The present invention relates to a process for preparing substituted 2-nitrobiphenyls via Suzuki coupling using a palladium catalyst with specific phosphorus ligands and a solvent mixture containing water and an organic solvent which is at least partially miscible with water.

Functionalized biphenyl compounds are of great interest especially as pharmaceuticals and pesticides, and as precursors of such active ingredients. For instance, 2-nitro and 2-aminobiphenyls are important precursors for aryl- and heteroarylcarboxamides which find use as fungicides, and for which boscalid, fluxapyroxad, bixafen or pyraziflumid are prominent representatives. For their synthesis, a series of organometallic methods is available, which offer efficient access to a multitude of biphenyl derivatives. The most frequently applied is the Suzuki coupling.

The Suzuki coupling (also called Suzuki-Miyaura coupling or Suzuki reaction or Suzuki- Miyaura reaction) is a cross coupling reaction in which an organoboron compound is reacted with an organic halogenide or sulfonate in the presence of a transition metal catalyst, mostly a Pd or Ni catalyst, and in general also of a base.

Principally, the known processes for preparing nitro- or aminobiphenyls via Suzuki coupling work well, at least on a laboratory scale. However, there is still room for improvement, especially with respect to an application in large-scale industrial processes. For instance, the amount of required Pd in the catalyst is still rather high.

WO 2015/01 1032 relates to a process for preparing chlorinated biphenylanilines or anilides by Suzuki coupling using a palladium catalyst containing an optionally substituted di-tert-butylphenyl phosphine or a salt thereof as ligand. This catalyst is said to avoid the undesired formation of triphenyl compounds. In the halide starting compound II the leaving group Hal is Br or I. In the examples the coupling reaction is carried out in a mixture of water and 1 -butanol as solvent in the presence of potassium carbonate as base. The Pd catalyst is used in an amount of 0.12 mol%, calculated on the basis of the Pd content and relative to 1 mol of the halide. Although in this process the amount of Pd is already reduced as compared to older processes, there is still room for improvement. Moreover, the use of aromatic bromides or iodides is not desirable, not only because of their cost, especially in case of the iodide, but also because of environmental concerns connected with bromide or iodide- containing waste water.

It was thus an object of the present invention to provide a process for producing nitro- substituted biphenyls via Suzuki coupling which avoids some of the drawbacks of the prior art processes, especially when these are applied on a large scale. Especially it was the object of the present invention to provide a process for producing nitro- substituted biphenyls via Suzuki coupling which requires distinctly lower amounts of palladium, suppresses homocoupling, avoids bromide- and iodide-containing waste water and is well-suited for large-scale applications.

The object is achieved by a process for preparing substituted biphenyls of the formula I

in which the substituents are each defined as follows: is hydrogen, cyano, F, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy or C1-C4- haloalkoxy; is cyano, nitro, F, CI, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C3-Cio-cycloalkyl which may carry 1 , 2, 3 or 4 C ₁ -C ₄ -alkyl substituents; C3-Cio-halocycloalkyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylcarbonyl, Ci-C6-haloalkylcarbonyl, C ₁ -C ₆ - alkoxycarbonyl, or Ci-C6-haloalkoxycarbonyl; and is 0, 1 , 2 or 3, where, in case that n is 2 or 3, the R ² radicals may have identical or different definitions; which comprises reacting a compound of the formula II

in which R ¹ is as defined above, in the presence of a base and of a palladium catalyst, where the palladium catalyst is introduced into the reaction in the form of

- a palladium source and a phosphorus ligand of the formula I I I or a salt thereof

in which

Ar is a C ₆ -C ₁₀ -aryl radical or a 5- or 6-membered heteroaryl ring containing 1 , 2, 3 or 4 heteroatoms selected from the group consisting of N and O as ring members, where the aryl radical and the heteroaryl ring are optionally substituted with 1 , 2 or 3 substituents independently selected from the group consisting of Ci-C6-alkyl, Ci-C6-alkoxy, trifluoromethyl and phenyl;

R ³ is Ci-Cs-alkyl or C3-Cio-cycloalkyl; and

R ⁴ is Ci-Cs-alkyl or C ₃ -Cio-cycloalkyl;

or

- a palladium complex containing at least one phosphorus ligand of the formula III as defined above or a salt thereof; in a solvent mixture of water and an organic solvent which is at least partially miscible with water, with an organoboron compound of the formula IV

wherein R ² and n are as defined above and the compound of formula IV is selected from the group consisting of

(i) boronic acids with o = 0, m = 2; p = 1 and Z = hydroxyl groups,

or their trimers;

(ϋ) boronic acid derivates with o = 0, m = 2; p = 1 and Z = halogen; C ₁ -C ₄ -alkyl, Ci-C6-alkoxy or C ₆ -C ₁₀ -aryloxy;

(iii) borinic acids or borinic acid derivatives with o = 0, m = 1 ; p = 2 and Z = hydroxy, halogen, C ₁ -C ₄ -alkyl, Ci-C6-alkoxy or C ₆ -C ₁₀ -aryloxy;

(iv) mixed borinic acids or borinic acid derivatives with o = 1 , m = 1 ; p = 1 , A = C1-C4- alkyl and Z = hydroxy, halogen, C ₁ -C ₄ -alkyl, Ci-C6-alkoxy or C ₆ -C ₁₀ -aryloxy; (v) cyclic boronic esters with o = 0, m = 2 and p = 1 , wherein the two Z groups form together a bridging group -0-(CH2) _q -0-, wherein q is 2 or 3, so that the two Z groups, together with the boron atom to which they are attached, form a 5- or 6-membered ring, where the CH2 groups are optionally substituted by one or two C ₁ -C ₄ -alkyl groups; (vi) boronates with o = 0, m = 3, p = 1 and Z = hydroxyl, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₆ - alkoxy or C ₆ -C ₁₀ -aryloxy, and accompanied by a cation which compensates the negative charge of the boronate anion;

(vii) triarylboranes with o = 0, m = 0 and p = 3;

(viii) tetraarylborates with o = 0, m = 0 and p = 4, and accompanied by a cation which compensates the negative charge of the borate anion; where the reaction is carried out at a temperature of from 80 to 140°C. 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. The prefix C _n -C _m indicates in each case the possible number of carbon atoms in the group.

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

The term "alkyl" as used herein and in the alkyl moieties of alkoxy, alkylcarbonyl, alkoxycarbonyl and the like refers to saturated straight-chain or branched hydrocarbon radicals having 1 to 2 ("Ci-C ₂ -alkyl"), 1 to 3 ("Ci-Cs-alkyI"), 1 to 4 ("Ci-C ₄ -alkyl"), 1 to 6 ("Ci-C ₆ -alkyl") or 1 to 8 ("Ci-C ₈ -alkyl") carbon atoms. Ci-C ₂ -Alkyl is methyl or ethyl. Ci-C3-Alkyl is additionally propyl and isopropyl. Ci-C ₄ -Alkyl is additionally n-butyl,

1 - methylpropyl (sec-butyl), 2-methylpropyl (isobutyl) or 1 ,1 -dimethylethyl (tert-butyl). Ci-C6-Alkyl is additionally also, for example, pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1 -ethylpropyl, 1 ,1 -dimethylpropyl,

1 ,2-dimethylpropyl, hexyl, 1 -methylpentyl, 2-methylpentyl, 3-methylpentyl,

4-methylpentyl, 1 ,1 -dimethylbutyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl,

2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, 1 ,1 ,2-trimethylpropyl, 1 ,2,2-trimethylpropyl, 1 -ethyl-1 -methylpropyl, or 1 -ethyl-

2- methylpropyl. d-Cs-Alkyl is additionally also, for example, heptyl, octyl and the isomers thereof.

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 ("Ci-C ₂ -haloalkyl"), 1 to 3 ("Ci-C ₃ -haloalkyl"), 1 to 4 ("Ci-C ₄ -haloalkyl") or 1 to 6 ("Ci-C6-haloalkyl") carbon atoms (as mentioned above), where some or all of the hydrogen atoms in these groups are replaced by halogen atoms as mentioned above: in particular Ci-C2-haloalkyl, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1 -chloroethyl, 1 -bromoethyl, 1 -fluoroethyl,

2- fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro- 2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl or pentafluoroethyl. Ci-C3-haloalkyl is additionally, for example, 1 -fluoropropyl, 2-fluoropropyl,

3- fluoropropyl, 1 ,1 -difluoropropyl, 2,2-difluoropropyl, 1 ,2-difluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, heptafluoropropyl, 1 ,1 ,1 -trifluoroprop-2-yl, 3-chloropropyl and the like. Examples for C ₁ -C ₄ -haloalkyl are, apart those mentioned for Ci-C3-haloalkyl, 4-chlorobutyl and the like.

"Methyl which is substituted by 1 , 2 or 3 fluorine atoms" is fluoromethyl, difluoromethyl or trifluoromethyl.

"Ci-C6-Hydroxyalkyl" is Ci-C6-alkyl, 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- 1 -methylethyl, 2-hydroxy-1 -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.

The term "cycloalkyl" as used herein refers to mono- or bicyclic saturated hydrocarbon radicals having 3 to 10 ("C3-Cio-cycloalkyl"), 3 to 8 ("Cs-Cs-cycloalkyl"), in particular 3 to 6 ("C ₃ -C ₆ -cycloalkyl") or 3 to 5 ("Cs-Cs-cycloalkyl") or 3 to 4 ("C ₃ -C ₄ - 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, bicyclo[4.3.0]nonyl (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,

bicyclo[3.2.1]octyl and the like. Preferably, the term cycloalkyl denotes a monocyclic saturated hydrocarbon radical.

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-Cio-halocycloalkyl" ) or 3 to 8 ("C3-C8- halocycloalkyl" ) or preferably 3 to 6 ("C ₃ -C ₆ -halocycloalkyl") or 3 to 5 ("C3-C5- halocycloalkyl") or 3 to 4 ("C3-C ₄ -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.

"Alkoxy" is an alkyl group attached via an oxygen atom. The term "Ci-C2-alkoxy" is a Ci-C2-alkyl group, as defined above, attached via an oxygen atom. The term

"Ci-C3-alkoxy" is a Ci-C3-alkyl group, as defined above, attached via an oxygen atom. The term "C ₁ -C ₄ -alkoxy" is a C ₁ -C ₄ -alkyl group, as defined above, attached via an oxygen atom. The term "Ci-C6-alkoxy" is a Ci-C6-alkyl group, as defined above, attached via an oxygen atom. Ci-C2-Alkoxy is methoxy or ethoxy. Ci-C3-Alkoxy is additionally, for example, n-propoxy and 1 -methylethoxy (isopropoxy). C ₁ -C ₄ -Alkoxy is additionally, for example, butoxy, 1 -methylpropoxy (sec-butoxy), 2-methylpropoxy (isobutoxy) or 1 ,1 -dimethylethoxy (tert-butoxy). Ci-C6-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-1 -methylpropoxy or 1 -ethyl-2- methylpropoxy.

"Haloalkoxy" is a haloalkyl group attached via an oxygen atom. The term "C1-C2- haloalkoxy" is a Ci-C2-haloalkyl group, as defined above, attached via an oxygen atom. The term "Ci-C3-haloalkoxy" is a Ci-C3-haloalkyl group, as defined above, attached via an oxygen atom. The term "C ₁ -C ₄ -haloalkoxy" is a C ₁ -C ₄ -haloalkyl group, as defined above, attached via an oxygen atom. The term "Ci-C6-haloalkoxy" is a Ci-C6-haloalkyl group, as defined above, attached via an oxygen atom. Ci-C2-Haloalkoxy is, for example, OCH ₂ F, OCHF ₂ , OCF ₃ , OCH ₂ CI, OCHC , OCCI ₃ , chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy,

2-bromoethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro- 2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy,

2,2,2-trichloroethoxy or OC2F5. Ci-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, 1 -(CH ₂ F)-2-fluoroethoxy, 1 -(CH ₂ CI)-2-chloroethoxy or 1 -(CH ₂ Br)-2- bromoethoxy. C ₁ -C ₄ -Haloalkoxy is additionally, for example, 4-fluorobutoxy,

4-chlorobutoxy, 4-bromobutoxy or nonafluorobutoxy. Ci-C6-Haloalkoxy is additionally, for example, 5-fluoropentoxy, 5-chloropentoxy, 5-brom pentoxy, 5-iodopentoxy, undecafluoropentoxy, 6-fluorohexoxy, 6-chlorohexoxy, 6-bromohexoxy, 6-iodohexoxy or dodecafluorohexoxy.

The term "alkylcarbonyl" is a Ci-C6-alkyl ("Ci-C6-alkylcarbonyl"), preferably a C ₁ -C ₄ -alkyl ("C ₁ -C ₄ -alkylcarbonyl") group, as defined above, attached via a carbonyl

[C(=0)] group. Examples are acetyl (methylcarbonyl), propionyl (ethylcarbonyl), propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl and the like.

The term "haloalkylcarbonyl" is a Ci-C6-haloalkyl ("Ci-C6-haloalkylcarbonyl"), preferably a C ₁ -C ₄ -haloalkyl ("C ₁ -C ₄ -haloalkylcarbonyl") group, as defined above, attached via a carbonyl [C(=0)] group. Examples are trifluoromethylcarbonyl,

2,2,2-trifluoroethylcarbonyl and the like. The term "alkoxycarbonyl" is a Ci-C6-alkoxy ("Ci-C6-alkoxycarbonyl"), preferably a C ₁ -C ₄ -alkoxy ("C ₁ -C ₄ -alkoxycarbonyl") group, as defined above, attached via a carbonyl [C(=0)] group. Examples are methoxycarbonyl, ethoxycarbonyl,

propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl and the like.

The term "haloalkoxycarbonyl" is a Ci-C6-haloalkoxy ("C ₁ -C ₆ - haloalkoxycarbonyl"), preferably a C ₁ -C ₄ -haloalkoxy ("C ₁ -C ₄ -haloalkoxycarbonyl") group, as defined above, attached via a carbonyl [C(=0)] group. Examples are trifluoromethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl and the like.

If the term "aryl" as used herein and in the aryl moieties of aryloxy is used without prefix (C _n -C _m ), it indicates an aryl group with 6 to 30, in particular 6 to 14, specifically 6 to 10 carbon atoms as ring members. Aryl is a mono-, bi- or polycyclic carbocyclic (i.e. without heteroatoms as ring members) aromatic radical. One example for a monocyclic aromatic radical is phenyl. In bicyclic aryl rings two aromatic rings are condensed, i.e. they 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, 1 H-benzo[a]phenalenyl, pyrenyl and the like.

"C ₆ -C ₁₀ -Aryl" is phenyl, 1 -naphthyl or 2-naphthyl.

"Aryloxy" is aryl, as defined above, bound via an oxygen atom to the remainder of the molecule.

"C ₆ -C ₁₀ -Aryloxy" is phenoxy, 1 -naphthyloxy or 2-naphthyloxy.

5- or 6-membered heteroaryl rings containing 1 , 2, 3 or 4 heteroatoms selected from the group consisting of N and O as ring members are monocyclic heteroaromatic rings. In the 6-membered heteroaryl rings the heteroatom ring members can only be nitrogen atoms. Examples for 5- or 6-membered heteroaromatic rings containing 1 , 2, 3 or 4 heteroatoms selected from N and O as ring members are 2-furyl, 3-furyl, 1 -pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1 -imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl,

4- isoxazolyl, 5-isoxazolyl, 1 ,3,4-triazol-1 -yl, 1 ,3,4-triazol-2-yl, 1 ,3,4-triazol-3-yl,

1 ,2,3-triazol-1 -yl, 1 ,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,5-oxadiazol-3-yl,

1 ,2,3-oxadiazol-4-yl, 1 ,2,3-oxadiazol-5-yl, 1 ,3,4-oxadiazol-2-yl, tetrazol-1 -yl, tetrazol-

2- yl, tetrazol-5-yl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 1 -oxopyridin-2-yl, 1 -oxopyridin-

3- yl, 1 -oxopyridin-4-yl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl,

5- pyrimidinyl, 2-pyrazinyl, 1 ,3,5-triazin-2-yl, 1 ,2,4-triazin-3-yl, 1 ,2,4-triazin-5-yl,

1 ,2,3,4-tetrazin-1 -yl, 1 ,2,3,4-tetrazin-2-yl, 1 ,2,3,4-tetrazin-5-yl and the like.

The remarks made below regarding preferred embodiments of the process according to the invention, especially regarding preferred embodiments of the radicals of the different reactants and products (to be more precise preferred embodiments of the variables of the compounds of formulae I, II, III, IV, V and VI, especially with respect to their substituents R ¹ , R ² , R ³ , R ⁴ , R ⁵ , Ar and n) and of the reaction conditions of the processes according to the invention, apply either taken alone or, more particularly, in any conceivable combination with one another.

The remarks to preferred embodiments of R ¹ apply both to formula I as well as to formula II, V and VI, unless explicitly specified otherwise. The remarks to preferred embodiments of R ² and n apply both to formula I as well as to formula IV, V and VI, unless explicitly specified otherwise.

In a particular embodiment, R ¹ is hydrogen or fluorine. Specifically, R ¹ is hydrogen.

In a specific embodiment, R ¹ is in para position to the nitro group (this definition of the position of R ¹ is of course only relevant if R ¹ is not hydrogen) . In case of the biphenyl compounds I, nitro group in this case refers of course to the nitro group on the same phenyl ring as R ¹ (and not to a possible nitro group R ² ).

In particular, R ² is F or CI.

Preferably, n is 1 , 2 or 3; specifically 1 or 3.

More particularly, R ² is F or CI and n is 1 , 2 or 3. Specifically, R ² is F or CI and n is 1 or 3.

In a particular embodiment, the biphenyl compound I is 4-chloro-2'-nitro-biphenyl, 3,4-dichloro-2'-nitro-biphenyl, 3,4-difluoro-2'-nitro-biphenyl, 3,4,5-trifluoro-2'-nitro- biphenyl, 3-chloro-4,5-difluoro-2'-nitro-biphenyl, 3,4-dichloro-5'-fluoro-2'-nitro-biphenyl or 3,5-dichloro-4-fluoro-2'-nitro-biphenyl. Specifically, the biphenyl compound I is 4-chloro-2'-nitro-biphenyl, 3,4-dichloro-2'-nitro-biphenyl, 3,4,5-trifluoro-2'-nitro-biphenyl or 3,4-dichloro-5'-fluoro-2'-nitro-biphenyl; very specifically 4-chloro-2'-nitro-biphenyl or 3,4,5-trifluoro-2'-nitro-biphenyl.

The organoboron compound IV as defined under (i) in which o = 0, m = 2; p = 1 and Z = OH is a boronic acid of formula IVa. Its trimer is a boroxine and has formula tri- IVa:

The boronic acid derivates as defined under (ii) with o = 0, m = 2; p = 1 and Z = halogen; C ₁ -C ₄ -alkyl, Ci-C6-alkoxy or C ₆ -C ₁₀ -aryloxy are compounds of formula IVb, wherein Z = halogen; C ₁ -C ₄ -alkyl, Ci-C6-alkoxy or C ₆ -C ₁₀ -aryloxy:

The borinic acids or borinic acid derivatives as defined under (iii) with o = 0, m = 1 ; p = 2 and Z = hydroxy, halogen, C ₁ -C ₄ -alkyl, Ci-C6-alkoxy or C ₆ -C ₁₀ -aryloxy are compounds of formula IVc (borinic acids ) or compounds of formula IVd (borinic acid d rivatives), wherein Z = halogen, C ₁ -C ₄ -alkyl, Ci-C6-alkoxy or C ₆ -C ₁₀ -aryloxy:

The mixed borinic acids or borinic acid derivatives as defined under (iv) with o = 1 , m = 1 ; p = 1 , A = C ₁ -C ₄ -alkyl and Z = hydroxy, halogen, C ₁ -C ₄ -alkyl, Ci-C6-alkoxy or C ₆ -C ₁₀ -aryloxy are compounds of formula IVe (mixed borinic acids ) or compounds of formula IVf (mixed borinic acid derivatives), wherein Z = halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₆ - alkoxy or C ₆ -C ₁₀ -aryloxy:

The cyclic boronic esters as defined under (v) with o = 0, m = 2 and p = 1 , wherein the two Z groups form together a bridging group -0-(CH2) _q -0-, wherein q is 2 or 3, so that the two Z groups, together with the boron atom to which they are attached, form a 5- or 6- membered ring, where the Chb groups are optionally substituted by one or two C ₁ -C ₄ -alkyl groups are compounds of formula IVg: wherein A is -C(R ^A1 )(R ^A2 )-C(R ^A3 )(R ^A4 )- or -C(R ^A1 )(R ^A2 )-C(R ^A3 )(R ^A4 )-C(R ^A5 )(R ^A6 )-, where R ^A1 , R ^A2 , R ^A3 , R ^M , R ^A5 and R ^A6 , independently of each other, are hydrogen or C ₁ -C ₄ - alkyl.

The boronates as defined under (vi) with o = 0, m = 3, p = 1 and Z = hydroxyl, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkoxy or C ₆ -C ₁₀ -aryloxy, and accompanied by a cation which compensates the negative charge of the boronate anion are compounds of formula IVh, wherein each Z is independently hydroxyl, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₆ - alkoxy or C ₆ -C ₁₀ -aryloxy and (M ^a+ )i/ _a is a cation equivalent:

IVh

The triarylboranes as defined under (vii) with o

pounds of formula IVi:

IVi

The tetraaryl borates as defined under (viii) with o = 0, m = 0 and p = 4, and accompanied by a cation which compensates the negative charge of the borate anion, are compounds of formula IVj, wherein (M ^a+ )i/ _a is a cation equivalent:

M in compounds IVh and IVj is preferably an alkali or earth alkaline metal cation or an ammonium cation (NR ^a R ^b R ^c R ^d ) ⁺ , wherein R ^a , R ^b , R ^c and R ^d , independently of each other, are hydrogen, Ci-C6-alkyl or Ci-C6-hydroxyalkyl. If M is an alkali metal cation or an ammonium cation, a is 1 . If M is an earth alkaline metal cation, a is 2. More preferably, M is an alkali metal cation.

In the above organoboron compounds R ² and n have one of the above general or, in particular, one of the above preferred meanings. In a particular embodiment, (R2) _n is 4-chloro, 3,4-dichloro, 3,4-difluoro, 3,4,5-trifluoro, 3-chloro-4,5-difluoro or

3,5-dichloro-4-fluoro. Specifically, (R2) _n is 4-chloro, 3,4-dichloro or 3,4,5-trifluoro. Very specifically, (R2) _n is 4-chloro or 3,4,5-trifluoro.The positions relate to the 1 -position of the attachment of the phenyl ring to the boron atom.

A in the mixed borinic acids or borinic acid derivatives as defined under (iv) is in particular methyl.

Preferably, the organoboron compound IV is a phenylboronic acid IVa or a diphenylborinic acid IVc

or a mixture of IVa and IVc, in which R ² and n have one of the above general or, in particular, one of the above preferred meanings. In particular, the organoboron compound IV is a phenylboronic acid IVa. In a particular embodiment, (R2) _n in IVa and IVc is 4-chloro, 3,4-dichloro,

3,4-difluoro, 3,4,5-trifluoro, 3-chloro-4,5-difluoro or 3,5-dichloro-4-fluoro, more particularly 4-chloro, 3,4-dichloro or 3,4,5-trifluoro, and specifically 4-chloro or

3,4,5-trifluoro. The positions relate to the 1 -position of the attachment point of the phenyl ring to the boron atom. The organoboron compounds as defined under (i) to (viii) and methods for preparing them are known in the art and described, for example, in WO 2015/01 1032 and the literature cited therein.

The compounds of formulae II and IV are used in a molar ratio of preferably from 5:1 to 1 :5, more preferably from 2:1 to 1 :2, even more preferably from 1 .5:1 to 1 :1 .5, in particular from 1.1 :1 to 1 :1.1 , specifically from 1.05:1 to 1 :1 .05, and very specifically of approximately 1 :1 . "Approximately" is intended to include deviations from ideal stoichiometry caused, for example, by weight errors. Such errors are in general below 10%, mostly below 5%.

The molar ratios of compounds IV as given above relate to the number of phenyl rings contained in the organoboron molecule IV which can react in the Suzuki reaction.

Thus, consequently, the molar ratio of compounds II and IVa, IVb, IVe, IVf, IVg or IVh (having one phenyl ring per organoboron molecule which can react in the Suzuki reaction), the compounds IV here counted as such, is preferably from 5:1 to 1 :5, more preferably from 2:1 to 1 :2, even more preferably from 1.5:1 to 1 :1.5, in particular from 1 .1 :1 to 1 :1.1 , specifically from 1.05:1 to 1 :1 .05, and very specifically of approximately 1 :1 ;

the molar ratio of compounds II and IVc or IVd (having two phenyl rings per organoboron molecule which can react in the Suzuki reaction), the compounds IV here counted as such, is preferably from 10:1 to 1 :2.5, more preferably 4:1 to 1 :1 , even more preferably from 3:1 to 1 :0.75, in particular from 2.2:1 to 1 :0.55, specifically from 2.1 :1 to 1 :0.53, and very specifically of approximately 2:1 ;

the molar ratio of compounds II and tri-IVa or IVi (having three phenyl rings per organoboron molecule which can react in the Suzuki reaction), the compounds IV here counted as such, is preferably from 15:1 to 1 :1.7, more preferably from 6:1 to 1 :0.7, even more preferably from 4.5:1 to 1 :0.5, in particular from 3.3:1 to 1 :0.37, specifically from 3.15:1 to 1 :0.35, and very specifically of approximately 3:1 ; and

the molar ratio of compounds II and IVj (having four phenyl rings per

organoboron molecule which can react in the Suzuki reaction), the compound IVj here counted as such, is preferably from 20:1 to 1 :1.25, more preferably from 8:1 to 1 :0.5, even more preferably from 6:1 to 1 :0.38, in particular from 4.4:1 to 1 :0.28, specifically from 4.2:1 to 1 :0.26, and very specifically of approximately 4:1.

As however the removal of the halogen compound II from the reaction mixture after completion of the reaction is sometimes more difficult than the removal of the organoboron compound IV, it may be advantageous to use the organoboron compound IV in at least equimolar amounts, better in slight excess, so that the halogen compound II is reacted more or less completely. In this case, compounds of formulae II and IV (the latter counted as the number of phenyl rings contained in the organoboron molecule IV which can react in the Suzuki reaction) are used in a molar ratio of preferably from 1 :1 to 1 :1 .5, more preferably from 1 :1 to 1 :1.1 , in particular from 1 :1 to 1 :1 .05 and specifically from 1 :1 .01 to 1 :1.05. However, the inverse stoichiometry is also possible; i.e. compound II can also be used in slight excess; meaning that compounds of formulae II and IV (the latter counted as the number of phenyl rings contained in the organoboron molecule IV which can react in the Suzuki reaction) are used in a molar ratio of preferably from 1 :1 to 1 .5:1 , more preferably from 1 :1 to 1 .1 :1 , in particular from 1 :1 to 1.05:1 and specifically from 1 .01 :1 to 1 .05:1.

Phenyl rings contained in compound IV which can react in the Suzuki reaction are those phenyl rings which are directly bound to the boron atom. Thus, phenyl rings contained in Z, if this is aryloxy, are not counted.

In case of compounds IV, "equimolar amounts" and "excess" amounts are of course related to the number of phenyl rings contained in compounds IV which can react in the Suzuki reaction.

In the phosphorus ligands III, Ar is preferably a C ₆ -C ₁₀ -aryl radical, optionally substituted with 1 , 2 or 3 substituents independently selected from the group consisting of Ci-C6-alkyl, Ci-C6-alkoxy, trifluoromethyl and phenyl. More preferably, Ar is phenyl which may carry 1 , 2 or 3 substituents independently selected from the group consisting of Ci-C6-alkyl, Ci-C6-alkoxy and trifluoromethyl, and is in particular unsubstituted phenyl.

R ³ and R ⁴ are preferably, independently of each other, Ci-Cs-alkyl, more preferably branched Cs-Cs-alkyl, and are in particular both tert-butyl.

Salts of the phosphorus ligands are acid addition salts, these thus having the formula: where X ^" is an anion. Principally any anion derived from a strong acid is suitable, but seeing the desire to avoid certain anions in the waste water, preferred anions are selected from the group consisting of chloride, sulfate, hydrogensulfate, phosphate, hydrogenphosphate, dihydrogenphosphate, perchlorate, tetrafluoroborate,

hexafluorophosphate, hydrogenhexafluorozirconate and hydrogenhexafluorotitanate. Specifically, X ^" is tetrafluoroborate (BF ₄ -).

In particular, the phosphorus ligand III is a compound of the formula Ilia or 1Mb in which Ar is phenyl and R ³ and R ⁴ are both tert-butyl where X ^" is an anion, preferably selected from the group consisting of chloride, sulfate, hydrogensulfate, phosphate, hydrogenphosphate, dihydrogenphosphate, perchlorate, tetrafluoroborate, hexafluorophosphate, hydrogenhexafluorozirkonate and

hydrogenhexafluorotitanate. Specifically, X ^" is tetrafluoroborate (BFV).

As said above, the palladium catalyst is introduced into the reaction in the form of a palladium source and a phosphorus ligand of the formula III or a salt thereof, or in form of a palladium complex containing at least one phosphorus ligand of the formula III as defined above or a salt thereof.

If the palladium catalyst is introduced into the reaction in the form of a palladium source and a phosphorus ligand of the formula III or a salt thereof, the complex with the ligand (III) is either formed before the Suzuki reaction starts or, in particular, is formed in situ.

The palladium source is preferably a palladium(ll) salt, a palladium complex with ligands different from the ligand of formula III or its salt, or is metallic palladium which is optionally bound to a carrier.

Suitable Pd(ll) salts are for example Pd(ll) acetate, PdC or Na ₂ PdCI ₄ .

Preference is given to Pd(ll) acetate and PdC . In particular, Pd(ll) acetate is used.

Suitable Pd(ll) complexes with ligands different from the ligand of formula III or its salt are for example Pd(ll) acetylacetonate or bisacetonitrile Pd(ll) chloride.

A suitable carrier for metallic palladium is charcoal.

The palladium complex containing at least one phosphorus ligand of the formula III as defined above or a salt thereof can be a pre-formed complex of palladium(O) and the ligand III or a salt thereof, or can be a pre-formed palladium(ll) complex and the ligand III or a salt thereof.

An example for a palladium complex containing at least one phosphorus ligand of the formula III as defined above or a salt thereof in which palladium is contained as Pd(ll) is Pd(ligand lll^C ; e.g. dichlorobis(di-(tert-butyl)-phenylphosphine)palladium(ll) (Pd(ll)[P(C6H ₅ )(C(CH3)3)2]2Cl2). This complex is commercially available.

An example for a palladium complex containing at least one phosphorus ligand of the formula III as defined above or a salt thereof in which palladium is contained as Pd(0) is Pd(ligand lll)2; e.g. bis(di-(tert-butyl)-phenylphosphine)palladium(0)

(Pd(0)[P(C6H ₅ )(C(CH3)3)2]2. This complex is commercially available.

In case that a Pd(ll) salt or a Pd(ll) complex is used, Pd(ll) is reduced to Pd(0) before the Suzuki reaction starts. The reduction generally takes place in situ.

In one preferred embodiment, the palladium catalyst is introduced into the reaction in form of a palladium(ll) salt, specifically Pd(ll) acetate or PdC , and the ligand III or a salt thereof.

In another preferred embodiment, the palladium catalyst is introduced into the reaction in form of a pre-formed complex of palladium(O) or (II) and the ligand III or a salt thereof, where the catalyst is specifically selected from the group consisting of bis(di-(tert-butyl)-phenylphosphine)palladium(0) and dichlorobis(di-(tert-butyl)- phenylphosphine)palladium(ll).

If the palladium catalyst is not introduced into the reaction in form of the preformed complex of palladium and the ligand III, but in form of a Pd source (e.g. a palladium(ll) salt, a palladium complex with ligands different from III (or its salt) or a palladium(O) source), and a phosphorus ligand of the formula III or a salt thereof, the Pd source (calculated on the basis of the Pd content) and the ligand of formula III or its salt are used in a molar ratio of preferably from 5:1 to 1 :5, more preferably from 2:1 to 1 :3, even more preferably from 1 .5:1 to 1 :2.5, in particular from 1.1 :1 to 1 :2.5, specifically from 1 .05:1 to 1 :2.2, very specifically from 1 :1 to 1 :2.

The Pd catalyst, to be more precise the Pd source or the preformed Pd complex containing at least one phosphorus ligand of the formula III as defined above or a salt thereof (in both cases calculated on the basis of the Pd content) can principally be used in an amount of up to 5 mol%, e.g. of from 0.0001 mol% to 5 mol%, relative to 1 mol of compound II or of compound IV (1 mol of compound II or of compound IV corresponding to 100 mol%). If compounds II and IV are not used in equimolar amounts, the above mol% relate to 1 mol of that compound II or IV which is not used in excess. The ligand III or its salt and the other reaction conditions allow however for the use of Pd in significantly lower amounts. Thus, preferably, the Pd catalyst (calculated on the basis of the Pd content) is used in an amount of from 0.0001 mol% to 0.5 mol%, more preferably from 0.0001 mol% to 0.1 mol%, in particular from 0.0001 mol% to 0.01 mol%, and specifically from 0.001 mol% to 0.007 mol%, very specifically from 0.002 to 0.006 mol%, relative to 1 mol of compound II or of compound IV (1 mol of compound II or of compound IV corresponding to 100 mol%). If compounds II and IV are not used in equimolar amounts, the above mol% relate to 1 mol of that compound II or IV which is not used in excess. Where the amount of the Pd catalyst is related to the compound IV, the latter is of course counted as the number of phenyl rings contained therein which can react in the Suzuki reaction. In other words, where the amount of the Pd catalyst is related to the compound IV, the amount of the Pd catalyst of course actually relates to 1 mol of phenyl rings contained in compound IV which can react in the Suzuki reaction. Thus, for example, in case of borinic acids IVc, which have two phenyl rings, x mol% Pd, relative to 1 mol of compound IVc, means in this case x mol% Pd relative to 1 mol of phenyl rings contained in IVc, and thus to 0.5 mol of compound IVc taken as such. Phenyl rings contained in compound IV which can react in the Suzuki reaction are those phenyl rings which are directly bound to the boron atom.

In case of compounds IV, "equimolar amounts" and "excess" amounts are of course related to the number of phenyl rings contained in compounds IV which can react in the Suzuki reaction.

The reaction is carried out in a solvent mixture of water and an organic solvent which is at least partially miscible with water. "Miscible" means that a homogenous solution is formed. In terms of the present invention, organic solvents which are at least partially miscible with water are solvents which have a miscibility with water of at least 50 g / 100 g of water, preferably of at least 100 g / 100 g of water, at 20°C.

The solvents are preferably polar aprotic.

Polar aprotic solvents are solvents without a functional group from which a proton can dissociate. Examples for suitable polar aprotic solvents are amides, such as Ν,Ν-dimethylformamide (DMF) and Ν,Ν-dimethylacetamide; sulfoxides, such as dimethylsulfoxide (DMSO); lactams, such as N-methylpyrrolidone (NMP); cyclic ethers, such as tetrahydrofuran, 1 ,3-dioxane and 1 ,4-dioxane; ketones, such as acetone and methylethylketone; nitriles, such as acetonitrile; lactones, such as γ-butyrolactone; nitro compounds, such as nitromethane; ureas, such as tetramethyl urea or

dimethylpropylene urea (DMPU); sulfones, such as sulfolan; and carbonic acid esters, such as dimethylcarbonate or ethylenecarbonate. Among the above solvents, preference is given to the cyclic ethers tetrahydrofuran, 1 ,3-dioxane and 1 ,4-dioxane. In particular, tetrahydrofuran is used.

In particular the solvent mixture in which the Suzuki reaction is carried out does not contain any other solvent than water and the organic solvent which is at least partially miscible with water. Preferably, in the solvent mixture water and the organic solvent which is at least partially miscible with water are contained in following amounts:

water: 0.1 to 80% by weight, based on the total amount of the solvent mixture; and organic solvent which is at least partially miscible with water: 20 to 99.9% by weight, based on the total amount of the solvent mixture;

where the amounts of water and organic solvent which is at least partially miscible with water add to 100% by weight.

More preferably, in the solvent mixture water and the organic solvent which is at least partially miscible with water are contained in following amounts:

water: 0.1 to 70% by weight, based on the total amount of the solvent mixture; and - organic solvent which is at least partially miscible with water: 30 to 99.9% by

weight, based on the total amount of the solvent mixture; where the amounts of water and organic solvent which is at least partially miscible with water add to 100% by weight.

Even more preferably, in the solvent mixture water and the organic solvent are contained in following amounts:

- water: 5 to 70% by weight, based on the total amount of the solvent mixture; and organic solvent which is at least partially miscible with water: 30 to 95% by weight, based on the total amount of the solvent mixture;

where the amounts of water and organic solvent add to 100% by weight.

Particularly preferably, in the solvent mixture water and the organic solvent are contained in following amounts:

water: 10 to 70% by weight, based on the total amount of the solvent mixture; and organic solvent which is at least partially miscible with water: 30 to 90% by weight, based on the total amount of the solvent mixture;

where the amounts of water and organic solvent add to 100% by weight.

In particular, in the solvent mixture water and the organic solvent are contained in following amounts:

water: 25 to 70% by weight, based on the total amount of the solvent mixture; and organic solvent which is at least partially miscible with water: 30 to 75% by weight, based on the total amount of the solvent mixture;

where the amounts of water and organic solvent add to 100% by weight.

Specifically, in the solvent mixture water and the organic solvent are contained in following amounts:

water: 35 to 70% by weight, based on the total amount of the solvent mixture; and organic solvent which is at least partially miscible with water: 30 to 65% by weight, based on the total amount of the solvent mixture;

where the amounts of water and organic solvent add to 100% by weight.

The Suzuki reaction is carried out in the presence of a base. Suitable are both inorganic and organic bases.

Suitable inorganic bases are for example from alkali metal carbonates, e.g.

U2CO3, Na2C03, K2CO3 or CS2CO3, earth alkaline metal carbonates, e.g. MgC03 or CaC03, alkali metal phosphates, e.g. U3PO4, Na3P0 ₄ , K3PO4 or CS3PO4, earth alkaline metal phosphates, e.g. Mg3(P0 ₄ )2 or Ca3(P0 ₄ )2, alkali metal hydrogenphosphates, e.g. U2HPO4, Na2HP0 ₄ , K2HPO4 or CS2HPO4, earth alkaline metal hydrogenphosphates, e.g. MgHP0 ₄ or CaHP0 ₄ , alkali metal hydroxides, LiOH, NaOH or KOH, and earth alkaline metal hydroxides, e.g. Mg(OH)2 or Ca(OH)2.

Examples for suitable organic bases are open-chained amines, e.g.

trimethylamine, triethylamine, tripropylamine, ethyldiisopropylamine and the like, or basic N-heterocycles, such as morpoline, pyridine, lutidine, DABCO, DBU or DBN.

Preference is however given to 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. More preference is given to alkali metal carbonates, alkali metal phosphates and alkali metal hydrogenphosphates. Even more preferred are alkali metal carbonates, such as the above-mentioned U2CO3, Na2C03, K2CO3 or CS2CO3. In particular, Na2C03 or K2CO3 are used. Specifically, K2CO3 is used. In view of corrosive properties of carbonates under certain conditions, it may however be more advantageous to use one of the above-listed phosphates. Thus, in an alternative even more preferred

embodiment, alkali metal phosphates, such as the above-mentioned U3PO4, Na3P0 ₄ , K3PO4 or CS3PO4, are used. Specifically, Na3P0 ₄ or K3PO4 are used.

The base is preferably used in an amount 0.5 to 5 mol per mol of compound II or of compound IV, more preferably from 1 to 4 mol per mol of compound II or of compound IV, in particular from 1 to 3 mol per mol of compound II or of compound IV, specifically from 1 to 2.2 mol per mol of compound II or of compound IV, and very specifically from 1 to 2 mol per mol of compound II or of compound IV. If compounds II and IV are not used in equimolar amounts, the above relation is to 1 mol of that compound II or IV which is not used in excess. Where the amount of the base is related to the compound IV, the latter is of course counted as the number of phenyl rings contained therein which can react in the Suzuki reaction. In other words, where the amount of the base is related to the compound IV, the amount of the base of course actually relates to 1 mol of phenyl rings contained in compound IV which can react in the Suzuki reaction. Thus, for example, in case of borinic acids IVc, which have two phenyl rings, x mol% of base, relative to 1 mol of compound IVc, means in this case x mol% of base relative to 1 mol of phenyl rings contained in IVc, and thus to 0.5 mol of compound IVc taken as such.

As said above, phenyl rings contained in compound IV which can react in the Suzuki reaction are those phenyl rings which are directly bound to the boron atom.

In case of compounds IV, "equimolar amounts" and "excess" amounts are of course related to the number of phenyl rings contained in compounds IV which can react in the Suzuki reaction.

The reaction is preferably carried out at a temperature of from 80 to 120°C; more preferably from 90 to 1 10°C, in particular of from 95 to 1 10°C. The reaction pressure is principally not critical. As however elevated

temperatures are used and in case that the solvents used have a boiling point beneath the desired temperature, the reaction is in this case generally carried out in a closed vessel. This results in an inherent pressure, which is generally in the range of from 1 .1 to 10 bar, in particular from 1.5 to 5 bar, specifically from 2 to 4 bar. The exertion of additional pressure, e.g. by pressurizing with an inert gas, is not necessary. The reaction can be carried out by standard proceedings for Suzuki reactions, 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 reaction is preferably carried out in an inert atmosphere in order to avoid the presence of oxygen, e.g. under an argon or nitrogen atmosphere.

The reaction 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 compound of the formula I is isolated in a customary manner. For example, the solvents are removed, for example under reduced pressure. Preferably, however, the work-up is effected by adding water to the reaction mixture, if desired removing the organic solvent which is at least partially miscible with water, e.g. via distillation, if expedient under reduced pressure, adding a non-polar organic solvent and separating the two phases (aqueous and organic phase).

Non-polar organic solvents in terms of the present invention 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 methyl- isobutylether, and higher alkanols, such as n-butanol or isobutanol. Specifically, a higher alkanol is used.

The product I is in the organic phase mainly formed by the non-polar organic solvent. Moreover, the organic phase also contains the Pd catalyst. To enhance the yield, the aqueous phase can be extracted once or more times with an organic solvent, such as the above listed non-polar organic solvents. If desired, the product I can then be separated from the catalyst and optionally from other undesired components, such as unreacted starting compounds II and/or IV, via customary means. For example, the compound I is crystallized from the organic phase. Alternatively, the solvent is removed from the organic phase, e.g. by distillation, e.g. under vacuum, optionally after drying the organic phase, and the solid matter is taken up in another solvent in which the compound I crystallizes better. In yet another alternative, the solid matter is submitted to a chromatographic separation.

Further purification of the product I can be effected if desired; for example by extraction, crystallization, distillation or by chromatography. If desired, the compound I can then be converted into products of value, such as the below described carboxamides of formula V. Thus, in a further aspect, the invention relates to a process for preparing compounds of the formula V

where R ¹ , R ² and n have one of the above general or, in particular, one of the above preferred meanings, and Q is Q ¹ , Q ² or Q ³

with R ⁵ being methyl, optionally substituted by 1 , 2 or 3 fluorine atoms, and

# being the attachment point to the remainder of the molecule; which process comprises

(a) preparing a compound of the formula I as defined above with a process as

defined above;

(b) reducing the nitro group of the compound of formula I obtained in step (a) to an amino group to obtain a compound of the formula VI

and

(c) reacting the amino compound of the formula VI with a compound Q ¹¹ , Q ²¹ or Q ³¹

where R ⁵ is as defined above and Y is a leaving group.

Reduction in step (b) may be carried out with hydrogen in the presence of a hydrogenation catalyst, such as Pt on charcoal, or with other reduction agents, such as SnCb/HCI, Fe/HCI or Fe/NH ₄ CI.

Reduction can be carried out according to known methods of converting aromatic nitro compounds into the corresponding aromatic amino compounds, such as described, for example, in R. J. Rahaim, R. E. Maleczka (Jr.), Org. Lett., 2005, 7, 5087- 5090, G. S. Vanier, Synlett, 2007, 131 -135, S. Chandrasekhar, S. Y. Prakash, C. L. Rao, J. Org. Chem., 2006, 71 , 2196-2199, H. Berthold, T. Schotten, H. Honig,

Synthesis, 2002, 1607-1610, and C. Yu, B. Liu, L. Hu, J. Org. Chem., 2001 , 66, 919- 924. To obtain compounds V, the amino compound VI is subjected in step (c) to an

N-acylation with an acyl precursor Q ¹¹ , Q ²¹ or Q ³¹ .

Suitable leaving groups Y are -OH, a halide, especially chloride or bromide, -OR ^A , or -0-C(0)-R ^B .

If compounds Q ¹¹ , Q ²¹ or Q ³¹ are acids, i.e. Y = OH, the reaction can be performed in the presence of a coupling reagent. Suitable coupling reagents

(activators) are well known in the art.

If Y = halide, the reaction is expediently performed in the presence of a base. Suitable bases are those listed above in context with the Suzuki coupling.

If Y = OR ^A , the compounds Q ¹¹ , Q ²¹ or Q ³¹ are esters. Suitable esters derive preferably from Ci-C ₄ -alkanols R ^A OH in which R ^A is Ci-C ₄ -alkyl, or from C2-C6-polyols such as glycol, glycerol, trimethylolpropane, erythritol, pentaerythritol and sorbitol. Alternatively, the ester is a so-called active ester, which is obtained in a formal sense by the reaction of the acid Q ¹¹ , Q ²¹ or Q ³¹ (Y = OH) with an active ester-forming alcohol, such as p-nitrophenol, N-hydroxybenzotriazole (HOBt), N-hydroxysuccinimide or OPfp (pentafluorophenol).

If compounds Q ¹¹ , Q ²¹ or Q ³¹ are anhydrides, i.e. Y = 0-C(0)-R ^B , these are either a symmetric anhydride or an asymmetric anhydride in which -0-OC-R ⁶ is a group which can be displaced easily by the 2-aminobiphenyl (VI) used in the reaction.

Suitable acid derivatives with which the carboxylic acid Q ¹¹ , Q ²¹ or Q ³¹ with Y = OH can form suitable mixed anhydrides are, for example, the esters of chloroformic acid, for example isopropyl chloroformate and isobutyl chloroformate, or of chloroacetic acid.

The acylation can be carried out under known conditions.

The method of the invention yields compounds I in high yields, although an aromatic chloride is used instead of the generally more reactive aromatic bromides or iodides, as used for example in WO 2015/01 1032. Moreover, the method requires distinctly lower amounts of Pd than most prior art processes. The Suzuki reaction proceeds very selectively, effectively suppressing homocoupling reactions. The process is very well suited for large scale production, and the workup is very simple. Moreover, as the required amounts of Pd are so low, the catalyst does not need to be recycled, which is a very time-consuming and costly procedure, but can be disposed of after the reaction.

The invention is further illustrated by the following examples. Examples Example 1 : Synthesis of 3,4,5-trifluoro-2'-nitrobiphenyl

3.9 mg of palladium acetate (0.017 mmol, 0.0024 mol%) and 5.4 mg of di-tert- butyl(phenyl)phosphonium tetrafluoroborate (0.017 mmol) were dissolved in 2 ml. of THF at 25°C to form a catalyst solution.

387 g of a potassium carbonate solution (50% in water, 194 g = 1 .40 mol of potassium carbonate) were placed in an autoclave. The pressure was reduced to 200 mbar two times and the autoclave filled with nitrogen. 784 g of a (3,4,5-trifluorophenyl)boronic acid solution (0.70 mol of the boronic acid, 15.7% in THF:water / 3:8; 0.70 mol of the boronic acid) and 212 g of a 1 -chloro-2-nitrobenzene solution (50% in THF, 106 g = 0.67 mol of 1 -chloro-2-nitrobenzene) were added together with the catalyst solution. 262 g of additional THF were used to transfer the starting materials completely. The reactor was evacuated to 200 mbar twice and filled with nitrogen. The pressure was reduced a third time to 200 mbar, the autoclave was closed and heated to 1 10°C outer temperature. Post-stirring was continued for 5 h. The autoclave was cooled to 25°C, the pressure was released and 350 g water were added.

THF was removed by distillation, isobutanol was added and the aqueous phase was removed at 70 °C. The product was crystallized by cooling to -5°C. The product was filtered and washed with water. 174 g of 1 ,2,3-trifluoro-5-(2-nitrophenyl)benzene (= 3,4,5-trifluoro-2'-nitrobiphenyl) containing 6.8 wt% of water and 1.1 wt% of isobutanol were obtained (calculated yield: 0.63 mol, 94%).

H-NMR: (400 MHz, CDCI ₃ ): 7.94 (d, 1 H), 7.65 (t, 1 H), 7.56 (t, 1 H), 7.41 (d, 1 H), 6.96 (t,2H) ppm.

Example 2: Synthesis of 4-chloro-2'-nitrobiphenyl

4.5 mg of palladium acetate (0.020 mmol) and 12.4 mg of di-tert-butyl(phenyl)- phosphonium tetrafluoroborate (0.040 mmol) were dissolved in 2.0 g of THF at 25°C to form a catalyst solution.

6.92 g of a potassium carbonate solution (50% in water, 3.46 g = 25 mmol of potassium carbonate), 2.05 g of (4-chlorophenyl)boronic acid (95% purity, 12.5 mmol of the boronic acid) and 2.31 g of a 1 -chloro-2-nitrobenzene solution (85% in THF, 1 .96 g = 12.5 mmol of 1 -chloro-2-nitrobenzene) were placed in an autoclave. 69 mg of the catalyst solution prepared above were added (0.68 μηηοΙ Pd, 0.0054 mol%) together with 4.7 g of THF. The pressure was reduced to 200 mbar twice and the autoclave filled with nitrogen. After reducing the pressure to 200 mbar the mixture was heated to 100°C. Post-stirring was continued for 5 h, after which the mixture was cooled to 25°C, 6.25 g of water was added and the phases were separated at 50 C. The organic phase was analyzed by HPLC: 86 area-% of the desired product 1 -(4-chlorophenyl)-2-nitro- benzene (4 area% remaining boronic acid, 4 area% 1 -chloro-2-nitrobenzene).

HPLC-method: Agilent 1050; column: Chromolith RP-18e 100x3 mm; mobile phase: acetonitrile/H ₂ 0 1 :1 + 0.5% 0.5 mol/L H ₂ S0 ₄ ; flow 1.0 mL/min; temperature 30°C.

1 -(4-chlorophenyl)-2-nitro-benzene (= 4-chloro-2'-nitrobiphenyl): retention time:

3.58 min

Example 3: Synthesis of 4-chloro-2'-nitrobiphenyl

1 .37 mg of palladium chloride (0.010 mmol) and 5.27 mg of di-tert-butyl(phenyl)- phosphonium tetrafluoroborate (0.020 mmol) were dissolved in 0.5 g of water and 0.4 g of THF at 25°C to form a catalyst solution.

99.8 g of a potassium carbonate solution (50% in water, 49.9 g = 0.362 mol of potassium carbonate), 189.2 g of a bis(4-chlorophenyl)borinic acid solution (12% in THF:water 95:5, 22.7 g = 0.091 mol of the borinic acid) and 35.6 g of 1 -chloro-2- nitrobenzene (used as an 80% solution in THF, 28.5 g = 0.181 mol of 1 -chloro-2- nitrobenzene) were placed in an autoclave. 0.885 g of the catalyst solution prepared above were added (0.010 mmol Pd, 0.0055 mol% based on transferred Cl-phenyl; i.e. relative to 0.5 mol of the borinic acid) together with 1.0 g of THF. After three times flushing the autoclave using 3.5 bar of nitrogen and releasing to 0.5 bar the mixture was heated to 105°C. Post-stirring was continued for 4 h after which the mixture was cooled to 30°C, 142 g of HCI 10% solution (0.394 mol) were added and the phases were separated at 30 °C. The organic phase was analyzed by HPLC showing complete conversion to the desired product 1 -(4-chlorophenyl)-2-nitro-benzene (= 4-chloro-2'- nitrobiphenyl) with no remaining borinic acid.

Example 4: Synthesis of 3,4,5-trifluoro-2'-nitrobiphenyl using sodium phosphate as a base

6.2 mg (0.010 mmol, 0.005 mol% relative to 1 mol of the boronic acid) of preformed dichlorobis(di-tert-butylphenylphosphine) palladium(ll) was dissolved in 2 ml. of THF at 25°C to form a catalyst solution. 34.6 g of phosphoric acid (85%, 300 mmol, 1 .5 equivalents relative to the boronic acid) was neutralised with 144.0 g of NaOH (25% in water, 900 mmol) to form a solution of sodium phosphate in an autoclave. The pressure was reduced to 200 mbar and the autoclave filled with nitrogen. 223.0 g of a (3,4,5-trifluorophenyl)boronic acid solution (200 mmol, 15.8% in THF:water / 3:8) and 64.5 g of a 1 -chloro-2-nitrobenzene solution (50% in THF, 32.3 g = 205 mmol of 1 - chloro-2-nitrobenzene) were added together with the catalyst solution. 45 g of additional THF were used to transfer the starting materials completely. The reactor was evacuated to 200 mbar and filled with nitrogen. The pressure was reduced again to 200 mbar, the autoclave was closed and heated to 1 10°C outer temperature. Post- stirring was continued for 5 h. The autoclave was cooled to 25°C, the pressure was released and the organic phase analysed by quantitative HPLC showing complete conversion to the desired product 3,4,5-trifluoro-2'-nitrobiphenyl with no remaining boronic acid. Example 5: Synthesis of 3,4,5-trifluoro-2'-nitrobiphenyl using potassium phosphate as base

12.4 mg (0.020 mmol, 0.005 mol% relative to 1 mol of the boronic acid) preformed dichlorobis(di-tert-butylphenylphosphine) palladium(ll) was dissolved in 2 mL of THF at 25°C to form a catalyst solution. 97.0 g of potassium phosphate monohydrate (95%, 400 mmol, 1 .0 equivalents relative to the boronic acid) was dissolved in 215 g of water and placed in an autoclave. The pressure was reduced to 200 mbar and the autoclave filled with nitrogen. 446.0 g of a (3,4,5-trifluorophenyl)boronic acid solution (400 mmol, 15.8% in THF:water / 3:8) and 128.6 g of a 1 -chloro-2-nitrobenzene solution (50% in THF, 64.3 g = 407 mmol of 1 -chloro-2-nitrobenzene) were added together with the catalyst solution. 90 g of additional THF were used to transfer the starting materials completely. The reactor was evacuated to 200 mbar and filled with nitrogen. The pressure was reduced again to 200 mbar, the autoclave was closed and heated to 1 10°C outer temperature. Post-stirring was continued for 5 h. The autoclave was cooled to 25°C, the pressure was released and the organic phase analysed by quantitative HPLC showing complete conversion to the desired product 3,4,5-trifluoro- 2'-nitrobiphenyl with no remaining boronic acid.