Exocyclic group dynamics

Partitioning of the various modes of reorientation—even for the simplest member of this class, a disaccharide molecule—is not an easy task. For instance, separation of rotatory diffusion from internal oscillations around the glycosidic bonds is not feasible because no ring carbon atom in the disaccharide moiety relaxes exclusively via the overall molecular motion. This problem becomes more serious if the internal motion of exocyclic substituents, such as a hydroxymethyl group, is considered in the process of dynamic modeling. 

The same authors, in a different paper (93JA3494), have shown that the N-R substituent prefers to be equatorial and that the conformation about the exocyclic N-R bond is due to a rapid equilibrium between two nearly eclipsed conformations (cf. Scheme 37b). The second ground state of the dynamic process, the own-conformation (after 180° of rotation), could not be detected experimentally but was calculated by molecular dynamics to be less stable by 5.5 kcal/mol than the preferred, vy -conformers, e.g., 99h (cf. Scheme 37). The transition state in 99b-e and 99g-l occurs when the exocyclic substituent has its maximum interaction with an equatorial methyl group about 120° on either side of the ground state. The dynamic behavior of 99h,i and 99o (R = Bu) was also studied by the MM3 force field (99CEJ449) the authors concluded that the experimental barriers of 99h,i and 99o belong to a complex combination of ring inversion, N-inversion and rotation about the exocyclic bond. 

---