Occurrence of an elongated p-oxo ketene intermediate in the dissociative alkaline hydrolysis of aryl (2E,4E)-5-(4'-hydroxyphenyl)pentadienoates

Article abstract of DOI:10.1021/jo0008439

The alkaline hydrolysis of title esters possessing acidic leaving groups follows an E1cB mechanism involving the participation of an 'extra extended' p-oxo ketene intermediate. For the hydrolysis of the 2,4-dinitrophenyl ester kinetic data, activation parameters and trapping of the intermediate clearly indicate that the dissociative pathway carries the reaction flux. Break in the Bronsted plot of the apparent second-order rate constants versus the pK(a) of the leaving group suggests that the reaction mechanism changes from E1cB to B(Ac)2 for esters having pK(a) higher than about 6.

Full text of DOI:10.1021/jo0008439

J . Org. Chem. 2000, 65, 7833-7838
7833
Occu r r en ce of a n Elon ga ted p-Oxo Keten e In ter m ed ia te in th e
Dissocia tive Alk a lin e Hyd r olysis of Ar yl
(2E,4E)-5-(4′-Hyd r oxyp h en yl)p en ta d ien oa tes
Giorgio Cevasco,* Daniele Vigo, and Sergio Thea*
C.N.R., Centro di Studio per la Chimica dei Composti Cicloalifatici ed Aromatic, Dipartimento di
Chimica e Chimica Industriale, Universita` di Genova, Via Dodecaneso 31, I-16146 Genova, Italy
giocev@chimica.unige.it
Received J une 1, 2000
The alkaline hydrolysis of title esters possessing acidic leaving groups follows an E1cB mechanism
involving the participation of an “extra extended” p-oxo ketene intermediate. For the hydrolysis of
the 2,4-dinitrophenyl ester kinetic data, activation parameters and trapping of the intermediate
clearly indicate that the dissociative pathway carries the reaction flux. Break in the Brønsted plot
of the apparent second-order rate constants versus the pKa of the leaving group suggests that the
reaction mechanism changes from E1cB to BAc2 for esters having pKa higher than about 6.
In the course of our studies on acyl transfer reactions
we have at first provided evidence that alkaline hydroly-
sis of aryl esters of 4-hydroxybenzoic acid occurs through
either associative (BAc2) or dissociative (E1cB, via inter-
mediate 1) mechanisms, depending on the basicity of the
leaving group.1 We have subsequently shown that the
hydrolyses of aryl 4-hydroxycinnamates2 and 2-hydroxy-
cinnamates3 in dioxane-water mixtures follow the same
mechanism with the participation, in their dissociative
paths, of the “extended” oxo ketene intermediates 2 and
3, respectively.
pathways, aiming to increase our knowledge on the
factors that control the reaction flux (associative vs.
dissociative) in ester hydrolysis (inter alia, stability of
the putative unsaturated intermediate), we have succes-
sively directed our attention toward other esters pos-
sessing different molecular architecture such as two
aromatic π systems linked by Z ) Y π-conjugated
systems, with Z and Y being N or CH. In other words we
have further enlarged the π-conjugated backbone, these
substrates possessing indeed three π units in the bridge.
In all cases our results indicate that these substrates
react through the usual associative BAc2 mechanism,5 and
this outcome has been tentatively ascribed to an exceed-
ingly large loss of aromaticity on going from substrate
to the transition state when two p-phenylene units are
present in the π-conjugated bridge.
Finally, in a recent communication6 we have reported
the first observation of the occurrence of the dissociative
route in the hydrolysis of an acyl derivative with three π
systems (a single p-phenylene unit and two vinylenic
groups) in its bridge: kinetic data and trapping experi-
ments strongly support the intervention of a dissociative,
E1cB-type mechanism with the participation of a new,
“elongated” oxo ketene intermediate (4, here depicted in
the s-trans form) in the hydrolysis of 2,4-dinitrophenyl
(2E,4E)-5-(4′-hydroxyphenyl)pentadienoate (5b).
We have thus found that the dissociative mechanism
carries the reaction flux when the internal nucleophile
(the hydroxyl group) is π-conjugated with the reaction
center in esters of the type HO-π-COOAr: the interven-
ing backbone being a single π-system, the aromatic ring
in the case of 4-hydroxybenzoates, or two π-units in the
case of hydroxycinnamates. Interposition of an extra
vinylene group between the internal nucleophile and the
reaction center seems to favor the dissociative mecha-
nism. We suggested that the observed reactivity enhance-
ment could be due to an increased stability of the
“extended” intermediates which, in turn, can be ascribed
to a more extended delocalization of π electrons. Analo-
gous results come from our recent studies4 on dissociative
sulfonyl group transfer reactions where “extended” sul-
foquinone intermediates are involved.
To improve the understanding of the effects of struc-
tural modifications of the π backbone on the hydrolytic
(2) Cevasco, G.; Thea, S. J . Org. Chem. 1994, 59, 6274-6278.
(3) Cevasco, G.; Thea, S. J . Org. Chem. 1995, 60, 70-73.
(4) Cevasco, G.; Thea, S. J . Org. Chem. 1998, 63, 2125-2129.
(5) Cevasco, G.; Thea, S. J . Org. Chem. 1999, 64, 5422-5426.
(6) Cevasco, G.; Vigo, D.; Thea, S. Org. Lett. 1999, 1, 1165-1167.
(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.
10.1021/jo0008439 CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/25/2000

7834 J . Org. Chem., Vol. 65, No. 23, 2000
Cevasco et al.
Ta ble 1. Hyd r olysis of Ar yl (2E,4E)-5-(4′-Hyd r oxyp h en yl)p en ta d ien oa tes (5a -h ) in 40% Dioxa n e a t 25 °C µ a n d ) 0.1
(p Kw ) 15.00)'
leaving substituted
a
b
subs.
phenoxides
pKLG
ka, s-1
kb, M-1 s-1
kapp, M-1 s-1
logkapp
Nc
pHd
5a
5b
5c
5d
5e
5f
2,6-dinitro
2,4-dinitro
3.71e
4.11
4.35e
5.22e
5.45
6.46
7.14
7.95
(7.08 ( 0.22) × 10-3
(1.14 ( 0.04) × 10-2
(2.65 ( 0.04) × 10-3
(2.04 ( 0.12) × 10-4
(5.32 ( 0.39) × 10-5
(7.35 ( 0.79) × 10-6
(5.78 ( 0.93) × 10-2
(5.25 ( 0.41) × 10-1
(2.60 ( 0.18) × 10-2
(2.09 ( 0.13) × 10-1
(1.28 ( 0.11) × 10-1
(5.62 ( 0.57) × 10-2
(1.06 ( 0.08) × 10-1
(6.59 ( 0.57) × 10-2
810.89
1418.27
260.00
22.77
2.909
3.152
2.415
1.357
0.592
9
11
9
8
8
8
3
8
8.71-13.99
8.28-13.99
8.71-13.99
8.80-13.99
9.75-13.99
9.74-13.99
12.69-13.99
9.74-13.99
2-methyl-4,6-dinitro
2,5-dinitro
2-chloro-4-nitro
4-chloro-2-nitro
4-nitro
3.90
0.61
-0.212
5g
5h
4-cyano
(5.96 ( 0.58) × 10-6
0.45
-0.351
a
J encks, W. P.; Regestein, J . Handbook of Biochemistry and Molecular Biology 3rd ed.; Fasman, G., Ed.; Chemical Rubber Co.: Cleveland,
1976. See text, Ka values are taken from Table 2. c Number of data points, not including duplicates. pH range employed. e Kortum, G.;
b
d
Vogel, W.; Andrussov, K. Dissociation Constants of Organic Acids in Aqueous Solution; Butterworths: London, 1961.
F igu r e 1. pH-rate profiles for the hydrolysis of 2,4-dinitro-
phenyl esters 5b (solid circles) and 6 (open circles) in 40% (v/
v) dioxane-water at 25 °C and 0.1 M ionic strength made up
with KCl. Lines are calculated from eqs 1 and 2, respectively.
F igu r e 2. pH-rate profiles for the hydrolysis of aryl (2E,4E)-
5-(4′-hydroxyphenyl)pentadienoates in 40% (v/v) dioxane-
water at 25 °C and 0.1 M ionic strength made up with KCl.
Lines are calculated from eq 1; the identity of the points is
given in Table 1.
We now report our results in greater detail together
with new data relative to more esters suggesting the
occurrence of a changeover from E1cB to BAc2 mechanism
in the alkaline hydrolysis of aryl (2E,4E)-5-(4′-hydroxy-
phenyl)pentadienoates as the pKa of the leaving phenol
increases.
Resu lts a n d Discu ssion
The observed pseudo-first-order rate constants for the
alkaline hydrolysis of aryl (2E,4E)-5-(4′-hydroxyphenyl)-
pentadienoates (5a -h , see Table 1), in 40% dioxane-
water (v/v) solvent at 25 °C and ionic strength 0.1 M
(KCl), were found to follow eq 1.
kobs ) (ka + kb[OH-])/(1 + aH/Ka)
(1)
F igu r e 3. pH-rate profiles for the hydrolysis of aryl (2E,4E)-
5-(4′-hydroxyphenyl)pentadienoates in 40% (v/v) dioxane-
water at 25 °C and 0.1 M ionic strength made up with KCl.
Lines are calculated from eq 1; the identity of the points is
given in Table 1.
The pH-rate profile for the hydrolysis of ester 5b is
illustrated in Figure 1 (b) and similar plots (Figures 2
and 3) were obtained for the other esters. In eq 1, aH is
the proton activity, ka is the pseudo-first-order rate
constant in the plateau region of pH, Ka is the ionization
constant of the hydroxyl group of the ester, and kb refers
to the bimolecular attack of hydroxide ion on the ionized
ester and gives rise to an upward curvature in the pH-
rate profile at high pH values. In Table 1 are collected
experimental conditions and the values of the kinetic
parameters, obtained from primary kinetic data by
iterative nonlinear curve-fitting performed with the Fig.P
program,7 for the hydrolysis of the substrates 5a -h . If
the reactivity of the ester under examination allows the
construction of a sufficiently detailed pH-rate profile (in
particular in and below the plateau region of pH) this
program provides, together with the rate constants, the
Ka values. Table 2 indicates that the kinetic pKa values
are in good agreement with those spectroscopically
measured.
The dependence on pH of the pseudo-first-order rate
constants for the hydrolysis of 2,4-dinitrophenyl (2E,4E)-
5-(4′-methoxyphenyl)pentadienoate (6) is also shown in
(7) Fig. P from Biosoft, Cambridge, UK, 1991.

Elongated p-Oxo Ketene Intermediate
J . Org. Chem., Vol. 65, No. 23, 2000 7835
Ta ble 2. Ion iza tion Con sta n ts of Ar yl (2E,4E)-5-(4′-h yd r oxyp h en yl)p en ta d ien oa tes (5a -h ) in 40% Dioxa n e a t 25 °C a n d µ
) 0.1
b
subs.
leaving substituted phenoxides
λ,a nm
1011Ka, M
pKa
pKa
5a
5b
5c
5d
5e
5f
2,6-dinitro
2,4-dinitro
430
426
430
430
420
430
420
420
11.75 ( 0.30
12.68 ( 0.10
10.41 ( 0.40
11.42 ( 0.20
7.51 ( 0.18
8.55 ( 0.18
7.79 ( 0.17
7.66 ( 0.22
9.93 ( 0.01
9.90 ( 0.02
9.98 ( 0.02
9.94 ( 0.01
10.12 ( 0.01
10.07 ( 0.01
10.11 ( 0.01
10.12 ( 0.01
9.97 ( 0.04
9.93 ( 0.04
9.98 ( 0.02
9.76 ( 0.04
2-methyl-4,6-dinitro
2,5-dinitro
2-chloro-4-nitro
4-chloro-2-nitro
4-nitro
5g
5h
4-cyano
a
b
Wavelength employed for the spectroscopic determination. Measured from the kinetics.
Ta ble 3. Activa tion P a r a m eter s for th e Hyd r olysis of
2,4-Din itr op h en yl Ester s in KOH 5 × 10-3 M, 40%
Dioxa n e, µ ) 0.1 M, p H 12.69 (a t 25 °C)a
Figure 1 and indicates, as expected, a simple second-order
rate law in hydroxide ion and ester concentrations (eq
2).
ester
∆Hq, kcal/mol
∆Sq,b cal/mol K
5b
6
23.1 ( 0.1
12.8 ( 0.4
10.4 ( 0.4
-23.8 ( 1.4
kobs ) kOH[OH-]
(2)
a
b
Temperature range: 16.5-40.6 °C. Calculated at 25 °C.
The kOH value for the unambiguous BAc2 attack of
hydroxide ion on this ester, in 40% dioxane-water (v/v)
solvent at 25 °C and ionic strength 0.1 M (KCl), is 3.9 (
0.1 M-1 s-1
.
The apparent second-order rate constant (kapp ) kaKa/
Kw ) ca. 1.4 × 103 M-1 s-1, Table 1) calculated for the
attack of hydroxide ion on neutral 5b (the pKw value of
15.00 has been reported8 for the medium employed in this
work) is larger, rather than smaller as expected (σp values
for OH and OMe are -0.37 and -0.27, respectively), than
the second-order rate constant related to the BAc2 attack
of hydroxide ion on 6, thus suggesting that the reactions
of these esters could occur through different pathways.
A better assessment, however, can be achieved by com-
puting the rate constant (kcalc) for the bimolecular attack
of hydroxide ion on neutral 5b from the Hammett
relationship log k/k0 ) 1.97Σσ for the alkaline hydrolysis
of substituted 2,4-dinitrophenyl benzoates.1a If the at-
tenuation factor of 0.54 related to the vinylene group9 is
taken into account, since the overall attenuation factor
is given roughly by the product of those of the intervening
groups,10 the relationship becomes log k/k0 ) 0.57Σσ and
is now valid for the BAc2 hydrolysis of substituted 2,4-
dinitrophenyl (2E,4E)-5-(X-phenyl)pentadienoates. Now,
from the kOH value for 6, using the σp values for the
hydroxy and methoxy groups (-0.37 and -0.27, respec-
tively) we finally obtain kcalc ) 3.4 M-1 s-1. The apparent
second-order rate costant (kaKa/Kw, ca. 1420 M-1 s-1) for
5b is therefore in excess of this kcalc by about 420-fold,
thus confirming the suggestion that the mechanism for
the ka term cannot be the associative one, and the
simplest hypothesis is that an E1cB process involving the
participation of the “elongated” oxo ketene 4 intermediate
occurs.
F igu r e 4. Brønsted plot for the hydrolysis of aryl (2E,4E)-5-
(4′-hydroxyphenyl)pentadienoates. The line is calculated from
eq 3; for the dashed line see text; the identity of the points is
given in Table 1.
The intervention of a dissociative mechanism in the
hydrolysis of 5b is also confirmed by trapping experi-
ments carried out with added nitrogen nucleophiles. In
the presence of 0.03 M p-toluidine, which has no effect
on reaction rate, ca. 30% of N-(4-methylphenyl) 5-(4′-
hydroxyphenyl)penta-2(E),4(E)-dienamide (7) was found
in the hydrolysis products. This result is clearly in
agreement with the proposed dissociative mechanism:
the intermediate 4 is trapped by the added nucleophile
after the rate-determining release of the leaving group.
The effect of the leaving group variation on reactivity
was also investigated. The plot of the logarithms of the
apparent second-order rate constants (kapp ) kaKa/Kw)
against the pKa of the leaving substituted phenoxide
(pKLG) is shown in Figure 4 (data taken from Table 1). It
appears that the point h , corresponding to the p-cy-
anophenyl ester deviates from the Brønsted equation (eq
3) correlating the other substrates.
Further evidence that the hydrolysis of these two esters
follows different pathways is provided by the evaluation
of activation entropy of the reactions (Table 3). For the
hydrolysis of 5b the value of ∆Sq for the ka term
(measured at pH 12.69) is large and positive as expected
for a unimolecular reaction, whereas the negative value
of ∆Sq for the hydrolysis of 6 (at the same pH) is
consistent with an associative process.11
(11) Schaleger, L. L.; Long, F. A. Adv. Phys. Org. Chem. 1963, 1, 1.
J encks, W. P. Catalysis in Chemistry and Enzymology; McGraw-Hill:
New York, 1969. Douglas, K. T. Prog. Bioorg. Chem. 1976, 4, 194.
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.
(8) Arned, H. S.; Fallon, L. J . Am. Chem. Soc. 1931, 61, 2374-2378.
(9) Williams, A. Chemistry of Enzyme Action; Page, M. I., Ed.;
Elsevier: Amsterdam, 1984; p 145.
(10) Page, M.; Williams, A. Organic and Bioorganic Mechanisms;
Addison-Wesley Longman: Harlow, 1997; p 57.

7836 J . Org. Chem., Vol. 65, No. 23, 2000
Cevasco et al.
log (kaKa/Kw) ) (8.0 ( 0.7) - (1.3 ( 0.2)pKLG (3)
The high âLG value (-1.29) is consistent with a dis-
sociative process,12 thus indicating that such esters can
hydrolyze through intermediate 4, and is in good agree-
ment with those we previously found for the E1cB
hydrolysis of aryl 4-hydroxybenzoates (-1.33),1a 4-hy-
droxycinnamates (-1.32),2 and 2-hydroxycinnamates
(-1.11).3
Since in our previous studies we have observed a break
in linearity in the Brønsted plots with upward curvature,
suggesting the occurrence of a change in mechanism from
E1cB to BAc2 as the nucleofugality of the leaving group
decreases, we believe that the presently investigated
substrates could behave similarly. Were this hypothesis
correct, the deviation of 5h could be simply due to the
fact that the hydrolysis of this ester occurs via the
associative mechanism rather than the E1cB route.
This proposal can be verified as follows. It is well-
known that associative processes in acyl group transfer
reactions involving carboxylic acid derivatives have âLG
values restricted in a narrow range (-0.20 to -0.25).
Now, if a line with a slope of -0.25 is drawn (dashed line
in Figure 4) through the point indicated as (f), which
represents the calculated value of the second-order rate
constant (kcalc ) 3.4 M-1 s-1, see above) for the BAc2-type
attack of hydroxide ion on the neutral 2,4-dinitrophenyl
ester 5b, it will go across the experimental line at pKLG
ca. 6.2 (changeover point) and the point corresponding
to ester 5h falls on this line. This strongly suggests that
5h actually hydrolyzes through the associative pathway,
thus confirming a change in mechanism. A further
outcome of this finding is that in the region around the
breakpoint both mechanisms can take place concurrently.
Unfortunately, for practical reasons it was not possible
to determine the ka value, and thus kapp, for the 4-nitro-
phenyl ester 5g (pKLG ) 7.14). Resort to the initial rates
technique, dictated by the exceedingly low reactivity of
this ester at pH values lower than about 12, was indeed
prevented by spectral characteristics of both substrate
and products. Finally, it is noteworthy that the changeover
point is close in value to those previously found for
related systems (i.e., 6.2 for 4-hydroxybenzoates,1a 6.7 for
4-hydroxycinnamates,2 and 6.0 for 2-hydroxycinna-
mates3).
The parameter kb (see eq 1), representing the bimo-
lecular attack of hydroxide ion on the conjugate base of
the esters, fits (omitting the two esters in which the 2,6-
positions of the phenolic moieties are substituted) a
Brønsted equation with a slope (âLG ) -0.21 ( 0.06, data
from Table 1) consistent with an associative process.
It is interesting to note that the logarithms of kapp
values for aryl (2E,4E)-5-(4′-hydroxyphenyl)pentadi-
enoates relate very well with those of the corresponding
4-hydroxycinnamates, as shown in Figure 5. The value
of the slope (0.89 ( 0.02) is less than unity thus
suggesting that, for a given leaving group, the fission of
the C-OAr bond in the transition state of the rate-
determining step is more advanced in the case of 4-hy-
droxycinnamates as compared with the present system,
reflecting the fact that the shorter is the π system the
F igu r e 5. Plot of the apparent second-order rate constants
for the hydrolysis of aryl (2E,4E)-5-(4′-hydroxyphenyl)penta-
dienoates (this work) and the corresponding aryl 4-hydroxy-
cinnamates (data taken from ref 2). The identity of the points
is given in Table 1.
stronger is the interaction between internal nucleophile
and reaction center. Closer inspection of this plot indi-
cates that all the points fall nicely on the regression line,
although the original Brønsted plots are somewhat
scattered (see Figure 4 and ref 2). Since this behavior
was observed in the cases of 4-hydroxybenzoates1 and
2-hydroxycinnamates3 as well, we infer that the standard
equilibrium usually employed in these Brønsted-type
LFER’s (phenol dissociation equilibrium) may not be fully
adequate, in particular when 2,6-disubstituted phenols
are involved.
In the preliminary communication6 we have reported
that reactivity comparisons between 2,4-dinitrophenyl
(2E,4E)-5-(4′-hydroxyphenyl)pentadienoates and 4′-hy-
droxybenzoate indicate that the presence of additional
vinylenic groups favors the hydrolytic process occurring
via the dissociative pathway. Analogous results were
found for 2,4-dinitrophenyl 4′-hydroxycinnamate,2 and it
was suggested that the higher reactivity of the latter
(with respect to 4′-hydroxybenzoate) could be due to extra
stabilization of the intermediate 2 with respect to inter-
mediate 1, owing to a more extended delocalization of π
electrons in the former.
Theoretical calculations are now planned in order to
obtain additional information on the stability of the
transition states leading to the intermediates 1, 2,
and 4.
Exp er im en ta l Section
Gen er a l. Starting reagents and solvents were purified and/
or distilled before use. Buffer materials were of analytical
reagent grade. Water was double distilled and preboiled to free
it from dissolved carbon dioxide. Dioxane was purged of
peroxides by passage of the analytical-grade product through
an activated alumina column under nitrogen; the absence of
peroxides was checked by the KI test. The 1H NMR spectra
were recorded with a 200 MHz spectrometer with TMS as
internal standard and acetone-d6 as solvent.
Syn th esis. Esters 5a -h , and 6 and the amide 7 were
prepared starting from the corresponding acids. The acids were
obtained through a Wittig-type reaction under phase-transfer
conditions13 from 4-hydroxybenzaldehyde (protected with the
(12) Williams, A.; Douglas, K. T. Chem. Rev. 1975, 75, 627-649.
Gordon, I. M.; Maskill, H.; Ruasse, M. F. Chem. Soc. Rev. 1989, 18,
123-151. Thatcher, G. R. J .; Kluger, R. Adv. Phys. Org. Chem. 1989,
25, 99-265.
(13) Yang, J . H.; Shi, L. L.; Xiao, W. J .; Wen, X. Q.; Huang, Y. Z.
Heteroatom Chem. 1990, 1, 75-81.

Elongated p-Oxo Ketene Intermediate
J . Org. Chem., Vol. 65, No. 23, 2000 7837
tert-butyldimethylsilyl group)14 or 4-methoxybenzaldehyde,
and 3-ethoxycarbonylallylidenetriphenylarsonium bromide,
prepared from triphenylarsine and commercial (Aldrich) ethyl
4-bromocrotonate as described.15 These reactions furnished,
in good yield, nearly a 4:1 mixture of the E,E/E,Z isomers, as
previously reported,13 and confirmed by 1H NMR spectroscopy
(the stereoisomers have well-resolved spectra in acetone-d6,
and the peak assignments and the attribution of the configu-
rations have been conveniently carried out by a simple
decoupling technique) but our attempts to obtain total conver-
sion of the mixture of isomers into the E,E isomer by treatment
with iodine in daylight5,13 failed. The mixtures of isomers were
subsequently hydrolyzed in aqueous sodium hydroxide (10%)
at reflux overnight. Such prolonged heating afforded, as
confirmed by 1H NMR spectroscopy, complete conversion to
the desired E,E isomer (as stated in the preliminary com-
munication,6 this stereoisomer is required to ensure π system
planarity), and removal of the silyl group. The cooled solutions
were washed with dichloromethane and then acidified afford-
ing the acids as crystalline precipitates which were collected
and dried. Ester 6 was finally prepared from the so obtained
(2E,4E)-5-(4′-methoxyphenyl)pentadienoic acid by condensa-
tion with 2,4-dinitrophenol in the presence of DCC. (2E,4E)-
5-(4′-Hydroxyphenyl)pentadienoic acid was reacted with tert-
butyldimethylchlorosilane,14 and the bissilylated compound
was subsequently treated with oxalyl chloride -DMF16 to give,
in very good yield, the acid chloride. The reaction of this
chloride with the appropriate phenol or amine furnished, after
removal of silyl group carried out by aqueous hydrofluoric
acid,17 the desired compounds 5a -h and 7.
(dd, 1, J ) 2.57; 8.75 Hz), 7.68 (dd, 1, J ) 10.01; 15.10 Hz),
7.54 (d, 1, J ) 8.75 Hz), 7.52 (d, 2, J ) 8.63 Hz), 7.10 (m, 2),
6.89 (d, 2, J ) 8.67 Hz), 6.21 (d, 1, J ) 15.18 Hz). Anal. Calcd
for C17H12NO5Cl: C, 59.1; H, 3.5; N, 4.1. Found: C, 59.5; H,
3.6; N, 4.0. 4-Nitr op h en yl (2E,4E)-5-(4′-h yd r oxyp h en yl)-
p en ta d ien oa te (5g): mp 196-7 °C; δ 8.83 (s, 1), 8.35 (d, 2, J
) 9.20 Hz), 7.70 (dd, 1, J ) 10.26; 15.38 Hz), 7.51 (m, 4), 7.11
(m, 2), 6.89 (d, 2, J ) 8.67 Hz), 6.20 (d, 1, J ) 15.26 Hz). Anal.
Calcd for C17H13NO5: C, 65.6; H, 4.2; N, 4.5. Found: C, 66.0;
H, 4.3; N, 4.2. 4-Cya n op h en yl (2E,4E)-5-(4′-h yd r oxyp h en -
yl)p en ta d ien oa te (5h ): mp 190-1 °C; δ 8.82 (s, 1), 7.88 (d,
2, J ) 8.67 Hz), 7.67 (dd, 1, J ) 9.85; 15.39 Hz), 7.51 (d, 2, J
) 8.67 Hz), 7.45 (d, 2, J ) 8.75 Hz), 7.10 (m, 2), 6.89 (d, 2, J
) 8.63 Hz), 6.19 (d, 1, J ) 15.10 Hz). Anal. Calcd for C18H13
-
NO3: C, 74.2; H, 4.5; N, 4.8. Found: C, 74.4; H, 4.6; N, 4.7.
2,4-Din itr op h en yl (2E,4E)-5-(4′-m eth oxyp h en yl)p en ta d i-
en oa te (6): mp 147-8 °C; δ 8.94 (d, 1, J ) 2.77 Hz), 8.69 (dd,
1, J ) 2.52; 8.79 Hz), 7.84 (d, 1, J ) 8.87 Hz), 7.75 (dd, 1, J )
9.89; 14.81 Hz), 7.61 (d, 2, J ) 8.96 Hz), 7.17 (m, 2), 7.00 (d,
2, J ) 8.87 Hz), 6.27 (d, 1, J ) 15.10 Hz), 3.85 (s, 3). Anal.
Calcd for C18H14N2O7: C, 58.4; H, 3.8; N, 7.5. Found: C, 58.7;
H, 4.0; N, 7.4. N-(4-Meth ylp h en yl) (2E,4E)-5-(4′-h yd r oxy-
p h en yl)p en ta d ien a m id e (7): mp 207-8 °C; δ 9.17 (s, 1), 8.67
(s, 1), 7.63 (d, 2, J ) 8.47 Hz), 7.43 (m, 3), 7.11 (d, 2, J ) 8.43
Hz), 6.88 (m, 4), 6.25 (d, 1, J ) 14.77 Hz), 2.27 (s, 3). Anal.
Calcd for C18H17NO2: C, 77.4; H, 6.1; N, 5.0. Found: C, 77.6;
H, 6.2; N, 5.0.
Meth od s. P r od u ct An a lysis. The products of ester hy-
drolyses were identified as phenol and acid by comparison of
the UV-vis spectra after completion of the reactions with
authentic samples of these compounds under the same condi-
tions.
The characteristics of the new compounds, purified through
column chromatography and recrystallized from toluene (un-
less otherwise stated), were as follows; mp is given together
with analytical data.
Kin etics. The hydrolyses of esters 5a -h and 6 in 40% v/v
dioxane-water solvent were followed spectrophotometrical-
ly: the choice of the appropriate wavelength was dictated by
the pH of the buffers employed in the particular kinetic run
since the ionization of the hydroxyl group of both substrates
and liberated acid in alkaline solutions causes large shift in
the UV-Vis spectra. The buffered solution (2.5 mL) was
equilibrated to the required temperature (( 0.1 °C) in a 1-cm
path-length quartz cell placed in the thermostated cell holder
of the spectrophotometer. The reaction was initiated by adding
10 µL of a stock solution of the substrate ca. 0.01 M in dioxane
to the buffer, and automated acquisition of 50-200 data points
for each kinetic run was performed. Reactions were carried
out with potassium hydroxide at different concentrations and
with phosphate, borate, carbonate, ammonia, and Tris buffers.
In all cases at least three different buffer concentrations, at
constant pH, were employed: when buffer effects were ob-
served the rate constants at zero buffer concentration were
obtained by extrapolation. The ionic strength was kept at 0.1
M with KCl. The pH of the buffered solutions were measured
before and after each kinetic run using a Ross combined
electrode, calibrated with standard buffers. All pH values
quoted for the dioxane-water solutions are relative values
measured directly, no further corrections being applied. The
pseudo-first-order rate constants (kobs) were obtained by
NLLSQ fitting of absorbance vs time data, and the values
reported are the averages of at least duplicate runs. Reactions
were normally followed over about seven half-lives. The rate
constants for the hydrolysis of 5f and 5h at pH values below
11 were obtained by initial rates: they were measured for each
run up to ca. 10% of the total reaction and were converted
to pseudo-first-order rate constants using infinity values
calculated from the known extinction coefficients of the
products.
2,6-Din itr op h en yl (2E,4E)-5-(4′-h yd r oxyp h en yl)p en ta -
d ien oa te (5a ): mp 149-150 °C (from methanol/water); 8.86
(s, 1), 8.50 (d, 2, J ) 8.23 Hz), 7.86 (t, 1, J ) 8.34 Hz), 7.74
(dd, 1, J ) 10.18; 15.18 Hz), 7.53 (d, 2, J ) 8.63 Hz), 7.14 (m,
2), 6.90 (d, 2, J ) 8.67 Hz), 6.24 (d, 1, J ) 15.18 Hz). Anal.
Calcd for C17H12N2O7: C, 57.3; H, 3.4; N, 7.9. Found: C, 57.3;
H, 3.4; N, 7.5. 2,4-Din it r op h en yl (2E,4E)-5-(4′-h yd r oxy-
p h en yl)p en ta d ien oa te (5b): mp 207-8 °C; δ 9.01 (s, 1), 8.93
(d, 1, J ) 2.69 Hz), 8.69 (dd, 1, J ) 2.85; 9.12 Hz), 7.84 (d, 1,
J ) 8.95 Hz), 7.74 (dd, 1, J ) 10.14; 15.22 Hz), 7.52 (d, 2, J )
8.67 Hz), 7.21 (d, 1, J ) 15.31 Hz), 7.07 (dd, 1, J ) 10.46; 15.42
Hz), 6.90 (d, 2, J ) 8.75 Hz), 6.24 (d, 1, J ) 15.26 Hz). Anal.
Calcd for C17H12N2O7: C, 57.3; H, 3.4; N, 7.9. Found: C, 57.4;
H, 3.5; N, 7.8. 2-Meth yl-4,6-d in itr op h en yl (2E,4E)-5-(4′-
h yd r oxyp h en yl)p en ta d ien oa te (5c): mp 178-9 °C; δ 8.86
(s, 1), 8.75 (d, 1, J ) 2.93 Hz), 8.60 (d, 1, J ) 2.93 Hz), 7.77
(dd, 1, J ) 10.01; 15.14 Hz), 7.53 (d, 2, J ) 8.67 Hz), 7.14 (m,
2), 6.90 (d, 2, J ) 8.67 Hz), 6.28 (d, 1, J ) 15.14 Hz), 2.48 (s,
3). Anal. Calcd for C18H14N2O7: C, 58.4; H, 3.8; N, 7.5. Found:
C, 58.8; H, 3.9; N, 7.2. 2,5-Din itr op h en yl (2E,4E)-5-(4′-
h yd r oxyp h en yl)p en ta d ien oa te (5d ): mp 170-2 °C; 8.83 (s,
1), 8.41 (s, 3), 7.73 (dd, 1, J ) 10.06; 15.18 Hz), 7.53 (d, 2, J )
8.67 Hz), 7.13 (m, 2), 6.90 (d, 2, J ) 8.71 Hz), 6.23 (d, 1, J )
15.02 Hz). Anal. Calcd for C17H12N2O7: C, 57.3; H, 3.4; N, 7.9.
Found: C, 57.5; H, 3.4; N, 7.5. 2-Ch lor o-4-n itr op h en yl
(2E,4E)-5-(4′-h ydr oxyph en yl)pen tadien oate (5e): mp 155-6
°C; δ 8.84 (s, 1), 8.43 (d, 1, J ) 2.65 Hz), 8.31 (dd, 1, J ) 2.68;
8.96 Hz), 7.74 (dd, 1, J ) 10.06; 15.27 Hz), 7.67 (d, 1, J ) 8.91
Hz), 7.52 (d, 2, J ) 8.63 Hz), 7.12 (m, 2), 6.90 (d, 2, J ) 8.62
Hz), 6.25 (d, 1, J ) 15.18 Hz). Anal. Calcd for C17H12NO5Cl:
C, 59.1; H, 3.5; N, 4.1. Found: C, 59.1; H, 3.5; N, 4.0. 4-Ch lor o-
2-n itr oph en yl (2E,4E)-5-(4′-h ydr oxyph en yl)pen tadien oate
(5f): mp 176-7 °C; δ 8.83 (s, 1), 8.18 (d, 1, J ) 2.52 Hz), 7.88
Tr a p p in g. The hydrolysis of 2,4-dinitrophenyl (2E,4E)-5-
(4′-hydroxyphenyl)pentadienoate in 0.05 M carbonate buffer
(fraction of base ) 0.5, 40% dioxane, ionic strength kept at
0.1 M with KCl, pH 11.40) was kinetically investigated at 364
nm in the presence of variable amounts of added p-toluidine:
no effect on the rate of hydrolysis was observed varying the
amine concentration in the range 0-0.03 M at constant pH.
The UV-vis spectra taken at the end of the reactions carried
out in the presence of the amine were significantly different
(14) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
6190.
(15) Huang, Y. Z., Shen, Y.; Zheng, J . H.; Zhang, S. X. Synthesis
1985, 57-58.
(16) Wissner, A.; Grudzinskas, C. V. J . Org. Chem. 1978, 43, 3972-
3974.
(17) Collington, E. W.; Finch, H.; Smith, I. J . Tetrahedron Lett. 1985,
26, 681-684.

7838 J . Org. Chem., Vol. 65, No. 23, 2000
Cevasco et al.
from that obtained in the absence of added amine, in particular
in the range 380-420 nm. The values of the molar extinction
coefficients at 400 and 415 nm of the amide, phenol, and acid
were determined employing authentic samples under the same
conditions, and the amide yield (ca. 30%) was calculated from
the absorbances measured at these wavelengths at the end of
the reaction carried out in the presence of 0.03 M p-toluidine.
Ion iza tion Con sta n ts. The determinations of pKa values
were carried out by spectrophotometric titration of the ioniz-
able substrates employing at least seven buffered solutions
for each determination and extrapolating the absorption to
zero time.
J O0008439