Quantifying the ability of the CF₂H group as a hydrogen bond donor

The CF₂H group can act as a hydrogen bond donor, serving as a potential surrogate for OH or SH groups but with a weaker hydrogen bond donation ability. Here, we describe a series of CF₂H group-containing moieties that facilitate hydrogen bond interactions. We survey hydrogen bond donation ability using several established methods, including ¹H NMR-based hydrogen bond acidity determination, UV-vis spectroscopy titration with Reichardt's dye, and ¹H NMR titration using tri-n-butylphosphine oxide as a hydrogen bond acceptor. Our experiments reveal that the direct attachment of the CF₂H group to cationic aromatic systems significantly enhances its hydrogen bond donation ability, a result consistent with theoretical calculations. We anticipate that this chemistry will be valuable for designing functional molecules for chemical biology and medicinal chemistry applications.