CN101374799B - Process for preparing substituted biphenyls - Google Patents

Process for preparing substituted biphenyls Download PDF

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CN101374799B
CN101374799B CN2007800034097A CN200780003409A CN101374799B CN 101374799 B CN101374799 B CN 101374799B CN 2007800034097 A CN2007800034097 A CN 2007800034097A CN 200780003409 A CN200780003409 A CN 200780003409A CN 101374799 B CN101374799 B CN 101374799B
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palladium
boric acid
fluoro
chloro
iii
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CN101374799A (en
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S·P·斯密特
J·迪茨
M·凯尔
T·格尔特
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BASF SE
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups

Abstract

The invention relates to a process for preparing substituted biphenyls of the formula (I) in which the substituents are defined as follows: X is fluorine or chlorine; R<1> is nitro, amino or NHR<3>; R<2> is cyano, nitro, halogen, C1-C6-alkyl, C1-C6-alkenyl, C1-C6-alkynyl, C1-C6-alkoxy, C1-C6-haloalkyl, C1-C6-alkylcarbonyl or phenyl; R<3> is C1-C4-alkyl, C1-C4-alkenyl or C1-C4-alkynyl; n is 1, 2 or 3, where in case that n is 2 or 3, the R<2> radicals may also be different, which comprises reacting the compound of the formula (II) in which Hal is halogen and X and R<1> are as defined above, in the presence of a base and of a palladium catalyst selected from the group of: a) palladium-triarylphosphine or -trialkylphosphine complex with palladium in the zero oxidation state, b) salt of palladium in the presence of triarylphospine or trialkylphosphine as a complex ligand or c) metallic palladium, optionally applied to support, in the presence of triarylphosphine or trialkylphosphine, in a solvent, with a diphenylborinic acid (III) in which R<2> and n are as defined above, where the triarylphosphines or trialkylphosphines used may be substituted.

Description

The method for preparing substituted biphenyl
The present invention relates to a kind of method for preparing the substituted biphenyl of formula I:
Figure S2007800034097D00011
Wherein the substituting group definition is as follows:
X is a fluorine or chlorine;
R 1Be nitro, amino or NHR 3
R 2Be cyanic acid, nitro, halogen, C 1-C 6Alkyl, C 1-C 6Alkenyl, C 1-C 6Alkynyl, C 1-C 6Alkoxyl group, C 1-C 6Haloalkyl, C 1-C 6-alkyl-carbonyl or phenyl;
R 3Be C 1-C 4Alkyl, C 1-C 4Alkenyl or C 1-C 4Alkynyl;
N is 1,2 or 3, wherein when n is 2 or 3, and radicals R 2Also can be different,
Said method is included under the existence of alkali and palladium catalyst, and the compound that makes formula II (III) reacts with phenylbenzene boric acid (diphenylborinic acid) in solvent in the presence of triaryl phosphine or trialkyl phosphine:
Figure S2007800034097D00012
Hal is a halogen in the compound of its Chinese style II, X and R 1Like above definition; Palladium catalyst is selected from
A) palladium be zero oxidation state palladium-triaryl phosphine or-the trialkyl phosphine title complex,
B) at triaryl phosphine or trialkyl phosphine as the palladium salt in the presence of the complex ligand, or
C) palladium metal of optional use on carrier;
R in the phenylbenzene boric acid (III) 2With n like above definition, wherein used triaryl phosphine or trialkyl phosphine can be substituted.
Tetrahedron Lett.32 is described in the yield that obtains through the linked reaction of using [1, two (the diphenylphosphine)-butane of 4-] palladium (II) dichloride catalyzer to carry out between phenyl-boron dihydroxide and the chlorobenzene and is merely 28% in the 2277th page (1991).
EP-A 0 888 261 discloses the method for preparing nitrobiphenyl, and it is through making the reaction of chloronitrobenzene and phenyl-boron dihydroxide in the presence of palladium catalyst and alkali.Need very high catalyst concn in the method.
Therefore, the purpose of this invention is to provide a kind of cost-effective method, this method can be implemented on technical scale, regioselectivity ground preparation substituted biphenyl, and under the palladium catalyst concentration that reduces, operate.
Thereby found at this specification sheets and started defined method.
Through optional substituted phenyl-magnesium-chloride V and trialkyl borate, the preferred boric acid trimethyl in the THF as solvent, reacts acquisition phenylbenzene boric acid (III) according to following scheme 1.
Scheme 1
Figure S2007800034097D00021
R 4Be C 1-C 4Alkyl, preferable methyl.
For the high yield of phenylbenzene boric acid (III), necessary is to use only 0.7 normal trialkyl borate in used replacement chlorobenzene (IV).Of EP-A 0 888 261, use 1.1 normal trialkyl borates can produce phenyl-boron dihydroxide.
Reduce and use trialkyl borate on preparation nitrobiphenyl (I), to have a lot of surprising advantages.Space-time yield increases.Owing to reduced the amount of expensive trimethyl borate, raw materials cost descends.Different with the phenyl-boron dihydroxide that uses among the EP-A0 888 261; Phenylbenzene boric acid (III) dissolves in THF; The improvement that this causes in the reaction process heat to remove, such improvement be accompanied by cooling power than low-loss, this so bring higher process safety.
Temperature of reaction at this operation stage is 10 to 30 ℃, preferred 15 to 25 ℃.
Can have separately in each case or combine to have following preferred substituted by the substituted biphenyl of the inventive method preparation:
R 1For nitro, amino, methylamino-, propyl group are amino, butyl is amino, allyl amino or propargyl are amino, more preferably nitro, amino or methylamino-, most preferably nitro or amino;
R 2Be cyanic acid, nitro, fluorine, chlorine, bromine, methyl, ethyl, propyl group, butyl, allyl group, propargyl, methoxyl group, oxyethyl group, trifluoromethyl or phenyl, more preferably fluorine, chlorine, methyl or methoxy, most preferably fluorine or chlorine;
R 3Be methyl, ethyl, propyl group, butyl, allyl group or propargyl, more preferably methyl, ethyl or allyl group, most preferable;
N is 1 or 2, preferred 2.
Carry out the Suzuki diaryl cross-coupling of follow-up homogeneous catalysis according to scheme 2.
Scheme 2:
Preferably the phenylbenzene boric acid from formula (III) begins, wherein R 2With n like above definition.
Further preferred feedstock is phenylbenzene boric acid (III), and wherein n is 1 or 2, particularly 2.Particularly preferably in 3-and the substituted phenylbenzene boric acid in 4-position (III).
More preferably with two (2, the 3-difluorophenyl) boric acid, two (3, the 4-difluorophenyl) boric acid, two (2, the 3-dichlorophenyl) boric acid, particularly two (3, the 4-dichlorophenyl) boric acid is as initial compounds (III).
Preferably start from following compound (II): 2-bromo-4-fluoroaniline, 2-chloro-4-fluoroaniline, particularly 2-chloro-4-fluoro-1-oil of mirbane or 2-bromo-4-fluoro-1-oil of mirbane.
In phenylbenzene boric acid (III) (phenylbenzene boric acid equivalent), compound (II) uses with equimolar amount usually, and preferably 20% excessive at the most, 50% is excessive especially at the most.
Used alkali can be organic bases, for example tertiary amine.Preferably use for example triethylamine or dimethylcyclohexylamine.
Used alkali is preferably alkali metal hydroxide, alkaline earth metal hydroxides, alkaline carbonate, alkaline earth metal carbonate, alkali metal hydrocarbonate, alkali metal acetate, earth alkali metal acetate, alkali metal alcoholates and alkaline-earth alkoxides, mixes or use especially separately.
Preferred especially alkali is alkali metal hydroxide, alkaline earth metal hydroxides, alkaline carbonate, alkaline earth metal carbonate and alkali metal hydrocarbonate.
Especially preferred alkali is alkali metal hydroxide, for example sodium hydroxide and Pottasium Hydroxide; And alkaline carbonate and alkali metal hydrocarbonate such as Quilonum Retard, yellow soda ash and salt of wormwood.
In the amount of phenylbenzene boric acid (III), the mark of the alkali that uses in the methods of the invention is preferably 100 to 500 moles of %, more preferably 150 to 400 moles of %.
Suitable palladium catalyst is that palladium is palladium salt or the optional use palladium metal to the carrier under the palladium-ligand-complexes, complex ligand of zero oxidation state exists, preferably in the presence of complex ligand.
Suitable complex ligand is uncharged part, and like triaryl phosphine and trialkyl phosphine, it can be chosen wantonly on aromatic ring and replace, for example triphenylphosphine (TPP), two-1-adamantyl-normal-butyl phosphine, three-tertiary butyl phosphine (TtBP) or 2-(dicyclohexyl phosphino-) biphenyl.
In addition, document has also been described the reactive complex ligand of having more of other structured sort, comprises chlorination 1, and 3-two (2; The 6-diisopropyl phenyl)-4, (for example referring to G.A.Grasa etc., Organometallics 2002 for the 5-H2-imidazoles; 21,2866) and tricresyl phosphite (2, the 4-di-tert-butyl-phenyl) ester (referring to A.Zapf etc.; Chem.Eur.J.2000,6,1830).
The reactivity of complex ligand can improve (for example referring to D.Zim etc., Tetrahedron Lett.2000,41,8199) through adding quaternary ammonium salt such as bromination four-normal-butyl ammonium (TBAB).
If desired, the water-soluble of palladium complex can be improved through various substituting groups such as sulfonic acid or sulfonate groups, carboxylic acid or carboxylate groups, phosphonic acids 、 Phosphonium or phosphonate groups, all alkyl ammonium, hydroxyl and polyether group.
Palladium is in the palladium-ligand-complexes of zero oxidation state, preferably uses tetrakis triphenylphosphine palladium and also has four [three (neighbour-tolyl) phosphine] palladium.
In the palladium salt that in the presence of complex ligand, uses, palladium exists with the positive oxidation state of divalence usually.Preferred Palladous chloride, acid chloride or the chlorination diacetonitrile palladium of using.Particularly preferably be the use Palladous chloride.
Usually with 6 to 60 equivalents, preferred 15 to 25 normal aforementioned complex ligands, particularly triphenylphosphine and tri-butyl phosphine and 1 normal palladium salt binding.
EP-A 0 888 261 has described whenever the amount palladium catalyst uses 2 to 6 normal triphenylphosphines.Highly excessive part is disadvantageous in document, to generally believe use, because expection can cause catalytic activity title complex inactivation (for example referring to J.Hassan etc., Chem.Rev.2002,102,1359) like this.
Therefore, surprisingly this high triphenylphosphine consumption combines the low catalyst consumption to cause the overall productivity of the inventive method to increase, and therefore causes the improvement of economic validity.
Palladium metal is preferably used or is loaded on the solid support material with powder-form and uses, for example with in the form of the palladium on the gac, the form, the form, the form, the form, form, the SiO that the silicoaluminate palladium if you would take off stone of palladium on the lime carbonate of palladium on the permanent white of palladium on the barium carbonate of palladium on the aluminum oxide 2On the form of form and the palladium on the lime carbonate of palladium use, palladium content is 0.5 to 12 weight % under every kind of situation.Except palladium and solid support material, these catalyzer may further include doping agent, and are for example plumbous.
When the palladium metal of using optional use on carrier; Especially preferably also use aforesaid complex ligand; Particularly at triphenylphosphine as the palladium that uses in the presence of the complex ligand on the gac, wherein the phenyl in triphenylphosphine is preferably replaced by one to three sulfonate groups altogether.
In the methods of the invention, in the amount of compound (II), palladium catalyst is with 0.001 to 1.0 mole of %, and the low mark of preferred 0.005 to 0.5 mole of % or 0.01 to 0.5 mole of %, particularly 0.005 to 0.05 mole of % uses.
The combination of the low usage quantity of palladium salt and the high usage quantity of complex ligand makes the inventive method have significant cost advantage with respect to the method for prior art.
The inventive method can be to carry out in the diphasic system that constitutes of catalyzer by water and solid phase.In this case, water can also comprise water-miscible organic solvent outside dewatering.
The organic solvent that is applicable to the inventive method is an ether; Like glycol dimethyl ether, diethylene glycol dimethyl ether, THF 、 diox and t-butyl methyl ether; Hydrocarbon such as normal hexane, normal heptane, hexanaphthene, benzene, toluene and YLENE; Alcohol is like methyl alcohol, ethanol, 1-propyl alcohol, 2-propyl alcohol, terepthaloyl moietie, 1-butanols, 2-butanols and the trimethyl carbinol; Ketone such as acetone, ethyl methyl ketone and isobutyl methyl ketone, acid amides such as N, N,N-DIMETHYLACETAMIDE and N-Methyl pyrrolidone use separately under every kind of situation or use with mixture.
Preferred solvent is ether such as glycol dimethyl ether, THF and diox, and hydrocarbon such as hexanaphthene, toluene and YLENE, alcohol use separately under every kind of situation or use with mixture like ethanol, 1-propyl alcohol, 2-propyl alcohol, 1-butanols and the trimethyl carbinol.
In the preferred especially variant of the inventive method, make water, one or more water-insoluble solvents and one or more water-soluble solvents, for example the mixture of water and diox; Or the mixture of water and THF; Or water 、 diox and alcoholic acid mixture, or water, THF and methanol mixture, or the mixture of water, toluene and THF; The mixture of preferably water and THF, or water, THF and methanol mixture.
The total amount of solvent is generally every mole compound (II) 3000 to 500 grams, preferred 2000 to 700 grams.
Suitably; Palladium catalyst through with compound (II), phenylbenzene boric acid (III), alkali and catalytic amount joins in the mixture of water and one or more inert organic solvents; Then at 50 ℃ to 120 ℃; Preferred 70 ℃ to 110 ℃, more preferably stirred under 90 ℃ to 100 ℃ the temperature 1 to 50 hour, preferably stirred 2 to 24 hours and carry out this method.
Depend on used solvent and temperature, set up 1 crust, the pressure of preferred 1 crust to 4 crust to 6 crust.
Preferably in water and THF, carry out this reaction.
This reaction can be carried out in being applicable to the conventional equipment of this method.
When accomplishing reaction, remove the palladium catalyst that obtains as solid, for example through removing by filter, and from crude product, remove and desolvate.
Under the not exclusively water-soluble situation of product, water-soluble palladium catalyzer or complex ligand are removed from crude product in aqueous phase separation fully.
Then, can be with those skilled in the art known and be applicable to that the method for concrete product is further purified, for example through recrystallize, distillation, distillation, zone melting, melt crystallization or chromatography.
Through the inventive method, can prepare for example following compounds: 3 ', 4 '-two chloro-5-fluorine biphenyl-2-base amine, 2 ', 3 '-two chloro-5-fluorine biphenyl-2-base amine, 3 '; 4 '-two chloro-3-fluorine biphenyl-2-base amine, 2 ', 3 '-two chloro-3-fluorine biphenyl-2-base amine, 3 ', 4 '-two chloro-4-fluorine biphenyl-2-base amine, 2 ', 3 '-two chloro-4-fluorine biphenyl-2-base amine, 3 '; 4 '-two chloro-6-fluorine biphenyl-2-base amine, 2 ', 3 '-two chloro-6-fluorine biphenyl-2-base amine, 3 ', 4 '-two fluoro-5-fluorine biphenyl-2-base amine, 2 ', 3 '-two fluoro-5-fluorine biphenyl-2-base amine, 3 '; 4 '-two fluoro-3-fluorine biphenyl-2-base amine, 2 ', 3 '-two fluoro-3-fluorine biphenyl-2-base amine, 3 ', 4 '-two fluoro-4-fluorine biphenyl-2-base amine, 2 ', 3 '-two fluoro-4-fluorine biphenyl-2-base amine, 3 '; 4 '-two fluoro-6-fluorine biphenyl-2-base amine, 2 ', 3 '-two chloro-6-fluorine biphenyl-2-base amine, 3 ', 4 '-two chloro-5-chlordiphenyls-2-base amine, 2 ', 3 '-two chloro-5-chlordiphenyls-2-base amine, 3 '; 4 '-two chloro-3-chlordiphenyls-2-base amine, 2 ', 3 '-two chloro-3-chlordiphenyls-2-base amine, 3 ', 4 '-two chloro-4-chlordiphenyls-2-base amine, 2 ', 3 '-two chloro-4-chlordiphenyls-2-base amine, 3 '; 4 '-two chloro-6-chlordiphenyls-2-base amine, 2 ', 3 '-two chloro-6-chlordiphenyls-2-base amine, 3 ', 4 '-two fluoro-5-chlordiphenyls-2-base amine, 2 ', 3 '-two fluoro-5-chlordiphenyls-2-base amine, 3 '; 4 '-two fluoro-3-chlordiphenyls-2-base amine, 2 ', 3 '-two fluoro-3-chlordiphenyls-2-base amine, 3 ', 4 '-two fluoro-4-chlordiphenyls-2-base amine, 2 ', 3 '-two fluoro-4-chlordiphenyls-2-base amine, 3 '; 4 '-two fluoro-6-chlordiphenyls-2-base amine, 2 ', 3 '-two chloro-6-chlordiphenyls-2-base amine, 3 ', 4 '-two chloro-5-fluoro-2 nitro biphenyls, 2 ', 3 '-two chloro-5-fluoro-2 nitro biphenyls, 3 '; 4 '-two chloro-3-fluoro-2 nitro biphenyls, 2 ', 3 '-two chloro-3-fluoro-2 nitro biphenyls, 3 ', 4 '-two chloro-4-fluoro-2 nitro biphenyls, 2 ', 3 '-two chloro-4-fluoro-2 nitro biphenyls, 3 '; 4 '-two chloro-6-fluoro-2 nitro biphenyls, 2 ', 3 '-two chloro-6-fluoro-2 nitro biphenyls, 3 ', 4 '-two fluoro-5-fluoro-2 nitro biphenyls, 2 ', 3 '-two fluoro-5-fluoro-2 nitro biphenyls, 3 '; 4 '-two fluoro-3-fluoro-2 nitro biphenyls, 2 ', 3 '-two fluoro-3-fluoro-2 nitro biphenyls, 3 ', 4 '-two fluoro-4-fluoro-2 nitro biphenyls, 2 ', 3 '-two fluoro-4-fluoro-2 nitro biphenyls, 3 '; 4 '-two fluoro-6-fluoro-2 nitro biphenyls, 2 ', 3 '-two chloro-6-fluoro-2 nitro biphenyls, 3 ', 4 '-two chloro-5-chloro-2 nitro biphenyls, 2 '; 3 '-two chloro-5-chloro-2 nitro biphenyls, 3 ', 4 '-two chloro-3-chloro-2 nitro biphenyls, 2 ', 3 '-two chloro-3-chloro-2 nitro biphenyls, 3 '; 4 '-two chloro-4-chloro-2 nitro biphenyls, 2 ', 3 '-two chloro-4-chloro-2 nitro biphenyls, 3 ', 4 '-two chloro-6-chloro-2 nitro biphenyls, 2 '; 3 '-two chloro-6-chloro-2 nitro biphenyls, 3 ', 4 '-two fluoro-5-chloro-2 nitro biphenyls, 2 ', 3 '-two fluoro-5-chloro-2 nitro biphenyls, 3 '; 4 '-two fluoro-3-chloro-2 nitro biphenyls, 2 ', 3 '-two fluoro-3-chloro-2 nitro biphenyls, 3 ', 4 '-two fluoro-4-chloro-2 nitro biphenyls, 2 '; 3 '-two fluoro-4-chloro-2 nitro biphenyls, 3 ', 4 '-two fluoro-6-chloro-2 nitro biphenyls, 2 ', 3 '-two chloro-6-chloro-2 nitro biphenyls.
The inventive method provides compound I with extraordinary purity and very high extremely quantitative yield.
Can be applicable to precursor (referring to WO03/070705) through the substituted biphenyl that the inventive method obtains as fungicidal Crop protection activeconstituents.
3 ', 4 '-two chloro-5-fluoro-2 nitro biphenyls synthetic
1: two-(3, the 4-dichlorophenyl) boric acid of embodiment
The solution (123mM) of 12.81 gram trimethyl borates and 30 milliliters of THF formation is heated to backflow.Introversive 3 of 245 grams, 18 weight %, the solution (177mM) of 4-dichlorophenyl magnesium bromide in THF of wherein being metered at one hour.After adding fully, reaction soln is refluxing and stirring 1 hour again.
Then reaction soln is handled with 110 milliliter of 10% aqueous hydrochloric acid, and stirred 30 minutes down at 40 ℃.After being separated, obtain two-(3, the 4-dichlorophenyl) solution of boric acid in THF.Through 32.1 grams of Crystallization Separation from 200 milliliters of hexanes, two-(4-chloro-phenyl-) boric acid (yield 57%).MS：m/z＝320[m+H] +，1H-NMR(DMSO，500MHz)：δ[ppm]＝7.51(s，1H)，7.38(d，1H，7Hz)，7.27(d，1H，7Hz)
The reaction of 2: two-(3, the 4-dichlorophenyl) boric acid of embodiment and 2-bromo-4-fluoroaniline
0.55 gram sodium hydroxide (13.7mM) and 50 ml waters of at first under 15 to 20 ℃, in reaction flask, packing into.
2.5 gram two-(3, the 4-dichlorophenyl) boric acid (7.8mM) in wherein being metered into 50 milliliters of dioxs and 0.199 gram triphenylphosphine (0.76mM).After adding fully, reaction soln was stirred 40 minutes down at 18-22 ℃.After the deoxidation, in reaction soln, add 27 milligrams of Palladous chlorides (II) and (0.15mM) restrain 2-bromo-4-fluoroanilines (7.4mM) with 1.4.Reaction soln is heated to 85 ℃ to be kept 6 hours.With the reaction mixture cooling, use the 2M hcl acidifying, and the evaporation diox.Resistates is used dichloromethane extraction, behind the evaporating solvent through column chromatography with 3 ', 4 '-two chloro-5-fluorine biphenyl-2-base amine separates (0.63 gram, yield is 33%).HPLC-MS：m/z＝256.0[m+H] +
The reaction of 3: two-(3, the 4-dichlorophenyl) boric acid of embodiment and 2-chloro-4-fluoro-1-oil of mirbane
0.55 gram sodium hydroxide (13.7mM) and 50 ml waters of at first under 15-20 ℃, in reaction flask, packing into.
2.5 gram two-(3, the 4-dichlorophenyl) boric acid (7.8mM) in wherein being metered into 50 milliliters of dioxs and 0.199 gram triphenylphosphine (0.76mM).After adding fully, reaction soln was stirred 40 minutes down at 18-22 ℃.After the deoxidation, in reaction soln, add 27 milligrams of Palladous chlorides (II) and (0.15mM) restrain 2-chloro-4-fluoro-1-oil of mirbane (7.4mM) with 1.3.Reaction soln is heated to 85 ℃ to be kept 6 hours.With reaction mixture cooling, with the 2M hcl acidifying and evaporate diox.Resistates is used dichloromethane extraction, behind the evaporating solvent with column chromatography separate 3 ', 4 '-two chloro-5-fluoro-2 nitro biphenyls (0.76 gram, yield 36%).GC-MS：m/z＝285.9[m-H]。 -

Claims (18)

1. method for preparing the substituted biphenyl of formula I:
Figure FSB00000706270000011
Wherein the substituting group definition is as follows:
X is a fluorine or chlorine;
R 1Be nitro, amino or NHR 3
R 2Be halogen;
R 3Be C 1-C 4Alkyl, C 1-C 4Alkenyl or C 1-C 4Alkynyl, wherein R 3Be not C 1Alkenyl or C 1Alkynyl;
N is 1,2 or 3, wherein when n is 2 or 3, and radicals R 2Also can be different,
Said method is included under the existence of alkali and palladium catalyst, and the compound that makes formula II reacts with phenylbenzene boric acid III in solvent in the presence of triaryl phosphine or trialkyl phosphine:
Figure FSB00000706270000012
Hal is a halogen in the compound of its Chinese style II, X and R 1Like above definition; Palladium catalyst is selected from
A) palladium be zero oxidation state palladium-triaryl phosphine or-the trialkyl phosphine title complex,
B) at triaryl phosphine or trialkyl phosphine as the palladium salt in the presence of the complex ligand, or
C) palladium metal of optional use on carrier;
R among the phenylbenzene boric acid III 2With n like above definition, wherein used triaryl phosphine or trialkyl phosphine can be substituted.
2. method according to claim 1, wherein used compound I I is 2-nitro-3-fluoro-chlorobenzene or 2-amino-3-fluoro-bromobenzene.
3. method according to claim 1, wherein initial compounds III is at the substituted phenylbenzene boric acid of 3-and 4-position.
4. method according to claim 2, wherein initial compounds III is at the substituted phenylbenzene boric acid of 3-and 4-position.
5. method according to claim 1, wherein used phenylbenzene boric acid III has fluorine or chlorine at 3-and 4-position.
6. method according to claim 2, wherein used phenylbenzene boric acid III has fluorine or chlorine at 3-and 4-position.
7. method according to claim 1, wherein initial compounds III is two (3, the 4-dichlorophenyl) boric acid.
8. method according to claim 2, wherein initial compounds III is two (3, the 4-dichlorophenyl) boric acid.
9. according to each described method among the claim 1-8, wherein used palladium catalyst according to claim 1 is tetrakis triphenylphosphine palladium or four (tri-butyl phosphine) palladium a).
10. according to each described method among the claim 1-8, wherein use palladium catalyst b according to claim 1).
11. according to each described method among the claim 1-8, wherein used palladium catalyst c according to claim 1) be the palladium metal on gac in the presence of triphenylphosphine, wherein phenyl is by 1 to 3 sulfonate groups replacement altogether.
12. method according to claim 10, wherein used palladium catalyst b) be Palladous chloride, acid chloride or chlorination diacetonitrile palladium.
13. method according to claim 10, wherein palladium catalyst b) to use whenever amount palladium salt uses the amount of 6 to 60 equivalent triphenylphosphines.
14. method according to claim 1 wherein in the amount of compound I I, is used the palladium catalyst of 0.001 to 1.0 mole of %.
15. method according to claim 1 wherein is reflected under 50 to 120 ℃ the temperature and carries out.
16. method according to claim 1 wherein is reflected in the mixture of water and organic solvent and carries out.
17. method according to claim 16, wherein used organic solvent is an ether.
18. method according to claim 1, wherein be reflected at 1 to 6 the crust pressure under carry out.
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