Expansion of the Classic Acetylacetone Physical Chemistry

Laboratory Experiment pubs.acs.org/jchemeduc

Expansion of the Classic Acetylacetone Physical Chemistry Laboratory NMR Experiment: Correlation of the Enol−Keto Equilibrium Position with the Solvent Dipole Moment Peter Olaf Sandusky* Department of Chemistry, Pomona College, Claremont, California 91711, United States S Supporting Information *

ABSTRACT: An expansion of the classic NMR study of the acetylacetone enol to keto equilibrium, now widely employed in a basic form as a physical chemistry laboratory course experiment, is described. Repeating the basic experiment in a series of aprotic solvents of increasing polarity focuses the laboratory exercise on the origin of solvent-induced shifts in the equilibrium position. The results may be rigorously interpreted in the context of the Onsager−Kirkwood theory. However, a simpler theoretical explanation, more readily appreciated by undergraduate students, can be based on the interaction energy between the solute and solvent dipole moments. KEYWORDS: Upper-Division Undergraduate, Laboratory Instruction, Physical Chemistry, Hands-On Learning/Manipulatives, Constitutional Isomers, Equilibrium, NMR Spectroscopy, Solutions/Solvents

T

Onsager−Kirkwood theory of solvent interactions for their theoretical analysis.9,13−15 In this theory products and reactants of higher polarity are stabilized, relative to products and reactants of lower polarity, by solvents with higher dielectric constants. As applied to the acetylacetone system the energy shift in the enol to keto equilibrium is then given by

he study of acetylacetone enol−keto tautomerism (Figure 1) by NMR is a classic experiment in upper-division

ΔΔG° ∝ Figure 1. Acetylacetone enol to keto equilibrium.

(1)

where ε is the dielectric constant of the solvent, and μe and μk are the dipole moments of the enol and keto tautomers, respectively. The (ε − 1)/(2ε +1) ratio is often referred to as the Onsager−Kirkwood factor. However, the Onsager−Kirkwood theory is beyond the scope of undergraduate physical chemistry courses. As an alternative this author has found a simple empirical linear relationship between ΔΔG° and solvent dipole moment, μs.

undergraduate physical chemistry courses, last discussed in this Journal in its basic form in 1976.1 The basic experiment involves acquiring proton NMR spectra of acetylacetone (2,4-pentadione), in one or perhaps two different solvents, assigning the position 3 and methyl peaks, and integrating the peaks to determine the relative concentrations of the enol and keto tautomers. This is how the experiment is described in major physical chemistry and instrumental analysis laboratory texts, and practiced in numerous physical chemistry laboratory courses.2−4 However, in the past six years a series of articles in this Journal have proposed various useful modifications to this basic experiment to increase its pedagogical value.5−8 In the same vein, this report advocates repeating the experiment in a series of aprotic solvents of varying polarities. In this way the laboratory exercise may be expanded to focus on the effect of solvent polarity on the Gibbs energy of the equilibrium, and thus be turned into a quantitative examination of the solute dipole− solvent dipole interactions and their effect on the reactant and product thermodynamic activities. Solvent effects on the β-diketone tautomer equilibrium have been studied extensively.9−14 It is well understood that, because the keto tautomer is more polar than the enol tautomer, more polar solvents will shift the equilibrium toward the keto species. Careful examinations of this effect have generally employed the © 2014 American Chemical Society and Division of Chemical Education, Inc.

⎛ ε−1⎞ 2 2 ⎜ ⎟ (μ − μ ) k ⎝ 2ε + 1 ⎠ e

ΔΔG° ∝ μs

(2)

This relationship is in itself interesting in that it suggests that the solute dipole−nearest neighbor solvent dipole interaction dominates the solvent-induced shift in the enol−keto equilibrium, at least in the case of aprotic solvents. It can also be used as the theoretical basis for an upper-division physical chemistry laboratory experiment that will be readily understood by students.

■

EXPERIMENTAL SECTION

Chemicals

Acetylacetone (2,4-pentadione) can be purchased from SigmaAldrich and used without further purification. More care should Published: April 21, 2014 739

dx.doi.org/10.1021/ed400583q | J. Chem. Educ. 2014, 91, 739−742

Journal of Chemical Education

Laboratory Experiment

Generally students can work in pairs when preparing the samples and acquiring the NMR spectra. The time required to prepare the samples is trivial, usually a half-hour or less. Sample preparation and acquisition of a complete set of NMR spectra can easily be completed in one 3 h laboratory period if the students are provided with the T1 values. If the students determine their own T1 values, two 3 h laboratory periods will be needed.

be taken with the deuterated solvents however. All solvents can be purchased from Cambridge Isotopes at a 99.9% level of deuteration. However, care should be taken to exclude water as much as possible from the hygroscopic solvents, acetone, acetonitrile, and dimethyl sulfoxide. These solvents should be purchased in sealed glass vials and opened immediately before sample preparation. For the results presented here, all samples were prepared as 1 mM solutions of acetylacetone in dry solvents.

■

HAZARDS There are no serious health risks or hazards involved in performing this experiment. While the students are briefly exposed to very small amounts of organic solvents during the sample preparation, exposure is at far lower levels than would be encountered in an introductory organic chemistry teaching laboratory. This danger may be completely avoided by preparing the samples in a fume hood. Benzene is a known carcinogen. If this is a concern, it may be replaced in the experiment by a nonpolar solvent such as deuterated cyclohexane.

NMR

All NMR spectra and results presented here were acquired at 300 K on a 500 MHz Bruker AVANCE II instrument equipped with a temperature controlled BBO probe, and processed using Bruker Topspin 2.1 software. The longitudinal relaxation time for each acetylacetone proton peak was determined in each sample using the inversion−recovery experiment with a 2 min relaxation delay. To ensure optimal integral accuracy, the standard 1D proton NMR spectra used for the relative concentration determination of the enol and keto species were taken with a 90° excitation pulse, and with the sum of the acquisition time and relaxation delay set equal to or greater than five times the longest acetylacetone peak T1 in the specific solvent:16 relaxation delay + acquisition time ≥ 5 × T1longest

■

RESULTS Representative proton NMR spectra of acetylacetone in a polar solvent (acetonitrile), and nonpolar solvent (benzene), are presented in Figure 2. Proton chemical shift assignments for

(3)

For each NMR spectrum eight, 64K point FID scans with a transformed sweep width of 10333 Hz were averaged. The averaged FIDs were apodized with 0.3 Hz exponential decay window before transformation. The ppm scales of the spectra were calibrated using the solvent residual proton peaks. Determination of Gibbs Energy

The relative keto to enol ratios were determined from the integration of the peaks in the 1D proton NMR spectrum, and the standard Gibbs energy for the reaction in the solvent was calculated from ΔG° = −RT ln

(keto) (enol)

(4)

where R is the gas constant and T is the temperature in Kelvin. ΔΔG° values presented here were calculated relative to ΔG° for the acetylacetone reaction measured in benzene, the least polar solvent used in this study. Solvent molecule electric dipole moments, measured in the gas phase using microwave spectroscopy or molecular beam electric resonance, were taken from the 89th edition of the CRC Handbook of Chemistry and Physics,17 and the 14th edition of Lange’s Handbook of Chemistry.18 Onsager−Kirkwood factors for the solvents were taken from Mills and Beak.14 Plots of ΔΔG° versus Onsager−Kirkwood factors and molecular dipole moments were generated using Microsoft Excel, and linear leastsquares regression lines were calculated using the Excel “Trendline” utility.

Figure 2. Representative 500 MHz proton NMR spectra of acetylacetone in a polar solvent, acetonitrile, and a nonpolar solvent, benzene. (A) enol position 3, (B) keto position 3, (C) enol methyl positions, (D) keto methyl positions, (S) solvent. Vertical gain has been reduced in insets in order to bring the methyl peaks on scale.

acetylacetone in the various solvents are listed in Table 1, along with the longest acetylacetone longitudinal relaxation time in each solvent, “T1 Long”. Solvent polarity properties are presented in Table 2. It is clear that there is a higher keto to enol ratio under polar solvent conditions, as expected. Initially the plot of the solvent-induced shift in the Gibbs energy of the enol to keto equilibrium, ΔΔG°, versus the Onsager−Kirkwood factor, (ε − 1)/(2ε + 1), may appear significantly curved, as shown in Figure 3. In fact close examination shows that the Onsager−Kirkwood theory works

Execution

The solvent polarity approach to the enol to keto NMR experiment has been used in three upper-level physical chemistry courses taught by the author over the last three years. These courses had a total enrollment of 37 students, almost all of them upper-level chemistry or biochemistry majors. The experiment was well received by the students and was, in general, the most popular experiment performed in the laboratory section during the semester. 740

dx.doi.org/10.1021/ed400583q | J. Chem. Educ. 2014, 91, 739−742

Journal of Chemical Education

Laboratory Experiment

Table 1. Proton NMR Assignments for Acetylacetone in Various Solvents NMR Assignments (ppm) Position 3

a

Methyls

Solvent

Enol

Keto

Enol

Keto

T1 Long (s)c

Benzene Chloroform Methylene chloride THFa Acetone Acetonitrile DMSOb

4.94 5.48 5.52 5.55 5.62 5.61 5.69

2.78 3.50 3.56 3.54 3.67 3.60 3.69

1.59 2.03 1.99 1.99 2.01 2.02 2.03

1.64 2.22 2.19 2.12 2.16 2.14 2.13

6.5 5.0 8.9 5.8 7.4 7.2 5.8

Figure 3. Onsager−Kirkwood plot for the acetylacetone enol to keto equilibrium. Data from methyl proton NMR peak integrals. The trendline excludes the DMSO data point.

Tetrahydrofuran. bDimethyl sulfoxide. cT1 for enol methine protons.

very well for solvents in the series chloroform to acetonitrile. These solvents are all aprotic solvents with moderate dipole moments between 1.05 and 3.92 D. The apparent curvature of the Figure 3 plot derives from the deviation of the data point for benzene, a solvent with no dipole moment. But what is particularly interesting is that a plot of ΔΔG° against solvent dipole moment is linear, as shown in Figure 4. The data presented in Figures 3 and 4 were calculated from the methyl position integrals, however completely equivalent results are achieved when position 3 integrals are used, as indicated in Table 2. Dimethyl sulfoxide (DMSO) appears as an anomaly in both plots in Figures 3 and 4, producing a much higher keto to enol ratio than would be expected. This aberrant behavior of DMSO as a solvent for the acetylacetone system has previously been observed in calorimetric studies, and can be attributed to ability of the solvent to disrupt the enol tautomer’s intramolecular hydrogen bond, thus destabilizing the enol form relative to the keto form.13

Figure 4. Plot of ΔΔG° for the acetylacetone enol to keto equilibrium vs the solvent molecule gas phase dipole moment. Data from methyl proton NMR peak integrals. The trendline excludes the DMSO data point.

■

The dipole moments of the enol and keto forms of acetylacetone have been determined to be 3 and 4 D, respectively.15 Thus, solvents with larger dipole moments would be expected to stabilize the keto form relative to the enol form, and decrease the ΔG° for the enol to keto equilibrium, as is observed in the experiment. The fact that the plot of ΔΔG° for the acetylacetone enol−keto reaction is linear when plotted against μs, rather than μs2, suggests that the dominant interaction responsible for the solvent-induced shift in equilibrium comes from the aligned solute dipole to nearest neighbor solvent dipole. The fact that the plot of ΔΔG° versus μs is linear, without being corrected for variations in solvent dielectric constant, supports this interpretation. T1 values measured in the inversion recovery experiments show that in every solvent the enol methine proton relaxes more

DISCUSSION The potential energy between two aligned dipoles, μA and μB, is given by their product as potential energy =

μA μB (1 − 3 cos2 θ ) 4πεRTr 3

(5)

where r and θ are the distance and angle between the dipole vectors, respectively. The average energy of interaction between the dipoles in a randomly disordered liquid would be given by the product of their squares as19 potential energy =

2μA 2 μB 2 3(4πε)2 RTr 6

(6)

Table 2. Solvent-Induced Shifts in the Acetylacetone Enol to Keto Equilibrium Position 3 Integrals

a

Solvent

Dipole Moment (D)

(ε − 1)/(2ε + 2)

Benzene Chloroform Methylene chloride THF Acetone Acetonitrile DMSO

0.00 1.05 1.60 1.75 2.88 3.92 3.96

0.23 0.36 0.42 0.40 0.47 0.48 0.48

a

b

Methyl Integrals

ΔG° (kJ/mol)

ΔΔG° (kJ/mol)

ΔG° (kJ/mol)

ΔΔG° (kJ/mol)

5.15 4.38 3.61 3.88 2.96 2.79 0.87

0.00 −0.77 −1.54 −1.27 −2.19 −2.36 −4.28

4.90 4.35 3.62 3.84 2.67 2.56 0.79

0.00 −0.54 −1.28 −1.06 −2.25 −2.34 −4.10

Data from refs 17 and 18. bData from ref 14. 741

dx.doi.org/10.1021/ed400583q | J. Chem. Educ. 2014, 91, 739−742

Journal of Chemical Education

■

slowly than the keto methylene proton. Thus, in setting up the NMR experiment the repeat time needs to be set to greater than or equal to five times the enol methine proton T1 value to avoid selective saturation, which would raise the measured keto to enol ratio, and lower the measured ΔΔG°. The methyl spins relax more quickly than the position 3 spins, so the integrals of the methyl peaks may also be used as a second measurement of the keto to enol ratio, giving the students two sets of measurements to analyze. The presence of water dissolved in the solvents will also raise the keto to enol ratio. Samples in hygroscopic solvents, such as acetone, acetonitrile, and DMSO, should be prepared from solvents stored in sealed vials opened immediately before sample preparation. The magnitude of the solvent-induced equilibrium position shift in enol−keto tautomerism of β diketone systems increases with the decrease in the solute to solvent ratio.1 Thus, success with this experiment depends on maintaining a constant solute concentration across the series of samples. But this is not difficult to do. The results presented here were obtained at a solute concentration of 1 mM, which corresponds to roughly a 1 to 100 solute volume to solvent volume ratio. But the linear correlation of ΔΔG° versus μs can be observed at higher solute concentrations of 10 or 15 mM. At concentrations higher than this, solute dipole to nearest neighbor solute dipole interactions will begin to affect the equilibrium position. Likewise, while the results presented here were acquired on a 500 MHz instrument, the experiment has also been performed successfully at 300 MHz. With the possible exception of the construction of binary liquid−vapor phase diagrams, there are relatively few standard undergraduate physical chemistry laboratory experiments that systematically and quantitatively examine the origins of nonideal solution behavior. Thus, the experiment described above can play an important role in the physical chemistry laboratory curriculum. The simple solute dipole−solvent dipole model presented above is particularly well suited as the theoretical basis for an upper-level physical chemistry laboratory experiment, as undergraduate students are generally familiar with the ideas and equations of the dipole−dipole interaction from their courses in physics and physical chemistry. The experiment is also easily modified to stress either the spectroscopic or the thermodynamic aspects of the phenomenon. To place the emphasis of the experiment on time domain NMR spectroscopy, for instance, the measurements of the longitudinal relaxation times using the inversion−recovery experiment may be done by the students. Alternatively the instructor may choose to provide the students with the T1 values and make the experiment more a demonstration of deviations from ideal solution behavior. The thermodynamics aspect of the experiment may also be expanded further by using variable temperature measurements to determine the solvent effects on ΔH and ΔS of the tautomeric reaction.6,20 In any case the students will have an excellent body of literature on the acetylacetone enol to keto reaction to inform the writing of their laboratory reports.

■

Laboratory Experiment

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

■

REFERENCES

(1) Drexler, E. J.; Field, K. W. An NMR study of Keto-Enol Tautomerism in β-dicarbonyl Compounds. J. Chem. Educ. 1976, 53, 392−393. (2) Garland, C. W.; Nibler, J. W. and Shoemaker, D. P. Experiments in Physical Chemistry, 8th ed.; Mcgraw-Hill: Boston, 2003; pp 466−474. (3) Sawyer, D. T.; Heiman, W. R.; Beebe, J. M. Chemistry Experiments for Instrumental Methods; John Wiley and Sons: New York, 1984; pp 297−300. (4) Chen, N. H. Practical Undergraduate Instrumental Analysis Laboratory Experiments; Nianhong Chen: 2013; pp 82−86. (5) Cook, G.; Feltman, P. M. Determination of Solvent Effects on KetoEnol Equilibria of 1,3-Dicarbonyl Compounds Using NMR. J. Chem. Educ. 2007, 84, 1827−1829. (6) Koudriavtsev, A. B.; Linert, W. Keto−Enol Equilibrium from NMR Data: A Closer Look at the Laboratory Experiment. J. Chem. Educ. 2009, 86, 1234−1237. (7) Nichols, M. A.; Waner, M. J. Kinetic and Mechanistic Studies of the Deuterium Exchange in Classical Keto−Enol Tautomeric Equilibrium Reactions. J. Chem. Educ. 2010, 87, 952−955. (8) Manbeck, K. A.; Boaz, N. C.; Bair, N. C.; Sanders, A. M. S.; Marsh, A. L. Substituent Effects on Keto−Enol Equilibria Using NMR Spectroscopy. J. Chem. Educ. 2011, 88, 1444−1445. (9) Powling, J.; Bernstein, H. J. The Effect of Solvents on Tautomeric Equilibria. J. Am. Chem. Soc. 1951, 73, 4353−4356. (10) Burett, J. L.; Rogers, M. T. Keto-Enol Tautomerism in βDicarbonyls Studied by Nuclear Magnetic Resonance Spectroscopy. I. Proton Chemical Shifts and Equilibrium Constants of Pure Compounds. J. Am. Chem. Soc. 1964, 86, 2105−2109. (11) Rogers, M. T.; Burett, J. L. Keto−Enol Tautomerism in βDicarbonyls Studied by Nuclear Magnetic Resonance Spectrocopy: II. Solvent Effects On Proton Chemical Shifts and on Equilibrium Constants. Can. J. Chem. 1965, 43, 1516−1525. (12) Lockwood, K. C. Solvent Effect on the Keto-Enol Equilibrium of Acetoacetic Ester. J. Chem. Educ. 1965, 42, 481−482. (13) Spencer, J. N.; Holmboe, E. S.; Kirchenbaum, M. R.; Firth, D. W.; Pinto, P. B. Solvent Effects on the Tautomeric Equilibrium of 2,4Pentanedione. Can. J. Chem. 1982, 60, 1178−1182. (14) Mills, S. G.; Beak, P. Solvent Effects on Keto-Enol Equilibria: Tests of Quantitative Models. J. Org. Chem. 1985, 50, 1216−1224. (15) Folkendt, M. M.; Weiss-Lopez, B. E.; Chauvel, J. P., Jr.; True, N. S. Gas-Phase Proton NMR Studies of Keto-Enol Tautomerism of Acetylacetone, Methyl Acetoacetate, and Ethyl Acetoacetate. J. Phys. Chem. 1985, 89, 3347−3352. (16) Keeler, J. Understanding NMR Spectroscopy; John Wiley and Sons: Chichester, England, 2005; pp 271−273. (17) Lide, D. R. CRC Handbook of Chemistry and Physics, 89th Edition, CRC-Press: Boca Raton, 2009; pp 9-50−9-58. (18) Dean, J. A. Lange’s Handbook of Chemistry, 14th ed.; McGrawHill: New York, 1992; 5.91−5.125. (19) Atkins, P.; de Paula, J. Physical Chemistry, 9th ed.; W. H. Freeman and Company: New York, 2010; p 634. (20) Dawber, J. G.; Crane, M. M. Keto-Enol Tautomerization: A Thermodynamic and Kinetic Study. J. Chem. Educ. 1967, 44, 150−152.

ASSOCIATED CONTENT

S Supporting Information *

Sample student experimental instructions and advice for laboratory instructors. This material is available via the Internet at http://pubs.acs.org. 742

dx.doi.org/10.1021/ed400583q | J. Chem. Educ. 2014, 91, 739−742