SYMMETRY-MODIFIED CONFORMATIONAL MAPPING AND CLASSIFICATION OF THE MEDIUM RINGS FROM CRYSTALLOGRAPHIC DATA .2. EXO-UNSATURATED AND HETEROCYCLIC 7-MEMBERED RINGS

Crystallographic results derived from the Cambridge Structural Database (CSD) have been used to perform a systematic conformational analysis for methylenecycloheptane, oxocycloheptane, azocycloheptane, oxepane, azepane and for the epsilon-lactone and epsilon-lactam fragments. Conformational mappings based on symmetry-adapted deformation coordinates and principal component scores show that ring conformations in these fragments fall almost exclusively on the chair-twist-chair pseudorotation pathway. Symmetry-modified Jarvis-Patrick clustering has been used to generate conformational classifications in a semi-automated manner. A manual classification was preferred for the oxocycloheptanes due to wide conformational diversity within a rather small data set. Energy calculations have also been carried out for these systems using force-field methods and a novel conformation-hunting algorithm that attempts to locate all local minima without recourse to ring cleavage and reformation. There is good qualitative agreement between the crystallographic observations of conformation and the calculated features of the potential energy hypersurface, despite the wide variety of substitution patterns covered by the crystallographic results.