Pyridin-2-yl Guanidine Derivatives: Conformational Control Induced by Intramolecular Hydrogen-Bonding Interactions

The synthesis and conformational analysis of a series
of pyridin-2-yl
guanidine derivatives using NMR, X-ray crystallography, and B3LYP/6-31+G**
theoretical studies are reported. A remarkable difference was observed
in the 1H NMR spectra of the guanidinium salts as compared
with their N,N′-di-Boc protected
and neutral analogues. This difference corresponds to a 180°
change in the dihedral angle between the guanidine/ium moiety and
the pyridine ring in the salts as compared to the Boc-protected derivatives,
a conclusion that was supported by theoretical studies, X-ray data,
and NMR analysis. Moreover, our data sustain the existence of two
intramolecular hydrogen-bonding systems: (i) between the pyridine
N1 atom and the guanidinium protons in the salts and (ii) within the tert-butyl carbamate groups of the Boc-protected derivatives.
To verify that the observed conformational control arises from these
intramolecular interactions, a new series of N-Boc-N′-propyl-substituted pyridin-2-yl guanidines were
also prepared and studied.