Novel Sulfanilamide-Derived Schiff Base: Synthesis, FT-IR spectroscopy, Crystal Structure, Hirshfeld Surface Analysis, and in silico ADME investigation

1. Introduction—Schiff bases are of significant importance in pharmaceutical chemistry due to their simple synthesis, structural flexibility, and broad biological activities. Sulfanilamide‑derived Schiff bases are particularly advantageous, as they combine the bioactive sulfonamide moiety with the azomethine linkage, often resulting in enhanced antibacterial, anticancer, and enzyme‑inhibitory properties. Their ability to form strong hydrogen bonds and π–π interactions further enhances their potential as therapeutic agents. In this work, we report the microwave-assisted synthesis, FT-IR characterization, crystal structure, Hirshfeld surface analysis, and ADME prediction of a new sulfanilamide-derived Schiff base, namely (Z)-4-(((4,5-dihydroxy-6-oxocyclohexa-2,4-dien-1-ylidene)methyl)-amino)benzenesulfonamide (I).
2. Experimental Section—Compound (I) was synthesized using microwave irradiation. The FT-IR spectra were recorded on a Diamond ATR spectrometer in the 4000–400 cm⁻¹range. Single-crystal X-ray data were collected at 296,15 K on a STOE IPDSII diffractometer, using Mo-Ka radiation and processed using the programs available in Olex2 [5]. Hirshfeld surface analysis was performed using CrystalExplorer21. ADME parameters were estimated using SwissADME(https://www.swissadme.ch).
3. Results and Discussion—The FT-IR spectra indicated the keto-enamine tautomeric form, displaying characteristic bands at 2900 and at 1610 cm^-1 corresponding to enamine and ketostretching modes, respectively. Single-crystal X-ray diffraction revealed that compound (I) crystallizes in the P -1 space group as a keto-enamine tautomer, with two crystallographically independent molecules in the asymmetric unit. The crystal features N–H⋯O, O–H⋯O and C–H⋯O hydrogen bonds, and ?⋯?. Additionally, Hirshfeld surface analysis revealed that O···H/H···O (39.0%), H···H (25.3%), and C···H/H···C (17.2%) contacts dominate the crystal packing, followed by C···C (8.5%). Finally, in silico ADME analysis suggested that (I) exhibits favorable physicochemical properties and good oral absorption, highlighting its potential as a viable pharmacological scaffold.

Conclusions—A new sulfanilamide-derived Schiff base was successfully synthesized and characterized. In silico SwissADME analysis revealed favorable physicochemical properties and good oral absorption, highlighting its potential as a promising pharmacological scaffold.