In this study, the
conformational properties of tertiary trifluoroacetamides
in dibenzoazepine (1aand1b) and benzodiazepine
(2aand2b) derivatives, which exist as
equilibratedE- andZ-amide conformers
in solution, were investigated by1H and19F
NMR spectroscopy. In all cases, one of the methylene protons neighboring
the nitrogen atom of the minor conformer showed a finely split pattern
due to coupling with the trifluoromethyl fluorine atoms, as confirmed
by19F-decoupling experiments. One-dimensional (1D) and
two-dimensional (2D)1H–19F heteronuclear
Overhauser spectroscopy (HOESY) experiments were performed to confirm
whether these couplings are attributable to through-bondspin–spin couplings (TBCs) or through-spacespin–spin couplings (TSCs). HOESY cross-peaks between CF3(19F) and one of the CH2–N protons
of the minor conformers indicate that the two nuclei are spatially
close to each other, thus establishing the stereochemistry of the
major (E-) and minor (Z-) conformers.
TheE-amide preferences of the trifluoroacetamides
are consistent with the results of density functional theory calculations
and X-ray crystallographic analyses. Furthermore, the otherwise incomprehensible1H NMR spectra were accurately assigned using the HOESY-determined
TSCs. The1H NMR assignments of theE-
andZ-methyl signals ofN,N-dimethyl trifluoroacetamide, the simplest tertiary trifluoroacetamide,
were revised for the first time in half a century.