Modulation of tautomeric equilibria by ionic clusters. Acetylacetone in solutions of lithium perchlorate-diethyl ether

Article abstract of DOI:10.1021/ja012725o

Acetylacetone (2,4-pentanedione, 1) is a molecule whose tautomeric forms are in dynamic equilibrium. Concentrated salt solutions in nonaqueous solvents exert a remarkable influence on the keto-enol ratio of this β-diketone. The keto content of 1 increases from 5% in pure diethyl ether to 84.5% in a 4.14 M lithium perchlorate-diethyl ether (LPDE) solution, a nearly 17-fold increase. The equilibrium expression, K = [keto]/[enol] = k_f/k_r, exhibits a linear dependence on [LiCIO₄], with the formal order of participation of lithium ion in the equilibrium being 1.0. A kinetic analysis reveals that k_f is independent of LPDE concentration, whereas k_r displays an inverse dependence on salt concentration, indicating preferential coordination of the keto tautomer with Li⁺. Although 1 exits as the enol in water only to the extent of 16%, the addition of lithium perchlorate further reduces this figure. In an aqueous 4.02 M LiCIO₄ solution, acetylacetone enol accounts for only 4.6% of the total amount of 2,4-pentanedione present. It has also been found that acetylacetone itself is an excellent solvent for LiCIO₄ as well as for NaCIO₄ with solutions containing up to 7.5 M LiCIO₄ attainable. The enol content of 1 decreases dramatically from 81% to 7.4% on going from the neat liquid to a solution of 6.39 M LiCIO₄ in acetylacetone.

Full text of DOI:10.1021/ja012725o

Published on Web 08/10/2002
Modulation of Tautomeric Equilibria by Ionic Clusters.
Acetylacetone in Solutions of Lithium Perchlorate-Diethyl
Ether‡
Y. Pocker* and Greg T. Spyridis†
Contribution from the Department of Chemistry, Box 351700, UniVersity of Washington,
Seattle, Washington 98195
Received December 18, 2001
Abstract: Acetylacetone (2,4-pentanedione, 1) is a molecule whose tautomeric forms are in dynamic
equilibrium. Concentrated salt solutions in nonaqueous solvents exert a remarkable influence on the keto-
enol ratio of this â-diketone. The keto content of 1 increases from 5% in pure diethyl ether to 84.5% in a
4.14 M lithium perchlorate-diethyl ether (LPDE) solution, a nearly 17-fold increase. The equilibrium
expression, K ) [keto]/[enol] ) kf/kr, exhibits a linear dependence on [LiClO4], with the formal order of
participation of lithium ion in the equilibrium being 1.0. A kinetic analysis reveals that kf is independent of
LPDE concentration, whereas kr displays an inverse dependence on salt concentration, indicating preferential
coordination of the keto tautomer with Li+. Although 1 exits as the enol in water only to the extent of 16%,
the addition of lithium perchlorate further reduces this figure. In an aqueous 4.02 M LiClO4 solution,
acetylacetone enol accounts for only 4.6% of the total amount of 2,4-pentanedione present. It has also
been found that acetylacetone itself is an excellent solvent for LiClO4 as well as for NaClO4 with solutions
containing up to 7.5 M LiClO4 attainable. The enol content of 1 decreases dramatically from 81% to 7.4%
on going from the neat liquid to a solution of 6.39 M LiClO4 in acetylacetone.
Scheme 1
Introduction
Ever since the classic work of Knorr and Meyer on the two
forms of acetylacetone, ethyl acetoacetate, and other â-diketones,
tautomerization has been the subject of intense interest.1a-e
Tautomeric equilibria, particularly keto-enol systems, play an
important role in many biological processes. In aromatic
heterocyclic systems in solution, the keto is the predominate,
even exclusive, species at equilibrium, while in the gas phase
the situation is reversed.1f,g For example, in ethanol 4-pyridone
is the only tautomer present but in the gas phase 4-hydroxy-
pyridine is the major form.1h,i In contrast to simple carbonyls,
â-diones such as acetylacetone, 2,4-pentanedione (1), are
enolized to such a large extent that both tautomers are present
in measurable concentration at equilibrium, Scheme 1.2
sensitive to solvent polarity and hydrogen-bonding capacity.
Acetylacetone is ca. 96% enolized in the gas phase, 95% in
cyclohexane and diethyl ether, and 62% in acetonitrile, but only
16% in aqueous solution, Table 1.4 In addition to stabilizing
interactions due to solvent polarity, there are strong hydrogen-
bonding interactions between the diketo form and water, which
are lost on going to the vapor phase or to a nonpolar,
hydrophobic solvent system. The enols of most acyclic â-dike-
tones and â-ketoesters exist in the cis enol form where they are
While the tautomerization of 1 is base catalyzed, it is quite
insensitive to catalysis by the hydronium ion.3a However, the
enolization of 1 is powerfully catalyzed by divalent metal ions.3b
This tautomeric equilibrium has been shown to be exquisitely
(2) (a) For an excellent review of â-diketones and â-thioxo ketones, see:
Emsley, J. J. Struct. Bonding, 1984, 57, 149-190. (b) For an outstanding
review on the biochemistry of tautomerization reactions, see: Pollack, R.
M.; Bounds, P. L.; Bevins, C. L. In The Chemistry of Functional Groups:
Enones; Patai, S., Rappoport, Z., Eds.; John Wiley & Sons: New York,
1989; pp 559-597. For reviews of acetylacetone and other â-diketones in
inorganic chemistry, see: (c) Mehrotra, R. C. Pure Appl. Chem. 1988, 60,
1349. (d) Saito, K.; Jido, H.; Nagasawa, A. Coord. Chem. ReV. 1990, 100,
427. For recent reviews of simple enols and their generation, see: (e)
Kresge, J. Acc. Chem. Res. 1990, 23, 43. (f) Hart, H. Chem. ReV. 1979,
79, 515. (g) Toullec, J. AdV. Phys. Org. Chem. 1982, 18, 1. (h) Capon, B.;
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1988, 21, 135. (i) Rappoport, Z.; Biali, S. E. Acc. Chem. Res. 1988, 23,
442. For simple enol systems where the enol is the major tautomer present
at equilibrium, see: (j) Linder, P. E.; Correa, R. A.; Gino, J.; Lemal, D.
M. J. Am. Chem. Soc. 1996, 118, 2556. (k) Linder, P. E.; Lemal, D. M. J.
Org. Chem. 1996, 61, 5109. (l) Correa, R. A.; Linder, P. E. J. Am. Chem.
Soc. 1994, 116, 10795.
* Address correspondence to this author. E-mail: forster@chem.
washington.edu.
‡ For the previous paper in this series, see: Pocker, Y.; Spyridis, G. T.
J. Am. Chem. Soc. 2002, 124, 7390-7394.
† Current address: Department of Chemistry, Seattle University, Seattle,
WA 98122.
(1) (a) Knorr, L. Ann. 1896, 70, 293. (b) Knorr, L. Ann. 1899, 76, 322. (c)
Meyer, K. H.; Koppelmeier, P. Ber. 1911, 44, 2718. (d) Meyer, K. H. Ber.
1912, 45, 2843. (e) Knorr, L.; Rothe, O.; Averbeck, H. Ber. 1911, 44, 1138.
(f) Katritzky, A. R.; Karelson, M.; Harris, P. A. Heterocycles 1991, 32,
329. (g) Beak, P. Acc. Chem. Res. 1977, 10, 186. (h) Beak, P.; Fry, F. S.,
Jr.; Lee, J.; Steele, F. J. Am. Chem. Soc. 1976, 98, 171. (i) For the use of
2-pyridone as a tautomeric catalyst, see: Rony, P. R. J. Am. Chem. Soc.
1969, 91, 6090.
(3) (a) Bell, R. P.; Lidwell, O. M. Proc. R. Soc. 1940, A176, 88. (b) Meany,
J. E. J. Phys. Chem. 1969, 73, 3421.
9
10.1021/ja012725o CCC: $22.00 © 2002 American Chemical Society
J. AM. CHEM. SOC. 2002, 124, 10373-10380
10373

A R T I C L E S
Pocker and Spyridis
+
-
Table 1. Enol Content of Acetylacetone in Different Solvents and
M LPDE, these solutions are composed of Li(OEt2)2 ClO4
in the Gas Phasea
+
-
ions, while above 4.25 M, a mixture of Li(OEt2)2 ClO4 and
solvent
ꢀb
percent enol
reference
Li(OEt2)+ ClO4 exists.10 The limit of solubility, 6.06 M,
-
gas phase
C6H12
dioxane
CCl4
C6H6
(CH3CH2)O
CHCl3
CH3CO2H
C5H5N
CH3CH2OH
neat
CH3OH
CH3CN
DMA
1.0
2.0
2.2
2.2
2.3
4.3
4.8
6.2
12.3
24.3
25.7
32.6
36.2
37.0
46.6
78.5
92, 93, 97.6
91, 96, 97
82c
4l, 4m, 4k
4g, 4f, 4e
4b
4j, 4e, 4f, 4b
4b, 4j
4b
4j, 4g
4b, 4g, 4j
4h
4j, 4b
corresponds to the ionic composition Li(OEt2)+ ClO4
.
-
Pocker and Buchholz used the ionization of triphenylmethyl
chloride as a sensitive probe of the ionic environment present
in these solutions and observed a 7 × 109 fold increase in trityl
cation formation on going from pure ether to a 5.0 M LPDE
solution.10 Similarly, the rate of rearrangement of 1-phenylallyl
chloride to cinnamyl chloride rises 8.56 × 104 fold on going
from ether to 3.39 M LPDE, while the aminolysis of 4-nitro-
phenyl acetate by imidazole is accelerated by a factor of
5.8 × 104 from 0 to 4.49 M LPDE.11,13,14 The solvatochro-
matic behavior of Reichardt’s dye, phenol blue, and sub-
stituted nitroanilines in these media has been explored as has
the ability of these solutions to facilitate proton-transfer
reactions.16-18 Braun and Sauer derived Ω values, and from
these approximate ET30 values, for LPDE solutions by observing
the endo/exo product ratio for the Diels-Alder reaction be-
tween cyclopentadiene and methyl acrylate.19 Forman and
Dailey noted a 8.9-fold rate increase for the [4+2] cycloaddi-
tion of 9,10-dimethylanthracene and acrylonitrile.20 Recent
work has focused on exploiting the synthetic utility of these
media.21
94.6, 95, 95, 96c
89,c 97
95c
82.6, 87
67,c 73, 73.4
82
74.4, 82c
80.9,c 81, 82
68, 74,c 74
52.9, 62c
66
4a, 4e, 4f
4j, 4b, 4e
4j, 4b
4e
(CH3)2SO
H2O
60,c 62, 63
15.5,d 16
4b, 4e, 4f
4i, 4e
a At 25 °C unless otherwise noted. b Taken from: Handbook of Chemistry
and Physics, 60th ed.; Weast, R. C., Ed.; CRC Press: Boca Raton, FL,
1980; pp E56-E58. c At 33 °C. d At 20 °C.
stabilized by conjugation and intramolecular hydrogen bonds,
Scheme 1.5 Furthermore, the two Kekule structures that can be
depicted for symmetrical acyclic enols such as acetylacetone
are equivalent, implying that the hydrogen bond is symmetrical.
This has been shown to be the case by electron diffraction
studies.5,6
We have expanded on our earlier observations by investigat-
ing the effects of these room-temperature molten salt solutions
Previous work in these laboratories has elaborated on the early
observations of Willard et al. and Sille´n et al. concerning the
extraordinary solubility of strictly anhydrous lithium perchlorate
in diethyl ether.7-18 Solutions containing up to 6.06 M lithium
perchlorate in ether, hereafter LPDE, are possible. These highly
polar concentrated salt solutions have been shown by conductiv-
ity and vapor pressure data to exist as complex ionic clusters
composed of LiClO4 and Et2O, rather than simple aggregates
of ions.8,9 Solubility-temperature curves, NMR spectroscopy,
and heats of solution measurements indicate that below 4.25
(7) (a) Willard, H. H.; Smith, G. F. J. Am. Chem. Soc. 1923, 45, 286. (b)
Schilt, A. A. Perchloric Acid and Perchlorates; G. Fredwick Smith
Chemical Co.: Columbus, OH, 1979; pp 32-38. (c) For a treatise on the
effects of added salt on organic and organometallic chemistry, see: Loupy,
A.; Tchoubar, B. Salt Effects in Organic and Organometallic Chemistry;
VCH: New York, 1992 (originally published in French under the title
Effects de sels en Chimie organique et organometallique; Editions
Bordas: Paris, 1988). For reviews of the role of electrostatics in biomo-
lecular recognition and control, see: (d) Carbeck, J. D.; Colton, I. J.; Gao,
J.; Whitesides, G. M. Acc. Chem. Res. 1998, 31, 343. (e) Koshland, D. E.,
Jr. Pure Appl. Chem. 1971, 25, 119.
(8) Eklelin, K.; Sille´n, L. G. Acta Chem. Scand. 1953, 7, 987.
(9) (a) Johnson, O. Ph.D. Thesis, University of Michigan, Ann Arbor, MI,
1948. (b) Chu, J. C. H. Ph.D. Thesis, University of Michigan, Ann Arbor,
MI, 1949.
(10) Pocker, Y.; Buchholz, R. F. J. Am. Chem. Soc. 1970, 92, 2075.
(11) Pocker, Y.; Buchholz, R. F. J. Am. Chem. Soc. 1970, 92, 4033.
(12) Pocker, Y.; Buchholz, R. F. J. Am. Chem. Soc. 1971, 93, 2905.
(13) Pocker, Y.; Ellsworth, D. L. J. Am. Chem. Soc. 1977, 99, 2276.
(14) Pocker, Y.; Ellsworth, D. L. J. Am. Chem. Soc. 1977, 99, 2284.
(15) Pocker, Y.; Ciula, J. C. J. Am. Chem. Soc. 1988, 110, 2904.
(16) Pocker, Y.; Ciula, J. C. J. Am. Chem. Soc. 1989, 111, 4728.
(17) Pocker, Y.; Spyridis, G. T. J. Am. Chem. Soc. 2002, 124, 7390.
(18) (a) Reuber, M. S.; Pocker, Y. Proceedings of the 6th International
Symposium on Solute-Solute-SolVent Interactions; Pergamon Press:
Oxford, 1982; 5P-13. (b) Rueber, M. S. Ph.D. Thesis, University of
Washington, Seattle, WA, 1987.
(4) (a) Burdett, J. L.; Rogers, M. T. J. Am. Chem. Soc. 1964, 86, 2105. (b)
Burdett, J. L.; Rogers, M. T. Can. J. Chem. 1965, 43, 1516. (c) Burdett, J.
L.; Rogers, M. T. J. Phys. Chem. 1966, 70, 939. (d) Billman, J. H.; Sojka,
S. A.; Taylor, P. R. J. Chem. Soc., Perkins Trans. 2 1972, 2034. (e) Spencer,
J. N.; Holmboe, E. S.; Kirshenbaum, M. R.; Firth, D. W.; Pinto, P. B.
Can. J. Chem. 1981, 60, 1178. (f) Allen, G.; Dwek, R. A. J. Chem. Soc. B
1966, 161. (g) Reeves, L. W. Can. J. Chem. 1957, 35, 1351. (h) Kondo,
G.; Takemoto, T.; Ikenone, T. J. Chem. Soc. Jpn. Ind. Chem. Sect. 1968,
68, 1404. (i) Schwarzenbach, G.; Felder, E. HelV. Chem. Acta 1944, 27,
1044. (j) Emsley, J.; Freeman, N. J. J. Mol. Struct. 1987, 161, 193. (k)
Folkendt, M. M.; Weiss-Lopez, B. E.; Chauvel, J. P., Jr.; True, N. S. J.
Phys. Chem. 1985, 89, 3347. (l) Mella, T. P.; Merrifield, R. J. Appl. Chem.
1969, 19, 79. (m) Strohmeier, W.; Huhne, I. Z. Naturforsch. 1952, 7B,
184. For 17O NMR work performed on acetylacetone and other â-diketones,
see: (n) Gorodetsky, M.; Luz, Z.; Mazur, Y. J. Am. Chem. Soc. 1967, 89,
1183. (o) Luz, Z.; Silver, B. J. Phys. Chem. 1966, 70, 1328.
(5) For the crystal structure of 1, see: (a) Boese, R.; Antipin, M. Y.; Bla¨ser,
D.; Lyssenko, K. A. J. Phys. Chem. B 1998, 102, 8654. (b) Lowery, A.
H.; D’Antonio, P.; George, C.; Karle, J. Am. Chem. Soc. 1971, 93, 6399.
(c) Andreassen, A. L.; Bauer, S. H. J. Mol. Struct. 1972, 12, 381. For recent
quantum mechanical calculations of the enol of 1, see: (d) Mavri, J.;
Grdadolnik, J. J. Phys. Chem. A 2001, 105, 2045. (e) Mavri, J.; Grdadolnik,
J. J. Phys. Chem. A 2001, 105, 2039.
(6) (a) Camerman, A.; Mastropaolo, D.; Camerman, N. J. Am. Chem. Soc.
1983, 105, 1584. These authors have published a structure of acetylacetone
in the presence of diphenylhydantoin and 9-ethyladenine where the
hydrogen bond is not symmetrical. They claim that there are no interactions
between the tautomers of acetylacetone and the cosolutes. Crystal structures
of other symmetrical â-diketones, such as 1,3-diphenyl-1,3-propanedione,
ref 6b, reveal symmetrical enols. An interesting case where an unsym-
metrical enol exists is that of 3-phenyl-1-(2,4,6-triphenylphenyl)propane-
1,3-dione, ref 6c. Here, steric considerations force the hydroxy group to
be in the neighborhood of the unsubstituted phenyl ring, and two different
C-O bond lengths are observed. (b) Kaitner, B.; Mestrovic, E. Acta
Crystallogr. 1993, C49, 1523. (c) Abram, S.; Abram, U.; Zimmermann, T.
Acta Crystallogr. 1993, C50, 765.
(19) Braun, R.; Sauer, J. Chem. Ber. 1986, 119, 1269.
(20) Forman, M. A.; Dailey, W. P. J. Am. Chem. Soc. 1991, 113, 2761.
(21) For the synthetic utility of the solvent system lithium perchlorate-diethyl
ether, see: (a) Heydari, A.; Larijani, H.; Emami, J.; Karami, B. Tetrahedron
Lett. 2000, 41, 2471. (b) Saito, N.; Grieco, P. A. Yuki Gosei Kagaku
Kyokaishi 2000, 58, 39. (c) Babu, B. S.; Balasubramanian, K. K. Carbohydr.
Lett. 1999, 3, 339. (d) Sankararaman, S.; Nesakumar, J. E. J. Chem. Soc.,
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K. R. Green Chem. 1999, 1, 23. (f) Babu, B. S.; Balasubramanian, K. K.
Tetrahedron Lett. 1998, 39, 9287. (g) Kawamura, M.; Kobayashi, S.
Tetrahedron Lett. 1999, 40, 2471. (h) Palani, N.; Chadha, A.; Balasubra-
manian, K. K. J. Org. Chem. 1998, 63, 5318. (i) Zarghi, A.; Naimi-Jamal,
M. R.; Webb, S. A.; Balalaie, S.; Saidi, M. R.; Ipaktschi, J. Eur. J. Org.
Chem. 1998, 197. (j) Jenner, G.; Ben Salem, R. Tetrahedron 1997, 53,
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A. I. Russ. J. Gen. Chem. 1997, 67, 1361. (l) Sudha, R.; Maloia, N. K.;
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Ipaktschi, J.; Eckert, T. Chem. Ber. 1995, 128, 1171. (n) Flohr, A.;
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10374 J. AM. CHEM. SOC. VOL. 124, NO. 35, 2002

Modulation of Tautomeric Equilibria
A R T I C L E S
on the keto-enol equilibrium of acetylacetone in various LPDE
solutions. We also carried out parallel studies with 1 in aqueous
salt solutions to ascertain if the extent of enolization can be
further reduced solely by an increase in solvent polarity even
in an extremely polar, hydrogen-bonding medium. The forward
and reverse rates of equilibration have been determined in an
attempt to provide a more complete analysis of the modulation
of tautomeric equilibria by such ionic clusters. The systems
chosen were solutions of LiClO4 in ether, water, and acetylac-
etone itself, where solutions up to ca. 7.5 M can be prepared.
In addition, sodium perchlorate was found to dissolve in
acetylacetone to the extent of ca. 1.7 M.
Experimental Section
General Methods. Kinetic runs were carried out on a Cary 210
spectrophotometer interfaced to an Apple IIe computer through a
bidirectional parallel interface. The cell compartment was maintained
at 25.0 ( 0.1 °C with a Forma-Temp Junior model 2095-2 constant-
temperature bath. Proton NMR spectra were recorded with a Varian
T-60 60 MHz instrument, using TMS as an internal standard, with the
sample well set at 33.0 ( 1.0 °C. Infrared spectra were taken on a
Perkin-Elmer PE-528 using NaCl plates and solution cells (Aldrich,
0.2083 mm path length).
Figure 1. Plot of ln(At - A∞) vs time for the re-equilibration of
acetylacetone in 4.14 M LiClO4-Et2O at 25.0 °C. Here ln(At - A∞) )
-0.804 - 0.530t (r ) 0.999).
Anhydrous lithium perchlorate and sodium perchlorate (GFS Chemi-
cals) were recrystallized twice from water and dried at 152 °C under
vacuum for at least 24 h. The anhydrous salts were stored under nitrogen
or argon in a tightly sealed flask in a desiccator over P2O5. Diethyl
ether was distilled under dry nitrogen or argon from excess lithium
aluminum hydride (Aldrich) just prior to use. Dioxane (Alfa) was
distilled under dry nitrogen from sodium and benzophenone. Acetyl-
acetone (Aldrich) was distilled through a jacketed, 50 cm vigreux
column (bp ) 134 °C at 760 Torr) immediately before use and found
to be 99.7% pure via gas chromatography (GC) analysis. Its 1H NMR
(neat) spectrum possesses the following resonances: δ 1.98 (s, 3H keto
methyl), δ 2.14 (s, 3H enol vinyl methyl), δ 3.57 (s, 2H, keto
methylene), δ 5.54 (s, 1H enol vinyl), δ 16.52 (s, 1H enol hydroxy).
kobsd ) kf + kr
(1)
From the above discussion, Beer’s law for this system can be expressed
as
A ) ꢀenolXenol[acetylacetone]total ) ꢀenol[enol]
(2)
where Xenol is the mole fraction of enol present and ꢀenol is the extinction
coefficient of acetylacetone enol. From the A0 values obtained from
the first-order plots and the fact that acetylacetone is 95% enolized in
ether, ꢀenol can be expressed as shown in eq 3.
Lithium acetylacetonate was prepared by titrating 1 with methyl-
lithium (Aldrich, 1.0 M in ether) in dry ether under nitrogen or argon
and stored under nitrogen at -20 °C. Lithium acetylacetonate possesses
a λmax of 292 nm and an ꢀ ) 39 800 M-1 cm-1 over the concentration
range 0.5-4.0 M LPDE. Its infrared spectrum, taken as a Nujol mull,
showed a νCdO ) 1610 cm-1 as well as a νCdC ) 1520 cm-1. Although
the lithium salt of acetylacetone is insoluble in ether, it is quite soluble
in all of the LPDE solutions investigated.
ꢀenol ) A0/(0.95[acetylacetone]total
)
(3)
By use of these extinction coefficients as well as the A∞ values ob-
tained from the trace of absorbance versus time, equilibrium con-
stants, K, for the ketonization of 1 (Scheme 1) can be calculated from
eq 4:
Kinetic Measurements in Ethereal and Aqueous Salt Solutions.
Kinetic runs were initiated by injecting 10.0 µL of a 1.2 × 10-2
M
K ) [keto]/[enol] ) {[acetylacetone]total - Q}/Q ) kf/kr (4)
acetylacetone-ether solution into 3.0 mL of LPDE solution and
monitoring the decrease in absorbance over time at 275 nm. Since 3,3-
dimethyl-2,4-pentanedione exists exclusively as the diketone, with a
λmax ) 310 nm and an ꢀ310nm ) 170 M-1 cm-1 in ether and ethanol, the
absorbance observed for acetylacetone at 275 nm is due solely to its
enol form.22 The decrease in absorbance over time is the result of a
decrease in enol concentration as the equilibrium shifts to accommodate
a medium of greater polarity, Scheme 1. As illustrated in Figure 1,
plots of ln(At - A∞) versus time reveal that the tautomerization of
acetylacetone obeys good first-order kinetics with respect to the
â-diketone.
where Q ) A∞/ꢀenol. Table 2 lists kobsd, kf, and kr for the ketonization of
acetylacetone in various LPDE solutions, while Table 3 lists values of
K and the percent enol, Pe, for the tautomerization of acetylacetone in
various LPDE solutions. Kinetic runs for a given salt concentration
were done at least in triplicate, and ꢀenol, kobsd, and K values were within
(5%.
For aqueous solutions, a similar method was used: 10.0 µL of a 1.5
× 10-2 M acetylacetone-dioxane solution was injected into various
LiClO4-H2O solutions, using 0.82 as the mole fraction of acetylacetone
enol present in dioxane.4b Table 4 lists values of K, Pe, kobsd, kf, and kr
for the ketonization of acetylacetone in various aqueous LiClO4
solutions.
Since tautomerization is a reversible process, the observed rate
constant, kobsd, refers to the sum of the first-order constants for the
forward, kf, and reverse, kr, processes; Scheme 1, eq 1.
Lithium and Sodium Perchlorate-Acetylacetone Solutions. Dur-
ing the course of this investigation, it was found that 2,4-pentanedione
can solubilize large quantities of alkali metal perchlorates. For
LiClO4-acetylacetone, saturation occurs at a 1:1 solute/solvent mole
(22) Yoffe, S. T.; Popov, E. M.; Yatsuro, K. V.; Tulikova, E. M.; Kabachnik,
M. I. Tetrahedron 1962, 18, 923.
9
J. AM. CHEM. SOC. VOL. 124, NO. 35, 2002 10375

A R T I C L E S
Pocker and Spyridis
Table 2. Values of kobsd, kf, and kr for the Ketonization of
Acetylacetone in Various LiClO4-Et2O Solutions at 25.0 °C
) 1.0 and thus [keto] ) [enol] at equilibrium occurs at ca. 1.5
M LPDE, which is well within the dietherate region of LPDE.
To better understand the dependence of the keto-enol equilib-
rium of acetylacetone on lithium perchlorate, the minimum order
of participation of Li+, n, can be determined as described in
eqs 6 and 7
[LPDE] (M)
k
obsd (min-1
)
k (min-1
)
k (min-1
)
f
r
0.00a
0.056
0.10
0.20
0.50
1.00
2.00
3.00
4.14
2.296
1.04
10.6 × 10-2
7.07 × 10-2
3.42 × 10-2
1.90 × 10-2
2.11 × 10-2
1.83 × 10-2
1.86 × 10-2
1.75 × 10-2
2.42 × 10-2
2.190
9.68 × 10-1
3.42 × 10-1
9.75 × 10-2
5.26 × 10-2
2.17 × 10-2
1.35 × 10-2
9.17 × 10-3
7.35 × 10-3
3.76 × 10-1
1.17 × 10-1
7.37 × 10-2
4.00 × 10-2
3.20 × 10-2
2.66 × 10-2
3.16 × 10-2
K ) ([keto]/[enol])[LiClO4]n
ln K ) n ln[LiClO4] + ln K′
(6)
(7)
where K′ ) [keto]/[enol] in diethyl ether. From Figure 3, it can
be seen that a plot of ln(K - K′) versus ln[LPDE] displays a
slope of 0.96 throughout the entire LPDE concentration range
investigated, a value extremely close to unity.
a The solution contained 0.33% methanol.
Table 3. Equilibrium Constants and the Percentage of Enol Form
of Acetylacetone Present at Equilibrium for the Tautomerization of
Acetylacetone in LiClO4-Et2O Solutions at 25.0 °C
From the crystal structure of the diketo form of acetylacetone,
the carbonyl groups form a dihedral angle of 48.6°, with an
O-O distance of 2.77 Å, 2.5b,5c The main factor which
determines the conformation of the keto form of â-dicar-
bonyls is the strong repulsion of the localized CdO bond
dipoles, and such conformations as depicted by 2 account for
the large dipole moments of â-dicarbonyls: 3.62 D for 2,4-
pentanedione and 3.39 D for ethyl acetoacetate.23 As lithium
ion is known to be tetrahedral in solution with a diameter of
1.56 Å, 3 is envisioned for the interaction of LiClO4-Et2O
clusters with the keto tautomer of acetylacetone in the dietherate
region of LPDE.16,18 Further intimate reactions with ions or ion
pairs is not required, and any additional stabilization is due to
an increase in the Coulombic forces present in solution upon
addition of salt.
a
[LPDE] (M)
K
P a
e
0.00b
0.00c,d
0.056
0.086
0.100
0.139
0.200
0.305
0.500
0.808
1.00
5.26 × 10-2
4.82 × 10-2
0.116
95.0
95.4
89.6
90.5
90.9
88.0
83.7
79.3
71.6
70.5
57.8
44.6
34.4
23.3
0.105
0.101
0.136
0.196
0.261
0.397
0.419
0.729
2.00
3.00
4.14
1.24
1.91
3.30
a K ) [keto]/[enol], with Pe ) 100/(K + 1). b Taken from ref 4b. c This
work. d The solution contained 0.33% methanol.
ratio (7.52 M), while for NaClO4-acetylacetone solutions, saturation
occurs at a solute/solvent mole ratio of 0.2:1.0 (1.73 M).
Since the rate of keto to enol conversion is slow with respect to the
NMR time scale, the individual proton and carbon resonances of each
tautomer are observed. Burdett and Rogers used the proton resonances
to calculate the percentage of enol present in various solvents as well
as in neat solutions of various â-diketones and â-ketoesters.4a-c Billman
et al. utilized the carbonyl resonances in the 13C NMR spectrum and
obtained equilibrium constants in good agreement with those obtained
via 1H NMR.4d The method of Burdett and Rogers was used to calculate
the keto-enol ratio at equilibrium for solutions of lithium perchlorate
and sodium perchlorate in acetylacetone, using eq 5.
K ) [keto]/[enol] ) (area of keto methylene)/2(area of enol vinyl)
(5)
Further evidence for the formation of 3 in LPDE solutions is
obtained from an analysis of kf and kr, Table 2. As the LPDE
concentration increases, the rate of re-equilibration decreases;
there is a 73-fold rise in the half-life of the reaction on going
from pure ether to 4.14 M LPDE. The ratio of ketonization rate
For a given salt concentration, the keto methylene and enol vinyl peaks
were integrated at least four times and values of K were within (5%.
Table 5 lists values of K and Pe for various LiClO4-acetylacetone and
NaClO4-acetylacetone solutions.
Results and Discussion
constants kf ether/kf4.14M LPDE ) 4.38, while kr ether/kr4.14M LPDE
)
298. Thus, the rate of diketo formation, enol to keto, is rela-
tively unaffected by salt, while the rate of enolization, keto to
enol, shows a marked decrease. From Figure 4, it can be
seen that the rate coefficient for the ketonization process dis-
plays an inverse dependence on LPDE concentration up to
Solutions of Lithium Perchlorate in Diethyl Ether and
Water. The addition of perchlorate salts to both nonpolar aprotic
and polar protic solvents can drastically alter the keto-enol ratio
present in acetylacetone. As outlined in Table 2 for acetylacetone
in LPDE solutions, the percentage of enol present at equilibrium
decreases from 95.4% in pure ether to 23.2% in 4.14 M LPDE,
producing a 66-fold increase in the equilibrium constant. As
can be seen in Figure 2, a plot of K versus [LiClO4] is linear
well past 3.0 M LPDE with a slope of 0.69. From Figure 2, K
(23) (a) Bouma, W. J.; Radom, L. Aust. J. Chem. 1978, 31, 1649. (b) Naoum,
M. M.; Botros, M. G. Indian J. Chem., Sect A 1986, 25, 427. (c) Emsley,
J.; Freeman, N. J.; Parker, R. J.; Overill, R. E. J. Chem. Soc., Perkin Trans.
2 1986, 1489. (d) Naoum, M. M.; Botros, M. G.; Abdel Moteleb, M. M.
Indian J. Chem., Sect A 1986, 25, 639.
9
10376 J. AM. CHEM. SOC. VOL. 124, NO. 35, 2002

Modulation of Tautomeric Equilibria
A R T I C L E S
Table 4. Equilibrium Constants, the Percentage of Acetylacetone Enol Present at Equilibrium, kobsd, kf, and kr for the Ketonization of
Acetylacetone in LiClO4-H2O Solutions at 25.0 °Ca
P a
k
obsd (s-1
)
k (s-1
)
k (s-1
)
a
[LiClO ] (M)
K
4
e
f
r
1.01 × 10-2
5.36 × 10-2
1.79 × 10-1
3.57 × 10-1
1.61
6.97
6.96
7.72
7.07
9.49
12.5
12.6
11.5
12.4
9.5
9.61 × 10-2
1.08 × 10-1
1.13 × 10-1
1.12 × 10-1
1.24 × 10-1
1.34 × 10-1
1.78 × 10-1
8.40 × 10-2
9.42 × 10-2
1.00 × 10-1
9.77 × 10-2
1.12 × 10-1
1.23 × 10-1
1.70 × 10-1
1.21 × 10-2
1.35 × 10-2
1.30 × 10-2
1.38 × 10-2
1.12 × 10-2
1.10 × 10-2
8.00 × 10-3
3.30
4.03
11.3
20.7
8.1
4.6
a K ) [keto]/[enol], with Pe ) 100/(K + 1).
Table 5. Equilibrium Constants and the Percentage of
Acetylacetone Enol Present at Equilibrium for the Tautomerization
of Acetylacetone in LiClO4-Acetylacetone and
NaClO4-Acetylacetone Solutions at 33.0 °C
a
[MClO ] (M)
K
P a
4
e
0.00b
0.00c
0.00d
0.00e
0.200f
0.562f
0.816f
0.944f
1.71f
0.236
0.235
0.220
0.231
0.306
0.278
0.398
0.431
0.646
1.07
2.27
4.07
12.4
0.332
0.429
0.500
0.577
0.836
80.9
81.0
82.0
81.2
76.5
78.2
71.5
69.8
60.7
48.3
30.5
19.7
7.4
2.31f
3.90f
5.05f
6.39f
0.362g
0.814g
1.13g
1.46g
1.61g
75.1
69.9
66.7
63.4
54.5
a K ) [keto]/[enol], with Pe ) 100/(K + 1). b Taken from ref 4a. c Taken
from ref 4e. d Taken from ref 4f. e This work. f LiClO4-acetylacetone
solutions. g NaClO4-acetylacetone solutions.
ca. 0.2 M and then becomes independent of added salt, while
the rate coefficient for the enolization reaction exhibits an
inverse dependence on LPDE concentration throughout the
entire range of salt concentration. Thus, stabilization of the
keto tautomer, as in 3, reduces the rate of enolization but
leaves the velocity of ketonization untouched, resulting in a
decrease in the overall reaction rate as the salt concentration is
increased.
Figure 2. Plot of K ) [keto]/[enol] vs [LiClO4] for the ketonization of
acetylacetone in the solvent system LiClO4-Et2O. The equation for the
linear portion of the curve is K ) 0.687[LiClO4] + 5.23 × 10-2 (r ) 0.997).
The inset shows the relationship between K and [LPDE] over the range
0.0-0.6 M LPDE.
Previous investigations concerning the effect of lithium
perchlorate on the reaction rates and positions of equilibria of
various reactions all showed increases in the formal order of
participation of lithium perchlorate as the [LPDE] increased.
For the ionization of trityl chloride and the acid-base re-
action of HCl with pyridine in LPDE, n increased steadily
from 2 to 12.10 For the first-order rate constant for the
rearrangement of 1-phenylallyl chloride to cinnamyl chloride,
n grew from 1 to 4 in several LiClO4-solvent mixtures as more
salt was added.13 Similar increases in n were observed in the
rate constant for the reaction of 4-nitrophenyl acetate with
imidazole in LPDE and the acid-base equilibrium between
nitrophenols and aromatic amines.14,18b However, for the proton-
transfer reaction between 2-nitrophenol and imidazole from 0.0
to 3.53 M LPDE, the formal order of participation of LiClO4
remained close to unity until ca. 3 M LiClO4, at which time it
began to approach 2.18b Pocker and Ciula reported a similar
phenomenon for the deprotonation of tropolone by pyridine
bases in LPDE; the order in salt increases from 1 to 2.16 In
these cases, a tertiary amine is reacting with an intramolecularly
hydrogen-bonded acid, and it is possible to think of the lithium
ion as replacing the proton in the hydrogen bond upon
deprotonation.
In pure ether, where 95% of the acetylacetone present exists
as the enol, the infrared spectrum of 1 is dominated by the
conjugated νCCO stretch centered around 1620 cm-1 4j,24
As the
.
LPDE concentration is increased, the bands corresponding to
the symmetric and asymmetric νCO stretching modes of the keto
tautomer centered around 1730 cm-1 increase in intensity due
to the increase in diketo concentration. As the salt concentration
increases, the symmetric and asymmetric stretching frequencies
of the keto carbonyls remain constant. At 0.2 M LPDE, the
ν
CCO of the enol begins to split into two peaks, one still at 1620
cm-1 and another at 1590 cm-1, a phenomenon that becomes
more pronounced as the LPDE concentration increases. This
(24) (a) Fevre, R. J. W.; Welsh, H. J. Chem. Soc. 1949, 2230. (b) Shigorin, D.
N. Zh. Fiz. Khim. 1950, 24, 924.
9
J. AM. CHEM. SOC. VOL. 124, NO. 35, 2002 10377

A R T I C L E S
Pocker and Spyridis
Figure 3. Plot of ln(KLPDE - Kether) vs ln[LiClO4] for the ketonization of
acetylacetone in the solvent system LiClO4-Et2O at 25.0 °C. The equation
for the line is ln(K - K′) ) -0.524 + 0.96 ln[LiClO4] (r ) 0.984).
Figure 4. Plot of ln kf (O) and ln kr (b) vs ln[LiClO4] for the ketonization
of acetylacetone in the solvent system LiClO4-Et2O at 25.0 °C.
hydrogen bonding, while the enol form can produce its own
intramolecular hydrogen bond, Scheme 1, as well as form
hydrogen bonds with H2O. Therefore, interactions between
lithium ion and the keto form, as in 3, are not required for
stabilization.4e,4i,25 The observed rate constant, kobsd, exhibits a
slight increase with added salt until 3.3 M salt and then begins
to increase rapidly, with the percentage of kobsd coming from
the rate of ketonization, kf, rising from 87.4% to 95.5%. A plot
of ln k versus ln[LiClO4] shows no dependence on lithium ion
for the keto-enol equilibrium until ca. 3 M salt, at which time
the forward rate, ketonization, displays a linear dependence on
Li+, while the reverse rate, enolization, exhibits an inverse
dependence. Due to the hydrogen-bonding capacity and high
polarity of water, large amounts of added salt are required in
order to observe substantial changes in the enol content of
acetylacetone.
Lithium and Sodium Perchlorate Solutions in Acetylac-
etone. Anhydrous lithium perchlorate is quite soluble in neat
acetylacetone (7.52 M), while NaClO4 is much less so (1.73
M). As listed in Table 5, the percentage of enol present at
equilibrium decreases from 81% in neat acetylacetone to 54.5%
in a 1.61 M sodium perchlorate-acetylacetone solution and
7.4% in a 6.39 M lithium perchlorate-acetylacetone solution,
the largest change observed in any of the solvent systems
investigated. This corresponds to a 52.5-fold increase in K for
mixtures of LiClO4-acetylacetone and a 3.5-fold increase for
NaClO4-acetylacetone solutions. Thus, at the solubility limit
observation is indicative of the interaction between lithium ion
and the enol tautomer as in 4.
This interaction is not as strong as that between Li+ and the
keto form of acetylacetone, as the velocity of enol disappearance,
kf, is only slightly reduced by added perchlorate. There is no
evidence of enolate ion formation as indicated by a lack of a
νCC at 1520 cm-1. Thus, the addition of LiClO4 to ether
dramatically reduces the enol content of acetylacetone by
increasing the dielectric constant of the medium, which favors
the more polar keto form, as well as by complexing with the
diketo tautomer to a much larger extent than with the enol form.
In aqueous solution, the addition of LiClO4 further reduces
the already small amount of acetylacetone enol present, Table
4. In pure water, acetylacetone is 16% enolized, while in an
aqueous 4.03 M LiClO4 solution that number falls to 4.6%, a
3.5-fold decrease which results in a 3.9-fold increase in the
equilibrium constant. As can be seen in Figure 5, a plot of ln(K
- K′) versus ln[LiClO4] shows no dependence on lithium
perchlorate until ca. 1 M LiClO4, after which the order of salt
participation approaches unity. At low salt concentrations, water
itself acts to stabilize the keto tautomer of 2,4-pentanedione via
(25) Toulllec, J. In The Chemistry of Functional Groups: The Chemistry of Enols;
Rappoport, Z., Ed.; John Wiley & Sons: New York, 1990; pp 324-398.
9
10378 J. AM. CHEM. SOC. VOL. 124, NO. 35, 2002

Modulation of Tautomeric Equilibria
A R T I C L E S
Figure 5. Plot of ln(Klithium
ketonization of acetylacetone in the solvent system LiClO4-H2O at
25.0 °C.
- Kwater) vs ln[LiClO4] for the
perchlorate-water
Figure 6. Plot of ln(Klithium perchlorate-acetylacetone - Kacetylacetone) vs ln[MClO4]
for the ketonization of acetylacetone in the solvent systems LiClO4-
acetylacetone (9) and NaClO4-acetylacetone (0) at 33.0 °C.
of lithium perchlorate in 2,4-pentanedione, the mixture is
composed almost entirely of a single tautomeric form of
acetylacetone. At ca. 2.3 M LiClO4-acetylacetone, [keto] )
[enol] at equilibrium, producing K ) 1.0. As can be seen in
Figure 6, a plot of ln(K - K′) versus ln[MClO4] (M ) Li or
Na) is curved upward, indicating that as the concentration of
perchlorate salt is increased, the order of participation of MClO4
with respect to the keto-enol equilibrium of acetylacetone
increases as well and that LiClO4 and NaClO4 behave similarly
in acetylacetone. For LiClO4-acetylacetone solutions, n ap-
proaches unity between 0.0 and 1.6 M salt and then rises to 2
up until 5 M LiClO4. Past 5 M LiClO4, slopes of 3 and higher
are observed. For NaClO4-acetylacetone mixtures, the order of
participation reaches a maximum value of 1. In the region where
n ) 1, complexes such as 5a, analogous to 3, are envisioned.
For n ) 2, where two lithium ions are interacting with a single
molecule of diketo, complexes such as 5b are possible, with
larger aggregates observed past 5 M LiClO4.
one]/[LiClO4] ratio approaches 1:1, the enol carbonyl band splits
into two peaks, indicative of lithium ion-enol interaction, such
as shown by 4, similar to the behavior observed in LPDE
solutions.
Conclusions. The addition of lithium perchlorate to an aprotic
solvent of low polarity such as diethyl ether has a dramatic effect
on the position of the keto-enol equilibrium of 2,4-pentanedione
in these media. As more salt is added, an increase in the polarity
of the medium in conjunction with one-to-one coordination of
the diketo form by lithium ion drives the position of equilibrium
away from the intramolecularly hydrogen-bonded enol toward
the more polar keto tautomer. The enol-to-keto rate constant is
unaffected by salt, while the rate of enolization, keto-to-enol,
decreases. Such stabilization can supplement the hydrogen-
bonding capacity present in hydroxylic solvents such as water,
where the addition of lithium perchlorate further reduces the
already low percentage of enol present. A similar situation is
observed when acetylacetone itself acts as the solvent for lithium
and sodium perchlorates. In this case, as the salt concentration
is increased, ionic clusters are formed composed of metal
perchlorate-â-diketone aggregates, clusters whose composition
varies as more salt is added. These observations, taken as a
whole, provide a clearer picture of the penetrating power of
Coulombic fields in hydrophobic media and in fused salts.
Acknowledgment is made to the donors of the Petroleum
Research fund, administered by the American Chemical Society,
for the support of this research. We also thank Professor John
As the keto form becomes the dominant tautomer, its νCO
stretching modes increase in intensity. When the [2,4-pentanedi-
9
J. AM. CHEM. SOC. VOL. 124, NO. 35, 2002 10379

A R T I C L E S
Pocker and Spyridis
E. Meany, Dr. Mark S. Rueber, and Dr. James C. Ciula for
helpful assistance and insightful discussions.
acetylacetone and NaClO4-acetylacetone solutions (PDF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
Supporting Information Available: Infrared spectra of 1 in
Et2O and LPDE solutions and infrared spectra of LiClO4-
JA012725O
9
10380 J. AM. CHEM. SOC. VOL. 124, NO. 35, 2002