Cyclodextrin effect on intramolecular catalysis

Article abstract of DOI:10.3390/50300405

HPCD inhibits the hydrolysis reaction of monoamides and monoesters of phthalic and maleic acid at pH 2. The magnitude of inhibition depends on the leaving group. For some of the substrates, the reaction in the cavity is more than 100 times slower than that in solution.

Full text of DOI:10.3390/50300405

405
Molecules 2000, 5
Cyclodextrin Effect on Intramolecular Catalysis
A.M. Granados, G.O. Andres and R. Hoyos de Rossi
Instituto de Investigaciones en Físico Química de Córdoba (INFIQC), Departamento de Química Or-
gánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. Ciudad Universitaria. 5000
Córdoba, Argentina
E-mail: ritah@dqo.fcq.unc.edu.ar
Abstract: HPCD inhibits the hydrolysis reaction of monoamides and monoesters of phthalic
and maleic acid at pH 2. The magnitude of inhibition depends on the leaving group. For
some of the substrates, the reaction in the cavity is more than 100 times slower than that in
solution.
Introduction
Cyclodextrins (CD) are doughnut-shaped, macrocyclic oligosacharides constructed of glucose units
linked by α- (1→4) bonds. The compound with seven glucose units is known as β-cyclodextrin (β-
CD)[1]. Hidroxypropyl-β-cyclodextrin is a derivative was several of the HO- groups are substituted by
hydroxypropyl groups and is more soluble in water than β-CD. Organic compounds included in CD
form complexes with different properties from those of the free substrate [2]. Meassuring the changes
occurring in some of these properties, it is possible to determine the association constant, Kas.
The mechanism of hydrolysis of monoamides and monoesters of phthalic acid [3] maleic acid [4] is
known to involve intramolecular catalysis by the neighboring carboxyl group. The formation of an in-
clusion complex with cyclodextrins may affect the efficiency of the catalysis by favoring or hindering
the interaction of the hydroxyl group with the reactive center. This effect should result in modification
of the hydrolysis rate. We report here results regarding the effect of HPCD on the hydrolysis of com-
pounds 1-3
Experimental
The substrates 1-3 were prepared by reaction of phthalic or maleic anhydride (sublimated) with ani-
line, 4-nitro-aniline, adamanthylamine and phenol. All products were purified and characterized by
MS and 1H and 13 C NMR.
The rate constants were determined by measuring the absorption changes with time at 380 nm for
1a, 276 nm for 1b and 2b, 225 nm for 1c, and 300 nm for 3b. The reaction conditions were: pH 2,
40°C for 1a,b,c 2b and 25°C for 3b, ionic strength 0.5 M using NaCl as compensating electrolyte and

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Molecules 2000, 5
water as solvent with 4% of dioxane (for 1) or acetonitrile (for 1b,c 2b and 3b).
Results and Discussion
The addition of HPCD decreased the hydrolysis rate of all the substrates. The Figure representative
plot of the observed rateconstant as a function of the HPCD concentration (1a (triangules), 1b
(squares) and 2b (cicles))
6
O
O
10
5
4
3
2
1
8
X R
COOH
N Ph
H
6
COOH
4
2b
X=NH, R= p-NO -Ph, 1a ;
2
2
Ph, 1b ; adamantyl, 1c
X= O, R= Ph ,3b
0.0 0.5 1.0 1.5 2.0 2.5 3.0
[HPCD], 10-2
M
These results are interpreted in terms of the formation of 1:1 complexes as shown in the following
scheme:
kc
Kas
S.HPCD
PRODUCTOS
S + HPCD
k0
Acknowledgements: This research was supported in part by CONICET, FONCYT, SECYT-UNC,
CONICOR and Antorchas Foundation.
References and Notes
1. Saenger, W. Angew. Chem. Int. Ed. Engl. 1980, 19, 344.
2. Bender, M.L.; Komiyama, M. Cyclodextrin Chemistry; Springer-Verlag: New York, 1978.
3. Hawkins, M.D. J.C.S. Perkin 2, 1975, 642.
4. (a) Kirby, A.J.; Lancaster, P.V. J.C.S. Perkin 2, 1972, 1206; (b) Kirby, A.J.; MacDonal, R.S.;
Smith, C.R. J.C.S. Perkin 2, 1974, 1495.