Unusual temperature-sensitive protonation behaviour of 4-(dimethylamino)pyridine

Stimuli-responsive, and, in particular, temperature-responsive smart materials have recently received much attention in variety of applications. On the other hand, 4-(dimethylamino)pyridine (DMAP) and related sructures are known as widely used nucleophilic catalysts, and also as specific parts of rationally-designed molecules, where reversible reactions of the pyridinic nitrogen with electrophiles are involved. In our study, we have found an unexpectedly significant impact of temperature on the protonation degree of DMAP derivatives, especially in case of protonation of 4-(dimethylamino)-1-(2,3,5,6-tetrafluoropyridin-4-yl)pyridinium cation, derived from the reaction of DMAP with pentafluoropyridine. Thus, when dissolved in TfOH-SO2ClF-CD2Cl2 acid system at 30 oC, this cation underwent a slight (<7%) protonation on the dimethylamino group, while the temperature decrease to −70 oC resulted in its complete protonation. Notably, such scale of this phenomenon has never observed before for other weak nucleophiles, being many times lower at the same change of temperature. The mechanistic aspects of these intriguing results are discussed.