Rotational isomerism about the C_α-CO bond in proline derivatives

Abstract

The 270 MHz ¹H n.m.r. spectrum of benzyloxycarbonyl-Pro-N-methylamide in CDCl₃ is exchange broadened at 293° K. Spectral lines due to two species are frozen out at 253° K and a dynamically averaged spectrum is obtained at 323° K. A selective broadening of the C^β and C^γ resonances in the ¹³C n.m.r. spectrum is observed at 253° K, with a splitting of the C^β and C^γ resonances into a pair of lines of unequal intensity. A similar broadening of C^β and C^γ peaks is also detected in pivaloyl-Pro-N-methylamide where cis-trans interconversion about the imide bond is precluded by the bulky t-butyl group. The rate process is thus attributed to rotation about the C^α-CO bond (ψ) and a barrier (ΔG^#) of 14kcal mol^-1 is estimated. ¹³C n.m.r. data for pivaloyl-Pro-N-methylamide in a number of solvents is presented and the differences in the C^β and C^γ chemical shifts are interpreted in terms of rotational isomerism about the C^α-CO bond.