Microwave-assisted synthesis of 1,3′-diaza-flavanone/flavone and their alkyl derivatives with antimicrobial activity

• Published in: Journal of heterocyclic chemistry 2012-01, Vol.49 (1), p.71-79
• Main Authors: Kahriman, Nuran, Iskender, Nagihan Yilmaz, Yücel, Murat, Yayli, Nurettin, Demir, Emine, Demirbağ, Zihni
• Format: Article
• Language: English
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.800

A simple environmentally friendly solid‐phase microwave‐assisted method was used to synthesis of the 1,3′‐diazaflavanone (2) and 1,3′‐diazaflavone (3) from the cyclization of 2′‐amino (E)‐3″‐azachalcone (1). Ten new N‐alkyl (C5–12,14,15)‐substituted 1,3′‐diazaflavanonium bromides (2a–j) were prepared from compound 2 with corresponding alkyl halides in acetonitrile under reflux. In addition, nine new N,N′‐dialkyl (C5–12,14)‐substituted 1,3′‐diazaflavonium bromides (3a–i) were also synthesized from compound 3 with corresponding alkyl halides using basic silica in acetonitrile. The antimicrobial activities of compounds 1–3, 2a–j, and 3a–i were tested against Gram‐positive (G+) (Bacillus subtilis, Staphylococcus epidermidis, Staphylococcus aureus, and Enterococcus faecalis) and Gram‐negative (G−) (Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella typhimirium, Yersinia pseudotuberculosis, and Enterobacter cloaceae) microorganisms. They showed good antimicrobial activity against the Gram‐positive bacteria tested with the minimal inhibitory concentration values less than 7.8 μg/mL in most cases. The optimum length of the alkyl chain for better and broader activity is situated in the range of 9–12 carbon atoms in the series of compounds 2a–j and five to six carbon atoms in the series of compounds 3a–i. The nonalkylated compounds 1–3 were not effective, as were the ones alkylated with five or six C alkyl groups (2a and 2b) and 8–13 C alkyl groups for N,N′‐dialkyl compounds (3c–3i). The antimicrobial activity increased as the length of the alkyl substitution increased from 8 to 12 carbons in compounds 2a–j. However, antimicrobial activity decreased as the length of the alkyl substitution increased from 7 to 13 carbons in compounds 3c–i. J. Heterocyclic Chem., (2012)