Sterically crowded five-membered heterocyclic systems. Part 2. Conformation of 2,2,5,5-tetramethylpyrrolidin-3-ol from nuclear magnetic resonance spectroscopy, crystal structure, and molecular mechanics calculations

Abstract

The conformation of 2,2,5,5-tetramethylpyrrolidin-3-ol (2) was investigated by ¹H n.m.r. spectroscopy, X-ray diffraction, and molecular mechanics calculations. In solution there is an equilibrium between the forms of the pyrrolidine ring with axial and equatorial orientations of the hydroxy group. The temperature dependence of the ³J(HH) coupling constants indicates a somewhat lower energy for the axial conformers. The puckering of the CH₂CHOH part of the ring was estimated from the extended R value method, optimized for a five-membered ring, to be 32.9° at 263 K. The crystal structure of (2) was solved by direct methods and refined to R = 0.045. Two independent molecules in the asymmetric unit adopt nearly identical conformations with the pyrrolidine ring in the ²T₃ twist form with the hydroxy group and the nitrogen proton in an axial orientation. Molecules are connected by O–H ⋯ N hydrogen bonds (O ⋯ N = 2.82 Å) into chains along the z-axis. There are also weak N–H ⋯ O bonds (N ⋯ O = 3.40 Å) between molecules in neighbouring chains. The conformational space of (2) was explored by molecular mechanics calculations. Several local energy minima were characterized. In all of them the ring is flattened around the fully substituted C-2 or C-5 atoms. The energy difference between these conformations is of the order of 5–7 kJ mol^–1. The conformation observed in the crystal corresponds very well to the calculated global energy minimum conformation.