Novel Fluorescent Schiff Base Derivatives of 4‐Aminoantipyrine with Large Stokes Shifts and Dual Emission Properties: Crystal Structure, Molecular Interactions, Molecular Surfaces, Conformational and DFT Analyses

Abstract

Two novel Schiff base analogs derived from 4‐aminoantipyrine, namely, (E)‐4‐(2‐nitrobenzylideneamino)‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one (3a) and (E)‐4‐(4‐nitrobenzylideneamino)‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one (3b), were synthesized using a mild and efficient method and characterized by FT‐IR, 1H NMR, mass spectrometry, and single‐crystal X‐ray diffraction studies. X‐ray analysis of a single crystal of 3a revealed an orthorhombic space group P2(1)2(1)2(1) structure, with an E‐configuration around the azomethine (C12N3) double bond. One unit cell was found to contain four molecules showing π−π and π−σ van der Waals stacking interactions. Plausible intermolecular interactions were analyzed using 3D Hirshfeld surfaces and the related 2D fingerprint plots. The optimized molecular structure, potential energy surface (PES) scan, vibrational frequencies, Mulliken charge distribution, molecular electrostatic potential (MEP) maps, frontier molecular orbitals (FMOs), and associated energies of 3a and 3b were calculated using density functional theory (DFT) calculations using the B3LYP method and the 6‐311G(d,p) basis set. PES scans showed that the conformational energy profiles of 3a and 3b were dissimilar around the torsion angles N3–C12–C13–C14/C18 and C12–N3–C3–C2/C1 due to substituent position effects on the benzylidene phenyl ring. Mulliken charge distribution analysis revealed that O1, N1, and N3 atoms of 3a and 3b could act as electron donors and coordinate with metals, while MEP analysis showed that O1, N3, and O2–O3 are the most suitable sites for electrophilic attack. Regarding drug–receptor interactions, molecular lipophilic potential (MLP) maps demonstrated that the benzylidene phenyl ring favors lipophilic contact and the pyrazolone ring hydrophilic contact. In addition, UV–vis and fluorescence spectroscopic experiments showed that both compounds have good absorbance and fluorescent properties and large Stokes shifts. Interestingly, both compounds showed dual emission in ethanol, acetone, and diethyl ether, possibly due to conformational isomerization induced by photoexcitation.