Synthesis of 2-aryl-1,2,4-triazol-3-one derivatives from β-nitroenamines

Abstract

The preparation of representatively selected 2-aryl-4,5-disubstituted-1,2,4-triazol-3-ones from cyclic β-nitroenamines in four steps is provided, with an overall yield of 8–70%. The nitrazone to amidrazone conversion (third step) could not proceed in absence of LiBr catalyst, and the crucial role of this mild Lewis acid is emphasized. The last cyclization step required the boosting effect of N-methylimidazole and elevated reaction temperature, as well. This reliable synthesis is highly versatile as well, and it could furnish a chemical library of 2,4,5-trisubstituted-1,2,4-triazol-3-ones with potential pharmacological activities. The usefulness of the umpolung that is accompanied by a wide transformability of nitroenamines is highlighted.

Graphical Abstract

Keywords:

• Amidrazone
• nitrazone
• nitroenamine
• 1,2,4-triazol-3-one

Acknowledgment

The authors are indebted to Mrs. Krisztina G. Kara for her great technical help. The financial support of the research grant IK-UK-2018 (University of Veterinary Medicine, Budapest, Hungary) is highly appreciated.