WO2001042197A1

WO2001042197A1 - Method for preparing a polyaromatic compound

Info

Publication number: WO2001042197A1
Application number: PCT/FR2000/003406
Authority: WO
Inventors: Thierry Schlama; Françoise COLOBERT; Anne-Sophie Castanet
Original assignee: Rhodia Chimie
Priority date: 1999-12-06
Filing date: 2000-12-06
Publication date: 2001-06-14
Also published as: AU2184501A; FR2801884A1

Abstract

The invention concerns a method for preparing a polyaromatic compound comprising at least chain formation of two aromatic cycles. Said method consists in reacting an aromatic compound bearing a leaving group and an arylboronic acid and/or derivatives thereof, in the presence of a base and an efficient amount of a palladium-based catalyst, said element capable of forming a complex with at least a co-ordinating agent or ligand. The invention is characterised in that the reaction is performed in an organic or hydro-organic medium and in the presence of an efficient amount of a phase-transfer catalyst.

Description

PROCESS FOR THE PREPARATION OF A POLYAROMATIC COMPOUND.

The present invention relates to a process for the preparation of a polyaromatic compound.

The invention relates in particular to a biphenyl type compound.

In the following description of the present invention, the term "polyclic aromatic compound" means a compound comprising at least one chain of two aromatic rings, carbocyclic and / or heterocyclic.

By "aromatic compound" is meant the classic notion of aromaticity as defined in the literature, in particular by Jerry MARCH, Advanced Organic Chemistry, 4 ^th edition, John Wiley and Sons, 1992, pp. 40 and following. In a simplified manner, the expression “aryl” will denote all the aromatic compounds whether they are carbocyclic aromatic compounds or heterocyclic aromatic compounds.

Biaryl-type structures are found in many molecules used in the agrochemical field, in particular in herbicides, pesticides or in the pharmaceutical field. In particular, a process for the preparation of compounds of the alkylbiphenyl or cyanobiphenyl type is sought.

It is described by Stanforth [Tetrahedron 54 (1998), 285 - 292], the preparation of biphenyl type compounds according to the Suzuki reaction which consists in reacting an arylboronic acid and a haloaromatic compound, in the presence of a palladium catalyst complexed with a triphenylphosphine, sodium carbonate, in the presence of an organic solvent. It was found that such a reaction, carried out under normal stirring conditions, did not allow high conversion and yield rates to be achieved. For example, during the reaction of 4-bromobenzonit and phenylboronic acid, the yield is limited to 60%.

It is possible to increase the latter by playing on the agitation of the reaction medium, but the use of very powerful agitation means is not compatible with industrial exploitation. It was therefore desirable to have an improved process allowing the coupling between a haloaromatic compound and an arylboronic acid.

It has now been found and this is what constitutes the object of the present invention a process for the preparation of a polycyclic aromatic compound comprising at least one chain of two aromatic rings which consists in reacting an aromatic compound carrying a leaving group and an arylboronic acid and / or its derivatives, in the presence of a base and an effective amount of a palladium catalyst, said element possibly being complexed with at least one coordinating agent or ligand characterized in that the reaction is carried out in an organic or hydro-organic medium and in the presence of an effective amount of a phase transfer catalyst.

In accordance with the process of the invention, it has been found that under the catalytic conditions defined according to the invention, the use of a phase transfer catalyst, in particular a tetraikylammonium halide, makes it possible to obtain an improvement in the rate conversion of the starting reagent and a better yield of the polyaromatic compound obtained.

An advantage of the process of the invention is that it is possible to carry out the reaction without it being necessary to have very strong stirring conditions.

More specifically, the aromatic compound carrying at least one leaving group, hereinafter designated "haloaromatic compound" corresponds to the general formula (I):

(D in which:

- A symbolizes the rest of a cycle forming all or part of a carbocyclic or heterocyclic, aromatic, monocyclic or polycyclic system,

- R, identical or different, represent substituents on the cycle,

- Y represents a leaving group, preferably, a halogen atom or a sulphonic ester group of formula - OSO ₂ - ^ in which ^ is a hydrocarbon group, - n represents the number of substituents on a cycle. In the formula of the sulfonic ester group, ^ is a hydrocarbon group of any kind, having from 1 to 20 carbon atoms. However, since Y is a leaving group, it is advantageous from an economic point of view for ^ to be of a simple nature, and more particularly represents a linear or branched alkyl group having from 1 to 4 carbon atoms, preferably a methyl or ethyl group, but it can also represent, for example, a phenyl or tolyl group or a trifluoromethyl group. Among the groups Y, the preferred group is a triflate group which corresponds to a group representing a trifluoromethyl group. As preferred leaving groups, a bromine or chlorine atom is preferably chosen.

The invention applies in particular to haloaromatic compounds corresponding to formula (I) in which A is the residue of a cyclic compound, preferably having at least 4 atoms in the ring, preferably 5 or 6, optionally substituted , and representing at least one of the following cycles:. an aromatic, monocyclic or polycyclic carbocycle,. an aromatic, monocyclic or polycyclic heterocycle comprising at least one of the heteroatoms O, N and S.

It will be specified, without however limiting the scope of the invention, that the optionally substituted residue A represents, the rest:

1 ° - of an aromatic, monocyclic or polycyclic carbocyclic compound. By "polycyclic carbocyclic compound" is meant:. a compound consisting of at least 2 aromatic carbocycles and forming between them ortho- or ortho- and pericondensed systems,. a compound consisting of at least 2 carbocycles of which only one of them is aromatic and forming between them ortho- or ortho- and pericondensed systems. 2 ° - of an aromatic, monocyclic or polycyclic heterocyclic compound. By "polycyclic heterocyclic compound", we define:. a compound consisting of at least 2 heterocycles containing at least one heteroatom in each cycle of which at least one of the two cycles is aromatic and forming between them ortho- or ortho- and pericondensed systems,. a compound consisting of at least one carbocycle and at least one heterocycle of which at least one of the rings is aromatic and forming between them ortho- or ortho- and pericondensed systems. More particularly, the optionally substituted residue A represents one of the following cycles: - an aromatic carbocycle

an aromatic bicycle comprising two aromatic carbocycles

- a partially aromatic bicycle comprising two carbocycles, one of which is aromatic:

an aromatic heterocycle:

- an aromatic bicycle comprising an aromatic carbocycle and an aromatic heterocycle:

- a partially aromatic bicycle comprising an aromatic carbocycle and a heterocycle:

an aromatic bicycle comprising two aromatic heterocycles:

- a partially aromatic bicycle comprising a carbocycle and an aromatic heterocycle:

- a tricycle comprising at least one carbocycle or an aromatic heterocycle

In ^'the method of the invention, there is preferably used a haloaromatic compound of formula (I) wherein A represents an aromatic nucleus, preferably a benzene or naphthalene nucleus. The aromatic compound of formula (I) can carry one or more substituents. The nature of the substituent can be arbitrary as long as it does not interfere with the reaction.

The number of substituents present on the cycle depends on the carbon condensation of the cycle and on the presence or not of unsaturations on the cycle.

The maximum number of substituents likely to be carried by a cycle, is easily determined by a person skilled in the art.

In the present text, the term "several" is generally understood to mean less than 4 substituents on an aromatic ring. Examples of substituents are given below, but this list is not limiting.

The group or groups R, which are identical or different, preferably represent one of the following groups:

. an alkyl group, linear or branched, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,

. a linear or branched alkenyl or alkynyl group having from 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms, such as vinyl, allyl, . a linear or branched alkoxy group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy groups, an alkenyloxy group, preferably an allyloxy group or a phenoxy group,. a cyclohexyl, phenyl or benzyl group,

. an acyl group having from 2 to 6 carbon atoms,. a group of formula:

-R-I-OH -R-I-SH -R-I-COOR2

-RI-CO-R2 -R ^ CHO -R- | -N = C = O .R ^ N≈C≈S ^' -R- | -NO ₂

-R- | -CN -R ₁ -N (R ₂ ) 2 -R ₁ -CO-N (R ₂ ) 2 -RI-SO3M -R ₁ -SO ₂ M

-RlX - _R1 -CF ₃ in said formulas, R- | represents a valential bond or a divalent, linear or branched, saturated or unsaturated hydrocarbon group having from 1 to 6 carbon atoms such as, for example, methylene, ethylene, propylene, isopropylene, isopropylidene; the identical or different R2 groups represent a hydrogen atom or a linear or branched alkyl group having from 1 to 6 carbon atoms or phenyl; M represents a hydrogen atom, an alkali metal preferably, sodium or a group R ₂ ; X symbolizes a halogen atom, preferably a chlorine, bromine or fluorine atom.

The present invention applies very particularly to halogenoaromatic compounds corresponding to formula (I) in which the group or groups

R represent:. an alkyl group, linear or branched, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, . a linear or branched alkenyl group having from 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms, such as vinyl, allyl,. a linear or branched alkoxy group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy groups, an alkenyloxy group, preferably an allyloxy group or a phenoxy group,. a group of formula:

-Ri -OH

-R -N (R ₂₎ 2 -R <|! -SO ₃ M in said formulas, R | represents a valential bond or a divalent, linear or branched, saturated or unsaturated hydrocarbon group, having from 1 to

6 carbon atoms such as, for example, methylene, ethylene, propylene, isopropylene, isopropylidene; the groups R, which are identical or different, represent a hydrogen atom or a linear or branched alkyl group having from 1 to 6 carbon atoms or phenyl; M represents a hydrogen atom or a sodium atom.

More preferably, R represents an alkyl group, linear or branched, having from 1 to 4 carbon atoms, and more particularly a methyl group or a cyano group.

In formula (I), n is a number less than or equal to 4, preferably equal to 1 or 2.

As examples of compounds corresponding to formula (I), mention may in particular be made of 4-bromoaniline, 4-bromo-3-methylaniline, 1-amino-3-bromonaphthalene, 2-chloro-3-aminopyridine, 4 -bromobenzonitrile.

According to the invention, the haloaromatic compound of formula (I) reacts with arylboronic acid which corresponds to the formula:

° - ^Q ₂ (II) in which:

- R3 represents a carbocyclic or heterocyclic, aromatic, monocyclic or polycyclic group,

- Q- | , Q, identical or different, represent a hydrogen atom, a saturated or unsaturated, linear or branched aliphatic group having from 1 to 20 carbon atoms or a group R3, - or Q- ₎ and Q can be linked together by an alkylene or alkylenedioxy group having from 1 to 4 carbon atoms,

- or Q- _| and Q can be linked together by -OBO- to form a boroxine group corresponding to formula (III) in which R3 has the meaning given above:

O - B / \

R, - B O

O— B \

^R3 (III)

More specifically, arylboronic acid corresponds to formula (II) or (III) in which the group R ₃ represents an aromatic carbocyclic or heterocyclic group. Thus, R ₃ can take the meanings given above for A. However, R3 more particularly represents a carbocyclic group such as a phenyl, naphthyl group or a heterocyclic group such as a pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl group, 1 , 3-thiazolyl, 1, 3,4-thiadiazolyl or thienyl.

The aromatic cycle can also be substituted. The number of substituents is generally at most 4 per cycle but most often equal to

1 or 2. We can refer to the definition of R for examples of substituents.

Preferred substituents are alkyl or alkoxy groups having 1 to 4 carbon atoms, an amino group, a nitro group, a cyano group, a halogen atom or a trifluoromethyl group.

As regards Q ^ Q, identical or different, they more particularly represent a hydrogen atom or an acyclic aliphatic group, linear or branched, having from 1 to 20 carbon atoms, saturated or comprising one or more unsaturations on the chain , preferably 1 to 3 unsaturations which are preferably single or conjugated double bonds.

Q-i, Q preferably represent an alkyl group having from 1 to 10 carbon atoms, preferably from 1 to 4 or an alkenyl group having from 2 to 10 carbon atoms, preferably a vinyie or 1-methylvinyl group,

Q1, Q ₂ can take the meanings given for R ₃ and in particular any cycle can also carry a substituent as described above.

R3 preferably represents a phenyl group.

It will not depart from the scope of the present invention to use derivatives of arylboronic acids such as anhydrides and esters and more particularly alkyl esters having from 1 to 4 carbon atoms. As examples of arylboronic acids, there may be mentioned in particular: benzenebororic acid, 2-thiopheneboronic acid, 3-thiopheneboronic acid, 4-methylbenzeneboronic acid, 3-methylthiophene-2-boronic acid, l 3-aminobenzeneboronic acid, 3-aminobenzeneboronic hemisulfate acid, 3-fluorobenzeneboronic acid, 4-fluorobenzeneboronic acid, 2-formylbenzeneboronic acid, 3-formylbenzeneboronic acid, 4-formylbenzeneboronic acid, l 2- methoxybenzeneboronic acid, 3-methoxybenzeneboronic acid, 4- methoxybenzeneboronic acid, 4-chlorobenzeneboronic acid, 5-chlorothiophene-2-boronic acid, benzo [b] furan-2-boronic acid , 4-carboxybenzeneboronic acid, 2,4,6-trimethylbenzeneboronic acid, 3-nitrobenzeneboronic acid, 4- (methylthio) benzeneboronic acid, 1-naphthaleneboronic acid, 2-naphthaleneboronic acid, 2-methoxy-1- naphthaleneboronic acid, 3-chloro-4 acid -fluorobenzeneboronic, 3- acetamidobenzeneboronic acid, 3-trifluoromethylbenzeneboronic acid, 4-trifluoromethylbenzeneboronic acid, 2,4-dichlorobenzeneboronic acid, 3,5-dichlorobenzeneboronic acid, 3,5-bis acid (trifluoromethyl) benzeneboronic, 4,4'-biphenyldiboronic acid, and the esters and anhydrides of such acids. The amount of reagents used is such that the molar ratio of arylboronic acid / haloaromatic compound is advantageously greater than or equal to 1 and preferably varies between 1 and 1, 2.

A palladium catalyst which may also be in the form of a complex is involved in the process of the invention. Palladium can be provided in the form of a finely divided metal or in the form of an inorganic derivative such as an oxide or a hydroxide. It is possible to use a mineral salt preferably, nitrate, sulfate, oxysulfate, halide, oxyhalide, silicate, carbonate, or an organic derivative preferably, cyanide, oxalate, acetylacetonate; alcoholate and even more preferably methylate or ethylate; carboxylate and even more preferably acetate. Can also be used complexes, in particular chlorinated or cyanated palladium and / or alkali metals, preferably sodium, potassium or ammonium

As examples of compounds capable of being used for the preparation of the catalysts of the invention, there may be mentioned in particular:

- palladium (0),

- palladium (II) bromide

- palladium (II) chloride - palladium (II) iodide

- palladium (II) cyanide

- hydrated palladium (II) nitrate

- palladium (II) oxide - palladium (II) sulfate dihydrate

- palladium (II) acetate

- palladium (II) propionate,

- palladium (II) butyrate,

- palladium (II) benzoate, - palladium (II) acetylacetonate

- palladium dibenzylideneacetone (0),

- ammonium tetrachloropalladate (ll)

- potassium hexachloropalladate (IV)

- palladium (II) tetramine nitrate - palladium (II) dichlorobis (acetonitrile)

- palladium (II) dichlorobis (benzonitrile)

- palladium (II) dichloro (1,5-cyclooctadiene)

- palladium (II) dichlorodiamine.

- palladium (II) tetrakistriphenylphosphine. It is also possible to use complexes of mineral or organic salts of palladium. In these complexes, the ligands or coordinating agents are advantageously hydrocarbon derivatives of the elements of column V.

Said hydrocarbon derivatives of the elements of column V derive from the valence III state of nitrogen such as amines or nitrogen heterocydes, phosphorus such as phosphines, arsenic such as arsines and antimony such as stilbines .

They are advantageously chosen from the hydrocarbon derivatives of the elements of column VB preferably of period greater than the 2nd, nitrogen such as for example, bipyridine, bisoxazoline; phosphorus such as phosphines.

In the latter case, this complex is generally produced in situ between the palladium derivative and the phosphine present. However, the said complex can also be prepared extemporaneously and introduced into the reaction medium. It is then possible to add or not an additional quantity of free phosphine.

Advantageously, aliphatic, cycloaliphatic, arylaliphatic or aromatic phosphines or mixed, aliphatic and / or cycloaliphatic and / or arylaliphatic and / or aromatic phosphines are used. These phosphines are organosoluble and are those which correspond in particular to the general formula (III):

^R 5

I ^R 4 ~ ^p - R _{6 (| | |)} in which the symbols R ₄ , R ₅ and R ₆ , identical or different, represent: - an alkyl group having from 1 to 12 carbon atoms,

- a cycloalkyl group having 5 or 6 carbon atoms,

- a cycloalkyl group having 5 or 6 carbon atoms, substituted by one or more alkyl groups having 1 to 4 carbon atoms, alkoxy having 1 or 4 carbon atoms, - a phenylalkyl group in which the aliphatic part contains from 1 to 6 carbon atoms,

one or two of the groups R, R ₅ and R ₆ represent a phenyl group or a phenyl group substituted by one or more alkyl groups having 1 to 4 carbon atoms or alkoxy groups having 1 to 4 carbon atoms. As examples of such phosphines, there may be mentioned, without limitation: tricyclohexylphosphine, trimethylphosphine, triethylphosphine, tri-n-butylphosphine, triisobutylphosphine, tri-terr-butylphosphine, tribenzylphosphine, triphenylphosphine, dicyclohephyline dimethylphenylphosphine, diethylphenylphosphine, di-te / τ- butylphenylphosphine.

According to a preferred variant of the process of the invention, palladium is combined with a ligand, which is preferably a phosphine.

The amount of palladium catalyst used expressed by the molar ratio of metal to arylboronic acid varies between 5.10 ^"7 and 0.2. The amount of ligand, preferably, a phosphine used represents from 100 to 500% of the stoichiometric amount of palladium.

If the catalyst is a palladium compound, it can be introduced in solid form or in aqueous solution. For example, the palladium chloride which is preferably chosen, can be introduced in solid form or in solution in an aqueous solution of hydrochloric acid, (for example at 5 or 10%). The compound in solution can be deposited on a support. Palladium in metallic form can also be deposited on a support.

The support is chosen so that it is inert under the reaction conditions. As examples of supports, one can use a mineral or organic support such as in particular carbon, activated carbon, acetylene black, silica, alumina, clays and more particularly, montmoπllonite or equivalent materials or alternatively or organic polymers, for example polyvinyl polymers PVC (polyvinyl chloride), PVDC (polyvinylidene chloride) or polystyrenics which can be functionalized with nitπle or polyacrylic functions (and in particular polyacrylonitπle)

Generally, the metal is deposited at a rate of 0.5% to 10%, preferably from 1% to 5% of the weight of the catalyst. Among the above-mentioned catalysts, the preferred catalyst is palladium chloride, palladium acetate or palladium deposited on carbon

The catalyst can be used in the form of a powder, pellets or else granules

In accordance with the process of the invention, the compounds (I) and (II) are reacted in the presence of a base and a phase transfer catalyst

By the expression "phase transfer catalyst" is meant a catalyst capable of passing the anion from the aqueous phase to the organic phase

In the process of the invention, use may be made of known phase transfer catalysts, in particular those described in the work by Jerry MARCH - Advanced Organic Chemistry, 3rd edition, John Wiley & Sons, 1985 p 320 and following

The catalysts preferably used in the process of the invention are the onium salts and, more particularly the quaternary ammonium and / or phosphonium salts

The onium salts which can be used in the process of the invention are those in which the onium ions are derived in particular from nitrogen, phosphorus, arsenic, sulfur, selenium, carbon and coordinated with hydrocarbon residues The onium ions deriving from nitrogen, phosphorus or arsenic will be quadπcoordinated, the onium ions deriving from sulfur, selenium, oxygen or carbon will be tπcoordinated while the onium ions deriving from iodine will be coordinated

The hydrocarbon radicals coordinated with these various elements are optionally substituted alkyl, alkenyl, aryl, cycloalkyl or aralkyl groups, two coordinated hydrocarbon radicals which can together form a single divalent group

The nature of the anions linked to these organic cations is not of critical importance All the "hard" or "intermediate" bases are suitable as anion By "hard" or "intermediate" base is meant any anion corresponding to the classic definition given by R. PEARSON in Journal of Chem. Ed. 45, pages 581-587 (1968), the terms "hard" and "intermediate" respectively having the meanings of the terms "hard" and "borderline" used in this reference.

Among the onium ions which can be used in the present process of the invention, particularly suitable are those corresponding to one of the following general formulas:

\ +

/ w - x _^ ³

X. (VI) in said formulas:

- Z represents N, P or As; - W represents S, Se or C;

- X ^, X, X and X ₄ , identical or different represent:

. a linear or branched alkyl group having 1 to 16 carbon atoms and optionally substituted by one or more phenyl, hydroxyl, halogen, nitro, alkoxy or alkoxycarbonyl groups or atoms, the alkoxy groups having 1 to 4 carbon atoms;

. an alkenyl group, linear or branched, having 2 to 12 carbon atoms; . an aryl group having 6 to 10 carbon atoms, optionally substituted by one or more alkyl groups or atoms having 1 to 4 carbon atoms, alkoxy, alkoxycarbonyl, the alkoxy group having 1 to 4 carbon atoms, or halogen,

- Two of said groups X .. to X, which can together form an alkylene, alkenylene or alkadienylene group, linear or branched having 3 to 6 carbon atoms.

Among the "hard" or "intermediate" bases which can constitute the anion of said onium salts, mention may be made of the ions: F ^" , CIO ^" , PF ^" , BF ^" , SnCI ₆ ^" , SbCL ^" , B (Ph) ^" , PO ₄ ^3_ , HPO ₄ ^2- , H ₂ PO ₄ -, CH ₃ SO ₃ ^" , Ph-SO ^, HSO, NO ^, SO ^" , CI ^" , Br ^" , I ^" , OH ^" , Ph representing a phenyl group, as well as all the other anions meeting the basic definition "hard" or "intermediate" of PEARSON. For reasons of convenience of use, said anions may be chosen from PO ₄ ^{3 "} , HPO ₄ ^2" , H ₃ PO ₄ ^" , CH ₃ SO ₃ ^" , Ph-SO ₃ ^" , NO ₃ ^" , SO ₄ ^{2 "} , PF ^" , CI ^" , Br ^" , I ^" , Ph having the above meaning. The anions Br ^" and Cf are advantageously chosen. As examples of onium ions corresponding to formula (V), it is possible to quote the cations:

- tetramethylammonium,

- triethylmethylammonium,

- tributylmethylammonium, - trimethylpropylammonium,

- tetraethylammonium,

- tetrabutylammonium,

- dodecyltrimethylammonium,

- methyltrioctylammonium (Aliquat 336), - heptyltributylammonium,

- tetrapropylammonium,

- tetrapentylammonium,

- tetrahexylammonium,

- tetraheptylammonium, - tetraoctylammonium,

- tetradecylammonium,

- butyltripropylammonium,

- methyltributylammonium,

- pentylthbutylammonium, - methyldiethylpropylammonium,

- ethyldimethylpropylammonium,

- tetradodecylammonium,

- tetraoctadecylammonium,

- hexadecyltrimethylammonium, - benzyltrimethylammonium,

- benzyldimethylpropylammonium,

- benzyldimethyloctylammonium,

- benzyltributylammonium,

- benzylthethylammonium, - phenyltrimethylammonium,

- benzyldimethyltetradecylammonium,

- benzyldimethylhexadecylammonium,

- dimethyldiphenylammonium, - methyltriphenylammonium,

- butene-2-yltriethylammonium,

- N, N-dimethyl-tetramethyleneammonium,

- N, N-diethyl-tetramethyleneammonium, - tetramethylphosphonium,

- tetrabutylphosphonium,

- ethyltrimethylphosphonium,

- trimethylpentylphosphonium,

- octyltrimethylphosphonium, - dodecyltrimethylphosphonium,

- trimethylphenylphosphonium,

- diethyldimethylphosphonium,

- dicyclohexyldimethylphosphonium,

- dimethyldiphenylphosphonium, - cyclohexyltrimethylphosphonium,

- triethylmethylphosphonium,

- methyltri (isopropyl) phosphonium,

- methyltri (n-propyl) phosphonium,

- methyltri (n-butyl) phosphonium, - methyltri (2-methyl-propyl) phosphonium,

- methyltricyclohexylphosphonium,

- methyltriphenylphosphonium,

- methyltribenzylphosphonium,

- methyltri (4-methylphenyl) phosphonium, - methyltrixylylphosphonium,

- diethylmethylphenylphosphonium,

- dibenzylmethylphenylphosphonium,

- ethyltriphenylphosphonium,

- tetraethylphosphonium, - ethyltri (n-propyl) phosphonium,

- triethylpentylphosphonium,

- hexadecyltributylphosphonium,

- ethyltriphenylphosphonium,

- n-butyltri (n-propyl) phosphonium, - butyltriphenylphosphonium,

- benzyltriphenylphosphonium,

- (β-phenylethyl) dimethylphenylphosphonium,

- tetraphenylphosphonium, - triphenyl (4-methylphenyl) phosphonium, - tetrakis (hydroxymethyl) phosphonium,

- tetraphenylarsonium.

As examples of onium ions corresponding to formula (VI), mention may be made of the cations:

- trimethylsulfonium, - triethylsulfonium,

- triphenylsulfonium,

- trimethylsulfoxonium, - triphenylcarbenium.

Among the onium ions which can be used in the context of the present process, quaternary ammonium ions and quaternary phosphonium ions are most often preferred.

Particularly suitable are ammonium ions, the four groups of which are alkyl groups having from 1 to 12 carbon atoms or a benzyl group.

As regards the choice of the anion, we will prefer Br ^' or Cf.

The catalysts which are entirely suitable for the present invention are tributylbenzylammonium or phosphonium chloride or bromide, tetramethylammonium or phosphonium chloride or bromide, tetraethylammonium or phosphonium chloride or bromide, tetrabutylammonium chloride or bromide or phosphonium, methyltrioctylammonium chloride or bromide or phosphonium.

Methyltrioctylammonium chloride or bromide is particularly preferred, the chlorinated derivative being more particularly preferred.

The onium salt can be introduced during the process of the invention, in the solid state or in the form of a solution in one of its solvents, most often water.

As regards the quantity of phase transfer catalyst used, this advantageously varies so that the molar ratio between said catalyst and arylboronic acid varies between 0.001 and 0.5, preferably between 0.05 and 0.2.

In accordance with the process of the invention, the compounds (I) and (II) are reacted in the presence of a base. As bases, use is made of alkali metal hydroxides, preferably sodium or potassium; to alkaline earth metal hydroxides, preferably calcium; or ammonium hydroxide; with alkali metal carbonates or hydrogen carbonates, preferably the sodium or potassium carbonate; metal phosphates, preferably sodium or potassium phosphae. It is also possible to use an amine, preferably a secondary or tertiary amine. Mention may be made, in particular, of diisopropylamine, pyrrolidine, morpholine, triethylamine, triethanolamine, diisopropylamine.

The amount of base used expressed by the ratio between the number of moles of OH ^~ and the number of moles of arylboronic acid is preferably chosen between 2 and 4 and more preferably around 2.0.

According to the invention, the coupling of the haloaromatic compound and of the arylboronic acid is advantageously carried out in an organic or hydro-organic medium.

Water is generally brought into the reaction medium, from the base. The amount of water added is such that the medium is likely to be agitated. It is advantageously between 10 and 200% of the weight of the reaction medium.

The starting reagent, namely the haloaromatic compound, can serve as a reaction solvent, but it is also possible to use an organic solvent.

An organic solvent is chosen, which is less activated than the starting substrate and which preferably dissolves it.

As examples of solvents suitable for the present invention, mention may be made in particular of aromatic hydrocarbons, halogenated or not, aliphatic, cycloaliphatic or aromatic ether-oxides.

As examples of aliphatic hydrocarbons, there may be mentioned more particularly, aromatic hydrocarbons and more particularly aromatic hydrocarbons such as in particular benzene, toluene, xylenes, cumene, petroleum fractions consisting of a mixture of alkylbenzenes in particular Solvesso type cuts.

With regard to aliphatic or aromatic halogenated hydrocarbons, there may be mentioned more particularly, dichloromethane, 1, 2-dichloroethane, monochlorobenzene.

It is also possible to use, as organic solvents, the aliphatic, cycloaliphatic or aromatic ether-oxides and, more particularly, dipropyl ether, diisopropyl ether, dibutyl ether, methyl tert-butyl ether, dimethyl ether of ethylene glycol (or glyme), dimethyl ether of diethylene glycol (or diglyme); phenyl oxide; dioxane, tetrahydrofuran (THF). As examples of aprotic, more polar organic solvents which can also be used in the process of the invention, there may be mentioned more particularly alphatic or aromatic nitriles such as acetonitrile, propionitrile, benzonitrile. The preferred solvent is toluene.

It is also possible to use a mixture of organic solvents.

As regards the concentration of arylboronic acid in the reaction medium, it is preferably between 10% and 50% by weight, and more preferably, between 20% and 30%. The reaction temperature is advantageously between room temperature (most often between 15 and 25 ° C) and 150 ° C, and preferably between 50 and 100 ° C.

Generally, the reaction is carried out under autogenous pressure of the reactants. According to a preferred variant of the process of the invention, the process of the invention is carried out under a controlled atmosphere of inert gases. One can establish an atmosphere of rare gases, preferably argon, but it is more economical to use nitrogen.

From a practical point of view, the method is simple to implement. All the reactants are loaded, preferably the catalyst last, and heated for the time necessary for the reaction to be completed.

The polyclic aromatic compound is recovered in a conventional manner, for example by extraction using an organic solvent, and mention may in particular be made of ethers-oxides, preferably isopropyl ether; aliphatic or aromatic hydrocarbons, halogenated or not, preferably toluene.

A polyaromatic compound is obtained which can be represented by formula (VII):

(VII) in said formula (VII), A, R, R and n have the meaning given above.

The invention applies more particularly to the preparation of 4-cyanobiphenyl and 4-methyl-4'-cyanobiphenyl.

The process of the invention allows, thanks to the presence of the phase transfer agent, to conduct the reaction under conventional conditions agitation, relatively low (quantified between 100 and 1000 rpm, preferably between 500 and 1000 rpm for magnetic stirring) and to obtain a yield gain of the order of 20 to 30%.

Examples of embodiment of the invention are given below by way of illustration and without limitation.

In the example, a yield (RT) is defined corresponding to the ratio between the number of moles of product formed and the number of moles of substrate transformed.

Example 1

Synthesis of 4-cvanobiphenyl:

180 mg (0.156.10 ³ mol, 0.02 eq.) Of tetrakistriphenylphosphine are charged into a 250 ml reactor stirred by a magnetic bar, equipped with a condenser and a thermocouple and maintained under an argon atmosphere. palladium II in 78 ml of solvent (dimethoxyethane or degassed toluene).

55 ml of distilled water previously degassed beforehand, conventionally by bubbling with nitrogen, 1.24 g (11.7 × 10 ³ mol, 1.5 eq.) Of carbonate are added under argon and at ambient temperature. sodium, 1.01 g (8.2.10 ³ mol, 1.06 eq) of phenylboronic acid. To this mixture are added 156 mg (0.39.10 ³ mol, 0.05 eq.) Of methyltrioctylammonium chloride (Aliquat 336), and 1.41 g (7.75.10 ³ mol, 1 eq.) Of 4-bromobenzonitrile

The stirring is fixed at the desired value (750 rpm) and the reaction mixture is brought to the desired temperature (85 ° C in dimethoxyethane or 60 to 85 ° C in toluene) for 3 hours.

The mixture is then cooled to room temperature. 60 ml of ethyl acetate are added and the organic phase is separated. The aqueous phase is then extracted twice with ethyl acetate (2 x 60 ml). The combined organic phases are washed with a saturated solution of sodium chloride and then dried over anhydrous magnesium sulfate and the solvents are evaporated on a rotary evaporator.

The residue is after dilution in ethyl acetate filtered on silica. The ethyl acetate is then evaporated and the solid obtained is recrystallized from n-hexane to yield 1.24 g of a white solid, ie a yield of 90%. Example 2

Synthesis of 4-methyl-4'-cvanobiphenyl:

64.5 mg (0.0558.10 ³ mol, 0.019 eq.) Of tetrakistriphenylphosphine of palladium II are loaded into 30 ml of solvent (degassed dimethoxyethane or toluene) into a reactor as described above.

21 ml of distilled water, degassed beforehand, 440 mg (4.15.10 ³ mol, 1.4 eq.) Of sodium carbonate, 434 mg (3.19.10 ³ mol, 1.07) are added at room temperature at room temperature. eq) p-tolylboronic acid.

To this mixture are added 60 mg (0.15 × 10 ³ mol, 0.05 eq.) Of methyltrioctylammonium chloride (Aliquat 336) and 542 mg (2.98 × 10 ⁻³ mol, 1 eq.) Of 4-bromobenzonitrile.

The stirring is fixed at the desired value (750 rpm) and the reaction mixture is brought to the desired temperature (85 ° C in dimethoxyethane or 60 to 85 ° C in toluene) for 3 hours. The mixture is then cooled to room temperature. 30 ml of ethyl acetate are added and the organic phase is separated.

The aqueous phase is then extracted twice with ethyl acetate (2 x 30 ml).

The combined organic phases are washed with a saturated solution of sodium chloride and then dried over anhydrous magnesium sulfate and the solvents are evaporated on a rotary evaporator.

The residue is after dilution in ethyl acetate filtered on silica.

The ethyl acetate is then evaporated and the solid obtained is recrystallized from n-hexane to yield 535 mg of a white solid, ie a yield of 93%.

Claims

1 - Process for the preparation of a polycyclic aromatic compound comprising at least one chain of two aromatic rings which consists in reacting an aromatic compound carrying a leaving group and an arylboronic acid and / or its derivatives, in the presence of a base and an effective amount of a palladium catalyst, said element possibly being complexed with at least one coordinating agent or ligand characterized in that the reaction is carried out, in organic or hydro-organic medium and in the presence of an effective amount of a phase transfer catalyst.

2 - Method according to claim 1 characterized in that the haloaromatic compound corresponds to the general formula (I):

^γ yr ^R) n

(I) in which:

- R, identical or different, represent substituents on the ring, - Y represents a leaving group, preferably, a halogen atom or a sulphonic ester group of formula - OSO - ^ in which ^ is a hydrocarbon group,

- n represents the number of substituents on a cycle.

3 - Process according to claim 2 characterized in that the haloaromatic compound corresponds to formula (I) in which Y is a bromine or chlorine atom or a sulfonic ester of formula - OSO ₂ - ^ in which ζ ^ is a linear or branched alkyl group having from 1 to 4 carbon atoms, preferably a methyl or ethyl group, a phenyl or tolyl group or a trifluoromethyl group.

4 - Method according to one of claims 2 and 3 characterized in that the haloaromatic compound corresponds to formula (I) in which A is the remainder of a cyclic compound, preferably having at least 4 atoms in the cycle, preferably 5 or 6, optionally substituted, and representing at least one of the following cycles:

. an aromatic, monocyclic or polycyclic carbocycle,. an aromatic, monocyclic or polycyclic heterocycle comprising at least one of the heteroatoms O, N and S.

5 - Method according to one of claims 2 to 4 characterized in that the haloaromatic compound corresponds to formula (I) in which the residue A optionally substituted represents an aromatic carbocycle, an aromatic bicycle comprising two aromatic carbocycles, a partially bicycle aromatic comprising two carbocycles, one of which is aromatic, an aromatic heterocycle, an aromatic bicycle comprising an aromatic carbocycle and an aromatic heterocycle, a partially aromatic bicycle comprising an aromatic carbocycle and a heterocycle, an aromatic bicycle comprising two aromatic heterocyds, a bicycle partially aromatic comprising a carbocycle and an aromatic heterocycle, a tricycle comprising at least one carbocycle or an aromatic heterocycle:

6 - Method according to one of claims 2 to 4 characterized in that the haloaromatic compound corresponds to formula (I) in which A represents a benzene or naphthalene nucleus.

7 - Method according to one of claims 2 to 6 characterized in that the haloaromatic compound of formula (I) carries one or more substituents R chosen from:

. an alkyl group, linear or branched, having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,. a linear or branched alkenyl or alkynyl group having from 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms, such as vinyl, allyl,

. a linear or branched alkoxy group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy groups, an alkenyloxy group, preferably an allyloxy group or a phenoxy group,

. a cyclohexyl, phenyl or benzyl group,

. an acyl group having from 2 to 6 carbon atoms,

. a group of formula: -RI-OH

-R-I-S

-R ₁ -COOR ₂

-R-I-CO-R2

-Rl-CHO

-R <| -N = C = O

-R <| N = C = O

-Rl-NO ₂

-R-I-CN

-R- | -N (R ₂ ) ₂

-R -CO-N (R ₂ ) ₂

-R-I-SO3M

-R < _| -SO ₂ M

-R-the-X

- _R1 -CF ₃ in said formulas, Ri represents a valential bond or a divalent, linear or branched, saturated or unsaturated hydrocarbon group having from 1 to 6 carbon atoms such as, for example, methylene, ethylene, propylene, isopropylene, isopropylidene; the same or different R groups represent a hydrogen atom or a linear or branched alkyl group having from 1 to 6 carbon atoms or phenyl; M represents a hydrogen atom, an alkali metal preferably, sodium or a group R; X symbolizes a halogen atom, preferably a chlorine, bromine or fluorine atom.

8 - Method according to one of claims 2 to 7 characterized in that the haloaromatic compound corresponds to formula (I) in which n is a number less than or equal to 4, preferably equal to 1 or 2.

9 - Method according to one of claims 2 to 8 characterized in that the haloaromatic compound of formula (I) is chosen from: 4-bromoaniline, 4-bromo-3-methylaniline, 1-amino-3- naphthalene, 2-chloro-3-aminopyridine, 4-bromobenzonitrile.

10 - Process according to claim 1 characterized in that the arylboronic acid corresponds to the formula:

in which :

- R3 represents a carbocyclic or heterocyclic, aromatic, monocyclic or polycyclic group, - Q- (, Q ₂ , identical or different, represent a hydrogen atom, a saturated or unsaturated, linear or branched aliphatic group, having from 1 to 20 carbon atoms or an R3 group,

- or Q- _| and Q can be linked to each other by an alkylene or alkylenedioxy group having from 1 to 4 carbon atoms, - or Q- | and Q can be linked together by -OBO- to form a boroxine group corresponding to formula (III) in which R ₃ has the meaning given above:

11 - Process according to claim 10 characterized in that the arylboronic acid corresponds to the formula (II) or (III) in which the group R3 represents an aromatic carbocyclic or heterocyclic group, preferably a phenyl or naphthyl group, a pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1, 3-thiazolyl, 1, 3,4-thiadiazolyl or thienyl group.

12 - Method according to one of claims 10 and 11 characterized in that the arylboronic acid has an aromatic ring carrying at least one substituent chosen from alkyl or alkoxy groups having from 1 to 4 carbon atoms, a group amino, a nitro group, a cyano group, a halogen atom or a trifluoromethyl group.

13 - Method according to one of claims 10 to 12 characterized in that the arylboronic acid corresponds to the formula (II) in which Q ^ Q ₂ , identical or different, represent a hydrogen atom or an acyclic aliphatic group , linear or branched, having from 1 to 20 carbon atoms, saturated or comprising ine or more unsaturations on the chain, preferably 1 to 3 unsaturations which are preferably single or conjugated double bonds; an R ₃ group, preferably a phenyl group.

14 - Method according to one of claims 10 to 13 characterized in that the arylboronic acid corresponding to formula (II) is chosen from: benzeneboronic acid, 2-thiopheneboronic acid, 3-thiopheneboronic acid , 4-methylbenzeneboronic acid, 3-methylthiophene-2-boronic acid, 3-aminobenzeneboronic acid, 3-aminobenzeneboronic hemisulfate acid, 3-fluorobenzeneboronic acid, 4-fluorobenzeneboronic acid, 2-formylbenzeneboronic acid, 3- formylbenzeneboronic acid, 4-formylbenzeneboronic acid, 2- methoxybenzeneboronic acid, 3-methoxybenzeneboronic acid, 4- methoxybenzeneboronic acid, 4-chlorobenzeneboronic acid, 5- chlorothiophene-2-boronic, benzo [b] furan-2-boronic acid, 4- carboxybenzeneboronic acid, 2,4,6-trimethylbenzeneboronic acid, 3-nitrobenzeneboronic acid, acid 4 - (methylthio) benzeneboronic, 1- naphthaleneboronic acid, ac ide 2-naphthaleneboronic, 2-methoxy-1- naphthaleneboronic acid, 3-chloro-4-fluorobenzeneboronic acid, 3- acetamidobenzeneboronic acid, 3-trifluoromethylbenzeneboronic acid, 4-trifluoromethylbenzeneboronic acid, 2,4-dichlorobenzeneboronic acid, 3,5-dichlorobenzeneboronic acid, 3,5-bis (trifluoromethyl) benzeneboronic acid, 4,4'-biphenyldiboronic acid, and the esters and anhydrides of such acids.

15 - Process according to claim 1 characterized in that the palladium catalyst comprises palladium provided in the form of a finely divided metal, or in the form of an inorganic derivative such as an oxide or a hydroxide; or a mineral salt preferably, nitrate, sulfate, oxysulfate, halide, oxyhalide, silicate, carbonate; or of an organic derivative preferably, cyanide, oxalate, acetylacetonate; alcoholate and even more preferably methylate or ethylate; carboxylate and even more preferably acetate; or of a chlorinated or cyan complex of palladium and / or alkali metals, preferably sodium, potassium or ammonium

16 - Process according to claim 15 characterized in that the palladium in metallic form or in the form of a compound in solution is deposited on a support. 17 - Method according to one of claims 15 and 16 characterized in that the palladium catalyst is chosen from palladium chloride, palladium acetate or palladium deposited on charcoal.

18 - Process according to claim 1 characterized in that the ligand is an aliphatic, cycloaliphatic or arylaliphatic phosphine or a mixed, aliphatic and / or cycloaliphatic and / or arylaliphatic and / or aromatic phosphine.

19 - Process according to claim 18 characterized in that the phosphine used corresponds to the general formula

FR _c I

R ₄ P - R _{6 (|||)} in which the symbols R ₄ , R ₅ and R ₆ , identical or different, represent:

an alkyl group having from 1 to 12 carbon atoms, a cycloalkyl group having from 5 to 6 carbon atoms,

a cycloalkyl group having 5 or 6 carbon atoms, substituted by one or more alkyl groups having 1 to 4 carbon atoms, alkoxy having 1 or 4 carbon atoms,

- a phenylalkyl group the aliphatic part of which contains from 1 to 6 carbon atoms,

one or two of the groups R ₄ , R ₅ and R ₆ represent a phenyl group or a phenyl group substituted by one or more alkyl groups having 1 to 4 carbon atoms or alkoxy groups having 1 to 4 carbon atoms.

20 - Method according to one of claims 18 and 19 characterized in that the phosphine used is chosen from thcyclohexylphosphine, trimethylphosphine, triethylphosphine, tri-n-butylphosphine, triisobutylphosphine, tri-te / f-butylphosphine , tribenzylphosphine, triphenylphosphine, dicyclohexylphenylphosphine, dimethylphenylphosphine, diethylphenylphosphine, d -tert- butylphenylphosphine.

21 - Process according to claim 1 characterized in that the phase transfer catalyst is an onium salt. 22 -. Process according to Claim 21, characterized in that the phase transfer catalyst is an onium salt, the onium of which corresponds to one of the following formulas:

(VI) in said formulas:

- Z represents N, P or As;

- W represents S, Se or C; - X .., X ₂ , X3 and X ₄ , identical or different represent:

. a linear or branched alkyl group having 1 to 16 carbon atoms and optionally substituted by one or more phenyl, hydroxyl, halogen, nitro, alkoxy or alkoxycarbonyl groups or atoms, the alkoxy groups having 1 to 4 carbon atoms; . an alkenyl group, linear or branched, having 2 to 12 carbon atoms;

. an aryl group having 6 to 10 carbon atoms, optionally substituted by one or more alkyl groups or atoms having 1 to 4 carbon atoms, alkoxy, alkoxycarbonyl, the alkoxy group having 1 to 4 carbon atoms, or halogen, - two of the said groups X ^ to X. which may together form an alkylene, alkenylene or alkadienylene group, linear or branched having from 3 to 6 carbon atoms.

23 - Process according to claim 22 characterized in that the anion of said onium salts is chosen from the ions: F ^" , CIO ^" , PF ^" , BF ^" , SnCI ^" , SbCL ^" , B (Ph) ₄ ^" , PO ₄ ^{3 "} , HPO ₄ ^2" , H ₂ PO ₄ ^" , CH ₃ SO ₃ ^" , Ph-SO ₃ ^" , HSO ₄ ^" , NO ₃ ^" , SO, CI ^" , Br ^" , I ^" , OH ^" , Ph representing a phenyl group; the anion of said onium salts being preferably chosen from the Br ^" and Cf ions.

24 - Process according to claim 22 characterized in that the phase transfer catalyst is chosen from: tributylbenzylammonium or phosphonium chloride or bromide, tetramethylammonium or phosphonium chloride or bromide, tetraethylammonium chloride or bromide or phosphonium, tetrabu- chloride or bromide tylammonium or phosphonium, methyltrioctylammonium chloride or bromide or phosphonium.

25 - Process according to claim 1 characterized in that the base is chosen from hydroxides of alkali metals, alkaline earth or ammonium, carbonates or hydrogen carbonates of alkali metals, preferably potassium carbonate, metal phosphates , preferably, sodium or potassium phosphate or secondary or tertiary amines.

26 - Process according to claim 1 characterized in that the organic solvent is chosen from aromatic hydrocarbons, halogenated or not, aliphatic, cycloaliphatic or aromatic ether-oxides, preferably toluene.

27 - Process according to claim 1 characterized in that the quantity of reagents used is such that the molar ratio of arylboronic acid / haloaromatic compound is greater than or equal to 1 and preferably varies between 1 and 1, 2.

28 - The method of claim 1 characterized in that the amount of palladium catalyst used expressed by the molar ratio of metal to arylboronic acid varies between 5.10 ^"7 and 0.2.

29 - Process according to claim 1 characterized in that the amount of ligand, preferably, a phosphine used represents from 100 to 500% of the stoichiometric amount of palladium.

30 - Process according to claim 1 characterized in that the amount of base used expressed by the ratio between the number of moles of OH ^~ and the number of moles of arylboronic acid is preferably chosen between 2 and 4 and more preferably around 2.0.

31 - Method according to claim 1 characterized in that the amount of phase transfer catalyst used is such that the molar ratio between said catalyst and arylboronic acid varies between 0.001 and 0.5, preferably between 0.05 and 0.2. 32 - Process according to claim 1 characterized in that the water is present in an amount: representing 10 and 200% of the weight of the reaction medium.

33 - Method according to one of claims 1 to 32 characterized in that the reaction temperature is between room temperature and 150 ° C, and preferably between 50 ° C and 100 ° C.

34 - Application of the process described in one of claims 1 to 33 to the preparation of 4-cyanobiphenyl and 4-methyl-4'-cyanobiphenyl.