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

Activation parameters and conformational stabilities characterizing the internal rotation about the peptide bond in a series of N,N-asymmetric dialkylformamides (HCONR<INF>1</INF>R<INF>2</INF>:  R<INF>1</INF> = CH<INF>3</INF>, R<INF>2</INF> = propyl, butyl, and isopropyl) and N,N-asymmetric dialkyltrifluoroacetamides (F<INF>3</INF>CCONR<INF>1</INF>R<INF>2</INF>:  R<INF>1</INF> = CH<INF>3</INF>, R<INF>2</INF> = propyl, butyl, and isopropyl) are determined from temperature-dependent gas-phase ¹H NMR spectra. Conformer free energy differences, ΔG⁰<INF>298</INF>(syn−anti), in cal mol^-1, and activation free energies, ΔG^&thermod;<INF>298</INF>, in kcal mol^-1 , for the formamides are −83(14)/19.4(0.1) for R<INF>2</INF> = propyl, −80(14)/19.3(0.1) for R<INF>2</INF> = butyl, and −91(13)/19.1(0.1) for R<INF>2</INF> = isopropyl and for the trifluoroacetamides 178(24) /16.8(0.1) for R<INF>2</INF> = propyl, 191(53)/16.6(0.1) for R<INF>2</INF> = butyl, and 218(29)/16.3(0.1) for R<INF>2</INF> = 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.