WO2007115685A1 - Method for producing biphenylamines from vinyl anilines - Google Patents

Abstract

The invention relates to a novel method for producing substituted biphenylamines (T), novel intermediate products and the production thereof, and to a method for producing fungicidal carboxamides. Formula (I).

Description

Process for the preparation of biphenylamines via vinylanilines

The present invention relates to a novel process for preparing substituted biphenylamines, novel intermediates and their preparation, and to a process for preparing fungicidally active carboxamides.

It is already known that biphenyl derivatives can be prepared from phenylboronic acids and phenyl halides by Suzuki or Stille coupling (cf., for example, WO 01/42223, WO 02/064562, WO 03/070705, Robertson and Hansen (eds.) PCBs, The University Press of Kentucky 2001, 57-60). Furthermore, it is known to obtain biphenyl derivatives by reacting aryl-zinc halides with aryl halides (Bull. Korean Chem. Soc. 2000, 21, 165-166).

A disadvantage of these methods are the high production costs. The preparation of a boronic acid requires a Grignard reaction, and transition metal-catalyzed cross-coupling (eg Suzuki) requires relatively high levels of palladium catalysts or (Bull. Korean Chem. Soc. 2000, 21, 165-166) the use of nearly equivalent amounts of zinc which must be disposed of as waste. To activate the zinc, moreover, the carcinogenic dibromoethane is needed.

Of particular disadvantage is the side reaction occurring homocoupling of boronic acids, which impairs the yield.

Furthermore, it is known that biphenyl derivatives are obtained by reacting alkynylanilides via a Diels-Alder reaction with dichlorothiophene dioxide (compare WO 2006/024388). The disadvantage here is that the alkynylanilide must be prepared over two stages, that it is decomposable and tends to form 2 + 2 adducts as by-products during the Diels-Alder step, which reduces the yield.

The object of the present invention was therefore to provide a new, economical process by which biphenylamines can be obtained with high overall yield and high purity.

The present invention thus relates to a process for the preparation of biphenylamines of the general formula (I)

in welcher(I)

in which

R ¹ represents hydrogen, fluorine, chlorine, dC ₄ alkyl, C _r C ₄ alkoxy, Ci-C ₄ alkylthio or C ₁ -C ₄ -

Haloalkyl is

X ^{1 is} fluorine, chlorine or bromine, X ^{2 is} fluorine, chlorine or bromine,

characterized in that (method A)

(1) in a first stage aniline compounds of the formula (II)

in welcher

in which

Hal is chlorine, bromine or iodine,

R ^{2 is} hydrogen,

R ^{3 is} hydrogen or the group A-CO- or a protecting group, or

R ² and R ³ together represent a protective group, A is one of the following radicals A ¹ to A 7:

R ^{5 is} C _r C ₃ -alkyl,

R ⁶ is hydrogen, halogen, C ₃ alkyl or C _r C ₃ -haloalkyl having 1 to 7 fluorine,

Chlorine and / or bromine atoms, R ^{7 is} hydrogen, halogen or C ₁ -C ₃ -alkyl,

R ^{8 is} hydrogen, halogen, C ₁ -C ₃ -alkyl, amino, mono- or di (C ₁ -C ₃ -alkyl) -amino, R ^{9 is} hydrogen, halogen, C ₁ -C ₃ -alkyl or C ₁ -C ₃ - Haloalkyl having 1 to 7 fluoro,

Chlorine and / or bromine atoms, R ¹⁰ is ₃ alkyl or C ₃ -haloalkyl having 1 to 7 fluorine, chlorine and / or bromine atoms is halogen, C, -C, R ¹¹ is halogen, C _r C ₃ - alkyl or C _r C ₃ -haloalkyl having 1 to 7 fluorine, chlorine and / or bromine atoms,

R ¹² is hydrogen, halogen, C _r C ₃ -alkyl or Ci-C is ₃ -haloalkyl having 1 to 7 fluorine, chlorine and / or bromine atoms, R ^{1 has} the meanings given above, reacted with ethene,

(2) in a second stage, the ethenyl aniline compounds of the formula (III) thus obtained

in welcher R¹, R² und R³ die oben angegebenen Bedeutungen haben, mit Thiophendioxiden der Formel (IV)

in which R ¹ , R ² and R ^{3 have} the meanings given above, with thiophene dioxides of the formula (IV)

in welcher X¹ und X² die oben angegebenen Bedeutungen haben, umsetzt, und

in which X ¹ and X ^{2 have} the meanings given above, and,

(3) in a third step, the dihydro-biphenylamides of the formulas (V-a) to (V-i) thus obtained

in welcher R¹, R², R³, X¹ und X² die oben angegebenen Bedeutungen haben, oxidiert, und

in which R ¹ , R ² , R ³ , X ¹ and X ^{2 have} the meanings given above, oxidized, and

in welcher(4) optionally in a fourth step, from the resulting biphenylamides of formula (VI)

in which

R ^{2 is} hydrogen and R ^{3 is} a protecting group, or

R ² and R ³ together represent a protecting group,

R ¹ , X ¹ and X ^{2 have} the meanings given above, the protective group split off at the nitrogen.

Surprisingly, the biphenylamines of the formula (I) can be prepared in good yields from inexpensive starting materials without a Grignard and Suzuki reaction by means of this reaction sequence. Compared to the prior art, the Diels-Alder reaction of the ethenyl aniline compounds with the thiophene derivatives surprisingly proceeds already at lower temperatures than with the alkynylanilides and thus allows a more selective course of the reaction with better yields and fewer side reactions of the reactants involved ,

If N- (2-bromo-4-fluoro-phenyl) -acetamide, ethene and 3,4-dichlorothiophene-1,1-dioxide are used as starting materials, process A according to the invention can be exemplified over all four stages by the following formula scheme.

Ethen / [Pd]

The protecting group can also be removed before the oxidation step, ie steps (3) and (4) can also be carried out in reverse order [first step (4) followed by step (3)]. Preference is given to carrying out process A according to the invention using starting materials in which the radicals indicated in each case have the following meanings. The preferred, particularly preferred and very particularly preferred meanings apply to all compounds in which the respective radicals occur.

Hal is preferably chlorine.

HaI is also preferred for bromine.

HaI is also preferred for iodine.

Hal is particularly preferably bromine.

R ¹ is preferably hydrogen.

R ¹ furthermore preferably represents fluorine, where fluorine is particularly preferably in the 3-, 4- or 5- position, very particularly preferably in the 3- or 5-position, in particular in the 5-position of the respective compound [cf. eg formula (I)]. R ¹ furthermore preferably represents chlorine, chlorine being particularly preferably in the 3- or 5-position of the respective compound.

R ¹ also preferably represents methyl or iso-propyl, with methyl or iso-propyl particularly preferably being in the 6-position of the respective compound.

R ¹ furthermore preferably represents trifluoromethyl, trifluoromethyl being particularly preferably in the 4- or 5-position of the respective compound.

R ¹ furthermore preferably represents methoxy or methylthio, with methoxy or methylthio particularly preferably being in the A, 5- or 6-position of the respective compound.

R ² and R ³ are each preferably hydrogen. In addition, R ² is preferably hydrogen and

R ³ is the group A-CO- or a protective group selected from methoxycarbonyl, 9-fluorenylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-

Trimethylsilylethoxycarbonyl, 1,1-dimethylpropoxycarbonyl, 1-methyl-1-phenylethoxycarbonyl, 1-methyl-1 - (4-biphenylyl) ethoxycarbonyl, 1, 1-dimethyl-2-haloethoxycarbonyl (wherein "halo" is fluorine or chlorine), 1, 1-dimethyl-2-cyanoethoxycarbonyl, t-butoxycarbonyl, cyclobutyloxycarbonyl, 1-methylcyclobutyloxycarbonyl, 1-adamantyloxycarbonyl, vinyloxycarbonyl, allyloxycarbonyl, cinnamyloxycarbonyl, 8-quinolyloxycarbonyl, N-hydroxypiperidinyloxycarbonyl, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 3,4-dimethoxy-6-nitrobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 5-benzisoxazolylmethoxycarbonyl, 9-anthrylmethoxycarbonyl,

Diphenylmethoxycarbonyl, isonicotinyloxycarbonyl, benzylthiocarbonyl, N- (N'-phenylamino) - - nothiocarbonyl) (which may optionally be substituted in the phenyl moiety), formyl, acetyl, propionyl, butyryl, pivaloyl, chloroacetyl, trichloroacetyl, trifluoroacetyl, o-nitrophenylacetyl, o-nitrophenoxyacetyl, acetoacetyl, 3-phenylpropionyl, 3- (p hydroxyphenyl) - propionyl, 2-methyl-2- (o-nitrophenoxy) propionyl, 2-methyl-2- (o -phenylazophenoxy) propionyl, 4-Chlorobutyryl, o-nitrocinnamoyl, N-picolinoyl, N ^λ -Acetylmethionyl , N-benzoyl,

Allyl, phenacyl, 3-acetoxypropyl, methoxymethyl, benzyloxymethyl, pivaloyloxymethyl, tetrahydropyranyl, 2,4-dinitrophenyl, benzyl, o-nitrobenzyl, di (p-methoxyphenyl) methyl, trityl, p- (methoxyphenyl) diphenylmethyl, diphenyl-4-pyridylmethyl , 2-picolyl N'-oxide, 5,5-dimethyl-3-oxo-1-cyclohexenyl, diphenylphosphinyl, dimethylthiophosphinyl, benzenesulfenyl, o-nitrobenzenesulfenyl, 2,4,6-trimethylbenzenesulfonyl, tosyl, mesyl, trifluoromethanesulfonyl , Benzenesulfonyl or phenacylsulfonyl.

In addition, R ² and R ^3, together with the nitrogen atom to which they are attached, are preferably 4,5-diphenyl-3-oxazolin-2-one, N-phthaloyl, N-dithiasuccinoyl, N, N'-isopropylidene, benzyli -, nitrobenzylidene or salicylidene. More preferably, R ^{2 is} hydrogen and

R ^{3 is} a protective group selected from methoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 1,1-dimethylpropoxycarbonyl, 1-methyl-1-phenylethoxycarbonyl, 1-methyl-1 - (4-biphenylyl) -ethoxycarbonyl, 1,1-dimethyl -2-haloethoxycarbonyl (in which "halo" is fluorine or chlorine), 1,1-dimethyl-2-cyanoethoxycarbonyl, t-butoxycarbonyl, cyclobutyloxycarbonyl, 1-methylcyclobutyloxycarbonyl, 1-adamantyloxycarbonyl, vinyloxycarbonyl,

Allyloxycarbonyl, cinnamyloxycarbonyl, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 9-anthryhnethoxycarbonyl, diphenyhnethoxycarbonyl, formyl, acetyl, pivaloyl, propionyl, butyryl, chloroacetyl, trichloroacetyl, trifluoroacetyl, o-nitrophenylacetyl, acetoacetyl, 3-phenylpropionyl, 3 (p-hydroxyphenyl) propionyl, 4-chlorobutyryl, N-benzoyl, allyl, phenacyl, 3-acetoxypropyl, methoxymethyl,

Benzyloxymethyl, pivaloyloxymethyl, tetrahydropyranyl, benzyl, benzenesulfenyl, 2,4,6-trimethylbenzenesulfonyl, tosyl, mesyl, trifluoromethanesulfonyl, benzenesulfonyl, phenacylsulfonyl.

In addition, R ² and R ³ together with the nitrogen atom to which they are attached are particularly preferred for N-phthaloyl, N, N'-isopropylidene, benzylidene or nitrobenzylidene. Most preferably, R ^{2 is} hydrogen and

R ^{3 is} a protective group selected from methoxycarbonyl, trichloroethoxycarbonyl, 1,1-dimethylpropoxycarbonyl, t-butoxycarbonyl, formyl, acetyl, pivaloyl, chloroacetyl, trichloroacetyl, trifluoroacetyl, acetoacetyl, benzoyl, mesyl, tosyl, phenylsulfonyl.

A is preferably Al, A2, A3, A4 or A5. A is particularly preferably Al or A2.

R ⁵ is preferably methyl.

R ⁶ is preferably iodine, methyl, difluoromethyl or trifluoromethyl.

R ⁶ particularly preferably represents methyl, difluoromethyl or trifluoromethyl.

R ⁷ is preferably hydrogen, fluorine, chlorine or methyl.

R ⁷ particularly preferably represents hydrogen or fluorine.

R ⁸ is preferably hydrogen, chlorine, methyl, amino or dimethylamino.

R ⁸ particularly preferably represents methyl.

R ⁹ is preferably methyl, difluoromethyl or trifluoromethyl.

R ¹⁰ is preferably chlorine, bromine, iodine, methyl, difluoromethyl or trifluoromethyl.

R ¹⁰ particularly preferably represents iodine, difluoromethyl or trifluoromethyl.

R ¹¹ is preferably bromine or methyl. R ¹¹ particularly preferably represents methyl.

R ¹² is preferably methyl or trifluoromethyl.

R ¹² particularly preferably represents methyl or trifluoromethyl.

X ¹ is preferably fluorine.

X ¹ is also preferably chlorine.

X ¹ is also preferably bromine.

X ² is preferably fluorine. X ² is also preferably chlorine.

X ² is also preferably bromine.

in welcher X¹ und X² die oben angegebenen Bedeutungen haben, erhalten.By the process A according to the invention, preference is given to biphenylamines of the formula (Ia)

in which X ¹ and X ^{2 have} the meanings given above, obtained.

Preferred starting materials are aniline compounds of the formula (II-a)

in welcher

in which

R ^{4 is} hydrogen, C _r C ₄ alkyl or Ci-C ₄ alkoxy, and

Hal have the meanings given above used.

In the aniline compounds of the formula (II-a), Hal has the preferred and particularly preferred meanings given above.

R ⁴ is preferably hydrogen, methyl, ethyl, iso-propyl, tert-butyl, methoxy, ethoxy, iso-propoxy or tert-butoxy.

R ⁴ particularly preferably represents methyl, tert-butyl, methoxy or tert-butoxy. R ⁴ is very particularly preferably methyl.

The aniline compounds of the formula (II) to be used as starting materials in carrying out the process A according to the invention in the first stage are known in some cases or can be obtained by known processes [cf. e.g. Synlett, 2003, (14), 2231; Recl. Trav. Chim. Pay-Bas. 1964, 83, 1142 ;. J. Het. Chem. 1969, 6, 243].

The ethenyl-aniline compounds of the formula (III) to be used as starting materials in carrying out the process A according to the invention in the second stage are partly new (in the case where R ^{1 is} fluorine) and are also the subject of this application. Ethenyl-aniline compounds of the formula (III) are obtained by the first step of the process A according to the invention. The thiophene dioxides of the formula (IV) to be used as starting materials in carrying out process A according to the invention in the second stage are known (cf., for example, J. Org. Chem. 1961, 26, 346-351, J. Fluorine Chem , 143-151; J. Amer. Chem. Soc. 2000, 122, 2440-2445).

Notes on the individual reaction stages:

First stage

The coupling of 2-bromo-aniline compounds and aryl halides with ethene (Heck reaction) is known in principle (compare J. Heterocyclic Chem. 1989, 26, 1405; Org. Process Res. Develop. 2002, 6, 67; Angew Chem. 1998, 110, 492; J. Het. Chem. 1990, 27, 1419; J. Org. Chem. 1978, 43, 2454).

The first step of the process A according to the invention is carried out in the presence of a transition metal. Precious metal catalyst carried out, preferably in the presence of a palladium catalyst such as Pd (OAc) ₂ , Pd (OH) ₂ , PdCl ₂ , Pd (acac) ₂ (acac = acetylacetonate), Pd (NO ₃ ) ₂ , Pd (dba) ₂ , Pd ₂ dba ₃ , (dba = dibenzylideneacetone), dichlorobis (triphenylphosphine) palladium (II), Pd (CH ₃ CN) ₂ Cl ₂ , tetrakis (triphenylphosphine) palladium (0), Pd / C or palladium nanoparticles.

In carrying out the first step of the process A of the invention is carried out in the presence of an inorganic or organic base. Examples of organic bases are diethylamine, dipropylamine, dibutylamine, dicyclohexylamine, piperidine, triethylamine, tripropylamine, tributylamine, DBU, DABCO. Examples of inorganic bases are potassium acetate, sodium acetate, potash, soda, potassium tert-butoxide, sodium tert-butoxide, sodium tert-amylate. Preferred are triethylamine, tributylamine, sodium acetate and potassium acetate.

In carrying out the first step of the process A of the invention can be carried out with or without the addition of ligands. Examples of ligands which may be mentioned are triarylphosphines, diarylalkylphosphines, diarylphosphines, dialkylphosphines, dialkylarylphosphines, trialkylphosphines, diaryl (dialkylamino) phosphines and arylbis (dialkylamino) phosphines. Preference is given to tri (o-tolyl) phosphine, triphenylphosphine, diphenylcycloalkylphosphines, di- and tri (cycloalkyl) phosphines, diadamantylphosphine, dinorbornyl-phosphine, di-tert-butylphosphine, dicyclohexylphosphine, diadamantylbutylphosphine, trialkyl phosphites and BINAP (BINAP = 2,2'-bis (diphenylphosphino) -1,1'-binaphthalene). It is also possible to use mixtures of the stated ligands. Particular preference is given to tri (o-tolyl) phosphine, triphenylphosphine, diphenyl-menthylphosphine, diphenyl-neomenthylphosphine, BINAP and mixtures of these phosphines. The molar ratio between metal and ligand can be varied widely, it is preferable to work at 1-6 equivalents.

The ligands are added either in the amount required for the desired molar ratio to the reaction mixture containing a ligand-free precursor of the catalyst such as a palladium salt such as PdCl ₂ or Pd (OAc) ₂ ; or one uses a complex already containing the ligand such as dichloro-bis (triphenylphosphine) palladium (II) or tetrakis (triphenylphosphine) palladium (0) and optionally additionally the same or a different ligand to set the desired molar ratio is.

If the first step of process A according to the invention is carried out in the presence of water, it is also possible to use triarylphosphines which are substituted on the aromatic such that the water solubility of the palladium complexes formed is increased. Such substituents may be, for example, sulfonic acid residues, carboxyl groups, phosphonic acid residues, phosphonium groups, peralkylammonium groups, hydroxy groups and polyether groups.

Furthermore, tetraalkonium salts such as tetrabutylammonium bromide, tetrabutyl ammonium acetate, AryUP-X (in which aryl is phenyl or o-tolyl and X is chlorine or bromine) can be used.

Further suitable ligands are, for example, EDTA, substituted diazabutadienes or 1,3-bis (aryl) imidazole carbenes.

When carrying out the first stage of process A according to the invention, the reaction is carried out in solvents or solvent mixtures. By way of example, mention may be made of N, N-dialkylalkanamides, e.g. N-methylpyrrolidone, dimethylformamide and dimethylacetamide, ketones such as acetone,

Diethyl ketone, methyl ethyl ketone and methyl isobutyl ketone, nitriles, e.g. Acetonitrile and

Butyronitrile, ethers, e.g. Dimethoxyethane (DME), tetrahydrofuran (THF), 2-methyl-THF and

Dioxane, alcohols such as e.g. Methanol, ethanol, n-propanol, isopropanol and isoamyl alcohol, water, ethylene carbonate or propylene carbonate.

In carrying out the first step of the process A according to the invention is generally carried out at temperatures in the range of 20 ⁰ C to 15O ⁰ C, preferably in the range of 50 ⁰ C to 130 ⁰ C. In the implementation of the first stage of the method A according to the invention for 1 mole of anilide of the formula (II) is generally an excess of ethylene (3-120 bar) and between 0.001 and 10 mol% transition metal catalyst and 0.5 to 10 moles of a base. Products of the first stage can also be obtained from 2-alkynyl-aniline compounds by reduction of the triple bond, for example with the aid of a Lindlar catalyst.

Second step

So far, only the reaction of some alkenes with tetrachlorothiophene-l, l-dioxide has been described (J. Org. Chem. 1980, 45, 856).

In carrying out the second stage of the process A according to the invention operates in the common AIl- at temperatures between 20 ⁰ C and 150 ⁰ C. The temperature is selected as low as possible to minimize side reactions and decomposition of the starting materials to be avoided, but high enough for the reaction to still running fast enough.

The second stage of process A according to the invention is preferably carried out in the presence of a solvent.

Suitable solvents for carrying out the second step of process A according to the invention are: aliphatic and aromatic hydrocarbons, chlorinated hydrocarbons, nitriles, alcohols, ketones, ethers, amides or esters. Specific examples which may be mentioned are: toluene, xylene, methylcyclohexane, mesitylene, decalin, tetralin, chlorobenzene, dichlorobenzene, nitrobenzene, nitrotoluene, butyronitrile, valeronitrile, cyclohexanone, ethylene glycol monoethyl ether, anisole, dimemylformamide, ethyl acetate, isopropyl acetate, butyl acetate. Toluene, xylene, butyronitrile or valeronitrile are preferably used.

In order to minimize the dimerization of thiophene dioxides of the formula (TV), an ethenyl anilide of the formula (III) can be initially charged in a solvent and a thiophene dioxide of the formula (IV) can be added.

It is possible to use, per mole of ethenyl anilide of the formula (III), 0.5 mol to 1.5 mol, preferably 0.9 mol to 1.25 mol, of thiophene dioxide of the formula (TV). In general, however, the thiophene dioxide of the formula (TV) is used in approximately equimolar amounts. The purification of the product is carried out by conventional methods of organic chemistry, for example by crystallization.

Third step

The oxidation of the dihydro stage to the aromatic can be carried out by oxidants, with the aid of oxidation catalysts, or by combination of oxidants with suitable Oxidationskata- catalysts. Catalysts which may be mentioned are noble metal catalysts such as Pd, Pt, iridium, Rhodium. The noble metals may be present on support materials such as activated carbon, Al ₂ O ₃ or silica gel, or as nanoparticles. They can be used either individually or as mixtures. The addition of other metals such as Fe, Co, Ni, Cu, Ag, V, Mn either in metallic form or as salts, such as halides, sulfates, nitrates or acetates, may be useful.

Metals such as Fe, Co ₅ Ni, Cu, Ag, V, Mn either in metallic form or as salts, such as halides, sulfates, nitrates or acetates and molybdovanadophosphoric also come as catalysts for air or oxygen-driven aromatizations in question.

Molybdovanadophosphoric acids (eg H ₅ [PMO _IO V ₂ O ₄₀ ] X 32.5 H ₂ O) can be prepared as described in the reference (Price, Anal. Chem. 1963, 35, 595) and immobilized on a carrier material such as activated carbon ( Chem., 1991, 56, 5707).

The addition of hydrogen acceptors may also be useful. In principle, all systems which are capable of accepting hydrogen, such as e.g. Nitroaromatics such as nitrobenzene or nitrotoluene, alkenes such as cyclopentene or cyclohexene, diethyl malonate, maleic anhydride, tetralin or acetylenes such as methyl butynol.

Suitable oxidizing agents are, for example, potassium permanganate, barium manganate, manganese dioxide, selenium dioxide, sodium periodate, lead (IV) acetate, ammonium molybdate, hydrogen peroxide, persulfates such as oxones, activated carbon, sulfur, oxygen, quinones such as benzoquinone, chloranil, 2,3-dichloro-5 , 6-dicyano-p-benzoquinone (DDQ), tetracyanoethylene, nitric acid, nitric acid esters, ceric ammonium nitrate, t-butyl nitrite, nitrogen oxides, K ₃ Fe [(CN) ₆ ] or electrochemical processes. The oxidizing agents may optionally be recycled in situ.

Suitable solvents are all solvents which are inert under the conditions, e.g. aliphatic and aromatic hydrocarbons, chlorinated hydrocarbons, nitriles, alcohols, ketones, ethers, amides or esters. In detail, be mentioned. Methylcyclohexane, mesitylene, decalin, tetralin, chlorobenzene, dichlorobenzene, nitrobenzene, nitrotoluene, toluene, xylene, acetic acid, propionic acid, acetonitrile, butyronitrile, valeronitrile, dimethylformamide, ethyl acetate, isopropyl acetate, butyl acetate, N-methylpyrolidinone, N, N-dimethylacetamide, ethylene glycol monoethyl ether, Methyl t-butyl ether, anisole, acetone, methyl isobutyl ketone, alcohols or water. It is also possible to use solvent mixtures. Toluene, xylene, butyronitrile or valeronitrile are preferably used.

It works depending on the oxidizing agent at temperatures between -10 ° and 200 ⁰ C. Of oxidizing agents must be used for a quantitative conversion at least equimolar amounts based on the oxidation equivalent. In some cases, up to 10 equivalents may be required. In the case of catalysts, 0.01 to 10 mol% are generally sufficient.

Examples of aromatization reactions are found in the literature (e.g., Pd / C / nitrobenzene / molecular sieve in Org. Lett., 2002, 4, 2557; Pd in Synth. Comm., 1996, 26, 4633).

Fourth Stage The deprotection of the respective protecting group on the nitrogen is carried out by conventional methods (see, for example, T.W. Greene, P.G.M. Wuts, Protective Groups in Organic Synthesis, Ed 3, New York, Wiley & Sons, 1999).

If the starting material used is a compound of the formula (II-a), the removal of the protective group [-C (OO) R ⁴ ] on the nitrogen can be carried out either basic or acidic by known methods (cf., for example, TW Greene, PGM Wuts, Protective Groups in Organic Synthesis, Ed. 3, New York, Wiley & Sons, 1999).

Steps 2, 3 and 4 of process A according to the invention are generally carried out under atmospheric pressure, unless stated otherwise. However, it is also possible to work under elevated or reduced pressure.

The biphenylamines of the formula (I) are valuable intermediates for the preparation of fungicidal active compounds.

Thus, fungicidally active carboxamides (cf., WO 03/070705) of the formula (VII)

in welcher

in which

R ^{1 is} hydrogen, fluorine, chlorine, C 1 -C ₄ -alkyl, C 1 -C ₄ -alkoxy, C 1 -C ₄ -alkylthio or QC ₄ -haloalkyl,

X ^{1 is} fluorine, chlorine or bromine, - -

X ^{2 is} fluorine, chlorine or bromine,

A is one of the following radicals A1 to A7:

R ⁵ is C _r C ₃ alkyl, R ⁶ is hydrogen, halogen, Ci-C ₃ alkyl or C _r C ₃ -haloalkyl having 1 to 7 fluorine, chlorine and / or bromine atoms,

R ^{7 is} hydrogen, halogen or C ₁ -C ₃ -alkyl,

R ⁸ is hydrogen, halogen, C ₃ alkyl, amino, mono- or di (Ci-C ₃ alkyl) amino, R ⁹ is hydrogen, halogen, _Ci-C3 alkyl or _Ci-C3 haloalkyl having 1 to 7 fluorine, chlorine and / or bromine atoms,

R ^{10 is} halogen, C _r C ₃ alkyl or C _r C ₃ haloalkyl having 1 to 7 fluorine, chlorine and / or

Bromsoms, R ^{11 is} halogen, C _r C ₃ alkyl or Ci-C ₃ haloalkyl having 1 to 7 fluorine, chlorine and / or

Bromine atoms, R ¹² ₃ alkyl or Ci-C is ₃ -haloalkyl having 1 to 7 fluorine, chlorine and / or bromine atoms, hydrogen, halogen, C _r C,

by making (method B)

(1) in a first stage aniline compounds of the formula (II)

in welcher

in which

Hal is chlorine, bromine or iodine,

R ^{2 is} hydrogen,

R ^{3 is} hydrogen or the group A-CO- or a protective group, or R ² and R ³ together represent a protective group,

R ¹ and A have the meanings given above, reacted with ethene, (2) in a second stage, the ethenyl aniline compounds of the formula (III) thus obtained

in welcher R¹, R² und R³ die oben angegebenen Bedeutungen haben, mit Thiophendioxiden der Formel (IV)

in which R ¹ , R ² and R ^{3 have} the meanings given above, with thiophene dioxides of the formula (IV)

in welcher X¹ und X² die oben angegebenen Bedeutungen haben, umsetzt, und

in which X ¹ and X ^{2 have} the meanings given above, and,

(3) in a third step, the dihydro-biphenylamides of the formulas (V-a) to (V-i) thus obtained

in welcher R¹, R², R³, X¹ und X² die oben angegebenen Bedeutungen haben, oxidiert, und

in which R ¹ , R ² , R ³ , X ¹ and X ^{2 have} the meanings given above, oxidized, and

in welcher(4) optionally in a fourth step, from the resulting biphenylamides of formula (VI)

in which

R ^{2 is} hydrogen and R ^{3 is} a protecting group, or

R ² and R ³ together represent a protecting group,

R ¹ , X ¹ and X ^{2 have} the meanings given above, the protective group is split off on the nitrogen, and

(5) optionally in a fifth step, the biphenylamines of the formula (I) thus obtained

in welcher R¹, X¹ und X² die oben angegebenen Bedeutungen haben, mit Carbonsäure-Derivaten der Formel (VIII)

in which R ¹ , X ¹ and X ^{2 have} the meanings given above, with carboxylic acid derivatives of the formula (VIII)

in welcher

in which

A has the abovementioned meanings and Y is halogen or hydroxyl, if appropriate in the presence of a catalyst, if appropriate in the presence of a condensing agent, if appropriate in the presence of an acid binder and if appropriate in the presence of a diluent.

Preference is given to carrying out process B according to the invention using starting materials in which the radicals indicated in each case have the following meanings. The preferred, particularly preferred and very particularly preferred meanings apply to all compounds in which the respective radicals occur.

Hal, A, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , X ¹ and X ² have the above preferred, particularly preferred and very particularly preferred meanings Y is preferably chlorine or hydroxyl. The first to fourth stages of method B correspond to the first to fourth stages of the method A according to the invention and are carried out as described above.

The carboxylic acid derivatives of the formula (VIII) to be used as starting materials in carrying out the process A according to the invention in the fifth stage are known and / or can be prepared by known processes (cf., WO 03/066609, WO 03/066610, cf. EP-A 0 545 099, EP-A 0 589 301, EP-A 0 589 313 and US 3,547,917).

Suitable diluents for carrying out the fifth step of process B according to the invention are all inert organic solvents. These include, preferably, aliphatic, alicyclic or aromatic hydrocarbons, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons, such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; Ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; Ketones such as acetone, butanone, methyl isobutyl ketone or cyclohexanone; Nitriles, such as acetonitrile, propionitrile, n- or i-butyronitrile or benzonitrile; Amides, such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; their mixtures with water or pure water.

The fifth step of process B according to the invention is optionally carried out in the presence of a suitable acid acceptor. As such, all customary inorganic or organic bases are suitable. These preferably include alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates or bicarbonates, such as, for example, sodium hydride, sodium amide, lithium diisopropylamide, sodium methoxide, sodium ethoxide, potassium tert-butoxide , Sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, potassium carbonate, potassium hydrogencarbonate, sodium bicarbonate or ammonium carbonate, and also tertiary amines, such as trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, N, N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-Methyhnorpholine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).

The fifth step of process B according to the invention is optionally carried out in the presence of a suitable condensing agent. As such, all condensing agents conventionally used for such amidation reactions are suitable. Examples which may be mentioned are acid halide biidners such as phosgene, phosphorus tribromide, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride or thionyl chloride; Anhydridbildner such as ethyl chloroformate, Chlorameisensäureme- ethyl ester, isopropyl chloroformate, isobutyl chloroformate or methanesulfonyl chloride; Carbodiimides, such as N, N'-dicyclohexylcarbodiimide (DCC), other conventional condensing agents, such as phosphorus pentoxide, polyphosphoric acid, N, N'-caprotyldidnazole, 2-ethoxy-N-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), triphenylphosphine, carbon tetrachloride or bromine. tripyrrolidinophosphonium hexafluorophosphate.

The fifth step of process B according to the invention is optionally carried out in the presence of a catalyst. Examples which may be mentioned are 4-dimethylaminopyridine, 1-hydroxybenzotriazole or dimethylformamide.

The reaction temperatures can be varied in carrying out the fifth step of the process B according to the invention in a wider range. In general, the reaction is carried out at temperatures of from ⁰ ° C. to 150 ^° C., preferably at temperatures of from ⁰ ° C. to 80 ^° C.

For carrying out the fifth step of the process B according to the invention for preparing the compounds of the formula (VII), in general 0.8 to 15 mol, preferably 0.8 to 8 mol, of biphenylamine are added per mole of the carboxylic acid derivative of the formula (VIII) Formula (I).

The process according to the invention for preparing biphenylamines and for preparing fungicidally active carboxamides is described in the following examples, which further illustrate the above description. However, the examples are not to be interpreted in a limiting sense.

- -

Preparation Examples

Step 1: N-r (4-fluoro-2-vinyl) phenyllacetamide

First embodiment with 1 mol% Pd catalyst and tri (o-tolyl) phosphine / Pd = 2:

To a mixture of 165.8 g (0.714 mol) of 2-bromo-4-fluoroacetanilide and 144.6 g (2 equivalents, 199.1 mL, 1.43 mol) of triethylamine in 1.3 L of DMF is added 4.35 g (2 mol%, 14.3 mmol) of tri (o-tolyl) phosphine and 1.6 g (1 mol%, 7.14 mmol) of palladium (II) acetate and stirred in an autoclave at an ethene pressure of 30 bar for 16 hours at 110 ⁰ C is then filtered off with suction, the residue washed twice with 60 ml of DMF and the filtrates were evaporated in vacuo at 65 ° C. The residue is taken up in 600 ml of ethyl acetate, stirred and again filtered with suction from insoluble constituents. The filtrate is washed three times with 200 ml of water and evaporated. This gives 125.5 g of the target compound with a purity of 92.7% (GC) (yield 90.9% of theory). This is taken up in 330 ml of toluene at 70 ⁰ C, cooled, filtered off and washed three times with 50 ml of toluene after. This gives 102.7 g of a finely crystalline residue (purity 98.8% (GC), yield 79.2% of theory) of the target compound with melting point 110-112 ° C. ¹ H-NMR (400 MHz; d _ö -DMSO): d = 2.0 (s, 3H, acetyl), 5.37 (d, IH, = CH ₂ ), 5.88 (d, IH, = CH ₂ ), 6.83 (dd, IH, CH), 7.1, 7.35, 7.48 (3m, 3xlH, aromat), 9.54 (s, IH, NH).

Exemplary embodiment with 0.5 mol% Pd catalyst and triphenylphosphine

To a mixture of 769.5 g (99.5% purity) (3.3 mol) of N- (2-bromo-4-fluorophenyl) acetamide and 667 g (6.6 mol) of triethylamine in 5.5 l DMF 17.48 g (66 mmol) of triphenylphosphine and 17.48 g (16 mmol) of palladium (II) acetate and stirred in an autoclave at an ethene pressure of 75 bar for 7.5 hours at 100 ^° C. The mixture is then filtered off with suction, the residue washed three times with 250 ml of DMF. The yield of target product in the mother liquor is 87.2% of theory (against standard). The filtrate is mixed with 0.5 g pyrocatechol and evaporated at 3, 5 -5mm / 58 ° C heating bath temperature. The residue is stirred four times with 4 l of toluene at 8O ⁰ C and sucked hot over a 3 cm high layer of silica gel. The filtrate is evaporated to 1.2 1, cooled with stirring to 0 ⁰ C and filtered off with suction. The residue is superficially stirred with 480 ml of methylcyclohexane and filtered with suction. This is repeated with 400 ml of methylcyclohexane. - -

As a result, the impurities dissolved in the residual toluene are pushed out of the filter cake by the MCH front, without their precipitation occurring in MCH. The target product is obtained in 74% yield (versus standard) and 93% purity with a melting point of 1 10-112 ⁰ C.

Second embodiment with 0.25 mol% Pd catalyst and triphenylphosphine To a mixture of 7.65 g (33 mmol) of N- (2-bromo-4-fluorophenyl) acetamide and 6.68 g (66 mmol) of triethylamine in 55 ml DMF is added 86.56 mg (0.33 mmol) of triphenylphosphine and 18.52 mg (0.083 mmol) of palladium (II) acetate and stirred in an autoclave at an ethene pressure of 30 bar for 16 hours at 110 ⁰ C. Subsequently filtered off with suction, the residue washed twice with 10 ml of DMF and the filtrate was evaporated in vacuo at 60 ⁰ C. The residue is taken up in ethyl acetate and again filtered with suction through insoluble constituents over Celite. The filtrate is then extracted by shaking once with 10 ml of water and then once with 10 ml of saturated aqueous ΝaCl solution, dried and evaporated. This gives 5.37 g of the target compound with a purity of 95.1% (GC), which corresponds to a yield of 86% of theory.

Third example with 0.25 mol% Pd catalyst and NaOAc as base:

86.56 mg (0.33 mmol) are added to a mixture of 7.65 g (33 mmol) of N- (2-bromo-4-fluorophenyl) acetamide and 5.41 g (66 mmol) of sodium acetate in 55 ml of DMF. Triphenylphosphine and 18.52 mg (0.083 mmol) of palladium (II) acetate and stirred in an autoclave at an ethene pressure of 30 bar for 16 hours at 110 ⁰ C is then filtered off with suction, the residue washed twice with 10 ml of DMF and the Filtrat in vacuo at 60 ⁰ C evaporated. The residue is taken up in ethyl acetate and again filtered with suction from insoluble constituents over Celite. The filtrate is then extracted by shaking once with 10 ml of water and then once with 10 ml of saturated aqueous ΝaCl solution, dried and evaporated. This gives 5.31 g of the target compound with a purity of 96.6% (GC), which corresponds to a yield of 87% of theory.

Step 2: Ν-f 2- (3,4-dichlorocyclohexa-2,4-dien-1-yl) -4-fluorophenylacetamide

First example 50 g (0.4 mol, purity 98.8%) of N - [(4-fluoro-2-vinyl) phenyl] acetamide and 53.5 g (1.05 equivalents, 0.288 mol, purity 99.6%) 3 , 4-Dichlorthiophen-l, l-dioxide are suspended in 1 1 of toluene, which is obtained after heating to 62 ° C, a 12% educt solution. The mixture is stirred at 62 ° C for 22 h. It sucks from the insoluble and evaporated. The residue is stirred with 600 ml of petroleum ether and filtered with suction. Yield 81.4 g (90% of theory, purity 91.4% GCMS / FID). Melting point 110-116 ⁰ C.

Second embodiment

To a 68-70 ⁰ C hot solution of 6 g (32 mmol, purity 95.7%) of N - [(4-fluoro-2-vinyl) phenyl] acetamide in 25 ml of toluene is added dropwise with stirring over 3 h from a dropping funnel cooled at 15.degree. C., a solution of 6.2 g (33.3 mmol, purity 99.4%) of 3,4-dichlorothiophene-1,1-dioxide in 60 ml of absolute toluene and stirred for 3.5 h 70 ⁰ C to. After removal of the solvent in vacuo, a total of 11.2 g of a solid, which still contains 15% toluene. Yield 87% of theory, purity 75% (GC-MS). ¹ H-NMR (400 MHz, ds-DMSO): d = 2.04 (s, 3H, acetyl), 2.48-2.62 (m, 2H, CH ₂ ), 4.04 (m, IH, = CH), 6.13 (d, IH, = CH), 6.27 (t, IH, = CH), 7.05-7.2 (m, 2H, 2aromat.), 7.21-7, 31 (m, IH, aromat), 9.44 (s, IH, NH).

Step 3: N- (3'.4'-dichloro-5-fluorobiphenyl-2-yl) acetamide

First embodiment with MnO ₂

A solution of 10.66 g (26.65 mmol, 75% purity) of Ν- [2- (3,4-dichloro-cyclohexa-2,4-dien-1-yl) -4-fluorophenyl] acetamide in 200 ml of toluene while stirring for 10 h at 95 ° C in portions with a total of 16.4 g (187 mmol, purity 99.4%) manganese dioxide added, while still warm with suction over Celite, the Celite washed several times with toluene and the combined organic solutions evaporated. This gives 8.7 g (purity 57% vs. standard, yield 62.9%) of the target compound.

Second embodiment with Pt

A solution of 0.82 g (2.39 mmol, purity 87.5%) of N- [2- (3,4-dichloro-cyclohexa-2,4-dien-1-yl) -4-fluorophenyl] acetamide in 20 ml 1,2-dichlorobenzene is mixed with 1 mol% of a platinum catalyst (1% Pt / C,

50% wet with water), 0.7 mg of silver mate and 0.332 mg of tetralin were added and treated for a total of 12 hours stirred at 160 ⁰ C. It is suctioned off on Celite, washed with ethyl acetate and evaporated the eluate in vacuo. This gives 0.64 g of crystals (purity 85.6% HPLC against standard, yield 77% of theory).

Third Ausföhrungsbeispiel with Pt

22 mmol (7.5 g, purity 87.5%) of N- [2- (3,4-dichloro-cyclohexa-2,4-dien-1-yl) -4-fluorophenyl] acetamide are dissolved in 137 g of DCB with 17 g (2 mol%) 1% Pt / C (50% wet), 5 mol% (199 mg) of Cu (OAc) ₂ , and one equivalent (2.89 g) of tetralin stirred at 160 ⁰ C for 3.5 hours, wherein at the beginning the water was distilled off. It is suctioned off on Celite, washed with ethyl acetate and evaporated in vacuo. Yield 3.5 g of crystals (72% of theory).

Fourth Embodiment with H ₅ [PMo _I0 V ₂ O ₄₀ ]

1. Catalyst preparation: 1 eq of MoO3 and 0.5 eq of NaVO3 are added to water at a rate of about 85 percent. Phosphoric acid and cook for 8 hours. After acidification with conc. HCl is extracted with ether, the ethereal phase evaporated and the residue dried in a drying oven. The catalyst (H ₅ [PMo _I oV ₂ O _4O ], is dissolved in methanol, treated with the appropriate amount of activated carbon and evaporated.

2. Aromatization: A solution of 27.5 g (80.9 mmol, purity 88%) of N- [2- (3,4-dichloro-cyclohexa-2,4-dien-1-yl) -4-fluorophenyl] acetamide in 450 ml of toluene is added with stirring to 30 g of 5% Polyoxomolybdovanadat on activated carbon (0.65 mmol = 1.5 g of pure cat, 0.8 mol%) and stirred at 100 ⁰ C for 16 h. It sucks at 70 ⁰ C on Celite, washed four times with warm toluene and evaporated. The target product is obtained in 86% purity and 87% yield.

Step 4: 3'.4'-dichloro-5-fluorobiphenyl-2-amine

To a suspension of 6.3 g (0.02 mol, purity: 95%) of N- (3 ', 4'-dichloro-5-fluorobiphenyl-2-yl) acetamide and 12 ml of 2-methoxyethanol are added 0 , 08 mol of an approximately 45% aqueous potassium hydroxide solution. It is heated to 100 ⁰ C, stirred for 4 hours, cooled and the solvent distilled off in vacuo. The residue is stirred with ice-water and extracted several times with toluene. After drying and distilling off the toluene, 4.8 g (yield: 92% of theory) of 3 ', 4'-dichloro-5-fluorobiphenyl-2-amine as a brown solid. Melting point: 58 ° C.

Step 5: N- (3'4'-Dichloro-5-fluorobiphenyl-2-yl) -3- (difluoromethvn-1-methyl-7H-pyrazole-4-carboxamide

782 mg (3 mmol, purity 98.3%) of 3 ', 4'-dichloro-5-fluorobiphenyl-2-amine and 606 mg (3 mmol, purity 96.3%) of 3- (difluoromethyl) -1-methyl- 7H-pyrazole-4-carbonyl chloride are dissolved in 6 ml of toluene and stirred at 110 ⁰ C for 1 hour. It is mixed at 30 ⁰ C with 20 ml of methylcyclohexane and filtered off the precipitated crystals. This gives 1.157 g (purity 96.7%; yield 90% of theory) of N- (3 ', 4'-dichloro-5-fluorobiphenyl-2-yl) -3- (difluoromethyl) -1-methyl-7H pyrazole-4-carboxamide with the logP (pΗ2.3) = 3.33.

Claims

Patent claims Process for producing biphenylamines of the general formula (I) in which R1 represents hydrogen, fluorine, chlorine, CrC4-alkyl, Ci-C4-AlkOXy, d-C4-alkylthio or C1 C4-haloalkyl, X1 represents fluorine, chlorine or bromine, represents hydrogen, R3 represents hydrogen or the group A-CO- or a protective group, or R2 and R3 together represent a protective group, A represents one of the following radicals Al to A7: R5 represents Ci-Cs-alkyl, R6 represents hydrogen, halogen, CrC3-alkyl or Q-Cs-haloalkyl with 1 to 7 fluorine, chlorine and/or bromine atoms, R7 represents hydrogen, halogen or C1-C3-AUCyI, R8 represents hydrogen, halogen, d- C3-alkyl, amino, mono- or di(Ci-C3-alkyl)amino, - - R9 represents hydrogen, halogen, d-C3-alkyl or d-C3-haloalkyl with 1 to 7 fluoro-, chloro- and / or bromine atoms, R10 represents halogen, CrC3-alkyl or Ci-C3-haloalkyl with 1 to 7 fluorine, chlorine and/or bromine atoms, R11 represents halogen, C,-C3-alkyl or QQ-haloalkyl with 1 to 7 fluorine, chlorine and/or bromine atoms, R12 represents hydrogen, halogen, Ci-C3-alkyl or Ci-C3-haloalkyl with 1 to 7 fluorine, chlorine and/or bromine atoms, R1 has the meanings given above, reacted with ethene, (2) in a second stage, the resulting ethenyl-AnUin compounds of the formula (JS) in which R 1, D R2. and..ndJ Γ R> 3 have the meanings given above, with thiophene dioxides of the formula (TV) in which X1 and X2 have the meanings given above, and (3) in a third stage, the dihydro-biphenylamides of the formulas thus obtained (Va) to (Vi) in which R1, R2, R3, X1 and and R3 represents a protective group, or R2 and R3 together represent a protective group, R1, X1 and X2 have the meanings given above, the protective group is removed on nitrogen. 2. The method according to claim 1, characterized in that the starting materials are aniline compounds of the formula (II-a) in which R4 is hydrogen, d-C4-alkyl or Ci-C4-AlkOXy, and HaI has the meanings given above , used. Process for producing biphenylamines of the general formula (I) in which R1 represents hydrogen, fluorine, chlorine, CrC4-alkyl, CrC4-alkoxy, d-C4-alkylthio or C1-C4-haloalkyl, X1 represents fluorine, chlorine or bromine , 7 fluorine, chlorine and/or bromine atoms, R7 represents hydrogen, halogen or Ci-C3-alkyl, R8 represents hydrogen, halogen, Ci-C3-alkyl, amino, mono- or di(Ci-C3-alkyl) amino, R9 represents hydrogen, halogen, Ci-C3-alkyl or Ci-C3-haloalkyl with 1 to 7 fluorine, chlorine and / or bromine atoms, R10 represents halogen, Ci-C3-alkyl or CrC3-haloalkyl with 1 up to 7 fluorine, chlorine and/or bromine atoms, R11 represents halogen, CrC3-alkyl or Ci-C3-haloalkyl with 1 to 7 fluorine, chlorine and/or bromine atoms, R12 represents hydrogen, halogen, d-C3 -Alkyl or d-C3-haloalkyl with 1 to 7 fluorine, chlorine and / or bromine atoms, prepared by (Procedure B) (1) in a first stage, aniline compounds of the formula (II) - -

in which Hal stands for chlorine, bromine or iodine, R ² stands for hydrogen, R ³ represents hydrogen or the group A-CO- or a protecting group, or R ² and R ³ together represent a protective group, R ¹ and A have the meanings given above, reacted with ethene, (2) in a second stage, the resulting ethenyl-aniline compounds of the formula (JS)

in which R ¹ , R ² and R ³ have the meanings given above, with thiophene dioxides of the formula (FV)

in which X ¹ and X ² have the meanings given above, and (3) in a third stage, the resulting dihydrobiphenylamides of the formulas (V-a) to (V-i)

- -

in which R ¹ , R ² , R ³ , X ¹ and X ² have the meanings given above, oxidized, and (4) optionally in a fourth stage from the thus obtained biphenylamides of the formula (VI)

in which R ² represents hydrogen and R ³ represents a protecting group, or R ² and R ³ together represent a protective group, R ¹ , X ¹ and X ² have the meanings given above, the protective group on the nitrogen is removed, and (5) optionally in a fifth stage the biphenylamines of the formula (I) thus obtained

in which R, X and X have the meanings given above, with carboxylic acid derivatives of the formula (VIII) O KY (VIII) in which A has the meanings given above and Y represents halogen or hydroxy, optionally in the presence of a catalyst, optionally in the presence of a Condensing agent, optionally in the presence of an acid binding agent and optionally in the presence of a diluent. 4. The method according to claim 3, characterized in that the starting materials are aniline compounds of the formula (II-a)

in which R ⁴ is hydrogen, dC ₄ alkyl or Ci-C ₄ alkoxy, and Hal has the meanings given above. 5. The method according to claim 1 or 3, characterized in that the starting materials are compounds of the formula (II)

in which Hal stands for chlorine, bromine or iodine, R ¹ represents hydrogen, fluorine, chlorine, Ci-C ₄ -alkyl ₅ C _r C ₄ -alkoxy, Ci-C ₄ -alkylthio or C ₁ -C ₄ -haloalkyl, R ² represents hydrogen, and R ³ represents methoxycarbonyl, trichlorethoxycarbonyl, 1,1-dimethylpropoxycarbonyl, t-butoxycarbonyl, formyl, acetyl, pivaloyl, chloroacetyl, trichloroacetyl, trifluoroacetyl, acetoacetyl, benzoyl, mesyl, tosyl, phenylsulfonyl. 6. Ethenyl-aniline compounds of the formula (III)

in which R ¹ represents fluorine and R ² and R ³ have the meanings given in claim 1. 7. Ethenyl-aniline compounds of formula (III-a)

in which R ⁴ represents hydrogen, dC ₄ alkyl or C,-C ₄ alkoxy. 8. Ethenyl-aniline compounds of the formula (III-a) according to claim 7, in which R ⁴ is methyl. 9. A process for producing ethenyl-aniline compounds of the formula (III) according to claim 6, characterized in that Aniline compounds of the formula (II)

in which, HaI, R ² and R ¹ have the meanings given in claim 1, reacted with ethene. 10. Dihydro-biphenylamides of the formulas (Va) to (Vi)

in which R, R, R, X and X have the meanings given in claim 1. 11. Dihydro-biphenylamides of the formulas (Va) to (Vi) according to claim 10, in which R ² is hydrogen, and R ³ represents methoxycarbonyl, trichlorethoxycarbonyl, 1,1-dimethylpropoxycarbonyl, t-butoxycarbonyl, formyl, acetyl, pivaloyl, chloroacetyl, trichloroacetyl, trifluoroacetyl, acetoacetyl, benzoyl, mesyl, tosyl, phenylsulfonyl. - - 12. Dihydro-biphenylamides of the formulas

in which R ⁴ represents hydrogen, dC ₄ alkyl or Ci-C ₄ alkoxy, and R ¹ , X ¹ and X ² have the meanings given in claim 1. 13. Dihydro-biphenylamide of the formula

14. Dihydro-biphenylamide of the formula

- - 15. A process for producing biphenylamides of the formulas (V-a) to (V-i) according to claim 10, characterized in that (1) in a first stage, aniline compounds of the formula (II)

in which Hal stands for chlorine, bromine or iodine, R ² stands for hydrogen, R ³ represents hydrogen or the group A-CO- or a protective group, or R ² and R ³ together represent a protective group, R ¹ and A have the meanings given in claim 1, reacted with ethene, (2) in a second stage, the resulting ethenyl-aniline compounds of the formula QU)

in which R ¹ , R ² and R ³ have the meanings given in claim 1, with thiophene dioxides of the formula (IV)

in which X ¹ and X ² have the meanings given in claim 1.