Regioselective formation of new 3-S-alkylated-1,2,4-triazole-quinolones

Abstract

Regioselective synthesis of quinolone-1,2,4-triazoles was established starting from 4-hydroxyquinol-2-ones. The strategy started by the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding acyl thiosemicarbazides. Finally, subjecting the thiosemicarbazide derivatives with ethyl bromoacetate, the reaction underwent internal cyclization and alkylation processes. Alkylation occurred regioselectivity to the sulfur atom of the thione group and not to the amino group. Thus 3-S-1,2,4-triazole-quinolones were obtained in good yields. The structure of the obtained compounds was proved by different spectroscopic techniques together with elemental analysis and X-ray crystallography.

Highlights

• Synthesis of novel quinoline-2-one/1,2,4-triazole hybrids in four steps.

• NMR, IR and mass spectra together with elemental analysis and X-ray crystallography proved the structure of 3-S-alkylated-1,2,4-triazole-quinolones and excluded the formation of 2-N-alkylated-1,3,4-thiadiazole-quinolones.

• Plausible mechanism for the formation of the targeted compounds was suggested.

GRAPHICAL ABSTRACT

KEYWORDS:

• Thiosemicarbazides
• 3-S-alkylated-1,2,4-triazole-quinolones
• 2-N-alkylated-1,3,4-thiadiazole-quinolones

Acknowledgments

The NMR spectrometer at Florida Institute of Technology was purchased with assistance from the U.S. National Science Foundation (CHE 03-42251).

Disclosure statement

No potential conflict of interest was reported by the author(s).