Synthesis and isomerization of acridine substituted 1,3-thiazolidin-4-ones and 4-oxo-1,3-thiazolidin-5-ylidene acetates. An experimental and computational study

Abstract

Acridine thiosemicarbazones 3a–g, obtained through a two-step reaction between aromatic isothiocyanates and hydrazine followed by the treatment with acridin-9-carbaldehyde, in reaction with bifunctional reagents; methyl bromoacetate (MBA) and diethyl acetylenedicarboxylate (DEAD) afforded acridin-thiazolidinone derivatives 4a–g and 7a–f and not their regioisomers 6a–g and 9a–f. Derivatives 4a–g and 7a–f exhibit ZC2N6EN7C8 configuration. Upon standing in DMSO-d6 the thiazolidinones 4a–g and 7a–f spontaneously isomerized into ZC2N6ZN7C8 isomers 5a–g and 8a–f to give a mixture of the both stereoisomers. All compounds were fully characterized by multinuclear NMR, mass spectrometry (MS) and X-ray crystal structure of 4b is also described. X-ray diffraction study revealed that the representative compound 4b crystallized in the monoclinic crystal system with the C2/c space group and Z = 4. Intramolecular C1′H1′⋯N-7 hydrogen bond between the acridine proton H-1′ and nitrogen N-7 of linker existed. This hydrogen bond is responsible for the E isomerism on C-8 atom which was observed in the NMR experiments. Quantum-chemical calculations and NOESY experiments confirmed ZC2N6ZN7C8 configuration of the transformed stereoisomers 5a–g and 8a–f.