The current study investigates the reactivity of 2-methylchromone toward nitrogen-containing heterocyclic amines, with the aim of assessing how substitution pattern and nucleophile type influence chromone ring opening and subsequent heterocycle formation. Reaction of 2-methylchromone (1) with selected heterocyclic amines afforded a series of heterocycle-linked enaminones 5, 8 and 9, which were found to preferentially adopt the Z-configuration based on spectroscopic analysis. In addition, reactions of substrate 1 with 1,3-binucleophilic reagents enabled the construction of novel pyrimidine-fused heterocycles via ring opening followed by intramolecular cyclization. DFT calculations (B3LYP/6-311+G(d,p)) were performed to study the electronic and nonlinear optical properties of the present compounds. Compound 5 was found to be the most stable than compound 3 and compound 4, consistent with experimental results. Theoretical IR and NMR spectra agreed well with experimental data. The high hyperpolarizability values of the prepared compounds suggest potential nonlinear optical applications. The synthesized compounds were evaluated for anticancer activity against HepG-2 cells, revealing compound 9 as the most active derivative, with potency exceeding that of cisplatin. Molecular docking studies against CDK1 supported the observed biological activity, while drug-likeness analysis indicated favorable pharmacokinetic profiles. Overall, this work highlights the utility of 2-methylchromone with diverse nucleophiles in generating structurally varied heterocycles, validated by combined experimental and theoretical studies.
Abdel‐Megid et al. (Thu,) studied this question.