A Series of Barbituric Acid Derivatives from Sulfa Drug: Synthesis and Antimicrobial Activity

Abstract

This paper reports the synthesis and characterization of some new barbituric acid derivatives from sulfadiazine. A reaction of sulfadiazine with chloroacetyl chloride gave 2-chloro-N-(4-(N-pyrimidin-2-ylsulfamoyl) phenyl) acetamide [A] which was reacted with thiourea and K2CO3 to give thiazole derivative [B]. Schiff base compounds [Sh1-Sh3] were prepared from condensation of thiazole derivative with different aromatic benzaldehydes. Then, addition reaction of acetyl chloride to Schiff bases afforded new tertiary amides compounds [D1-D3]. The latter compounds were allowed to react with 1, 3-bis (hydroxyl methyl) barbituric acids derivatives [E1-E2] via Williamson reaction to form new barbituric acid derivatives [F1-F3] and [G1-G3]. Thin layer chromatography, melting points, Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR) and carbon-13 nuclear magnetic resonance (13C-NMR) techniques confirmed formation of the prepared compounds. Antimicrobial studies of the synthesized compounds were assayed against three different types of bacteria, including Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, and against two types of fungi Aspergillus flavus and Candida Albicans. Biological applications of the synthesized compounds showed a greater effect on antimicrobial activities than the standard.

Keywords

• sulfadiazine
• thiazole
• schiff base
• barbituric acid
• antimicrobial activity