Determination of the pKa Value of a Brønsted Acid by 19F NMR Spectroscopy

Brønsted acids, such as phosphoric acids derived from chiral 1,1′-bi-2-naphthol (BINOL), are important catalysts in the formation of carbon–carbon and carbon–heteroatom bonds, for example. The catalytic activity of these Brønsted acids is strongly linked to their acidity, and as such, the evaluation of compounds to determine pK_a values provides insight into their catalytic activity. Herein, a ¹⁹F{¹H} NMR methodology is detailed to determine the pK_a of a fluorinated binaphthyl-derived phosphinic acid, rac-1, in acetonitrile and in the presence of a fluorinated sulfonamide reference compound (2–4). The approach was tested initially using 2 and 3, with the ΔpK_a (0.08) in strong agreement with previously reported values (6.6 for 2 and 6.68/6.73 for 3). Sigmoidal curves of normalised chemical shift change (Δδ) against equivalents of the base phosphazene P₁-^tBu added overlapped for 2 and 3, but in the case of rac-1 and either 2, 3 or 4, there was significant separation. A variety of different approaches for determining the ΔpK_a were compared. Values of pK_a determined when the normalised Δδ was 90% were optimal for 2 and 3, whereas a normalised Δδ of 75% was optimal for 4, resulting in the pK_a of rac-1 being determined to be 8.47–8.71.