Supramolecular assembly involving weak hydrogen bonds, anti-parallel ??? stacking and O???C tetrel bonding interactions and LOX studies in a 1H-pyrazol-1-yl)thiazole-4-carboxylate derivative: An experimental and theoretical study

In this manuscript, we synthesized a novel ethyl 2-(5-(4-methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl) thiazole-4-carboxylate (5) from the reaction acetophenone with 3-methoxybenzaldehyde in basic condition to afford the chalcone derivative (3) which has ability to cyclized with thiosemicarbazide to afford the corresponding dihydro-1H-pyrazole-1-carbothioamide (4). Compound 4 easily reacts with ethyl-3-bromo-2-oxopro-panoate to give the ethyl-2-(5-(3-methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole-4-carboxylate (5). The structure of the synthesized compound was confirmed through spectral analysis (FT-IR, 1HNMR, 13CNMR). Moreover, the crystal structure of compound (5) has been solved using single-crystal X-ray diffraction measurements. These results indicate that 5 crystallizes in the monoclinic crystal system in the P21/n space group. The solid-state structure is mainly stabilized by a combination of intermolecular interactions such as weak hydrogen bonds, C-H & sdot;& sdot;& sdot;pi, pi & sdot;& sdot;& sdot;pi stacking and O & sdot;& sdot;& sdot;C tetrel bonding interactions involving the O-atom of the ester group and the C-atom of the methoxy moiety. In order to confirm the presence of the mentioned intermolecular contacts, we have performed Hirshfeld surface analysis and their associated two-dimensional fingerprint plots. In addition, the strength and nature of the intermolecular interactions have been evaluated by using different computational tools including QTAIM and NCIplot index analysis. Molecular docking analysis was performed with both the enantiomers of pyrazolyl thiazole carboxylate and it was found that 1R bounds deeply into the pocket than 1S, furthermore 1R and indomethacin forms hydrogen bonds while 1S do not. The Molecular results are in good agreement with the experimental data