Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted Rearrangement

Considering the astounding biomedicine properties of pharmaceutically active drug, 4-aminophenazone, also known as 4-aminoantipyrine, work reported in this manuscript details formation novel cocrystals rearranged 4-aminophenazone and 4-nitro-N-(4-nitrobenzoyl) benzamide 1:1 stoichiometry under employed conditions for thiourea synthesis by exploiting use its amino component. However, detailed analysis via various characterization techniques such FT-IR, nuclear magnetic resonance spectroscopy single crystal XRD, unforeseen, but useful cocrystalline synthetic adduct (4 5) prompted us to delve into mechanistic pathway provided reaction conditions. The coformer originates nucleophilic addition following tetrahedral mechanism between para-nitro substituted benzoyl amide acid halide (1). While enamine on 4-nitrosubstituted aroyl isothiocyanates reflux temperature suggests emergence counterpart cocrystal named N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carbonothioyl)-4-nitrobenzamide. Crystallographic studies reveal triclinic system P-1 space group depicts two different crystallographically independent molecules with prominent C–H···O N–H···O hydrogen bonding effective structure stabilization. Hirshfeld surface displays van der Waals interactions dominant packing. Further insight methodologies supported occurrence solution-based evaporation/cocrystallization methodology our case during purification step, promoting first-ever promising future application medicinal industry.