Compositions – Chemically interactive reactants – Organic reactant admixed with inorganic reactant
Reexamination Certificate
1999-07-19
2001-03-20
Shaver, Paul F. (Department: 1621)
Compositions
Chemically interactive reactants
Organic reactant admixed with inorganic reactant
C252S183110
Reexamination Certificate
active
06203721
ABSTRACT:
This application is an application under 35 U.S.C. Section 371 of International Application Number PCT/FR97/02062, filed on Nov. 17, 1997.
The present invention relates to a process useful for perfluoroalkylation and to a reagent for implementing this process. It relates more particularly to a reagent and a process for grafting a substituted difluoromethyl group onto a compound containing at least one electrophilic functional group. It relates more particularly to a technique for perfluoroalkylating various compounds by nucleophilic substitution or addition reactions which are typically carried out by organometallic derivatives.
Perfluoroalkylation or equivalent techniques generally employ derivatives of the perfluoroalkyl bromide or iodide type in the presence of zinc. This technique is therefore expensive, and necessitates installations for processing the metallic wastes, which need to be treated since zinc is a major pollutant of waterways. Furthermore, compounds of the trifluoromethyl bromide type contribute considerably to the greenhouse effect.
Other techniques, in which the perfluoroalkyl radical does not form a stabilized reactive intermediate of the organometallic type, are generally difficult to implement owing to the very low stability of the free perfluorinated anions in the reaction media. These techniques generally lead to products of the carbene type which, when they react, have lost one of their substituents. Therefore, one of the aims of the present invention is to provide a reagent which permits perfluoroalkylation according to a mechanism of the type involving a carbanion without requiring the use of organometallic compounds of transition metals such as zinc.
Attempts have often been made to use perfluorocarboxylic acids as a source of perfluoroalkyl radicals and, more generally, of trifluoromethyl radicals, by employing decomposition reactions whose aim is to remove the carboxyl fragment of the said acids, in the course of which carbon dioxide is released. However, the successes which have been achieved have been very modest and have used particularly complex catalyst systems. The perfluoroalkyl radicals, or their equivalents, brought into being by the decomposition of the said perfluorocarboxylic acids, moreover, have been unstable in the reaction medium and have necessitated the use of stabilizers.
More recently, Shono, in an article entitled “a novel trifluoromethylation of aldehydes and ketones promoted by an electrogenerated base” and published in J. Org. Chem. 1991, 56, 2-4, attempted to carry out perfluoromethylation reactions starting from fluoroform and showed that it was very difficult to obtain positive results in the absence of the base consisting of the pyrrolidonyl anion in combination with a quaternary ammonium cation and that this was so only subject to the express proviso that the said base had been brought into being by electrolysis.
In the course of this comparative study, which took as the test reaction the trifluoromethylation of benzaldehyde by the technique known as Barbier's technique (which consists in adding base and fluoroform to the substrate), this author concluded that the results obtained starting from other bases gave yields which were zero or mediocre and that the competing reactions, and especially the Cannizaro reaction (dismutation of benzaldehyde to benzoic acid and benzyl alcohol), were predominant [however, the procedures relating to the usual bases (potassium tert-butoxide, sodium hydride, etc) are not described therein].
However, the techniques described by this author and using bases brought into being by electrolysis require, on the one hand, a complex apparatus and, on the other hand, such dexterity that they are difficult to reproduce and extremely difficult to scale up to the industrial scale. Finally, the use of quaternary ammoniums, which are very hygroscopic, involves a great deal of care.
The object of the present invention is to overcome the disadvantages of the existing processes by providing an environmentally benign reagent which is capable of leading to the desired products with a satisfactory yield.
Another aim of the present invention is to provide reagents and operating conditions which overcome the disadvantages of quaternary ammoniums and which therefore allow them to be used.
These aims and others which will become evident below are achieved by means of a reagent which comprises at least one of the compounds of formula:
in which Y represents a chalcogen atom, advantageously oxygen;
M
+
represents a cation, advantageously a monovalent cation and preferably a cation selected from alkali metals and phosphoniums;
R
1
is a radical selected from hydrogen, hydrocarbon radicals such as aryl (including alkylaryl) and alkyl (including aralkyl and cycloalkyl);
R
2
is a radical selected from hydrocarbon radicals such as aryl (including alkylaryl), alkyl (including aralkyl and cycloalkyl), and from amine functions, which are advantageously persubstituted (that is, their nitrogen no longer carries hydrogen), acyloxy functions and hydrocarbyloxy functions, with the provisos that, when M
+
is alkali metal or phosphonium and R1 is hydrogen, R2 is neither phenyl nor dimethylamino;
and that, when M+ is quaternary ammonium, the said reagent additionally comprises at least [lacuna] trivalent nitrogen derivative which is persilylated (by persilylated is meant a derivative which contains no hydrogen and at least two silyl groups, preferably three);
and which reagent can be obtained by contacting, in a polar medium which is non-protic or not very protic, a substance of formula RfH and a base with a substrate which carries at least one double bond of the type >C═Y and has the formula
The addition compound of fluoroform with DMF had possibly already been obtained, although not identified, during the test (by the Grignard method) used as an example in the French application FR95/13996, which was unpublished on the filing date of the earliest priority application (FR96/14133) of the present application.
According to the present invention, the said reagent can additionally comprise a polar solvent (or solvent mixture) which is non-protic or not very protic.
According to a preferred embodiment, the said compound of formula IV is present in a concentration of at least one millimole per liter, advantageously at least 5 millimoles per liter and, preferably, 10 millimoles per liter.
The abovementioned reagent can be obtained by the use of another reagent, which is also useful for obtaining a fluoro derivative and which comprises, for successive or simultaneous addition:
a silicophilic base; and
a substance of formula Rf—Z where Z is selected from hydrogen and —Si(R′)
3
, in which the radicals R′ are identical or different and are hydrocarbon radicals of 1 to about 20 carbon atoms, advantageously 1 to 10 and, preferably, 1 to 5, the total carbon number of Rf—Si(R′)
3
being advantageously not more than 50, preferably not more than 30;
with the proviso that, if Z is hydrogen, it additionally comprises a persilylated trivalent nitrogen derivative, advantageously in an at least stoichiometric amount.
The persilylated trivalent nitrogen derivative can in particular be a persilylated amide whose anion is highly basic (for example persilylated formamide); however, preference is given to persilylated amines.
For various reasons, especially that of economy, the case where Z is H is preferred. In this case, the reagent comprises, for successive or simultaneous addition:
a substance of formula RfH;
a silicophilic base; and
a persilylated trivalent nitrogen derivative.
The reaction can be represented as follows:
RfH+B
−
+>N—Si(R′)
3
→Rf
−
+>NH+B—Si(R′)
3
with, in general, an equilibrium as follows:
Rf
−
+>NH←→RfH+>N
−
It is desirable for the base obtained (>N
−
) after desilylation of the said persilylated trivalent nitrogen derivative to be at least as strong as the met
Langlois Bernard
Large Sylvie
Roques Nicolas
Russell James
Saint-Jalmes Laurent
Rhodia Chimie
Seugnet Jean-Louis
Shaver Paul F.
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