Hydrolytic instability of C–F bonds in 2,2,2-trifluoroethyl-phosphinic acid systems: formation of carboxymethylphosphinic acid derivatives

Abstract

The trifluoromethyl group in 2,2,2-trifluoroethylphosphonic acid remains stable against hydrolysis. However, in contrast, 2,2,2-trifluoroethylphosphinic acid and its derivatives display unexpectedly low hydrolytic stability of the C–F bond in alkaline solutions. When treated with bases such as alkali metal hydroxides or tetramethylammonium hydroxide, these compounds undergo hydrolysis of the R–CF₃ group, producing R–COO⁻ and F⁻ quantitatively. This phenomenon is easily observed using ¹⁹F NMR spectroscopy, which provides a clear analytical signature of the transformations. Although the resulting carboxymethylphosphinic acid derivatives somewhat resemble malonic or phosphonoacetic acid derivatives, they demonstrate remarkable stability in both strong acidic and alkaline solutions, where decarboxylation analogous to the malonic ester synthesis or dephosphorylation similar to the Horner–Wadsworth–Emmons reaction would be expected. The observed hydrolytic instability of the 2,2,2-trifluoroethylphosphinic acid fragment brings the possibility to introduce a bifunctional carboxymethylphosphinic acid chelating group(s) in, e.g., chelators used in radiomedicine.