Stability and Lifetime of Quadruply Hydrogen Bonded 2-Ureido-4[1 H]-pyrimidinone Dimers

Abstract

2-Ureido-4[1 H ]-pyrimidinones are known to dimerize via a strong quadruple hydrogen bond array. A detailed study of the dimerization constant and lifetime of the dimer is presented here. Excimer fluorescence of pyrene-labeled 2-ureido-4[1 H ]-pyrimidinone 1b was used to determine a dimerization constant K dim of 6 × 10 7 M - 1 in CHCl 3, 1 × 10 7 M - 1 in chloroform saturated with water, and 6 × 10 8 M - 1 in toluene (all at 298 K). Under these conditions, the preexchange lifetime of the similar dimers of both 1d and 1e is 170 ms in CDCl 3, 80 ms in wet CDCl 3, and 1.7 s in toluene- d 8, as determined by dynamic NMR spectroscopy. Association rate constants were calculated from the K dim values and the preexchange lifetimes. The resulting values are significantly lower than the diffusion-controlled association rate constants calculated using the Stokes−Einstein and the Debeije equations. This difference is ascribed to a tautomeric equilibrium of the monomer between the dimerizing 4[1 H ]-pyrimidinone and nondimerizing 6[1 H ]-pyrimidinone tautomers, which is unfavorable for dimerization.