionally substituted by halogen, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl,

and

L⁵represents one of the following groups:

wherein represents the point of attachment to a phenyl group,

and wherein the radicals

Ar¹And

is different in that it is a mixture of,

reacting a 4, 6-dichloropyrimidine derivative of the general formula (II),

wherein

X is as defined above, and X is as defined above,

a) first, in a first step, it is reacted with a compound of the general formula (III),

Ar¹-OH， (III)

wherein

Ar¹As defined above, the above-mentioned,

if a diluent is suitable and if an acid acceptor is suitable,

then, in a second step, the resulting compound of formula (IV)

Wherein

Ar¹And X are each as defined above

With a compound of the general formula (V),

wherein

L¹，L²，L³，L⁴And L⁵Each as defined above, is capable of,

if appropriate in the presence of a solvent, if appropriate in the presence of a base and with addition of 2 to 40 mol% of 1, 4-diazabicyclo [2.2.2] octane (DABCO),

or

b) First, in a first step, it is reacted with a compound of the general formula (V),

wherein

L¹，L²，L³，L⁴And L⁵Each as defined above, is capable of,

if a diluent is suitable and if an acid acceptor is suitable,

then converting the resulting compound of formula (VI)Compound (I)

Wherein

X，L¹，L²，L³，L⁴And L⁵Each as defined above, is capable of,

in a second step, with a compound of the general formula (III),

Ar¹-OH， (III)

wherein

Ar¹As defined above, the above-mentioned,

if appropriate in the presence of a solvent, if appropriate in the presence of a base, and 2 to 40 mol% of 1, 4-diazabicyclo [2.2.2] octane (DABCO) are added.

In the above definitions, a saturated or unsaturated hydrocarbon chain, such as alkyl, alkanediyl, alkenyl or alkynyl, is each straight-chain or branched and includes a heteroatom in combination, such as, for example, alkoxy, alkylthio or alkylamino. Unless otherwise specified, hydrocarbon chains having 1 to 6 carbon atoms are preferred. Unless otherwise specified, hydrocarbon chains having 2 to 6 carbon atoms are preferably alkenyl or alkynyl groups.

Halogen generally represents fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine, in particular fluorine or chlorine.

Aryl represents an aromatic, mono-or polycyclic hydrocarbon ring, such as, for example, phenyl, naphthyl, anthryl, phenanthryl, preferably phenyl or naphthyl, in particular phenyl.

Heterocyclyl represents saturated or unsaturated, as well as aromatic, cyclic compounds in which at least one ring atom is a heteroatom, i.e. an atom different from carbon. If there are more than one heteroatom in the ring, they may be the same or different. Preferred heteroatoms are oxygen, nitrogen or sulfur. If there are multiple oxygen atoms in the ring, they are not adjacent. If appropriate, the cyclic compounds form, together with further carbocyclic or heterocyclic rings, fused or bridged rings, polycyclic ring systems. Preference is given to mono-or bicyclic ring systems, in particular mono-or bicyclic aromatic ring systems.

Cycloalkyl represents a saturated carbocyclic compound, such as is suitable together with other carbocyclic, fused or bridged rings to form a polycyclic ring system.

The polycyclic ring system may be attached to a heterocyclic ring or a fused carbocyclic ring. The heterocyclic group may also be preferably mono-or polysubstituted with methyl, ethyl or halogen. Preference is given to mono-or bicyclic ring systems, in particular mono-or bicyclic aromatic ring systems.

Haloalkoxy represents partially or fully halogenated alkoxy. In the case of polyhalogenated haloalkoxy groups, the halogen atoms may be the same or different. Preferred halogen atoms are fluorine and chlorine, especially fluorine. If the haloalkoxy group carries further substituents, the maximum number of halogen atoms possible is reduced to the remaining free valencies. Unless otherwise specified, hydrocarbon chains having 1 to 6 carbon atoms are preferred.

Haloalkyl represents partially and fully halogenated alkyl groups. In the case of polyhalogenated haloalkyl groups, the halogen atoms may be the same or different. Preferred halogen atoms are fluorine and chlorine, especially fluorine. If the haloalkyl group also carries further substituents, the maximum number of halogen atoms possible is reduced to the remaining free valences. Unless otherwise specified, hydrocarbon chains having 1 to 6 carbon atoms are preferred.

The starting materials of the formulae (III) and (V), the intermediates of the formulae (IV) and (VI) and the end products of the general formula (I) can be present as pure isomers of the various isomeric types possible, for example the E or Z isomer, or, if appropriate, as mixtures of the various isomeric types possible, in particular the heteroisomers, for example E/Z mixtures.

In general, Ar¹In particular, it represents:

a heterocyclic group having 3 to 7 ring atoms, which heterocyclic group may be optionally substituted with halogen or alkyl, alkoxy, haloalkyl, haloalkoxy each having 1 to 4 carbon atoms;

or represents phenyl or naphthyl, each of which is optionally mono-to tetrasubstituted by identical or different substituents, preferably the following substituents:

halogen, cyano, nitro, formyl, carboxy, carbamoyl, thiocarbamoyl;

alkyl, oxoalkyl, alkoxy, alkoxyalkyl, alkylthioalkyl, dialkoxyalkyl, alkylthio, alkylsulfinyl or alkylsulfonyl, each of which is straight-chain or branched and each has 1 to 8 carbon atoms;

each straight-chain or branched, alkenyl or alkenyloxy having in each case 2 to 6 carbon atoms;

haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulfinyl or haloalkylsulfonyl, each of which is straight-chain or branched and each of which has 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms;

haloalkenyl or haloalkenyloxy each straight-chain or branched, each having 2 to 6 carbon atoms and 1 to 11 identical or different halogen atoms;

each is a straight or branched chain dialkylamino group;

alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aralkylaminocarbonyl, dialkylaminocarbonyloxy, alkenylcarbonyl or alkynylcarbonyl having 1 to 6 carbon atoms in the respective hydrocarbon chain;

cycloalkyl or cycloalkoxy each having 3 to 6 carbon atoms;

alkylene having 3 or 4 carbon atoms, oxyalkylene having 2 or 3 carbon atoms or dioxyalkylene having 1 or 2 carbon atoms, each of which is optionally mono-to tetrasubstituted by identical or different substituents from the group consisting of fluorine, chlorine, oxo, methyl, trifluoromethyl and ethyl, bonded via respective double bonds (Zweifach);

or groupWherein

A¹Represents hydrogen, hydroxyl or alkyl having 1 to 4 carbon atoms or cycloalkyl having 1 to 6 carbon atoms and

A²represents hydroxy, methoxy, ethoxy, amino, methylamino, phenyl, benzyl or represents in each case optionally cyano-, alkoxy-, alkylthio-, alkylamino-, dialkylamino-or phenyl-substituted alkyl or alkoxy having 1 to 4 carbon atoms or represents in each case 2 to 4 carbon atoms alkenyloxy or alkynyloxy,

and phenyl, benzoyl, benzoylvinyl, cinnamoyl, heterocyclyl or phenylalkyl, phenylalkoxy or heterocyclylalkyl each optionally mono-to trisubstituted on its ring by halogen and/or straight or branched alkyl or alkoxy having 1 to 4 carbon atoms, each having 1 to 3 carbon atoms in the respective alkyl moiety.

Preference is given to compounds in which Ar is¹Represents:

thienyl, pyridyl or furyl optionally substituted by methyl-, ethyl-, methoxy-, ethoxy-, trifluoromethyl-or trifluoromethoxy;

or represents phenyl which is in each case optionally mono-to tetrasubstituted by identical or different substituents, preferably the following substituents:

fluorine, chlorine, bromine, iodine, cyano, nitro, formyl, carboxyl, carbamoyl, thiocarbamoyl,

methyl, ethyl, n-or i-propyl, n-, i-, s-or t-butyl, 1-, 2-, 3-, neo-pentyl, 1-, 2-, 3-, 4- (2-methylbutyl), 1-, 2-, 3-hexyl, 1-, 2-, 3-, 4-, 5- (2-methylpentyl), 1-, 2-, 3- (3-methylpentyl), 2-ethylbutyl, 1-, 3-, 4- (2, 2-dimethylbutyl), 1-, 2- (2, 3-dimethylbutyl), 3-oxobutyl, methoxymethyl, dimethoxymethyl, methoxy, ethoxy, n-or i-propoxy,

methylthio, ethylthio, n-or isopropylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl or ethylsulfonyl,

vinyl, allyl, 2-methallyl, propen-1-yl, crotonyl, propargyl, vinyloxy, allyloxy, 2-methallyloxy, propen-1-yloxy, crotonyloxy, propargyloxy,

the group consisting of trifluoromethyl, trifluoroethyl,

difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, trifluoromethylthio, difluorochloromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl,

a dimethylamino group, a diethylamino group,

acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dimethylaminocarbonyloxy, diethylaminocarbonyloxy, benzylaminocarbonyl, acryloyl, propioloyl,

a cyclopentyl group, a cyclohexyl group,

each of which is optionally mono-to tetrasubstituted by identical or different substituents from the group consisting of fluorine, chlorine, oxo, methyl and trifluoromethyl,

or groupWherein

A¹Represents hydrogen, methyl or hydroxy and

A²represents hydroxy, methoxy, ethoxy, amino, methylamino, phenyl or benzyl, and

phenyl, benzoyl, benzoylvinyl, cinnamoyl, benzyl, phenethyl, phenylpropyl, benzyloxy, 5, 6-dihydro-1, 4, 2-dioxazin-3-ylmethyl, triazolylmethyl, benzoxazol-2-ylmethyl, 1, 3-dioxan-2-yl, benzimidazol-2-yl, dioxolan-2-yl, oxadiazolyl, the ring portions of the above groups being optionally mono-to trisubstituted by halogen and/or straight or branched alkyl or alkoxy groups having 1 to 4 carbon atoms.

Even more particularly preferred group of compounds, Ar¹Represents a mono-to tetrasubstituted phenyl group, wherein the substituents are selected from the group consisting of:

halogen, cyano, each straight-chain or branched, in particular alkyl or haloalkyl having 1 to 4 carbon atoms.

In general, X represents in particular fluorine or chlorine.

Particular preference is given to compounds in which X represents fluorine.

In general, L¹，L²，L³，L⁴And L⁵Which may be identical or different and each independently of the others represents, in particular, hydrogen, halogen, cyano, nitro, formyl, alkylcarbonyl having 1 to 6 carbon atoms, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl, each having 1 to 6 carbon atoms and each being optionally substituted by 1 to 5 halogen atoms,

or

L¹，L²，L³And L⁴Which may be identical or different and each independently of the others represents, in particular, hydrogen, halogen, cyano, nitro, formyl, alkylcarbonyl having 1 to 6 carbon atoms, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl each having 1 to 6 carbon atoms and each being optionally substituted by 1 to 5 halogen atoms and

L⁵in particular one of the following groups:

wherein represents the point of attachment to the phenyl group.

Preferred compounds are those wherein L¹，L²，L³And L⁴Which may be identical or different and each independently preferably represents hydrogen, fluorine, chlorine, bromine, cyano, nitro, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, methyl, ethyl, n-or i-propyl, n-, i-, s-or t-butyl, methoxy, ethoxy, n-or i-propoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl or ethylsulfonyl, trifluoromethyl, trifluoroethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, difluorochloromethylthio, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl.

Of the more particularly preferred compound groups, L¹，L²，L³And L⁴Represents hydrogen or methyl.

Even more particularly preferred compounds of the group of compounds, L¹，L²，L³And L⁴Represents hydrogen.

Preferably wherein L⁵Those compounds representing one of the following groups:or

Wherein represents the point of attachment to the phenyl group.

In a more particularly preferred group of compounds, L⁵Represents one of the following groups:

wherein represents the point of attachment to the phenyl group.

The general or preferred radical definitions indicated above apply both to the end products of the formula (I) and correspondingly to the starting materials or intermediates required in the respective preparation process.

In addition to the radical definitions given for each of these radicals, the radical definitions in each of the radical combinations or preferred radical combinations given for these radicals can also be replaced arbitrarily by radical definitions of other preferred ranges.

It is particularly surprising that in the process of the present invention asymmetric 4, 6-bis (aryl) oxypyrimidine derivatives can be obtained in high selectivity and high yield when 2 to 40 mol% of the tertiary amine 1, 4-diazabicyclo [2.2.2] octane (DABCO) is added to react with the aryloxyhalogenated pyrimidine derivative. Since the prior art (cf. EP-A1-794177, U.S. Pat. No. 3, 5,849,990 and U.S. Pat. No. 5,977,363) already mentions that the above-mentioned reaction requires at least one molar equivalent of a tertiary amine, it is very surprising that the reaction can also be carried out using 2 to 40 mol% of DABCO, giving excellent yields. This was confirmed by a comparative experiment in which the reaction was carried out without adding DABCO (see example 4, second step). The product is isolated in very low yield.

The process of the present invention has many advantages. Asymmetric 4, 6-bis (aryloxy) pyrimidine derivatives can be obtained in high yield and purity. Furthermore, 4, 6-dichloropyrimidine derivatives which are more readily available than 4, 6-difluoropyrimidine derivatives can be used as starting materials. Also, it is not necessary to recover the amine because only catalytic amounts of DABCO are required to carry out the reaction.

The compounds of the formula (II) used as starting materials in the process of the invention are known and can be prepared by known methods (cf. DE-A1-19710609, WO97/49605, DE-A1-19642533 and DE-A1-19531299) or are commercially available products.

The compounds of the formula (III) used as starting materials in the process according to the invention are customary commercial products or are prepared from the latter by simple processes.

The compounds of the formulA (V) used as starting materials in the process of the invention are known and can be prepared by known methods (cf. DE-A119611653, WO-A-95/24396, WO95/04728, WO97/27189, WO97/14687, WO98/23155, WO98/21189, WO98/55461, WO99/09026, WO 99/57116). All other starting materials are customary commercial products or can be prepared from the latter by simple methods.

Suitable diluents in the first step of the process according to the invention are all inert organic solvents. These organic solvents include, by way of example and preferably, aliphatic, alicyclic or aromatic hydrocarbons, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons, such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 1, 2-dimethoxyethane, 1, 2-diethoxyethane or anisole; ketones, such as acetone, butanone, methyl isobutyl ketone or cyclohexanone, nitriles, such as acetonitrile, propionitrile, N-or isobutyronitrile or benzonitrile, amides, such as N, N-dimethylformamide, N-dimethylacetamide, N-methylformamide, N-methylpyrrolidone or hexamethylphosphoric triamide; esters, such as methyl acetate or ethyl acetate; sulfoxides, such as dimethyl sulfoxide, sulfones, such as sulfolane; or mixtures thereof with water. In the first step of the process according to the invention, preference is given to using ketones, in particular methyl isobutyl ketone.

The first step of the process of the invention is, if appropriate, carried out in the presence of a suitable acid acceptor. Suitable acid acceptors are all customary inorganic or organic bases. These bases include, by way of example and preferably, alkaline earth metal or alkali metal hydroxides, acetates, carbonates or bicarbonates, such as sodium hydroxide, potassium hydroxide, sodium acetate, potassium acetate, sodium carbonate, potassium bicarbonate or sodium bicarbonate; tertiary amines, for example trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, N, N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N, N-dimethylaminopyridine, Diazabicyclononene (DBN) or Diazabicycloundecene (DBU); and alkaline earth metal or alkali metal hydrides, such as calcium hydride, sodium hydride or potassium hydride. In the first step of the process of the invention, preference is given to using alkaline earth metal or alkali metal carbonates, in particular potassium carbonate or sodium carbonate.

In the first step of the process of the invention, the reaction temperature can be varied within a relatively wide range. Generally, the reaction is carried out at 0 ℃ to 100 ℃, preferably 40 ℃ to 80 ℃.

In the preparation process of the present invention, generally, 1 to 4 moles, preferably 1 to 1.1 moles, of the 4, 6-dichloropyrimidine derivative of the formula (II) are used per mole of the compound of the formula (III).

In the preparation process of the present invention, generally, 1 to 4 moles, preferably 1 to 1.1 moles, of the 4, 6-dichloropyrimidine derivative of the formula (II) are used per mole of the compound of the formula (V).

The following steps are generally employed in carrying out the first step of the process of the present invention. The 4, 6-dichloropyrimidine derivative of formula (II) is combined with a base, if appropriate in the presence of a diluent. The compound of formula (III) or the compound of formula (V) is added, if appropriate in the presence of a diluent, and the mixture is stirred, if appropriate at elevated or reduced temperature, until the reaction is complete. After the reaction is complete, the reaction mixture is worked up by conventional methods or directly subjected to the second reaction stage of the process of the invention in situ.

In the first step of the process of the invention, the compound of the formula (III) or the compound of the formula (V) is added, if appropriate in the presence of a diluent, in particular by metering in, for example, a compound of the formula (II) which is suitable for dissolving in a ketone, in particular methyl isobutyl ketone. The addition step is carried out once or within 12 hours, preferably once or over 6 hours.

Suitable diluents in the second step of the process according to the invention are all inert organic solvents. These organic solvents include, by way of example and preferably, aliphatic, alicyclic or aromatic hydrocarbons, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons, such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 1, 2-dimethoxyethane, 1, 2-diethoxyethane or anisole; ketones, such as acetone, butanone, methyl isobutyl ketone or cyclohexanone; nitriles, for example acetonitrile, propionitrile, n-or isobutyronitrile or benzonitrile; amides, such as N, N-dimethylformamide, N-dimethylacetamide, N-methyl-formanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; esters, such as methyl acetate or ethyl acetate; sulfoxides, such as dimethyl sulfoxide, sulfones, such as sulfolane; or mixtures thereof with water. In the second step of the process of the invention, preference is given to using ketones, in particular methyl isobutyl ketone.

If appropriate, the second step of the process of the invention is carried out in the presence of a suitable acid acceptor. Suitable acid acceptors are all customary inorganic or organic bases. These bases include, by way of example and preferably, alkaline earth metal or alkali metal hydroxides, acetates, carbonates or bicarbonates, such as sodium hydroxide, potassium hydroxide, sodium acetate, potassium acetate, sodium carbonate, potassium bicarbonate or sodium bicarbonate; and alkaline earth metal or alkali metal hydrides, such as calcium hydride, sodium hydride or potassium hydride. In the second step of the process of the invention, preference is given to using alkaline earth metal or alkali metal carbonates, in particular potassium carbonate or sodium carbonate.

The second step of the process of the invention is carried out in the presence of a catalytic amount of 1, 4-diazabicyclo [2.2.2] octane (DABCO).

When carrying out the second step of the process of the present invention, the reaction temperature can be varied within a wide range. In general, the reaction is carried out at from 0 ℃ to 100 ℃, preferably from 40 ℃ to 90 ℃, in particular from 50 ℃ to 80 ℃.

In the production process of the present invention, usually, 0.8 to 4 moles, preferably 0.95 to 1.05 moles of the compound of the formula (V) are used per mole of the compound of the formula (IV).

In the preparation process of the present invention, usually, 0.8 to 4 moles, preferably 0.95 to 1.05 moles of the compound of the formula (III) are used per mole of the compound of the formula (VI).

In the preparation process according to the invention, in general, from 2 to 40 mol%, preferably from 2 to 20 mol%, of 1, 4-diazabicyclo [2.2.2] octane are employed per mole of compound of the formula (IV).

In the preparation process according to the invention, in general, from 2 to 40 mol%, preferably from 2 to 20 mol%, of 1, 4-diazabicyclo [2.2.2] octane are employed per mole of compound of the formula (VI).

The second step of a) which is an option of the preparation process according to the invention is generally carried out by the following process. The compound of formula (V) is combined with a base and 1, 4-diazabicyclo [2.2.2] octane, if appropriate in the presence of a diluent. If appropriate in the presence of a diluent, and if appropriate stirring the mixture at elevated temperature. After completion of the reaction, the reaction mixture is worked up by conventional methods.

Alternatively, the second step of an alternative a) of the preparation process according to the invention can also be carried out by mixing the compound of the formula (IV) with a base and 1, 4-diazabicyclo [2.2.2] octane, if appropriate in the presence of a diluent. If appropriate in the presence of a diluent, and if appropriate stirring the mixture at elevated temperature. After completion of the reaction, the reaction mixture is worked up by conventional methods.

The second step of b) which is another alternative of the preparation process according to the invention is generally carried out by the following process. The compound of formula (III) is combined with a base and 1, 4-diazabicyclo [2.2.2] octane, suitably in the presence of a diluent. If appropriate in the presence of a diluent, and if appropriate stirring the mixture at elevated temperature. After completion of the reaction, the reaction mixture is worked up by conventional methods.

Alternatively, step b) of the process of the invention may be carried out by mixing the compound of formula (VI) with a base and 1, 4-diazabicyclo [2.2.2] octane, e.g. in the presence of a suitable diluent. If appropriate in the presence of a diluent, and if appropriate stirring the mixture at elevated temperature. After completion of the reaction, the reaction mixture is worked up by conventional methods. In a particular embodiment, the process of the invention is carried out as a one-pot reaction (Eintopfree).

The following examples will serve to illustrate the invention. However, the present invention is not limited to these examples.

Examples

Example 1

Scheme a) or b) of the preparation method

4-chloro-5-fluoro-6- [ 4-fluoro-3- (trifluoromethyl) phenoxy]Pyrimidines

(first step)

4, 6-dichloro-5-fluoropyrimidine (1.67g, content: 98.9%) and potassium carbonate (1.72g) were first added to methyl isobutyl ketone (5ml), and then a solution of 1.8g of 4-fluoro-3- (trifluoromethyl) phenol in 5ml of methyl isobutyl ketone was added dropwise to the mixture at 60 ℃ over 3 hours. The mixture was stirred at 60 ℃ for 1.5 hours, then cooled, mixed with water, the organic phase was separated off, the aqueous phase was re-extracted with methylisobutylketone, the organic extracts were combined and dried over sodium sulfate, and the solvent was then evaporated off. This gave 4-chloro-5-fluoro-6- [ 4-fluoro-3- (trifluoromethyl) phenoxy ] -pyrimidine as an oil (2.74g, content: 93.9%, yield 83.8% of theory).

4- [ 4-chloro-3- (trifluoromethyl) phenoxy]-5-fluoro-6- [ 4-fluoro-3- (trifluoromethyl) phenoxy]Pyrimidines

(second step)

4-chloro-3- (trifluoromethyl) phenol (0.98g) was first added to a methyl isobutyl ketone/water mixture (8ml, 7/1) with potassium carbonate (0.9g) and 1, 4-diazabicyclo [2.2.2] octane (DABCO) (28mg) and mixed with a solution of 4-chloro-5-fluoro-6- [ 4-fluoro-3- (trifluoromethyl) phenoxy ] pyrimidine (1.56g, content: 98.8%) in 7ml of methyl isobutyl ketone at 70-80 ℃. The mixture is stirred at 70-80 ℃ for 2 hours, then cooled, water is added, the organic phase is separated off, the aqueous phase is extracted with methylisobutylketone, the combined organic extracts are dried over sodium sulfate and the solvent is evaporated off. Thus, 4- [ 4-chloro-3- (trifluoromethyl) phenoxy ] -5-fluoro-6- [ 4-fluoro-3- (trifluoromethyl) phenoxy ] pyrimidine (1.92g, content: 96.5%, yield 79.2% of theory) was obtained as a solid.

Example 2

Scheme a of the preparation method

4-chloro-6- (3-chloro-2-methylphenoxy) -5-fluoropyrimidine

(first step)

4, 6-dichloro-5-fluoropyrimidine (16.7g, content: 99.7%) and potassium carbonate (20.2g) were first added to methyl isobutyl ketone (50ml), and then a solution of 14.3g of 3-chloro-2-methylphenol in 50ml of methyl isobutyl ketone was added dropwise at 60 ℃ over 3.5 hours. The mixture was stirred for 2 hours at 60 ℃ and then cooled, mixed with water, the organic phase was separated off, the aqueous phase was re-extracted with methylisobutylketone, the organic extracts were combined and dried over sodium sulfate and the solvent was evaporated off. Thus, 4-chloro-6- (3-chloro-2-methylphenoxy) -5-fluoropyrimidine (26.8g, content: 96.7%, yield 95.2% of theory) was obtained as a solid.

(2E) -2- (2- { [6- (3-chloro-2-methylphenoxy) -5-fluoro-4-pyrimidinyl]Oxy } phenyl) -2- (methoxyimino) -N-methylacetamide

(second step)

(2E) -2- (2-hydroxyphenyl) -2- (methoxyimino) -N-methylacetamide (4.16g, content: 99.7%) together with potassium carbonate (3.7g) and DABCO (110mg) were first added to methylisobutylketone (30ml), followed by mixing at 50 ℃ with a solution of 4-chloro-6- (3-chloro-2-methylphenoxy) -5-fluoropyrimidine (5.46g, content: 98.1%) in 30ml of methylisobutylketone. The mixture is stirred for 4 hours at 50 ℃ and then cooled, water is added, the organic phase is separated off, the aqueous phase is extracted with methylisobutylketone, the combined organic extracts are dried over sodium sulfate and the solvent is evaporated off. Thus, an oil was obtained, (2E) -2- (2- { [6- (3-chloro-2-methylphenoxy) -5-fluoro-4-pyrimidinyl ] oxy } phenyl) -2- (methoxyimino) -N-methylacetamide (9.15g, content: 94.2%, yield 96, 9% of theory).

Example 3

Scheme a of the preparation method

4-chloro-6- (2-chlorophenoxy) -5-fluoropyrimidine

(first step)

4, 6-dichloro-5-fluoropyrimidine (33.5g, content: 98.9%) and potassium carbonate (34.4g) were first added to a methyl isobutyl ketone/water mixture (120ml, 5/1), to which was added dropwise a methyl isobutyl ketone solution (100 ml) containing 25.7g of o-chlorophenol at 60 ℃ over 3 hours. The mixture is stirred for 6 hours at 60 ℃ and then cooled, the organic phase is separated off and washed with 5% NaOH, the aqueous phase is extracted with methylisobutylketone, the organic extracts are combined, dried over sodium sulfate and the solvent is distilled off. This gave 4-chloro-6- (2-chlorophenoxy) -5-fluoropyrimidine as an oil (48.4g, content: 95.6%, yield 90.3% of theory).

(E) - (2- { [6- (2-chlorophenoxy) -5-fluoro-4-pyrimidinyl]Oxy } phenyl) - (5, 6-dihydro-1, 4, 2-dioxazin-3-yl) methanone O-methyloxime

(second step)

First, (E) -5, 6-dihydro-1, 4, 2-dioxazin-3-yl- (2-hydroxyphenyl) methanone O-methyloxime (11.8g) was added with potassium carbonate (9.0g) and DABCO (280mg) to a methylisobutylketone/water mixture (80ml, 7/1), followed by mixing at 80 ℃ with 70ml of a methylisobutylketone solution of 4-chloro-6- (2-chlorophenoxy) -5-fluoropyrimidine (13.1g, content: 98.1%). The mixture was stirred at 80 ℃ for 1.5 h, then cooled, water was added, the organic phase was separated off, the aqueous phase was extracted with methylisobutylketone, the combined organic extracts were dried over sodium sulfate and the solvent was evaporated off. Thus was obtained (E) -2- (2- { [6- (2-chlorophenoxy) -5-fluoro-4-pyrimidinyl ] oxy } phenyl) - (5, 6-dihydro-1, 4, 2-dioxazin-3-yl) methanone O-methyloxime (23.4g, content: 95.2%, yield 97.9% of theory) as a solid.

Example 4

Scheme a of the preparation method

4-chloro-6- (2-chlorophenoxy) -5-fluoropyrimidine

(first step)

First, 4, 6-dichloro-5-fluoropyrimidine (33.5g, content: 98.9%) and potassium carbonate (34.4g) were added to a methyl isobutyl ketone/water mixture (120ml.5/1), and a solution of 25.7g of o-chlorophenol in 100ml of methyl isobutyl ketone was added dropwise thereto at 60 ℃ over 3 hours. The mixture is stirred for 6 hours at 60 ℃ and then cooled, the organic phase is separated off and washed with 5% NaOH, the aqueous phase is extracted with methylisobutylketone, the organic extracts are combined, dried over sodium sulfate and the solvent is distilled off. This gave 4-chloro-6- (2-chlorophenoxy) -5-fluoropyrimidine as an oil (48.4g, content: 95.6%, yield 90.3% of theory).

(E) - (2- { [6- (2-chlorophenoxy) -5-fluoro-4-pyrimidinyl]Oxy } phenyl) - (5, 6-dihydro-1, 4, 2-dioxazin-3-yl) methanone O-methyloxime

(second step, comparative test)

First, (E) -5, 6-dihydro-1, 4, 2-dioxazin-3-yl- (2-hydroxyphenyl) methanone O-methyloxime (11.8g) and potassium carbonate (9.0g) were added to a methylisobutylketone/water mixture (80ml, 7/1) and mixed with a solution of 4-chloro-6- (2-chlorophenoxy) -5-fluoropyrimidine (13.1g, content: 98.1%) in 70ml of methylisobutylketone at 50 ℃. The mixture is stirred for 24 hours at 50 ℃ and then cooled, water is added, the organic phase is separated, the aqueous phase is extracted with methylisobutylketone, the combined organic extracts are dried over sodium sulfate and the solvent is evaporated off. Thus, oil, (E) -2- (2- { [6- (2-chlorophenoxy) -5-fluoro-4-pyrimidinyl ] oxy } phenyl) - (5, 6-dihydro-1, 4, 2-dioxazin-3-yl) methanone O-methyloxime (26.4g, content: 33.3%, yield 38.6% of theory) was obtained.

Example 5

Scheme b of the preparation method

(E) - {2- [ (6-chloro-5-fluoro-4-pyrimidinyl) oxy]Phenyl } (5, 6-dihydro-1, 4, 2-dioxazin-3-yl) methanone O-methyloxime

(first step)

4, 6-dichloro-5-fluoropyrimidine (31.8g, content: 98.9%) and potassium carbonate (31.5g) were first added to acetone (115ml), and 44.9g of a 350ml acetone solution of (E) -5, 6-dihydro-1, 4, 2-dioxazin-3-yl- (2-hydroxyphenyl) methanone O-methyloxime was added dropwise thereto at 60 ℃ over 6 hours. The mixture was stirred at 60 ℃ for 2 hours, acetone was distilled off, the mixture was mixed with dichloromethane and water, the organic phase was separated, the aqueous phase was extracted with dichloromethane, the organic extracts were combined, washed with 5% NaOH, dried over sodium sulfate and the solvent was evaporated off. Thus, as a solid, (E) - {2- [ (6-chloro-5-fluoro-4-pyrimidinyl) oxy ] phenyl } - (5, 6-dihydro-1, 4, 2-dioxazin-3-yl) methanone O-methyloxime (68.0g, content: 95.8%, yield 94.5% of theory) was obtained.

Claims (11)

1. A process for the preparation of a compound of the general formula (I),

wherein

Ar¹Represents a substituted or unsubstituted aryl or heterocyclic group,

x represents hydrogen, fluorine, chlorine or bromine,

L¹，L²，L³，L⁴and L⁵Are identical or different and each independently represent hydrogen, halogen, cyano, nitro, alkylcarbonyl, formyl, alkaneOxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl, each of which is optionally substituted by halogen,

or

L¹，L²，L³And L⁴Are identical or different and each independently represent hydrogen, halogen, cyano, nitro, alkylcarbonyl, formyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl which is in each case optionally substituted by halogen, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl,

and

L⁵represents one of the following groups:

wherein represents the point of attachment to a phenyl group,

and wherein the radicals

Ar¹And

is different in that it is a mixture of,

it is characterized in that

Reacting a 4, 6-dichloropyrimidine derivative of the general formula (II),

wherein

X is as defined above, and X is as defined above,

a) first, in a first step, it is reacted with a compound of the general formula (III),

Ar¹-OH， (III)

wherein

Ar¹As defined above, the above-mentioned,

if a diluent is suitable and if an acid acceptor is suitable,

then, in a second step, the resulting compound of formula (IV)

Wherein

Ar¹And X is as defined above

With a compound of the general formula (V),

wherein

L¹，L²，L³，L⁴And L⁵As defined above, the above-mentioned,

if appropriate in the presence of a solvent, if appropriate in the presence of a base and with addition of 2 to 40mo 1% of 1, 4-diazabicyclo [2.2.2] octane (DABCO),

or

b) First, in a first step, it is reacted with a compound of the general formula (V),

wherein

L¹，L²，L³，L⁴And L⁵As defined above, the above-mentioned,

if a diluent is suitable and if an acid acceptor is suitable,

the resulting compound of formula (VI) is then reacted

Wherein

X，L¹，L²，L³，L⁴And L⁵As defined above, the above-mentioned,

in a second step, with a compound of the general formula (III),

Ar¹-OH， (III)

wherein

Ar¹As defined above, the above-mentioned,

if appropriate in the presence of a solvent, if appropriate in the presence of a base, and 2 to 40mo 1% of 1, 4-diazabicyclo [2.2.2] octane (DABCO) are added.

2. A process according to claim 1, characterized in that in the process according to the invention for preparing the compound of formula (I), 2 to 20 mol% of 1, 4-diazabicyclo [2.2.2] octane are used per mole of compound of formula (IV).

3. A process according to claim 1, characterized in that in the process according to the invention for preparing the compound of formula (I), 2 to 20 mol% of 1, 4-diazabicyclo [2.2.2] octane are used per mole of compound of formula (VI).

4. Process according to at least one of claims 1 to 3, characterized in that the process for the preparation of the compounds of the formula (I) is carried out as a one-pot reaction.

5. The process according to at least one of claims 1 to 4, characterized in that 1 to 4 mol of the 4, 6-dichloropyrimidine derivative of the formula (II) are used per mol of the compound of the formula (III).

6. The process according to at least one of claims 1 to 4, characterized in that 1 to 4 mol of the 4, 6-dichloropyrimidine derivative of the formula (II) are used per mol of the compound of the formula (V).

7. Process according to at least one of claims 1 to 6, characterized in that 0.8 to 4 mol of compound of the formula (V) are used per mol of compound of the formula (IV).

8. Process according to at least one of claims 1 to 6, characterized in that 0.8 to 4 mol of compound of the formula (III) are used per mol of compound of the formula (VI).

9. Method according to at least one of claims 1 to 8, characterized in that

Ar¹Represents a heterocyclic group having 3 to 7 ring atoms, which heterocyclic group is optionally substituted by halogen or by alkyl, alkoxy, haloalkyl, haloalkoxy, each having 1 to 4 carbon atoms;

or represents phenyl or naphthyl, each of which is optionally mono-to tetrasubstituted by identical or different substituents, preferably the following substituents:

halogen, cyano, nitro, formyl, carboxy, carbamoyl, thiocarbamoyl;

alkyl, oxoalkyl, alkoxy, alkoxyalkyl, alkylthioalkyl, dialkoxyalkyl, alkylthio, alkylsulfinyl or alkylsulfonyl, each of which is straight-chain or branched and each has 1 to 8 carbon atoms;

each straight-chain or branched, alkenyl or alkenyloxy having in each case 2 to 6 carbon atoms;

haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulfinyl or haloalkylsulfonyl, each of which is straight-chain or branched and each of which has 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms;

haloalkenyl or haloalkenyloxy each straight-chain or branched, each having 2 to 6 carbon atoms and 1 to 11 identical or different halogen atoms;

each is a straight or branched chain dialkylamino group;

alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aralkylaminocarbonyl, dialkylaminocarbonyloxy, alkenylcarbonyl or alkynylcarbonyl having 1 to 6 carbon atoms in the respective hydrocarbon chain;

cycloalkyl or cycloalkoxy each having 3 to 6 carbon atoms;

alkylene having 3 or 4 carbon atoms, oxyalkylene having 2 or 3 carbon atoms or dioxyalkylene having 1 or 2 carbon atoms, each of which is optionally mono-to tetrasubstituted by identical or different substituents from the group consisting of fluorine, chlorine, oxo, methyl, trifluoromethyl and ethyl;

or groupWherein

A¹Represents hydrogen, hydroxyl or alkyl having 1 to 4 carbon atoms or cycloalkyl having 1 to 6 carbon atoms and

A²represents hydroxy, methoxy, ethoxy, amino, methylamino, phenyl, benzyl or represents eachAlkyl or alkoxy having 1 to 4 carbon atoms which is optionally substituted by cyano, alkoxy, alkylthio, alkylamino, dialkylamino or phenyl, or represents alkenyloxy or alkynyloxy having in each case 2 to 4 carbon atoms,

and in each case optionally mono-to trisubstituted on the ring by halogen and/or linear or branched alkyl or alkoxy having 1 to 4 carbon atoms, benzoyl, benzoylvinyl, cinnamoyl, heterocyclyl or phenylalkyl, phenylalkoxy or heterocyclylalkyl having in each case 1 to 3 carbon atoms in the respective alkyl moiety,

x represents fluorine or chlorine, and X represents fluorine or chlorine,

L¹，L²，L³，L⁴and L⁵Which may be identical or different and each independently of the others represents hydrogen, halogen, cyano, nitro, formyl, alkylcarbonyl having 1 to 6 carbon atoms, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl, each having 1 to 6 carbon atoms and each being optionally substituted by 1 to 5 halogen atoms,

or

L¹，L²，L³And L⁴Which may be identical or different and each independently of the others represents hydrogen, halogen, cyano, nitro, formyl, alkylcarbonyl having 1 to 6 carbon atoms, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl each having 1 to 6 carbon atoms and each being optionally substituted by 1 to 5 halogen atoms and

L⁵in particular one of the following groups:

wherein represents the point of attachment to the phenyl group.

10. Method according to at least one of claims 1 to 8, characterized in that

Ar¹Represents thienyl, pyridyl or furyl which are optionally substituted by methyl, ethyl, methoxy, ethoxy, trifluoromethyl or trifluoromethoxy;

or represents phenyl which is in each case optionally mono-to tetrasubstituted by identical or different substituents, preferably the following substituents:

fluorine, chlorine, bromine, iodine, cyano, nitro, formyl, carboxyl, carbamoyl, thiocarbamoyl,

methyl, ethyl, n-or i-propyl, n-, i-, s-or t-butyl, 1-, 2-, 3-, neo-pentyl, 1-, 2-, 3-, 4- (2-methylbutyl), 1-, 2-, 3-hexyl, 1-, 2-, 3-, 4-, 5- (2-methylpentyl), 1-, 2-, 3- (3-methylpentyl), 2-ethylbutyl, 1-, 3-, 4- (2, 2-dimethylbutyl), 1-, 2- (2, 3-dimethylbutyl), 3-oxobutyl, methoxymethyl, dimethoxymethyl,

methoxy, ethoxy, n-or i-propoxy,

methylthio, ethylthio, n-or isopropylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl or ethylsulfonyl,

vinyl, allyl, 2-methallyl, propen-1-yl, crotonyl, propargyl, vinyloxy, allyloxy, 2-methallyloxy, propen-1-yloxy, crotonyloxy, propargyloxy,

the group consisting of trifluoromethyl, trifluoroethyl,

difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, trifluoromethylthio, difluorochloromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl,

a dimethylamino group, a diethylamino group,

acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dimethylaminocarbonyloxy, diethylaminocarbonyloxy, benzylaminocarbonyl, acryloyl, propioloyl,

a cyclopentyl group, a cyclohexyl group,

each of which is optionally mono-to tetrasubstituted, identically or differently, by fluorine, chlorine, oxo, methyl and trifluoromethyl,

or groupWherein

A¹Represents hydrogen, methyl or hydroxy and

A²represents hydroxy, methoxy, ethoxy, amino, methylamino, phenyl or benzyl, and

phenyl, benzoyl, benzoylvinyl, cinnamoyl, benzyl, phenethyl, phenylpropyl, benzyloxy, 5, 6-dihydro-1, 4, 2-dioxazin-3-ylmethyl, triazolylmethyl, benzoxazol-2-ylmethyl, 1, 3-dioxan-2-yl, benzimidazol-2-yl, dioxolan-2-yl, oxadiazolyl, the ring part of each of which is optionally mono-to trisubstituted by halogen and/or straight-chain or branched alkyl or alkoxy having 1 to 4 carbon atoms,

x represents fluorine, and X represents fluorine,

L¹，L²，L³and L⁴Which may be identical or different and each independently of the others, each represents hydrogen, fluorine, chlorine, bromine, cyano, nitro, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, methyl, ethyl, n-or i-propyl, n-, i-, s-or t-butyl, methoxy, ethoxy, n-or i-propoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulphonyl or ethylsulphonyl, trifluoromethyl, trifluoroethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, difluorochloromethylthio, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulphonyl and

L⁵represents one of the following groups:or

Wherein represents the point of attachment to the phenyl group.

11. Method according to at least one of claims 1 to 8, characterized in that

Ar¹Represents thienyl, pyridyl or furyl which are optionally substituted by methyl, ethyl, methoxy, ethoxy, trifluoromethyl or trifluoromethoxy;

or represents phenyl which is in each case optionally mono-to tetrasubstituted by identical or different substituents, preferably the following substituents:

fluorine, chlorine, bromine, iodine, cyano, nitro, formyl, carboxyl, carbamoyl, thiocarbamoyl,

methyl, ethyl, n-or i-propyl, n-, i-, s-or t-butyl, 1-, 2-, 3-, neo-pentyl, 1-, 2-, 3-, 4- (2-methylbutyl), 1-, 2-, 3-hexyl, 1-, 2-, 3-, 4-, 5- (2-methylpentyl), 1-, 2-, 3- (3-methylpentyl), 2-ethylbutyl, 1-, 3-, 4- (2, 2-dimethylbutyl), 1-, 2- (2, 3-dimethylbutyl), 3-oxobutyl, methoxymethyl, dimethoxymethyl,

methoxy, ethoxy, n-or i-propoxy,

methylthio, ethylthio, n-or isopropylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl or ethylsulfonyl,

vinyl, allyl, 2-methallyl, propen-1-yl, crotonyl, propargyl, vinyloxy, allyloxy, 2-methallyloxy, propen-1-yloxy, crotonyloxy, propargyloxy,

the group consisting of trifluoromethyl, trifluoroethyl,

difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, trifluoromethylthio, difluorochloromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl,

a dimethylamino group, a diethylamino group,

acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dimethylaminocarbonyloxy, diethylaminocarbonyloxy, benzylaminocarbonyl, acryloyl, propioloyl,

a cyclopentyl group, a cyclohexyl group,

each of which is optionally mono-to tetrasubstituted, identically or differently, by fluorine, chlorine, oxo, methyl and trifluoromethyl,

or groupWherein

A¹Represents hydrogen, methyl or hydroxy and

A²represents hydroxy, methoxy, ethoxy, amino, methylamino, phenyl or benzyl, and

phenyl, phenoxy, phenylthio, benzoyl, benzoylvinyl, cinnamoyl, benzyl, phenethyl, phenylpropyl, benzyloxy, benzylthio, 5, 6-dihydro-1, 4, 2-dioxazin-3-ylmethyl, triazolylmethyl, benzoxazol-2-ylmethyl, 1, 3-dioxan-2-yl, benzimidazol-2-yl, dioxolan-2-yl, oxadiazolyl, the ring moieties of each of which are optionally mono-to trisubstituted by halogen and/or straight-chain or branched alkyl or alkoxy having 1 to 4 carbon atoms,

x represents fluorine, and X represents fluorine,

L¹，L²，L³and L⁴Represents hydrogen, and

L⁵represents one of the following groups:

wherein represents the point of attachment to the phenyl group.