Gas-phase NMR studies of N,N-dimethylamides. Inter- and intramolecular contributions to internal rotation activation energies

Abstract

Temperature-dependent gas-phase 'H NMR spectra of six C-substituted TV,TV-dimethylamides (XCON(CH3)2) obtained at 500 MHz are consistent with the following free activation energies, AG*29i (kcal/mol): X = Cl, 15.4 (0.2); Br, 14.1 (0.2); N3, 16.5 (0.1); CN, 19.0 (0.1); CH2F, 15.2 (0.1); CHF2, 17.4 (0.1). For all of the amides studied, the observed first-order unimolecular rate constants are consistent with gas-phase <3*298 values for the internal rotation process which are 1-2 kcal/mol lower than reported condensed phase values and, in each case, consistent with a process proceeding via a transition state which has greater steric requirements than the equilibrium conformation.

Gas-Phase NMR Studies of N,N-Dimethylthioamides. Influence of the Thiocarbonyl Substituent on the Internal Rotation Activation Energies

“…The effect of substituent electronegativity on amide rotational barriers has been studied in both the gas 35 and solution phase. 36,37 In both phases, the C-N rotational barriers in the series of N,Ndimethylcarbamyl halides (X ) Br, Cl, F) increase with halogen substituent electronegativity.…”

“…Model 1 predicts that the transition state is destabilized by electronegative substituents since its carbon is positively charged and the barrier should increase with increasing electronegativity of the carbonyl substituent. 8,35 The contribution from resonance form III is determined by the overlap between the lone pair electrons in a 2p z , 3p z ,or 4p z halogen atom orbital with a carbon 2p z orbital and the halogen atom electronegativity and therefore is expected to follow the trend Br > Cl > F. The higher barrier of DMCF may be explained by its smaller size and greater electronegativity. However, Model 1 does not explain either the lower barriers in the (thio)carbamyl halides compared to DMTF or why the thioamides (which are not characterized by a significantly electron deficient carbonyl carbon) show an analogous trend.…”

“…Model 3 predicts that there is no significant delocalization of charge to either sulfur or oxygen in the planar ground state. 35 The thioamides show a different trend. During rotation, charge flows back from the amide nitrogen to the carbonyl carbon.…”

Barriers to Rotation of Secondary Amide Peptide Bonds

“…Light absorption by the trans peptide bond causes photoisomerization into an excess population of cis conformer that provides the tool for measuring isomerization kinetics. Given the rate effects found for N-substituted amides, − extrapolation from the isomerization rates of k cis → trans = 2.3 ± 0.3 s -1 ( N -methylacetamide) and k cis → trans = 14 ± 2 s -1 (Gly-Gly) would lead to faster isomerization rates for any peptide bond but Xaa-Gly linkages.…”

Gas-Phase Nuclear Magnetic Resonance Study of (15N)Trifluoroacetamide: Comparison of Experimental and Computed Kinetic Parameters

“…Unfortunately, gas-phase dynamic NMR studies of primary amides are difficult for several reasons. First, the vapor pressure of primary amides is extremely low, usually less than that for the tertiary amides that have been more extensively studied. − Vaporization of enough amide for acquisition of gas-phase spectra is further impaired by the affinity of the amide hydrogens for the glass NMR tube. Also, whereas dimethyl amides have three equivalent protons at the exchanging sites, primary amides have only one.…”