MXPA00000548A

MXPA00000548A - Method for the production of n-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides and new intermediate products

Info

Publication number: MXPA00000548A
Application number: MXPA/A/2000/000548A
Authority: MX
Inventors: Hupperts Achim; Wilhelm Drewes Mark; Erdman David; Lantzsch Reinhard
Original assignee: Bayer Ag 51373 Leverkusen De
Priority date: 1997-07-24
Filing date: 2000-01-14
Publication date: 2001-05-17

Abstract

The invention relates to a method for producing N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides. In a first step, 2-amino-4,5-difluoro-benzonitrile is reacted with sulphonic acid halogenides in the presence of an acid acceptor and a diluting agent at temperatures between 0°C and 150°C. In a second step, the N-(2-cyano-4,5-difluoro-phenyl)-sulphonamide and/or N-(2-cyano-4,5-difluoro-phenyl)-sulphonamides are reacted, either in the pure state or mixed, with ammonia in the presence of a diluting agent at temperatures between 100°C and 200°C. The invention also relates to new intermediate products of this method.

Description

PROCESS FOR THE OBTAINING OF N- (5-AMINO-2- CYAN-4-FLUOR-PHENYL) SULFONAMIDES AND NEW INTERMEDIATE PRODUCTS Field of the Invention The invention relates to a new process for the preparation of N- (5-amino- 2-cyano-4-fluoro-phenyl) -sulfonamides, which are known as intermediates for the preparation of herbicides, to novel N- (2-cyano-4, 5-difluorophenyl) -sulfonamides and N- (2- cyano-4, 5-difluoro-phenyl) -sulfonamides as intermediates thereto and methods for obtaining them.

BACKGROUND OF THE INVENTION It is known that certain N- (5-a ino-2-cyano-4-fluoro-phenyl) -alkanesulfonamides are obtained, such as for example N- (5-amino-2-cyano-4-fluoro) phenyl) -methanesulfonamide, if corresponding halogenated benzene derivatives, such as for example l-amino-4-cyano-2,5-difluoro-benzene, are heated with alkanesulfonamides, such as for example methanesulfonamide in the presence of an acceptor agent of acid, such as for example potassium carbonate, and in the presence of a diluent, such as for example REF .: 32446 N-methyl-pyrrolidone (see EP-A-648772). The desired products are obtained, however, according to this procedure, with unsatisfactory yields. There is therefore a need for a more favorable obtaining procedure for the N- (5-amino-2-cyano-4-fluoro-phenyl) -sulfonamides.

DETAILED DESCRIPTION OF THE INVENTION It has now been found that N- (5-amino-2-cyano-4-fluoro-phenyl) -sulfonamides of the general formula (I) are obtained with high yields and with a very good quality. wherein R means alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, respectively substituted, if reacted, in a first step, 2-amino-4,5-difluoro- benzonitrile of the formula (II), with sulfonyl halides of the general formula (III) X-S02-R (III) wherein R has the meaning indicated above and X means halogen, in the presence of an acid acceptor and in the presence of a diluent, at temperatures between 0 ° C and 150 ° C and the N- (2-cyano) is reacted -4, 5-difluoro-phenyl) -sulfonamides of the general formula (IV) and / or the N- (2-cyano-4,5-difluoro-phenyl) -sulfonamides of the general formula (V), obtained if given as intermediate products (IV) (V) wherein R means has the meaning indicated above, as pure products or as mixtures, in a second step, with ammonia in the presence of a diluent, at temperatures comprised between 100 ° and 200 ° C. Surprisingly, N- (5-amino-2-cyano-4-fluoro-phenyl) -sulfonamides of the general formula (I) can be obtained relatively easily in high yields and with very good qualities, and can be prepared in accordance with the process according to the invention. through a mixture of the intermediate products a pure final product. The intermediates of the formulas (IV) and (V) can be obtained as mixtures with practically quantitative yields. In the process according to the invention, it is advantageous above all that the use of 2,2,4-trifluorobenzonitrile, which is relatively expensive, can be dispensed with, and the problematic exchange of a fluorine substituent by a sulfonylamino group is eliminated. The compound consisting of 2-amino-4,5-difluorobenzonitrile to be used as a starting material of the formula (II) is not known in the literature. This is also an object of the present invention as a new product. The new compound of the formula (II) is obtained, if 4,5-difluoro-2-nitro-benzonitrile of the formula (VI) is reacted with a conventional reducing agent for the conversion of an aromatic nitro compound into the corresponding amino compound, such as for example (a) hydrogen in the presence of a catalyst such as platinum or palladium (if necessary "poisoned" the two mentioned last, on a support material, such as activated carbon or barium sulfate), in the presence of a diluent, such as for example tetrahydrofuran or dioxane, or (b) metals or metal salts, such as for example tin, stannic chloride ( II), iron (powder) in the presence of an acid such as, for example, hydrochloric acid or acetic acid, and optionally also in the presence of a diluent, such as, for example, methanol or ethanol, at temperatures between 0 ° C and 150 ° C. ° C, preferably between 10 ° C and 100 ° C (see the preparation examples). The intermediates of formulas (IV) and (V) are not yet known from the literature; these also constitute an object of the present invention as new products. The 4,5-difluoro-2-nitro-benzonitrile necessary as a starting material of the formula (VI) is already known (see JP 07070041 - cited in Chem. Abstracts 123: 111678). According to the aforementioned patent literature, 4,5-difluoro-2-nitro-benzonitrile can be prepared by reaction of 2-bromo-4,5-difluoro-nitrobenzene with cuprous cyanide (I) in N, N-dimet i-formamide. . The compound of the formula (VI) is obtained, however, 3,4-difluoro-benzonitrile is also reacted with nitric acid, if appropriate in the presence of sulfuric acid, at temperatures between -10 ° C and + 30 ° C. (see the procurement examples). Surprisingly, this nitration is carried out in a very unitary (regioselective) manner and the expected hydrolysis can only be observed in a very small proportion under the conditions of nitration. The sulfonyl halides to be further employed as starting materials in the process according to the invention for the preparation of the N- (5-amino-2-cyano-4-fluoro-phenyl) -sulfonamides of the general formula (I), they are defined in general by means of formula (III).

In the formulas (I), (III), (IV) and (V) preferably, R means alkyl, alkenyl or alkyl with respectively up to 6 carbon atoms, respectively substituted, if appropriate, by halogen, means cycloalkyl or cycloalkylalkyl with respectively With 6 carbon atoms in the cycloalkyl group and optionally 1 to 4 carbon atoms in the alkyl part, respectively substituted, if appropriate, by halogen or by alkyl with 1 to 4 carbon atoms, it means aryl or arylalkyl with 6 to 10 carbon atoms. carbon atoms in the aryl group and optionally 1 to 4 carbon atoms in the alkyl part, optionally substituted by nitro, by cyano, by halogen, by alkyl with 1 to 4 carbon atoms, by halogenalkyl with 1 a 4 carbon atoms, by alkoxy with 1 to 4 carbon atoms, by haloalkoxy with 1 to 4 carbon atoms or by alkoxycarbonyl with 1 to 4 carbon atoms, or means heterocyclyl or heterocyclylalkyl with respectively at 5 carbon atoms and 1 or 2 nitrogen atoms and / or one oxygen or sulfur atom in the heterocyclyl group and, optionally, 1 to 4 carbon atoms in the alkyl part, respectively substituted by cyano, halogen, by alkyl with 1 to 4 carbon atoms, by halogenalkyl with 1 to 4 carbon atoms, by alkoxy with 1 to 4 carbon atoms or by halogenalkoxy with 1 to 4 carbon atoms, and X means fluorine, chlorine or bromine . In the above formulas especially: R stands for methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, ethenyl, propenyl, butenyl, ethynyl, propynyl or butynyl substituted respectively by fluorine or chlorine, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl or cyclohexylmethyl respectively substituted, where appropriate, by fluorine, chlorine, methyl or ethyl, means phenyl or benzyl, respectively substituted by nitro, by cyano, by fluorine, by chlorine, by bromine, by methyl or by ethyl, by n- or i-propyl, by n-, i-, s- or t-butyl, by trifluoromethyl, by methoxy by ethoxy, by n - or i-propoxy, by n-, i-, s- or t-butoxy, by difluoromethoxy, by trifluoromethoxy, by methoxycarbonyl, by ethoxycarbonyl, by n- or i-propoxycarbonyl, or means heterocyclyl of the furyl series, thienyl , oxazolyl, isoxazolyl, pyrazolyl, pyridinyl, substituted pyrimidinyl, optionally by cyano, by fluorine, by chlorine, by bromine, by methyl, by ethyl, by non-propyl, by n-, i-, s- or t-butyl, by trifluoromethyl, by methoxy, by ethoxy , by n- or i-propoxy, by n-, i-, s- or t-butoxy, by difluoro ethoxy or by trifluoromethoxy, and X means chloro.

The process according to the invention for the preparation of N- (5-amino-2-cyano-4-fluoro-phenyl) -sulfonamides of the general formula (I) is carried out, in the first step, using an acceptor of acid. In general, the bases or acceptors of usual inorganic or organic acids are suitable. These preferably include acetates, amides, carbonates, bicarbonates, hydrides, hydroxides or alkanolates of alkali metals or alkaline earth metals, such as, for example, sodium, potassium or calcium acetate, lithium amide, sodium, potassium or sodium amide. calcium, sodium, potassium or calcium carbonate, sodium, potassium or calcium bicarbonate, lithium, sodium, potassium or calcium hydride, lithium, sodium, potassium or calcium hydroxide, methanolate, ethanolate, n- or i-propanolate, n-, i-, s- or sodium or potassium t-butanolate; furthermore basic organic nitrogenous compounds, such as for example tri-methylamine, triethylamine, tripropylamine, tributylamine, ethyl-diisopropylamine, N, N-dimethyl-cyclohexylamina, dicyclohexylamine, ethyl-dicyclohexylamine, N, N-dimethyl-aniline, N, N-dimethyl-yl-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-dimethyl-amino-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). Preferably, organic basic nitrogen compounds are used as acid acceptors. Suitable diluents for carrying out the first stage of the process according to the invention are, in particular, inert organic solvents. These include especially aliphatic, alicyclic or aromatic hydrocarbons, if appropriate halogenated, such as, for example, benzene, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetrachloride; ethers, such as diethylether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycoli ethyl or odiethylether; ketones, such as acetone, butanone, 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 hexamethylphosphorotriamide; esters such as methyl acetate or ethyl acetate, sulfoxides, such as dimethylsulfoxide. Preferably, polar organic aprotic solvents, especially acetone or acetonitrile, or basic organic nitrogenous compounds, such as pyridine or 5-ethyl-2-methyl-pyridine, are used as diluents. The reaction temperatures in the embodiment of the first stage of the process according to the invention can vary within wide limits. In general, work is carried out at temperatures between 0 ° C and 150 ° C, preferably between 10 ° C and 120 ° C. The first stage of the process according to the invention is generally carried out at normal pressure. However, it is possible to carry out the process according to the invention under higher pressure or at a lower pressure in general between 0.1 bar and 10 bar. For carrying out the first step of the process according to the invention, 1 mole of 2-amino-4,5-difluoro-benzonitrile of the formula (II) is used in general between 1 mole and 10 mole, preferably between 2 mole and 5 moles of sulfonyl halide of the general formula (III) and between 1 mol and 10 mol, preferably between 2 mol and 5 mol of acid acceptor. In a preferred embodiment of the first step of the process according to the invention, the 2-amino-, 5-difluoro-benzonitrile of the formula (II) is arranged together with an acid acceptor and with a diluent and is metered slowly into it. mix the sulfonyl halide of the general formula (III) under stirring-and if appropriate under cooling. The complete mixture of the reaction is then stirred b - if necessary at elevated temperature - until the end of the conversion. The preparation of the mixture of the intermediates of the formulas (IV) and (V) can be carried out in the usual manner. For example, it is stirred with water or dilute aqueous acid, the organic phase is separated off, the aqueous phase is subsequently extracted, if appropriate with an organic solvent practically immiscible with water, such as, for example, ethyl acetate, the organic phases gathered they are dried and filtered. To isolate the intermediate mixture, the solvent of the filtrate is carefully removed by distillation under reduced pressure. The mixtures thus obtained of the intermediates of the formulas (IV) and (V) can be advantageously used without further purification for the conversion according to the second step of the process according to the invention. The second stage of the process according to the invention is carried out, preferably with the use of a diluent. Suitable diluents are, in particular, inert organic solvents. These include, in particular, aliphatic, alicyclic or aromatic halogenated hydrocarbons, such as, for example, benzene, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetrachloride.; ethers, such as diethyl ether, diisopropyl ether, t-butyl methyl ether, t-pentyl methyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl-o-diethyl ether; ketones, such as acetone, butanone, methylisobutyl ketone; nitriles, such as acetonitrile, propionitrile or butyronitrile, amides, such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-formanilide, N-methyl-pyrrolidone or hexamethylphosphorotriamide; esters such as methyl acetate or ethyl acetate, sulfoxides, such as dimethylsulfoxide. Preferably, polar organic aprotic solvents, especially diisopropyl ether, t-butyl methyl ether, t-pentyl methyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, or diethyl ether, are used as diluents.

The reaction temperatures in the embodiment of the second stage of the process according to the invention can vary within wide limits. In general, work is carried out at temperatures between 50 ° C and 200 ° C, preferably between 100 ° C and 180 ° C. The second stage of the process according to the invention is generally carried out in a closed reaction vessel, especially in the autoclave (at elevated pressure) depending on the pressure of the set temperature and the solvent used. For carrying out the second step of the process according to the invention, 1 mol of the sum formed by the intermediates of the formulas (IV) and (V) are generally used between 1 and 100 mol, preferably between 5 mol. and 50 moles of ammonia. In a preferred embodiment of the second step of the process according to the invention, the reaction components of the formula (IV) and / or (V) are mixed with ammonia and with a diluent at room temperature (at approximately 20 ° C) and they are heated in a closed reaction vessel until the conversion is complete. The preparation and isolation of the products of the formula (I) can be carried out according to usual methods. The reaction mixture is filtered after cooling and the solvent of the filtrate is carefully removed by distillation under reduced pressure. The product can thus be obtained as a 'residue in general with a good quality. The compounds of the formula (I), to be obtained according to the process of the invention, can be used as intermediates for the preparation of compounds with herbicidal activity (see EP-A-648749, EP-A-648772, WO- A-95/29158). The intermediate products of the formulas (IV) and (V) can be used, if appropriate, as raw materials for the preparation of herbicides (see EP-A-609734).

Examples of obtaining: Example 1 First stage g (130 mmol) of methanesulfonyl chloride are added, dropwise, under stirring, to a mixture constituted by 3.7 g (24 mmol) of 2-amino-4,5-difluoro-benzonitrile, 5.0 g (33 mmoles) of 1,8- "diazabicyclo [5, 4, 0] -undec-7-ene (DBU), and 50 ml of pyridine and the reaction mixture is then stirred for approximately 1 hour at 50 ° C. C. It is then concentrated by evaporation to the water pump vacuum, the residue is stirred with 100 ml of 20% hydrochloric acid and 10 ml of ethyl acetate and the crystalline product formed is isolated by filtration by suction. 3.3 g (44% of theory) of 4,5-difluoro-2- (bis-methanesulfonylamino) benzonitrile with a melting point of 144 ° C.

Second stage 2 ml of ammonia are condensed in a 100 ml autoclave and 2.0 g (6.4 mmoles) of 4,5-difluoro-2- (bis-methanesulfonyl-ami or) -benzonitrile are added as well as 40 ml of tetrahydrofuran. . The reaction mixture is then heated in the closed autoclave for 15 hours at 150 ° C. After cooling it is filtered and the filtrate is concentrated by evaporation under vacuum of the water pump. After washing with 2N hydrochloric acid and with water, 0.50 g (34% of theory) of N- (5-amino-2-cyano-4-fluoro-phenyl) -methanesulfonamide having a melting point of 235 ° is obtained. C. Example 2 First stage 4.6 g (40 mmol) of methanesulfonyl chloride are added, dropwise, under stirring, to a mixture, consisting of 1.54 g (10 mmol) of 2-amino-4,5-difluoro-benzonitrile, , 0 g (40 mmol) of triethylamine and 50 ml of acetonitrile and the whole reaction mixture is then heated to about 1 hour of reflux. After cooling, the mixture is stirred for 30 minutes with 100 ml of ice water and, after separation of the phases, the aqueous phase is subsequently extracted with 50 ml of ethyl acetate. The combined organic phases are washed with saturated aqueous sodium bicarbonate solution and then with water, dried over sodium sulphate and filtered. The solvent is carefully removed by vacuum distillation of the filtrate water tube. As residue, 2.9 g of a mixture consisting of 43% of 4,5-difluoro-2- (bis-methylsulfonylamino) -benzonitrile and 57% of 4,5-difluoro-2-methylasulfonylamino- benzonitrile (according to GC / MS), which corresponds to a quantitative total yield.

Second stage 4.5 ml of ammonia are condensed in a 100 ml autoclave and the product mixture obtained according to step 2 (2.9 g) as well as 50 ml of tetrahydrofuran is added. The reaction mixture is then heated for 15 hours at 150 ° C in the autoclave. After cooling it is filtered and the filtrate is concentrated by evaporation under vacuum of the water pump. After washing with 2N hydrochloric acid and with water, 1.0 g (44% of theory) of N- (5-amino-2-cyano-4-fluoro-phenyl) -methanesulfonamide having a melting point of 235 ° is obtained. C. Example 3 First stage .1 g (40 mmol) of ethanesulfonyl chloride are added, dropwise, under stirring, to a mixture consisting of 1.54 g (10 mmol) of 2-amino-4,5-difluoro-benzonitrile, 4, 0 g (40 mmol) of triethylamine and 50 ml of acetonitrile and the whole reaction mixture is then heated for about 2 hours under reflux. After cooling, stir for 30 minutes with 100 ml of ice water and, after separation of the phases, the aqueous phase is extracted again with 50 ml of ethyl acetate. The combined organic phases are dried with sodium sulfate and filtered. The solvent is carefully removed by vacuum distillation of the filtrate water tube. 3.0 g of a mixture consisting of 67% of 4,5-difluoro-2- (bis-ethylsulphonylamino) -benzonitrile and 33% of 4,5-difluoro-2-ethylsulfoni-lamino-benzonitrile are obtained as a residue. according to GC / MS), which corresponds to a quantitative total yield. Second stage 4 ml of ammonia are condensed in a 100 ml autoclave and 3.0 g of the product mixture from stage 1 as well as 50 ml of tetrahydrofuran are added. The reaction mixture is heated for 15 hours at 150 ° C in the closed autoclave and filtered after cooling. The filtrate is concentrated by evaporation under vacuum of the water pump, washed with 2N hydrochloric acid and with water and dried. 1.1 g (45% of the theory of a 95.5% product) of 4-amino-5-fluoro-2-ethylsulfonylamino-benzonitrile with a melting point of 170 ° C are obtained. Starting compound of the formula (II). Example (II) -1). 3.68 g (20 mmol) of 4,5-di-fluor-2-nitro-benzonitrile are dissolved in 40 ml of dioxane and 300 mg of platinum on carbon (5%) are added. The suspension is then stirred at 20 ° C to 25 ° C under hydrogen until 1.45 liters of hydrogen have been absorbed. The mixture is then filtered through silica gel and the filtrate is concentrated by vacuum evaporation of the water tube. The residue is then worked up by column chromatography (silica gel, hexane / ethyl acetate). 2.19 g (72% of theory) of 2-amino-4,5-difluoro-benzonitrile having a melting point of 114 ° C and, from another fraction, 0.52 g (15% strength) are obtained. the theory) of 2-amino-4,5-difluoro-benzamide. Example (II-2). 11.0 g (59 mmol) of 4,5-difluoro-2-nitro-benzonitrile are dissolved in 175 ml of acetic acid ("glacial acetic acid") and 20 g (358 mmoles) of iron are added in portions. (dust). The temperature of the reaction is maintained at 40 ° C to 50 ° C. In this case by cooling with a water bath. The whole reaction mixture is then stirred for another 3 hours at 50 ° C. After cooling to room temperature, pour the mixture over 200 ml of ice water. It is extracted twice with 50 ml of ethyl acetate each time, the organic extraction solutions are added, washed with saturated sodium bicarbonate solution and then with water, dried over sodium sulphate and filtered. The filtrate is concentrated by evaporation under vacuum of the water pump and the residue is worked up by column chromatography (silica gel hexane / ethyl acetate). 7.7 g (85% of theory) of 2-amino-4,5-difluoro-benzonitrile with a melting point of 114 ° C are obtained. Starting compounds of the formula (VI): Example (V -1) A mixture consisting of 40 ml of sulfuric acid (97%) and 30 ml of nitric acid (98%) is cooled to 0 ° C. Then 13 are added, 9 g (0.10 mole) of 3,4-difluoro-benzonitrile in portions, such that the reaction temperature remains below 5 ° C. The whole reaction mixture is stirred for 5 hours at 5 ° C to 10 ° C and, after heating to 20 ° C, it is stirred for another 2 hours. The mixture is then poured onto 400 g of ice, the crystalline product formed is isolated by suction filtration and taken up in 20 ml of methylene chloride. The aqueous phase is subsequently extracted twice with 30 ml each time of methylene chloride. The organic phases are washed with saturated sodium bicarbonate solution and with water, dried over sodium sulphate and filtered. The solvent is carefully removed by vacuum distillation of the filtrate water tube. 10.2 g (55% of theory) of 4,5-difluoro-2-nitro-benzonitrile are obtained with a melting point of 75 ° C. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, property is claimed as contained in the following:

Claims

R E I V I N D I C A C I O N S

1. Process for the preparation of N- (5-amino-2-cyano-4-fluoro-phenyl) -sulfonamide of the general formula (I) wherein R means alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, respectively substituted, characterized by the following steps: A) reaction of 2-amino-4,5-difluoro- benzonitrile of the formula (II), (ll) with sulfonyl halides of the general formula (III) X-SO2-R (III) wherein R has the meaning indicated above and X means halogen, in the presence of an acid acceptor and in the presence of a diluent, at temperatures between 0 ° C and 150 ° C and B) reaction of the N- (2-cyano-4,5-difluoro-pheny1) -sulfonamides of the general formula (IV) and / or the N- (2-cyano-4) , 5-difluoro-phenyl) -sulfonamides of the general formula (V), obtained in step A) (IV) (V) in which R means has the meaning indicated above, as pure products or in the form of mixtures, with ammonia in the presence of a diluent, at temperatures comprised between 100 ° and 200 ° C.

2. Process according to claim 1, characterized in that it means alkyl, alkenyl or alkyl with respectively up to 6 carbon atoms, respectively substituted, if appropriate, by halogen, means cycloalkyl or cycloalkylalkyl with respectively 3 to 6 carbon atoms in the cycloalkyl group and, if appropriate 1 to 4 carbon atoms in the alkyl part, respectively substituted, if appropriate, by halogen or by alkyl with 1 to 4 carbon atoms, means aryl or arylalkyl with 6 to 10 carbon atoms in the aryl group and, if appropriate, 1 a 4 carbon atoms in the alkyl part respectively substituted, where appropriate, by nitro, by cyano, by halogen, by alkyl with 1 to 4 carbon atoms, by halogenalkyl with 1 to 4 carbon atoms, by alkoxy with 1 to 4 carbon atoms; carbon, by haloalkoxy with 1 to 4 carbon atoms or by alkoxy-carbonyl with 1 to 4 carbon atoms, or means heterocyclyl or heterocyclylalkyl with respectively 3 to 5 carbon atoms and 1 or 2 nitrogen atoms and / or an oxygen or sulfur atom in the heterocyclyl group and, where appropriate, 1 carbon atom in the alkyl part, optionally substituted by cyano, halogen, by alkyl with 1 to 4 carbon atoms, by halogenalkyl with 1 to 4 carbon atoms, by alkoxy with 1 to 4 carbon atoms or by halogenalkoxy with 1 to 4 carbon atoms, and X means fluorine, chlorine or bromine

3. Procedure according to the claim 2, characterized in that R stands for methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, ethenyl, propenyl, butenyl, ethynyl, propynyl or butynyl substituted respectively by fluorine or by chloro means cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl or cyclohexylmethyl substituted respectively where appropriate by fluorine, chlorine, methyl or ethyl, means phenyl or benzyl substituted, if appropriate by nitro, by cyan, by fluorine, by chlorine, by bromine, by methyl or by ethyl, by n- or i-propyl, by n-, i-, s- or t-butyl by trifluoromethyl, pr methoxy, pr ethoxy, by n- or i -propoxy, by n-, i-, s- or t-butoxy, by difluoromethoxy, by trifluoromethoxy, by methoxycarbonyl, by ethoxycarbonyl, by n- or i-propoxycarbonyl, or means heterocyclyl of the furyl, thienyl, oxazolyl series, isoxazolyl, pyrazolyl, pyridinyl, pyrimidinyl substituted respectively in case or by cyano, by fluorine, by chlorine, by bromine, by methyl, by ethyl, by non-propyl, by n-, i-, s- or t-butyl, by trifluoromethyl, by methoxy, by ethoxy, by n - or i-propoxy, by n-, i-, s- or t-butoxy, by di-fluoromethoxy or by trifluoromethoxy, and X means chlorine.

4. Process according to one of claims 1 to 3, characterized in that basic organic nitrogen compounds are used as acid acceptors.

5. Process according to one of claims 1 to 4, characterized in that acetone and / or acetonitrile are used as diluents in stage A) and pyridine and / or 5-ethyl-2-methyl-pyridine are used in step B).

6. The 2-amino-4,5-difluoro-benzonitrile.

7. Process for the preparation of 2-amino-4,5-difluorobenzonitrile, characterized in that 4,5-difluoro-2-nitrobenzonitrile is reacted with a conventional reaction agent for the conversion of aromatic nitro compounds to the corresponding amino compounds. temperatures between 0 ° C and 150 ° C. '

8. The N- (2-cyano-4, 5-difluoro-phenyl) -sulfonamides of the general formula (IV) (IV) wherein R has the meaning indicated in one of claims 1 to 3.

9. The N- (2-cyano-4, 5-difluoro-phenyl) -sulfonamides of the general formula (V) (V) wherein R has the meaning indicated in one of claims 1 to 3.