Gas-Phase 1H NMR Studies of Internal Rotation Activation Energies and Conformer Stabilities of Asymmetric N,N-Disubstituted Formamides and Trifluoroacetamides

Abstract

Activation parameters and conformational stabilities characterizing the internal rotation about the peptide bond in a series of N,N-asymmetric dialkylformamides (HCONR1R2: R1 = CH3, R2 = propyl, butyl, and isopropyl) and N,N-asymmetric dialkyltrifluoroacetamides (F3CCONR1R2: R1 = CH3, R2 = propyl, butyl, and isopropyl) are determined from temperature-dependent gas-phase 1H NMR spectra. Conformer free energy differences, ΔG0298(syn−anti), in cal mol-1, and activation free energies, ΔG⧧298, in kcal mol-1 , for the formamides are −83(14)/19.4(0.1) for R2 = propyl, −80(14)/19.3(0.1) for R2 = butyl, and −91(13)/19.1(0.1) for R2 = isopropyl and for the trifluoroacetamides 178(24) /16.8(0.1) for R2 = propyl, 191(53)/16.6(0.1) for R2 = butyl, and 218(29)/16.3(0.1) for R2 = isopropyl. The preferred conformer in both the gas and liquid phases has the N-methyl group syn to the carbonyl oxygen in the formamide systems and the N-methyl group anti to the carbonyl oxygen in the trifluoroacetamides. The gas-phase results are compared to liquid-phase values.