Metal-free iodine/NaHCO ₃ -promoted domino synthesis of spiro-pyrimidines at room temperature with preliminary molecular docking evaluation

A metal-free protocol for the synthesis of spiro-pyrimidine derivatives has been developed via an iodine/NaHCO3-promoted domino reaction of barbituric acids with aromatic aldehydes at room temperature in 1-1.5 h. Using an EtOH-H2O (1:1) medium, the method affords diverse spiro frameworks in good to excellent yields (up to 94%) under mild and operationally simple conditions, without transition metals or harsh reagents. Mechanistic insights suggest a sequential pathway of Knoevenagel condensation, Michael addition, and iodine-assisted intramolecular cyclization. Preliminary molecular docking studies suggest possible interactions with EGFR and CYP51 targets, supporting further biological evaluation. This protocol provides a practical and sustainable route to synthetically valuable spiro-pyrimidine scaffolds.