Perfluoroalkylaromatic compounds

Trifluoromethyl-substituted compounds find applications as both pharmaceutical and plant protection products. As these compounds have to undergo rigorous tests before being placed on the market, improved methods are required for the introduction of the trifluoromethyl group which could be applied to the production of ¹⁴C-labelled molecules for use in metabolic studies. Two sources of the trifluoromethyl group mentioned only briefly in the literature, bis(trifluoromethyl)mercury and sodium trifluoroacetate, were both developed as reagents for the synthesis of substituted trifluoromethylbenzenes. Trifluoromethylation with sodium trifluoroacetate was extended to the preparation of alkyl, alkenyl, and heterocyclic trifluoromethyl compounds, and up to three groups were introduced into an aromatic nucleus. The mechanism of this interesting copper-promoted reaction was investigated and an intermediate of the form [CF₃CuI]⁻ is proposed. Introduction of higher perfluoroalkyl groups from their respective sodium perfluoroalkanecarboxylic acids was attempted and the mechanistic features compared with those of the trifluoromethylation reaction. A poly-substituted trifluoromethyl aromatic compound, 1,3,5-tris(trifluoromethyl)benzene, was produced by fluorination of trimesic acid with sulphur tetrafluoride and its chemistry investigated. It is fairly unreactive but readily forms a sterically hindered lithium derivative which undergoes many reactions typical of an organolithlum compound. Mercury and copper derivatives were also prepared and used in coupling reactions with iodobenzene.