SYNTHESIS OF THIENO[2,3-D][1,3]OXAZINE-2,4-DIONES FROM 4,5-DISUBSTITUTED 2-AMINOTHIOPHENE-3-CARBOXYLIC ACIDS AND THEIR ANTIMICROBIAL ACTIVITIES

Background. Thieno[2,3-d][1,3]oxazine-2,4-diones has attracted a great deal of attention in the last decades. Condensation of its thiophene portion by many various ring systems has given rise to a large array of analogues. A synthesis, development and antimicrobial screening on the methods of preparation of oxazine-2,4-diones is given herein. Purpose. Synthesis of 5,6-disubstituted thieno[2,3-d][1,3]oxazine-2,4-diones from their appropriate acids using triphosgene as reagent. Search perspective antimicrobial oxazines among this series and prepare more building-blocks toward the synthesis of thienopyrimidine scaffolds. Methodology. Thieno[2,3-d][1,3]oxazine-2,4-diones was obtained via 2-amino-4,5disubstitutedthiophene-3-carboxylic acids and triphosgene in dry dioxane by reflux. NMR spectra were recorded with a Varian 400 MHz NMR spectrometer. Antimicrobial testing was carried out by agar method. Originality. Herein a convenient synthesis of some novel thieno[2,3-d][1,3]oxazine-2,4-diones is described using triphosgene. Substituents at position 4 and 5 in thiophene moiety were studied. Methyl and methylene groups influence on microbial strains.Findings. A convenient one-pot synthesis of 5,6-di-substituted thieno[2,3-d][1,3]oxazine-2,4-diones was reported. It was found that triphosgene is best reagent for synthesis of fused oxazines. Some synthesized compounds showed average antimicrobial activity. Highlights: - synthesis of 5,6-di-substituted thieno[2,3-d][1,3]oxazine-2,4-diones using triphosgene; - some of the synthesized compounds were found as antimicrobial agents; - oxazines as building-blocks for synthesis of novel thienopyrimidine