Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2000-11-29
2003-04-01
Rotman, Alan L. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S716000, C568S780000, C570S128000
Reexamination Certificate
active
06541674
ABSTRACT:
The present invention relates to a process which makes it possible to condense, in a basic medium, one or more carbonyl compounds with aromatic derivatives.
A more specific object of the present invention is to provide a novel synthetic route for functionalizing aromatic derivatives with one or more carbonyl derivatives which advantageously does not require the formation of an intermediate.
The Applicant Company has unexpectedly demonstrated that it is possible to efficiently condense, in a single stage, at least one carbonyl derivative carrying at least one electron-withdrawing group, like, for example, fluoral, with an aromatic derivative.
This novel access route to functionalized aromatic derivatives is all the more advantageous industrially as these compounds are important synthetic intermediates in the preparation of compounds with pharmacological or plant-protection activity or of materials such as liquid crystals and/or pigments.
A subject-matter of the present invention is consequently a process for condensing at least one carbonyl compound carrying at least one electron-withdrawing group with an aromatic derivative carrying at least one hydroxyl functional group, wherein the electron-withdrawing group present on the carbonyl compound is selected from fluoroalkyl derivatives, esters, including orthoesters, and nitriles and said condensation is carried out in a basic medium.
A non-nitrogenous basic medium will be favored in the context of the present invention.
The claimed process is particularly advantageous since it allows to condense one or several molecules of a carbonyl compound with an aromatic derivative.
In fact, it is possible to control the condensation number per aromatic by various means like in particular the temperature of the reaction of condensation (the lower the temperature, the lower the number of condensation), the ratio between carbonyl compound and the aromatic, and/or the presence of some substituents on the aromatic cycle.
Thus, the condensation of carbonyl compound(s) with an aromatic derivative can be carried out in accordance with the present invention according to several alternative forms.
Generally, one of the best way to control the number of condensed carbonyl derivative per aromatic is to act on the molar ratio between carbonyl compound and the aromatic (carbonyl compound/aromatic). For a mono condensation, specially when said aromatic presents more than one position, the chose ratio is at most ½ and preferably of at most ¼ equivalents of aromatic value.
In other words, the latter value constitutes an excellent compromise for obtaining the condensation of a single carbonyl compound with the aromatic derivative. Thus, according to a specific form of the invention, the condensation is carried out in the presence of a stoechiometrical deficiency of carbonyl compound, in particular by using the carbonyl derivative in a ratio of 0.25 to 1 and preferably of 0.25 to 0.5 equivalents of aromatic derivative.
According to the second alternative form, when there is no risk of further condensation, this condensation is carried out in the presence of a stoechiometrical excess of carbonyl compound. To this end, it is preferably carried out using the carbonyl derivative in a ratio of at most 1 to 2 and preferably of at most 1 to 1.25 equivalents of aromatic derivative.
As regards more particularly the other parameters of the reaction, namely the time or the temperature, their adjustment is generally a function of the electron density of the aromatic derivative to be functionalized and of the pK
a
of the base used.
Generally, the condensation reaction is preferably carried out with heating. To this end, the reaction medium can be brought to a temperature of between approximately 40 and 100° C. and preferably of the order of 50° C. This heating is carried out in a way which is sufficiently prolonged over time to produce an optimum degree of conversion, DC, of the aromatic derivative.
For a temperature of greater than 50° C., it is possible to observe the condensation of several carbonyl compounds with the aromatic derivative.
However, it is clear that such a risk of polycondensation does not exist for some aromatics as they have for example substituents on some reactive positions. It is then possible to increase the reaction temperature above 50° C. for the sole purpose of reducing the time necessary for the condensation.
With regards to the substituents present on the aromatic cycle, the reactive positions of the aromatic cycle are the carbon atoms positioned in ortho and para to the hydroxyl functional group.
Accordingly, the presence of substituents in one or several of these three positions allows to direct the rate of condensation of the carbonyl compound at the aromatic ring.
As regards more particularly the carbonyl compound, the electron-withdrawing group is preferably positioned alpha to the carbonyl functional group.
The term “electron-withdrawing group” is understood to mean a group as defined by H. C. Brown in the work by Jerry March, “Advanced organic Chemistry”, 3rd edition, chapter 9, pages 243 and 244.
This electron-withdrawing group is preferably characterized by a &sgr;
p
at least equal to 0.30 and advantageously greater than or equal to 0.40 and less than 0.75 and preferably less than 0.65.
According to a preferred form of the invention, the electron-withdrawing group present on the carbonyl derivative is a fluoroalkyl derivative, advantageously a polyfluoroalkyl derivative.
As regards the corresponding alkyl group, it can be in particular a linear or branched C
1
to C
15
, preferably C
1
to C
10
, group. In addition to the required fluorine atom or atoms, this alkyl group can comprise other substituents, such as other halogen atoms, like chlorine, for example. Of course, these other substituents must remain inert during the condensation reaction.
The number of fluorine atoms present on this alkyl group can vary significantly insofar as these fluorine atoms confer, if appropriate in combination with the other substituents present on the alkyl group, a &sgr;
p
in accordance with the present invention.
According to a preferred form of the invention, the electron-withdrawing group is a polyfluoroalkyl derivative corresponding to a radical of formula:
—(CX
2
)
p
-EWG
in which
the X units, which are identical or different, are a hydrogen atom, a halogen atom, preferably fluorine, or a radical of formula C
n
X
2n+1
with n being an integer at most equal to 5, preferably to 2;
p is an integer at most equal to 2;
the symbol EWG is an electron-withdrawing group, the possible functional groups of which are inert under the reaction conditions, advantageously a fluorine atom or a perfluorinated residue of formula C
n′
X
2n′+1
with n′ being an integer at most equal to 8, advantageously to 5, with the proviso that at least one of the X or EWG units present on the carbon &agr; to the carbonyl functional group is a fluorine atom, and
with the total number of carbon atoms of the polyfluoroalkyl derivative between 1 and 15, preferably between 1 and 10.
The polyfluorinated derivatives and in particular those defined by the preceding formula in which X is a fluorine atom or an EWG group with EWG being a fluorine atom or a perfluorinated residue of formula C
n′
X
2n′+1
are very particularly suitable as polyfluorinated derivative.
In addition to the electron-withdrawing group as defined above, the carbonyl compound to be condensed can carry, at its carbonyl functional group, either a hydrogen atom or a group selected from C
5
to C
18
aryls, linear or branched C
1
to C
13
alkyls or linear or branched C
2
to C
14
alkenyls, if appropriate substituted. The substituents can in particular be a hydroxyl group, a halogen atom, a C
1
-C
11
alkyl group and/or an amino group.
In addition, it is possible for the two substituents of the carbonyl functional group to be bonded to one another to form a C
4
to C
8
ring.
Mention may be in particular be made, as carbonyl derivatives very particularly
Jacquot Roland
Spagnol Michel
Burns Doane Swecker & Mathis L.L.P.
Desai Rita
Rhodia Chimie
Rotman Alan L.
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