Dynamic Structure of Molecules in Solution According to NMR Data and Quantum Chemical Calculations: V. Conformations and Acid–Base Equilibria of N-Benzylideneaniline Derivatives

The dynamics of restricted internal rotation of benzene rings in N-benzylideneaniline derivatives and their protonated forms have been studied by NMR spectroscopy and quantum chemical calculations. 15N–1H and 15N–13C spin–spin coupling constants have been determined for a series of [15N]-enriched N-benzylideneanilines substituted at the ortho position of the benzene ring linked to the CH=N carbon atom. The conformation of their molecules has been found to strongly depend on the substituent nature. The presence of a methyl group weakly affects the molecular conformation in going from the neutral to protonated form. In contrast, the protonated forms of compounds with fluoro, hydroxy, and methoxy substituents are additionally stabilized (by 6–7 kcal/mol) due to hydrogen bonding between the heteroatom and proton on the azomethine nitrogen atom, which leads to rotation of the substituted benzene ring by 180°. The change of conformation upon protonation of such molecules can be utilized in the design of new pH-dependent molecular switches. The energy of the pH-induced molecular switching of N-(2-fluorobenzylidene)[15N]aniline is ~7 kcal/mol, which is one of the highest values for pH-dependent molecular switches.