Indian Patents. 268982:"A PROCESS FOR PREPARING CARBOXAMIDES OF THE GENERAL FORMULA (I)"

Title of Invention	"A PROCESS FOR PREPARING CARBOXAMIDES OF THE GENERAL FORMULA (I)"
Abstract	The invention relates to a novel method for producing known fungicidally active alkylanilides from 2-alkyl haloaromatics and heterocyclylamides.

Full Text	Method for producing alkylanilides from halobenzene derivatives The present invention relates to a process for preparing known fungicidally active alkylanilides from 2-alkylhaloaromatics and heterocyclylamides. EP-A-0 824 099 and WO-A-03010149 disclose that alkylanilides are obtained by reacting the appropriate acid chloride with the appropriate alkylaniline derivative. Both preparation and handling of the acid chlorides and the preparation of the alkylanilides are associated with a considerable level of technical complexity. For example, the acid chlorides have to be purified before the reaction by a time-consuming and costly distillation step. The anilines are prepared typically, as described in WO-A-3074491, by a complicated synthesis from the corresponding bromoaromatics and benzophenone imine or at temperatures of 150°C and pressures of from 75 to 85 bar with ammonia gas, as described in WO-A-06061226. Alkylanilines, however, frequently exhibit toxic properties and are potentially mutagenic. The prior art discloses that aryl halides can be reacted with amides under palladium or copper catalysis to give alkylanilides (J. Am. Chem. Soc. 2002,124, 7420). It is frequently found, however, that metal-catalyzed reactions with heterocycles which can function as chelating ligands are inhibited. Furthermore, ortho-substituted haloaromatics are sterically hindered for a halogen exchange. It is therefore an object of the present invention to provide a process for simple and selective preparation of alkylanilides, which does not have the disadvantages described in the prior art. Surprisingly, conditions have been found under which heterocyclylamides can be reacted efficiently with ortho-substituted haloaromatics. The present invention thus provides a process for preparing alkylanilides of the formula (I) in which R1 is hydrogen, halogen, -CR' (R' = hydrogen, fluorine or O-C1-4-alkyl), more preferably hydrogen; R2 is -CH(Me)-CH2-CHMe2, -CH2-CH2-t-But, or v , particular preference being given to -CH(Me)-CH2-CHMe2 and A is the radical of the formula (Al) (FORMULA REMOVED) in which R3 is hydrogen, cyano, halogen, nitro, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C3-C6-cycloalkyl, C1-C4-haloalkyl, C1-C4-haloalkoxy or C1-C4-haloalkylthio having in each case from 1 to 5 halogen atoms, aminocarbonyl or aminocarbonyl-C1-C4-alkyl; R4 is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy or C1-C4-alkylthio; R5 is hydrogen, C1-C4-alkyl, hydroxy-C1-C4-alkyl, C2-C6-alkenyl, C3-C6-cycloalkyl, C1-C4-alkylthio-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-haloalkyl, C1 -C4-haloalkylthio-C 1 -C4-alkyl, C1 -C4-haloalkoxy-C 1 -C4-alkyl having in each case from 1 to 5 halogen atoms, or phenyl; or A is the radical of the formula (A2) (FORMULA REMOVED in which 7 R6 and R' are each independently hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R8 is halogen, cyano or C1-C4-alkyl, or C1-C4-haloalkyl or C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms, or A is the radical of the formula (A3) (FORMULA REMOVED in which R9 and R10 are each independently hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R11 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, (FORMULA REMOVED in which R12 is hydrogen, halogen, hydroxyl, cyano, C1-C6-alkyl, C1-C4-haloalkyl, C1-C4-haloalkoxy or C1-C4-haloalkylthio having in each case from 1 to 5 halogen atoms, or A is the radical of the formula (A5) (FORMULA REMOVED in which R is halogen, hydroxyl, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1- C4-haloalkyl, C1-C4-haloalkylthio or C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms, R14 is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms, C1-C4-alkylsulfinyl or C1-C4-alkylsulfonyl, or A is the radical of the formula (A6) (FORMULA REMOVED in which R15 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R16 is C1-C4-alkyl, Q1 is S (sulfur), O (oxygen), SO, SO2 or CH2, p is 0, 1 or 2, where R16 represents identical or different radicals when p is 2, or A is the radical of the formula (A7) (FORMULA REMOVED in which R17 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A8) (FORMULA REMOVED in which R18 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A9) (FORMULA REMOVED in which R19 and R20 are each independently hydrogen, halogen, amino, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R21 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (Al 0) (FORMULA REMOVED in which R22 and R23 are each independently hydrogen, halogen, amino, nitro, C1-C4-alkyl or C1-C4-haloalkyl having 1 to 5 halogen atoms, R24 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (All) (FORMULA REMOVED in which R25 is hydrogen, halogen, amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R26 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A12) (FORMULA REMOVED n which R27 is hydrogen, halogen, amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R28 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A 13) (FORMULA REMOVED in which R29 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, Or A is the radical of the formula (A 14) (FORMULA REMOVED in which >30 R30 is hydrogen or C1-C4-alkyl, R31 is halogen or C1-C4-alkyl, or A is the radical of the formula (A 15) R32 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (Al 6) (FORMULA REMOVED in which R33 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A 17) (FORMULA REMOVED in which R34 is halogen, hydroxyl, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkylthio or C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms, or A is the radical of the formula (Al 8) (FORMULA REMOVED in which R35 is hydrogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl having from 1 to 5 halogen atoms, C1-C4-alkoxy-C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C4-alkylsulfonyl, di(C1-C4-alkyl)aminosulfonyl, C1-C6-alkylcarbonyl or in each case optionally substituted phenylsulfonyl or benzoyl, R36 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R37 is hydrogen, halogen, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R38 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A 19) (FORMULA REMOVED in which R39 is C1-C4-alkyl, characterized in that, in a first step, carboxamides of the formula (II) (FORMULA REMOVED in which the A radical is as defined above are reacted with haloalkylbenzenes of the formula (III) (III) 2 in which the R1 and R2 radicals are each as defined above and the substituent R1 is preferably in the meta or para position, more preferably in the 4 position (para to X) of the aromatic; and the X radical is a halogen, preferably C1 or Br, more preferably Br, in a metal-catalyzed reaction. The present invention further relates to compounds of the formula (III) (FORMULA REMOVED) where R1 'is hydrogen, halogen, -CR'(CF3)2 (R'= hydrogen, fluorine or O-C1-4-alkyl), more preferably hydrogen, and the substituent R1 is preferably in the meta or para position, more preferably in the 4 position (para to X) of the aromatic; and R2 is -CH(Me)-CH2-CHMe2 and -CH2-CH2-t-But, or R1 is halogen, -CR'(CF3)2 (R'= hydrogen, fluorine or O-C1-4alkyl), more preferably hydrogen, and the substituent R1 is preferably in the meta or para position, more preferably in the 4 position (para to X) of the aromatic; and (FORMULA REMOVED and X is a halogen, preferably C1 or Br, more preferably Br. The present invention additionally relates to the compounds of the formulae (IV) to (FORMULA REMOVED A further aspect of the present invention relates to the use of the compounds of one of the formulae (II), (III), (IV), (V) and (VI) as reactants/intermediates in the process according to the invention described above. (FORMULA REMOVED (Scheme I) In connection with the present invention, the term "halogen" (X) encompasses elements which are selected from the group consisting of fluorine, chlorine, bromine and iodine, preference being given to using chlorine and bromine, and particular preference to using bromine. Optionally substituted radicals may be mono- or polysubstituted, where the substituents may be the same or different in the case of polysubstitutions. The definition "C1-C6-alkyl" encompasses the largest range for an alkyl radical defined herein. SpeC1fically, this definition encompasses the meanings of methyl, ethyl, n-, isopropyl, n-, iso-, sec-, tert-butyl, and in each case all isomeric pentyls and hexyls. The definition "C2-C6-alkenyl" encompasses the largest range for an alkenyl radical defined herein. SpeC1fically, this definition encompasses the meanings of ethenyl, n-, isopropenyl, n-, iso-, sec-, tert-butenyl, and in each case all isomeric pentenyls and hexenyls. The inventive compounds can optionally be used as mixtures of different possible isomeric forms, espeC1ally of stereoisomers, for example E and Z, threo and erythro, and also optical isomers, and if appropriate also of tautomers. It is possible to use both the E and the Z isomers, and also the threo and erythro isomers, and also the optical isomers, any mixtures of these isomers, and also the possible tautomeric forms. The haloalkylbenzenes required are known in the prior art, for example from WO-A-03074491, or can be prepared by known methods by Friedel-Crafts alkylation or electrophilic aromatic halogenation. A further possibility is that of reacting 2-halobenzaldehydes with Wittig reagents, in which case the propenone derivatives thus obtained, as described in WO-A-03 074491, can be converted to cyclopropyl compounds. Other possibilities are the hydroxyalkylation of aromatics or metalated aromatics with ketones or aC1d chlorides and, respectively, the subsequent elimination and reduction thereof. Proceeding from 1,2-dibromobenzene, this is illustrated by way of example in scheme (II): (FORMULA REMOVED Alternatively, it is also possible to obtain the halogen compounds in question from aniline derivatives by diazotization and Sandmeyer reaction. According to the present invention, the haloalkylbenzene of the formula (IX) in which X is a halogen atom, espeC1ally Br, is a preferred reactant. Only some of the aC1d amides required are known, and they can be obtained from known aC1d halides, aC1ds, esters or nitriles by known reactions. This will be illustrated by the following example according to scheme (III): (FORMULA REMOVED The nitrogen source used may be aqueous or gaseous ammonia or one of its salts, for example ammonium acetate or sodium amide. Useful solvents for the preparation of the aC1d amides include all solvents which are stable under the reaction conditions, for example ethers such as THF, 2-methyl-THF, dioxane, methyl t-butyl ether (MTBE), diethylene glycol, diethoxymethane, dimethoxymethane; aromatic hydrocarbons such as toluene, xylene, chlorobenzene, dichlorobenzene, benzene; aliphatic hydrocarbons such as petroleum ether, heptane, hexane, methylcyclohexane, cyclohexane; dimethylformamide (DMF); dimethylacetamide; N-methylpyrrolidone (NMP); dimethyl sulfoxide (DMSO), acetonitrile; butyronitrile; water; ketones such as acetone, methyl isobutyl ketone (MIBK); alcohols such as methanol, ethanol, isopropanol. For the inventive reaction of the aC1d amide with the halobenzene derivative, metal catalysts are used. For this purpose, palladium and copper in all oxidation states are useful, for example in metallic form or in the form of salts. According to the present invention, for example, Pd(OAc)2, Pd(OH)2, PdCb, Pd(acac)2 (acac = acetylacetonate), Pd(NO3)2, Pd(dba)2, Pd2dba3, (dba - dibenzylideneacetone), dichlorobis(triphenylphosphine)palladium(II), Pd(CH3CN)2Cl2, tetrakis(triphenylphosphine)palladium(0), Pd/C or palladium nanoparticles, Cul, CuCl, CuSCN, Cu2O, CuO, CuCl2, CuSO4, CuBr, CuBr2, Cu2S, Cu(OAc)2, Cu(acac)2 are suitable, preference being given to using the copper compounds or mixtures thereof. According to the present invention, the catalysts are used in catalytic amounts. This means that the metal catalysts are used in concentrations of from 0.01 to 50.0 mol%, preferably of 1.0 to 20.0 mol%, based on the carboxamides of the formula (II). The inventive reaction is preferably performed in the presence of ligands. In the case of palladium catalysis, suitable ligands are, for example, selected from the group of carbene and phosphine ligands, particular preference being given to using xantphos and tris(t-butyl)phosphine. In the case of copper catalysis, suitable ligands are, for example, selected from the group consisting of diamines, for example N,N"-dimethyl-1,2-cyclohexanediamine (C1s or trans, racemic or as an enantiomer), NjN'-dimethylethylenediamine, ethylenediamine, N-methylethylenediamine, N-butylethylenediamine, N,N,N"-trimethylethylenediamine or else 1,10-phenanthroline, ethylenediaminetetraacetic aC1d, tetra-n-butylammonium fluoride, tris(3,6-trioxaheptyl)amine (TDA-1), particular preference being given to using N,N'-dimethyl-1,2-cyclohexanediamine. The ligands are added to the metal catalyst in such a ratio that the desired catalytic action occurs. According to the present invention, the ratio of ligand to metal catalyst is between 0.5 to 10 equivalents, preferably between 1 to 5 equivalents. The reaction is preferably carried out in the presence of bases. Useful examples include alkali metal and alkaline earth metal hydroxides such as KOH, NaOH, Ca(OH)2, fluorides such as KF, phosphates such as K3PO4, and carbonates such as potash, soda, cesium carbonate or phosphazene bases, alkoxides such as sodium tert-butoxide, or phenoxides such as sodium phenoxide. According to the present invention, the bases are used in concentrations of from 0.5 to 5 equivalents, preferably from 1.0 to 3 equivalents, based on the carboxamides of the formula (II). The inventive reaction of the aC1d amide with the halobenzene derivative is preferably carried out in a solvent. The solvents used are preferably dioxane, THF, diglyme, toluene, xylene, DMF. According to the present invention, the aC1d amides and the halobenzene derivatives are reacted with one another in an equimolar ratio. In an alternative embodiment, the halobenzene derivative can also be used in excess, for example as a solvent. According to the invention, the aC1d amides are reacted with the halobenzene derivatives at temperatures in the range from 20 to 200°C, preferably from 70 to 150°C. In a particularly preferred embodiment of the invention, carboxamides of the formula (V) are reacted with compounds of the formula (X) in which the X radical is a halogen to give carboxamides of the formula (XI) (FORMULA REMOVED The examples which follow are intended to illustrate the subject matter of the invention in detail, but without restricting it thereto. Working examples l-Bromo-2-(l,3-dimethylbutyl)benzene 28.4 g of 2-(l,3-dimethylbutyl)aniline in 134.9 g (667 mmol) of 40 percent hydrobromic aC1d in glaC1al acetic aC1d at 10°C are admixed with 12.5 g (181 mmol) of sodium nitrite in portions with stirring within 1.5 h. Thereafter, 0.5 g of copper powder is added and the mixture is boiled under reflux for 1 h hour. Subsequently, 120 ml of water and sodium hydroxide solution are added until pH 12 is attained, and the organic phase is removed, washed with dilute hydrochloric aC1d and concentrated by evaporation under reduced pressure. After distillation in a Kugelrohr apparatus at 0.3 mbar/70°C and purification of the main fraction by means of preparative HPLC, 8.3 g of a yellowish oil with a purity of 99.4 % (determined by HPLC) are obtained. ]H NMR (400 MHz, CDC13): 0.89 (dd, 6H), 1.17 (d, 3H), 1.32-1.38 and 1.46-1.53 (2m, AB, 2xlH), 1.54-1.6 (m, 1H), 3.34 (m, 1H), 7 (m, 1H), 7.21-7.28 (m, 2H), 7.52 (d, 1H). (FORMULA REMOVED 5-FIuoro-l,3-dimethyl-lH-pyrazole-4-carboxamide 19.9 g of 5-fluoro-1,3-dimethyl-lH-pyrazole-4-carbonyl chloride are added dropwise at 20-35°C to a mixture of 35 g of 25 percent aqueous ammonia and 170 ml of THF. After stirring for 4 h, the organic solvent fraction is concentrated by evaporation under reduced pressure and 0.2 mol of potash and sodium chloride are added to saturation. After extracting four times with ethyl acetate and concentrating the combined organic phases by evaporation under reduced pressure, 16.6 g of a yellow solid are obtained. *H NMR (400 MHz, d6-DMSO): 2.64 (s, 3H), 3.63 (s, 3H), 6.9 (broad s, 1H), 7.18 (broad s, 1H). N-[2-(l,3-Dimethylbutyl)phenyl]-5-fluoro-l,3-dimethyl-lH-pyrazole-4-carboxamide A mixture of 0.221 g (1.16 mmol) of copper iodide, 3.21 g (23.22 mmol) of potash and 2.189 g of 5-fluoro-l,3-dimethyl-lH-pyrazole-4-carboxamide is admixed under argon with 330 mg (2.322 mmol) of N,N"-dimethyl-1,2-cyclohexanediamine, 2.8 g (11.6 mmol) of l-bromo-2-(l,3-dimethylbutyl)benzene and 30 ml of toluene. After boiling under reflux for one day, the mixture is poured onto water and 10 ml of a 5% EDTA solution. Subsequently, the mixture is extracted three times with ethyl acetate and concentrated by evaporation under reduced pressure. The oily residue is dissolved in toluene and stirred into n-hexane. After the preC1pitated crystals have been filtered off with suction, 3.3 g (89% of the theoretical yield) of N-[2-(l,3- dimethylbutyl)phenyl]-5-fluoro-l,3-dimethyl-lH-pyrazole-4-carboxamide are obtained with a purity (HPLC) of 99 %. Claims: A process for preparing carboxamides of the general formula (I) (formula removedin which R1 is hydrogen, halogen, -CR' where R' = hydrogen, fluorine or O-C1-4-alkyl; R2 is-CH(Me)-CH2-CHMe2, -CH2-CH2-t-But or A is the radical of the formula (A 1) (formula removed)in which R3 is hydrogen, cyano, halogen, nitro, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C3-C6-cycloalkyl, C1-C4-haloalkyl, C1-C4-haloalkoxy or C1-C4-haloalkylthio having in each case from 1 to 5 halogen atoms, aminocarbonyl or aminocarbonyl-C1-C4-alkyl; R4 is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy or C1-C4-alkylthio; R5 is hydrogen, C1-C4-alkyl, hydroxy-C1-C4-alkyl, C2-C6-alkenyl, C3-C6-cycloalkyl, C1-C4-alkylthio-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, Cr C4-haloalkyl, C1 -C4-haloalkylthio-C 1 -C4-alkyl, C1 -C4-haloalkoxy-C 1 -C4-alkyl having in each case from 1 to 5 halogen atoms, or phenyl; or A is the radical of the formula (A2) (formula removed) in which R6 and R'7are each independently hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R8 is halogen, cyano or C1-C4-alkyl, or C1-C4-haloalkyl or C1-C4-ha-loalkoxy having in each case from 1 to 5 halogen atoms, or A is the radical of the formula (A3) -i^R- in which R9 and R10 are each independently hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R11 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A4) (formula removed) in which R12 is hydrogen, halogen, hydroxyl, cyano, C1-C6-alkyl, C1-C4-haloalkyl, C\-C4-haloalkoxy or C1-C4-haloalkylthio having in each case from 1 to 5 halogen atoms, or A is the radical of the formula (A5) (formula removed) in which R13 is halogen, hydroxyl, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkylthio or C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms, R14 is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms, C1-C4-alkylsulfinyl or C1-C4-alkylsulfonyl, or A is the radical of the formula (A6) (formula removed) in which R13 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R16 is C1-C4-alkyl, Q1 is S (sulfur), O (oxygen), SO, SO2 or CH2, p is 0, 1 or 2, where R16 represents identical or different radicals when p is 2, or A is the radical of the formula (A7) (formula removed)in which R17 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms , or A is the radical of the formula (A8) in which R18 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A9) (formula removed) in which R19 and R20 are each independently hydrogen, halogen, amino, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R21 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A 10) (formula removed) in which R22 and R23 are each independently hydrogen, halogen, amino, nitro, C1-C4-alkyl or C1-C4-haloalkyl having 1 to 5 halogen atoms, R24 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (All) (formula removed) in which R is hydrogen, halogen, amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R26 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A 12) (formula removed) in which R27 is hydrogen, halogen, amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R28 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A 13) (formula removed) in which R is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (A 14) (formula removed) in which R30 is hydrogen or C1-C4-alkyl, R31 is halogen or C1-C4-alkyl, or A is the radical of the formula (Al 5) (formula removed) R32 is C1-C4-alkyl or C1-C4-haloalkyl having frorn 1 to 5 halogen atoms, or A is the radical of the formula (A 16) (formula removed) in which R33 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (Al 7) (formula removed) in which R34 is halogen, hydroxyl, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkylthio or C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms, or A is the radical of the formula (Al 8) (formula removed) in which R35 is hydrogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl having from 1 to 5 halogen atoms, C1-C4-alkoxy-C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C4-alkylsulfonyl, di(C1-C4-alkyl)aminosulfonyl, C1-C6-alkylcarbonyl or in each case optionally substituted phenylsulfonyl or benzoyl, R36 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R37 is hydrogen, halogen, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, R38 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (Al 9) (formula removed) in which R39 is C1-C4-alkyl, characterized in that, in a first step, carboxamides of the formula (II) O in which the A radical is as defined above are reacted with haloalkylbenzenes of the formula (III) (no in which the R and R radicals are each as defined above and the X radical is a halogen atom in a metal-catalyzed reaction. 2. The process as claimed in claim 1, wherein carboxamides of the formula (II) which are selected from the group consisting of compounds of the formulae (IV) to (VI) (formula removed) are converted to carboxamides of the general formula (VIII) (formula removed) R and R radicals are each as defined in claim 1, Z is methyl, difluoromethyl or trifiuoromethyl and Y is hydrogen, methyl or fluorine. 3. The process as claimed in either of claims 1 or 2, characterized in that carboxamides of the formula (V) (formula removed) in which the X radical is a halogen atom to give a carboxamide of the formula (XI) (formula removed) 4. The process as claimed in any one of claims 1 to 3, characterized in that the metal catalyst is selected from palladium and copper catalysts. 5. The process as claimed in any one of claims 1 to 4, characterized in that at least one copper compound in catalytic amounts is used in the presence of a ligand. The process as claimed in any one of claims 1 to 5 using a base. The process as claimed in claim 5, wherein the Hgands used are diamines. A compound of the formula (III) (formula removed) in which R1 is hydrogen, halogen, -CR'(CF3)2 where R'= hydrogen, fluorine or 0-C1_ 4-alkyl, and R2 is -CH(Me)-CH2-CHMe2, -CH2-CH2-t-But or R1 is halogen, -CR'(CF3)2 where R'= hydrogen, fluorine or O-C1-4-alkyl, and (formula removed) and X is a halogen atom. A compound as claimed in claim 8 of the formula (IX) in which X is a halogen atom. A compound of the formulae (IV) to (VI) (formula removed) 11. The use of at least one compound as claimed in any one of claims 8 to 10 in a process as claimed in any one of claims 1 to 7.

Full Text

Method for producing alkylanilides from halobenzene derivatives
The present invention relates to a process for preparing known fungicidally active alkylanilides from 2-alkylhaloaromatics and heterocyclylamides.
EP-A-0 824 099 and WO-A-03010149 disclose that alkylanilides are obtained by reacting the appropriate acid chloride with the appropriate alkylaniline derivative.
Both preparation and handling of the acid chlorides and the preparation of the alkylanilides are associated with a considerable level of technical complexity. For example, the acid chlorides have to be purified before the reaction by a time-consuming and costly distillation step.
The anilines are prepared typically, as described in WO-A-3074491, by a complicated synthesis from the corresponding bromoaromatics and benzophenone imine or at temperatures of 150°C and pressures of from 75 to 85 bar with ammonia gas, as described in WO-A-06061226.
Alkylanilines, however, frequently exhibit toxic properties and are potentially mutagenic.
The prior art discloses that aryl halides can be reacted with amides under palladium or copper catalysis to give alkylanilides (J. Am. Chem. Soc. 2002,124, 7420).
It is frequently found, however, that metal-catalyzed reactions with heterocycles which can function as chelating ligands are inhibited. Furthermore, ortho-substituted haloaromatics are sterically hindered for a halogen exchange.
It is therefore an object of the present invention to provide a process for simple and selective preparation of alkylanilides, which does not have the disadvantages described in the prior art.
Surprisingly, conditions have been found under which heterocyclylamides can be reacted efficiently with ortho-substituted haloaromatics.
The present invention thus provides a process for preparing alkylanilides of the formula (I)

in which
R1 is hydrogen, halogen, -CR' (R' = hydrogen, fluorine or O-C1-4-alkyl), more preferably hydrogen;

R2 is -CH(Me)-CH2-CHMe2, -CH2-CH2-t-But, or v , particular
preference being given to -CH(Me)-CH2-CHMe2 and A is the radical of the formula (Al)

(FORMULA REMOVED)

in which
R3 is hydrogen, cyano, halogen, nitro, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C3-C6-cycloalkyl, C1-C4-haloalkyl, C1-C4-haloalkoxy or C1-C4-haloalkylthio having in each case from 1 to 5 halogen atoms, aminocarbonyl or aminocarbonyl-C1-C4-alkyl;
R4 is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy or C1-C4-alkylthio;
R5 is hydrogen, C1-C4-alkyl, hydroxy-C1-C4-alkyl, C2-C6-alkenyl, C3-C6-cycloalkyl, C1-C4-alkylthio-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-haloalkyl, C1 -C4-haloalkylthio-C 1 -C4-alkyl, C1 -C4-haloalkoxy-C 1 -C4-alkyl having in each case from 1 to 5 halogen atoms, or phenyl;
or
A is the radical of the formula (A2)
(FORMULA REMOVED

in which
7
R6 and R' are each independently hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,

R8 is halogen, cyano or C1-C4-alkyl, or C1-C4-haloalkyl or C1-C4-haloalkoxy
having in each case from 1 to 5 halogen atoms,
or
A is the radical of the formula (A3)
(FORMULA REMOVED
in which
R9 and R10 are each independently hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R11 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
(FORMULA REMOVED

in which
R12 is hydrogen, halogen, hydroxyl, cyano, C1-C6-alkyl, C1-C4-haloalkyl, C1-C4-haloalkoxy or C1-C4-haloalkylthio having in each case from 1 to 5 halogen atoms,
or
A is the radical of the formula (A5)
(FORMULA REMOVED
in which
R is halogen, hydroxyl, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-
C4-haloalkyl, C1-C4-haloalkylthio or C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms,
R14 is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms, C1-C4-alkylsulfinyl or C1-C4-alkylsulfonyl,
or
A is the radical of the formula (A6)
(FORMULA REMOVED
in which
R15 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R16 is C1-C4-alkyl,
Q1 is S (sulfur), O (oxygen), SO, SO2 or CH2,
p is 0, 1 or 2, where R16 represents identical or different radicals when p is 2,
or
A is the radical of the formula (A7)
(FORMULA REMOVED

in which
R17 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or

A is the radical of the formula (A8)
(FORMULA REMOVED

in which
R18 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (A9)
(FORMULA REMOVED

in which
R19 and R20 are each independently hydrogen, halogen, amino, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R21 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (Al 0)
(FORMULA REMOVED

in which
R22 and R23 are each independently hydrogen, halogen, amino, nitro, C1-C4-alkyl or C1-C4-haloalkyl having 1 to 5 halogen atoms,
R24 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (All)
(FORMULA REMOVED

in which
R25 is hydrogen, halogen, amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R26 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (A12)

(FORMULA REMOVED

n which
R27 is hydrogen, halogen, amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R28 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (A 13)
(FORMULA REMOVED

in which
R29 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
Or

A is the radical of the formula (A 14)
(FORMULA REMOVED

in which
>30
R30 is hydrogen or C1-C4-alkyl,
R31 is halogen or C1-C4-alkyl,
or
A is the radical of the formula (A 15)
R32 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms, or A is the radical of the formula (Al 6)
(FORMULA REMOVED

in which
R33 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (A 17)

(FORMULA REMOVED

in which
R34 is halogen, hydroxyl, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkylthio or C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms,
or
A is the radical of the formula (Al 8)

(FORMULA REMOVED
in which
R35 is hydrogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl having from 1 to 5 halogen atoms, C1-C4-alkoxy-C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C4-alkylsulfonyl, di(C1-C4-alkyl)aminosulfonyl, C1-C6-alkylcarbonyl or in each case optionally substituted phenylsulfonyl or benzoyl,
R36 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R37 is hydrogen, halogen, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R38 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (A 19)

(FORMULA REMOVED
in which
R39 is C1-C4-alkyl,
characterized in that,
in a first step, carboxamides of the formula (II)
(FORMULA REMOVED
in which the A radical is as defined above
are reacted with haloalkylbenzenes of the formula (III)
(III)
2
in which
the R1 and R2 radicals are each as defined above and the substituent R1 is preferably in the meta or para position, more preferably in the 4 position (para to X) of the aromatic; and
the X radical is a halogen, preferably C1 or Br, more preferably Br,
in a metal-catalyzed reaction.
The present invention further relates to compounds of the formula (III)
(FORMULA REMOVED)

where
R1 'is hydrogen, halogen, -CR'(CF3)2 (R'= hydrogen, fluorine or O-C1-4-alkyl), more preferably hydrogen, and the substituent R1 is preferably in the meta or para position, more preferably in the 4 position (para to X) of the aromatic; and
R2 is -CH(Me)-CH2-CHMe2 and -CH2-CH2-t-But,
or
R1 is halogen, -CR'(CF3)2 (R'= hydrogen, fluorine or O-C1-4alkyl), more preferably hydrogen, and the substituent R1 is preferably in the meta or para position, more preferably in the 4 position (para to X) of the aromatic; and
(FORMULA REMOVED
and
X is a halogen, preferably C1 or Br, more preferably Br.
The present invention additionally relates to the compounds of the formulae (IV) to (FORMULA REMOVED
A further aspect of the present invention relates to the use of the compounds of one of the formulae (II), (III), (IV), (V) and (VI) as reactants/intermediates in the process according to the invention described above.
(FORMULA REMOVED

(Scheme I)
In connection with the present invention, the term "halogen" (X) encompasses elements which are selected from the group consisting of fluorine, chlorine, bromine and iodine, preference being given to using chlorine and bromine, and particular preference to using bromine.
Optionally substituted radicals may be mono- or polysubstituted, where the
substituents may be the same or different in the case of polysubstitutions.
The definition "C1-C6-alkyl" encompasses the largest range for an alkyl radical defined herein. SpeC1fically, this definition encompasses the meanings of methyl, ethyl, n-, isopropyl, n-, iso-, sec-, tert-butyl, and in each case all isomeric pentyls and hexyls.
The definition "C2-C6-alkenyl" encompasses the largest range for an alkenyl radical defined herein. SpeC1fically, this definition encompasses the meanings of ethenyl, n-, isopropenyl, n-, iso-, sec-, tert-butenyl, and in each case all isomeric pentenyls and hexenyls.
The inventive compounds can optionally be used as mixtures of different possible isomeric forms, espeC1ally of stereoisomers, for example E and Z, threo and erythro, and also optical isomers, and if appropriate also of tautomers. It is possible to use both the E and the Z isomers, and also the threo and erythro isomers, and also the optical isomers, any mixtures of these isomers, and also the possible tautomeric forms.
The haloalkylbenzenes required are known in the prior art, for example from WO-A-03074491, or can be prepared by known methods by Friedel-Crafts alkylation or electrophilic aromatic halogenation.
A further possibility is that of reacting 2-halobenzaldehydes with Wittig reagents, in which case the propenone derivatives thus obtained, as described in WO-A-03 074491, can be converted to cyclopropyl compounds.
Other possibilities are the hydroxyalkylation of aromatics or metalated aromatics with ketones or aC1d chlorides and, respectively, the subsequent elimination and reduction thereof. Proceeding from 1,2-dibromobenzene, this is illustrated by way of example in scheme (II):
(FORMULA REMOVED

Alternatively, it is also possible to obtain the halogen compounds in question from aniline derivatives by diazotization and Sandmeyer reaction.
According to the present invention, the haloalkylbenzene of the formula (IX)

in which X is a halogen atom, espeC1ally Br, is a preferred reactant.
Only some of the aC1d amides required are known, and they can be obtained from known aC1d halides, aC1ds, esters or nitriles by known reactions.
This will be illustrated by the following example according to scheme (III):

(FORMULA REMOVED

The nitrogen source used may be aqueous or gaseous ammonia or one of its salts, for example ammonium acetate or sodium amide.
Useful solvents for the preparation of the aC1d amides include all solvents which are stable under the reaction conditions, for example ethers such as THF, 2-methyl-THF, dioxane, methyl t-butyl ether (MTBE), diethylene glycol, diethoxymethane, dimethoxymethane; aromatic hydrocarbons such as toluene, xylene, chlorobenzene, dichlorobenzene, benzene; aliphatic hydrocarbons such as petroleum ether, heptane, hexane, methylcyclohexane, cyclohexane; dimethylformamide (DMF); dimethylacetamide; N-methylpyrrolidone (NMP); dimethyl sulfoxide (DMSO), acetonitrile; butyronitrile; water; ketones such as acetone, methyl isobutyl ketone (MIBK); alcohols such as methanol, ethanol, isopropanol.
For the inventive reaction of the aC1d amide with the halobenzene derivative, metal catalysts are used. For this purpose, palladium and copper in all oxidation states are useful, for example in metallic form or in the form of salts.
According to the present invention, for example, Pd(OAc)2, Pd(OH)2, PdCb,
Pd(acac)2 (acac = acetylacetonate), Pd(NO3)2, Pd(dba)2, Pd2dba3, (dba -
dibenzylideneacetone), dichlorobis(triphenylphosphine)palladium(II),
Pd(CH3CN)2Cl2, tetrakis(triphenylphosphine)palladium(0), Pd/C or palladium nanoparticles, Cul, CuCl, CuSCN, Cu2O, CuO, CuCl2, CuSO4, CuBr, CuBr2, Cu2S, Cu(OAc)2, Cu(acac)2 are suitable, preference being given to using the copper compounds or mixtures thereof.
According to the present invention, the catalysts are used in catalytic amounts. This means that the metal catalysts are used in concentrations of from 0.01 to 50.0 mol%, preferably of 1.0 to 20.0 mol%, based on the carboxamides of the formula (II).
The inventive reaction is preferably performed in the presence of ligands.
In the case of palladium catalysis, suitable ligands are, for example, selected from the group of carbene and phosphine ligands, particular preference being given to using xantphos and tris(t-butyl)phosphine.
In the case of copper catalysis, suitable ligands are, for example, selected from the group consisting of diamines, for example N,N"-dimethyl-1,2-cyclohexanediamine (C1s or trans, racemic or as an enantiomer), NjN'-dimethylethylenediamine, ethylenediamine, N-methylethylenediamine, N-butylethylenediamine, N,N,N"-trimethylethylenediamine or else 1,10-phenanthroline, ethylenediaminetetraacetic aC1d, tetra-n-butylammonium fluoride, tris(3,6-trioxaheptyl)amine (TDA-1), particular
preference being given to using N,N'-dimethyl-1,2-cyclohexanediamine.
The ligands are added to the metal catalyst in such a ratio that the desired catalytic action occurs.
According to the present invention, the ratio of ligand to metal catalyst is between 0.5 to 10 equivalents, preferably between 1 to 5 equivalents.
The reaction is preferably carried out in the presence of bases. Useful examples include alkali metal and alkaline earth metal hydroxides such as KOH, NaOH, Ca(OH)2, fluorides such as KF, phosphates such as K3PO4, and carbonates such as potash, soda, cesium carbonate or phosphazene bases, alkoxides such as sodium tert-butoxide, or phenoxides such as sodium phenoxide.
According to the present invention, the bases are used in concentrations of from 0.5 to 5 equivalents, preferably from 1.0 to 3 equivalents, based on the carboxamides of the formula (II).
The inventive reaction of the aC1d amide with the halobenzene derivative is preferably carried out in a solvent.
The solvents used are preferably dioxane, THF, diglyme, toluene, xylene, DMF.
According to the present invention, the aC1d amides and the halobenzene derivatives are reacted with one another in an equimolar ratio. In an alternative embodiment, the halobenzene derivative can also be used in excess, for example as a solvent.
According to the invention, the aC1d amides are reacted with the halobenzene derivatives at temperatures in the range from 20 to 200°C, preferably from 70 to 150°C.
In a particularly preferred embodiment of the invention, carboxamides of the formula (V) are reacted with compounds of the formula (X)
in which the X radical is a halogen
to give carboxamides of the formula (XI)
(FORMULA REMOVED

The examples which follow are intended to illustrate the subject matter of the invention in detail, but without restricting it thereto.
Working examples l-Bromo-2-(l,3-dimethylbutyl)benzene
28.4 g of 2-(l,3-dimethylbutyl)aniline in 134.9 g (667 mmol) of 40 percent hydrobromic aC1d in glaC1al acetic aC1d at 10°C are admixed with 12.5 g (181 mmol) of sodium nitrite in portions with stirring within 1.5 h. Thereafter, 0.5 g of copper powder is added and the mixture is boiled under reflux for 1 h hour. Subsequently, 120 ml of water and sodium hydroxide solution are added until pH 12 is attained, and the organic phase is removed, washed with dilute hydrochloric aC1d and concentrated by evaporation under reduced pressure. After distillation in a Kugelrohr apparatus at 0.3 mbar/70°C and purification of the main fraction by means of preparative HPLC, 8.3 g of a yellowish oil with a purity of 99.4 % (determined by HPLC) are obtained.
]H NMR (400 MHz, CDC13): 0.89 (dd, 6H), 1.17 (d, 3H), 1.32-1.38 and 1.46-1.53 (2m, AB, 2xlH), 1.54-1.6 (m, 1H), 3.34 (m, 1H), 7 (m, 1H), 7.21-7.28 (m, 2H), 7.52 (d, 1H).

(FORMULA REMOVED

5-FIuoro-l,3-dimethyl-lH-pyrazole-4-carboxamide
19.9 g of 5-fluoro-1,3-dimethyl-lH-pyrazole-4-carbonyl chloride are added dropwise

at 20-35°C to a mixture of 35 g of 25 percent aqueous ammonia and 170 ml of THF. After stirring for 4 h, the organic solvent fraction is concentrated by evaporation under reduced pressure and 0.2 mol of potash and sodium chloride are added to saturation. After extracting four times with ethyl acetate and concentrating the combined organic phases by evaporation under reduced pressure, 16.6 g of a yellow solid are obtained.
*H NMR (400 MHz, d6-DMSO): 2.64 (s, 3H), 3.63 (s, 3H), 6.9 (broad s, 1H), 7.18 (broad s, 1H).
N-[2-(l,3-Dimethylbutyl)phenyl]-5-fluoro-l,3-dimethyl-lH-pyrazole-4-carboxamide
A mixture of 0.221 g (1.16 mmol) of copper iodide, 3.21 g (23.22 mmol) of potash
and 2.189 g of 5-fluoro-l,3-dimethyl-lH-pyrazole-4-carboxamide is admixed under
argon with 330 mg (2.322 mmol) of N,N"-dimethyl-1,2-cyclohexanediamine, 2.8 g
(11.6 mmol) of l-bromo-2-(l,3-dimethylbutyl)benzene and 30 ml of toluene. After
boiling under reflux for one day, the mixture is poured onto water and 10 ml of a 5%
EDTA solution. Subsequently, the mixture is extracted three times with ethyl acetate
and concentrated by evaporation under reduced pressure. The oily residue is dissolved
in toluene and stirred into n-hexane. After the preC1pitated crystals have been filtered
off with suction, 3.3 g (89% of the theoretical yield) of N-[2-(l,3-
dimethylbutyl)phenyl]-5-fluoro-l,3-dimethyl-lH-pyrazole-4-carboxamide are
obtained with a purity (HPLC) of 99 %.

Claims:
A process for preparing carboxamides of the general formula (I)

(formula removedin which
R1 is hydrogen, halogen, -CR' where R' = hydrogen, fluorine or O-C1-4-alkyl;

R2 is-CH(Me)-CH2-CHMe2, -CH2-CH2-t-But or
A is the radical of the formula (A 1)
(formula removed)in which
R3 is hydrogen, cyano, halogen, nitro, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C3-C6-cycloalkyl, C1-C4-haloalkyl, C1-C4-haloalkoxy or C1-C4-haloalkylthio having in each case from 1 to 5 halogen atoms, aminocarbonyl or aminocarbonyl-C1-C4-alkyl;
R4 is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy or C1-C4-alkylthio;
R5 is hydrogen, C1-C4-alkyl, hydroxy-C1-C4-alkyl, C2-C6-alkenyl, C3-C6-cycloalkyl, C1-C4-alkylthio-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, Cr C4-haloalkyl, C1 -C4-haloalkylthio-C 1 -C4-alkyl, C1 -C4-haloalkoxy-C 1 -C4-alkyl having in each case from 1 to 5 halogen atoms, or phenyl;
or
A is the radical of the formula (A2)

(formula removed)

in which

R6 and R'7are each independently hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R8 is halogen, cyano or C1-C4-alkyl, or C1-C4-haloalkyl or C1-C4-ha-loalkoxy having in each case from 1 to 5 halogen atoms,
or
A is the radical of the formula (A3)
-i^R-
in which

R9 and R10 are each independently hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R11 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (A4)

(formula removed)

in which
R12 is hydrogen, halogen, hydroxyl, cyano, C1-C6-alkyl, C1-C4-haloalkyl, C\-C4-haloalkoxy or C1-C4-haloalkylthio having in each case from 1 to 5 halogen atoms,
or

A is the radical of the formula (A5)

(formula removed)

in which
R13 is halogen, hydroxyl, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkylthio or C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms,
R14 is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms, C1-C4-alkylsulfinyl or C1-C4-alkylsulfonyl,
or
A is the radical of the formula (A6)

(formula removed)

in which
R13 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R16 is C1-C4-alkyl,
Q1 is S (sulfur), O (oxygen), SO, SO2 or CH2,
p is 0, 1 or 2, where R16 represents identical or different radicals when p
is 2,
or
A is the radical of the formula (A7)
(formula removed)in which
R17 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms ,

or
A is the radical of the formula (A8)
in which
R18 is C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (A9)
(formula removed)

in which
R19 and R20 are each independently hydrogen, halogen, amino, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R21 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (A 10)
(formula removed)

in which
R22 and R23 are each independently hydrogen, halogen, amino, nitro, C1-C4-alkyl or C1-C4-haloalkyl having 1 to 5 halogen atoms,

R24 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,

or
A is the radical of the formula (All)
(formula removed)

in which
R is hydrogen, halogen, amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino,
cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R26 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5
halogen atoms,
or
A is the radical of the formula (A 12)

(formula removed)

in which
R27 is hydrogen, halogen, amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R28 is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (A 13)
(formula removed)

in which
R is halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5
halogen atoms,
or
A is the radical of the formula (A 14)
(formula removed)

in which
R30 is hydrogen or C1-C4-alkyl,
R31 is halogen or C1-C4-alkyl,
or
A is the radical of the formula (Al 5)
(formula removed)

R32 is C1-C4-alkyl or C1-C4-haloalkyl having frorn 1 to 5 halogen atoms, or A is the radical of the formula (A 16)
(formula removed)

in which
R33 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (Al 7)

(formula removed)

in which
R34 is halogen, hydroxyl, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkyl, C1-C4-haloalkylthio or C1-C4-haloalkoxy having in each case from 1 to 5 halogen atoms,
or
A is the radical of the formula (Al 8)
(formula removed)

in which
R35 is hydrogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl having from 1 to 5 halogen atoms, C1-C4-alkoxy-C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C4-alkylsulfonyl, di(C1-C4-alkyl)aminosulfonyl, C1-C6-alkylcarbonyl or in each case optionally substituted phenylsulfonyl or benzoyl,
R36 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R37 is hydrogen, halogen, cyano, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
R38 is hydrogen, halogen, C1-C4-alkyl or C1-C4-haloalkyl having from 1 to 5 halogen atoms,
or
A is the radical of the formula (Al 9)

(formula removed)

in which
R39 is C1-C4-alkyl,
characterized in that,
in a first step, carboxamides of the formula (II)
O
in which the A radical is as defined above
are reacted with haloalkylbenzenes of the formula (III)
(no
in which the R and R radicals are each as defined above and the X radical is a halogen atom
in a metal-catalyzed reaction.
2. The process as claimed in claim 1, wherein carboxamides of the formula (II)
which are selected from the group consisting of compounds of the formulae (IV) to (VI)
(formula removed)

are converted to carboxamides of the general formula (VIII)
(formula removed)

R and R radicals are each as defined in claim 1,
Z is methyl, difluoromethyl or trifiuoromethyl and
Y is hydrogen, methyl or fluorine.
3. The process as claimed in either of claims 1 or 2, characterized in that carboxamides of the formula (V)
(formula removed)

in which the X radical is a halogen atom to give a carboxamide of the formula (XI)
(formula removed)

4. The process as claimed in any one of claims 1 to 3, characterized in that the metal catalyst is selected from palladium and copper catalysts.
5. The process as claimed in any one of claims 1 to 4, characterized in that at least one copper compound in catalytic amounts is used in the presence of a ligand.
The process as claimed in any one of claims 1 to 5 using a base.
The process as claimed in claim 5, wherein the Hgands used are diamines.
A compound of the formula (III)

(formula removed)

in which
R1 is hydrogen, halogen, -CR'(CF3)2 where R'= hydrogen, fluorine or 0-C1_ 4-alkyl, and
R2 is -CH(Me)-CH2-CHMe2, -CH2-CH2-t-But
or
R1 is halogen, -CR'(CF3)2 where R'= hydrogen, fluorine or O-C1-4-alkyl, and
(formula removed)

and
X is a halogen atom.
A compound as claimed in claim 8 of the formula (IX)

in which
X is a halogen atom. A compound of the formulae (IV) to (VI)
(formula removed)

11. The use of at least one compound as claimed in any one of claims 8 to 10 in a process as claimed in any one of claims 1 to 7.

Documents:

http://ipindiaonline.gov.in/patentsearch/GrantedSearch/viewdoc.aspx?id=auKpS4WW7mz7gLQkG2DJ/Q==&loc=+mN2fYxnTC4l0fUd8W4CAA==

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Patent Number

268982

Indian Patent Application Number

210/DELNP/2009

PG Journal Number

40/2015

Publication Date

02-Oct-2015

Grant Date

25-Sep-2015

Date of Filing

12-Jan-2009

Name of Patentee

BAYER INTELLECTUAL PROPERTY GMBH

Applicant Address

ALFRED-NOBEL-STR. 50, 40789 MONHEIM, GERMANY.

Inventors:

#	Inventor's Name	Inventor's Address
1	ALEXANDER STRAUB	WOTANSTR 13, 42117 WUPPERTAL, GERMANY.

PCT International Classification Number

C07D 231/14

PCT International Application Number

PCT/EP2007/006177

PCT International Filing date

2007-07-12

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	10 2006 033 090.0	2006-07-14	Germany