Regiochemical Control of Pyrazoles by Solvent and β‐Enamino Diketone Structure: Regioselective Synthesis of 4,5‐Disubstituted <i>N</i>‐Phenylpyrazoles

Abstract

Abstract A simple method for the regiocontrolled synthesis of the 4,5‐disubstituted N ‐phenylpyrazole regioisomers 2 and 3 from β‐enamino diketones and phenylhydrazine is described. Pyrazole 2 was prepared regioselectively by carrying out the reaction in a protic solvent, whereas pyrazole 3 was obtained as the main product by using an aprotic solvent. Steric factors regarding the β‐enamino diketones also influenced the regiochemistry of 2 and 3 . The influence of solvent on the reaction outcome can be rationalized by using Fukui indices. The structures of 2 and 3 were unambiguously elucidated by 1 H and 13 C NMR spectroscopy, two‐dimensional HMBC experiments, high resolution mass spectrometry, and X‐ray crystallographic analysis.