Synthesis of Thiophene-Based Flavone Schiff Base Derivatives and a Comparison of Biological Activities with Furanflavone Analogs

In this investigation, a series of thiophene-based flavone Schiff base derivatives were synthesized starting from phloroglucinol. Initially, the acetophenone derivative of phloroglucinol, 2-hydroxy-4,6-di-O-methyl phloroglucinol (3) was prepared by acetylation followed by selective O-methylation. Later, compound 3 was condensed with thiophene aldehyde to obtain respective thiophene chalcone and was cyclized with I-2/DMSO to get the corresponding thiophene-based flavones intermediate. In the final stage, the titled Schiff base derivatives were obtained by formylation at the 8(th) position of the flavone skeleton followed by condensation with various amines. All the synthesized compounds were tested for their antibacterial and anticancer activities. Among the tested compounds, compound 8h (3-Cl, 4-NO2) showed good to excellent antibacterial activity on four microorganisms. Further, the compounds were compared with corresponding Schiff's base analogs of furan-flavone Schiff's bases.