Process for preparing aromatic amines from aryl chlorides

Abstract

The present invention relates to process for preparing an aromatic amine (I) which comprises reacting an aromatic chloride (II) with an aminating agent (IV) selected from ammonia, an aliphatic or cycloaliphatic primary or secondary amine in the presence of a copper catalyst comprising copper and a ligand of the formula (III) or a salt thereof (III) where X, Y are identical or different and selected from the group consisting of halogen, OH, OR1, NH2, NHR2, N(R2)2, SH, SR3, SO3H, S(O)kR4 with k being 1, 2 or 3, where R1, R2, R3, R4 independently of each other are selected from the group of C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C6-C10 aryl and C6-C10 aryl-C1-C4-alkyl, where aryl in the last two mentioned moieties is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals Ra, where Ra is selected form F, CN, NO2, OH, SO3H, CH3, CF3 and OCH3; Z are both H or together form –CH=CH-.

Description

[0001] Process for preparing aromatic amines from aryl chlorides

[0002] The present invention relates to a process for preparing aromatic amines from aryl chlorides via the cross-coupling of aryl chlorides with an aminating agent, selected from ammonia, primary and secondary amines, using a copper catalyst with specific nitrogen containing ligands.

[0003] TECHNICAL BACKGROUND

[0004] Aromatic amines, in particular aromatic primary amines are of greatest interest for example as active ingredients in pharmaceuticals and agricultural chemicals but also as building blocks for active ingredients, dyes or in the synthesis of monomers like aromatic isocyanates (see: Amines, Aromatic in Ullmann’s Encyclopedia of Industrial Chemistry, DOI: 10.1002 / 14356007. a02_037)

[0005] Besides the reduction of nitro groups in aromatic nitro compounds, one of the most relevant routes to synthesize primary aromatic amines is the amination via crosscoupling of an ary I- halide with a corresponding nitrogen source such as ammonia. For this cross-couplings, metal catalysts are required which are usually based on palladium, nickel or copper (see: ACS Catalysis, 2018, 8, 405-418). To reduce catalyst costs and avoid the use of harmful metals such as nickel, copper as the active catalyst metal is preferred, preferably in as low as possible loadings. The use of aryl chlorides as starting materials is preferred, as they are significantly cheaper than the corresponding aryl bromides and aryl iodides. However, they are usually considered less reactive than their bromo and iodo analogues. Additionally, the cross coupling of aryl chlorides is often carried out in harmful or critical solvents, such as dimethylsulfoxide (DMSO; about its hazardous properties see: Org.

[0006] Process. Res. Dev. 2020. 24, 916-939), N,N-Dimethylformamide (DMF; see: Green Chem. 2016, 18, 288-296) or N-methyl-pyrrolidone (NMP; see: Green Chem. 2016, 18, 288-296 for the classification of NMP and DMF as hazardous solvents). Therefore, it is highly desirable to reduce the amount of such solvents in the reaction medium or even to completely avoid them to achieve a sustainable process.

[0007] Certain processes have been disclosed in the prior art, where the cross-coupling of aryl chlorides with aminating agents have been successfully achieved using copperbased catalysts and avoiding the use of the critical solvents DMSO, DMF or NMP.

[0008] For example, J. Chin. Chem. Soc. 2010, 57, 604-611 discloses the cross coupling of different aryl chlorides with aqueous ammonia in the presence of CuSO4as the catalyst and using a polyethylene glycol imidazolium compound and methyl cyclohexane as solvent / ligand. A drawback of this system is the large amount of copper-catalyst required (50 mol%) to achieve good product yields and also the requirement of a large amount of polyethylene glycol imidazolium compound as co- solvent / ligand.

[0009] Eur. J. Org. Chem. 2011, 4523-4527 discloses the cross coupling of aryl chlorides with aqueous ammonia in the presence of 50 mol% oxalyl dihydrazide, 100 mol% hexane-2, 5-dione, 25 mol% tetrabutylammonium bromide and 200 mol% K3PO4in water as the solvent using 10 mol% CuO as catalyst. Fundamental drawbacks of this approach are the large number and amount of additives in the reaction which result in relatively high costs for the additives and large amounts of waste formed in the work-up.

[0010] CN102557858A discloses a CuSO4catalyzed cross coupling of aryl chloride compounds, such as chlorobenzene or 4-nitrochlorobenzene, with aqueous ammonia as aminating agent in the presence of polyethylenglycol-800 as cosolvent and stoichiometric amounts of sugars such as sucrose or glucose. Despite the high loadings of the copper catalyst of 60 mol%, the desired arylamines are only formed in low yields, for example 26% in case of aniline from chlorobenzene.

[0011] US5091580 discloses a Cu2O catalyzed cross coupling of 2,6-d if I uro chlorobenzene with aqueous ammonia without an additional solvent at 160° C for 42 hours. The cross coupling requires a long reaction time and high loads of copper of 10 mol% of Cu2O which means 20 mol% of copper. Moreover, the process is limited to the use of electron poor aromatics with two fluoro substituents. A similar reaction is disclosed in CN101245020B with a reduced loading of Cu2O of 2 mol% corresponding to 4 mol% copper. Again, the reaction is limited to the electron poor aromatics with two fluoro-substituents.

[0012] RSC Advances, 2013, 3, 5819-5823 discloses a ligand free cross coupling of some aryl chlorides using 5 mol% Cui at 200° C under hydrothermal conditions with aqueous NH3is described. Despite this relatively harsh temperatures of 200° C, the best yield is 71 % of the desired aromatic amine and in all other cases only moderate yields of 54-69 % could be achieved.

[0013] It is apparent from the foregoing that the prior art leaves room for improvement, especially with respect to an application in large-scale industrial production processes. For instance, the amount of required copper in the catalyst is still rather high and minimizing the amount of hazardous organic solvents or even avoid them at all is for economic as well as ecologic reasons desired. SUM MARY OF TH E INVENTION

[0014] Therefore, there is a need for providing a process of cross coupling of aryl chlorides with an aminating agent in the presence of copper as a catalyst which avoids at least some of the drawbacks of the processes of the prior art, especially when these processes are carried on a large scale, e. g. on industrial production scale. I n particular, it is an object of the present invention to provide a process for producing aromatic amines via the cross-coupling of aryl chlorides with aminating agents selected form ammonia, primary and secondary amines in the presence of copper as a catalyst, which process requires low amounts of copper. Moreover, the process should be applicable to a broad variety of aryl chlorides. Furthermore, the process should allow for reducing or avoid the use of organic additives, such as organic solvents, organic co-solvents, phase transfer catalysts and surfactants, and which is well-suited for large-scale production.

[0015] The object is achieved by a process for preparing aromatic amines, in particular those of the formula (I) as described herein, which comprises reacting an aromatic chloride (I I) in the presence of a copper catalyst comprising copper and a ligand of the formula (I II) or a salt thereof, as described herein, with an aminating agent (IV) selected from ammonia, an aliphatic or cycloaliphatic primary or secondary amines, where the reaction is in particular carried out in an aqueous reaction mixture containing aminating agent (I II) and where the reaction is in particular carried out in the presence of a base different from the aminating agent.

[0016] Therefore, the present invention relates to process for preparing an aromatic amine (I) which comprises reacting an aromatic chloride (II) with an aminating agent (IV) selected from ammonia, an aliphatic or cycloaliphatic primary or secondary amine in the presence of a copper catalyst comprising copper and a ligand of the formula (II I) or a salt thereof where

[0017] X, Y are identical or different and selected from the group consisting of halogen, OH, OR1, NH2, NHR2, N(R2)2, SH, SR3, SO3H, S(O)kR4with k being 1, 2 or 3, where R1, R2, R3, R4independently of each other are selected from the group of CJ-CJQ alkyl, C C^ haloalkyl, C3-C10cycloalkyl, C6-C10aryl and C6-C10aryl-C1-C4-al kyl, where aryl in the last two mentioned moieties is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals Ra, where Rais selected form F, CN, NO2, OH, SO3H, CH3, CF3and OCH3;

[0018] Z are both H or together form -CH=CH-; where the reaction is preferably carried in the presence of a base different from the aminating agent (IV) and where the reaction is preferably carried out in an aqueous reaction mixture containing aminating agent (IV).

[0019] The process of the present invention provides the aromatic amines in high yields with comparatively low catalyst loads. The process can be carried out without requiring organic solvents, co-solvents and phase transfer catalysts. In particular, the process can be carried out with high efficiency in an aqueous reaction medium without requiring the use of surfactants, phase transfer catalyst or other organic additives, such as organic solvents or co-solvents. In particular, the process does not require the use of hazardous or otherwise problematic organic solvents, such as DMSO, NMP or DMF. Therefore, their amount can be significantly reduced or even they can be completely avoided. Moreover, the process should be applicable to a broad variety of aryl chlorides. Furthermore, the process is well-suited for large- scale production, i.e. production on industrial scale.

[0020] DETAILED DESCRIPTION OF THE INVENTION

[0021] The organic moieties mentioned in the above definitions of the variables are - like the term halogen - collective terms for individual listings of the individual group members.

[0022] The term “Cn-Cm" as used herein refers to the range of the number of carbon atoms a moiety may have.

[0023] The term halogen denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine.

[0024] The term "alkyl" as used herein and in the alkyl moieties of alkoxy and the like refers to saturated straight-chain or branched hydrocarbon radicals having 1 to 2 ("C1-C2-alkyl"), 1 to 3 ("C1-C3-alkyl"),l to 4 ("C1-C4-alkyl"), 1 to 6 ("Cj-Cg-alkyl") or 1 to 10 ("Cj-Cjo-alkyl") carbon atoms. C1-C2-Alkyl is methyl or ethyl. C1-C3-Alkyl is additionally propyl and isopropyl. C1-C4-Alkyl is additionally n-butyl, 1- methylpropyl (sec-butyl), 2-methylpropyl (isobutyl) or 1, 1 -di methy lethyl (tert-butyl). Cj-Cg-Alkyl is additionally also, for example, pentyl, 1-methylbutyl, 2-methylbutyl, 3- methylbutyl, 2,2-di methyl propyl, 1 -ethyl propyl , 1,1-dimethylpropyl, 1,2- dimethyl propyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4- methylpentyl, 1,1-dimethylbutyl, 1 ,2-d imethyl butyl , 1,3-dimethylbutyl, 2.2- dimethyl butyl , 2,3-dimethylbutyl, 3, 3-d imethyl butyl , 1 -ethyl butyl , 2-ethy I butyl , 1,1,2- trimethyl propyl , 1,2,2-trimethylpropyl, 1-ethyl-l-methylpropyl, or l-ethyl-2- methylpropyl. Cj-CjQ-Alkyl is additionally also, for example, heptyl, octyl, nonyl and decyl and the isomers thereof.

[0025] The term "haloalkyl" as used herein, which is also expressed as "alkyl which is partially or fully halogenated", refers to straight-chain or branched alkyl groups having 1 to 2 ("C1-C2-haloalkyl"), 1 to 3 ("C1-C3-haloalkyl"), 1 to 4 ("Cj-C^- haloalkyl"), 1 to 6 ("Cj-Cg-haloalkyl") or 1 to 10 ("Cj-Cjo-haloalkyl") carbon atoms (as mentioned above), where some or all of the hydrogen atoms in these groups are replaced by halogen atoms, in particular by fluorine or chlorine as mentioned above: in particular C1-C2-haloalkyl, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1- fluoroethyl, 2-f I uoroethyl , 2,2-dif I uoroethyl , 2,2,2-trif I uoroethyl , 2-chloro-2- fluoroethyl, 2-chloro-2,2- difluoroethyl, 2,2-dich loro-2-f I uoroethyl , 2,2,2- trichloroethyl or pentafluoroethyl. C1-C3-haloalkyl is additionally, for example, 1- fluoropropyl, 2-f I uoropropy I, 3- fluoropropyl, 1,1-difluoropropyl, 2,2-dif luoropropyl, 1,2-difluoropropyl, 3,3-difluoropropyl, 3,3,3-trif luoropropyl, heptafluoropropyl, 1,1,1- trif I uoroprop-2-yl , 3-chloropropyl and the like. Examples for C1-C4-haloalkyl are, apart those mentioned for C1-C3- haloa I kyl, 4-chlorobutyl and the like. Haloalkyl is in particular “Methyl which is substituted by 1, 2 or 3 fluorine atoms” such as fluoromethyl, difluoromethyl or trifluoromethyl.

[0026] The term "C2-C10alkenyl" as used herein denotes monounsaturated straight-chain or branched hydrocarbon radicals having 2 to 6 ("C2-C6alkenyl") or 2 to 10 ("C2-C10alkenyl") carbon atoms and a double bond in any position, for example C2-C6alkenyl, such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2- butenyl, 3-butenyl, 1-methyl-l-propenyl, 2-methyl-l-propenyl, l-methyl-2- propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,

[0027] 1-methyl-l-butenyl, 2-methyl-l-butenyl, 3-methyl-l-butenyl, l-methyl-2-butenyl,

[0028] 2-methyl-2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2-methyl-3-butenyl,

[0029] 3-methyl-3-butenyl, l,l-dimethyl-2-propenyl, 1,2-dimethyl-l-propenyl, 1,2- dimethyl-2-propenyl, 1-ethyl-l-propenyl, l-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-l-pentenyl, 2-methyl-l-pentenyl, 3- methyl-l-pentenyl, 4-methyl-l-pentenyl, l-methyl-2-pentenyl, 2-methyl-2- pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, l-methyl-3-pentenyl, 2- methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, l-methyl-4- pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1- dimethyl-2-butenyl, l,l-dimethyl-3-butenyl, 1,2-dimethyl-l-butenyl, 1,2-dimethyl- 2-butenyl, l,2-dimethyl-3-butenyl, 1,3-dimethyl-l-butenyl, l,3-dimethyl-2-butenyl, l,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-l-butenyl, 2,3- dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-l-butenyl, 3,3-dimethyl- 2-butenyl, 1-ethyl-l-butenyl, l-ethyl-2-butenyl, l-ethyl-3-butenyl, 2-ethyl-l- butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1, 1 ,2-tri methyl -2- propenyl , 1-ethy 1-1- methyl -2- ropenyl, 1 -ethyl -2- methyl -1- ropenyl, 1 -ethyl -2- methyl -2- propenyl and the like, or C2-C10alkenyl, such as the radicals mentioned for C2-C6- alkenyl and additionally 1-heptenyl, 2-heptenyl, 3-heptenyl, 1-octenyl, 2-octenyl, 3- octenyl, 4-octenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 4-nonenyl, 1-decenyl, 2- decenyl, 3-decenyl, 4-decenyl, 5-decenyl and the positional isomers thereof. In particular, "C2-C10alkenyl" is "C2-C4alkenyl", such as ethenyl or l-propen-2-yl.

[0030] The term "haloalkenyl" as used herein, which is also expressed as "alkenyl which is partially or fully halogenated", refers to straight-chain or branched alkenyl groups having 2 to 3 ("C2-C3-haloalkenyl"), 2 to 4 ("C2-C4-haloalkenyl"), 2 to 6 ("C2-C6- haloalkenyl") or 2 to 10 ("C2-C10-haloalkyl") carbon atoms (as mentioned above), where some or all of the hydrogen atoms in these groups are replaced by halogen atoms, in particular by fluorine or chlorine as mentioned above.

[0031] The term “Cj-CjQ-Hydroxyalkyl” refers Cj-C^-al kyl , as defined above, where one hydrogen atom is replaced by a hydroxy group. Examples are hydroxymethyl, 1- hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, 1- hydroxy-l-methylethyl, 2-hydroxy-l-methylethyl, 1-hydroxybutyl, 2-hydroxybutyl, 3- hydroxybutyl, 4-hydroxybutyl, 1-hydroxypentyl, 2-hydroxypentyl, 3-hydroxypentyl, 4- hydroxypentyl, 5-hydroxypentyl, 1-hydroxyhexyl, 2-hydroxyhexyl, 3-hydroxyhexyl, 4- hydroxyhexyl, 5-hydroxyhexyl, 6-hydroxyhexyl, and the like.

[0032] The term “alkoxy” refers to an alkyl group as defined above, which is attached via an oxygen atom and which typically has 1 to 10 carbon atoms ("Cj-CjQ-alkoxy"). The term "C1-C2-alkoxy" is a C1-C2-alkyl group, as defined above, attached via an oxygen atom. The term "C1-C3-alkoxy" is a C1-C3-alkyl group, as defined above, attached via an oxygen atom. The term "Cj-^-alkoxy" is a Cj-^-alkyl group, as defined above, attached via an oxygen atom. The term "Cj-Cg-alkoxy" is a Cj-Cg-alkyl group, as defined above, attached via an oxygen atom. C1-C2-Alkoxy is methoxy or ethoxy. CrC3-Alkoxy is additionally, for example, n-propoxy and 1-methylethoxy (isopropoxy). C1-C4-Alkoxy is 5 additionally, for example, butoxy, 1-methylpropoxy (sec-butoxy),

[0033] 2-methylpropoxy (isobutoxy) or 1,1-dimethylethoxy (tert-butoxy). Cj-Cg-Alkoxy is additionally, for example, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3- methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1- ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4- methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2- dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2- ethylbutoxy, 1,1,2- trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-l- methylpropoxy or l-ethyl-2-methylpropoxy.

[0034] The term “haloalkoxy” refers to a haloalkyl group as defined above, which is attached via an oxygen atom and which typically has 1 to 10 carbon atoms (CJ-CJQ- haloalkoxy). The term "C1-C2-haloalkoxy" is a C1-C2-haloalkyl group, as defined above, attached via an oxygen atom. The term "C1-C3-haloalkoxy" is a Cj-C^- haloalkyl group, as defined above, attached via an oxygen atom. The term "Cj-CTr haloalkoxy" is a C1-C4-haloalkyl group, as defined above, attached via an oxygen atom. The term "Cj-Cg-haloalkoxy" is a Cj-Cg-haloalkyl group, as defined above, attached via an oxygen atom. C1-C2-Haloalkoxy is, for example, OCH2F, OCHF2, OCF3, OCH2CI, OCHCI2, OCCI3, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2- iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trif luoroethoxy, 2-chloro-2-fluoroethoxy, 2- chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2- trichloroethoxy or OC2F5. C1-C3-Haloalkoxy is additionally, for example, 2-fluoropropoxy, 3- fluoropropoxy, 2,2-difluoropropoxy, 2,3-difluoropropoxy, 2-chloropropoxy, 3- chloropropoxy, 2,3-dichloropropoxy, 2-bromopropoxy, 3- bromopropoxy, 3,3,3- trifluoropropoxy, 3,3,3-trichloropropoxy, OCH2-C2F5, OCF2-C2F5, l-(CH2F)-2- fluoroethoxy, l-(CH2CI)-2-chloroethoxy or l-(CH2Br)-2-bromoethoxy. Cj-C4- Haloalkoxy is additionally, for example, 4-fluorobutoxy, 4-chlorobutoxy, 4- bromobutoxy or nonafluorobutoxy. Cj-Cg-Haloalkoxy is additionally, for example, 5- fluoropentoxy, 5-chloropentoxy, 5-brompentoxy, 5-iodopentoxy, undecafluoropentoxy, 6-fluorohexoxy, 6-chlorohexoxy, 6-bromohexoxy, 6- iodohexoxy or dodecafluorohexoxy.

[0035] The term “Hydroxy-Cj-Cjo-alkoxy” refers Cj-C^-alkoxy, as defined above, where one hydrogen atom is replaced by a hydroxy group. Examples are hydroxymethoxy, 1-hydroxyethyloxy, 2-hydroxyethyloxy, 1-hydroxypropyloxy, 2-hydroxypropyloxy,

[0036] 3- hydroxy propyl oxy, 1-hydroxy-l- methyl ethyl oxy, 2- hydroxy-1 -methylethyloxy,

[0037] 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl, 1-hydroxypentyl,

[0038] 2-hydroxypentyloxy, 3-hydroxypentyloxy, 4-hydroxypentyloxy, 5-hydroxypentyloxy, 1-hydroxyhexyloxy, 2-hydroxyhexyloxy, 3-hydroxyhexyloxy, 4-hydroxyhexyloxy, 5-hydroxyhexyloxy, 6-hydroxyhexyloxy, and the like. The term "cycloalkyl" as used herein refers to mono- or bicyclic saturated hydrocarbon radicals having 3 to 10 ("C3-C10-cycloalkyl"), 3 to 8 ("C3-C8-cycloalkyl"), in particular 3 to 6 ("C3-C6-cycloalkyl") carbon atoms. Examples of monocyclic radicals having 3 to 4 carbon atoms are cyclopropyl and cyclobutyl. Examples of monocyclic radicals having 3 to 5 carbon atoms are cyclopropyl, cyclobutyl and cyclopentyl. Examples of monocyclic radicals having 3 to 6 carbon atoms are cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Examples of monocyclic radicals having 3 to 8 carbon atoms are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Examples of monocyclic radicals having 3 to 10 carbon atoms are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl. The bicyclic radicals can be condensed or bridged rings. Examples of bicyclic condensed radicals having 6 to 10 carbon atoms comprise bicyclo[3.1.0] hexyl, bicyclo[3.2.0] heptyl, bicyclo[3.3.0]octyl (1,2, 3, 3a, 4, 5, 6, 6a- octahydropentalenyl), bicyclo[4.2.0]octyl, bi eye I o [4.3.0] n o ny I (2, 3, 3a, 4, 5, 6, 7,7a- octahydro-1 H-indene), bicyclo[4.4.0]decyl (decalinyl) and the like. Examples of bridged bicyclic condensed radicals having 7 to 10 carbon atoms comprise bicyclo[2.2.1] heptyl, bicyclo[3.1.1 ] heptyl, bicyclo[2.2.2]octyl, 30 bicyc I o [3.2.1] octy I and the like. Preferably, the term cycloalkyl denotes a monocyclic saturated hydrocarbon radical.

[0039] The term "halocycloalkyl" as used herein, which is also expressed as "cycloalkyl which is partially or fully halogenated", refers to mono- or bicyclic saturated hydrocarbon groups having 3 to 10 ("C3-C10-halocycloalkyl") or 3 to 8 ("C3-C8- halocycloalkyl") or preferably 3 to 6 ("C3-C6-halocycloalkyl") or 3 to 5 ("C3-C5- halocycloalkyl") or 3 to 4 ("C3-C4-halocycloalkyl") carbon ring members (as mentioned above) in which some or all of the hydrogen atoms are replaced by halogen atoms as mentioned above, in particular fluorine, chlorine and bromine.

[0040] The term "alkynyl" as used herein refers to straight-chain or branched aliphatic hydrocarbon radicals having in general 2 to 10 ("C2-C10-alkynyl") carbon atoms, specifically 2 to 6 ("C2-C6-alkynyl") or 2 to 4 ("C2-C4-alkynyl") carbon atoms, and one triple bond in any position. "C2-C3-Alkynyl" indicates straight-chain or branched hydrocarbon radicals having 2 to 3 carbon atoms and one triple bond in any position. "C2-C4-Alkynyl" indicates straight-chain or branched hydrocarbon radicals having 2 to 4 carbon atoms and one triple bond in any position. "C2-C6-Alkynyl" indicates straight-chain or branched hydrocarbon radicals having 2 to 6 carbon atoms and one triple bond in any position. "C2-C8-Alkynyl" indicates straight-chain or branched hydrocarbon radicals having 2 to 8 carbon atoms and one triple bond in any position. "C2-C10-Alkynyl" indicates straight-chain or branched hydrocarbon radicals having 2 to 10 carbon atoms and one triple bond in any position; etc. Examples for C2-C3-alkynyl are ethynyl, 1-propynyl or 2-propynyl. Examples for C2- C4-al kynyl are ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl,

[0041] 1-methyl-2-propynyl and the like. Examples for C2-C6-alkynyl are ethynyl, 1- propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, l-methyl-2-propynyl, 1- pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, l-methyl-2-butynyl, l-methyl-3- butynyl, 2-methyl-3-butynyl, 3-methyl-l-butynyl, l,l-dimethyl-2-propynyl, 1-ethyl-

[0042] 2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, l-methyl-2- pentynyl, l-methyl-3-pentynyl, l-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2- methyl-4-pentynyl, 3-methyl-l-pentynyl, 3-methyl-4-pentynyl, 4-methyl-l-pentynyl, 4-methyl-2-pentynyl, l,l-dimethyl-2-butynyl, l,l-dimethyl-3-butynyl, 1 ,2-d imethyl -

[0043] 3-butynyl, 2,2-di methyl -3- buty ny 1 , 3,3-dimethyl-l-butynyl, l-ethyl-2-butynyl, 1- ethyl-3-butynyl, 2-ethyl-3-butynyl, l-ethyl-l-methyl-2-propynyl and the like.

[0044] The term "haloalkynyl" as used herein, which is also expressed as "alkynyl which is partially or fully halogenated", refers to straight-chain or branched alkynyl as defined herein, where some or all of the hydrogen atoms in these groups are replaced by halogen atoms as mentioned above, in particular fluorine, chlorine and bromine. Haloalkynyl has in particular 2 to 10 ("C2-C10-haloalkynyl") carbon atoms, specifically 2 to 6 ("C2-C6-haloalkynyl") or 2 to 4 ("C2-C4-haloalkynyl") carbon atoms, and one triple bond in any position. "C2-C3-Haloalkynyl" indicates straightchain or branched hydrocarbon radicals having 2 to 3 carbon atoms and one triple bond in any position, where some or all of the hydrogen atoms in these groups are replaced by halogen atoms as mentioned above, in particular fluorine, chlorine and bromine. "C2-C4-Haloalkynyl" indicates straight-chain or branched hydrocarbon radicals having 2 to 4 carbon atoms and one triple bond in any position, where some or all of the hydrogen atoms in these groups are replaced by halogen atoms as mentioned above, in particular fluorine, chlorine and bromine.

[0045] If the term "aryl" as used herein and in the aryl moieties of aryloxy is used without prefix (Cn-Cm), it indicates an aryl group with 6 to 22, in particular 6 to 14, specifically 6 to 10 carbon atoms as ring members. Aryl may be a mono-, bi- or polycyclic carbocyclic aromatic radical which does not have heteroatoms as ring members. One example for a monocyclic aryl is phenyl. In bicyclic aryl rings two aromatic rings are condensed or fused, i.e. the fused rings share two vicinal C atoms as ring members. One example for a bicyclic aromatic radical is naphthyl. In polycyclic aryl rings, three or more rings are condensed. Examples for polycyclic aryl radicals are phenanthrenyl, anthracenyl, tetracenyl, l-H-benzo[a]phenalenyl, pyrenyl and the like. “C6-C10-Aryl” is in particular phenyl, 1-naphthyl or 2-naphthyL The term “aryloxy” refers to aryl, as defined above, bound via an oxygen atom to the remainder of the molecule. “C6-C10-Aryloxy” is in particular phenoxy, 1-naphthyloxy or 2-naphthyloxy.

[0046] The term 5- to 20-membered heterocyclic aryl, also referred to as 5- to 20- membered hetaryl, refers to heteroaromatic, monocyclic, bicyclic or tricyclic condensed systems with 5 to 20 ring member atoms, in which at least one of the rings is aromatic and which contain 1, 2, 3 or 4 heteroatoms selected from N, S or 0 as ring member atoms the remaining ring member atoms being carbon atoms. In the 6-membered heteroaryl rings the heteroatom ring members can only be nitrogen atoms. Monocyclic hetaryl groups are preferably 5- or 6-membered hetaryl groups comprising 1, 2 or 3 heteroatoms selected from 0, S or N such as 2-furyl (furan-2-yl), 3-furyl (furan-3-yl), 2-thienyl (thiophen-2-yl), 3-thienyl (thiophen- 3-yl), lH-pyrrol-2-yl, 1 H - pyrrol -3-yl , pyrrol-l-yl, imidazol-2-yl, i m idazol -1 -y I, imidazol-4-yl, pyrazol-l-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, 3-isoxazolyl, 4- isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 4- oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, l,3,5-triazin-2-yl and 1 ,2,4-triazi n -3-y I . Bicyclic throughout aromatic heteroaryl is typically 9- or 10-membered and contains 1, 2, 3 or 4 heteroatoms selected from 0, S or N. Examples are quinolinyl, isoquinolinyl, indolyl, isoindolyl, indolizinyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, benzoxadiazolyl, benzothiadiazolyl, benzoxazinyl, benzopyrazolyl, benzimidazolyl, benzotriazolyl, benzotriazinyl. Examples for tricyclic hetaryl are carbazolyl, dibenzofuranyl, acridinyl, phenazinyl, phenoxazinyl, phenothiazinyl, and phenoxathiinyl.

[0047] The term “3- to 10-membered saturated or partially unsaturated heterocyclic ring” as used herein, which is also referred to as "C3-C10heterocyclyl", denotes mono-, bi- or tricyclic saturated or partially unsaturated ring system having as ring members 3 to 10 carbon atomes and 1 to 4 heteroatoms or heteroatom-containing groups selected from 0, N, S, SO and S(O)2. Examples of C3-C10heterocyclyl are oxetanyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, oxazolidinyl, tetrahydrofuryl, dioxolanyl, dioxanyl, hexahydroazepinyl, hexyhydrooxepinyl, hexahydrothiepinyl, di- and tetrahydropyridinyl, pyrrolinyl, oxazolinyl, dihydrofuryl, tetrahydroazepinyl, tetrahydrooxepinyl, tetrahydrothiepinyl and the like.

[0048] The term “C6-C10a ryl -Cj-C^a I ky I ” refers to Cj-C^alkyl which is substituted by 1 C6- C10aryl group as defined herein, in particular by phenyl. Examples of C6-C10aryl-Cj- C4-al kyl include benzyl, 1 - p he ny I ethy I and 2-phenylethyL Here and in the following the term aryl chloride, aryl chloride (I I), compound (I I) and aromatic chloride (II) are used synonymously.

[0049] According to the present invention, the process is carried out in the presence of a copper catalyst comprising copper and a ligand of the formula (I II) or a salt thereof. The ligand may be a 2,2’- bipy ridine, i. e. the radicals Z = H, carrying identical or different moieties X and Y in the 4- and 4’-positions of the 2,2’ - bi py rid i ne (Formula (111 -1) , or a 1,10-phenanthroline, i. e. the radicals Z together form a -CH=CH- moiety, carrying identical or different moieties X and Y in the 4- and 7-positions of the 1,10-phenanthroline (Formula (111-2).

[0050] (l ll-l) (H I-2)

[0051] In formula (I II) and likewise in formulae (lll-l) and (111-2), X and Y are preferably selected from the group consisting of halogen, SH, SR3, SO3H, S(O)kR4, and especially from the group consisting of chlorine, bromine, OH and OR1, where R1, R3and R4are as defined above and in particular phenyl, benzyl or 0^4 alkyl, especially 0^4 alkyl such as methyl or ethyl. In formula (I II) and likewise in formulae (ll l-l) and (111-2), X and Y are in particular identical.

[0052] Irrespective of their occurrence, R1, R2, R3, R4are independently of each other selected from the group of Cj-Cg alkyl, 0^4 haloalkyl, C5-C6cycloalkyl, naphthyl, phenyl and phenyl-Cj-C^alkyl such as benzyl, 1- phenylethyl or 2-phenylethyl, where phenyl in the last five mentioned moieties is unsubstituted or substituted by 1 or 2 radicals Ra, where Rais selected form F, ON, NO2, OH, SO3H, CH3, CF3and 0CH3. In particular, R1, R2, R3, R4are independently of each other selected from the group of Cj-Cg alkyl, C C4haloalkyl, C5-Cg cycloalkyl, naphthyl, phenyl and phenyl-Cj-C^alkyl such as benzyl, 1- phenylethyl or 2-phenylethyl, where phenyl in the last five mentioned moieties is unsubstituted. More particularly, R1, R2, R3, R4are independently of each other selected from the group of phenyl, benzyl and C!-C4alkyl, especially C!-C4alkyl such as methyl or ethyl.

[0053] Particularly preferred examples of the ligand of the formula (I II) include but are not limited to 4,4’ -d ic h I o ro-2,2 ’ - bi py rid i ne (Illa), 4,4’ -d i hyd roxy-2,2 ’ - bi py rid i n e (I II b), 4,4’-dimethoxy-2,2’-bipyridine (lllc), 4,7-dichloro-l,10-phenanthroline (Hid), 4,7- dihydroxy-l,10-phenanthroline (llle), 4,7-dimethoxy-l,10-phenanthroline (II If), 4,4’- dibromo-2,2’-bipyridine (Illg), 4,7-dibromo-l,10-phenanthroline (II Ih), and the salts thereof.

[0054] Suitable salts of the ligand of the ligand of the formulae (III), (lll-l) and (111 -2) are acid addition salts of the ligand of formulae (III), (lll-l) and (HI-2) with a Bronsted acid, wherein one or both of the nitrogen atoms are protonated (formulae (lll-H and 111-2H) . Typical Bronsted acids include those of the formula H-Q, where Q is chloride, sulfate, hydrogensulfate, methosulfate, phosphate, hydrogenphosphate, dihydrogenphosphate, perchlorate, tetrafluoroborate, hexafluorophosphate, hydrogenhexafluorozirconate and hydrogenhexafluorotitanate. In particular Q is chloride, sulfate or hydrogensulfate.

[0055] It is apparent to a skilled person that in case Q" represents a sulfate anion, only 1 / 2 sulfate ion is required per the protonated ligand (lll-H) to achieve electroneutrality.

[0056] The copper catalyst further comprises copper. It is believed that the ligand of the formula (III) and the copper form a complex where the copper is chelated by the ligand (III). For this, the copper catalyst may be introduced into the reaction in the form of a copper source and a ligand of the formula III or a salt thereof, or in form of a copper complex containing at least one ligand of the formula III as defined above or a salt thereof.

[0057] If the copper catalyst is introduced into the reaction in the form of a copper source and a copper ligand of the formula III or a salt thereof, the complex with the ligand (III) is either formed before the cross-coupling reaction starts or, in particular, is formed in situ.

[0058] The copper source is e. g. a copper(ll) salt, a copper(l) salt, a copper oxide, a copper(l) complex compound, a copper(ll) complex compound, a copper(l)- or copper(ll)complex with ligands different from the ligand of formula (III) or is elemental (metallic) copper, e. g. copper powder which is optionally bound to a carrier, or mixtures of the before mentioned compounds, for example but not limiting mixtures of copper(ll)salts and elemental copper or mixtures of copper(l)salts and elemental copper.

[0059] Suitable copper(ll) salts or complexes include salts and complexes of copper(l l) with monocarboxylic acids, dicarboxylic acids, hydroxycarboxylic acids or E-ketocarboxylic acids and the hydrates thereof, such as Cu(ll)formiate, e. g. Cu(HCOO)2*H2O, Cu(ll)acetate, Cu(ll) benzoate, Cu(ll)2-ethylhexanoate, Cu(l l) neodecanoate, Cu(ll)isobutyrate, Cu(ll)butyrate, Cu(ll)ethylacetoacetate, bis(t- butylacetoacetato)copper(ll), copper(l l) naphthenate, Cu(ll)oxalate*H2O, Cu(ll)tartate*H2O, and Cu(ll)gluconate; salts and complexes of copper(l l) with alcohols or amino alcohols, such as bis(dimethylamino-2-propoxy)copper(ll) and Cu(OCH3)2; complexes of copper (I I) with E-diketones, such as copper(l l) hexafl uoroacetylacetonate, bis (2,2,6, 6-tetra methyl -3,5- he ptaned io nato) copper(l l), Cu(ll)acetyl acetonate, Cu (I l)trifl uoroacety I acetonate; copper(l l) halides, copper(ll) sulfates, copper(ll) nitrates, copper(l l) perchlorate, copper(ll) tetrafluoroborate, copper(ll) carbonates and the hydrates and amine complexes thereof, including CuF2, CuCI2,CuCI2*2H2O, copper(l l) sulfonates such as Cu(CF3SO3)2and Cu(MeSO3)2;

[0060] Suitable copper(l) salts or complexes are for example CuCI, CuBr, Cui, Cu2SO4, bis(triphenylphosphine) copper(l) nitrate, bromo(l,10-phenanthroline) (tri phenyl phosphine) copper(l), ch loro[l ,3- bis (2,6-d i-i- propyl phenyl) imidazol-2- ylidene]copper(l), Cu(l)acetate, Cu(l)CN, Cu2O, Cu2S, copper(l) phenylacetylide, Cu(l)SCN, cyclopentadienyl(triethylphosphine)copper(l), (1,10- phenanthroline) bis(triphenylphosphine)copper(l) nitrate, KCu(l)(CN)2and [(CH3CN)4CU] [PF6],

[0061] The copper source is preferably a copper(ll) salt, in particular a copper(ll) sulfate or a hydrate or amine complex thereof, such as CuSO4, CuSO4*5H2O, CuSO4*H2O, CUSO4*3H2O, [CU (NH3)4]SO4*H2O. The copper complex containing at least one ligand of the formula (III) as defined above or a salt thereof can also be a pre-formed complex of copper(l) or copper(ll) and the ligand (III) or a salt thereof.

[0062] In one preferred embodiment, the copper catalyst is introduced into the reaction in form of a copper(ll) salt, specifically CuSO4or CuSO4*5H2O and the ligand of formula (III) or a salt thereof. In another preferred embodiment, the copper catalyst is introduced into the reaction in form of a pre-formed complex of copper(l) or (II) and the ligand of formula (III) or a salt thereof.

[0063] Preferably, the process of the present invention is carried out such that the molar ratio of copper and the ligand of the formula (III) is in the range of 5:1 to 1:5, more preferably in the range of 2:1 to 1:3, even more preferably in the range of 1.5:1 to 1:2.5, in particular in the range of 1.1:1 to 1:2.5, more particularly in the range of 1.05:1 to 1:2.2, especially in the range of 1:1 to 1:2. For example, if the copper catalyst is not introduced into the reaction in form of the preformed complex of copper and the ligand of the formula (III), but in form of a copper source, the copper source, calculated on the basis of the copper content, and the ligand of formula (III) or its salt are used in a molar ratio of preferably in the range of 5:1 to 1:5, more preferably in the range of 2:1 to 1:3, even more preferably in the range of 1.5:1 to 1:2.5, in particular in the range of 1.1:1 to 1:2.5, more particularly in the range of 1.05:1 to 1:2.2, especially in the range of 1:1 to 1:2. If a preformed complex of copper and the ligand of the formula (III) is used, the molar ratio of copper to the ligand of formula (III) is typically 1:1. However, the preformed complex may also be used with an excess of ligand (III) or an excess of copper, preferably such that the molar ratio is in the above ranges.

[0064] The copper catalyst may be used in an amount of up to 30 mol%, e.g. of from 0.00001 mol% to 30 mol%, relative to 1 mol of the aromatic chloride (II) and calculated based on the amount of copper in the catalyst. However, lower amounts such as up to 10 mol%, in particular up to 5 mol%, or up to 2.5 mol% especially up to 2 mol-%, relative to 1 mol of the aromatic chloride (II) and calculated based on the amount of copper in the catalyst, are preferred. In particular, the copper catalyst is used in amounts of at least 0.0001 mol%, more particularly at least 0.001 mol%, preferably at least 0.01 mol%, more preferably at least 0.1 mol%, especially at least 0.2 mol%, relative to 1 mol of the aromatic chloride (II) and calculated based on the amount of copper in the catalyst. In particular, the copper catalyst is used in an amount in the range of 0.001 to 10 mol%, more particularly in the range of 0.01 mol% to 5 mol%, preferably in the range of 0.1 mol% to 2.5 mol%, especially in the range of 0.2 mol% to 2 mol%, relative to 1 mol of the aromatic chloride (II) and calculated based on the amount of copper in the catalyst. According to the invention, the aromatic chloride (I I) is reacted with an aminating agent (IV) to yield the aromatic amine (I). The aromatic chloride (I I) is in particular a compound of the formula (I I),

[0065] Ar-CI (II) where Ar is 6- to 22-membered carbocyclic aryl or 5- to 20-membered heterocyclic aryl having 1, 2, 3 or 4 heteroatoms selected from N, 0 and S as ring members, where carbocyclic aryl and heterocyclic aryl are unsubstituted or carry m radicals RAr, which are identical or different, where m is 1, 2, 3, 4 or 5 and

[0066] RAris selected from the group consisting of F, Cl, OH, cyano, nitro, NR5R6, C(=O)NR5R6, CJ-CJO alkoxy, C C^ haloalkoxy, C C^ alkyl, C C^ haloalkyl, CrC10hydroxyalkyl, C C^ alkoxy-C C^-alkyl, C2-C10alkenyl, C2-C10haloal kenyl, C2-C10alkynyl, C2-C10haloalkynyl, C3-C10cycloalkyl, which is unsubstituted or carries n radicals Rb, C6-C10aryl which is unsubstituted or carries p radicals Rc, C6-C10aryl-Cj-C^alkyl, where C6-C10aryl is unsubstituted or carries p radicals Rc, 3- to 10-membered saturated or partially unsaturated heterocyclic rings containing 1, 2, 3 or 4 heteroatoms or heteroatom groups selected from, N, 0, S, SO and SO2as ring members, which is unsubstituted or carries q radicals Rd, and 5- to 10-membered heterocyclic aryl having 1, 2, 3 or 4 heteroatoms selected from N, O and S as ring members, where heterocyclic aryl is unsubstituted or carries r radicals Re, where

[0067] R5, R6independently of each other are selected from the group of CJ-CJQ alkyl, CJ-CJQ haloalkyl, C3-C10cycloalkyl, C6-C10aryl and C6-C10aryl-Cj- C4-al kyl, where aryl in the last two mentioned moieties is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals Rf, n is 1, 2, 3, 4 or 5, p is 1, 2, 3, 4 or 5, q is 1, 2, 3, 4 or 5, r is 1, 2, 3, 4 or 5,

[0068] Rbis selected form F, CN, OH, CH3, CF3and OCH3,

[0069] Rcis selected form F, Cl, CN, OH, NO2, SO3H, CH3, CF3and OCH3,

[0070] Rdis selected form F, CN, OH, NO2, SO3H, CH3, CF3and OCH3or 2 radicals Rdwhich are bound to the same C-Atom of the heterocyclic ring may form a carbonyl group together with the carbon atom to which they are bound,

[0071] Reis selected form F, Cl, CN, NO2, OH, SO3H, CH3, CF3and OCH3,

[0072] Rfis selected form F, CN, NO2, OH, SO3H, CH3, CF3and OCH3.

[0073] In formula (II) and likewise in formula (I) below the variables on their own or in combination have preferably the following meanings:

[0074] Ar is selected from 6- to 10-membered carbocyclic aryl or 5- to 10-membered heterocyclic aryl having 1 or 2 heteroatoms selected from N and S as ring members, where carbocyclic aryl and heterocyclic aryl are unsubstituted or carry m radicals RAr, which are identical or different.

[0075] RAris selected from the group consisting of F, Cl, alkoxy, haloalkoxy, C C^ alkyl, C C^ haloalkyl,

[0076] C3-C6cycloalkyl, which is unsubstituted or carries n radicals Rb,

[0077] C6-C10aryl which is unsubstituted or carries p radicals Rc,

[0078] C6-C10aryl-Cj-C^alkyl, where C6-C10aryl is unsubstituted or carries p radicals Rc, and heterocyclic aryl having 1, 2, 3 or 4 heteroatoms selected from N, O and S as ring members, where heterocyclic aryl is unsubstituted or carries r radicals Re; n is 1, 2 or 3, especially 1 or 2; p is 1, 2 or 3, especially 1 or 2; q is 1, 2 or 3, especially 1 or 2; r is 1, 2 or 3, especially 1 or 2.

[0079] In formula (II) and likewise in formula (I) below the variables on their own or in combination have in particular the following meanings:

[0080] Ar is selected from phenyl, naphthyl, indolyl, thienyl and pyridyl, which are unsubstituted or substituted by 1, 2 or 3 identical or different radicals RAr;

[0081] RAris selected from F, Cl, NO2, alkyl, fluorinated alkyl, alkoxy, alkylthio, phenyl, phenyl-Cj-^ alkyl, pyridyl, pyrrolyl and thienyl, where the phenyl rings of phenyl and phenyl-Cj-^ alkyl are unsubstituted or substituted by 1, 2 or 3 radicals Rcand are unsubstituted or substituted by 1, 2 or 3 radicals Re, where Rcand Reare as defined above and where Rcand Reare in particular selected from methyl, fluorine, chlorine and methoxy.

[0082] In formula (II) and likewise in formula (I) below the variables on their own or in combination have especially the following meanings: Ar is selected from phenyl, naphthyl, indolyl, thienyl and pyridyl, which are unsubstituted or substituted by 1, 2 or 3 identical or different radicals RAr;

[0083] RAris selected from F, Cl, NO2, OH, Cj-Cg alkyl, fluorinated methyl, Cj-Cg alkoxy, phenyl, phenyl-Cj^ alkyl, pyridyl, pyrrolyl and thienyl, where the phenyl rings of phenyl and phenyl-Cj^ alkyl are unsubstituted or substituted by 1, 2 or 3 radicals Rcand are unsubstituted or substituted by 1, 2 or 3 radicals Re, where Rcand Reare as defined above and where Rcand Reare in particular selected from methyl, fluorine, chlorine and methoxy.

[0084] In particular, the aromatic chloride of the formula (II) is selected from the group consisting of chlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4- dichlorobenzene, l-chloro-2-methylbenzene, l-chloro-3-methylbenzene, 1-chloro- 3,4-di methyl benzene, 1,3 -die hl oro-2- methyl benzene, l,3-dichloro-4- methylbenzene, l-chloro-4-tert-butylbenzene, l-chloro-2-phenylbenzene, 1-chloro- 4-phenylbenzene, l-chloro-2,3-difluorobenzene, l-chloro-3,4-difluorobenzene, 1- chloro-2,3,4-trifluorobenzene, 4-chlorodiphenylmethane, 4,4’- d ic h I orodi phenyl methane,

[0085] 2-phe ny 1-2- (4-chlo ro phenyl) pro pane, 2, 2-bis(4-chloro phenyl) pro pane, l-chloro-2- methoxybenzene, l-chloro-3-methoxybenzene, l-chloro-4-methoxybenzene, 1- chloro-4-methylthiobenzene, l-chloro-2-nitrobenzene, l-chloro-4-nitrobenzene, 1- chloro-4- (trifluoro meth oxy) benzene, 1 -ch loro-3- (trifluoromethoxy) benzene, 2- chloro-N- methyl -benzamide, 3-ch loro- N- methyl -benzamide, 4-ch loro-N- methyl - benzamide, 2-chloro-3,N-dimethyl-benzamide, 2-ch loropyridine, 3-chloropyridine,

[0086] 3-chlorothiophene,

[0087] 1-chloronaphthalene, 2-chloronaphthalene, 5-chloro-lH-indole, 4-(pyrrol - 1 -y I) - 1 - chlorobenzene.

[0088] The aminating agent is ammonia, a primary aliphatic or cycloalphatic amine or a secondary aliphatic or cycloaliphatic amine. The primary aliphatic or cycloalphatic amine or a secondary aliphatic or cycloaliphatic amine are preferably water miscible, i. e. their miscibility in deionized water is at least 10 g / L, in particular at least 50 g / L at 20° C and 1 bar.

[0089] Suitable aminating agents can be described by the following formula (IV):

[0090] HNR7R8(IV) where R7, R8are identical or different selected from the group consisting of H, C C^ alkyl or C3-C10cycloalkyl, where CJ-CJQ alkyl is unsubstituted or substituted by one of OH, Cj-CjQ alkoxy and hydroxy-C C^-alkoxy or R7, R8together with the nitrogen atom to which they are bound, form a saturated N-heterocycle which optionally has one further heteroatom, selected from 0 and S as ring member.

[0091] Preferred aminating agents of the formula (IV) are those, where

[0092] R7, R8are identical or different selected from the group consisting of H, Cj-C4alkyl, where Cj-C4alkyl is unsubstituted or substituted by one of OH, C1-C4alkoxy and hydroxy-C2-C4-alkoxy or

[0093] R7, R8together with the nitrogen atom to which they are bound, form a saturated 5 or 6-membered N-heterocycle which optionally has one further heteroatom, selected from 0 and S as ring member and which is preferably selected from morpholine, piperidine, thiomorpholine and pyrrolidine.

[0094] In a particular preferred group of embodiments of the present invention, the aminating agent is ammonia, i. e. both R7and R8are hydrogen.

[0095] In another particular preferred group of embodiments of the present invention, the aminating agent is of the formula (IV), where R7and R8are identical or different selected from the group consisting of H, Cj-C4alkyl and hydroxy-Cj-C^ alkyl, such as methylamine, ethylamine, dimethylamine, diethylamine, 2-aminoethanol, 2- hydroxypropylamine, diethanolamine (= bis(2-hydroxyethyl)amine and bis(2- hydroxy propyl) amine.

[0096] In the process of the invention the relative amount of the aminating agent (IV) with respect to the aromatic chloride (II) is generally in in the range of 1 to 100 mol, in particular in the range of 5 to 50 mol per 1 mol of the aromatic chloride (II). If an excess of the aminating agent (IV) is used, unreacted aminating agent (IV) can, if appropriate work-up is done, the excess of the aminating agent (IV) with respect to the aryl chloride (II) can be removed and reused in a following run.

[0097] The aromatic amine (I) which results from the reaction of the aromatic chloride of formula (II) with the aminating agent of the formula (IV) can thus be described by the formula (I)

[0098] Ar-NR7R8(IV) where Ar is as defined for formula (II) and R7and R8are as defined for formula (IV) and where Ar, R7and R8have in particular the meanings preferred or particularly preferred.

[0099] Examples of aromatic amines of the formula (IV) which can be obtained by the process of the invention include but are not limited to the compounds depicted in the following scheme 1:

[0100] lao 'aP

[0101] It has been found beneficial, if the process of the invention is carried out in the presence of a base different from the aminating agent (IV). Suitable include both inorganic and organic bases. Suitable inorganic bases are for example from alkali metal carbonates, such as l_i2CO3, Na2CO3, K2CO3or Cs2CO3, earth alkaline metal carbonates, such as MgC03 or CaCO3, alkali metal phosphates, such as l_i3PO4, Na3PO4, K3PO4or Cs3PO4, earth alkaline metal phosphates, such as Mg3(PO4)2or Ca3(PO4)2, alkali metal hydrogenphosphates, such as Li2HPO4, Na2HPO4, K2HPO4or Cs2H PO4, earth alkaline metal hydrogenphosphates, such as MgH PO4or CaHPO4, alkali metal hydroxides, such as LiOH, NaOH or KOH, and earth alkaline metal hydroxides, such as Mg(OH)2or Ca(OH)2.

[0102] Examples for suitable organic bases are tertiary amines, e.g. trimethylamine, triethylamine, tripropylamine, ethyldiisopropylamine and the like, or basic N- heterocycles, such as pyridine, lutidine, diazabicyclooctane (DABCO), diazabicycloundecene (DBU) or diazabicyclononene (DBN).

[0103] Preference is given to additional bases selected from the group consisting of tertiary amines, alkalimetal hydroxides, earth alkaline metal hydroxides, alkalimetal carbonates, alkalimetal monohydrogen phosphates and alkalimetal orthophosphates, and combinations thereof.

[0104] Preference is also given to additional bases selected from the group consisting of inorganic bases, such as to the above alkali metal carbonates, earth alkaline metal carbonates, alkali metal phosphates, earth alkaline metal phosphates, alkali metal hydrogenphosphates, earth alkaline metal hydrogenphosphates, alkali metal hydroxides and earth alkaline metal hydroxides.

[0105] More preference is given to alkali metal carbonates, alkali metal phosphates and alkali metal hydroxides such as the above-mentioned K3PO4, Na3PO4, K2HPO4, Na2HPO4, Na2CO3, K2CO3, NaOH or KOH.

[0106] The additional base is generally used in an amount of at least 0.5 mol, in particular at least 1 mol per 1 mol of the aryl chloride (II). The amount of the additional base will generally not exceed 5 mol per 1 mol of the aryl chloride (II). The additional base is in particular used in an amount in the range of 0.5 to 5 mol, preferably in the range of 1 to 4 mol, more preferably in the range of 1 to 3 mol, even more preferably in the range of 1 to 2.2 mol, and especially in the range of 1 to 2 mol of the aryl chloride (II).

[0107] In the process of the invention, the reaction of the aromatic chloride (II) with the aminating agent (IV) is preferably carried out in an aqueous reaction mixture containing the aminating agent (IV).

[0108] Organic solvents other than DMSO, DM F or NMP can be present in the aqueous reaction mixture in small amounts, generally in an amount of not more than 10%, preferably in an amount of less than 5% and most preferred less than 3% of weight of total solvent. In a preferred embodiment, no organic solvent is added to the reaction mixture. In the embodiment of the invention, no surfactants, organic cosolvents or phase transfer catalysts are added to the reaction mixture. In particular, the reaction is carried out in a reaction mixture which does not contain more than 10% by weight, in particular less than 3% by weight of organic solvents, based on the total weight of the reaction mixture. More preferably, the reaction mixture which does not contain more than 5% by weight, in particular less than 3% by weight of organic matter other than the ligand, the aryl chloride (II) and the aminating agent (IV) (if different from ammonia) and the optional additional base.

[0109] If the aminating agent (IV) is ammonia, the reaction is preferably carried out in aqueous ammonia as the main solvent as well as reagent. Preferably the ammonia concentration in water is in the range of 1 to 32 weight %, preferably int the range of 10 to 32 weight% and more preferably in the range of 25 to 32 weight %. The amount of aqueous ammonia used is in a range of 1 to 100 equivalents of NH3with respect to the aryl chloride (II), preferably in a range of 5 to 50 equivalents of NH3with respect to the aryl chloride (II) and in particular in a range of 8 to 32 equivalents of NH3with respect to the aryl chloride (II). Unreacted NH3can, if appropriate work-up is done, be reused.

[0110] The process is preferably carried out at a reaction temperature in the range of 60 to 220° C, in particular in the range of 100 to 200° C and especially in the range of 150 to 190° C. As elevated temperatures are used and the aminating agent, which his usually volatile and optional water present, may develop pressure. This will result in an inherent pressure in the reaction vessel to keep the aminating agent in the reaction mixture. Frequently, the pressure in the rection vessel is therefore in the range of 1.1 to 150 bar, in particular in the range of 1.5 to 100 bar, especially in the range of 2 to 90 bar.

[0111] The process of the invention can be carried out by standard proceedings for cross coupling reactions with ammonia, e.g. by mixing all reagents, inclusive catalyst or catalyst precursor and ligand, base and the solvent mixture, and reacting them at the desired temperature. Alternatively, the reagents can be added gradually, especially in the case of a continuous or semicontinuous process. The process of the invention can also be carried out in an inert atmosphere in order to avoid the presence of oxygen, e.g. under an argon or nitrogen atmosphere. The process of the invention is preferably carried out in a pressure vessel, e.g. an autoclave. After completion of the reaction, the reaction mixture is worked up and the aromatic amine (I) is isolated in a customary manner. For example, the water and unreacted aminating agent (IV), in particular ammonia, are removed, for example under reduced pressure. The aromatic amine (I) with a moderate or low vapor pressure can for example easily be separated from the reaction mixture via fractional distillation after removal of the water.

[0112] It is also possible that the work-up comprises the addition of an extraction solvent to the reaction mixture, to extract the aromatic amine from the aqueous reaction mixture and leaving the salt by-products in the aqueous phase.

[0113] Organic solvents for extraction are those which have a miscibility with water of below 20 g / 100 g of water at 20° C. Examples are aliphatic hydrocarbons, such as alkanes, e.g. pentane, hexane, heptane, octane, mixtures thereof and technical mixtures, such as petrol ether; cycloaliphatic hydrocarbons, such as cycloalkanes, e.g. cyclohexane, cycloheptane, or cyclooctane; chlorinated aliphatic hydrocarbons, such as halogenalkanes, e.g. dichloromethane, trichloromethane, tetrachloromethane, dichloroethane or tetrachloroethane, aromatic hydrocarbons, such as benzene, toluene, the xylenes, ethylbenzene, cumene (isopropylbenzene), chlorobenzene, o-dichlorobenzene or nitrobenzene, open-chained, ethers, such as diethylether, dipropylether, methyl-tert-butylether or methylisobutylether, higher alkanols, such as n-butanol or isobutanol or esters as ethylacetate or butylacetate.

[0114] The aromatic amine (I) will be enriched in the organic phase mainly formed by the non-polar organic solvent. To enhance the yield, the aqueous phase can be extracted one or more times with an organic solvent, such as the above listed nonpolar organic solvents. If desired, the aromatic amine (I) can then be separated from other undesired components, such as unreacted starting aryl chlorides (II) via customary means. For example, the aromatic amine (I) can be crystallized from the organic phase or separated via distillation.

[0115] In yet another alternative, the aromatic amine (I) is submitted to a chromatographic separation. Further purification of the aromatic amine (I) can be effected if desired; for example by extraction, crystallization, distillation or by chromatography.

[0116] The invention is further illustrated by the following examples.

[0117] Examples

[0118] The invention is to be illustrated by non-limiting examples which follow.

[0119] 1. Abbreviations: % w / w: % by weight eq: molar equivalent

[0120] DPA: diphenyl amine DPE: diphenyl ether Et: ethyl

[0121] Et3N: trimethylamine HCI: hydrogen chloride

[0122] Me: methyl

[0123] MeCN: acetonitrile MeO: methoxy OAc acetate Ph: phenyl

[0124] PPh3: triphenyl phosphine SM: starting material

[0125] TBME: tert-butyl methyl ether

[0126] 2. Analytics

[0127] NMR:

[0128] NMR-spectra were recorded on Bruker AV-300, AV-400, AV-500 or AV-600 spectrometers. The residual solvent signals were used as references for and13C NMR spectra (CDCI3: <5 H = 7.26 ppm, <5 C = 77.16 ppm, CD2CI2: <5 H = 5.32 ppm, 3 C = 53.84 ppm).19F NMR spectra were not calibrated by an internal reference.

[0129] 3. Preparation Examples

[0130] Examples 1 to 5 (according to the invention) and Comparative Examples Cl to C21 (not according to the invention):

[0131] Ligands for the Cu(l l)-catalyzed amination of aryl chlorides in aqueous ammonia with copper(ll) sulfate

[0132] CUSO4-5H2O (2.5 mol%) Ligand (2.5 mol%)

[0133] General procedure: CuSO4-5H2O (0.025 eq), one of the ligands of formulae Il la, H id, llle, l llf or Il lg (0.025 eq) listed in Table 1 below, K3PO4(1.2 eq), 3,4-difluoro-l- chlorobenzene (compound of formula Hr, 1 mmol), and 2 mL of 29 % w / w aqueous ammonia (30.7 eq) were added into a 16 mL stainless steel pressure tube containing a stirring bar. The tube was sealed and kept under stirring at 180 ° C for 18 h. The tube was then cooled in an ice bath for 15 min. The tube was opened, mesitylene was added as internal standard (1 mmol) and the content of the tube was taken up with 15 mL of ethanol. After stirring for 10 minutes, an aliquot of 400 pL was applied in a short silica column (5 cm), which was flushed with ethyl acetate (1.5 mL) and the sample was analyzed via GC-FID and GC-MS. The determined yield (GC area%) of the product of formula Ir is given for each example in Table 1.

[0134] Table 1:

[0135] Examples 6 to 10 (according to the invention) and Comparative Examples C22 to C31 (not according to the invention):

[0136] Ligands for Cu-catalyzed amination of aryl chlorides in aqueous ammonia with copper(l) iodide / Copper(0) system

[0137] Cui (5 mol%) Cu ° (5 mol%) Ligand (5 mol%) aq. NH3(29% wt) (1 mL)

[0138] 0.5 mmol 180 °C; 18h Hr

[0139] General procedure: In a glovebox copper(l) iodide (0.025 eq) and copper(O) (0.025 eq; copper powder <425 pm, 99.5% purity) as copper source, one of the ligands of formulae I He, Hid, llle, II If or lllh summarized in Table 2 below (0.025 eq), NEt3(1.2 eq), and 3,4-difluoro-l-chlorobenzene (compound of formula Hr, 0.5 mmol) were introduced into a 16 mL stainless steel pressure tube containing a stirring bar. Then, the tube was sealed and placed outside the glovebox. The tube was opened under a stream of argon and 1 mL of 29 % w / w aqueous ammonia (30.7 eq) were added and the tube was again sealed and kept with stirring at 180 ° C for 18 h. The system was then cooled in an ice bath for 15 min. The tube was opened, mesitylene was added as internal standard (1 mmol) and the content of the tube was taken up with 15 mL of ethanol. After stirring for 10 minutes, an aliquot of 400 pL was applied in a short silica column (5 cm), which was flushed with ethyl acetate (1.5 mL) and the sample was analyzed via GC-FID and GC-MS. The determined yield (GC area%) of the product of formula Ir is given for each example in Table 2. Table 2:

[0140] Examples 11 to 20:

[0141] Different copper sources for Cu-catalyzed amination of aryl chlorides in aqueous ammonia with 4,7-dimethoxytphenanthroline

[0142] Hr

[0143] General procedure: In a glovebox a copper source (0.025 eq) listed in Table 3 below, 4,7-dimethoxyphenanthroline (ligand of formula lllf, 0.025 eq), NEt3(1.2 eq), and 3,4-difluoro-l-chlorobenzene (compound of formula Hr, 0.5 mmol) were introduced into a 16 mL stainless steel pressure tube containing a stirring bar. The tube was sealed and placed outside the glovebox. The tube was opened under a stream of argon and 1 mL of 29 % w / w of aqueous ammonia (30.7 eq) were added followed by sealing the tube again and keeping it with stirring at 180 ° C for 18 h. The tube was then cooled in an ice bath for 15 min. The tube was opened, mesitylene was added as internal standard (1 mmol) and the content of the tube was taken up with 15 mL of ethanol. After stirring for 10 minutes, an aliquot of 400 pL was applied in a short silica column (5 cm), which was flushed with ethyl acetate (1.5 mL) and the sample was analyzed via GC-FID and GC-MS. The determined yield (GC area%) of the product of formula Ir is given for each example in Table 3.

[0144] Table 3:

[0145] Examples 21 to 25:

[0146] Bases for Cu-catalyzed amination of aryl chlorides in aqueous ammonia with copper(l) iodide / 4,7-dimethoxytphenanthroline system

[0147] Cul (5 mol%) ligand lllf (5 mol%)

[0148] Hr

[0149] General procedure: In a glovebox Cui as copper source (0.025 eq), 4,7-dimethoxy- phenanthroline (ligand of formula I Ilf, 0.025 eq), the base listed in Table 4 below (1.2 eq), and 3,4-difluoro-l-chlorobenzene (compound of formula Hr, 0.5 mmol) were introduced into a 16 mL stainless steel pressure tube containing a stirring bar. The tube was sealed and placed outside the glovebox. The tube was opened under a stream of argon and 1 mL of 29 % w / w aqueous ammonia (30.7 eq) were added followed by sealing the tube and keeping it with stirring at 180 ° C for 18 h. The tube was then cooled in an ice bath for 15 min. The tube was opened, mesitylene was added as internal standard (1 mmol) and the content of the tube was taken up with 15 mL of ethanol. After stirring for 10 minutes, an aliquot of 400 pL was applied in a short silica column (5 cm), which was flushed with ethyl acetate (1.5 mL) and the sample was analyzed via GC-FID and GC-MS. The determined yield (GC area%) of the product of formula Ir is given for each example in Table 4.

[0150] Table 4:

[0151] Examples 26 to 29:

[0152] Base load for Cu-catalyzed amination of aryl chlorides in aqueous ammonia with copper(ll) sulfate / 4,7-dimethoxytphenanthroline system

[0153] General procedure: CuSO4-5H2O (0.025 eq), the ligand of formula lllf (0.025 eq), K3PO4 in an amount listed in Table 5 below (0 to 1.6 eq), 3,4-dif luoro-1- chlorobenzene (compound of formula Hr, 1 mmol), and 2 mL of 29 % w / w aqueous ammonia (30.7 eq) were introduced into a 16 mL stainless steel pressure tube containing a stirring bar followed by sealing the tube and keeping it with stirring at 1800C for 18 h. Then, the tube was cooled in an ice bath for 15 min. The tube was opened, mesitylene as was added as internal standard (1 mmol) and the content of the tube was taken up with 15 mL of ethanol. After stirring for 10 minutes, an aliquot of 400 pL was applied in a short silica column (5 cm), which was flushed with ethyl acetate (1.5 mL) and the sample was analyzed via GC-FID and GC-MS. The determined yields (GC area%) of the product of formula Ir is given for each example in Table 5.

[0154] Table 5: Examples 31 to 33:

[0155] Ligand load effect on Cu(ll)-catalyzed amination of aryl chlorides in aqueous ammonia

[0156] General procedure for examples 31-33:

[0157] CUSO4-5H2O (0.025 eq), ligand of the formula lllf in an amount listed in Table 6 below (0.025 to 0.075 eq), K3PO4(1.2 eq), 3,4-difluoro-l-chlorobenzene (compound of the formula Hr, 1 mmol), and 2 mL of 29 % w / w aqueous ammonia (30.7 eq) were introduced into a 16 mL stainless steel pressure tube containing a stirring bar followed by sealing the tube and keeping it with stirring at 1800C for 18 h. The tube was then cooled in an ice bath for 15 min. The tube was opened, mesitylene was added as internal standard (1 mmol) and the content of the tube was taken up with 15 mL of ethanol. After stirring for 10 minutes, an aliquot of 400 pL was applied in a short silica column (5 cm), which was flushed with ethyl acetate (1.5 mL) and the sample was analyzed via GC-FID and GC-MS. The determined yields (GC area%) of the product of formula Ir is given for each example in Table 6.

[0158] Table 6:

[0159] Examples 34 to 42:

[0160] Effects of ammonia concentration on the Cu(ll)-catalyzed amination of aryl chlorides in aqueous ammonia General procedure for examples 34-38 and 42: CuSO4-5H2O (0.025 eq), the ligand of formula II If (0.025 eq), K3PO4(1.2 eq), 3,4-difluoro-l-chlorobenzene (compound of formula Hr, 1 mmol), and 2 ml of an aqueous ammonia (NH3) solution obtained by mixing 29 % w / w (15.35 mol / L) aqueous ammonia with water so that the NH3concentration and NH3equivalents listed in Table 7 were reached in each case were introduced into a 16 mL stainless steel pressure tube containing a stirring bar followed by sealing the tube and keeping it with stirring at 180 ° C for 18 h. The same procedure was followed for examples 39, 40 and 41, except that instead of 1 mmol of the compound of formula Hr, 8 mmol, 4 mmol and 2 mmol thereof, respectively, were used. The tube was then cooled in an ice bath for 15 min. The tube was opened, mesitylene was added as internal standard (1 mmol) and the content of the tube was taken up with 15 mL of ethanol. After stirring for 10 minutes, an aliquot of 400 pL was applied in a short silica column (5 cm), which was flushed with ethyl acetate (1.5 mL) and the sample was analyzed via GC-FID and GC-MS. The determined yields (GC area%) of the product of formula Ir is given for each example in Table 7.

[0161] Table 7: a) 8 mmol of compound of formula Hr were used;b) 4 mmol of compound of formula Hr were used;c) 2 mmol of compound of formula Hr were used;

[0162] Examples 43 to 47:

[0163] Effect of solvent on the Cu(ll)-catalyzed amination of aryl chlorides in aqueous ammonia Hr

[0164] General procedure: In a glovebox CuSO4(0.025 eq), 4,7-dimethoxyphenanthroline (ligand of formula lllf, 0.025 eq), K3PO4(1.2 eq), 3,4-difluoro-l-chlorobenzene (compound of formula Hr, 1 mmol), 1 mL of 29 % w / w aqueous ammonia (15.35 eq) and the solvent indicated in Table 8 below (2 mL) were introduced into a 16 mL stainless steel pressure tube containing a stirring bar and equipped with a ball valve. The tube was sealed, placed outside the glovebox and flushed with ammonia 5 times. Then, the system was pressurized with ammonia (5 bar) and kept with stirring for 15 min under ammonia pressure from the line. The ball valve was closed and the tube was kept with stirring at 1800C for 18 h. The tube was then cooled in an ice bath for 15 min. The tube was opened, mesitylene was added as internal standard (1 mmol) and the content of the tube was taken up with 15 mL of ethanol. After stirring for 10 minutes, an aliquot of 400 pL was applied in a short silica column (5 cm), which was flushed with ethyl acetate (1.5 mL) and the sample was analyzed via GC-FID and GC-MS. The determined yields (GC area%) of the product of formula Ir is given for each example in Table 8.

[0165] Table 8:

[0166] Examples 48 to 79:

[0167] Cu(ll)-catalyzed amination of different (het)aryl chlorides in aqueous ammonia

[0168] 1 mmol 180 °C; 18h

[0169] I

[0170] II General procedure for examples 48-64 and 67-73: CuSO4-5H2O (0.025 eq), 4,7- dimethoxyphenanthroline (ligand of formula I Ilf, 0.025 eq), K3PO4(1.2 eq), one of the (het)aryl chlorides of formula II listed in Table 9 below (1 mmol) and 2 mL of 29 % w / w aqueous ammonia were introduced into a 16 mL stainless steel pressure tube containing a stirring bar followed by sealing the tube and keeping it with stirring at 180 ° C (oil bath temperature) for 18 h. The same procedure was followed for examples 65 and 66, except that 0.05 eq of CuSO4-5H2O and 0.05 eq of 4,7-dimethoxyphenanthroline were used and the reaction was carried out at 150

[0171] C for 96 h. The system was then cooled in an ice bath for 15 min. The tube was opened and its content was taken-up with water (20 mL). The tube was also washed with tert-Butyl methyl ether (TBME), which was used for extracting the aqueous phase (5 x 10 mL). The combined organic phase was dried with magnesium sulfate, filtered through a 50 mL fritted funnel and the collected solid was washed with TBME (3 x 5 mL). The solvent volume of the organic phase was reduced under reduced pressure and there were added 15 mL of a 2 molar solution of HCI in diethyl ether. The suspension was filtered through a 15 mL fritted funnel. The collected solid was washed with diethyl ether (3 x 5 mL) and TBME (3 x 5 mL). The solid was then dried under vacuum inside a desiccator containing activated silica-gel. The yields of the thus obtained isolated hydrochloride salt of the (het)arylamine of formula I is summarized in Table 9. The GC yields are also listed in Table 9 were determined in a similar manner as in Examples 1 to 47 from the crude product of the (het)arylamine I.

[0172] Table 9:

[0173] a) n.d. = not determined,b) catalyst load: 5 mol%; 150° C for 96 h.

[0174] Examples 80-85 and comparative example C32

[0175] General Procedure: CuSO4-5H2O (0.025 eq), 4,7-dimethoxy-l,10-phenanthroline (0.025 eq) as depicted in table 10, K3PO4(1.2 eq), chlorobenzene (1 mmol), and 2 mL of aqueous amine source (16-41 eq) were introduced into a 16 mL stainless steel pressure tube containing a stirring bar followed by sealing the tube and keeping it with stirring at 180 ° C for 18 h. The tube was then cooled in an ice bath for 15 min. The tube was opened and Mesitylene was added as internal standard (1 mmol) and the content of the tube was taken up with 15 mL of ethanol. After stirring for 10 minutes, an aliquot of 400 uL was applied in a short silica column (5 cm), which was flushed with ethyl acetate (1.5 mL) and the sample was analyzed via GC-FID and GC-MS. The determined yields (GC area%) are summarized in table 10.

[0176] Table 10:

Claims

Claims1. A process for preparing an aromatic amine (I) which comprises reacting an aromatic chloride (II) with an aminating agent (IV), selected from ammonia, an aliphatic or cycloaliphatic primary or secondary amine in the presence of a copper catalyst comprising copper and a ligand of the formula (I II) or a salt thereofwhereX, Y are identical or different and selected from the group consisting of halogen, OH, OR1, NH2, NHR2, N(R2)2, SH, SR3, SO3H, S(O)kR4with k being 1, 2 or 3, whereR1, R2, R3, R4independently of each other are selected from the group of CJ-CJO alkyl, CJ-CJO haloalkyl, C3-C10cycloalkyl, C6-C10aryl and C6-C10aryl -Cj-C^a I kyl , where aryl in the last two mentioned moieties is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals Ra, where Rais selected form F, ON, NO2, OH, SO3H, CH3, CF3and OCH3;Z are both H or together form -CH=CH-.

2. The process of claim 1, where the variables X and Y in formula (I I I) are identical and selected from the group consisting of chlorine, bromine, OH and OR1.

3. The process of any one of the preceding claims, where the molar ratio of copper and the ligand (I II) is in the range of 1:5 to 5:1.

4. The process of any one of the preceding claims, where the catalyst is used in such an amount that the molar amount of copper, calculated as copper atoms,is in the range of 0.0001 mol-% to 30 mol-% per 1 mol of the of the aromatic chloride (II).

5. The process of any one of the preceding claims, where the catalyst is formed in situ by using a copper source and the ligand of the formula (III) or a salt thereof.

6. The process of claim 5, where the copper source is selected from elemental copper, copper(l) salts, copper(l) complex compounds, copper(ll) salts, and copper(ll) complex compounds and mixtures thereof, and where the copper source is in particular selected from copper(ll) salts and especially is a copper(ll) sulfate.

7. The process of any one of claims 1 to 4, where the catalyst is used as a preformed complex of copper(l) or copper(ll) and the ligand of the formula(III) or a salt thereof.

8. The process of any one of the preceding claims, where the aminating agent(IV) is of the formula (IV)HNR7R8(IV) whereR7, R8are identical or different selected from the group consisting of H, CJ-CJQ alkyl or C3-C10cycloalkyl, where CJ-CJQ alkyl is unsubstituted or substituted by one of OH, Cj-C^ alkoxy and hydroxy-Cj-Cjo-alkoxy or R7, R8together with the nitrogen atom to which they are bound, form a saturated N-heterocycle which optionally has one further heteroatom, selected from O and S as ring member.

9. The process of claim 8, where the aminating agent (IV) is ammonia (R1=R2= H).

10. The process of any one of the preceding claims, where the process is carried out in the presence of a base different from the aminating agent (IV).

11. The process of claim 10, where the base different from the aminating agent (IV) is selected from the group consisting of tertiary amines, alkalimetal hydroxides, earth alkaline metal hydroxides, alkalimetal carbonates, alkalimetal monohydrogen phosphates and alkalimetal orthophosphates, and combinations thereof.

12. The process of any one of the preceding claims, where the relative amount of the aminating agent (IV) with respect to the aromatic chloride (II) is in in the range of 1 to 100 mol, in particular range of 5 to 50 mol of the aminating agent (IV) per 1 mol of the aryl chloride (I I).

13. The process of any one of the preceding claims, where the reaction of the aromatic chloride (II) with the aminating agent (IV) is carried out in an aqueous reaction mixture containing the aminating agent (IV).

14. The process of any one of the preceding claims, where the reaction mixture does not contain more than 5% by weight, based on the total weight of the reaction mixture, of a water-immiscible organic solvent.

15. The process of any one of the preceding claims, where the aryl chloride is a compound of the formula (II)Ar-CI (II) where Ar is 6- to 22-membered carbocyclic aryl or 5- to 20-membered heterocyclic aryl having 1, 2, 3 or 4 heteroatoms selected from N, 0 and S as ring members, where carbocyclic aryl and heterocyclic aryl are unsubstituted or carry m radicals RAr, which are identical or different, where m is 1, 2, 3, 4 or 5 andRAris selected from the group consisting of F, Cl, OH, cyano, nitro, NR5R6, C(=O)NR5R6, CJ-CJO alkoxy, C C^ haloalkoxy, C C^ alkyl, C C^ haloalkyl, CJ-CJO hydroxyalkyl, CJ-CJO alkoxy-Cj-Cjo-alkyl, C2-C10alkenyl, C2-C10haloalkenyl, C2-C10alkynyl, C2-C10haloalkynyl, C3-C10cycloalkyl, which is unsubstituted or carries n radicals Rb, C6-C10aryl which is unsubstituted or carries p radicals Rc, C6-C10aryl-Cj-C^alkyl, where C6-C10aryl is unsubstituted or carries p radicals Rc,3- to 10-membered saturated or partially unsaturated heterocyclic rings containing 1, 2, 3 or 4 heteroatoms or heteroatom groups selected from, N, 0, S, SO and SO2as ring members, which is unsubstituted or carries q radicals Rd, and5- to 10-membered heterocyclic aryl having 1, 2, 3 or 4 heteroatomsselected from N, 0 and S as ring members, where heterocyclic aryl is unsubstituted or carries r radicals Re, whereR5, R6independently of each other are selected from the group of C C10alkyl, CJ-CJQ haloalkyl, C3-C10cycloalkyl, C6-C10aryl and C6- C10aryl-C1-C4-al kyl, where aryl in the last two mentioned moieties is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals Rf, n is 1, 2, 3, 4 or 5, p is 1, 2, 3, 4 or 5, q is 1, 2, 3, 4 or 5, r is 1, 2, 3, 4 or 5,Rbis selected form F, CN, OH, CH3, CF3and OCH3,Rcis selected form F, Cl, CN, OH, NO2, SO3H, CH3, CF3and OCH3,Rdis selected form F, CN, OH, NO2, SO3H, CH3, CF3and OCH3or 2 radicals Rdwhich are bound to the same C-Atom of the heterocyclic ring may form a carbonyl group together with the carbon atom to which they are bound,Reis selected form F, Cl, CN, NO2, OH, SO3H, CH3, CF3and OCH3, Rfis selected form F, CN, NO2, OH, SO3H, CH3, CF3and OCH3.

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