Perfluoroalkylation method and reagent therefor

Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing

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564503, 570124, 570134, C07C21500, C07C 2300, C07C 1908

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active

060969261

DESCRIPTION:

BRIEF SUMMARY
The subject-matter of the present invention is a process of use in perfluoroalkylation and a reactant for making use of this process. The invention more particularly relates to a reactant and a process for grafting a substituted difluoromethyl group onto a compound containing at least one electrophilic functional group. It more particularly relates to a technique for perfluoroalkylating different compounds by addition or nucleophilic substitution reactions typically carried out with organometallic derivatives.
Perfluoroalkylation techniques, or equivalent techniques, generally use derivatives of the perfluoroalkyl iodide type, in the presence of zinc. This technique is thus expensive, while requiring plants for the treatment of the metal wastes which it is advisable to treat, as zinc is a significant pollutant of water courses.
Other techniques, where the perfluoroalkyl radical does not form a stabilized reactive intermediate of the organometallic type, are generally difficult to employ because of the very low stability of the free perfluoro anions in the reaction mixtures. The latter generally result in products of the carbene type, which, when they react, have lost one of their substituents.
This is why one of the aims of the present invention is to provide a reactant which makes possible perfluoroalkylation according to a mechanism of the type involving a carbanion, without resorting to organometallic derivatives of transition metals, such as zinc.
Attempts have often been made to use perfluorocarboxylic acids as source of perfluoroalkyl radicals, more generally of trifluoromethyl radicals, by employing decomposition reactions targeted at removing the carboxyl fragment from the said acids with release of carbon dioxide. However, the successes which had been achieved were very mixed and used particularly complicated catalytic systems. The perfluoroalkyl radicals or their equivalents generated by the decomposition of the said perfluorocarboxylic acids were, in addition, unstable in the reaction mixture and required the use of stabilizing agents.
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 from fluoroform and showed that it was very difficult to obtain positive results in the absence of the base, composed of the pyrrolidonyl anion in combination with a quaternary ammonium cation, this being under the express condition that this base was generated by electrolysis.
During this comparative study, taking, as test reaction, the trifluoromethylation of benzaldehyde according to the so-called Barbier technique (which will be given in detail hereinbelow), this writer concluded that the results obtained from other bases gave zero or poor yields and that the side reactions, and in particular the Cannizzaro reaction (disproportionation of benzaldehyde to benzoic acid and benzyl alcohol), predominated [but the procedures relating to the usual bases (potassium tert-butoxide, sodium hydride, and the like) are not described therein].
However, the techniques using the electrogenerated bases described by this writer require, on the one hand, complex equipment and, on the other hand, a dexterity such that they are problematic to reproduce and extremely difficult to extrapolate to industrial scales. Finally, the use of quaternary ammonium compounds, which are very hygroscopic, implies great care.
The present invention provides a remedy for the disadvantages of the existing processes by providing a reactant which is non-toxic to the environment and which is capable of resulting in the desired products with a satisfactory yield. These aims and others which will appear subsequently are achieved by means of a process which comprises a stage in which a material of formula RfH and a base (or a species capable of generating a strong base in the presence of a compound containing mobile hydrogen, such as, for example, toluene; mention may be

REFERENCES:
CA: 126 : 72214 abstract of JP 08311036, Nov. 1996.

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