EandZConformations of Esters, Thiol Esters, and Amides

Abstract

Populations and free-energy differences for the E and Z conformations of S-methyl, cyclopropyl, isopropyl, and cyclopentyl thioformate were determined by low-temperature 1H NMR spectroscopy, and free-energy barriers of 10.63 and 11.84 kcal/mol were obtained for interconversion of E and Z conformations of S-methyl thioformate at −52.4 °C. Populations and free-energy differences were also determined at room temperature by using 13C NMR for a series of N-substituted formamides and N-cyclopropylacetamide in 1% solutions in CD2Cl2/CH2Cl2. In both sets of compounds, electron-withdrawing groups attached to sulfur or nitrogen appear to favor the E conformations. The electronegativities of the groups are taken to increase in the order methyl < vinyl ∼ phenyl ∼ cyclopropyl < hydrogen < ethynyl. Data from the literature are discussed in these terms, including the E−Z energy differences for formic acid and its ethynyl, vinyl, and methyl esters.

Vibrational Stark Effects of Carbonyl Probes Applied to Reinterpret IR and Raman Data for Enzyme Inhibitors in Terms of Electric Fields at the Active Site

“…This may be due to the broad absorbance of the C=O peak of ethyl acetate in water, which has a prominent shoulder and complicates the analysis. This observation is consistent with studies on similar alkyl acetates where the solvents exhibit altered conformations of the terminal methyl group, resulting in differences in the E/Z-rotamer populations, 77–79 or the presence of different H-bonding configurations as observed by MD simulations and 2D IR. 80–82 Consistent with multiple H-bonding configurations, post-processing of MD trajectories by Pazos et al .…”

E/Z Energetics for Molecular Modeling and Design

“…For N -methylacetamide ( 2 ), the present results concur with other high-level calculations and experiments that the enthalpy difference at 298 K is in the 2.1 - 2.5 kcal/mol range 11,20,23,24,30. The difference diminishes to 1.0 – 1.2 kcal/mol for N -methylformamide owing to reduced steric crowding in the E form 20,37…”

2‐Methoxy‐Δ3‐1,3,4‐oxadiazoline, a Multipurpose Precursor for the Generation of a Carbene, an Ylide, or a Diazo Compound

“…Merely due to dipole-dipole and also to steric interactions, esters are better stabilized in the Z-conformation. [20] Therefore, Z-16a decomposes readily to norbornenylidene 17 by overcoming a low barrier of 0.6 kcal/mol [ Figure 3, TS(Z-16a/17), +10.7 kcal/mol in comparison to norbornenylidene and methyl acetate, +0.6 kcal/mol from ylide Z-16a]. Ylide Z16b was not even found; instead oxadiazoline 13b directly gives carbene 17 because the decomposition of Z-16b is further facilitated by anchimeric assistance from the double bond.…”