Michael versus retro-Michael reaction in the regioselective synthesis of N-1 and N-3 uracil adducts

By controlling the temperature or reaction time in the base-catalysed Michael-type addition of 5-substituted uracil derivatives we were able to synthesise N-1 or N-3 uracil adducts using methyl acrylate and acrylonitrile as acceptors. The mechanism of this chemical inequivalence was established using 1H NMR spectroscopic studies. The investigations revealed that formation of the N-1 adduct was achievable under kinetically controlled conditions irrespective to the type of the base used (TEA, DBU). In turn, synthesis of the N-3 adducts proceeded from the initially formed N-1,N-3 diadduct via a retro-Michael reaction which dominates at elevated temperature or prolonged reaction time.