JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 10, 461–465 (1997)
MECHANISTICALLY OPTIMIZED INTRAMOLECULAR CATALYSIS IN
THE HYDROLYSIS OF ESTERS. GLOBAL CHANGES INVOLVED IN
MOLECULAR REACTIVITY
1
1
2
1
´
SANTIAGO F. YUNES, JOSE C. GESSER, HERNAN CHAIMOVICH AND FARUK NOME *
1
Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil
2
Instituto de Qu ´ı mica, Universidade de S a˜ o Paulo, S a˜ o Paulo, SP, Brazil
The hydrolysis of the 2Ј,2Ј,2Ј-trifluoroethyl monoester of 1,8-naphthalic acid (1) proceeds via the monoanion with the
intermediate formation of the corresponding anhydride. The rate constant for the formation of 1,8-naphthalic
anhydride (2) is ca 2500 times faster than its rate of hydrolysis. The isotope effect in the plateau region and theoretical
calculations at the PM3 level suggest that elimination of the alkoxide is the rate-limiting step for the reaction.
4
Accordingly, decomposition of the isopropyl monoester of naphthalic acid proceeds 10 times slower than the
spontaneous decomposition of 1. The remarkably high rate of monoester decomposition derives from the special
configuration of the substrates and important contributions that arise from relief of torsional strain, which clearly
includes electron redistribution due to the decrease in steric hindrance to resonance and the fact that proximity obviates
solvation. © 1997 by John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 10, 461–465 (1997) No. of Figures: 3 No. of Tables: 0 No. of References: 17
Keywords: mechanistically optimized intramolecular catalysis; ester hydrolysis; molecular reactivity.
Received 11 October 1996; revised 5 February 1997; accepted 12 February 1997
INTRODUCTION
a system which we believe contributes significantly to the
understanding of reactivity in biological systems.
In recent decades, the fascination with enzyme catalysis has
led chemists on a continuing search for simpler models
where the rates and selectivity of biological catalysts are
mimicked. Intramolecular accelerations are classical and
EXPERIMENTAL
Materials. The isopropyl monoester of 1,8-naphthalic
acid was prepared by reacting 1,8-naphthalic anhydride (2)
with sodium isopropoxide in propa-2-nol. The reaction
1–3
simple examples of this type of work.
At present,
however, there is no comprehensive theory, accepted by all
involved, that can explain, or predict, the factors by which
an enzymatic and/or intramolecular reaction will be faster
mixture was treated with HCl, extracted with CHCl and
3
finally the solvent was removed under vacuum. IR (KBr),
4–10
Ϫ1
1
(or slower) than the intermolecular counterpart.
Despite
max 3444, 2976, 1703, 1688 cm
; H NMR (CDCl3 ,
complications, quantitative comparisons between intra- and
intermolecular reactions are commonly expressed as effec-
200 MHz), ␦ 8·17–7·26 (m, ArH, 6 H), 5·33 (septuplet, CH,
13
1 H), 1·41 ppm (d, CH3 , 6 H);
C NMR (DMSO,
tive molarities (EM) taken as the ratios of the
200 MHz), ␦ 174·2, 168·5, 134·4, 133·2, 132·2, 130·8,
130·6, 130·1, 128·8, 125·8, 125·5, 125·2, 69·4, 21·9,
21·9 ppm; analysis, calculated for C H O , C 69·76, H
Ϫ1
intramolecular rate constant (k , s ) to the intermolecular
1
Ϫ1 Ϫ1
2
rate constant (k , lmol
s
), i.e. EM=k /k ( ). The wide
M
2
1
2
15 14
4
range of EMs for different types of reactions has generated
descriptive theories where the putative causes of large EMs
range from simple proximity to spatiotemporal descrip-
tions. In this paper, we report and analyze the remarkably
high rate of hydrolysis of monoesters of 1,8-naphthalic acid,
5·46, O 24·78; found, C 69·58, H 5·39, O 25·02%.
The 2Ј,2Ј,2Ј-trifluoroethyl monoester of 1,8-naphthalic
acid (1) was prepared in situ by a procedure identical with
4
–11
Ϫ1
that described above. IR, 2977, 2946, 1735, 1568 cm ;
max
1
H NMR (CF CH OH, 200 MHz), ␦ 8·15–7·45 (m, ArH,
3
2
13
6
2
1
H), 4·75 ppm (q, CH , 2 H); C NMR (CF CH OH,
2
3
2
00 MHz), ␦ 177·1, 167·8, 135·8, 133·8, 132·8, 130·1,
29·7, 129·2, 128·0, 125·3, 124·5, 124·3, 123·9, 59·7 ppm.
*
Correspondence to: F. Nome.
Contract grant sponsor: CNPq.
Contract grant sponsor: PADCT.
Contract grant sponsor: FINEP.
Methods. Rates of formation of the anhydride products
from monoesters of 1,8-naphthalic acid were followed
©
1997 by John Wiley & Sons, Ltd.
CCC 0894–3230/97/060461–05 $17.50