A novel, simple and straightforward route to 5-monoalkylbarbiturates by FeCl₃·6H₂O catalyzed domino reactions of 6-aminouracils, water and α,β-unsaturated ketones, where water plays a key dual role as both reactant and solvent, is described. Significantly, all the reactions efficiently furnished exclusively 5-monoalkylbarbiturates and not pyrido[2,3-d]pyrimidines as generally produced from the reactions of 6-aminouracils and α,β-unsaturated carbonyls.