Strong Dimerization of Ureidopyrimidones via Quadruple Hydrogen Bonding

TLDR

6‑Methyl‑2‑butylureidopyrimidone forms a four‑hydrogen‑bond dimer in both solid state and CHCl₃ solution through a DDAA hydrogen‑bonding array in its 4[1H]-pyrimidinone tautomer. An intramolecular NH–O hydrogen bond preorganizes the molecules, facilitating dimerization. The dimer shows a very high association constant (>10⁶ M⁻¹) in CHCl₃, remains in equilibrium with the monomer in CHCl₃/DMSO, and analogous high‑constant dimers form via a DADA array in related derivatives, making the ureidopyrimidone motif a convenient building block for supramolecular chemistry.

Abstract

6-Methyl-2-butylureidopyrimidone dimerizes via four hydrogen bonds in the solid state as well as in CHCl3 solution via a donor−donor−acceptor−acceptor (DDAA) array of hydrogen bonding sites in the 4[1H]-pyrimidinone tautomer. An intramolecular hydrogen bond from the pyrimidine NH group to the urea oxygen atom preorganizes the molecules for dimerization. The dimerization constant of the dimer in CHCl3 exceeds 106 M-1. In CHCl3 containing DMSO, the dimer is in equilibrium with the monomeric 6[1H]-pyrimidinone tautomer. In 6-phenyl-2-butylureidopyrimidone, the 4[1H]-pyrimidinone tautomer coexists with the pyrimidin-4-ol form, which dimerizes with similar high dimerization constants via four hydrogen bonds in a DADA array. The latter tautomer predominates in derivatives with electronegative 6-substituents, like 6-nitrophenyl- and 6-trifluoromethyl-2-butylureidopyrimidone. Due to its simple preparation and high dimerization constant, the ureidopyrimidone functionality is a useful building block for supramolecular chemistry.