Impact of chlorine substitution on supramolecular architecture and non-covalent interactions in Ethyl 2-amino-6-chloro-4-aryl-7-hydroxy-4H-benzo[4,5-e]pyran-3-carboxylate Isomers: a combined experimental, crystallographic, theoretical, and antioxidant study

Two positional isomers, ethyl 2-amino-6-chloro-4-(2-chlorophenyl)-7-hydroxy-4H-benzo-[4,5-e]pyran-3-carboxylate (1) and ethyl 2-amino-6-chloro-4-(3-chlorophenyl)-7-hydroxy-4H-benzo- [4,5-e] pyran-3-carboxylate (2) were synthesized by a one pot multi-component reaction (MCR) between 4-chlororesorcinol, ethyl cyanoacetate, 2-/3-chlorobenzaldehyde and K<inf>2</inf>CO<inf>3</inf> as a catalyst. Structure establishment was made by UV–Vis., FT-IR, ¹H and ¹³C NMR spectroscopy, and confirmed by single-crystal X-ray diffraction analysis. Both compounds crystallized as monoclinic crystal system with P2<inf>1</inf>/c for compound 1 and C2/c space group for compound 2, respectively. The Hirshfeld surface analysis suggests that the intermolecular H···H, H···Cl, H···O, and H···C contacts significantly contribute their crystal packing. The relative contribution of these contacts is comparable in both compounds and the isomeric effect is very marginal. However, a significant deviation is observed in the H···H and C···Cl contacts. The solid-state arrangements of these two isomers are quite similar, with comparable lattice energies. The Coulomb-London-Pauli-PIXEL (CLP-PIXEL) energy analysis identified the most significant intermolecular dimers in the crystal packing with respect to the total intermolecular interaction energy. These molecular dimers are held together by different non-covalent interactions, such as N − H···O, O − H···O, C − H···O, C − H···Cl, C − H···π, halogen bond and other molecular stacking interactions. The strength of the intra- and intermolecular interactions was evaluated using the quantum theory of atoms in molecules (QTAIM) approach. The UV–Vis absorbance (in chloroform) of compounds 1 and 2 are very similar and this experimental result is in good agreement with the time-dependent density-functional theory (TD-DFT) calculations. The compounds 1 and 2 were examined for antioxidant activity using DPPH assay. The results revealed that the two compounds possess potential antioxidant activity in combating oxidative damage.