A new, "elongated" oxo ketene intermediate in the dissociative hydrolysis of 2,4-dinitrophenyl (2E,4E)-5-(4′-hydroxyphenyl)pentadienoate

Article abstract of DOI:10.1021/ol990796a

(matrix presented) Reactivity comparison, Arrhenius parameters, and trapping of the above-depicted unsaturated intermediate strongly suggest that the alkaline hydrolysis of the title ester follows a mechanism of the E1cB type. This is the first observation of the occurrence of a dissociative route in the hydrolysis of an acyl derivative with three π-systems interposed between the hydroxyl group (the internal nucleophile upon ionization) and the reaction center. Comparison with the hydrolysis of 2,4-dinitrophenyl 4′-hydroxybenzoate shows that interposition of the vinylenic groups is beneficial to the dissociative route.

Full text of DOI:10.1021/ol990796a

ORGANIC
LETTERS
1999
Vol. 1, No. 8
1165-1167
A New, “Elongated” Oxo Ketene
Intermediate in the Dissociative
Hydrolysis of 2,4-Dinitrophenyl
(2E,4E)-5-(4′-Hydroxyphenyl)pentadienoate
Giorgio Cevasco,* Daniele Vigo, and Sergio Thea*
CNR, Centro di Studio per la Chimica dei Composti Cicloalifatici ed Aromatici,
Dipartimento di Chimica e Chimica Industriale, Via Dodecaneso, 31,
16146 GenoVa, Italy
gioceV@chimica.unige.it
Received July 12, 1999
ABSTRACT
Reactivity comparison, Arrhenius parameters, and trapping of the above-depicted unsaturated intermediate strongly suggest that the alkaline
hydrolysis of the title ester follows a mechanism of the E1cB type. This is the first observation of the occurrence of a dissociative route in
the hydrolysis of an acyl derivative with three π-systems interposed between the hydroxyl group (the internal nucleophile upon ionization)
and the reaction center. Comparison with the hydrolysis of 2,4-dinitrophenyl 4′-hydroxybenzoate shows that interposition of the vinylenic
groups is beneficial to the dissociative route.
We are interested in the factors governing the competition
among different mechanisms in acyl transfer processes, in
particular, dissociative (E1cB) and associative (BAc2) path-
ways. We have previously found1 that the alkaline hydrolyses
of aryl 4-hydroxybenzoates having leaving groups with a
pKa lower than about 6.5 do not follow the usual associative
pathway but proceed via an E1cB mechanism with the
participation of an unprecedented p-oxo ketene intermediate
(1).
their dissociative paths, of the “extended” oxo ketene
intermediates 2 and 3, respectively.
In these acyl derivatives the internal nucleophile, the
ionized hydroxyl group, is conjugated with the reaction center
through an interposed bridge, a single π-system, the aromatic
ring in hydroxybenzoates, or two π-systems linked by a
single bond in the case of hydroxycinnamates. Our studies
indicate that the interposition of an extra vinylene group
between the internal nucleophile and the carbonyl carbon
favors the dissociative mechanism. As suggested, the kinetic
advantage could be ascribed to a gain in stability of the
“extended” intermediates, most likely due to increased
delocalization of π electrons.
To get a better knowledge of the role played by the nature
of the interposed bridge on the hydrolytic mechanism, we
have recently undertaken a kinetic study4 on the alkaline
hydrolysis of the 2,4-dinitrophenyl ester 4, and we have
(1) (a) Cevasco, G.; Guanti, G.; Hopkins A. R.; Thea, S.; Williams, A.
J. Org. Chem. 1985, 50, 479-484. (b) Thea, S.; Cevasco, G.; Guanti, G.;
Kashefi-Naini, N.; Williams, A. J. Org. Chem. 1985, 50, 1867-1872.
(2) Cevasco, G.; Thea, S. J. Org. Chem. 1994, 59, 6274-6278.
(3) Cevasco, G.; Thea, S. J. Org. Chem. 1995, 60, 70-73.
Subsequently, we have demonstrated that the hydrolyses
of aryl 4-hydroxycinnamates2 and 2-hydroxycinnamates3
behave almost in the same way with the participation, in
(4) Cevasco, G.; Thea, S. J. Org. Chem. 1999, 64, 5422-5426.
10.1021/ol990796a CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/23/1999

found that this species, provided with three π-conjugated
systems in the bridge, hydrolyzes through the usual associa-
tive pathway. This finding has been tentatively rationalized
by taking into account that two p-phenylene units are present
in the bridge of 4 and, therefore, the loss of aromaticity
involved in reaching the rate-determining transition state of
the E1cB path could be large enough to make this route
unfavorable.
Figure 1. pH-rate profiles for the hydrolysis of 2,4-dinitrophenyl
esters 5 (solid circles) and 6 (open circles) in 40% dioxane buffers
at 25 °C and ionic strength 0.1 M (KCl). Lines are calculated from
eqs 1 and 2.
We now report the preliminary results of a study on the
hydrolysis of ester 5, which has a single p-phenylene unit
and two vinylenic groups in its π-bridge, together with those
concerning the methoxy derivative 6. This latter, being
devoid of acidic hydrogen, can react only via the associative
route.
Esters 5 and 6 were prepared from the corresponding acid
and 2,4-dinitrophenol.5 The acids were obtained through a
Wittig-type reaction6 starting from ethyl 4-bromocrotonate
and the appropriate aldehyde.
Molecular mechanics calculations7 indicate that ester 5 is
nearly planar only if it has (E,E) stereochemistry: π-system
planarity is a prerequisite to allow the conjugative interaction
between the hydroxyl group and the carbonyl carbon atom
and therefore the feasibility of the dissociative path.
The hydrolyses of esters 5 and 6 were carried out under
pseudo-first-order conditions in 40% dioxane/water (v/v) at
25 °C and ionic strength held constant (0.1 M) with added
potassium chloride, as previously described.4 The progress
of the reactions was followed by monitoring the change of
absorbance due to disappearance of the substrate or liberation
of products. The products of the reactions in alkaline solution
were identified as the anions of 2,4-dinitrophenol and the
appropriate acid. This was achieved by comparison of the
UV-vis spectra after completion of the reactions with
authentic samples of these products under the same condi-
tions.
is the pseudo-first-order rate constant in the plateau region
of the pH-rate profile, and kb is the second-order term related
to the bimolecular attack of hydroxide ion on the ionized
ester. Ka was spectrophotometrically determined in separate
experiment as (1.27 ( 0.10) × 10-10 M, and from this value,
the kinetic constants can be calculated from primary kinetic
data by iterative nonlinear curve fitting performed with the
Fig.P program.8 The following values, ka ) (1.14 ( 0.04)
× 10-2 s-1 and kb ) 0.53 ( 0.04 M-1s-1, were obtained. In
eq 2 Kw is the ionic product of water in the employed
medium (pKw ) 15.00 at 25 °C)9 and a value of 3.9 ( 0.1
M-1 s-1 was obtained for kOH, the second-order rate constant
related to the unambiguous BAc2 attack of hydroxide ion on
the substrate, from kobs values.
The apparent second-order rate constant for the hydrolysis
of the hydroxy ester 5 was calculated, as it is customary, by
way of eq 3:
kapp ) kaKa/Kw
(3)
The value of kapp (ca. 1420 M-1 s-1) is considerably larger
(about 350-fold) rather than smaller, as expected from
substituent effects, than the second-order rate constant related
to the BAc2 attack of hydroxide ion on 6. This large kinetic
advantage suggests that the mechanism carrying the reaction
flux in the hydrolysis of 5 cannot be a BAc2-type process,
and the simplest hypothesis is that an E1cB path is followed.
In this process the conjugate base of 5 eliminates unimo-
lecularly the leaving group in the rate-determining step,
affording the “extra-extended” oxo ketene intermediate
depicted in the abstract, which rapidly adds water to furnish
the final product.
The pH dependence of the pseudo-first-order rate constants
for the hydrolyses of esters 5 and 6 obeys eqs 1 and 2,
respectively, and is depicted in Figure 1.
kobs ) (ka + kb[OH-])/(1 + aH/Ka)
kobs ) kOHKw/aH
(1)
(2)
In eq 1 (and eq 2 as well), aH is the proton activity, Ka is
the ionization constant of the hydroxyl group of the ester, ka
Such a proposal is corroborated by the effect of temper-
ature on reaction rates. Activation parameters for ester
(5) Esters 5 and 6 and the amide gave satisfactory elemental and
spectroscopic analyses.
(6) Yang, J. H.; Shi, L. L.; Xiao, W. J.; Wen, X. Q.; Huang, Y. Z.
Heteroatom Chem. 1990, 1, 75-81.
(7) PCModel, Serena Software, Bloomington, IN, 1993.
(8) Fig.P from Biosoft, Cambridge, U.K., 1991.
(9) Arned, H. S.; Fallon, L. J. Am Chem. Soc. 1931, 61, 2374-2378.
1166
Org. Lett., Vol. 1, No. 8, 1999

hydrolyses are reported in Table 1; activation entropy has
been frequently used to distinguish E1cB from BAc2 mech-
anisms.10
phenyl)penta-2(E),4(E)-dienamide (identified by comparison
with an authentic sample)5 was found in the hydrolysis
products. This result is consistent with amine attack on the
unsaturated intermediate after leaving group departure in the
rate-determining step.
The ka value of 5 is about 30-fold larger than that of the
corresponding 4-hydroxybenzoate (3.4 × 10-4 s-1 in 40%
dioxane at 25 °C),11 thus indicating that the presence of
additional vinylene groups favors the hydrolytic process
occurring via the dissociative path. This conclusion holds
also if the difference in acidity (in other words, the difference
in internal nucleophilicity) between these two esters is taken
into account simply by employing the same procedure
previously described in the case of 2,4-dinitrophenyl 4′-
hydroxycinnamate.2
Table 1. Activation Parameters for the Hydrolysis of
2,4-Dinitrophenyl Esters in 5 × 10-3 M KOH, 40% Dioxane/
Water, µ ) 0.1 Ma
∆Hq, kcal/mol
∆Sq,bcal/mol K
5
6
23.1 ( 0.1
12.8 ( 0.4
10.4 ( 0.4
-23.8 ( 1.4
a Temperature range: 16.5-40.6 °C. b Calculated at 25 °C.
As it is shown in the table, the activation entropy for the
hydrolysis of the 5-(4′-hydroxyphenyl)pentadienoate 5 is
large and positive as expected for a unimolecular reaction,
whereas the negative value for the methoxy derivative 6 is
consistent with an associative process.
Further evidence for the dissociative nature of the mech-
anism of hydrolysis of ester 5 is offered by trapping
experiments carried out in the presence of a nitrogen
nucleophile. Variable amounts of p-toluidine in carbonate
buffer at pH ca. 11.4 have no effect on reaction rate but at
0.03 M p-toluidine about 30% of N-(p-tolyl)-5-(4′-hydroxy-
In conclusion, we have provided, for the first time, strong
evidence that the E1cB mechanism occurs in the alkaline
hydrolysis of acyl derivatives having three conjugated
π-systems interposed between the internal nucleophile and
the reaction center. This outcome sheds more light on the
role played by the stability of the reaction intermediate in
our systems, giving support to rationalization previously
advanced by us for compound 4.
Supporting Information Available: Elemental analyses
and some 1H NMR data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(10) Vlasak, P.; Mindl, J. J. Chem. Soc., Perkin Trans. 2 1997, 1401-
1403. Safraoui, A.; Calmon, M.; Calmon, J.-P. J. Chem. Soc., Perkin Trans.
2 1991, 1349-1352. Broxton, T. J. Aust. J. Chem. 1985, 38, 77-83.
(11) Cevasco, G.; Pardini R.; Thea, S. Eur. J. Org. Chem. 1998, 665-
669.
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