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

Abstract 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 NO 2 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 ν CO frequencies of the q-ax , s-cl and q-eq conformers calculated in the gas phase. The unique IR ν CO band in CCl 4 may be ascribed to the most stable q-ax conformer. The more intense (60%) high frequency doublet component in CHCl 3 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 ν CO band in both CH 2 Cl 2 and CH 3 CN supports the fact that the ν CO 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 CCl 4 , to CHCl 3 , to CH 2 Cl 2 and to CH 3 CN. X-ray single crystal analysis of 5 indicates that this compound displays a quasi-axial geometry with respect to the [O C CH S] 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 C H⋯O interactions along with π ⋯ π interactions between adjacent benzene rings.