Nucleophilic transformation of 3-substituted-6,8-dimethylchromones with phenylhydrazine under various reaction conditions: Theoretical, Spectroscopic characterization and in silico ADME studies

The chemical behavior of 3-substituted-6,8-dimethylchromones 1-3 was examined towards phenylhydrazine under various reaction conditions. Under different molar ratio, reaction of aldehyde 1 with phenylhydrazine produced hydrazone 4 and pyrazole 5. Depending on the solvent used, reacting carbonitrile 2 with phenylhydrazine produced a variety of products; through ring-opening and ring-closure mechanisms. Reaction of carboxamide 3 with phenylhydrazine, afforded chromeno[4,3-c]pyrazole derivative 8. Finally, boiling carboxamide 3 in KOH solution gave 4-hydroxy-6,8-dimethylcoumarin-3-carboxaldehyde (9). Molecular geometries were examined using density functional theory, (DFT/B3LYP) with 6-311 G(d,p) basis sets, to investigate the bond lengths of certain bonds. DFT was also used to compute some global reactivity descriptors including electronegativity (χ), chemical potential (μ), electrophilicity index (ω), softness (S) and hardness (η). Compound 4 is the softest, while compound 9 is more electrophilic and more electronegative. In addition, MEP surface maps were investigated to predict the chemical reactivity of the current molecules. The chemical shifts values of 1H and 13C NMR were assessed utilizing the GIAO method, and the results were compared with those obtained experimentally. The current compounds are appropriate for non-linear optical applications, according to their first order hyperpolarizability values which found 1.5–3 times greater than those of urea. SwissADME was used to explore the features of current compounds' absorption, delivery, metabolism, and excretion (ADME).