Abstract
Two cis-3,5-dibenzylpiperidin-4-ones have been synthesized to explore the effects of through-bond interactions on the molecular and packing structure of substituted donor-��-acceptor molecules in the solid state. Highlighted is the X-ray crystal structure of cis-3,5-dibenzyl-1-phenylpiperidin-4-one (3) that is disordered; both the equatorial (3-eq) and axial (3-ax) nitrogen epimers are accommodated in the crystal lattice in a 3:1 ratio (at 173 K) based on refined values of occupancy factors. The result allows a unique opportunity to explore both configurations in similar solid-state environments. Extensive first principles calculations, including natural bond orbital analysis, show that the 3-ax configuration is stabilized by through-bond interactions relative to 3-eq. Moreover, the predicted energy differences for the isomers in the gas phase are consistent with the experimental observations. Theoretical studies with structural derivatives reveal how piperidone nitrogen and ring substituents can affect the relative energies of the axial and equatorial forms, and that the axial form is in many cases predicted to be lower in energy.
