Conformational preferences for some 3-(4′-substituted phenylsulfonyl)-1-methyl-2-piperidones through spectroscopic and theoretical studies

The analysis of the infrared (IR) carbonyl band of some 3-(4′-substituted phenylsulfonyl)-1-methyl-2-piperidones 1–5 bearing as substituents: OMe 1, Me 2, H 3, Cl 4 and NO2 5, supported by B3LYP/6-31G(d,p) calculations along with NBO analysis (for 1, 3 and 5) and X-ray diffraction (for 5), indicated the existence of three stable conformations i.e. quasi-axial (q-ax), syn-clinal (s-cl) and quasi-equatorial (q-eq). In the gas phase, the q-ax conformer is calculated as the most stable (ca. 88%) and the least polar, the s-cl conformer is less stable (ca. 12%) but more polar, and the q-eq conformer is the least stable (ca. 1%) and the most polar of the three conformers evaluated. The sum of the most important orbital interactions from NBO analysis and the trend of the electrostatic interactions accounts for the relative populations as well as for the νCO frequencies of the q-ax, s-cl and q-eq conformers calculated in the gas phase. The unique IR νCO band in CCl4 may be ascribed to the most stable q-ax conformer. The more intense (60%) high frequency doublet component in CHCl3 may be assigned to the summing up of the least stable q-eq and the less stable s-cl conformers, as their frequencies are almost coincident. The occurrence of only a single νCO band in both CH2Cl2 and CH3CN supports the fact that the νCO band of the two more polar conformers appear as a single band. Additional support to this rationalization is given by the single point PCM method, which showed a progressive increase of the q-eq + s-cl/q-ax population ratio going from the gas phase to CCl4, to CHCl3, to CH2Cl2 and to CH3CN. X-ray single crystal analysis of 5 indicates that this compound displays a quasi-axial geometry with respect to the [OCCHS] moiety, and that the 2-piperidone ring assumes a slightly distorted half-chair conformation. In the crystal packing, molecules of 5 are arranged into supramolecular layers linked through CH⋯O interactions along with π⋯π interactions between adjacent benzene rings.