Dynamic NMR studies of base-catalyzed intramolecular single vs. intermolecular double proton transfer of 1,3-bis(4-fluorophenyl)triazene

The kinetic H/D isotope effects are small, especially in the catalysis by 2, indicating a major heavy atom rearrangement and absence of tunneling. Semi-empirical PM3 and ab initio DFT calculations indicate a reaction pathway via a hydrogen bond switch of the protonated amine representing the transition state. The Arrhenius curves of all processes exhibit strong convex curvatures. This phenomenon is explained in terms of the hydrogen bond association of 1 with the added bases, preceding the proton transfer. At low temperatures, all catalysts are in a hydrogen bonded reactive complex with 1, and the rate constants observed equal to those of the reacting complex. However, at high temperatures, dissociation of the complex occurs, and the temperature dependence of the observed rate constants is affected also by the enthalpy of the hydrogen bond association. Finally, implications of this study for the mechanisms of enzyme proton transfers are discussed.