Fig. 2. (A) Experimental rotational barriers between two monoamide isomers 4a and 4b were determined by a series of 1D EXSY experiments in different solvents at 298 K (see ESI Chapter 7†). The two isomers were populated in a 1 : 1 ratio and their structures were elucidated via HOESY spectrum. The fastest rotation was measured in wet CDCl₃, whereas the slowest rotation was in deuterated methanol. The experimental rate constants and free energies of rotation are summarised in the table. (b) Rotational barriers in a simple difluoroacetamide 5 as well as conformational preference of difluoromethyl group matches the experimental barrier in chloroform. The Gibbs free energies ΔG₂₉₈ were computed at DLPNO-CCSD(T1)/def2-QZVPP level of theory based on B3LYP-D3(BJ)/def2-TZVP structures and include SMD solvation correction in chloroform.