Conformational behaviour of 3-methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-one: a sudden story of three desmotropes

Abstract

The conformational behaviour of 3-methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-one was studied using a combination of X-ray diffraction, NMR spectroscopy in solution and solid state, and DFT calculations in the gas phase. The compound can adopt four different tautomers, determined by the combination of the keto–enol tautomerism of pyrazolone and the attached 4-acyl carbonyl group. Potential energy surface simulations in gas phase show that each of the tautomeric forms has stable conformers, defined by energy minima, which could potentially be obtained in solid state. NMR analyses indicate that the keto–enol conformations with intramolecular H-bonding are preferred in solutions. Crystallization trials produced five different crystal phases; three yellow and two colorless. The single crystal XRD and solid state NMR structural analyses revealed that three desmotropes are obtained, two of them as two different conformational polymorphs. The difference in the coloration is attributed to the displacement of the double bond producing different conjugations of the pyrazolone. Studies on the effect of the solvent on the solid state structure could not produce a systematic trend and in fact most of the studied crystal phases could be obtained from acetone and ethanol–water solutions. Investigations on the factors governing the crystallization of different phases, temperature, concentration and solvent nature, are in progress.