Abstract <p>This study presents the synthesis and spectroscopic and quantum chemical calculations of novel 2-imino-thiazolidin-4-one derivatives. The synthetic strategy was divided into three key stages. Initially, 2-amino-4-(substituted phenyl)-1,3-thiazoles were obtained through the reaction of thiourea with substituted acetophenone in the presence of iodine. At the next step, the resulting heterocyclic amines were treated with chloroacetyl chloride in benzene to obtain 2-chloroacetamido-4-(substituted phenyl)-1,3-thiazole. Finally, the latter was subjected to heteroannulation with potassium thiocyanate to form the target 2-imino-3-[4-(substituted phenyl)-1,3-thiazol-2-yl]thiazolidin-4-ones. The molecular structure of the five newly synthesized compounds was elucidated by IR and ¹H and ¹³C NMR spectroscopy. A variety of quantum-chemical methods, including reduced density gradient (RDG) analysis, natural bond orbital (NBO) analysis, and analysis of potential energy maps (PEMs), HOMO–LUMO energy gaps, topological, and thermodynamic parameters were employed to study the structural and electronic properties and reactivity of the products, with potential implications for chemical and biological applications.</p>