Compositions – Compositions containing a single chemical reactant or plural... – Organic reactant
Reexamination Certificate
1998-12-01
2002-10-15
McKane, Joseph K. (Department: 1626)
Compositions
Compositions containing a single chemical reactant or plural...
Organic reactant
C562S605000
Reexamination Certificate
active
06464895
ABSTRACT:
The present invention relates to a reagent and a process for grafting a substituted difluoromethyl group onto a compound containing at least one electrophilic function. The invention relates more particularly to a technique for perfluoroalkylating various compounds by nucleophilic substitution reactions or addition reactions typically performed by organometallic derivatives.
The present invention further relates to a process for the preparation of fluoroalkanesulphinic and sulphonic acids and their salts.
It relates more particularly to the preparation of polyhalosulphinic and sulphonic, especially difluoro- or trifluoromethanesulphinic and sulphonic, acids.
The techniques of perfluoroalkylation, or equivalent techniques, generally use derivatives of the perfluoroalkyl iodide type, in the presence of zinc. This technique is thus expensive, while at the same time requiring treatment plants for the metallic waste which should be treated, since zinc is a great pollutant of water courses.
The other techniques, in which the perfluoroalkyl radical does not form a stabilized reactive intermediate of the organometallic type, are generally difficult to carry out on account of the very low stability of the free perfluoro anions in the reaction media. These anions generally lead to products of the carbene type, by loss of one of their substituents.
Perhaloalkanesulphonic acids and more particularly trifluoromethanesulphonic acid are used as catalysts or as intermediates in organic synthesis.
Initially, the only known process for the manufacture of trifluoromethanesulphonic acid was electro-chemical fluorination as described especially by R. D. Howels, J. D. McCown in Chemical Reviews, 1977, 77, 69.
The process for the preparation of trifluoromethanesulphinic acid, which is described in the European patent published under the number EP-165 135, is also known which consists in exposing to sulphur dioxide a metal selected from zinc, aluminium, manganese, cadmium, magnesium, tin, iron or even nickel and cobalt, in an aprotic polar solvent and then in adding a trifluoromethyl halide at a pressure greater than 10
5
Pa. This process makes it possible to obtain a product in the form of trifluoromethanesulphinate with good yields. The sulphinate obtained is present in a medium containing a large quantity of zinc salt. The separation of the sulphinate and the other zinc salts poses, at the industrial level, a problem which has to be solved.
Moreover, this technique, as well as the one described in the French application published under the number 2,593,808, required the use of perfluoroalkyl bromides which are reputed to be particularly harmful for the atmospheric layers, especially because of their high greenhouse effect and their reputedly damaging effect on ozone.
Consequently, one of the aims of the present invention is to provide a reagent which allows a perfluoroalkylation according to a mechanism of the type involving a carbanion, without using organometallic reagents of transition metals such as zinc.
Accordingly, another aim of the present invention is to provide a reagent for the preparation of oxysulphide-containing and fluorine-containing organic derivatives, by reacting with an oxide of sulphur, which makes it possible to use products which are less harmful for the environment than trifluoromethyl bromide while remaining low in price.
It has often been sought to use as a source of perfluoroalkyl radicals, more generally of trifluoromethyl radicals, perfluorocarboxylic acids, by carrying out decomposition reactions aimed at eliminating the carboxylic fragment from the said acids, releasing carbon dioxide. However, the successes which were obtained were very mitigated and used particularly complex catalytic systems. The perfluoroalkyl radicals or equivalents thereof generated by the decomposition of the said perfluorocarboxylic acids were, in addition, unstable in the reaction medium and required the use of stabilizing agents.
G. Stahly has also reported, in Journal of Fluorine Chemistry, 45 (1989), 431-433 and in U.S. Pat. No. 4,990,699, that the thermal decomposition of perfluoroalkanoic salts in the presence of aromatic compounds such as 1,3,5-trinitrobenzene leads to the formation of trifluoromethyl anions CF
3
−
, demonstrated by the formation of a Meisenheimer complex. The complex may subsequently be converted by oxidation to give the perfluoroalkyl derivative on the corresponding aromatic ring.
However, the need to carry out this oxidation makes this route for the perfluoroalkylation of aromatic derivatives tedious.
The present invention proposes to circumvent the drawbacks of the existing processes by providing a reagent which is non-hazardous to the environment and capable of leading to the desired products in a satisfactory yield.
In the course of the study which led to the present invention, it has been demonstrated that a fluoroalkylation reaction was possible with a fluorocarboxylic acid salt, without a catalyst and without an agent capable of stabilizing the various envisaged intermediates obtained during the decomposition of the various perfluorocarboxylic acids.
It appeared that, in order thus to obtain a decomposition of the fluorocarboxylic acids, two conditions were essential; one is the choice of the solvent, and the other the content of impurities in the mixture constituting the reagent according to the present invention. Thus, it was possible to demonstrate the absolutely critical role of the content of labile hydrogens in the system, or more precisely of releasable protons, which must be less than the content of fluoro groups released by the decomposition of the fluorocarboxylic acid salts. The terms labile hydrogen and releasable proton refer to a hydrogen atom which is capable of being removed out in the form of a proton by a strong base. In practice, these are protons of acidic functions which have a pKa of less than about 20 (by “about”, it is emphasized that the number 20 has only one significant figure).
The above-mentioned aims and others, which will appear later, are achieved by means of a nucleophilic reagent which is useful for grafting a substituted difluoromethyl group onto a compound containing at least one electrophilic function, or which is useful for the synthesis of oxysulphide-containing and fluorine-containing organic derivatives by reacting with an oxide of sulphur, especially sulphur dioxide, wherein said reagent comprises:
a) a fluorocarboxylic acid of formula Ew—CF
2
—COOH where Ew represents an electron-withdrawing atom or group, at least partially salified with an organic or inorganic cation, and
b) a polar aprotic solvent;
and wherein the content of releasable protons carried by its various components, including their impurities, is at most equal to half the initial molar concentration of the said fluorocarboxylic acid.
The electrophilic functions capable of reacting with the reagent of the present invention are the functions which usually react with organometallic reagents and will be detailed later.
The lower the content of releasable protons in the reagent, the lower the risk of side reactions will be and the better the yield will be.
Thus, it is preferable for the content of labile hydrogen atoms in the reagent to be at most equal to 10%, preferably to 1% (in moles), relative to the initial content of the said fluorocarboxylic acid.
The main impurity, as a carrier of labile hydrogen atoms, is generally water, which is capable of releasing up to two hydrogen atoms per molecule.
In general, it is preferable to use carefully dehydrated reagents and solvents, so that the weight content of water in the reagent is at most equal to 1 per 1000 relative to the total mass of the reagent.
Depending on the overall reaction conditions, such water contents may be satisfactory, but in certain cases, it may be advantageous to work at lower levels, for example of about 1 per 10,000.
However, it is not necessarily essential to remove all of the water and a water/fluorocarboxylic acid molar ratio of less than 10% may be tolerated.
Moreover, it w
Forat Gerard
Mas Jean-Manuel
Saint-Jalmes Laurent
Anderson Rebecca
Burns Doane Swecker & Mathis L.L.P.
McKane Joseph K.
Rhodia Chimie
LandOfFree
Reagent and process which are useful for grafting a... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Reagent and process which are useful for grafting a..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Reagent and process which are useful for grafting a... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2994857