EP1194419A1

EP1194419A1 - Method for producing 2-heterocyclyl methyl benzoic acid derivatives

Info

Publication number: EP1194419A1
Application number: EP00940367A
Authority: EP
Inventors: Heinz-Jürgen Wroblowsky; Otto Schallner; Hans-Georg Schwarz
Original assignee: Bayer AG
Current assignee: Bayer CropScience AG
Priority date: 1999-06-26
Filing date: 2000-06-13
Publication date: 2002-04-10
Also published as: DE19929348A1; CN1358176A; BR0012451A; HK1047932A1; MXPA01013263A; JP2003503396A; WO2001000595A1; IL146662A0; AU5532500A

Abstract

The invention relates to a novel method for the production of 2-heterocyclyl methyl benzoic acid derivatives of general formula (I), wherein n, X and Z have the meaning cited in the description, providing good yields and high purity. The invention is characterized in that phthalide of general formula (II), wherein n and X have the meaning cited in the description, is reacted with nitrogen heterocycles of general formula (III): H-Z, wherein Z has the meaning cited in the description, or with nitrogen heterocycle metal salts of general formula (II) in the presence of an aprotic polar diluent and optionally in the presence of a basic auxiliary reaction agent.

Description

Process for the preparation of 2-heterocyclylmethyI-benzoic acid derivatives

The invention relates to a new process for the preparation of 2-heterocyclyl-methyl-benzoic acid derivatives, which as intermediates for the preparation of

Active ingredients for pharmaceutical and agricultural applications can be used.

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

However, it is also known that the reaction of phthalides with arylalkylamines does not give the 2-arylalkylaminomethylbenzoic acids to be expected in the same course of the reaction, but N-arylalkyl-2-hydroxymethylbenzamide derivatives (cf. Arch. Pharm. 318: 640-649 (1985).

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 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 phthalates of the general formula (II)

in which

n and X have the meaning given above,

with nitrogen heterocycles of the general formula (III)

H-Z (III)

in which

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 the general formula (1) can be obtained selectively in good yields and in high purity by the process according to the invention, although according to the prior art given above, the formation of N-heterocyclyl to a large extent as a side reaction -2-hydroxymethyl-benzamide derivatives was expected. The process according to the invention represents a technically well practicable route to 2-heterocyclylmethyl-benzoic acid derivatives based on phthalides which are easily accessible by known methods. The desired benzoic acid derivatives are immediately obtained when the ring is opened. i

The alternative synthesis via the reaction of 2-halomethyl benzoic acid esters with nitrogen heterocycles of the formula (II) requires the often complex and multi-stage synthesis of 2-methyl benzoic acid esters. The corresponding benzoic acids would have to be prepared by cleaving the esters, however

) not all other substituents are stable under the conditions of the ester cleavage.

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, each optionally substituted by halogen, Cj -C ^ alkoxy, C] -C4-alkylthio, C] -C4-alkylsulfinyl or -C-C4-alkylsulfonyl-substituted alkyl, alkoxy,

Alkylthio, alkylsulfinyl or alkylsulfonyl, each with up to 4 carbon atoms in the alkyl groups, or for alkylamino, dialkylamino or dialkylaminosulfonyl, each with up to 4 carbon atoms in the alkyl groups

Z preferably represents one of the heterocyclic group

in which the bond shown in dashed lines is a single bond or a double bond,

Q represents oxygen or sulfur,

Rl for hydrogen, hydroxyl, mercapto, cyano, halogen, for alkyl optionally substituted by cyano, halogen, C 1 -C 4 alkoxy, C] -C 4 alkylthio, C 1 -C 4 alkylsulfinyl or C 1 -C 4 alkylsulfonyl , 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, each optionally using halogen Substituted alkenyl, alkynyl, alkenyloxy, alkenylthio or alkenylamino, each having up to 6 carbon atoms in the alkenyl or alkynyl groups, for each cycloalkyl, cycloalkyloxy, cycloalkylthio optionally substituted by halogen.

Cycloalkylamino, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylalkylthio or cycloalkylalkylamino each having 3 to 6 carbon atoms in the cycloalkyl groups and optionally up to 4 carbon atoms in the alkyl part, or for each optionally by Halogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy substituted phenyl, phenyloxy, phenylthio, phenylamino, benzyl, benzyloxy, benzylthio or benzylamino, or - in the event that two adjacent radicals R ¹ and R ¹ are attached to a double bond are - together with the adjacent radical R ¹ also represents a benzo group, and

R ^ for hydrogen, hydroxy, A ino, alkylidene amino with up to 4 carbon atoms, for each optionally substituted by cyano, halogen or C _] -C4-alkoxy alkyl, alkoxy, alkylamino, dialkylamino or alkanoylamino each with up to 6 carbon atoms in the alkyl groups, each for alkenyl, alkynyl or alkenyloxy optionally substituted by halogen, each having up to 6 carbon atoms in the alkenyl or alkynyl groups, for cycloalkyl, cycloalkylalkyl or cycloalkylamino, each 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, C1-C4-alkyl or Cj-C4-alkoxy, or together with an adjacent radical R ^ or R ^ for optionally by halogen or Cj -C4-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 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-propylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl or ethylsulfonyl substituted methyl, ethyl, n- or i-propyl, n-, i-, s - or t-butyl, for methoxy, ethoxy, n- or i-propoxy optionally substituted by fluorine and / or chlorine, methoxy, ethoxy, n- or i-propoxy, for methylthio optionally substituted by fluorine and / or chlorine, Ethylthio, n- or i-propylthio, methylsulfinyl, ethylsulfinyl, n- or i-propylsulfinyl, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl, or for methylamino, ethylamino, n- or i-propylamino, dimethylamino, diethylamino, Dime hylaminosulfonyl or diethylaminosulfonyl.

particularly preferably represents one of the following heterocyclic

groups

in which the bond shown in dashed lines is a single bond or a double bond,

Q represents oxygen or sulfur.

R '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, ethylsulfinyl, n- or i -Propylsulfinyl, methylsulfonyl, ethylsulfonyl, n- or i- propylsulfonyl substituted methyl, ethyl, n- or i-propyl, n-, i-, 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-butylamino, dimethylamino, diethylamino, di-n-propylamino or di-i-propylamino, each optionally with fluorine and / or chlorine-substituted ethenyl, propenyl, butenenyl, ethynyl, propynyl, butynyl, propenyloxy, butenyloxy, propenylthio, butenylthio, propenylamino or butenylamino, for each cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyloxy, cyclohexyl, cyclopropyloxy, optionally substituted by fluorine and / or chlorine , Cyclopentyloxy, Cyclohexyloxy, Cyclopropylthio, Cyclobutylthio, Cyclopentylthio, Cyclohexylthio, Cyclopropylamino, Cyclobutylamino, Cyclopentylamino, Cyclohexylamino, Cyclopropylmethyl, Cyclobutylmethyl, Cyclopentylmethyl, Cyclohexylmethyl, Cyclopropylmethyl, Cyclopropylmethyl xy, cyclopentylmethoxy, cyclohexylmethoxy, cyclo propylmethylthio, Cyclobutylmethylthio, Cyclopentylmethylthio, cyclohexylmethylthio, cyclopropylmethylamino, cyclobutylmethyl amino, cyclopentylmethylamino or cyclohexylmethylamino, or represents in each case optionally substituted by fluorine, 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, or - in the event that two adjacent radicals R and R are on a double bond - together with the adjacent radical R ¹ also for one

Benzo grouping stands, and R ^ 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, for each optionally substituted by fluorine and / or chlorine, ethenyl, propenyl, ethynyl, propynyl or propenyloxy, for each optionally substituted by fluorine and / or chlorine, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl , Cyclobutylmethyl, 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 Rl or R ^ each represents propane-1,3-diyl (trimethylene), butane which is optionally substituted by methyl and / or ethyl

1,4-diyl (tetramethylene) or pentane-1,5-diyl (pentamethylene is

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.

very particularly preferably represents one of the following heterocyclic

groups

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

Among the very particularly 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-l (3H) -one and l-oxo-2 (1H) - phthalazine are used as starting materials, the course of the reaction can be carried out in accordance with the invention

Procedures can be outlined by the following formula scheme:

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

The nitrogen heterocycles of the general formula (III) which are further required as starting materials in the process according to the invention are largely known synthetic chemicals.

As the metal salts of the nitrogen heterocycles of the general formula (III), in particular the alkali metal and alkaline earth metal salts, such as the lithium, sodium, rubidium, cesium, magnesium, calcium and barium salts, very particularly preferably the sodium and potassium salts of these compounds become.

The process according to the invention for the preparation of the compounds of the general

Formula (I) is carried out using an aprotic polar diluent. These include in particular ethers such as diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl or diethyl ether; Ketones such as acetone, butanone, methyl isopropyl ketone or methyl isobutyl ketone; Nitriles such as acetonitrile, propionitrile or butyronitrile; Amides such as N, N-dimethylformamide,

N, N-dimethylacetamide, N-methyl-formanilide, N-methyl-pyrrolidone or hexamethylphosphoric triamide; Esters such as methyl acetate or ethyl acetate, sulfoxides such as dimethyl sulfoxide, and sulfones such as tetramethylene sulfone (sulfolane).

Ketones, such as methyl isobutyl ketone, and amides, such as N, N-dimethyl formamide and N, N-dimethyl acetamide, 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 carried out using a basic reaction auxiliary. As a reaction aid for the process according to the invention the usual inorganic or organic bases or acid acceptors are generally suitable. These preferably include alkali metal or alkaline earth 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 methoxide, ethanolate, n or i-propanolate, n, i, s or t-butanolate; also basic organic nitrogen compounds, such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyl diisopropylamine, N, N-dimethylcyclohexylamine, dicyclohexylamine, ethyldicyclohexylamine, N, N-dimethylaniline, 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 very particularly preferred as basic reaction auxiliaries.

The reaction temperatures can be varied within a substantial range when carrying out the process according to the invention. In general, 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. 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 carry out the process according to the invention, 1 mole of phthalide of the general formula (II) is generally between 0.8 and 1.2 mole, preferably between 0.95 and 1.05 mole, of nitrogen heterocycle of the general formula (III) or a salt of this one.

In a preferred embodiment, the reaction components are mixed at room temperature or with 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. For example, the mixture is concentrated under reduced pressure, the residue is washed with an organic solvent which is practically immiscible with water, then in

Water taken up, precipitated by adding a strong acid, such as hydrochloric acid, and isolated by suction (see. The preparation examples).

The 2-heterocyclylmethylbenzoic acid derivatives of the general formula (I) to be prepared by the process according to the invention can be used as intermediates for

Production of active ingredients for pharmaceutical and agricultural applications can be used (see. Arzneimittelforschung 27 (1977), 2364-2368 - cited in Chem. Abstracts 88: 98893; GB-A-1427408; DE-A-19833360).

Preparation Examples:

example 1

10.0 g (60 mmol) of 4-methyl-5-trifluoromethyl-2,4-dihydro-3H-l, 2,4-triazol-3-one are 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 dried at 80 ° C. under reduced pressure.

1.03 g (5 mmol) of the potassium salt of 4-methyl-5-trifluoromethyl-2,4-dihydro-3H-l, 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-dimethylformamide and the reaction mixture is heated under reflux for 8 hours. It is then concentrated in a water jet vacuum, 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-lH-l, 2,4-triazol-l -yl are obtained ) -mefhyl] -benzoic acid with a melting point of 132 ° C.

Η NMR (CDCh, δ): 3.46 (s), 5.59 (s), 7, 1 1 (d), 7.41 (t), 7.55 (t), 8.1 1 ( 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 is used to stir the mixture 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. It is then 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-l, 2,4-triazol-1-yl) methyl are obtained ] -benzoic acid with a melting point of 122 ° C.

Η NMR (CDC1 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, it is also possible, for example, to prepare the compounds of the general formula (I) listed in Table 1 below.

Table 1: Examples of the compounds that can be produced according to the invention

Claims

Patentansprtiche

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 stands for nitro, cyano, carbamoyl, thiocarbamoyl, halogen, or for optionally substituted alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino or dialkylaminosulfonyl, and

Z represents heterocyclyl bound via N (nitrogen),

characterized in that phthalates 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) -

2. The method according to claim 1, characterized in that the reaction 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 in each case optionally substituted by halogen, C] -C4-alkoxy, C] -C4-alkylthio, -C-C4-alkylsulfinyl or Cι-C4-alkylsulfonyl-substituted alkyl, alkoxy, alkylthio, Alkylsulfinyl or alkylsulfonyl each having up to 4 carbon atoms in the alkyl groups, or represents alkylamino, dialkylamino or dialkylaminosulfonyl each having up to 4 carbon atoms in the alkyl groups,

Z for one of the heterocyclic groupings below

stands, in each case in which the dashed bond is 5 a single bond or a double bond, and

Q represents oxygen or sulfur,

Rl for hydrogen, hydroxy, mercapto, cyano, halogen, for 10 each optionally by cyano, halogen, Cj-C4-alkoxy,

C1-C4- alkylthio, -C -C alkyl sulfinyl or C1 -C4 alkylsulfonyl substituted alkyl, alkylcarbonyl, alkoxy, alkoxycarbonyl, alkylthio, alkylsulfinyl or alkylsulfonyl each having up to 6 carbon atoms in the alkyl groups, for 15 each optionally substituted by halogen Alkylamino or dialkylamino, each having up to 6 carbon atoms in the alkyl groups, for alkenyl, alkynyl, alkenyloxy, alkenylthio or alkenylamino each having up to 6 carbon atoms in the alkenyl or alkynyl groups, each optionally substituted by halogen halogen-substituted cycloalkyl, cycloalkyloxy, cycloalkylthio, cycloalkylamino, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylalkylthio or cycloalkylalkylamino 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, 5 benzylthio or benzylamino optionally substituted by halogen, C1-C4-alkyl or C1-C4-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

10 R2 for hydrogen, hydroxy, amino, alkylidene amino with up to

4 carbon atoms, each for alkyl, alkoxy, alkylamino, dialkylamino or alkanoylamino, each optionally substituted by cyano, halogen or C1-C4alkoxy, each having up to 6 carbon atoms in the alkyl groups, each for

15 also alkenyl, alkynyl or substituted by halogen

Alkenyloxy, each with up to 6 carbon atoms in the alkenyl or alkynyl groups, for cycloalkyl, cycloalkylalkyl or cycloalkylamino, each optionally substituted by halogen, with 3 to 6 carbon atoms in each

20 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, C1-C4-alkyl or C1-C4-alkoxy, or together with an adjacent radical Rl or R ^ for optionally by halogen or

25 C1-C4-alkyl-substituted alkanediyl having 3 to 5 carbon atoms,

where the individual radicals R and R ^~ - insofar as several of them are bonded to the same heterocyclic groupings, the same or

Can have 30 different meanings within the scope of the above definition. Method according to one of claims 1 to 3, characterized in that

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, ethylsulfinyl, n- or i-propylsulfinyl, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl, or represents methylamino, ethylamino, n- or i-propylamino, dimethylamino, diethylamino, dimethylaminosulfonyl or diefhylaminosulfonyl,

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,

5

R1 for hydrogen, hydroxyl, 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-

10 butylthio, methylsulfinyl, ethylsulfinyl, n- or i-propylsulfinyl, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl-substituted methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl , Methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy, methylthio, ethylthio, n- or i-propylthio, n-,

15 i-, s- or t-butylthio, methylsulfinyl, ethylsulfinyl, n- or i-

Propylsulfinyl, 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- i-propylamino, for

20 Ethenyl, propenyl, butenenyl, ethynyl, propynyl, butynyl, propenyloxy, butenyloxy, propenylthio, butenylthio, propenylamino or butenylamino, each optionally substituted by fluorine and / or chlorine, for cyclopropyl, cyclo-

25 butyl, cyclopentyl, cyclohexyl, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio, cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, cyclobylylmethyl, cyclopropylmethyl

30 methyl, cyclohexylmethyl, cyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, cyclo- propylmethylthio, cyclobutylmethylthio, cyclopentylmethylthio, cyclohexylmethylthio, cyclopropylmethylamino, cyclobutylmethylamino, cyclopentylmethylamino or cyclohexylmethylamino, or for each optionally by fluorine, 5 chlorine, methyl, ethyl, n- or i-propyl, n-, i-, i-, i-, i-, i- t-butyl,

Methoxy, ethoxy, n- or i-propoxy substituted phenyl, phenyloxy, phenylthio, phenylamino, benzyl, benzyloxy, benzylthio or benzylamino, or - in the event that two adjacent radicals R ¹ and R ¹ are attached to a double bond are - together with the adjacent radical R ¹ also represents a benzo group, and

R ^ for hydrogen, hydroxy, amino, each optionally substituted by fluorine and / or chlorine, methoxy or ethoxy

15 ized methyl, ethyl, n- or i-propyl, n-, i- or s-butyl,

Methoxy, ethoxy, n- or i-propoxy, methylamino, ethylamino or dimethylamino, for each optionally substituted by fluorine and / or chlorine, ethenyl, propenyl, ethynyl, propynyl or propenyloxy, each optionally by

20 fluorine and / or chlorine substituted cyclopropyl, cyclobutyl,

Cyclopentyl, cyclohexyl, cyclopropylmefhyl, cyclobutylmethyl, 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

25 isopropoxy-substituted phenyl or benzyl, or together with an adjacent radical R * or R ^ each represents propane-1,3-diyl (trimethylene), butane-1,4-diyl (optionally substituted by methyl and / or ethyl) Tetramethylene) or pentane-1,5-diyl (pentamethylene is where the individual radicals R ¹ and R ² — insofar as several of them are bonded to the same heterocyclic groupings — can have the same or different meanings in the context of the above definition.