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

摘要

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 (C _(5-12,14,15))-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 (C _(5-12,14))-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 lg/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,N0-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.