WO1997033876A1

WO1997033876A1 - Process for producing substituted aromatic thiocarboxylic acid amides

Info

Publication number: WO1997033876A1
Application number: PCT/EP1997/001061
Authority: WO
Inventors: Heinz-Jürgen Wroblowsky; Rudolf Thomas
Original assignee: Bayer Aktiengesellschaft
Priority date: 1996-03-14
Filing date: 1997-03-03
Publication date: 1997-09-18
Also published as: DE19610786A1; EP0888314A1; IL126098A0; AU2094997A; HUP9902109A2; JP2000506177A; BR9708186A; CZ293098A3

Abstract

A novel process makes it possible to produce substituted aromatic thiocarboxylic acid amides of general formula (I) in which R?1, R2, R3¿ and Z have the meanings given in the description, by reacting substituted aromatic nitriles of formula (II) with thioacetic acid, possibly in the presence of a diluent and of a catalyst at temperatures between 0 and 150 °C.

Description

Process for the production of substituted aromatic thiocarboxylic acid amides

The invention relates to a new process for the preparation of substituted aromatic thiocarboxamides, which are known as herbicidally active compounds.

It is known that thiocarboxamides can be obtained by reacting nitriles with an alcoholic solution of an alkali metal hydrogen sulfide or ammonium hydrogen sulfide under elevated pressure (cf. Justus Liebigs

Ann. Chem. 421 (1923), 201-205). The disadvantage of this synthesis method for implementation on an industrial scale is the increased pressure required.

It is also known that thiocarboxamides by reacting nitriles with

Hydrogen sulfide in pyridine in the presence of a strong base, e.g. Triethylamine, can be synthesized (see. J. Chem. Soc. 1952. 742-744). The work-up is carried out by pouring the reaction mixture into water and suction. A disadvantage of this method is the occurrence of an aqueous mother liquor containing pyridine and auxiliary base, from which the organic

Components can only be separated in a relatively complex process.

It is also known that thiocarboxamides can also be obtained by reacting nitriles with thioacetamide in the presence of gaseous hydrogen chloride (hydrogen chloride) in dimethylformamide (cf. J. Am. Chem. Soc. £ 2

(1960), 2656-2657). With this method, however, the need to use gaseous hydrogen chloride is unfavorable for the technical feasibility.

It is also known that thiocarboxamides can be obtained by reacting nitriles with thioacetic acid (cf. Chem. Ber. 4 & (1915),

470-473; loc. cit. 22: 910-916 (1959); Acta Chem. Scand. 4 & (1994), 372-376). However, this implementation is very slow and often incomplete, i.e. even with unsatisfactory yields. Better results are reported after working with boron trifluoride etherate or aluminum trichloride as catalyst, if appropriate with exposure to light (cf. Phosphorus, Sulfur, and Silicon 95-96 (1994),

325-326). The high amounts of catalyst, the solvents used and the exposure that may have to be carried out, however, is unfavorable for a technical process.

It is also known that certain substituted aromatic thiocarboxamides by reacting corresponding substituted aromatic nitriles with

Hydrogen sulfide (hydrogen sulfide, H ₂ S) or with thioacetamide can be produced (cf. WO 95/30661). For working up, the mixture is concentrated under reduced pressure and the product remaining in the residue is obtained in crystalline form by treatment with aqueous hydrochloric acid and / or with a suitable organic solvent. Here too, the problem of recovering the organic reaction components remains unsolved.

It has now been found that substituted aromatic thiocarboxamides of the general formula (I)

in which

R ^{1 represents} hydrogen or halogen,

R ^{2 represents} the grouping below,

-A ^ -A ³

woπn

A ¹ for a single bond, for oxygen, sulfur, -SO-, -SO ₂ -,

-CO- or the grouping -NA ⁴ -, wherein A ^{4 stands} for hydrogen, hydroxy, alkyl, alkoxy, aryl, alkylsulfonyl or arylsulfonyl, or (A ¹ ) for optionally substituted alkanediyl. Alkenediyl, alkindiyl, cycloalkanediyl, cycloalkendiyl or arendiyl, A ^{2 represents} a single bond, oxygen, sulfur, -SO-, -SO ₂ -, -CO- or the grouping -NA ⁴ -, wherein A ⁴ represents hydrogen, hydroxy, alkyl, aryl, alkoxy, alkylsulfonyl or Arylsulfonyl, or (A ² ) stands for optionally substituted alkanediyl, alkenediyl, alkynediyl, cycloalkanediyl, cycloalkenediyl or arendiyl, and

A ³ for hydrogen, hydroxy, amino, cyano, isocyano, thiocyanato,

Nitro, carboxy, carbamoyl, thiocarbamoyl, sulfo, chlorosulfonyl, halogen or for each optionally substituted alkyl,

Alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, alkoxycarbonyl, dialkoxy (thio) phosphoryl, alkenyl, alkenyloxy, alkenylamino, alkylidenamino, alkenyloxycarbonyl, alkynyl, alkynyloxy, alkynylamino, alkynyloxycarbonyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl amino, cycloalkyloxycarbonyl, cycloalkylalkoxycarbonyl, aryl, aryloxy, arylalkyl, arylalkoxy, aryloxycarbonyl, arylalkoxycarbonyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkoxy or heterocyclylalkoxycarbonyl,

R ^{3 represents} hydrogen, halogen or together with R ^{2 represents} an alkanediyl or an alkenediyl group, which may be at the beginning (or

End) or an oxygen atom within the hydrocarbon chain

Contains sulfur atom, an NH group, an N-alkyl group, a carbonyl group and / or a thiocarbonyl group, and

Z represents in each case optionally substituted monocyclic or bicyclic, saturated or unsaturated heterocyclyl, heterocyclylamino or heterocycliclimino,

obtained in very good yields and in high purity if substituted aromatic nitriles of the general formula (II)

in which

R ¹ , R ² . R ³ and Z have the meanings given above,

with thioacetic acid (CH ₃ -CO-SH) if appropriate in the presence of a diluent and if appropriate in the presence of a catalyst at temperatures between 0 ° C. and 150 ° C.

Surprisingly, aromatic thioamides of the general formula (I) which have been substituted by the process according to the invention can be described in considerably higher yields than hitherto and can be obtained in very good quality, it being possible to use inexpensive and technically manageable catalysts and diluents and the work-up and Isolation of the reaction products in a very simple manner - generally by simple suction - is possible.

The method according to the invention thus represents a valuable enrichment of the prior art.

The process according to the invention preferably relates to the preparation of compounds of the formula (I) in which

R ^{1 represents} hydrogen, fluorine, chlorine or bromine,

R represents the grouping below,

-A ^ -A ³

in which

A ^{1 stands} for a single bond, for oxygen, sulfur, -SO-, -SO ₂ -, -CO- or the grouping -NA ⁴ -, in which A ^{4 stands} for water toff, hydroxy, C, -C ₄ alkyl, C, -C ₄ alkoxy, phenyl, C, -C ₄ alkyl sulfonyl or phenyl sulfonyl, or (A ¹ ) for each optionally substituted by fluorine or chlorine C, -C ₆ -alkanediyl, C ₂ -C ₆ - alkenediyl, C ₂ -C ₆ alkynediyl, C ₃ -C ₆ -cycloalkanediyl, C ₃ -C ₆ -cycloalkyl is alkenediyl or phenylene,

A ^{2 represents} a single bond, represents oxygen, sulfur, -SO-, -SO ₂ -, -CO- or the grouping -NA ⁴ -, wherein A ⁴ represents hydrogen, hydroxy, C, -C ₄ alkyl, C, -C ₄ -alkoxy, phenyl, C _r C ₄ -alkylsulfonyl or phenylsulfonyl, or (A ² ) for each optionally substituted by fluorine or chlorine substituted C _r C ₆ - alkanediyl, C ₂ -C ₆ - Alkenediyl, C ₂ -C ₆ , alkindiyl, C ₃ -C ₆ cycloalkanediyl, C ₃ -C ₆ cycloalkenediyl or phenylene,

A ³ for hydrogen, hydroxy, amino, cyano, isocyano, thiocyanato,

Nitro, carboxy, carbamoyl, thiocarbamoyl, sulfo, chlorosulfonyl, halogen, for alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, alkoxycarbonyl or dialkoxy (thio) phosphoryl, each optionally substituted by halogen or C 1 -C 4 alkoxy in each case 1 to 6 carbon atoms in the alkyl groups, for alkenyl, alkenyloxy, alkenylamino, alkylideneamino, alkenyloxycarbonyl, alkynyl, alkynyloxy, alkynylamino or alkynyloxycarbonyl each having 2 to 6 carbon atoms in the alkenyl, alkylidene or alkynyl groups, each optionally substituted by halogen for respectively optionally substituted by halogen, cyano, carboxy, Cι-C ₄ - alkyl and / or C, -C ₄ - alkylalkyl alkoxy-carbonyl-substituted cycloalkyl, cycloalkyloxy, cycloalkyl, cycloalkylalkoxy, Cycloalkylidenamino, cycloalkyloxy carbonyl or cycloalkylalkoxycarbonyl having 3 to 6 carbon atoms each in the cycloalkyl groups and optionally 1 to 4

Carbon atoms in the alkyl groups, or if appropriate by nitro, cyano, carboxy, halogen, C, -C ₄ alkyl, C _r C ₄ haloalkyl, C _r C ₄ alkyloxy, C, -C ₄ haloalkyloxy and / or C _j -C ₄ alkoxy-carbonyl substituted phenyl, phenyloxy, phenyl-C _] -C ₄ alkyl, phenyl-C _r C ₄ alkoxy, phenyloxycarbonyl or

Phenyl-C _] -C ₄ -alkoxycarbonyl, (in each case optionally fully or partially hydrogenated) pyrrolyl, pyrazolyl, imidazolyl, triazolyl, Furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, triazinyl, pyrazolyl-C, -C ₄ -alkyl, furyl-C, -C ₄ -alkyl, thienyl-C, -C _4- alkyl, oxazolyl-C, - C ₄ -alkyl, isoxazole-C _r C ₄ -alkyl, thiazole-C, -C ₄ -alkyl, pyridinyl-C _r C ₄ -alkyl, pyrimidinyl-C _r C ₄ -alkyl , Pyrazolylmethoxy, furylmethoxy, represents perhydropyranylmethoxy or pyridylmethoxy,

R ^{3 represents} hydrogen, fluorine, chlorine, bromine or together with R ^{2 represents} an alkanediyl or alkenediyl group, each having up to 4 carbon atoms, which may optionally be at the beginning (or end) or within the

Hydrocarbon chain contains an oxygen atom, a sulfur atom, an NH group, an NC _j -C ₄ alkyl group, a carbonyl group and / or a thiocarbonyl group, and

Z for each monocyclic or bicyclic, saturated or unsaturated

Heterocyclyl, heterocyclylamino or heterocyclylimino, each having 2 to 6 carbon atoms and 1 to 4 nitrogen atoms in the heterocyclic ring system, which optionally additionally contains an oxygen or sulfur atom and / or optionally up to three groups from the series -CO-, -CS-, -SO- and / or SO ₂ -, and which is optionally substituted by one or more groups from the series nitro, hydroxy, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, halogen, C _r C ₆ alkyl (which is optionally substituted by Halogen or C _j -C ₄ alkoxy is substituted), C ₂ -C ₆ alkenyl or C ₂ -C ₆ alkynyl (which are each optionally substituted by halogen), C, -C ₆ alkoxy or C, -C ₆ -

Alkoxy-carbonyl (which are each optionally substituted by halogen or C _] -C ₄ alkoxy), C ₂ -C ₆ alkenyloxy or C ₂ -C ₆ alkynyloxy (which are each optionally substituted by halogen), C _j -C ₆ - alkylthio, C ₂ -C ₆ alkenylthio or C ₂ -C ₆ alkynylthio (which are each optionally substituted by halogen), C _j -C ₆ alkylamino or DHC _j -

C ₄ alkyl) amino, C ₃ -C ₆ -cycloalkyl or C ₃ -C ₆ -cycloalkyl-C _r C ₄ -alkyl (which are in each case stituiert sub¬ optionally substituted by halogen and / or C _j -C ₄ alkyl ), Phenyl. Phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl or phenylamino (each of which may be nitro, cyano, halogen, C _r C ₄ alkyl, C _r C ₄ haloalkyl, C _r C ₄ alkyloxy, C _r C ₄ -

Haloalkyloxy and / or C, -C ₄ alkoxy-carbonyl are substituted). The process according to the invention relates in particular to the preparation of compounds of the formula (I) in which

R ^{1 represents} hydrogen, fluorine or chlorine,

R ^{2 represents} the grouping below,

-A'-A ² -A ³

in which

A ^{1 stands} for a single bond, for oxygen, sulfur, -SO-, -SO ₂ -, -CO- or the grouping -NA ⁴ -, wherein A ^{4 stands} for hydrogen, hydroxy, methyl, ethyl, n- or i Propyl, methoxy, ethoxy, n- or i-propoxy, methylsulfonyl or ethylsulfonyl, or

(A ^ for methylene, ethane-l, l-diyl, ethane-l, 2-diyl, propane-l, l-diyl, propane-l, 2-diyl, propane-l, 3-diyl, ethene-l, 2-diyl, propene-1,2-diyl, propene-1,3-diyl, ethyne-1,2-diyl or propyne-1,3-diyl,

A ² for a single bond, for oxygen, sulfur, -SO-, -SO ₂ -,

-CO- or the grouping -NA ⁴ -, where A ⁴ represents hydrogen, hydroxy, methyl, ethyl, n- or i-propyl, methoxy, ethoxy, n- or i-propoxy, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl or phenylsulfonyl, or (A ² ) is methylene, ethane-1,1-diyl, ethane-1,2-diyl, propane-1,1-diyl, propane-1,2-diyl, Propane-

1,3-diyl, ethene-1,2-diyl, propene-1,2-diyl, propene-1,3-diyl, ethyne-1,2-diyl or propyne-1,3-diyl,

A ³ for hydrogen, hydroxy, amino, cyano, nitro, carboxy, carbamoyl, sulfo, fluorine, chlorine, bromine, for each methyl, ethyl, n- or i-propyl optionally substituted by fluorine, chlorine, methoxy or ethoxy, n- , i-, s- or t-butyl, n-, i-, s- or t-pentyl, methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy, n- , i-, s- or t-pentyloxy, methylthio, ethylthio, n- or i-propylthio, n-, i-, s- or t-butylthio, methylsulfinyl, ethylsulfinyl, n- or i-propylsulfinyl, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl, methylamino, ethylamino, n- or i-propylamino, - o -

n-, i-, s- or t-butylamino, dimethylamino, diethylamino, methoxycarbonyl, ethoxycarbonyl, n- or i-propoxycarbonyl, dimethoxyphosphoryl, diethoxyphosphoryl, dipropoxyphosphoryl or diisopropoxyphosphoryl, for propenyl, butenyl, propenyl, each optionally substituted by fluorine or chlorine

Butenyloxy, propenylamino, butenylamino, propylidene amino, butylidene amino, propenyloxycarbonyl, butenyloxycarbonyl, propynyl, butinyl, propynyloxy, butynyloxy, propynylamino, butynylamino, propynyloxycarbonyl or butynyloxycarbonyl, each optionally with fluorine, chlorine, cyano, carboxy, methyl, ethyl or i-propyl, methoxycarbonyl or ethoxycarbonyl-substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclo-propylmethoxy, cyclo-propylmethoxy , Cyclohexylmethoxy, Cyclopentylidenamino, Cyclohexylidenamino, Cyclopentyloxycarbonyl, Cyclohexyloxycarbonyl, Cyclopentylmethoxycarbonyl or Cyclohexylmethoxycarbonyl, or for each optionally by nitro, cyano, carboxy, fluorine, chlorine, bromine, methyl, ethyl, n- or i-propyl, trifluoromethyl,

Methoxy, ethoxy, n- or i-propoxy, difluoromethoxy, trifluoromethoxy, methoxycarbonyl and / or ethoxycarbonyl substituted phenyl, phenyloxy, benzyl, phenylethyl, benzyloxy, phenyloxycarbonyl, benzyloxycarbonyl, (each optionally fully or partially hydrogenated) pyrrolyl, pyrazolyl , Imidazolyl, triazolyl,

Furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, triazinyl, pyrazolylmethyl, furylmethyl, thienylmethyl, oxazolylmethyl, isoxazolmethyl, thiazolmethyl, pyridylmethyl, pyridylmethyl, pyridylmethyl, pyridylmethyl, pyridylmethyl, pyridylmethyl, pyridinylmethyl ,

for hydrogen. Fluorine, chlorine or together with R ^{2 represents} an alkanediyl or alkenediyl grouping each having 1 to 3 carbon atoms, which optionally has an oxygen atom, a sulfur atom, an NH-- at the beginning (or end) or within the hydrocarbon chain.

Grouping, an N-methyl group, a carbonyl group and / or a thiocarbonyl group, and Z for each monocyclic or bicyclic, saturated or unsaturated

Heterocyclyl, heterocyclylamino or heterocyclylimino each having 2 to 5 carbon atoms and 1 to 3 nitrogen atoms in the heterocyclic ring system, which optionally additionally contains an oxygen or sulfur atom and / or optionally up to two groups from the

Contains -CO-, -CS-, -SO- and / or SO ₂ -, and which is optionally substituted by one or more groups from the series nitro, hydroxy, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, fluorine, chlorine , Bromine; Methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl (which are optionally substituted by fluorine, chlorine, methoxy or ethoxy); Propenyl, butenyl, propynyl or butynyl (which are each optionally substituted by fluorine or chlorine); Methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy, methoxycarbonyl or ethoxycarbonyl (which are each optionally substituted by fluorine, chlorine, methoxy or ethoxy); Propenyloxy, butenyloxy, propynyloxy or

Butynyloxy (which are optionally substituted by fluorine or chlorine); Methylthio, ethylthio, n- or i-propylthio, n-, i-, s- or t-butylthio, propenylthio, butenylthio, propynylthio or butynylthio (which are each optionally substituted by fluorine or chlorine); Methylamino, ethylamino, n- or i-propylamino, n-, i-, s- or t-butylamino,

Dimethylamino or diethylamino; Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl or cyclohexylmethyl (which are each optionally substituted by fluorine, chlorine, methyl, ethyl, n- or i-propyl), phenyl, phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl or Phenylamino (which in each case optionally by nitro, cyano, fluorine, chlorine, bromine, methyl, ethyl, n- or i-propyl, trifluoromethyl, methoxy, ethoxy, n- or i-propoxy, difluoromethoxy, trifluoromethoxy, methoxycarbonyl or Are substituted ethoxycarbonyl).

For example, 2- (2-fluoro-4-cyano-5-methoxy-phenyl) -4-methyl-5-difluoromethyl-2,4-dihydro-3H-1, 2,4-triazol-3-one and thioacetic acid are used as starting materials, the course of the reaction in the process according to the invention can be outlined using the following formula: 97/33876 1 * C 1 / I! .1 * »// W1U0J

- 10 -

Formula (II) provides a general definition of the substituted aromatic nitriles to be used as starting materials in the process according to the invention for the preparation of the compounds of the general formula (I). In formula (II), R ¹ , R ² , R ³ and Z preferably or in particular have those meanings which have already been mentioned above in connection with the description of the compounds of the formula (I) as preferred or as particularly preferred for R ¹ , R ² , R ³ and Z were given.

The starting materials of the formula (II) are known and / or can be prepared by known processes (cf. EP 370 332; EP 597 360; EP 609 734; EP 648 749).

The thioacetic acid to be used in the process according to the invention is a known synthetic chemical.

The process according to the invention for the preparation of substituted aromatic thiocarboxamides is preferably carried out in the presence of a diluent. Non-polar or moderately polar organic solvents are particularly suitable as diluents. These include in particular aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, gasoline, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, methylcyclohexane, dichloromethane, chloroform, carbon tetrachloride; Ethers, such as diethyl ether, diisopropyl ether, diisobutyl 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 n- or i-butyronitrile; Esters such as methyl acetate, ethyl acetate, n- or i-propyl ester, n-, i- or s-butyl ester.

Toluene is particularly preferably used as the solvent in the process according to the invention. The process according to the invention is optionally carried out in the presence of a catalyst. Protonic acids are preferably used as catalysts. These include in particular mineral acids, such as. Hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen iodide or sulfuric acid, but also organic acids, such as acetic acid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid.

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 150 ° C, preferably between 30 ° C and

120 ° C, especially between 50 ° C and 100 ° C.

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

To carry out the process according to the invention, generally 1 to 10 mol, preferably 1.5 to 5.0 mol, in particular 2.0 to 4.0 mol, of thioacetic acid and ge are used per mol of substituted aromatic nitrile of the formula (II) optionally 0.1 to 2.0 mol, preferably 0.2 to 1.0 mol, of a catalyst.

In general, the substituted aromatic nitrile and the thioacetic acid - optionally together with a catalyst - are mixed in a suitable solvent, and the mixture is then - preferably at elevated

Temperature - stirred until the end of the reaction.

Working up can be carried out in the usual way. In most cases, the product is obtained directly from the reaction mixture in crystalline form and can be isolated by suction.

The substituted aromatic thiocarboxamides of the formula (I) to be prepared by the process according to the invention are already known as herbicidally active compounds (cf. WO 95/30661). Her _$ teHunt.sbeispje | e;

example 1

10.0 g (25.4 mmol) of 2- (2-fluoro-4-cyano-5-ethylsulfonylaminophenyl) -4-methyl-5-trifluoromethyl-2,4-dihydro-3H-l, 2,4- triazol-3-one are suspended in 50 ml of toluene, and after the addition of 7.2 ml (0.1 mol) of thioacetic acid, the mixture is heated to about 80 ° C. for about 15 hours. After removing the heating source, the mixture is allowed to cool slowly to room temperature (approx. 20 ° C) and the crystalline product is isolated by suction.

9.4 g (96.1% product, ie 83.2% of theory) of 2- (2-fluoro-4-thio-carbamoyl-5-ethylsulfonylamino-phenyl) -4-methyl-5-trifluoromethyl- 2,4-dihydro-3H-l, 2,4-triazol-3-one with a melting point of 202 ° C.

After concentrating the mother liquor to about half the volume, another 3.2 g of 40.9% product (i.e. 9.4% of theory) are obtained.

Total yield: 92.6% of theory.

Example 2

10.0 g (25.4 mmol) of 2- (2-fluoro-4-cyano-5-ethylsulfonylamino-phenyl) -4-methyl-5-trifluoromethyl-2,4-dihydro-3H-l, 2,4-triazole 3-ones are suspended in 50 ml of toluene, and after adding 4.2 g (0.56 mol) of thioacetic acid and 1.2 g (125 mmol) of methanesulfonic acid, the mixture is brought to about 80 ° C. for about 15 hours heated. After removing the heating source, the mixture is allowed to cool slowly to room temperature (approx. 20 ° C) and the crystalline product is isolated by suction.

10.0 g (94.9% product, ie 92.2% of theory) of 2- (2-fluoro-4-thio-caamoyl-5-ethylsulfonylamino-phenyl) -4-methyl-5-trifluoromethyl- 2,4-dihydro-3H-l, 2,4-triazol-3-one with a melting point of 202 ° C.

Example! 3

10.0 g (25.4 mmol) of 2- (2-fluoro-4-cyano-5-ethylsulfonylaminophenyl) -4-methyl-5-trifluoromethyl-2,4-dihydro-3H-l, 2,4- triazol-3-one are suspended in 50 ml of toluene, and after adding 4.4 ml (0.75 mol) of thioacetic acid, the mixture is heated to approximately 80 ° C. At this temperature, approx. 2 g (0.5

Mol) hydrogen chloride (hydrogen chloride) is introduced and the mixture is then stirred for about 15 hours at about 80 ° C. After removing the heating source, the mixture is allowed to cool slowly to room temperature (approx. 20 ° C.) and the crystalline product is isolated by suction.

10.4 g (98.2% product, ie 96.3% of theory) of 2- (2-fluoro-4-thio-carbamoyl-5-ethylsulfonylamino-phenyl) -4-methyl-5-trifluoromethyl- 2,4-dihydro-3H-l, 2,4-triazol-3-one with a melting point of 202 ° C.

Example 4

A mixture of 10.0 g (23.8 mmol) of 1- (4-cyano-5-ethylsulfonylamino-2-fluorophenyl) -3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl -1 (2H) -pyrimidine, 7.24 g (95 mmol) of thioacetic acid, 1.14 g (12 mmol) of methanesulfonic acid and 50 ml of toluene is stirred at 80 ° C. for about 15 hours. After cooling to room temperature (approx. 20 ° C), the crystalline product is isolated by suction.

10.5 g (93.5%, ie 91% of theory) of 1- (5-ethylsulfonylamino-2-fluoro-4-thiocarbamoyl-phenyl) -3,6-dihydro-2,6-dioxo-3 are obtained -methyl-4-trifluoromethyl-l (2H) -pyrimidine with a melting point of 208 ° C.

Claims

claims

1. Process for the preparation of substituted aromatic thiocarboxamides of the general formula (I)

in which

R ^{1 represents} hydrogen or halogen,

R represents the grouping below,

-A'-A ² -A ³

wherein

A ^{1 represents} a single bond, oxygen, sulfur, -SO-, -SO ₂ -, -CO- or the grouping -NA ⁴ -, wherein A ^{4 represents} hydrogen, hydroxy, alkyl, alkoxy, aryl, alkyl sulfonyl or Arylsulfonyl, or (A ¹ ) stands for optionally substituted alkanediyl, alkenediyl, alkindiyl, cycloalkanediyl, cycloalkenediyl or arendiyl,

A ² for a single bond, for oxygen, sulfur, -SO-,

-SO ₂ -, -CO- or the grouping -NA ⁴ -, in which A ^{4 stands} for hydrogen, hydroxy, alkyl, aryl, alkoxy, alkyl sulfonyl or aryl sulfonyl, or (A ² ) for alkanediyl which is optionally substituted , Alkenediyl, alkindiyl, cycloalkanediyl, cycloalkendiyl or arendiyl, and

A ³ for hydrogen, -hydroxy, amino, cyano, isocyano, thiocyanato, nitro, carboxy, carbamoyl, thiocarbamoyl, sulfo, Chlorosulfonyl, halogen or for each optionally substituted alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, alkoxy carbonyl, dialkoxy (thio) phosphoryl, alkenyl, alkenyloxy, alkenylamino, alkylidenamino, alkenyloxycarbonyl, alkynyl, alkynyloxy ,

Alkynylamino, alkynyloxycarbonyl, cycloalkyl, cycloalkyloxy, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylidene amino, cycloalkyloxycarbonyl, cycloalkylalkoxycarbonyl, aryl, aryloxy, arylalkyl, arylalkoxy, aryloxycarbonyl, arylalkoxycarbonyl, heterocyclyl, heterocyloxycyclyllyloxycylyloxycarbonylcyloxycarbonylcyloxycarbonylcyloxycarbonylcyloxycarbonylcyloxycarbonylcyloxycarbonylcyloxycyclylloxycyclylloxy

R ^{3 represents} hydrogen, halogen or together with R ^{2 represents} an alkanediyl or an alkenediyl group, which may be at the beginning (or end) or within the hydrocarbon chain

Contains oxygen atom, a sulfur atom, an NH group, an N-alkyl group, a carbonyl group and or a thiocarbonyl group, and

Z represents in each case optionally substituted monocyclic or bicyclic, saturated or unsaturated heterocyclyl, heterocyclylamino or heterocyclylimino,

characterized in that substituted aromatic nitriles of the general formula (II)

in which

R ¹ , R ² , R ³ and Z have the meanings given above, with thioacetic acid (CH ₃ -CO-SH) if appropriate in the presence of a diluent and if appropriate in the presence of a catalyst at temperatures between 0 ° C. and 150 ° C.

Process according to Claim 1, characterized in that substituted aromatic nitriles of the formula (II) are used in which

R ^{1 represents} hydrogen, fluorine, chlorine or bromine,

R ^{2 represents} the grouping below,

-A ^! -A ² -A ³

in which

A ^{1 represents} a single bond, represents oxygen, sulfur, -SO-, -SO ₂ -, -CO- or the grouping -NA ⁴ -, wherein A ^{4 represents} hydrogen, hydroxy, C ₁ -C ₄ alkyl, C _] -C ₄ -alkoxy, phenyl, C _j -C ₄ - alkylsulphonyl or phenylsulphonyl, or (A ¹⁾ in each case optionally sub¬ stituiertes by fluorine or chlorine C, -C ₆ - alkanediyl, C ₂ -C ₆ - alkenediyl, C ₂ -C ₆ alkynediyl, C ₃ -C ₆ cycloalkanediyl, C ₃ -C ₆ cycloalkenediyl or phenylene,

A ² for a single bond, for oxygen, sulfur, -SO-,

-SO ₂ -, -CO- or the grouping -NA ⁴ -, wherein A ^{4 is} hydrogen, hydroxy, C _r C ₄ alkyl, C _r C ₄ alkoxy, phenyl, C ₁ -C ₄ alkylsulfonyl or phenylsulfonyl group, or (A ²⁾ for each sub- stituiertes optionally substituted by fluorine or chlorine, C _r C ₆ - alkanediyl, C ₂ -C ₆ - alkenediyl, C ₂ -C ₆ Alkin¬ diyl, C ₃ -C ₆ -cycloalkanediyl Is C ₃ -C ₆ cycloalkenediyl or phenylene,

A ³ for hydrogen, hydroxy, amino, cyano, isocyano, thiocyanato. Nitro, carboxy, carbamoyl, thiocarbamoyl, sulfo,

Chlorosulfonyl, halogen, for alkyl, alkoxy optionally substituted by halogen or C 1 -C ₄ -alkoxy, Alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkyl-a ino, alkoxy carbonyl or dialkoxy (thio) phosphoryl each having 1 to 6 carbon atoms in the alkyl groups, for alkenyl, alkenyloxy, alkenylamino, alkylideneamino, alkenyloxycarbonyl, optionally substituted by halogen, Alkynyl, alkynyloxy, alkynylamino or alkynyloxycarbonyl, each having 2 to 6 carbon atoms in the alkenyl, alkylidene or alkynyl groups, for each optionally by halogen, cyano, carboxy, C, -C ₄ -alkyl and / or C _j - C ₄ alkoxy-carbonyl substituted cycloalkyl,

Cycloalkyloxy, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylidenamino, cycloalkyloxycarbonyl or cycloalkylalkoxycarbonyl each having 3 to 6 carbon atoms in the cycloalkyl groups and optionally 1 to 4 carbon atoms in the alkyl groups, or for each optionally by nitro, cyano, carboxy, halogen, C. ₁ -C ₄ alkyl, C _] -C ₄ - haloalkyl, C _] -C ₄ alkyloxy, C, -C ₄ haloalkyloxy and / or C _j -C ₄ alkoxycarbonyl substituted phenyl, phenyloxy, phenyl-C _] -C ₄ alkyl, phenyl-C _j -C ₄ alkoxy, phenyloxycarbonyl or phenyl-C, -C ₄ alkoxycarbonyl,

(in each case fully or partially hydrogenated) pyrrolyl, pyrazolyl, imidazolyl, triazolyl, furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, triazinyl, pyrazolyl-C, -C ₄ -alkyl, fur C _r C ₄ alkyl, thienyl C _r C ₄ alkyl,

Oxazolyl-C _r C ₄ -alkyl, isoxazole-C _r C ₄ -alkyl, thiazole-C _j -C ^ alkyl, pyridinyl-C ₁ -C ₄ -alkyl, pyrimidinyl-C _r C ₄ -alkyl, pyrazolylmethoxy, furylmethoxy, represents perhydropyranyl methoxy or pyridyl methoxy,

represents hydrogen, fluorine, chlorine, bromine or together with R ^{2 represents} an alkanediyl or alkenediyl grouping each having up to 4 carbon atoms, which may optionally have an oxygen atom, a sulfur atom, at the beginning (or end) or within the hydrocarbon chain , an NH group, an NC, -C ₄ alkyl

Grouping, a carbonyl group and / or a thiocarbonyl group contains, and Z represents in each case monocyclic or bicyclic, saturated or unsaturated heterocyclyl, heterocyclylamino or heterocyclylimino each with 2 to 6 carbon atoms and 1 to 4 nitrogen atoms in the heterocyclic ring system, which optionally additionally has an oxygen or sulfur atom and or optionally up to three groups from the series -CO-, -CS-, -SO- and / or SO ₂ -, and which is optionally substituted by one or more groups from the series nitro, hydroxy, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, halogen , C _j -C ₆ alkyl (which is optionally substituted by halogen or C _j -C ₄ alkoxy), C ₂ -C ₆ alkenyl or C ₂ -C ₆ alkynyl (which in each case optionally by halogen are substituted), C, -C ₆ alkoxy or C, - C ₆ alkoxy-carbonyl (which are each optionally substituted by halogen or C _j -C ₄ alkoxy), C ₂ -C ₆ alkenyloxy or C ₂ - C ₆ - alkynyloxy (which each against are also substituted by halogen), C, -C ₆ -alkylthio, C ₂ -C ₆ -alkenylthio or C ₂ -C ₆ -alkynylthio (which are each optionally substituted by halogen), C _j -C ₆ - Alkylamino or di- (C, -C ₄ -alkyl) -amino, C ₃ -C ₆ -cycloalkyl or C ₃ -C ₆ -cycloalkyl-C _] -C ₄ -alkyl (which in each case by halogen and / or C, -C ₄ alkyl are substituted),

Phenyl, phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl or phenylamino (which in each case optionally by nitro, cyano, halogen, C, -C ₄ -alkyl, C, -C ₄ -haloalkyl, C _r C ₄ -alkyloxy, C _r C ₄ - Haloalkyloxy and / or C _j -C ₄ alkoxy-carbonyl are substituted).

R ^{1 represents} hydrogen, fluorine or chlorine,

R ^{2 represents} the grouping below,

-A ^! -A ² -A ³

in which A ¹ for a single bond, for oxygen, sulfur, -SO-,

-SO ₂ -, -CO- or the grouping -NA ⁴ -, in which A ^{4 represents} hydrogen, hydroxy, methyl, ethyl, n- or i-propyl,

Methoxy, ethoxy, n- or i-propoxy, methylsulfonyl or ethylsulfonyl, or (A ^ is methylene, ethane-1,1-diyl,

Ethane-1,2-diyl, propane-1,1-diyl, propane-1,2-diyl, propane-1,3-diyl, ethene-1,2-diyl, propene-1,2-diyl, propene- 1,3-diyl, ethyne-1,2-diyl or propyne-1,3-diyl,

A ² for a single bond, for oxygen, sulfur, -SO-,

-SO ₂ -, -CO- or the grouping -NA ⁴ -, wherein A ^{4 represents} hydrogen, hydroxy, methyl, ethyl, n- or i-propyl, methoxy, ethoxy, n- or i-propoxy, methylsulfonyl, ethyl ¬ sulfonyl, n- or i-propylsulfonyl or phenylsulfonyl, or (A ² ) is methylene, ethane-1,1-diyl, ethane-1,2-diyl,

Propane-1,1-diyl, propane-1,2-diyl, propane-1,3-diyl, ethene-1,2-diyl, propene-1,2-diyl, propene-1,3-diyl, ethyne 1, 2-diyl or propyne-1,3-diyl,

A ³ for hydrogen, hydroxy, amino, cyano, nitro, carboxy,

Carbamoyl, sulfo, fluorine, chlorine, bromine, for each methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl which is optionally substituted by fluorine, chlorine, methoxy or ethoxy, n-, i-, s- or t-pentyl, methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy, n-, i-, s- or t-pentyloxy,

Methylthio, ethylthio, n- or i-propylthio, n-, i-, s- or t-butylthio, methylsulfinyl, ethylsulfinyl, n- or i-propylsulfinyl, methylsulfonyl, ethylsulfonyl, n- or i-propylsulfonyl, Methylamino, ethylamino, n- or i-propylamino, n-, i-, s- or t-butylamino, dimethylamino, diethylamino,

Methoxycarbonyl, ethoxycarbonyl, n- or i-propoxycarbonyl, dimethoxyphosphoryl, diethoxyphosphoryl, dipropoxyphosphoryl or diisopropoxyphosphoryl, for propenyl, butenyl, propenyloxy, butenyloxy, propenyl-aminyl-butylamino, propylidene-amylcarbonyl, each optionally substituted by fluorine or chlorine , Propynyl, butynyl, Propinyloxy, butynyloxy, propynylamino, butynylamino, propynyloxycarbonyl or butynyloxycarbonyl, each optionally with fluorine, chlorine, cyano, carboxy, methyl, ethyl, n- or i-propyl, methoxycarbonyl or ethoxy

5 carbonyl substituted cyclopropyl, cyclobutyl, cyclopentyl,

Cyclohexyl, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclo-propyl-methoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclo-

10 hexylmethoxy, cyclopentylidene amino, cyclohexylidene amino,

Cyclopentyloxycarbonyl, cyclohexyloxycarbonyl, cyclopentylmethoxycarbonyl or cyclohexylmethoxycarbonyl, or for each optionally by nitro, cyano, carboxy, fluorine, chlorine, bromine, methyl, ethyl, n- or i-

15 propyl, trifluoromethyl, methoxy, ethoxy, n- or i-propoxy,

Difluoromethoxy, trifluoromethoxy, methoxycarbonyl and / or ethoxycarbonyl substituted phenyl, phenyloxy, benzyl, phenylethyl, benzyloxy, phenyloxycarbonyl, benzyloxycarbonyl, (in each case in whole or in part, if appropriate

20 hydrogenated) pyrrolyl, pyrazolyl, imidazolyl, triazolyl, furyl,

Thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, triazinyl, pyrazolylmethyl, furylmethyl, thienylmethyl, oxazolylmethyl, isoxazolmethyl, thiazolmethyl, pyridinylmethyl,

25 pyrimidinylmethyl, pyrazolylmethoxy, furylmethoxy or

Pyridylmethoxy stands,

R ³ for hydrogen, fluorine, chlorine or together with R ² for one

Alkanediyl or alkenediyl grouping, each with 1 to 3 carbon

30 substance atoms, which optionally contains an oxygen atom, a sulfur atom, an NH group, an N-methyl group, a carbonyl group and / or a thiocarbonyl group at the beginning (or end) or within the hydrocarbon chain, and

35 for each monocyclic or bicyclic, saturated or unsaturated heterocyclyl, heterocyclylamino or heterocyclylimino each with 2 to 5 carbon atoms and 1 to 3 nitrogen atoms in the heterocyclic ring system, which optionally additionally contains an oxygen or sulfur atom and / or optionally up to two groups from the series -CO-, -CS-, -SO - and / or SO ₂ -, and which is optionally substituted by one or more groupings from the series nitro, hydroxyl, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, fluorine, chlorine, bromine; Methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl (which are optionally substituted by fluorine, chlorine, methoxy or ethoxy); Propenyl, butenyl, propynyl or butynyl

(which are each optionally substituted by fluorine or chlorine); Methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy, methoxycarbonyl or ethoxycarbonyl (which are each optionally substituted by fluorine, chlorine, methoxy or ethoxy); Propenyloxy, butenyloxy, propynyloxy or butynyloxy (which are optionally substituted by fluorine or chlorine); Methylthio, ethylthio, n- or i-propylthio, n-, i-, s- or t-butylthio, propenylthio. Butenylthio, propynylthio or butynylthio (which are each optionally substituted by fluorine or chlorine); Methylamino, ethylamino, n- or i-propylamino, n-, i-, s- or t-butylamino, dimethylamino or diethylamino; Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl or cyclohexylmethyl (which are each optionally substituted by fluorine, chlorine, methyl, ethyl, n- or i-propyl), phenyl, phenoxy, phenylthio, phenylsulfinyl,

Phenylsulfonyl or phenylamino (which are each optionally substituted by nitro, cyano, fluorine, chlorine, bromine, methyl, ethyl, n- or i-propyl, trifluoromethyl, methoxy, ethoxy, n- or i-propoxy, difluoromethoxy, trifluoromethoxy, methoxycarbonyl or Ethoxycarbonyl are substituted).