Theoretical study on structural and mechanistic aspects of synthesis of a 3-aminopyrazole derivative

Svetlana Marković, Milan D. Joksović, Petra Bombicz, Vukadin M. Leovac, Violeta Marković, Ljubinka Joksović

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4 Citations (Scopus)

Abstract

The structure of 5-hydroxy-3,5-dimethyl-1-S-methylisothiocarbamoyl-2- pyrazolinium iodide (HDMCPI), a cyclic intermediate for a 3-aminopyrazole derivative, was determined by means of X-ray analysis and spectroscopic techniques. In a treatment of HDMCPI in alkaline aqueous solution, 4-acetyl-3(5)-amino-5(3)-methylpyrazole (AAMP) was unexpectedly yielded. The reaction of HDMCPI was monitored by 1H and 13C NMR spectroscopy. It was shown that keto-imine tautomer appears as the only tautomeric form. Density functional theory explained the spontaneous formation of keto-imine tautomer, whose existence is the main condition for generating a carbanion in alkaline medium. The carbanion further undergoes cyclization and elimination of MeSH, thus yielding AAMP. In the reaction of acetylacetone with thiosemicarbazide instead of S-methylisothiosemicarbazide, there were no traces of AAMP. This result can be attributed to the absence of keto-imine form in the tautomeric equilibrium, which would provide the formation of a carbanion for a nucleophilic attack and further cyclization.

Original languageEnglish
Pages (from-to)6205-6211
Number of pages7
JournalTetrahedron
Volume66
Issue number32
DOIs
Publication statusPublished - Aug 7 2010

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Keywords

  • 3-Aminopyrazole
  • Crystal structure
  • DFT
  • Keto-imine tautomer
  • Reaction mechanism

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Marković, S., Joksović, M. D., Bombicz, P., Leovac, V. M., Marković, V., & Joksović, L. (2010). Theoretical study on structural and mechanistic aspects of synthesis of a 3-aminopyrazole derivative. Tetrahedron, 66(32), 6205-6211. https://doi.org/10.1016/j.tet.2010.05.093