Keto–Enol Tautomerization of Acetylacetone in Mixed Solvents by NMR Spectroscopy. A Physical Chemistry Experiment on the Application of the Onsager-Kirkwood Model for Solvation Thermodynamics

Abstract

Keto–enol tautomerism is a fundamental concept that examines the migration of a proton between two constitutional isomers, the keto and enol tautomer. Many experiments have been proposed to understand the concept behind Meyer’s Rule, which states that the keto tautomer is favored as the solvent polarity increases. However, all the experiments have only been performed in a single solvent. A new physical chemistry experiment is introduced to determine tautomerization equilibrium in binary solvent mixtures using nuclear magnetic resonance (NMR) spectroscopy, by systematically varying the molar ratio of the solvents. This approach allows the students to explore the variation of the polarity of the solvent system as a continuous variable. Furthermore, using an empirical method, the solvent polarity at any binary solvent condition can be converted to an effective dielectric constant of the sample. Because of this ability, the keto–enol tautomerization equilibrium constant can be directly related to the solvation Gibbs energy using the Onsager–Kirkwood theory. Detailed experimental procedures for the direct adaptation of the experiment using a high-resolution or desktop NMR spectrometer is provided in the Supporting Information.

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

“…The 1 H NMR spectra of 1-phenyl-1,3-butanedione ( 2a ) in CDCl 3 and in methanol- d 4 indicated that the enol tautomer of the 1,3-diketone was predominant in CDCl 3 , while the keto tautomer was predominant in methanol- d 4 , which is a more polar solvent than CDCl 3 ( Figure 7 ). Our observations thus reinforce Meyer’s rule [ 34 – 35 ], which states that the keto tautomer is favored as the solvent polarity increases. This also corroborates our observations and explains why under mild basic conditions, the 3,4,5-trisubstituted isoxazole 3a was formed exclusively in polar solvents like water or methanol ( Table 1 , entries 11–13), whereas the furoxan 4 was formed predominantly in nonpolar solvents such as chloroform or dichloromethane ( Table 1 , entries 9 and 10).…”

Explanation of Substituent Effects on the Enolization of β-Diketones and β-Ketoesters

“…For example, Drexler and Field were among the first to report such an experiment on the study of solvent and temperature effects on the keto–enol equilibria of β-diketones and β-ketoesters . Since then, many variants of this experiment have been developed including the study of electronic and substituents effects, , solvation thermodynamics, − molecular conformation, as well as the kinetics and mechanism of this fundamental organic reaction.…”

“…Despite the popularity of this classic experiment, it is to the authors' surprise that there is currently not a clear explanation for simple substituent effects such as the preferential enolization of β-diketones (e.g., 1) relative to corresponding β-ketoesters (e.g., 2), or the enol-promoting effect of electron-withdrawing groups (e.g., 3). Figure 1 presents the experimentally measured enol content of four representative molecules: acetylacetone (1), ethyl acetoacetate (2), 1,1,1-trifluoropentane-2,4-dione (3), and ethyl-4,4,4-trifluoroacetoacetate (4).…”

Students Thinking Like Physical Chemists Using an Inquiry-Based NMR Experiment

“…The experiment described herein, the study of the keto–enol tautomerization process in 2,4-pentanedione using nuclear magnetic resonance has been part of the physical chemistry laboratory curriculum for several decades and has been discussed many times in this journal and other sources. − The ketone form of 2,4-pentanedione readily tautomerizes into its enol form as shown in the reaction scheme below (Scheme ).…”