Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2000-07-05
2003-04-22
Rotman, Alan L. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C570S128000
Reexamination Certificate
active
06552228
ABSTRACT:
A subject-matter of the present invention is a process for the synthesis of compounds comprising both a perfluorinated carbon and an aniline functional group from its carbamoyl fluoride or from the corresponding isocyanate comprising chlorine atoms in place of fluorine atoms on the perfluorinated carbon.
The perfluorinated carbon is, in this case, a carbon of aliphatic nature, that is to say that it has sp
3
hybridization.
The present invention is more particularly targeted at a process for exchange and hydrolysis in the same reaction medium (that is to say without intermediate isolation), in particular based on hydrofluoric acid, and often in the same reactor.
In recent times and more specifically in the last decade, compounds comprising a perfluorinated aliphatic atom have become increasingly important in the field of agrochemistry and pharmaceuticals. This is because these perfluorinated products, generally comprising a perfluoromethyl or perfluoroethyl radical, have physiological properties which render the molecules which comprise them particularly active.
Numerous proposals have consequently been put forward for a process resulting in such products. Generally, the fluorinating agent is liquid hydrofluoric acid and the starting substrate is an isocyanate.
Mention may thus be made of the Occidental Chemical Corporation Patents No. EP-A-129 214 and the patent of the legal predecessor of the Applicant Company, namely the European patent filed on behalf of Rhône-Poulenc Spécialités Chimiques under No. 152 310. More recently, a European patent on behalf of Hoechst AG has been published under No. 639 556.
These documents makes known various alternative treatment forms in the hydrofluoric acid route.
According to this technique, the starting point is the protection of the amine functional group with an isocyanate functional group, for example by phosgenation. The carbon which in the final stage must be in a perfluorinated form is then chlorinated, generally in the radical fashion. Finally, the chlorinated compound thus obtained is subjected to a stage of chlorine/fluorine exchange in an anhydrous liquid hydrofluoric acid medium.
Two alternative forms have been explored to date: the release of the amine by means of heating in the presence of a large excess of hydrofluoric acid (anhydrous, of course) to give fluorophosgene or alternatively hydrolysis in a hydrofluoric acid medium with a relatively small amount of water.
The technique using the decomposition of carbamoyl fluorides to fluorophosgene exhibits the undoubted disadvantage of being accompanied by the evolution of fluorophosgene, the toxicity of which is supposed to be much greater than that of phosgene proper, which was used as a poison gas during the First World War.
Another disadvantage of this technique is the increased consumption of hydrofluoric acid, which is a relatively expensive reagent since it has to be used in a large excess.
The other techniques, namely techniques using in situ hydrolysis of the carbamoyl fluoride, give yields which are far from being excellent.
These low yields put a serious strain on the cost price of the final product and thus on the profitability of the complete operation.
Furthermore, the use of very large excesses of hydrofluoric acid, which involves a, to say the least, expensive recycling and inventory, as well as a subsequent dehydration, is also extremely penalizing as regards the cost price of the operation.
Finally, during the study which has led to the present invention, it was shown that even when the aromatic nucleus of the molecule was depleted in electrons, the reactivity of the carbamoyl fluorides was very high and resulted in many by-products which were harmful to the conversion yield, that is to say to the selectivity of the conversion.
It is for this reason that one of the aims of the present invention is to provide a process for obtaining aniline, additionally comprising a perfluorinated carbon atom, from the corresponding isocyanate or carbamoyl fluoride, which makes it possible to obtain high yields, that is to say exhibiting a conversion yield (CY) at least equal to 75%, preferably to 80%, more preferably to 90%.
Another aim of the present invention is to provide a process of the above type which makes it possible to have a degree of conversion (DC) at least equal to 80%, preferably at least equal to 90%.
Another aim of the present invention is to provide a process of the above type which makes it possible to have a reaction yield (RY=DC×CY) at least equal to 80%, preferably at least equal to 90%.
Another aim of the present invention is to provide a process of the above type which makes it possible to obtain a good yield with a minimum amount of hydrofluoric acid.
Another aim of the present invention is to provide a process of the above type which makes it possible to avoid the evolution, or at least to limit the evolution, of fluorophosgene.
These aims and others which will become apparent subsequently are achieved by means of a process for bringing a carbamoyl fluoride or an isocyanate into contact with hydrofluoric acid in the liquid phase and with water, characterized in that the ratio of the carbamoyl fluoride to the hydrofluoric acid (HF/substrate) is maintained for the duration of the reaction at a value at least equal to approximately 4, advantageously to 4.0, preferably to 5, more preferably to 6, and in that this ratio is advantageously at most equal to approximately 11, preferably to 10, more preferably to 8.
In the present description, the term “approximately” is employed to emphasize the fact that the values which follow it correspond to values which have been rounded off mathematically and in particular that, in the absence of a decimal point, when the figure or figures furthest to the right of a number are zeros, these zeros are positional zeros and not significant figures, unless, of course, it is otherwise specified.
As regards the exchange, the upper limit value has only economical importance. However, this low value of the upper limit has an effect on the addition of the water, as will be made known later.
This is because the studies which have led to the present invention have shown that, starting from the ratio of 4, the hydrofluoric acid plays a protective role with respect to side reactions involving the carbamoyl fluoride. Below these values, a large amount of side reactions, in particular formation of biuret, reaction in which heavy products are formed by condensation of the acyl halide with the aromatic nucleus, and the like, is observed.
It should be pointed out that the constraint relating to the ratio of 4 is strict and that, if the ratio is below this value or if the ratio falls below this value during the reaction, it is advisable to add hydrofluoric acid again in order to maintain this ratio above 4 during the reaction.
Thus, for example, if carbamoyl fluoride is introduced into the hydrofluoric acid in the form of an isocyanate and there are 3 chlorine atoms to exchange with fluorine, it will be necessary to add sufficient liquid hydrofluoric acid for this value to be observed throughout the reaction. This addition may just as easily be carried out at the beginning of as during the exchange. The first option is the simpler.
The simpler, in the preceding case, is to observe an overall ratio of the order of 8, namely 4, in order to provide for the reactions for exchange and for addition to the isocyanate functional group of the substrate, and 4, in order to provide for a good ratio of carbamoyl fluoride to hydrofluoric acid.
According to the present invention and in view of the constraints occasioned by a value of less than or equal to approximately 20 for the ratio of the carbamoyl fluoride to the hydrofluoric acid (HF/substrate), it has been shown that it is preferable for the addition of water to take place only at specific phases of the process.
If it is desired to control the amount of water in the medium, the hydrofluoric acid used is, of course, essentially anhydrous. However, it is possible to envisage the additio
Guidot Gilbert
Rochin Christophe
Saint-Jalmes Laurent
Reys Hector M
Rhodia Chimie
Rotman Alan L.
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