Mechanism of unusual formation of 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones and 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides and their antimicrobial evaluation

6/6,7-Substituted 3-formylchromones (9a–e) react with 2 equivalents of 2-phenyl-4-dimethylamino-1-thia-3-azabuta-1,3-diene (10) or thiobenzamide (11) in refluxing toluene to furnish novel substituted 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones (12a–e). However, reactions of substituted 2-anilino-3-formylchromones (15a–d) with thiobenzamide (11, 2 equivalents) in refluxing xylene furnish 4-oxo-4H-chromene-3-carbothioic acid N-phenylamide (17a–d) in high yields. A mechanistic rationalization of the conversion of 2-anilino-3-formylchromones (15a–d) to N-phenylamides (17a–d), and 3-formylchromones (9a–e) to the corresponding thioaldehydes, is proffered. All the compounds (12a–e, 17a–d) display very high antifungal and antibacterial activities against a number of strains. Dithiazole 12d exhibits a very high antifungal activity (MIC 5 μg/ml) against Geotrichum candidum, better than fluconazole (MIC 09 μg/ml) and also possesses good antibacterial activity (MIC 52 μg/ml) against Shigella flexneri.

Graphical abstractSynthesis, antimicrobial evaluation and mechanistic rationalization of substituted 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones and 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides are presented. All synthesized compounds display high antifungal and antibacterial activities.Figure optionsDownload full-size imageDownload as PowerPoint slide