Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2002-09-03
2004-10-05
Davis, Brian J. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C546S311000
Reexamination Certificate
active
06800784
ABSTRACT:
The present invention relates to a process for preparing a polyaromatic compound comprising a concatenation of two aromatic cycles and carrying at least one amino group on one of the aromatic cycles.
In particular, the invention relates to a biphenyl type compound, one of the benzene cycles of which carries an amino group.
In the present disclosure of the invention, the term “polycyclic aromatic compound carrying an amino group” means a compound resulting from a concatenation of two aromatic cycles wherein one of the hydrogen atoms of one of the aromatic cycles being replaced by an NH
2
group.
The term “aromatic compound” means the conventional notion of aromaticity as defined in the literature, in particular by Jerry MARCH, Advanced Organic Chemistry, 4
th
Edition, John Wiley & Sons, 1992, pp. 40 ff.
For simplicity, the expression “aryl” designates all aromatic compounds, whether they are carbocyclic aromatic compounds or heterocyclic aromatic compounds.
Biphenyl type structures are encountered in many molecules used in the pharmaceutical field. In particular, a process for preparing compounds of the N-(biaryl)-amine type, in particular N-(biphenyl)-amine is sought.
Michael Hird et al. (Synlett 1999, No. 4, 438-440) have described the preparation of such compounds using a coupling reaction between an arylboronic acid and a halogenoaniline, in the presence of a palladium catalyst complexed with a triphenylphosphine, sodium carbonate, dimethoxyethane and water. That publication mentions that the coupling reaction is accompanied by very substantial deamination of the reactant and of the product formed.
A. D. Hamilton et al. [Journal of Medicinal Chemistry 1996, 39, p. 217-223] recommend coupling a 3-methylphenylarylboronic acid with 4-bromonitrobenzene to produce a nitrobiphenyl. It is then necessary to reduce the nitro group to an amino group using hydrogen in the presence of palladium on charcoal.
D. Badone et al., J. Org. Chem 1997, 62, 7170-7173 have proposed coupling an arylboronic acid with a halogenoaniline, where the amino group is protected by an acetyl group. After the coupling reaction, liberation of the amino group involves a supplemental acid treatment step.
Thus, the provision of a process that can effect direct coupling between an arylamine and an arylboronic acid is desirable.
We have now discovered, and this constitutes the subject matter of the present invention, a process for preparing a polycyclic aromatic compound comprising at least one concatenation of two aromatic cycles and carrying at least one amino group on one of the aromatic cycles, characterized in that it consists of reacting an aromatic compound carrying at least one amino group and a leaving group with an arylboronic acid and/or its derivatives in an aqueous medium and in the presence of an effective quantity of a palladium catalyst.
In accordance with the process of the invention, an aromatic compound carrying at least one amino group and a leaving group is reacted with an arylboronic acid: the reaction takes place in an aqueous medium and in the presence of a palladium catalyst to produce a biphenyl carrying an amino group. This latter is obtained without deamination, which is surprising in view of the descriptions in the literature.
More precisely, the aromatic compound carrying at least one amino group and a leaving group, hereinafter designated an “aminoaromatic compound” has general formula (I):
in which:
A designates the residue of a cycle forming all or a portion of an aromatic, monocyclic or polycyclic, carbocyclic or heterocyclic system;
R, which can be identical or different, represents the substituents on the cycle;
Y represents a leaving group, preferably a halogen atom or a sulphonic ester group with formula-OSO
2
-R, where R is a hydrocarbon group;
n represents the number of substituents on the cycle.
In the formula for the sulphonic ester, R is a hydrocarbon group of any nature containing 1 to 20 carbon atoms. However, given that Y is a leaving group, it is economically advantageous for R to be simple in nature, and more particularly it represents a linear or branched alkyl group containing 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. A preferred group Y is the triflate group, corresponding to a group R representing a trifluoromethyl group.
Preferred leaving groups are a bromnine or chlorine atom.
The invention is applicable to aminoaromatic compounds with formula (I) in which A is the residue of a cyclic compound preferably containing 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 containing at least one of heteroatoms O, N or S.
More precisely, and without limiting the scope of the invention, optionally substituted residue A can represent the residue:
1° of an aromatic, monocyclic or polycyclic carbocyclic compound.
The term “polycyclic carbocyclic compound” means:
a compound constituted by at least 2 aromatic carbocycles and forming ortho- or ortho- and peri-condensed systems between them;
a compound constituted by at least 2 carbocycles only one of which is aromatic and forming ortho- or ortho- and peri-condensed systems between them;
2° of an aromatic, monocyclic or polycyclic heterocyclic compound.
The term “polycyclic heterocyclic compound” means:
a compound constituted by at least 2 heterocycles containing at least one heteroatom in each cycle wherein at least one of two cycles is aromatic and forming ortho- or ortho- and peri-condensed systems between them;
a compound constituted by at least one carbocycle and at least one heterocycle wherein at least one of the cycles is aromatic and forming ortho- or ortho- and peri-condensed systems between them.
More particularly, 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 process of the invention, an aminoaromatic compound with formula (I) is preferably used in which A represents an aromatic ring, preferably a benzene or naphthalene ring.
The aromatic compound with formula (I) can carry one or more substituents. The substituent can be of any type provided that it does not interfere with the reaction.
The number of substituents present on a cycle depends on the carbon condensation of the cycle and on the presence or absence of unsaturated bonds on the cycle.
The maximum number of substituents that can be carried by a cycle can readily be determined by the skilled person.
In the present text, the term “plurality” generally means less than 4 substituents on an aromatic ring.
Examples of substituents are given below, but this list is not limiting in nature.
Groups R, which may be identical or different, preferably represent one of the following substituents:
a linear or branched alkyl group containing 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl;
a linear or branched alkenyl or alkynyl group containing 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyl or allyl;
a linear or branched alkoxy group containing 1 to 6 carbon atoms, preferably 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 gro
Bigouraux Jean-Christophe
Schlama Thierry
Davis Brian J.
Rhodia Chimie
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