Geometrical optimizations, NMR analyses, and novel crystal structures of 3-oxa-7-benzyl-7-azabicyclo[3.3.1]-nonan-9-one and 3-thia-7-benzyl-7-azabicyclo[3.3.1]nonan-9-one; Structural analysis of the corresponding 3,7-diheterabicyclo[3.3.1]nonane hydroperchlorates

An investigation has been made of the structures of the title compounds via theoretical calculations, high resolution NMR analysis, and X-ray diffract ion analysis. Conformational analyses of these compounds in the gas phase w ere performed using ab inito methods with GAUSSIAN 94. Single point calcula tions at the MP4/6-31G level for 3-oxa-7-azabicyclo[3.3.1]nonan-9-one revea led an energy difference of only Delta E = 1.497 kcal/mole between the chai r-chair (CC) and boat-chair (BC) conformers. Full geometry optimization of the oxygen-containing ketone at the Hartree-Fock (HF) level using a 6-31G b asis set indicated only a negligible variation in interatomic distances in the equilibrium geometry when the phenyl group was included in the calculat ion versus when the phenyl group was replaced by hydrogen. Full geometry op timization for the sulfur-containing ketone (phenyl replaced by a hydrogen) at the HF level using the 6-31G basis set again demonstrated that the BC f orm was slightly more stable than the CC form, identical to that found with the oxygen counterpart. Full geometry optimization of the two hydroperchlo rates (phenyl replaced by hydrogen) resulted in the CC form being suggested as the more stable with H-bonding between the hydrogen on nitrogen and the respective heteroatom, a situation which likely enhances stability. Proton NMR analyses of both compounds using NOESY techniques strongly supported a predominance of the BC form in solution for the oxygen-containing ketone. Severe signal overlap in the sulfur ketone (even at 600 MHz) prevented in d epth analysis of the structure. Using NOESY, DQCOSY, and HMBC techniques, N MR analyses of the corresponding hydroperchlorates implied CC forms for eac h in solution. The X-ray diffraction analysis of the oxygen-containing keto ne revealed a CC in the solid state.