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

Abstract

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 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 compared to the Boc protected derivatives; a conclusion which was supported by theoretical studies, X-ray data and NMR analysis. Moreover, our data sustains 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 was also prepared and studied.