DE19929348A1 - Pure 2-heterocyclylmethyl-benzoic acid derivative preparation in high yield, for use as pharmaceutical or agrochemical intermediate, from phthalide compound and nitrogen-containing heterocycle - Google Patents

Abstract

Preparation of 2-((N-bonded heterocyclyl)-methyl)-benzoic acid derivatives (I) involves reacting a phthalide (II) with a nitrogen-containing heterocycle (III) (or its metal salt) in presence of a polar aprotic diluent and a optionally a basic reaction auxiliary. Preparation of 2-heterocyclylmethyl-benzoic acid derivatives of formula (I) involves reacting a phthalide of formula (II) with a nitrogen-containing heterocycle of formula H-Y (III) (or its metal salt) in presence of a polar aprotic diluent and a optionally a basic reaction auxiliary. n = 0-3; X = NO2, CN, CONH2, CSNH2, halo or (all optionally substituted) alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino or dialkylaminosulfonyl; Y = N-bonded heterocyclyl.

Description

The invention relates to a new process for the preparation of 2-heterocyclyl methyl-benzoic acid derivatives, which are intermediates for the production of Active ingredients used for pharmaceutical and agricultural applications can be.

It is known that the reaction of 2-benzofuran-1 (3H) -ones ("phthalides") with Phthalimide potassium salt to corresponding N- (2-carboxy-benzyl) phthalimide deriva ten leads (cf. Organic Syntheses Coll. Vol. IV (1963), 810-812; Arch. Pharm. 318 (1985), 640-649; Synthetic Communications 28 (1998), 4525-4530).

But it is also known that in the reaction of phthalides with arylalkyl amines not the 2-arylalkyl to be expected in the same course of the reaction aminomethyl-benzoic acids, but N-arylalkyl-2-hydroxymethyl-benzamide-Deri vate can be obtained (see Arch. Pharm. 318 (1985), 640-649).

It has now been found that 2-heterocyclylmethylbenzoic acid derivatives of the general formula (I)

in which
n represents the numbers 0, 1, 2 or 3,
X stands for nitro, cyano, carbamoyl, thiocarbamoyl, halogen, or for optionally optionally substituted alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino or dialkylaminosulfonyl, and
X stands for nitro, cyano, carbamoyl, thiocarbamoyl, halogen, or for optionally optionally substituted alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino or dialkylaminosulfonyl, and
Z represents heterocyclyl bound via N (nitrogen),
obtained in good yields and in high purity if phthalides of the general formula (II)

in which
n and X have the meaning given above,
with nitrogen heterocycles of the general formula (III)

HZ (III)

in which
Z has the meaning given above,
- or with metal salts of nitrogen heterocycles of the general formula (II) -
in the presence of an aprotic polar diluent and, if appropriate, in the presence of a basic reaction auxiliary.

Surprisingly, the 2-heterocyclylmethyl-benzoic acid derivatives of all general formula (I) by the process of the invention selectively in good shape  loot and be obtained in high purity, although according to the above State of the art on a larger scale as a side reaction the formation of N-heterocyclyl-2-hydroxymethyl-benzamide derivatives were expected.

The method according to the invention provides a technically practical path 2-heterocyclylmethyl-benzoic acid derivatives based on known methods easily accessible phthalides added benzoic acid derivatives.

The alternative synthesis via the implementation of 2-halomethyl-benzoic acid esters with nitrogen heterocycles of the formula (I) sets the often complex and multi-stage synthesis of 2-methyl-benzoic acid esters. The corresponding Benzoic acids would have to be produced by cleaving the esters, however not all other substituents are stable under the conditions of the ester cleavage are.

Preferred substituents or ranges of the formulas and radicals listed above and below are defined below.
n is preferably the number 0, 1, 2 or 3.
X preferably represents nitro, cyano, carbamoyl, thiocarbamoyl, halogen, in each case optionally by halogen, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio, C ₁ -C ₄ alkylsulfinyl or C ₁ -C ₄ - Alkylsulfonyl substituted alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl, each with up to 4 carbon atoms in the alkyl groups, or for alkylamino, dialkylamino or di alkylaminosulfonyl, each with up to 4 carbon atoms in the alkyl groups
Z is preferably one of the heterocyclic groups below

in which the bond shown in dashed lines is a single bond or a double bond,
Q represents oxygen or sulfur,
R ¹ for hydrogen, hydroxy, mercapto, cyano, halogen, for each ge optionally by cyano, halogen, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkyl thio, C ₁ -C ₄ alkylsulfinyl or C ₁ - C ₄ -alkylsulfonyl-substituted alkyl, alkylcarbonyl, alkoxy, alkoxycarbonyl, alkylthio, alkylsulfinyl or alkylsulfonyl each having up to 6 carbon atoms in the alkyl groups, for each alkylamino or dialkylamino optionally substituted by halogen, each having up to 6 carbon atoms in the alkyl groups, for alkenyl, alkynyl, alkenyloxy, alkenylthio or alkenylamino each optionally substituted by halogen, each having up to 6 carbon atoms in the alkenyl or alkynyl groups, for cycloalkyl, cycloalkyloxy, cycloalkylthio, cycloalkylamino, cycloalkylalkyl, cycloalkylalkoxy, cycloalkyl alkylthio or optionally substituted by halogen Cycloalkylalkylamino, each with 3 to 6 carbon atoms in the cycloalkyl groups and optionally up to 4 K. oh lenstoffatomen in the alkyl part, or for phenyl, phenyloxy, phenylthio, phenylamino, benzyl, benzyloxy, benzylthio or benzylamino optionally substituted by halogen, C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy, or - for the case that two adjacent radicals R ¹ and R ¹ are located on a double bond - together with the adjacent radical R ¹ also represents a benzo group, and
R ² for hydrogen, hydroxy, amino, alkylidene amino having up to 4 carbon atoms, for alkyl, alkoxy, alkylamino, dialkyl amino or alkanoylamino, each optionally substituted by cyano, halogen or C ₁ -C ₄ alkoxy, each having up to 6 carbon atoms in the alkyl groups, for alkenyl, alkynyl or alkenyloxy optionally substituted by halogen, each having up to 6 carbon atoms in the alkenyl or alkynyl groups, for each cycloalkyl, cycloalkylalkyl or cycloalkylamino optionally substituted by halogen, each having 3 to 6 carbon atoms in the Cycloalkyl groups and optionally up to 3 carbon atoms in the alkyl part, or for phenyl or benzyl optionally substituted in each case by halogen, C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy, or together with an adjacent radical R ¹ or R ² optionally represents alkanediyl having 3 to 5 carbon atoms which is substituted by halogen or C ₁ -C ₄ alkyl,
where the individual radicals R ¹ and R ² — insofar as several of them are bound to the same heterocyclic groupings, can have the same or different meanings within the scope of the above definition,
n particularly preferably represents the numbers 0, 1 or 2.
X particularly preferably represents nitro, cyano, carbamoyl, thiocarbamoyl, fluorine, chlorine, bromine, each optionally by fluorine and / or chlorine, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, n- or i-propyl thio, methylsulfinyl, ethylsulfinyl, methylsulfonyl or ethylsulfonyl substituted methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, each optionally with fluorine and / or chlorine, methoxy, ethoxy, n - or i- propoxy substituted methoxy, ethoxy, n- or i-propoxy, for methylthio, ethylthio, n- or i-propylthio, methyl- sulfinyl, ethylsulfinyl, n- or i-propylsulfinyl optionally substituted by fluorine and / or chlorine, Methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl, or for methyl amino, ethylamino, n- or i-propylamino, dimethylamino, diethylamino, dimethylaminosulfonyl or diethylaminosulfonyl.
Z particularly preferably represents one of the heterocyclic groupings below

in which the bond shown in dashed lines is a single bond or a double bond,
Q represents oxygen or sulfur,
R ¹ for hydrogen, hydroxy, mercapto, cyano, fluorine, chlorine, bromine, iodine, for each optionally by fluorine, chlorine, methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy , Methylthio, ethylthio, n- or i-propylthio, n-, i-, s- or t-butylthio, methylsulfinyl, ethylsulfmyl, n- or i-propylsulfinyl, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl substituted methyl, ethyl , n- or i-propyl, n-, 1-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy, methylthio, ethylthio, n - or i-Propylthio, n-, i-, s- or t-butylthio, methylsulfinyl, ethylsulfinyl, n- or i-propylsulfinyl, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl, for methyl amino, ethylamino, n- or i-propylamino, n-, i-, s- or t-butyl amino, dimethylamino, diethylamino, di-n-propylamino or di-i-propylamino, for ethenyl, propenyl, butenenyl optionally substituted by fluorine and / or chlorine, Ethynyl, propynyl, butynyl, propenyloxy, butenylox y, propenylthio, butenylthio, propenylamino or butenylamino, each for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cyclopropylthio, cyclobutylthio, cyclopentylamio, cyclopentylamino, cyclopentylamio amino, cyclohexylamino, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylmethoxy, cyclo butylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, cyclo propylmethylthio, cyclobutylmethylthio, cyclopentylmethylthio, cyclohexylmethylminomethyl, cyclohexylmethylmylmethylminomethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethylmethyl Ethyl, n- or i-propyl, n-, i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy substituted phenyl, phenyloxy, phenylthio, phenylamino, benzyl, benzyloxy, benzylthio or benzylamino, or - for the Case that two adjacent radicals R ¹ and R ¹ are located on a double bond - together with the adjacent radical R ¹ also represents a benzo group, and
R ² for hydrogen, hydroxyl, amino, for methyl, ethyl, n- or i-propyl, n-, i- or s-butyl, methoxy, ethoxy, n-, each optionally substituted by fluorine and / or chlorine, methoxy or ethoxy or i-propoxy, methylamino, ethylamino or dimethylamino, each for ethenyl, propenyl, ethynyl, propynyl or propenyloxy, optionally substituted by fluorine and / or chlorine, for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl optionally substituted by fluorine and / or chlorine , Cyclopropylmethyl, Cyclo butylmethyl, Cyclopentylmethyl or Cyclohexylmethyl, or for each optionally by fluorine, chlorine, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy-substituted phenyl or benzyl, or together with a neighboring R ¹ or R ^{2 be} each propane-1,3-diyl (trimethylene), butane-1,4-diyl (optionally substituted by methyl and / or ethyl) ( Tetramethylene) or pentane-1,5-diyl (pentamethyl en) stands
where the individual radicals R ¹ and R ² - if several of them are bound to the same heterocyclic groupings - may have the same or different meanings within the scope of the above definition.
Z very particularly preferably represents one of the heterocyclic groupings below

where Q, R ¹ and R ^{2 are defined} as in the particularly preferred definitions of Z.

Among the most preferred definitions for Z, the following heterocyclic group should be emphasized:

where R ¹ and R ^{2 are defined} as in the most particularly preferred definitions of Z.

If, for example, 5-fluoro-2-benzofuran-1 (3H) -one and 1-oxo-2 (1H) phthalazine are used as starting materials, the course of the reaction in the process according to the invention can be outlined using the following formula:

The phthalides required as starting materials in the process according to the invention general formula (II) are known and / or can according to known Ver drive are produced (cf. Heterocycles 31 (1990), 1261-1270; Synth. Commun. 20: 2641-2652 (1990); J. Org. Chem. 57 (1992), 2029-2033).

The stick further required as starting materials in the method according to the invention Substance heterocycles of the general formula (III) are largely known synthesis chemicals.

As metal salts of nitrogen heterocycles of the general formula (III) can ins especially the alkali metal and alkaline earth metal salts, such as the lithium, sodium, Rubidium, cesium, magnesium, calcium and barium salts, especially before adds the sodium and potassium salts of these compounds.

The process according to the invention for the preparation of the compounds of the general Formula (I) is made using an aprotic polar diluent carried out. These include in particular ethers, such as diisopropyl ether, dioxane, Tetrahydrofuran or ethylene glycol dimethyl or diethyl ether; Ketones like Acetone, butanone, methyl isopropyl ketone or methyl isobutyl ketone; Nitriles, like Acetonitrile, propionitrile or butyronitrile; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-formanilide, N-methyl-pyrrolidone or hexa methylphosphoric triamide; Esters such as methyl acetate or acetic acid  ethyl esters, sulfoxides, such as dimethyl sulfoxide, and sulfones, such as tetramethylene sulfone (Sulfolan).

Ketones such as methyl isobutyl ketone and amides such as N, N-dimethylformamide and N, N-dimethylacetamide are very particularly preferred as diluents.

The process according to the invention for the preparation of the compounds of the general Formula (I) is optionally using a basic reaction auxiliary carried out by means. As a reaction aid for the process according to the invention generally come the usual inorganic or organic bases or Acid acceptors into consideration. These preferably include alkali metal or earth alkali metal, acetates, amides, carbonates, bicarbonates, hydrides, hydroxides or alkanolates, such as sodium, potassium or calcium acetate, Lithium, sodium, potassium or calcium amide, sodium, potassium or calcium carbonate, sodium, potassium or calcium hydrogen carbonate, lithium, sodium, Potassium or calcium hydride, lithium, sodium, potassium or calcium hydroxide, Sodium or potassium, methanol, ethanolate, n or i propanolate, n, i, i or -t-butanolate; also basic organic nitrogen compounds, such as for example trimethylamine, triethylamine, tripropylamine, tributylamine, ethyl-di isopropylamine, N, N-dimethyl-cyclohexylamine, dicyclohexylamine, ethyl-dicyclo hexylamine, N, N-dimethyl-aniline, N, N-dimethyl-benzylamine, pyridine, 2-methyl, 3- Methyl, 4-methyl, 2,4-dimethyl, 2,6-dimethyl, 3,4-dimethyl and 3,5-dimethyl pyridine, 5-ethyl-2-methyl-pyridine, 4-dimethylamino-pyridine, N-methyl-piperidine, 1,4-diazabicyclo [2,2,2] octane (DABCO), 1,5-diazabicyclo [4,3,0] non-5-ene (DBN), or 1,8-diazabicyclo [5,4,0] -undec-7-ene (DBU).

Alkali metal and alkaline earth metal hydrides, hydroxides and alkanolates, such as Lithium, sodium, potassium or calcium hydride, lithium, sodium, potassium or Calcium hydroxide, sodium or potassium methoxide, ethanolate, n or i propanolate, -n-, -i-, -s- or -t-butanolate, are used as basic reaction aids very particularly preferred.  

The reaction temperatures can be carried out when carrying out the process according to the invention Process can be varied over a wide range. Generally you work at temperatures between 0 ° C and 200 ° C, preferably between 10 ° C and 180 ° C.

The process according to the invention is generally carried out under normal pressure leads. However, it is also possible to increase the process according to the invention or reduced pressure - generally between 0.1 bar and 10 bar to lead.

To carry out the process according to the invention, 1 mol of phthalide is used of the general formula (II) generally between 0.8 and 1.2 mol, preferably between 0.95 and 1.05 mol, nitrogen heterocycle of the general formula (III) or a salt thereof.

In a preferred embodiment, the reaction components are Room temperature or mixed under cooling and the reaction mixture is then - preferably at elevated temperature - stirred until the end of the reaction.

The workup can be carried out according to customary methods. Example is concentrated under reduced pressure, the residue with a Washed water practically immiscible organic solvent, then in Water absorbed by adding a strong acid such as salt acid, precipitated and isolated by suction (see the manufacturing examples).  

The 2-heterocyclylmethyl Benzoic acid derivatives of the general formula (I) can be used as intermediates for Manufacture of active ingredients for pharmaceutical and agricultural applications be used (cf. Pharmaceutical Research 27 (1977), 2364-2368 - cited in Chem. Abstracts 88: 98893; GB-A-1427408; DE-A-198 33 360).  

Manufacturing examples

example 1

10.0 g (60 mmol) of 4-methyl-5-trifluoromethyl-2,4-dihydro-3H-1,2,4-triazol-3-one taken up in 100 ml of methyl isobutyl ketone and added in portions with stirring 4.0 g (60 mmol) of 85% potassium hydroxide were added. After stirring overnight the solid is isolated by suction and under reduced pressure at 80 ° C. dried.

1.03 g (5 mmol) of the potassium salt of 4-methyl-5-trifluoromethyl-2,4-dihydro-3H-1,2,4-triazol-3-one thus obtained and 0.67 g (5 mmol) 2 -Benzofuran-1 (3H) -one (phthalide) are taken up in 8 ml of N, N-dimethyl-formamide and the reaction mixture is heated under reflux for 8 hours. It is then concentrated in vacuo in a water jet, the residue is washed with diethyl ether, dissolved in water and acidified with 2N hydrochloric acid. The crystalline product is isolated by suction.
1.1 g (74% of theory) of 2 - [(4-methyl-3-trifluoromethyl-5-oxo-4,5-di hydro-1H-1,2,4-triazol-1-yl) - methyl] benzoic acid, melting point 132 ° C.
¹ H NMR (CDCl ₃ , δ): 3.46 (s), 5.59 (s), 7.11 (d), 7.41 (t), 7.55 (t), 8.11 ( dd).

Example 2

2.9 g (20 mmol) of 4-methyl-5-methylthio-2,4-dihydro-3H-1,2,4-triazol-3-one are dissolved in 60 ml of N, N-dimethylformamide and after addition 0.88 g (22 mmol) of sodium hydride, the mixture is stirred for 30 minutes at room temperature (approx. 20 ° C). 2.68 g (20 mmol) of 2-benzofuran-1 (3H) -one (phthalide) are then added and the reaction mixture is heated under reflux for 2 hours. Then it is concentrated in a water jet vacuum, the residue is washed with diethyl ether, then dissolved in water and acidified with 2N hydrochloric acid. The product obtained in crystalline form is isolated by suction.
3.5 g (63% of theory) of 2 - [(4-methyl-3-methylthio-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl) methyl are obtained ] -benzoic acid with a melting point of 122 ° C.
¹ H NMR (CDCl ₃ , δ): 2.55 (s), 3.25 (s), 5.44 (s), 7.18 (d), 7.39 (dt), 7.49 ( dt), 7.99 (dd).

Analogously to Examples 1 and 2 and in accordance with the general description of the production process according to the invention, for example the compounds of the general formula (I) listed in Table 1 below can also be prepared.

Table 1

Examples of the compounds that can be produced according to the invention

Claims (4)

1. Process for the preparation of 2-heterocyclylmethyl-benzoic acid derivatives of the general formula (I) in which
n represents the numbers 0, 1, 2 or 3,
X represents nitro, cyano, carbamoyl, thiocarbamoyl, halogen, or for each optionally substituted alkyl, alkoxy, alkylthio, alkyl sulfinyl, alkylsulfonyl, alkylamino, dialkylamino or dialkyl aminosulfonyl, and
Z represents heterocyclyl bound via N (nitrogen),
characterized in that phthalides of the general formula (II)
in which
n and X have the meaning given above,
with nitrogen heterocycles of the general formula (III)
HZ (III)
in which
Z has the meaning given above,
- or with metal salts of nitrogen heterocycles of the general formula (III) -
in the presence of an aprotic polar diluent and, if appropriate, in the presence of a basic reaction auxiliary. 2. The method according to claim 1, characterized in that the implementation is carried out at temperatures between 0 ° C and 200 ° C. 3. The method according to claim 1 or 2, characterized in that
n represents the numbers 0, 1, 2 or 3,
X for nitro, cyano, carbamoyl, thiocarbamoyl, halogen, for each GE optionally by halogen, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio, C ₁ -C ₄ alkylsulfmyl or C ₁ -C ₄ alkylsulfonyl substituted alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl each having up to 4 carbon atoms in the alkyl groups, or represents alkylamino, di alkylamino or dialkylaminosulfonyl each having up to 4 carbon atoms in the alkyl groups,
Z for one of the heterocyclic groupings below
is, in each case in which the dashed bond is a single bond or a double bond, and
Q represents oxygen or sulfur,
R ¹ for hydrogen, hydroxy, mercapto, cyano, halogen, for each optionally by cyano, halogen, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio, C ₁ -C ₄ alkylsulfinyl or C ₁ -C ₄ -Alkyl sulfonyl substituted alkyl, alkylcarbonyl, alkoxy, alkoxy carbonyl, alkylthio, alkylsulfinyl or alkylsulfonyl, each with up to 6 carbon atoms in the alkyl groups, for each optionally substituted by halogen, alkyl amino or dialkylamino, each with up to 6 carbon atoms in the alkyl groups, for each optionally substituted by halogen-substituted alkenyl, alkynyl, alkenyloxy, alkenyl thio or alkenylamino, each having up to 6 carbon atoms in the alkenyl or alkynyl groups, for cycloalkyl, cycloalkyloxy, cycloalkylthio, cycloalkylamino, cycloalkylalkyl, cycloalkylalkoxy, optionally substituted by halogen Cycloalkylalkylthio or cycloalkylalkyl amino each having 3 to 6 carbon atoms in the cyclo alkyl groups and optionally up to 4 carbon atoms in the alkyl part, or for phenyl, phenyloxy, phenylthio, phenylamino, benzyl, benzyloxy, benzylthio or benzylamino optionally substituted by halogen, C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy, or - in the case that two adjacent radicals R ¹ and R ¹ are located on a double bond - together with the adjacent radical R ¹ also represents a benzo group, and
R ² for hydrogen, hydroxy, amino, alkylidene amino with up to 4 carbon atoms, for alkyl, alkoxy, alkylamino, dialkylamino or alkanoylamino, each optionally substituted by cyano, halogen or C ₁ -C ₄ alkoxy, each having up to 6 carbon atoms in the alkyl groups , for each optionally substituted by halogen substituted alkenyl, alkynyl or alkenyloxy each having up to 6 carbon atoms in the alkenyl or alkynyl groups, for each optionally substituted by halogen cycloalkyl, cycloalkylalkyl or cycloalkylamino each having 3 to 6 carbon atoms in the cycloalkyl groups and optionally to to 3 carbon atoms in the alkyl part, or phenyl or benzyl optionally substituted by halogen, C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy, or together with a neighboring radical R ¹ or R ² for optionally by Halogen or C ₁ -C ₄ alkyl-substituted alkanediyl having 3 to 5 carbon atoms,
where the individual radicals R ¹ and R ² — insofar as several of them are bound to the same heterocyclic groupings — can have the same or different meanings in the context of the above definition. 4. The method according to any one of claims 1 to 3, characterized in that
n represents 0, 1 or 2,
X for nitro, cyano, carbamoyl, thiocarbamoyl, fluorine, chlorine, bromine, each optionally with fluorine and / or chlorine, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, n- or i-propylthio, methylsulfinyl, Ethylsulfinyl, methylsulfonyl or ethylsulfonyl substituted methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, each optionally with fluorine and / or chlorine, methoxy, ethoxy, n- or i- Propoxy-substituted methoxy, ethoxy, n- or i-propoxy, for each methylthio, ethylthio, n- or i-propylthio optionally substituted by fluorine and / or chlorine, methylsulfinyl, ethyl sulfinyl, n- or i-propylsulfinyl, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl, or represents methylamino, ethylamino, n- or i-propylamino, dimethylamino, diethylamino, dimethylaminosulfonyl or diethylaminosulfonyl,
Z for one of the heterocyclic groupings below
in which the bond shown in dashed lines is a single bond or a double bond,
Q represents oxygen or sulfur,
R ¹ for hydrogen, hydroxy, mercapto, cyano, fluorine, chlorine, bromine, iodine, for each optionally by fluorine, chlorine, methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy , Methylthio, ethylthio, n- or i-propylthio, n-, i-, s- or t-butylthio, methylsulfinyl, ethylsulfmyl, n- or i-propyl sulfmyl, methylsulfonyl, ethylsulfonyl, n- or i-propyl sulfonyl substituted methyl , Ethyl, n- or i-propyl, n-, i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy, n-, 1-, s- or t-butoxy, methylthio, ethylthio , n- or i-propylthio, n-, i-, s- or t-butylthio, methylsulfinyl, ethylsulfinyl, n- or i-propylsulfmyl, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl, for methylamino, ethylamino, n- or i-propylamino, n-, i-, s- or t-butylamino, dimethylamino, diethylamino, di-n-propylamino or di-ipropylamino, each for ethenyl, propenyl, butenenyl optionally substituted by fluorine and / or chlorine, Ethynyl, propynyl, butynyl, propenyloxy, butenyloxy , Propenylthio, butenylthio, propenylamino or butenylamino, for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyloxy, cyclobutyl oxy, cyclopentyloxy, cyclohexyloxy, cyclopropylthio, cyclobutylthio, cyclobentylamino, cyclobentylamino, cyclopentylamino , Cyclopentylamino, Cyclohexylamino, Cyclopropylmethyl, Cyclobutylmethyl, Cyclopentyl methyl, Cyclohexylmethyl, Cyclopropylmethoxy, Cyclobutyl methoxy, Cyclopentylmethoxy, Cyclohexylmethoxy, Cyclo propylmethylthio, Cyclobutylmethylthio, Cyclopentylmethylthylmethyl, Cycloamylamylmethyl, Cyclohexylmethylmethyl, Cyclohexylmethylmethyl, Cyclohexamethylmethyl, Cyclohexylmethylmethyl, Cyclohexylmethylmethyl, Cycloamethylmethylmethyl, Cyclohexamethylmethyl, Cyclohexamethylmethyl, Cyclohexylmethylmethyl, Cycloamylmethylmethyl, Cycloamylmethyl, Cycloamethylmethylmethyl, Cycloamethylmethylmethyl, Cycloamethylmethylmethyl, Cycloamethylmethylmethyl, Cycloamethylmethylmethyl, , Chlorine, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy substituted phenyl, phenyloxy, phenylthio, phenylamino, benzyl, benzyloxy, Benzylthio or Benzylamino stands, or - for r in the event that two adjacent radicals R ¹ and R ¹ are located on a double bond - together with the adjacent radical R ¹ also represents a benzo group, and
R ² for hydrogen, hydroxyl, amino, for methyl, ethyl, n- or i-propyl, n-, i- or s-butyl, methoxy, ethoxy, n, each substituted by fluorine and / or chlorine, methoxy or ethoxy - or i-Propoxy, methylamino, ethyl amino or dimethylamino, for ethenyl, propenyl, ethynyl, propynyl or propenyloxy, each optionally substituted by fluorine and / or chlorine, for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl optionally substituted by fluorine and / or chlorine , Cyclopropylmethyl, Cyclobutyl methyl, Cyclopentylmethyl or Cyclohexylmethyl, or for each optionally by fluorine, chlorine, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy-substituted phenyl or benzyl, or together with an adjacent radical R ¹ or R ^2, each propane-1,3-diyl (trimethylene), butane-1,4-diyl (optionally substituted by methyl and / or ethyl) ( Tetramethylene) or pentane-1,5-diyl (pentamethylene ) stands,
where the individual radicals R ¹ and R ² — insofar as several of them are bound to the same heterocyclic groupings — can have the same or different meanings in the context of the above definition.