Hydrogen-bonded complexes of diaminopyridines and diaminotriazines: Opposite effect of acylation on complex stabilities

The association behavior of several 2,4-diamino-s-triazines, 2,6-diaminopyridines, and their acylated derivatives with uracil derivatives was studied. In solution H-1-NMR and IR spectroscopy were used, and in the solid state as (co)crystals X-ray diffraction was used. Acylation of 2,6-diaminopyridine leads to an increase of the association constant in CDCl3 of the complexes with N-propylthymine from 84 to 440-920 M(-1), whereas acylation of diamino-s-triazines leads to a dramatic fall in the association constant of the complexes with N-propylthymine from 890 to ca. 6 M(-1). This phenomenon is related to different conformational preferences of these compounds. The amide groups in bis(acylamino)pyridines prefer a trans conformation, with the carbonyl group anti with respect to the ring nitrogen and coplanar with the aromatic ring. The amides of bis(acylamino)triazines, however, reside predominantly in a cis conformation. Repulsive secondary electrostatic interactions between the cis-amide and uracil carbonyl groups are thought to be responsible for the low association constant of complexes of bis(acylamino)triazines with uracils. The relatively high dimerization constants of bis(acylamino)triazines have been rationalized by the strong tendency to dimerize via quadruple hydrogen bonding.