Pyrazole formation: Examination of kinetics, substituent effects, and mechanistic pathways

Abstract

Reaction kinetics for the condensation of 1,3-diketones 1a-o with selected arylhydrazines (aryl = Ph, 4-NO2Ph, 4-CH3OPh, and 2,4-diNO2Ph) was studied using 19F NMR spectroscopy. Product regioselectivity is modulated by reactant ratios, substituents, and acidity. Reaction rates were found to be influenced by substituents on the diketones and on phenylhy-drazines as well as by acidity of the reaction medium with rates varying as much as 1000-fold. Hammett p values for these cyclizations were determined. The reaction was found to be first order in both the diketone and arylhydrazine. The rate-determining step for pyrazole formation shifts as a function of pH. Mechanistic details and reaction pathways supporting these findings are proposed. © 2008 Wiley Periodicals, Inc.