Intramolecular dynamics in 4- to 6-membered saturated azacycles: A MM3 study

We show that the MM3 force field provides a reasonable modeling of the transition states of dynamic processes related to ring inversion for azetidines, pyrrolidines and piperidines. These involve isolated ring inversion (RI) and concerted ring inversion-nitrogen inversion-C-N rotation (RINIR). Pseudorotation and concerted pseudorotation-nitrogen inversion are additional processes for piperidines. The schemes of conformational transformations (including a relationship of conformers with corresponding transition states) were established for these amines using a normal mode vibrational analysis. Pyramidal nitrogen inversion was found to occur only as the RINTR process for azetidine and pyrrolidine compounds, while nitrogen inversion as well as RINIR are inherent to N-Me piperidine. Only the Cs mode was attributed to interconversion of the piperidine ring (differing from the known cyclohexane case). The designed conformational schemes allowed the reassignment of the previously measured barriers (NMR) for these cyclic amines.