“Synthesis and E/Z equilibrium of N-acyl-n´-aryl-1,n-diamines”

MARÍA CRUZ MOLLO; LILIANA R. ORELLI

Congreso; IV Ibero-American NMR Meeting - VI GERMN Bienal Meeting-III Iberian NMR Meeting.; 2012

Structural features of amides have been widely studied by NMR spectroscopy and molecular modelling, as they represent model compounds for the peptide bond.1 The partial double bond character of the (O)C–N bond in amides causes a substantial rotational barrier, which ranges between 15 and 23 kcal/mol. N-monosubstituted amides exist as a single diastereoisomer, with the exception of formamides. However, in tertiary amides the non-isolable E/Z diastereoisomers can be observed by RMN spectroscopy as two different sets of signals. As part of ongoing research on the E/Z equilibrium in amides,2,3 we present the synthesis and stereochemical study of a series of novel N-acyl-N’-aryl-1,n-diamines with different substitution patterns. We focused our interest in secondary and tertiary formamides and tertiary acetamides, all of which display E/Z isomerism. 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. Within formamides, we specifically evaluated the formation of an intramolecular H bond, the effect of increasing steric hindrance of the R2 substituent and of chain length (n). A comparison between formamides and acetamides showed the effect of the R1 substituent on the relative populations of the diastereoisomers.