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

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.