Measurement of an Equilibrium Constant by NMR
It is well known that ketones such as acetone have another isomeric structure that results from proton movement; this other structure is called the enol tautomer. The enol tautomer is an unsaturated alcohol:
For acetone, and the majority of cases in which this keto-enol tautomerism is possible, the keto form is far more stable and little if any enol can be detected. However, with ，-diketones and ，-ketoesters, such factors as intramolecular
hydrogen bonding and conjugation increase the stability of the enol form and the equilibrium can be significantly shifted to the right.
The proton chemical environments are quite different for the keto and enol tautomers and the interconversion rate constants k and k, between these forms 1;1
are small enough that distinct NMR spectra are obtained for both forms. In principle, the two enols are also distinguishable when R' ； X. However, the
intramolecular OH proton transfer is quite rapid at normal temperatures, so that a single (averaged) OH resonance is observed. In general, such averaging occurs when the conversion rates k and k (in Hz) exceed the frequency separation 2;2
！ – ！ (also in Hz) of the OH resonance for the two enol forms. The magnetic 12
field at the OH proton is thus averaged and resonance occurs at (！ – ！) /2. 12
Similarly, rapid rotation about the C–C bonds of the keto form explains why
spectra due to different keto rotational conformers are not observed. Thus, distinct spectra are expected only for the two tautomers and these can be used to determine the equilibrium constant for keto-to-enol conversion:
where brackets denote concentrations in any convenient units.
The keto arrangement is the configuration which is electrostatically most favorable, but the steric repulsions between X and Y groups will be larger for this keto form than for the enol configuration. Indeed, experimental studies have confirmed that the enol concentration is larger when X and Y are bulky. This steric effect is less important in the ，-ketoesters in which the X ... Y separation is
greater. For both ，-ketoesters and ，-diketones, ？ substitution of large R' groups
results in steric hindrance between R' and X (or Y) groups, particularly for the enol tautomer, whose concentration is thereby reduced. Inductive effects have also been explored; in general, ？ substitution of electron-withdrawing groups such
a Cl or CF favor the enol form. 3
The solvent plays an important role in determining K. This can occur through c
specific solute-solvent interactions such as hydrogen bonding or charge transfer. In addition, the solvent can reduce solute-solute interactions by dilution and thereby change the equilibrium if such interactions are different in enol-enol, enol-keto, or keto-keto dimers. Finally, the dielectric constant of the solution will depend on the solvent and one can expect the more polar tautomeric form to be favored by polar solvents. Some of these aspects are explored in this experiment.
You will be using the Bruker 300 MHz NMR spectrometer. Obtain several milliliters each of acetylacetone (CH3OCH2COCH3, MW = 100.11,density =0.98 1;g mL) and ethyl acetoacetate (CH3CH2OCOCH2COCH3, MW = 130.45, density 1;= 1.03 g mL). Prepare small volumes of these solutions:
6Solution 1: 0.10 mole fraction of acetylacetone in benzene-d
6Solution 2: 0.10 mole fraction of acetylacetone in DMSO-d
6Solution 3: 0.10 mole fraction of ethyl acetoacetate in benzene-d
6Solution 3: 0.10 mole fraction of ethyl acetoacetate in DMSO-d
Prepare an NMR tubes containing the four solutions and record the NMR spectra. The enol OH peak is shifted substantially downfield.
Integrate the bands carefully at least three times, expanding the vertical scale by known factors as necessary in order to obtain accurate relative intensity measurements.
Assign all spectral features using NMR reference sources. Tabulate your results and use your integrated intensities to calculate the percentage enol present in each solution. Indicate clearly how you used the intensities to calculate the percentage enol.
For both the enol and the keto form, compare experimental and theoretical ratios of the integrated intensities for different types of protons (e.g., methyl to methylene protons in the keto form).
Calculate K and the corresponding standard free energy difference ？G( for the c
change in state keto ， enol in each solution.
Use Spartan and the 6-31G method to calculate the energies of the keto and enol forms. If the entropy does not change in the isomerization, we can estimate the ？G( ~ energy difference between keto and enol. Compare his value with the experimental value.
Discuss briefly your assignments of chemical shifts and spin-spin splitting patterns of acetylacetone and ethyl acetoacetate. Which compound has a higher concentration of enol form and what reasons can you offer to explain this result? What changes would you expect in the NMR spectra of these two compounds if the interconversion rate between enol structures were much slower? Compare the value of Kc for acetylacetone in CCl with that in CHOH. What does 43
your result suggest regarding the relative polarity of the enol and keto forms? Which form is favored by hydrogen bonding and why?
Compare your values of ？G( with those for the gas phase (？G( = -9.2 ? 2.1 kJ 11;;mol for acetylacetone, ？G( = -0.4 ? 2.5 kJ mol for ethyl acetoacetate). What
solvent properties might account for any differences you observe?