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A new method of introducing a trifluoromethyl group into an aromatic ring

✍ Scribed by Marko Zupan; Zvonko Bregar


Publisher
Elsevier Science
Year
1990
Tongue
French
Weight
158 KB
Volume
31
Category
Article
ISSN
0040-4039

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✦ Synopsis


Trifluoromethyi derivatives of aromatic molecules were prepared from aromatic halides, converted to dithiocarboxylic acids through formation of Grigmrd reagents, followed by fluorination with xenon diiluoridc at room temperature. The physicochemical properties and biological activities of various aromatic and heteroaromatic molecules, when functionalised with a trifluoromethyl group, resulted in an increasing popularity of these types of compounds'. However, methods available for direct introduction of a trifluoromethyl group into aromatic or hetreoaromatic compounds are still scarce. Another strategy for the introduction of a trifluoromethyl function into a molecule is based on the use of an appropriate "trifluoromethyl building block" such as trifluoroacetic acid, N-substituted trifluoroacetimidoyl chlorides' etc. Classical approaches for synthesis are bared on the following types of reactions': conversion of an acid group using sulphur tetrafluoride; halogen exchange by the use of Swartz-type catalysts, generation of trifluoromethyl radical either photochemically or thermally by the use of peroxides, reactions proceeding via a "trifluoromethyl-metal" intermediate. Recently the following approaches were recommended: trifluoromethyl-M-X', where M =Zn, Cu, Cd, tri-n-butyl(trifluoromethy1) silanes, methyl fluorosulphonyldifluoroacetate6 and trifluoroacetic acid or trimethylsilyl trifluoroacetate in the presence of xenon difluoride'. We now wish to report a new method of introducing a trifluoromethyl substituent into an aromatic molecule based on the following sequence. Aromatic halides, preferentially bromides, were converted with magnesium into the corresponding Grignsrd reagents, further addition to carbon disulphide resulted in formation of dithiocarboxylic acids that, without prior purification, reacted with xenon difluoride at room temperature in methylene chloride as solvent, giving trifluoromethyl substituted aromatics.


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