3388 J. Am. Chem. Soc., Vol. 118, No. 14, 1996
Chiang et al.
reactivity of hydroxide ion toward ketenes is not very much
greater than that of water,13a and catalysis by hydroxide ion is
consequently weak.
Least squares analysis of the data making up the rate profile
shown in Figure 1 gives the following rate constants: k ) (1.54
( 0.07) × 106 s-1 for the uncatalyzed reaction and k ) (1.86
( 0.03) × 108 M-1 s-1 for the hydroxide-ion-catalyzed process.
These results show acetylketene to be a remarkably reactive
substance; its uncatalyzed reaction, for example, is 42 000 times
more rapid than the uncatalyzed reaction of ketene itself, for
which k ) 36.5 s-1 10b
This enhanced reactivity may be
.
attributed to the ability of the acetyl substituent to stabilize
negative charge: in the reaction of ketenes with nucleophiles,
the substrate takes on such charge which can then be delocalized
into the acetyl group.
Figure 1. Rate profiles for the hydration of acetylketene (∆) and the
ketonization of acetoacetic acid enol (O) in aqueous solution at 25 °C.
is due to ketonization of the acetoacetic acid enol hydration
product (eq 2). This assignment is supported by the response
of the rates of these absorbance changes to changes in the acid-
base and isotopic properties of the solvent, as detailed below:
the chemistry revealed by these changes is typical of the
behavior of ketene-hydration and enol-ketonization reactions.
Rates of hydration of acetylketene were measured in aqueous
perchloric acid and sodium hydroxide solutions and also in water
with no acid or base added. Acid and base concentrations were
varied, but ionic strength was kept constant at 0.10 M. The
data are summarized in Tables S1-S39 and are displayed as
the upper rate profile of Figure 1.
These results show that the hydration of acetylketene is not
acid-catalyzed up to an acidity of [H+] ) 0.10 M but is weakly
catalyzed by the hydroxide ion. Such behavior is characteristic
of ketene hydration reactions: their rate profiles commonly show
large uncatalyzed regions with weak or nonexistent acid catalysis
and weak base catalysis. Acid catalysis, when present, is known
to occur by rate-determining proton transfer to the â-carbon
atom of the ketene followed by rapid hydration of the ensuing
acylium ion (eq 4).10 Substituents such as phenyl that stabilize
This enhanced reactivity of acylketenes has been noted before,
and the suggestion has been advanced that it may be due to a
carbonyl-assisted pathway in which the nucleophile experiences
a stabilizing interaction with the acyl oxygen atom of the
ketene.14 Some support for this suggestion comes from an
isotope effect determined in the present study. Rates of
hydration of acetylketene were measured in acidic and basic
D2O solution, and the data, summarized in Tables S1 and S3,9
when combined with results obtained in H2O, provide the
solvent isotope effects kH/kD ) 1.11 ( 0.03 on the uncatalyzed
reaction and kH/kD ) 1.87 ( 0.07 on the hydroxide-ion-catalyzed
process. The first of these isotope effects is unremarkable: it
is similar to the small solvent isotope effects found on other
uncatalyzed ketene hydrations,8b,10 and it simply reinforces our
conclusion that this process is a ketene-hydration reaction. The
other isotope effect, however, that on the hydroxide-ion-
catalyzed hydration, is unusual in that solvent isotope effects
on hydroxide-ion-consuming processes such as this are generally
inverse.15 In the present case, this expected inverse component
must be offset by a contribution in the normal (kH/kD > 1)
direction, and that could be supplied by a carbonyl-assisted
pathway. This assistance could take the form of strong
hydrogen bond formation between the hydroxide ion and the
carbonyl oxygen atom, as shown in eq 6, or it may even involve
proton transfer down such a hydrogen bond while nucleophilic
attack occurs.
carbon-carbon double bonds impede this process by lowering
the energy of the initial state, thus suppressing acid catalysis.8b,11
Since acyl groups stabilize carbon-carbon double bonds,12 acid
catalysis of acetylketene hydration should also be suppressed,
as observed.
The uncatalyzed and hydroxide-ion-catalyzed ketene hydra-
tion reactions occur by a different mechanism, one known to
involve nucleophilic attack of water or hydroxide ion on the
R-carbon atom of the ketene followed by ketonization of the
carboxylic acid enol thus formed (eq 5).13 The nucleophilic
Enol Ketonization. Rates of ketonization of acetoacetic acid
enol were measured in aqueous solutions of perchloric acid and
sodium hydroxide as well as acetic acid, biphosphate ion, and
tris(hydroxymethyl)methylammonium ion buffers. All mea-
surements, except those in perchloric acid at [HClO4] ) 0.20,
2.4, and 3.2 M, were done at a constant ionic strength of 0.10
M. The data are summarized in Tables S4-S6.9
(9) Supporting information; see paragraph at the end of this paper
regarding availablility.
(10) (a) Allen, A. D.; Kresge, A. J.; Schepp, N. P.; Tidwell, T. T. Can.
J. Chem. 1987, 65, 1719-1723. (b) Andraos, J.; Kresge, A. J. J. Photochem.
Photobiol. A 1991, 57, 165-173.
(11) Allen, A. D.; Stevenson, A.; Tidwell, T. T. J. Org. Chem. 1989,
54, 2843-2848. Allen, A. D.; Baigre, L. M.; Gong, L.; Tidwell, T. T. Can.
J. Chem. 1991, 69, 138-145. Andraos, J.; Kresge, A. J.; Schepp, N. P.
Can. J. Chem. 1995, 73, 539-543.
The measurements in buffers were carried out in series of
solutions of constant buffer ratio and therefore constant hydrogen
(14) Allen, A. D.; McAllister, M. A.; Tidwell, T. T. Tetrahedron Lett.
1993, 34, 1095-1098.
(12) Hine, J.; Skoglund, M. J. J. Org. Chem. 1982, 47, 4758-4766.
(13) (a) Tidwell, T. T. Acc. Chem. Res. 1990, 23, 273-279. (b) Allen,
A. D.; Andraos, J.; Kresge, A. J.; McAllister, M. A.; Tidwell, T. T. J. Am.
Chem. Soc. 1992, 114, 1878-1879. Andraos, J.; Kresge, A. J. J. Am. Chem.
Soc. 1992, 114, 5643-5646.
(15) (a) Gold, V.; Grist, S. J. Chem. Soc., Perkin Trans. 2 1972, 89-
95. (b) Kresge, A. J.; More O’Ferrall, R. A.; Powell, M. F. In Isotopes in
Organic Chemistry; Buncel, E., Lee, C. C., Eds.; Elsevier: Amsterdam,
1987; Vol. 7, pp 177-273. (c) Washabaugh, M. W.; Jencks, W. P. J. Am.
Chem. Soc. 1989, 111, 683-692.