Internal rotation about the C–N bond of amides

Abstract

The internal rotation about the C–N bond of formamide (FA), acetamide (AA), N-methylformamide (NMF), N-methylacetamide (NMA), N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) in the gas phase, chloroform and water has been investigated at the HF level of theory with 6-31G(d), 6-31G(d,p) and 6-31+G(d) basis sets in order to figure out the appropriate level of theory in describing the cis–trans isomerization of the X-non-Pro and X-Pro peptide bonds. The conductor-like polarizable continuum model (CPCM) was used to calculate solvation free energies. The conformational electronic energies calculated at three levels predicted satisfactorily the experimental rotational barriers ΔG ‡ of FA, DMF and DMA, and the observed relative enthalpy changes Δ H cis/ trans of cis conformers for NMF and NMA to trans ones in the gas phase. The CPCM method at the HF/6-31+G(d) level predicted well experimental solvation free energies of acetamide derivatives. The ΔG ‡ for FA, NMF, DMF, NMA and DMA, and Δ H cis/ trans for NMF and NMA in chloroform and water were satisfactorily described by the CPCM method at HF/6-31G(d) and HF/6-31+G(d) levels. These results may indicate that the HF/6-31+G(d) level with the CPCM method appears to be the appropriate method in describing the cis–trans isomerization of the X-non-Pro and X-Pro peptide bonds in solutions.