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

作者：Kelly Brendan; O'Donovan Daniel H; O'Brien John; McCabe Thomas; Blanco Fernando; Rozas Isabel^*

来源：Journal of Organic Chemistry, 2011, 76(22): 9216-9227.

DOI：10.1021/jo200954c

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 H-1 NMR spectra of the guanidinium salts as compared with their N,N'-di-Boc protected and neutral analogues. This difference corresponds to a 180 degrees 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 tertbutyl 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.

• 出版日期2011-11-18