Conformational study of the structure of free 18-crown-6

A conformational search was performed for 18-crown-6 using the CONLEX method at the MM3 level. To have a more accurate energy order of the predicted conformations, the predicted conformations were geometry optimized at the HF/STO-3G level and the 198 lowest energy conformations, according to the HF/STO-3G energy order, were geometry optimized at the HF/6-31+G* level. In addition, the 47 nonredundant lowest energy conformations, according to the MP2/6-31+G* energy order at the HF/6-31+G* optimized geometry, hereafter the MP2/6-31+G*//HF/6-31+G* energy order, were geometry optimized at the B3LYP/6-31+G* level. According to the MP2/6-31+G*//B3LYP/6-31+G* energy order, three conformations had energies lower than the experimentally known Ci conformation of 18c6. At the MP2/6-31+G*//B3LYP/6-31+G* level, the S6 lowest energy conformation is more stable by 1.96 kcal/mol than this Ci conformation. This was confirmed by results at the MP2/6-31+G* level with an energy difference of 1.84 kcal/mol. Comparison between the structure of the S6 conformation of 18c6 and the S4 lowest energy conformation of 12-crown-4, as well as other important conformations of both molecules, is made. It is concluded that the correlation energy is necessary to have an accurate energy order of the predicted conformations. A rationalization of the conformational energy order in terms of the hydrogen bonding and conformational dihedral angles is given. It is also suggested that to have a better energy order of the predicted conformations at the MM3 level, better empirical force fields corresponding to the hydrogen bond interactions are needed. © 2005 American Chemical Society.