Method of producing biaryls

Details Method of producing biaryls Method of producing biaryls

2002-02-04

2003-05-20

Dang, Thuan D. (Department: 1764)

Chemistry of hydrocarbon compounds

Aromatic compound synthesis

By condensation of entire molecules or entire hydrocarbyl...

C585S455000, C585S457000, C568S628000, C549S412000, C562S093000, C564S409000

Reexamination Certificate

active

06566571

ABSTRACT:

DESCRIPTION
The present invention relates to a process for preparing biaryls using catalysts based on palladium compounds with phosphite ligands.
Biaryl compounds, in particular biphenyl compounds, are industrially important as fine chemicals, intermediates for pharmaceuticals, optical brighteners and agro-chemicals.
A method which is frequently employed for the synthesis of biaryls on a laboratory scale is the Suzuki reaction in which iodoaromatics or bromoaromatics or in exceptional cases chloroaromatics are reacted with arylboronic, vinylboronic or alkylboronic acid derivatives in the presence of palladium catalysts. Review articles describing this methodology may be found, for example, in N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457. Catalysts used for the purposes of the Suzuki reaction are in general palladium and nickel compounds. Despite the economic advantage of nickel catalysts (cf. A. F. Indolese, Tetrahedron Lett. 1997, 38, 3513), palladium catalysts are preferred to nickel catalysts because of the lower toxicity and the greater tolerance to functional groups. When using palladium catalysts, both palladium(II) and palladium(0) complexes are employed in Suzuki reactions (cf. M. Beller, H. Fischer, W. A. Herrmann, K. Öfele, C. Bro&bgr;mer, Angew. Chem. 1995, 107, 1992). According to the literature, coordinatively unsaturated 14- and 16-electron palladium(0) species stabilized by means of donor ligands such as phosphines are formulated as catalytically active species. Particularly when using relatively low-cost starting materials such as aryl bromides or aryl chlorides, it is necessary to add stabilizing ligands in order to achieve a satisfactory catalytic activation of the starting materials.
A substantial disadvantage of the Suzuki reactions described is that satisfactory catalytic turnover numbers (TONs) can be achieved only when using uneconomical starting materials such as iodoaromatics and activated (i.e. electron-deficient) bromoaromatics. Otherwise, when using deactivated (i.e. electron-rich) bromoaromatics or chloroaromatics, large amounts of catalysts, usually from 1 to 5 mol %, have to be added so as to achieve industrially usable conversions. Owing to the complexity of the reaction mixtures, simple catalyst recycling is also not possible, so that catalyst costs, too, generally stand in the way of industrial implementation. Relatively recent catalyst systems based on water-soluble phosphines do give satisfactory catalytic activities in the industrially important reaction of 2-chlorobenzonitrile with p-tolylboronic acid, but the catalysts comprise relatively expensive sulfonated phosphines. Furthermore, a number of chloroaromatics cannot be activated in an industrially satisfactory manner even by means of these catalysts (cf. S. Haber, Fine Chemical Syntheses, in B. Cornils, W. A. Herrmann, Aqueous Phase Organometallic Catalysis, Wiley-VCH: Weinheim, N.Y., Chichester 1998, p. 440 ff.).
It is an object of the present invention to provide a novel process for preparing biaryls which does not display the disadvantages of the known processes, is suitable for industrial implementation and gives biaryls in high yield, catalyst productivity and purity.
This object is achieved by a process for preparing monofunctional, bifunctional and/or polyfunctional biaryls of the formula (I)
Ar—Ar′  (I)
where Ar and Ar′ are each, independently of one another,
an aromatic radical having up to 14 carbon atoms or
a heteroaromatic selected from the group consisting of five-, six- or seven-membered rings having at least one nitrogen, oxygen and/or sulfur atom in the ring;
by reacting haloaromatics of the formula (II)
Ar—X  (II)
with boron compounds of the formula (IIIa), (IIIb) and/or (IIIc)
where, in the formulae (II), (IIIa), (IIIb) and (IIIc),
Ar and Ar′ are as defined for formula (I);
X is selected from the group consisting of chlorine, bromine, iodine, OSO
2
CF
3
, OSO
2
aryl-(C
6
-C
10
), OSO
2
alkyl-(C
1
-C
8
) and N
2
+
Y
−
, where Y is a chlorine, bromine or iodine atom or a tetrafluoro-borate or tetraphenylborate anion;
Q
1
and Q
2
are selected independently from the group consisting of OH, fluorine, chlorine, bromine, iodine, alkyl-(C
1
-C
4
), aryl-(C
6
-C
10
), alkoxy-(C
1
-C
4
) and aryloxy-(C
6
-C
10
);
in the presence of at least one palladium complex of the formula (IVa) or (IVb),
where
the radicals R
1
to R
4
are each, independently of one another, a (C
1
-C
18
)-alkyl radical or one of the above-described radicals Ar;
E is a carbon bridge having from two to seven carbon atoms; and
n is an integer from 1 to 4.
In a further embodiment of the invention,
the aromatic radicals Ar and Ar′ have up to eight substituents;
the heteroaromatic has up to five substituents; and/or
the radicals R
1
to R
4
have up to eight substituents which are selected independently from the group consisting of fluorine, chlorine, CF
3
, OH, NO
2
, CN, R
5
, O—R
5
, CHO, CO—R
5
, COOH, COO—R
5
, OCO—R
5
, SiR
5
3
, NH
2
, NH—R
5
, N—R
5
2
, SO—R
5
, SO
2
—R
5
, SO
3
H, SO
3
—R
5
, CONH
2
, NHCOH, NHCO—R
5
, NHCOO—R
5
, CHCH—CO
2
-alkyl-(C
1
-C
8
), PO—R
5
2
, P—R
5
2
, PO
3
H
2
, PO(O-alkyl-(C
1
-C
6
))
2
and CHCHCO
2
H; where R
5
is an alkyl radical having from 1 to 8 carbon atoms or an aryl radical having from 6 to 10 carbon atoms, e.g. phenyl.
In the formula (IVb), the carbon bridge E can have up to seven substituents selected independently from the group consisting of (C
1
-C
4
)-alkyl, O-alkyl-(C
1
-C
4
), OH and Ar, where Ar is as defined for formula (I).
It is likewise possible for Q
1
and Q
2
in the formula (IIIa) each to be, independently of one another, a (C
1
-C
4
)-alkyl, (C
1
-C
4
)-alkoxy, (C
6
-C
10
)-aryl or (C
6
-C
10
) -aryloxy radical which is substituted by at least one halogen atom or a (C
1
-C
4
)-alkoxy or (C
1
-C
4
)-alkyl radical; or for Q
1
and Q
2
in the formula (IIIa) together to form an alkylenedioxy or alkylene group which has from one to four carbon atoms and may be substituted by up to four (C
1
-C
4
)-alkyl and/or (C
6
-C
10
)-aryl radicals.
The radicals Ar and Ar′ can each be, independently of one another, a heteroaromatic in which up to four further aromatic, heteroaromatic and/or aliphatic rings are fused onto the heteroaromatic ring. The process of the invention is particularly suitable for the synthesis of biaryls in which Ar and Ar′ are each a substituted phenyl, naphthyl, anthryl, phenanthryl, biphenyl radical and/or a five-, six- or seven-membered heteroaromatic having nitrogen, oxygen or sulfur atoms in the ring. In the case of hetero-aromatics, particular preference is given to hetero-aromatics such as substituted pyridines, pyrimidines, oxazoles, imidazoles, pyrazines, quinolines, indoles, furans, benzofurans and/or thiophenes.
The process of the invention has been found to be particularly useful for preparing compounds of the formula (I) in which the radicals Ar and Ar′ each have, independently of one another, up to 5 substituents selected from the group consisting of alkyl-(C
1
-C
8
), O-alkyl-(C
1
-C
8
), OCO-alkyl-(C
1
-C
8
), N-alkyl
2
-(C
1
-C
8
), phenyl, aryl, fluorine, chlorine, NO
2
, CN, COOH, CHO, SO
2
-alkyl-(C
1
-C
4
), NH-alkyl-(C
1
-C
8
), COO-alkyl-(C
1
-C
8
), CONH
2
, CONH-alkyl-(C
1
-C
8
), CO-alkyl-(C
1
-C
8
), CO-phenyl and PO-phenyl
2
.
The reaction generally takes place in the presence of at least one solvent selected from the group consisting of water, aliphatic ethers, aromatic or aliphatic hydrocarbons, alcohols, esters, aromatic or aliphatic nitrites and dipolar aprotic solvents such as dialkyl sulfoxides, N,N-dialkylamides of aliphatic carboxylic acids or alkylated lactams. The solvent is preferably THF, dioxane, diethyl ether, diglyme, MTBE, DME, acetonitrile, toluene, xylenes, anisole, ethyl acetate, methanol, ethanol, butanol, ethylene glycol, ethylene carbonate, propylene carbonate, dimethyl sulfoxide, N,N-dimethylacetamide, N,N-dimethylformamide or N-methylpyrrolidone.
Since an acid is formed in the reaction, it is advantageous

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