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Can. J. Chem. Vol. 83, 2005
Table 1. Rate constants for the formation of maleic anhydride in
the hydrolysis of Z-aryl hydrogen maleates in the presence of
different competitors and at constant HPCD concentration.
solution (6, 7), and this effect has resulted in multiple indus-
trial applications (8, 9). As a result of the host–guest interac-
tion between the organic substrate and the cyclodextrin, the
rate of the reactions usually change and it can also be re-
sponsible for interesting changes in reaction mechanisms
that are well-documented in the literature (10–12). CDs have
been frequently used as microreactors that can catalyze or
inhibit organic reactions by including the substrate in their
cavity (13, 14).
a
p-CH3
Hb
Competitor concentration
kiobs (×10–3 s–1)
kiobs (×10–3 s–1)
Cyclohexanol (×10–3 mol/L)
0
25
50
1.37 0.04
2.21 0.02
4.24 0.01
5.3 0.3
4.12 0.03
5.93 0.4
10.1 0.1
11.7 0.6
CDs have also been derivatized to improve some desired
property (7, 15), such as hydrophilicity or hydrophobicity
(16, 17).
100
tert-Butyl alcohol (×10–3 mol/L)
100 2.06 0.02
We are interested in the cyclodextrin effect on the intra-
molecular catalysis because inclusion in the cyclodextrin
cavity may change the geometry of the substrate and there-
fore make intramolecular reaction more favorable (18) or
more unfavorable (19) than the reaction of the free substrate.
In previous work, we studied the effect of CD on the hy-
drolysis of aryl hydrogen phthalate esters (20, 21). We sug-
gested that the Z-aryl ring is included in the CD cavity, and
the structure of the substrate is distorted making the
intramolecular attack of the carboxylate on the carbonyl of
the ester more difficult, and consequently, the rate of the
intramolecular reaction decreases. In this paper we report the
effect of cyclodextrins on the hydrolysis reaction of Z-aryl
hydrogen maleate (1) where hydroxypropyl-β-cyclodextrin
(HPCD) produces an important decrease in the rate of the
anhydride formation, but the behavior is somewhat different
from that found for aryl hydrogen phthalate esters indicating
differences in the mechanism of the cyclodextrin mediated
reaction.
5.6 0.1
Note: Rate constants were obtained in a conventional spectrophotometer
at pH 2.00, HPCD concentration 0.03 mol/L, ionic strength 0.5 mol/L,
temperature 25 °C, acetonitrile 3.85%. The standard errors were obtained
from at least two determinations.
aλ = 281 nm.
bλ = 271 nm.
imental error, at both pH. The ratio between the rate con-
stant at the highest HPCD concentration (30 mmol/L) and
the rate constants without HPCD were 0.93 and 1.01 at
pH 2.00 and 3.00, respectively (Supplementary material, Ta-
ble D1).3 We also studied the hydrolysis of maleic anhydride
at the highest HPCD concentration with different concentra-
tions of a potential competitor for the cyclodextrin cavity
(11). The rate constants were not affected by compounds
that are known to form inclusion complexes and the ob-
served rate constants were always the same within experi-
mental error (Table D2).3
The hydrolysis reaction of phenyl-, p-methylphenyl-, m-
methylphenyl-, p-chlorophenyl-, and m-chlorophenyl hydro-
gen maleate was studied at pH 1.00, 2.00, 2.50, and 3.00 in
the presence of a variable concentration of HPCD (Tables
D3–D7).3 Two kinetic processes were observed at some
wavelengths, and they are associated with the formation and
hydrolysis of maleic anhydride. To calculate the rate con-
stants for the system we choose a wavelength where the an-
hydride did not absorb and the formation of Z-phenol is the
only process measured. Under these conditions the data can
be fitted by a single exponential equation and the rate con-
stants calculated correspond to the formation of the maleic
anhydride.
The addition of HPCD decreases the rate of formation of
the anhydride, whereas γ-cyclodextrin did not show any ef-
fect and α-cyclodextrin showed a minor decrease in rate (Ta-
ble D8),3 therefore, the size of the cavity plays an important
role on the inhibition observed.
We studied the effect of guests that may be included in the
cyclodextrin cavity on the cyclodextrin retarded hydrolysis.
At constant HPCD concentration (30 mmol/L) in the pres-
ence of cyclohexanol (25–100 mmol/L) and tert-butyl alco-
hol (100 mmol/L), the observed rate constants are higher
than in the absence of the competitor (Table 1). The ratios
between the rate constants for the hydrolysis in the presence
of cyclohexanol at the higher concentration used
O
Z
O
OH
O
1
Z = H, p-CH3, m-CH3, p-Cl, m-Cl
Results and discussion
Rate constants for the hydrolysis of Z-aryl hydrogen ma-
leates (Z = p-CH3, m-CH3, H, p-Cl, m-Cl) and maleic anhy-
dride were obtained by measuring the change in the
absorbance at an appropriate wavelength with time. All the
kinetics studies were carried out in water containing 3.85%
v/v of acetonitrile (ACN) as the co-solvent and at 25 °C.
Maleic anhydride is an intermediate in the hydrolysis of
monoaryl maleate esters (22, 23), therefore it is important to
determine the effect of CD on its rate of hydrolysis to under-
stand the effect of cyclodextrin on the hydrolysis of the es-
ters. The reactions of maleic anhydride were studied at
pH 2.00 and 3.00 at seven different concentrations of
hydroxypropyl-β-cyclodextrin (HPCD) between 2.5 and
30 mmol/L. Only one kinetic process was observed in all
cases and the rate constants were the same, within the exper-
3 Supplementary data for this article are available on the Web site or may be purchased from the Depository of Unpublished Data, Document
Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0S2, Canada. DUD 4026. For more information on obtaining mate-
© 2005 NRC Canada