E/Z equilibrium in tertiary amides – Part 3: N-acyl-N′-arylhexahydro-1,3-diazepines

The 1H and 13C NMR spectroscopic study of a series of N-acyl-N′-arylhexahydro-1,3-diazepines 1 is presented. Due to hindered rotation around the (O)C–N bond, tertiary amides 1 exist as a mixture of non separable E/Z diastereoisomers, which show separate signals in their NMR spectra. For some selected derivatives, differential assignment of the 1H resonances of the E/Z rotamers was made on the basis of the magnitude of ASIS (anisotropic solvent induced shifts) effects and confirmed by NOESY. The corresponding 13C signals were unambiguously attributed by HSQC experiments. The influence of steric and electronic features of the substituents on the relative populations of E/Z rotamers is analyzed. The effect of the ring size was also investigated by comparison with the corresponding hexahydropyrimidine homologs.

► We present the NMR spectral characterization of N-acyl-N′-arylhexahydrodiazepines 1. ► Compounds 1 display E/Z isomerism and display two sets of signals. ► Differential assignment was made by analysis of ASIS effects, NOESY and HSQC spectra. ► The influence of both N-substituents and ring size on the E/Z equilibrium is analyzed. ► This is the first stereochemical study on N-acylhexahydrodiazepines in the literature.