Synthesis and characterization of celecoxib peroxide: crystal structure, theoretical analysis, thermochemistry and bond dissociation energy

Celecoxib peroxide (systematic name: 4-{5-[4-(hydroperoxymethyl)phenyl]-3-(trifluoromethyl)-1 H -pyrazol-1-yl}benzenesulfonamide), C 17 H 14 F 3 N 3 O 4 S, a compound identified in destruction experiments and the long-term storage of the active pharmaceutical ingredient (API) celecoxib, was synthesized and characterized using a variety of techniques, including NMR ( 1 H and 13 C), UV, IR, MS and single-crystal X-ray diffraction (SC-XRD). Powder XRD and thermal differential scanning calorimetry/thermogravimetry (DSC/TG) techniques were also employed to further elucidate the features of the crystal. The structure analysis revealed that the molecule is disordered, with the peroxide O atoms distributed over two sites with occupancies of 0.598 (6) and 0.402 (6). The crystal structure features three distinct O—H...N and N—H...O hydrogen bonds, with the latter forming a heterosynthon that results in an R 4 2 (8) ring motif. Hirshfeld surface (HS) analysis revealed that O...H/O...H interactions were dominant, accounting for 25.3% of the total HS. Energy framework studies were conducted to assess the energetic contribution of supramolecular motifs in stabilizing interaction forces, encompassing dispersion energy and Coulombic energy. The molecular electrostatic potential surfaces (MEPS) indicated a maximum energy of 53.1 kcal mol −1 and a minimum energy of −35.2 kcal mol −1 . Furthermore, the bond dissociation energies (BDEs) of the peroxide bonds were calculated using the B3LYP density functional theory (DFT) functional with the 6-311+G(d,p) basis set. The results of these calculations suggested that the peroxide bonds possess relatively low energies.