Aminolysis of Y-substituted phenyl X-substituted cinnamates and benzoates: Effect of modification of the nonleaving group from benzoyl to cinnamoyl

Article abstract of DOI:10.1021/jo0705061

(Chemical Equation Presented) A kinetic study is reported for reactions of Y-substituted phenyl X-substituted cinnamates (1a-e and 3a-g) and benzoates (2a-e and 4a-g) with a series of alicyclic secondary amines in 80 mol % H ₂O/20 mol % DMSO at

Full text of DOI:10.1021/jo0705061

Aminolysis of Y-Substituted Phenyl X-Substituted Cinnamates and
Benzoates: Effect of Modification of the Nonleaving Group from
Benzoyl to Cinnamoyl
Ik-Hwan Um,*,‡ Youn-Min Park,‡ Mizue Fujio,† Masaaki Mishima,† and Yuho Tsuno†
DiVision of Nano Sciences and Department of Chemistry, Ewha Womans UniVersity,
Seoul 120-750, Korea, and Institute for Materials Chemistry and Engineering, Kyushu UniVersity,
Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
ihum@ewha.ac.kr
ReceiVed March 11, 2007
A kinetic study is reported for reactions of Y-substituted phenyl X-substituted cinnamates (1a-e and
3a-g) and benzoates (2a-e and 4a-g) with a series of alicyclic secondary amines in 80 mol % H2O/20
mol % DMSO at 25.0 ( 0.1 °C. Reactions of 2,4-dinitrophenyl X-substituted cinnamates (1a-e) and
benzoates (2a-e) with amines result in linear Yukawa-Tsuno plots. The FX values are much smaller for
the reactions of 1a-e than for those of 2a-e. A distance effect and the nature of the reaction mechanism
(i.e., a concerted mechanism for 1a-e) have been suggested to be responsible for the small FX values.
The Brønsted-type plots for the reactions of 2,4-dinitrophenyl X-substituted cinnamates (1a, 1c, and 1e)
with amines are curved with a decreasing ânuc value from 0.65 to 0.3-0.4. The reactions of Y-substituted
phenyl cinnamates (3a-g) with morpholine also result in a curved Brønsted plot, while the corresponding
reactions of Y-substituted phenyl benzoates (4a-e) exhibit a linear Brønsted plot. It has been concluded
that the curved Brønsted plots found for the reactions of the cinnamates (1a, 1c, 1e, and 3a-g) are not
due to a change in the rate-determining step (RDS) but due to a normal Hammond effect for a concerted
mechanism, that is, an earlier transition state (TS) for a more reactive amine or substrate.
Introduction
mechanism depending on the reaction conditions. Williams et
al. have found a linear Brønsted-type plot for reactions of
4-nitrophenyl acetate with a series of substituted phenoxides
There is continuous interest in acyl group transfer reactions
due to the importance in biological processes as well as synthetic
applications.1-10 Reactions of aryl acetates with aryloxides have
been suggested to proceed through a concerted or stepwise
(4) (a) Sung, D. D.; Koo, I. S.; Yang, K.; Lee, I. Chem. Phys. Lett. 2006,
426, 280-284. (b) Sung, D. D.; Koo, I. S.; Yang, K.; Lee, I. Chem. Phys.
Lett. 2006, 432, 426-430. (c) Oh, H. K.; Oh, J. Y.; Sung, D. D.; Lee, I. J.
Org. Chem. 2005, 70, 5624-5629. (d) Oh, H. K.; Park, J. E.; Sung, D. D.;
Lee, I. J. Org. Chem. 2004, 69, 9285-9288. (e) Oh, H. K.; Ha, J. S.; Sung,
D. D.; Lee, I. J. Org. Chem. 2004, 69, 8219-8223. (f) Oh, H. K.; Park, J.
E.; Sung, D. D.; Lee, I. J. Org. Chem. 2004, 69, 3150-3153.
(5) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6970-
6980.
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3600. (b) Castro, E. A.; Valdivia, J. L. J. Org. Chem. 1986, 51, 1668-
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1983, 453-457.
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2005, 70, 778-7791. (b) Castro, E. A.; Aguayo, R.; Bessolo, J.; Santos, J.
G. J. Org. Chem. 2005, 70, 3530-3536. (c) Castro, E. A.; Vivanco, M.;
Aguayo, R.; Aguayo, R.; Santos, J. G. J. Org. Chem. 2004, 69, 5399-
5404. (d) Castro, E. A.; Aguayo, R.; Santos, J. G. J. Org. Chem. 2003, 68,
8157-8161.
* To whom correspondence should be addressed. Tel: 82-2-3277-2349.
Fax: 82-2-3277-2844.
‡ Ewha Womans University.
† Kyushu University.
(1) (a) Jencks, W. P. Chem. ReV. 1985, 85, 511-527. (b) Castro, E. A.
Chem. ReV. 1999, 99, 3505-3524. (c) Lee, I.; Sung, D. D. Curr. Org. Chem.
2004, 8, 557-567. (d) Page, M. I.; Williams, A. Organic and Bio-organic
Mechanisms; Longman: Harlow, U.K., 1997; Chapter 7.
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(c) Boume, N.; Chrystiuk, E.; Davis, A. M.; Williams, A. J. Am. Chem.
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971-975. (b) Um, I. H.; Hwang, S. J.; Buncel, E. J. Org. Chem. 2006, 71,
915-920.
10.1021/jo0705061 CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/25/2007
4816
J. Org. Chem. 2007, 72, 4816-4821

Y-Substituted Phenyl X-Substituted Cinnamates and Benzoates
SCHEME 1
whose pKa values straddle the basicity of the leaving 4-nitro-
phenoxide, and they concluded that the reactions proceed
through a concerted mechanism.2 On the contrary, Buncel et
al. have suggested that reactions of substituted phenyl acetates
with phenoxide proceed through an addition intermediate with
its formation being the rate-determining step (RDS) on the basis
of the fact that σo constants result in better Hammett correlation
with rate constants than σ- constants.3
substituted benzoates, benzenesulfonates, and related compounds
in 80 mol % H2O/20 mol % DMSO.8-11 We have found that
the Hammett plots for these reactions are curved downwardly
as the substituent in the nonleaving group changes from EWGs
to electron-donating groups (EDGs). Traditionally, such a curved
Hammett plot has been interpreted as a change in the RDS.12
However, we have suggested that the nonlinear Hammett plots
are not due to a change in the RDS since the Yukawa-Tsuno
plots for the same reactions exhibit an excellent linearity with
large r values.8-11 The r value in the Yukawa-Tsuno equation
(eq 1) represents the resonance demand of the reaction center
or the extent of resonance contribution.13,14 Thus, we have
concluded that ground-state (GS) stabilization through resonance
interactions as illustrated by the resonance structures I T II is
responsible for the nonlinear Hammett plots.8-11
Aminolyses of esters with a good leaving group have often
resulted in a curved Brønsted-type plot, which has generally
been interpreted as a change in the RDS.1,4-10 The RDS has
o
been suggested to change at pKa , defined as the pKa at the
center of the Brønsted curvature, from breakdown of a zwitte-
rionic tetrahedral intermediate (T() to its formation as the amine
basicity increases.1,4-10 An intriguing aspect is whether the pKao
value is influenced by the electronic nature of the substituent
in the nonleaving group (i.e., the acyl moiety of esters) or not.
Gresser and Jencks have reported that the pKao value increases
as the substituent in the nonleaving group becomes a stronger
electron-withdrawing group (EWG) for quinuclidinolysis of
diaryl carbonates.5 This was explained through the argument
that the departure of amine from T( is favored over that of the
leaving group, as the substituent in the nonleaving group
becomes a stronger EWG.5 Castro et al. have found a similar
result for pyridinolysis of 2,4-dinitrophenyl X-substituted ben-
zoates (i.e., pKao ) 9.5 when X ) H but pKao > 9.5 when X )
Cl, CN, NO2)6 and (S)-2,4-dinitrophenyl X-substituted thioben-
zoates (i.e., pKao increases from 8.5 to 8.9 and 9.9 as X changes
from 4-Me to H and 4-NO2, respectively) in aqueous ethanol.7
In contrast, we have shown that the pKao value does not vary
on changing the electronic nature of the substituent X in the
nonleaving group for aminolyses of 2,4-dinitrophenyl X-
log kX/kH ) FX[σo + r(σ+ - σo)]
(1)
To obtain further information about the effect of a nonleaving
group on acyl transfer reactions, we have extended our study
to reactions of Y-substituted phenyl X-substituted cinnamates
(1a-e and 3a-g) and benzoates (2a-e and 4a-g) with a series
of alicyclic secondary amines whose pKa values range from
11.02 to 5.95 (Scheme 1). Modification of the nonleaving group
(11) Um, I. H.; Lee, E. J.; Seok, J. A.; Kim, K. H. J. Org. Chem. 2005,
70, 7530-7536.
(8) (a) Um, I. H.; Hwang, S. J.; Baek, M. H.; Park, E. J. J. Org. Chem.
2006, 71, 9191-9197. (b) Um, I. H.; Lee, J. Y.; Ko, S. H.; Bae, S. K. J.
Org. Chem. 2006, 71, 5800-5803. (c) Um, I. H.; Jeon, S. E.; Seok, J. A.
Chem.sEur. J. 2006, 12, 1237-1243. (d) Um, I. H.; Lee, J. Y.; Lee, H.
W.; Nagano, Y.; Fujio, M.; Tsuno, Y. J. Org. Chem. 2005, 70, 4980-
4987. (e) Um, I. H.; Kim, K. H.; Park, H. R.; Fujio, M.; Tsuno, Y. J. Org.
Chem. 2004, 69, 3937-3942. (f) Um, I. H.; Min, J. S.; Ahn, J. A.; Hahn,
H. J. J. Org. Chem. 2000, 65, 5659-5663.
(9) (a) Um, I. H.; Hong, J. Y.; Seok, J. A. J. Org. Chem. 2005, 70, 1438-
1444. (b) Um, I. H.; Chun, S. M.; Chae, O. M.; Fujio, M.; Tsuno, Y. J.
Org. Chem. 2004, 69, 3166-3172. (c) Um, I. H.; Hong, J. Y.; Kim, J. J.;
Chae, O. M.; Bae, S. K. J. Org. Chem. 2003, 68, 5180-5185.
(12) (a) Carrol, F. A. PerspectiVes on Structure and Mechanism in
Organic Chemistry; Brooks/Cole: New York, 1998; pp 371-386. (b)
Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic
Chemistry, 3rd ed.; Harper Collins Publishers: New York, 1987; pp 143-
151. (c) Swansburg, S.; Buncel, E.; Lemieux, R. P. J. Am. Chem. Soc. 2000,
122, 6594-6600.
(13) (a) Tsuno, Y.; Fujio, M. AdV. Phys. Org. Chem. 1999, 32, 267-
385. (b) Tsuno, Y.; Fujio, M. Chem. Soc. ReV. 1996, 25, 129-139. (c)
Yukawa, Y.; Tsuno, Y. Bull. Chem. Soc. Jpn. 1959, 32, 965-970.
(14) (a) Fujio, M.; Umezaki, Y.; Alam, Md. A.; Kikukawa, K.; Fujiyama,
R.; Tsuno, Y. Bull. Chem. Soc. Jpn. 2006, 79, 1091-1099. (b) Fujio, M.;
Uchida, M.; Okada, A.; Alam, Md. A.; Fujiyama, R.; Siehl, H. U.; Tsuno,
Y. Bull. Chem. Soc. Jpn. 2005, 78, 1834-1842. (c) Fujio, M.; Rappoport,
Z.; Uddin, M. K.; Kim, H. J.; Tsuno, Y. Bull. Chem. Soc. Jpn. 2003, 76,
163-169. (d) Nakata, K.; Fujio, M.; Nishimoto, K.; Tsuno, Y. J. Phys.
Org. Chem. 2003, 16, 323-335.
(10) (a) Um, I. H.; Lee, J. Y.; Fujio, M.; Tsuno, Y. Org. Biomol. Chem.
2006, 4, 2979-2985. (b) Um, I. H.; Lee, J. Y.; Kim, H. T.; Bae, S. K. J.
Org. Chem. 2004, 69, 2436-2441. (c) Um, I. H.; Ahn, J. A.; Kang, S.;
Buncel, E. J. Org. Chem. 2002, 67, 8475-8480.
J. Org. Chem, Vol. 72, No. 13, 2007 4817

Um et al.
TABLE 1. Summary of Second-Order Rate Constants for
Reactions of 2,4-Dinitrophenyl X-Substituted Cinnamates (1a-e)
(and Benzoates 2a-e, in Parenthesis) with Alicyclic Secondary
Amines in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °Ca
kN/M-1 s-1
substituent
piperidine
morpholine
piperazinium ion
a
b
c
X ) 4-NO2
640
(2880)
253
(371)
193
(174)
140
(100)
92.5
(56.2)
65.0
(138)
27.0
(32.7)
22.7
(19.6)
15.8
(11.2)
10.6
(5.77)
1.48
(1.83)
0.748
(0.675)
0.707
(0.467)
0.501
(0.306)
0.354
(0.162)
X ) 4-Cl
X ) H
d
e
X ) 4-CH3
X ) 4-CH3O
a The data in the parenthesis are the kN values for the reactions of the
benzoates 2a-e taken from ref 8e.
FIGURE 1. Yukawa-Tsuno plots for reactions of 2,4-dinitrophenyl
X-substituted cinnamates (A) and benzoates (B) with piperidine (b),
morpholine (9), and piperazinium ion (2) in 80 mol % H2O/20 mol %
DMSO at 25.0 ( 0.1 °C. The identity of points is given in Table 1.
from benzoyl to cinnamoyl should provide insights into the
reactivity and the comparative reaction mechanism. We have
probed the effect of changing the substrate from the benzoates
(2a-e and 4a-g) to the cinnamates (1a-e and 3a-g) on the
reactivity, the reaction mechanism, and, notably, the r value in
their Yukawa-Tsuno plots and report the kinetic results herein.
that the reactions proceed without changing the RDS or reaction
mechanism on changing the substituent X in the cinnamoyl
moiety. This result is consistent with our recent reports that the
substituent in the nonleaving group does not influence the
reaction mechanism for reactions of aryl-substituted benzoates
and related compounds with various nucleophiles.8-11
The Yukawa-Tsuno plots for the corresponding reactions
of 2a-e are also linear (Figure 1B). It is noted that the reactions
of 1a-e exhibit larger r values with much smaller FX values
than those of 2a-e. The r in the Yukawa-Tsuno equation (eq
1) represents the resonance demand of the reaction center or
the extent of resonance contribution.13,14 Since the r values are
larger for the reactions of 1a-e than for those of 2a-e, the
presence of the -CHdCH- bond in the cinnamates 1a-e
increases the resonance contribution in the GS as illustrated in
the resonance structures III T IV.
Results and Discussion
All reactions in this study obeyed pseudo-first-order kinetics
over 90% of the total reaction. Pseudo-first-order rate constants
(kobsd) were determined from the equation ln(A∞ - At) ) -kobsd
t
+ C. The correlation coefficients for the linear regressions were
usually higher than 0.9995. The plots of kobsd versus amine
concentration were linear, passing through the origin, indicating
that general base catalysis by a second amine molecule is absent
and the contribution of H2O and/or OH- from hydrolysis of
amine to the kobsd is negligible. Thus, the rate law is given by
eq 2, in which [S] and [NH] represent the concentration of the
substrate and amine, respectively. The second-order rate con-
stants (kN) were determined from the slopes of the linear plots
of kobsd versus amine concentration and are summarized in
Tables 1-3.
The uncertainty in the kN values is estimated to be less than
3% from replicate runs. The detailed reaction conditions and
kinetic results are given in the Supporting Information.
Many factors have been suggested to influence the FX value.
These include the charge type and the basicity of nucleophiles,
the distance from the reaction site to the substituent, and the
nature of reaction mechanism in a given reaction medium.8,10a,15-19
Reactions with anionic nucleophiles have been reported to
exhibit larger FX values than for those with neutral amines.10a
For reactions with neutral amines, the more basic amine exhibits
a larger FX value than the less basic one.8 In fact, in the current
study, the FX value decreases from 0.63 to 0.41 and 1.46 to
0.72 for the reactions of 1a-e and 2a-e, respectively, as the
amine changes from strongly basic piperidine to a weakly basic
rate ) kobsd[S], where kobsd ) kN[NH]
(2)
Effect of a Nonleaving Group Substituent on Reactivity,
r, and Mechanism. As shown in Table 1, the reactivity of 1a-e
decreases as the substituent X in the cinnamoyl moiety changes
from a strong EWG to an EDG. A similar result is shown in
the parenthesis for the corresponding reactions of 2a-e.
Interestingly, the cinnamates with a strong electron-withdrawing
substituent (i.e., 1a and 1b) are less reactive than the corre-
sponding benzoates (i.e., 2a and 2b), while the cinnamates with
an electron-donating substituent (i.e., 1c-e) are more reactive
than the corresponding benzoates (i.e., 2c-e).
The effect of substituent X on reactivity is illustrated in panels
A and B of Figure 1 for the reactions of 1a-e and 2a-e,
respectively. The Yukawa-Tsuno plots for the reactions of
1a-e exhibit good linear correlations. This contrasts the
Hammett plots for the same reactions in which 1d and 1e exhibit
negative deviations (Figure S1 in the Supporting Information).
The linear Yukawa-Tsuno plots shown in Figure 1A indicate
(15) Carrol, F. A. PerspectiVes on Structures and Mechanism in Organic
Chemistry; Brooks/Cole: New York, 1998; pp 371-380.
(16) Jencks, W. P. Catalysis in Chemistry and Enzymology; McGraw-
Hill: New York, 1969; pp 480-483.
(17) (a) Menger, F. M.; Smith, J. H. J. Am. Chem. Soc. 1972, 94, 3824-
3829. (b) Kim, T. H.; Huh, C.; Lee, B. S.; Lee, I. J. Chem. Soc. Perkin
Trans. 2 1995, 2257-2261.
(18) (a) Jaffe, H. H. Chem. ReV. 1953, 53, 191-261. (b) O’Ferrall, R.
M.; Miller, S. I. J. Am. Chem. Soc. 1963, 85, 2440-2444.
(19) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165-195.
4818 J. Org. Chem., Vol. 72, No. 13, 2007

Y-Substituted Phenyl X-Substituted Cinnamates and Benzoates
TABLE 2. Summary of Second-Order Rate Constants for
Reactions of 2,4-Dinitrophenyl X-Substituted Cinnamates 1a (X )
4-NO2), 1c (X ) H), and 1e (X ) 4-MeO) with Alicyclic Secondary
Amines in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C
kN/M-1s-1
amine
piperidine
3-methyl piperidine
piperazine
morpholine
1-formyl piperazine
piperazinium ion
pKa
1a
640
621
264
65.0
20.7
1.48
1c
193
186
115
22.7
7.37
0.707
1e
1
2
3
4
5
6
11.02
10.8
9.85
8.65
7.98
5.95
92.5
83.8
50.7
10.6
3.46
0.354
piperazinium ion. It has also been reported that insertion of one
-CH2- or -CHdCH- group between the reaction site and
the substituent causes a decrease in FX by a half.15,18 One can
see from Figure 1A and 1B that the FX values for the reactions
of 1a-e are about one-half of those for the corresponding
reactions of 2a-e. Accordingly, one might attribute the small
FX values found for the reactions of 1a-e to a distance effect
due to the presence of the -CHdCH- bond between the
reaction site and the substituent.
However, if the distance effect is solely responsible for the
small FX values obtained for the reactions of 1a-e, the FX(1a-
e)/FX(2a-e) ratio should be independent of the basicity of the
amines studied. One can calculate from Figure 1A and 1B that
the FX(1a-e)/FX(2a-e) ratio increases from 0.43 to 0.55 and
0.57 as the amine changes from piperidine to morpholine and
piperazinium ion, respectively. The dependence of the FX(1a-
e)/FX(2a-e) ratio on the basicity of amines suggests that the
distance effect is not solely responsible for the small FX values.
One can suggest that the nature of reaction mechanism (i.e., a
concerted mechanism for the reaction of 1a-e) might be another
cause for the small FX value since reactions which proceed
through a concerted mechanism often result in a small FX
value.15-19 However, the present FX value alone cannot provide
any conclusive information on the reaction mechanism.
Effect of Amine Basicity on Reactivity and Mechanism.
As shown in Table 2, the reactivity of amines toward the
cinnamates 1a, 1c, and 1e decreases as the basicity of amines
decreases. The effect of amine basicity on reactivity is illustrated
in Figure 2. The Brønsted-type plots for the reactions of 1a,
1c, and 1e with the six amines are curved when the pKa and kN
values were statistically corrected using p and q.20
A downward curvature in Brønsted-type plots has generally
been interpreted as a change in the RDS or in the TS structures
depending on the degree of the curvature.1,4-10 Aminolysis of
esters with a good leaving group has often been reported to
result in a curved Brønsted-type plot; that is, ânuc decreases from
0.8-1.0 to 0.1-0.3 as the amine becomes more basic than the
leaving group by 4-5 pKa units.1,4-10 Such a large change in
ânuc values has been suggested as a change in the RDS from
breakdown of T( to its formation as the basicity of amines
increases.1,4-10
FIGURE 2. Brønsted-type plots for reactions of 2,4-dinitrophenyl
X-substituted cinnamates with alicyclic secondary amines in 80 mol
% H2O/20 mol % DMSO at 25.0 ( 0.1 °C. The identity of points is
given in Table 2.
suggested to proceed through a concerted mechanism.4-7 Thus,
one can propose that the curved Brønsted-type plots shown in
Figure 2 are not due to a change in the RDS but due to a change
in the TS structure in accordance with a normal Hammond effect
for a concerted mechanism, that is, an earlier TS for the reaction
with a more reactive amine.21 A similar conclusion has been
drawn for reactions of substituted benzoyl fluorides with primary
amines. Song and Jencks have found curved Brønsted-type plots
(â2 ) 0.67 at a low pKa region and â1 ) 0.23 at a high pKa
region) and concluded that a normal Hammond effect is
responsible for the curved Brønsted-type plots.22 Castro et al.
have also concluded that reactions of bis(4-nitrophenyl) thiono-
carbonate and 2,4-dinitrophenyl 4-methylphenyl carbonate with
secondary amines proceed through a concerted mechanism since
the Brønsted-type plots obtained for these reactions exhibit only
a small downward curvature (i.e., â2 ) ca. 0.5 and â1 ) 0.10).23
To examine the above proposal, reactions of Y-substituted
phenyl cinnamates (3a-g) and benzoates (4a-g) with piperidine
and morpholine have been investigated. The effect of substituent
Y in the leaving group on reactivity and mechanism is discussed
in the following section.
Effect of a Leaving Group Substituent on Reactivity and
Mechanism. Table 3 demonstrates that the reactivity of 3a-g
and 4a-g decreases as the substituent Y in the leaving group
becomes a weaker EWG. It is also shown that 3a-g are more
reactive than 4a-g except for the reactions of 3a and 4a with
piperidine. The effect of the substituent Y in the leaving group
on reactivity is illustrated in Figure 3. The Brønsted-type plots
for the reactions of 3a-g and 4a-g with piperidine are curved
As shown in Figure 2, the ânuc value for the reactions of 1a,
1c, and 1e with amines decreases from 0.65 to ca. 0.3-0.4.
The change in the ânuc value for the current reactions is much
smaller than that reported for reactions which proceed through
a stepwise mechanism with a change in the RDS. Besides, the
ânuc value of 0.65 is typical for reactions which have been
(21) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334-338.
(22) Song, B. D.; Jencks, W. P. J. Am. Chem. Soc. 1989, 111, 8479-
8484.
(23) (a) Castro, E. A.; Santos, J. G.; Tellez, J.; Umana, M. I. J. Org.
Chem. 1997, 62, 6568-6574. (b) Castro, E. A.; Andujar, M.; Campodonico,
P.; Santos, J. G. Int. J. Chem. Kinet. 2002, 34, 309-315.
(20) Bell, R. P. The Proton in Chemistry; Methuen: London, U.K., 1959;
p 159.
J. Org. Chem, Vol. 72, No. 13, 2007 4819

Um et al.
TABLE 3. Summary of Second-Order Rate Constants for
Reactions of Y-Substituted Phenyl Cinnamates (3a-g) and
Benzoates (4a-g, in Parenthesis) with Piperidine and Morpholine in
80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C
kN/M-1s-1
Y-PhOH
pKa
piperidine
morpholine
a
b
c
d
e
f
Y ) 3,4-(NO2)2
5.42
156
13.2
(10.1)
0.531
(191)a
12.3
Y ) 4-NO2
Y ) 4-CHO
Y ) 4-COMe
Y ) 4-CO2Et
Y ) 3-Cl
7.14
7.66
8.05
8.50
9.02
9.19
(5.94)a
4.03
(0.0876)b
0.0970
(0.00878)
0.0296
(0.00299)
0.0226
(0.00136)
0.00394
(-)c
(0.852)a
1.71
(0.236)a
1.24
(0.139)
0.297
(0.0159)a
0.160
g
Y ) 3-COCH3
0.00160
(0.00650)a
(-)c
a Data taken from ref 8b. b Data taken from ref 8f. c The reactivity was
too low to determine rate constants.
FIGURE 4. Brønsted-type plots for reactions of Y-substituted phenyl
cinnamates (b; 3a-g) and benzoates (O; 4a-e) with morpholine in
80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C. The identity of
points is given in Table 3.
a change in the RDS.8b However, for the reactions of 3a-g,
the decrease in the âlg value from -1.00 to -0.26 is much
smaller than that reported for reactions which proceed through
a stepwise mechanism with a change in the RDS (e.g., from
-1.50 to -0.36 for the reactions of 4a-g with piperidine). Thus,
one can suggest that the curved Brønsted-type plot for the
reactions of 3a-g with piperidine is not due to a change in the
RDS.
To examine the above suggestion, Brønsted-type plots for
the reactions of 3a-g and 4a-e with morpholine have been
constructed. As shown in Figure 4, the Brønsted-type plot is
linear for the reactions of 4a-e but curved for those of 3a-g.
Since the pKa of the conjugate acid of morpholine has been
o
reported to be 8.65 in the current reaction medium, the pKa
should have been detected at the pKa between 3.65 and 4.65 if
the reactions of 3a-g and 4a-e with morpholine proceeded
through a stepwise mechanism with a change in the RDS. As
shown in Figure 4, the center of the Brønsted curvature for the
reactions of 3a-g with morpholine is 6.1, indicating that this
curved Brønsted-type plot is clearly not due to a change in the
RDS. Thus, one can conclude that the reactions of 3a-g with
piperidine and morpholine proceed through a concerted mech-
anism and the nonlinear Brønsted-type plots in Figures 3 and 4
are also due to a normal Hammond effect,21 that is, an earlier
TS structure for a more reactive substrate.
FIGURE 3. Brønsted-type plots for reactions of Y-substituted phenyl
cinnamates (b; 3a-g) and benzoates (O; 4a-g) with piperidine in 80
mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C. The identity of points
is given in Table 3.
downwardly; that is, the âlg value decreases from -1.00 to
-0.26 and from -1.50 to -0.36 for the reactions of 3a-g and
4a-g, respectively.
Generally, the RDS of ester aminolysis has been reported to
change from the breakdown of T( to its formation as the
attacking amine becomes more basic than the leaving group or
the leaving group becomes less basic than the amine by 4-5
Conclusions
o
pKa units.1,4-10 The pKa , defined as the pKa at the center of
the Brønsted curvature, is 6.4 for the current reactions of 3a-g
and 4a-g with piperidine, which is ca. 4.6 pKa units smaller
than the pKa of the conjugate acid of piperidine (pKa ) 11.02).
Thus, one might suggest that a change in the RDS is responsible
for the nonlinear Brønsted-type plots in Figure 3 on the basis
of the pKao value. In fact, we have recently attributed the curved
Brønsted-type plot for the reactions of 4a-g with piperidine to
The current study has allowed us to conclude the following:
(1) The reactions of 1a-e with amines result in much smaller
FX values but larger r values than those of 2a-e. The larger r
values found for the reactions of 1a-e compared to those for
the reactions of 2a-e suggest that the presence of the -CHd
CH- bond in 1a-e facilitates the ground-state resonance. (2)
A distance effect and the nature of reaction mechanism (i.e., a
4820 J. Org. Chem., Vol. 72, No. 13, 2007

Y-Substituted Phenyl X-Substituted Cinnamates and Benzoates
4.43 (q, J ) 7.5 Hz, 2H), 6.60-6.67 (d, J ) 17.5 Hz, 1H), 7.24-
7.28 (d, J ) 10 Hz, 2H), 7.43-7.45 (m, 3H), 7.58-7.62 (dd, J1 )
7.5 Hz, J2 ) 2.5 Hz, 2H), 7.86-7.93 (d, J ) 17.5 Hz, 1H), 8.10-
8.14 (d, J ) 10 Hz, 2H). Anal. Calcd for C18H16O4: C, 72.96; H,
5.44. Found: C, 72.98; H, 5.45.
3-Chlorophenyl cinnamate (3f): mp 62-64 °C; 1H NMR (250
MHz, CDCl3) δ 6.58-6.65 (d, J ) 17.5 Hz, 1H), 7.10-7.11 (m,
1H), 7.21-7.23 (m, 1H), 7.25-7.26 (m, 1H), 7.31-7.37 (t, J )
7.5 Hz, 1H), 7.42-7.45 (m, 3H), 7.58-7.62 (dd, J1 ) 7.5 Hz, J2
) 2.5 Hz, 2H), 7.84-7.91 (d, J ) 17.5 Hz, 1H). Anal. Calcd for
C15H11ClO2: C, 69.64; H, 4.29. Found: C, 69.67; H, 4.30.
3-Acetylphenyl cinnamate (3g): mp 69-71 °C; 1H NMR (250
MHz, CDCl3) δ 2.62-2.65 (s, 3H), 6.62-6.68 (d, J ) 15 Hz, 1H),
7.38-7.41 (m, 1H), 7.42-7.46 (m, 3H), 7.49-7.55 (t, J ) 7.5 Hz,
1H), 7.59-7.63 (dd, J1 ) 7.5 Hz, J2 ) 2.5 Hz, 2H), 7.76-7.77
(m, 1H), 7.84-7.87 (d, J ) 15 Hz, 1H), 7.93 (s, 1H). Anal. Calcd
for C17H14O3: C, 76.68; H, 5.30. Found: C, 76.51; H, 5.31.
Kinetics. The kinetic study was performed with a UV-vis
spectrophotometer for slow reactions (t1/2 > 10 s) or a stopped-
flow spectrophotometer for fast reactions (t1/2 e 10 s) equipped
with a constant temperature circulating bath. The reactions were
followed by monitoring the appearance of Y-substituted phenoxide
at a fixed wavelength corresponding to the λmax. Due to the low
solubility of the substrates in pure water, aqueous DMSO (80 mol
% H2O/20 mol % DMSO) was used as the reaction medium. Doubly
glass distilled water was further boiled and cooled under nitrogen
just before use.
All of the reactions were carried out under pseudo-first-order
conditions in the presence of excess amines. Typically, the reaction
was initiated by adding 5 µL of a 0.01 M of substrate solution in
MeCN by a 10 µL gastight syringe to a 10 mm quartz UV cell
containing 2.50 mL of the thermostated reaction mixture made up
of solvent and an aliquot of amine stock solution. The stock solution
of amines (ca. 0.2 M) was prepared in a 25.0 mL volumetric flask
under nitrogen by adding 2 equiv of amines and 1 equiv of
standardized HCl solution to obtain a self-buffered solution. All of
the solutions were transferred by gastight syringes under nitrogen.
Generally, the concentration of amines was varied over the range
of (1-100) × 10-3 M, while the substrate concentration was 2 ×
10-5 M. The plots of ln(A∞ - At) versus time were linear over ca.
90% of the total reaction. Usually, five different concentrations of
amines were used to determine the kN value from the slope of the
linear plot of kobsd versus amine concentration.
concerted mechanism for the reactions of 1a-e) have been
suggested to be responsible for the small FX values found for
the reactions of 1a-e. (3) The Brønsted-type plots for the
reactions of 1a, 1c, and 1e with alicyclic secondary amines
exhibit a downward curvature; that is, the ânuc value decreases
from 0.65 to 0.3-0.4 as the basicity of amines increases. (4)
The Brønsted-type plots for the reactions of 3a-g with
piperidine and morpholine are also curved, indicating that these
curved Brønsted-type plots are not due to a change in the RDS
but due to a normal Hammond effect for a concerted mechanism,
that is, an earlier TS for a more reactive substrate.
Experimental Section
Materials. Y-Substituted phenyl X-substituted cinnamates (or
benzoates) were readily prepared as reported24 from the reactions
of Y-substituted phenol and X-substituted cinnamoyl chloride under
the presence of triethylamine in anhydrous ether and purified by
column chromatography. Their purity was checked by their melting
points for the known compounds, and the identity of unreported
compounds (1a, 1b, 1d, 1e, 3c, 3e, 3f, and 3g) was confirmed by
elemental analysis and 1H NMR spectra (Supporting Information).
1
All unreported compounds gave good elemental analyses and H
NMR spectra. Amines and other chemicals used are of the highest
quality available.
2,4-Dinitrophenyl 4-nitrocinnamate (1a): mp 170-172 °C; 1H
NMR (250 MHz, CDCl3) δ 6.77-6.84 (d, J ) 17.5 Hz, 1H), 7.59-
7.62 (d, J ) 7.5 Hz, 1H), 7.77-7.81 (d, J ) 10 Hz, 2H), 7.96-
8.03 (d, J ) 17.5 Hz, 1H), 8.31-8.35 (d, J ) 10 Hz, 2H),
8.57-8.61 (dd, J1 ) 7.5 Hz, J2 ) 2.5 Hz, 1H), 9.02-9.03 (d, J )
2.5 Hz, 1H). Anal. Calcd for C15H9N3O8: C, 50.15; H, 2.53.
Found: C, 50.40; H, 2.75.
2,4-Dinitrophenyl 4-chlorocinnamate (1b): mp 139-140 °C;
1H NMR (250 MHz, CDCl3) δ 6.61-6.68 (d, J ) 17.5 Hz, 1H),
7.42-7.46 (d, J ) 10 Hz, 2H), 7.55-7.58 (d, J ) 7.5 Hz, 1H),
7.57-7.61 (d, J ) 10 Hz, 2H), 7.88-7.95 (d, J ) 17.5 Hz, 1H),
8.55-8.59 (dd, J1 ) 7.5 Hz, J2 ) 2.5 Hz, 1H), 8.99-9.00 (d, J )
2.5 Hz, 1H). Anal. Calcd for C15H9ClN2O6: C, 51.67; H, 2.60.
Found: C, 51.65; H, 2.67.
2,4-Dinitrophenyl 4-methylcinnamate (1d): mp 138-140 °C;
1H NMR (250 MHz, CDCl3) δ 6.59-6.65 (d, J ) 15 Hz, 1H),
7.25-7.28 (d, J ) 7.5 Hz, 2H), 7.51-7.54 (d, J ) 7.5 Hz, 2H),
7.57-7.61 (d, J ) 10 Hz, 1H), 7.91-7.97 (d, J ) 15 Hz, 1H),
8.53-8.58 (dd, J1 ) 10 Hz, J2 ) 2.5 Hz, 1H), 8.98-8.99 (d, J )
2.5 Hz, 1H). Anal. Calcd for C16H12N2O6: C, 58.54; H, 3.68.
Found: C, 58.49; H, 3.70.
2,4-Dinitrophenyl 4-methoxycinnamate (1e): mp 132-134 °C;
1H NMR (250 MHz, CDCl3) δ 6.49-6.55 (d, J ) 15 Hz, 1H),
6.95-7.00 (dd, J1 ) 10 Hz, J2 ) 2.5 Hz, 2H), 7.57-7.61 (d, J )
10 Hz, 1H), 7.65-7.68 (d, J ) 7.5 Hz, 1H), 7.89-7.95 (d, J ) 15
Hz, 1H), 8.53-8.57 (dd, J1 ) 7.5 Hz, J2 ) 2.5 Hz, 1H), 8.97-
8.98 (d, J ) 2.5 Hz, 1H). Anal. Calcd for C16H12N2O7: C, 55.82;
H, 3.51. Found: C, 55.81; H, 3.53.
Product Analysis. Y-Substituted phenoxide was liberated quan-
titatively and identified as one of the reaction products by
comparison of the UV-vis spectra after the completion of the
reactions with those of the authentic samples under the same
reaction conditions.
Acknowledgment. This work was supported by a grant from
KOSEF of Korea (R01-2004-000-10279-0).
Supporting Information Available: Figure S1 for Hammett
plots for the reactions of 1a-e with piperidine, morpholine, and
4-Formylphenyl cinnamate (3c): mp 82-85 °C; 1H NMR (250
MHz, CDCl3) δ 6.61-6.67 (d, J ) 15 Hz, 1H), 7.36-7.39 (d, J )
7.5 Hz, 2H), 7.43-7.48 (m, 3H), 7.59-7.63 (dd, J1 ) 7.5 Hz, J2
) 2.5 Hz, 2H), 7.88-7.94 (d, J ) 15 Hz, 1H), 7.95-7.98 (d, J )
7.5 Hz, 2H), 10.0 (s, 1H). Anal. Calcd for C16H12O3: C, 76.18; H,
4.79. Found: C, 75.84; H, 4.75.
1
piperazinium ion. H NMR spectra for 1a, 1b, 1d, 1e, 3c, 3e, 3f,
and 3g, Tables S1-S24 for the kinetic data for reactions of 1a-e
with secondary amines, Tables S25-S38 for the kinetic data for
reactions of 3a-g with secondary amines, Table S39 for the kinetic
data for reactions of 4e with piperidine, and Tables S40-S43 for
the kinetic data for reactions of 4a, 4c, 4d, and 4e with morpholine.
This material is available free of charge via the Internet at
http://pubs.acs.org.
4-(Ethoxycarbonyl)phenyl cinnamate (3e): mp 89-91 °C; 1H
NMR (250 MHz, CDCl3) δ 1.37-1.43 (t, J ) 7.5 Hz, 3H), 4.35-
(24) (a) Womack, E. B.; McWhirter, J. Org. Synth. 1940, 20, 77. (b)
Suh, J.; Lee, B. H. J. Org. Chem. 1980, 45, 3103-3107.
JO0705061
J. Org. Chem, Vol. 72, No. 13, 2007 4821