Synthesis, reactivity, antimicrobial, and anti-biofilm evaluation of fluorinated 4-amino-3-mercapto-1,2,4-triazin-5(4H)-one and their derivatives

Abstract

New fluorinated 1,2,4-triazin-4-ones 2–24 have been prepared using straightforward approaches. The reaction of 4-amino-3-mercapto-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-one (2) with aromatic aldehydes produced 4-((4-substitutedbenzylidene)amino)-3-mercapto-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-ones (5–9), which were cyclized by thioglycolic acid to give 2-(4-subsitiutedphenyl)-3-(3-mercapto-5-oxo-6-(trifluoromethyl)-1,2,4-triazin-4(5H)-yl)thiazolidin-4-ones (10–14). 7-Methyl-3-(trifluoromethyl)-4H-[1, 3, 4]thiadiazolo[2,3-c][1, 2, 4]triazin-4-one (4) was synthesized by the condensation of 2 with acetaldehyde or by reaction with cyano compounds, followed by self-cyclization in dry benzene. Cyclization of compound 2 by reaction with aromatic acids yielded 7-substitutedphenyl-3-(trifluoromethyl)-4H-[1, 3, 4]thiadiazolo[2,3-c][1, 2, 4]triazin-4-ones (15–19). Reaction of compound 2 with cyanamide produced 1-(4-oxo-3-(trifluoromethyl)-4H-[1, 3, 4]thiadiazolo[2,3-c][1, 2, 4]triazin-7-yl)guanidine (20). Alkylation of compound 2 with phenacyl bromide produced 4-amino-3-((2-oxo-2-phenylethyl)thio)-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-one (21) which upon heating in the same media furnished 7-phenyl-3-(trifluoromethyl)-4H,8H-[1, 2, 4]triazino[3,4-b][1, 3, 4]thiadiazin-4-one (22). The reaction of Schiff′s bases 5 or 6 with phenacyl bromide gave 8-benzoyl-7-(4-halophenyl)-3-(trifluoromethyl)-4H,8H-[1, 2, 4]triazino[3,4-b][1, 3, 4]thiadiazin-4-ones (23–24). All of the newly synthesized compounds were characterized by spectral measurements and elemental analysis. The biological evaluation was also described. All compounds were screened for antibacterial, antifungal, and anti-biofilm activities. The findings confirm that the fluorinated 1,2,4-triazin-4-ones appear to be promising compounds as antibacterial, antifungal, and anti-biofilm agents.

Graphical Abstract

Keywords:

• Taguchi method
• Schiff′s base
• fluorinated 1,2,4-triazine
• thiazolidines
• thiadiazoles
• thiadiazines
• antimicrobial
• antibiofilm

Acknowledgment

The authors thank Dr. Ahmed Hamed for performing the biological activity studies at National Research Center, Egypt.

Disclosure statement

The authors report there are no competing interests to declare.