Eco‐Friendly Synthesis and Computational Exploration of Ethoxy Functionalized‐Schiff's Base Derivatives as Antimicrobial Applications

Abstract

An efficient and sustainable strategy was developed for synthesizing ethoxy‐functionalized Schiff's bases SB(1–7) through solvent‐free microwave‐assisted condensation using recoverable sulfated titania as a solid‐acid catalyst. The methodology afforded the target compounds in 95% yield within 6 min, while the catalyst was recovered and reused for four cycles with approximately 90% yield retention. The synthesized SB(1‐7)  were characterized by FT‐IR and NMR spectroscopy, with the crystal structure of SB5 confirmed by single‐crystal X‐ray diffraction and Hirshfeld surface analysis. DFT calculations provided molecular‐level insights into the electronic structure, stability, reactivity, and substituent‐dependent properties of SB(1–7) . The study further integrated in vitro antibacterial and antifungal assays with molecular docking and ADMET/drug‐likeness analyses to correlate molecular structure with biological activity. SB2 exhibited the strongest predicted binding affinity toward the 1ACX target (‐7.85 kcal mol −1 ), whereas SB6 showed the strongest antibacterial activity against Staphylococcus aureus . Several derivatives also displayed notable antifungal activity, particularly against Candida albicans . Overall, this recyclable green protocol, combined with comprehensive structural, computational, and biological evaluation, provides a sustainable platform for the development and preliminary screening of ethoxy‐functionalized Schiff bases as potential antimicrobial candidates.