Hydrolysis of 1-(X-substituted-benzoyl)-4-aminopyridinium ions: Effect of substituent X on reactivity and reaction mechanism

Article abstract of DOI:10.1039/c1ob06137b

A kinetic study is reported for hydrolysis of 1-(X-substituted-benzoyl)-4- aminopyridinium ions 2a-i, which were generated in situ from the nucleophilic substitution reaction of 2,4-dinitrophenyl X-substituted-benzoates 1a-i with 4-aminopyridine in 80 mol% H₂O/20 mol% DMSO at 25.0 ± 0.1 °C. The plots of pseudo-first-order rate constants k_obsdvs. pyridine concentration are linear with a large positive intercept, indicating that the hydrolysis of 2a-i proceeds through pyridine-catalyzed and uncatalyzed pathways with the rate constant k_cat and k_o, respectively. The Hammett plots for k_cat and k_o consist of two intersecting straight lines, which might be taken as evidence for a change in the rate-determining step (RDS). However, it has been proposed that the nonlinear Hammett plots are not due to a change in the RDS but are caused by stabilization of 2a-i in the ground state through a resonance interaction between the π-electron-donor substituent X and the carbonyl functionality. This is because the corresponding Yukawa-Tsuno plots exhibit excellent linear correlations with ρ_X = 1.45 and r = 0.76 for k_cat while ρ_X = 1.39 and r = 0.72 for k_o. A possibility that the hydrolysis of 2a-i proceeds through a concerted mechanism has been ruled out on the basis of the large ρ_X values. Thus, the reaction has been concluded to proceed through a stepwise mechanism in which the leaving group departs after the RDS since OH^- is more basic and a poorer nucleofuge than 4-aminopyridine. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1ob06137b

View Article Online / Journal Homepage / Table of Contents for this issue
Organic &
Biomolecular
Chemistry
Dynamic Article Links
Cite this: Org. Biomol. Chem., 2011, 9, 8062
www.rsc.org/obc
PAPER
Hydrolysis of 1-(X-substituted-benzoyl)-4-aminopyridinium ions: effect of
substituent X on reactivity and reaction mechanism†‡
Ik-Hwan Um,* Eun-Hee Kim and Ji-Sun Kang
Received 10th July 2011, Accepted 1st September 2011
DOI: 10.1039/c1ob06137b
A kinetic study is reported for hydrolysis of 1-(X-substituted-benzoyl)-4-aminopyridinium ions 2a–i,
which were generated in situ from the nucleophilic substitution reaction of 2,4-dinitrophenyl
X-substituted-benzoates 1a–i with 4-aminopyridine in 80 mol% H2O/20 mol% DMSO at 25.0 0.1 ◦C.
The plots of pseudo-first-order rate constants kobsd vs. pyridine concentration are linear with a large
positive intercept, indicating that the hydrolysis of 2a–i proceeds through pyridine-catalyzed and
uncatalyzed pathways with the rate constant kcat and ko, respectively. The Hammett plots for kcat and ko
consist of two intersecting straight lines, which might be taken as evidence for a change in the
rate-determining step (RDS). However, it has been proposed that the nonlinear Hammett plots are not
due to a change in the RDS but are caused by stabilization of 2a–i in the ground state through a
resonance interaction between the p-electron-donor substituent X and the carbonyl functionality. This
is because the corresponding Yukawa-Tsuno plots exhibit excellent linear correlations with rX = 1.45
and r = 0.76 for kcat while rX = 1.39 and r = 0.72 for ko. A possibility that the hydrolysis of 2a–i proceeds
through a concerted mechanism has been ruled out on the basis of the large rX values. Thus, the
reaction has been concluded to proceed through a stepwise mechanism in which the leaving group
departs after the RDS since OH- is more basic and a poorer nucleofuge than 4-aminopyridine.
reactions of various types of esters.4–7 It is well known that
Introduction
reactions of esters with amines proceed through a concerted
The Yukawa-Tsuno eqn (1) was originally derived to account for
mechanism or through a stepwise pathway depending on re-
the resonance effect in decomposition of w-diazoacetophenones in
acetic acid.1 The r valuein eqn (1) represents the resonance demand
of the reaction center or the extent of resonance contribution,
action conditions (e.g., the nature of the electrophilic center
and reaction medium).4–11 Aminolysis of X-substituted phenyl
diphenylphosphinates has been reported to proceed through a
concerted mechanism since the kinetic data result in an excellent
linear Yukawa-Tsuno plot with rX = 1.91 and r = 0.30.7a A similar
conclusion has been drawn for the corresponding reactions of
X-substituted phenyl diphenylphosphinothioates.7d In contrast,
aminolysis of carboxylic esters possessing a good leaving group
(e.g., 2,4-dinitrophenoxide) has been reported to proceed through
a stepwise mechanism on the basis of a curved Brønsted-type
plot.4,8–11 The rate-determining step (RDS) has been suggested to
be dependent on the basicity of the incoming amine and the leaving
group, i.e., the RDS changes from the breakdown of a zwitterionic
tetrahedral intermediate T to its formation as the incoming amine
becomes more basic than the leaving group by 4 to 5 pKa units or
the leaving group becomes less basic than the amine.4,8–11
+
while the term (sX - sXo) is the resonance substituent constant
that measures the capacity for p-delocalization of the p-electron
donor substituent.1 Eqn (1) becomes the Hammett equation when
r = 0, but becomes the Brown-Okamoto equation when r = 1.
It has widely been accepted that eqn (1) is a powerful tool for
investigation of resonance effects in solvolyses of benzylic and
related systems, in which a partial positive charge is developing in
the transition state (TS).1–3
o
+
log (kX/kH) = rX[sX + r(sX - sXo)]
(1)
We have shown that eqn (1) is highly effective in clarifying
ambiguities in reaction mechanisms for nucleophilic substitution
Pyridinolysis of esters has also intensively been investigated
and the reaction mechanisms are fairly well understood.4a,12–15
It has been reported that reactions of pyridines with acid
derivatives including esters produce acylpyridinium ions, which
hydrolyze in H2O.4a,12–15 Although scattered information on
hydrolysis of acylpyridinium ions is available, the reaction
mechanism is not yet clearly understood.12,13,14a Castro et al.
have recently investigated pyridine-catalyzed hydrolysis of
Department of Chemistry and Nano Science, Ewha Womans University,
Seoul, 120-750, Korea. E-mail: ihum@ewha.ac.kr
† This paper is dedicated with respect and affection to the late Professor
Yuho Tsuno a true gentleman and an inspiring mentor.
‡ Electronic supplementary information (ESI) available: Kinetic condi-
tions and results for hydrolysis of 2a–i with 4-aminopyridine (Tables S1–
S9), plots of kobsd vs. 4-aminopyridine concentration (Figs. S1–S8), and 1H
NMR spectra for 2,4-dinitrophenyl X-substituted benzoates 1a–i (Figs.
S9–S17). See DOI: 10.1039/c1ob06137b
8062 | Org. Biomol. Chem., 2011, 9, 8062–8067
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
Table 1 Summary of kinetic data for the hydrolysis of 1-(X-substituted
benzoyl)-4-aminopyridinium ions (2a–i) in 80 mol% H2O/20 mol% DMSO
1-(aryloxythiocarbonyl)pyridinium ions, generated in situ from the
reactions of phenyl and 4-nitrophenyl chlorothioformates with
five diffefernt Y-substituted pyridines (Y = 3,4-Me2, 4-Me, H,
3-COMe, and 4-CN) in H2O.14a They have shown that the rate
constant for pyridine-catalyzed hydrolysis of the pyridinium ions
increases only slightly as pyridine basicity increases, e.g., the slope
of the Brønsted-type plots is ca. 0.2. The small Brønsted coefficient
has been attributed to the fact that as pKa increases the effect of a
better pyridine catalyst is compensated by a worse leaving pyridine
from the corresponding acylpyridinium ions.14a
We have recently reported that pyridinolysis of 2,4-
dinitrophenyl X-substituted benzoates 1a–i proceeds through a
stepwise mechanism, in which the RDS is dependent on the
basicity of the incoming pyridine (Scheme 1).4a However, it has
been shown that the electronic nature of the substituent X in the
benzoyl moiety does not affect the RDS, since the Yukawa-Tsuno
plots exhibit excellent linear correlations with rX = 0.92 ~ 1.31 and
r = 0.79 ~ 0.92.4a
at 25.0 0.1 ◦
C
X
102 kcat/M-1s-1
103 ko/s-1
2a
2b
2c
2d
2e
2f
2g
2h
2i
4-NMe2
4-MeO
4-Me
3-Me
H
4-Cl
3-Cl
4-CN
4-Cl-3-NO2
0.518
11.6
27.3
46.1
60.1
107
226
760
965
0.204
4.08
8.84
13.4
18.0
37.8
64.0
135
310
(Fig. 1 and Figs. S1–S8 in the ESI), indicating that the contribution
of H2O and/or OH- ion from hydrolysis of 4-aminopyridine to
k
obsd is significant. Thus, one can derive a rate equation as eqn (2),
in which kcat and ko represent the second-order rate constant for
the pyridine-catalyzed reactions and the first-order rate constant
for the uncatalyzed reactions (i.e., the reactions with H2O and/or
OH-), respectively. Thus, the kcat and ko values were determined
from the slope and intercept of the linear plots of kobsd vs. pyridine
concentration, respectively. The uncertainty in these values is
estimated to be less than 3% from replicate runs. The kcat and
ko values calculated are summarized in Table 1.
Scheme 1 Pyridinolysis of 2,4-dinitrophenyl X-substituted benzoates
1a–i.
kobsd = kcat[4-aminopyridine] + ko
(2)
We have now carried out hydrolysis of 1-(X-substituted-
benzoyl)-4-aminopyridinium ions 2a–i, generated in situ from the
reactions of 1a–i with 4-aminopyridine. The reactions of 2a–i were
carried out in a self-buffered solution (i.e., 4-aminopyridine/4-
aminopyridinium-ion = 1.0/1.0) to investigate the effect of
the substituent X on the reaction mechanism. The hydrolysis
of 2e was also performed in 5-different buffered solutions
(i.e., 4-aminopyridine/4-aminopyridinium-ion = 3.0/1.0, 2.0/1.0,
1.0/1.0, 1.0/1.9, and 1.0/2.9) to characterize the reacting species.
Analysis of our kinetic data using the Yukawa-Tsuno equation has
led us to conclude that the hydrolysis of 2a–i proceeds through a
stepwise mechanism with the first step being the RDS for both
pyridine-catalyzed and uncatalyzed reactions (Scheme 2).
Effect of substituent X on reactivity and mechanism
As shown in Table 1, kcat increases as the substituent X on the
benzoyl moiety of 2a–i changes from an electron-donating group
(EDG) to an electron-withdrawing group (EWG), e.g., it increases
from 5.18 ¥ 10-3 M-1s-1 to 6.01 ¥ 10-1 and 9.65 M-1s-1 as X changes
from 4-NMe2 to H and 4-Cl-3-NO2, in turn. A similar result is
shown for ko, although the magnitude of ko is smaller than that of
kcat.
The effect of the substituent X on the reactivity of 2a–i is
illustrated in Fig. 2. One can see that each Hammett plot consists
of two intersecting straight lines (i.e., rX = 2.38 ~ 2.53 for
substrates possessing EDGs while rX = 1.30 ~ 1.39 for those
bearing EWGs). Traditionally, nonlinear Hammett plots have been
taken as evidence for a change in the reaction mechanism or RDS
depending on the shape of curvature.16 Upward curvature often
found for nucleophilic substitution reactions of benzylic systems
has been interpreted as a change in mechanism, i.e., from SN1 for
substrates possessing an EDG to SN2 for those bearing an EWG.16
In contrast, downward curvature has been attributed to a change
Results and discussion
All reactions in this study obeyed pseudo-first-order kinetics in the
presence of a large excess of 4-aminopyridine compared with the
substrate. Pseudo-first-order rate constants (kobsd) were calculated
from the equation, ln (A• - At) = -kobsdt + c. The plots of kobsd vs.
pyridine concentration were linear with a large positive intercept
Scheme 2 Hydrolysis of 1-(X-substituted benzoyl)-4-aminopyridinium ions 2a–i.
The Royal Society of Chemistry 2011 Org. Biomol. Chem., 2011, 9, 8062–8067 | 8063
This journal is
©

View Article Online
pyridine-catalyzed process, since one might expect that an EDG
in the benzoyl moiety would retard nucleophilic attack (i.e., a
decrease in k3 in Scheme 2) but would accelerate departure of the
leaving group (i.e., an increase in k4 in Scheme 2). In contrast,
an EWG would increase k3 but decrease k4. Thus, the nonlinear
Hammett plot might be interpreted as a change in RDS upon
changing the substituent X in the benzoyl moiety of 2a–i from
EDGs to EWGs.
Origin of the nonlinear Hammett plot
However, we propose that the nonlinear Hammett plots shown
in Fig. 2 are not due to a change in the RDS on the basis of
the following reasons: (1) The RDS should be determined by
the k4/k-3 ratio (i.e., RDS = the k3 step when k4/k-3 > 1 or
RDS = the k4 step when k4/k-3 < 1) but not by the magnitude
of k3 and k4. Furthermore, k3 and k4 values cannot be compared
directly since the former is a second-order rate constant while the
latter is a first-order rate constant. (2) Both k4 and k-3 processes
would be accelerated by an EDG in the benzoyl moiety but would
be retarded by an EWG, since the nuclefuges depart with the
bonding electrons. Thus, the k4/k-3 ratio would be independent of
the electronic nature of the substituent X in the benzoyl moiety.
The origin of the nonlinear Hammett plots that we propose
is stabilization of pyridinium ions 2a–i in the ground state
(GS) through resonance interactions as modeled by resonance
structures I and II. Such resonance interactions would stabilize
their GS and cause a decrease in their reactivity, as suggested
previously for solvolysis of methyl chloroformate.17 This idea is
consistent with the fact that the pyridinium ions possessing an
EDG in the benzoyl moiety deviate negatively from the linear
Hammett plot composed of those bearing EWGs (i.e., 2e–i).
Furthermore, such negative deviation is more significant for the
pyridinium ion bearing a stronger EDG.
Fig. 1 Plot of kobsd vs. 4-aminopyridine concentration for the hydrolysis
of 1-benzoyl-4-aminopyridinium ion 2e in 80 mol% H2O/20 mol% DMSO
at 25.0 0.1 ◦C.
To examine the validity of the above argument, Yukawa–Tsuno
plots have been constructed. As shown in Fig. 3, the Yukawa–
Tsuno plots exhibits excellent linear correlation with rX = 1.45
and r = 0.76 for the catalyzed reaction while rX = 1.39 and r =
0.72 for the uncatalyzed process. The linear Yukawa–Tsuno plots
clearly indicate that the nonlinear Hammett plots are not due to
a change in RDS but are caused by the stabilization of 2a–i in the
GS through resonance interactions as mentioned above. This idea
is consistent with our previous proposal that deduction of reaction
mechanisms based solely on a linear or nonlinear Hammett plot
can be misleading.4–6
Fig. 2 Hammett plots for the hydrolysis of 2a–i in 80 mol% H2O/20 mol%
DMSO at 25.0 0.1 ◦C: ( for kcat and for k ). The identity of the points
is given in Table 1.
᭹
᭺
o
in RDS upon changing the substituent from EDGs to EWGs.16 In
fact, the downward Hammett plot found for reactions of a series
of X-substituted benzaldehydes with semicarbarzide in a weakly
acidic medium (e.g., pH = 3.9) has been concluded to be a change
in RDS.16b
Accordingly, one might suggest that the nonlinear Hammett
plots in Fig. 2 are due to a change in RDS, i.e., from the formation
of an intermediate to its breakdown to yield the reaction products
as the substituent X in the benzoyl moiety of 2a–i changes from
EDGs to EWGs. This idea appears to be reasonable for the
Deduction of reaction mechanism
To investigate the reacting species, hydrolysis of 2e has been per-
formed in five different pyridine/pyridinium-ion buffer solutions
(i.e., pyridine/pyridinium-ion = 3.0/1.0, 2.0/1.0, 1.0/1.0, 1.0/1.9,
and 1.0/2.9). The kinetic results are summarized in Table 2 and
illustrated in Fig. 4A and 4B.
As shown in Fig. 4A, the plots of kobsd vs. [pyridine]tot, the total
concentration of pyridine and pyridinium ion, are linear with
8064 | Org. Biomol. Chem., 2011, 9, 8062–8067
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
0.61 0.01 M-1s-1), although the intercept of the plots (i.e., ko)
is dependent on the buffer ratios. It is noted that the intercepts
in Fig. 4A are identical to those in Fig. 4B. Besides, one can
get a rate constant of 0.61 0.01 M-1s-1 by dividing the slopes
in Fig. 4A by the fraction of pyridine in the buffer solutions.
These results indicate clearly that pyridine (but not pyridinium
ion) catalyzes the reaction as a general-base catalyst and OH- ion
is also a nucleophilic species in this study.
To prove the above argument that OH- ion is also a nucleophilic
species in this study, the ko values in Table 2 have been dissected
into the rate constants for OH- and H2O reactions. The rate
constant measured for the hydrolysis of 2e in the absence of the
pyridine/pyridinium-ion buffer is 0.0095 s-1 (i.e., the contribution
of H2O reaction to ko).18 Since ko represents the total rate constants
for the reactions with OH- and H2O, one can calculate the rate
constant for the OH- reaction by subtracting 0.0095 s-1 from
the ko value determined from the intercept of the linear plots
in Fig. 4. The pHs of the buffer solutions can be calculated
from the Henderson–Hasselbalch equation using the pKa value of
8.93 reported previously for 4-aminopyridinium ion in 80 mol%
H2O/20 mol% DMSO4e and the buffer ratios employed in this
study (Table 2). As shown in Fig. 5, the plot of log (ko - 0.0095)
vs. the pH of the reaction medium exhibits an excellent linear
correlation with a slope of 0.97 0.03. This supports clearly the
preceding argument that OH- ion is a nucleophilic species in this
study.
Table 2 Summary of the kinetic results for hydrolysis of 1-benzoyl-4-
aminopyridinium ion 2e in 5 different pyridine/pyridinium-ion buffer
solutions at 25.0 0.1 ◦
C
Pyridine/pyridinium-ion
pH
103 kcat/M-1s-1
103 ko/s-1
3.0/1.0
2.0/1.0
1.0/1.0
1.0/1.9
1.0/2.9
9.41
9.23
8.93
8.66
8.47
616
611
601
617
619
33.4
26.8
18.0
13.9
12.6
Fig. 3 Yukawa-Tsuno plots for the hydrolysis of 2a–i in 80 mol%
H2O/20 mol% DMSO at 25.0 0.1 ◦C: ( for kcat and
for k ). The
᭹
᭺
o
identity of the points is given in Table 1.
Fig. 5 Plot of log (ko - 0.0095) vs. pH of the reaction medium
for the hydrolysis of 1-benzoyl-4-aminopyridinium ion 2e in 80 mol%
H2O/20 mol% DMSO at 25.0 0.1 ◦C.
Fig.
4
Plots of kobsd vs. [4-aminopyridine]tot (A) and kobsd vs.
[4-aminopyridine]free (B) for hydrolysis of 1-benzoyl-4-aminopyridinium
ion 2e in 5 different pyridine/pyridinium-ion buffer solutions at 25.0
0.1 ◦C. pyridine/pyridinium-ion = 3.0/1.0 (ꢀ), 2.0/1.0 (ꢁ), 1.0/1.0 ( ),
᭹
The reaction of 2a–i with OH- ion would proceed through
an SN2-like concerted mechanism with a TS structure similar to
TS1 or through a stepwise pathway with an intermediate. The
latter mechanism can have one of the two TS structures (i.e.,
TS2 and TS3) depending on the RDS, i.e., TS2 represents the TS
structure in the rate-determining formation of the intermediate
1.0/1.9 (♦), 1.0/2.9 (᭡).
different slopes and intercepts (i.e., the slope and intercept decrease
as the fraction of pyridine in the buffer solutions decreases). In
contrast, the plots of kobsd vs. [pyridine]free, the concentration of the
free pyridine, in Fig. 4B exhibit almost the same slope (i.e., kcat
=
This journal is The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 8062–8067 | 8065
©

View Article Online
while TS3 applies to that in the rate-determining breakdown of
the intermediate.
Other chemicals used were of the highest quality. Doubly glass-
distilled water was further boiled and cooled under nitrogen just
before use.
Kinetics
The kinetic studies were performed at 25.0 0.1 ◦C with a UV-Vis
spectrophotometer equipped with a constant temperature circu-
lating bath. The pyridine-catalyzed hydrolysis of 1-(X-substituted
benzoyl)-4-aminopyridinium ions (i.e., 2a–i) was followed at
307 nm by monitoring the disappearance of the pyridinium ion
obtained in situ from the reaction of 1a–i with 4-aminopyridine. All
the reactions were carried out under pseudo-first-order conditions
in which the concentration of 4-aminopyridine was at least 20
times greater than that of the substrate. Typically, reaction was
initiated by adding 5 mL of 0.02 M of substrate 1a–i solution in
MeCN by a 10 mL syringe into a 10 mm UV cell containing 2.50 mL
of the reaction medium and 4-aminopyridine. The pyridine stock
solution of ca. 0.2 M was prepared in a 25.0 mL volumetric flask
under nitrogen by adding 2 equiv. of 4-aminopyridine to 1 equiv.
of standardized HCl solution in order to obtain a 1 : 1 self-buffered
solution. All the transfers of reaction solutions were carried out
by means of gas-tight syringes.
It is well known that rX for reactions which proceed through
an SN2 mechanism is small (e.g., rX = -0.2 0.1 for solvolysis of
2-phenylethyl tosylates and benzyl tosylates, and rX = 0.3 0.1
for nucleophilic substitution reactions of diaryl chlorophosphates
with anilines).19,20 Thus, a small rX value would be expected if the
current reactions proceed through a concerted mechanism with
a TS structure similar to TS1. The rX value of 1.45 or 1.39 for
the current reactions appears to be too large for reactions which
proceed through a concerted mechanism. Thus, one might suggest
that the hydrolysis of 2a–i proceeds through a stepwise mechanism
with a TS structure similar to TS2 or TS3.
It is noted that OH- ion is the nucleophilic species for both
pyridine-catalyzed and uncatalyzed hydrolyses of 2a–i. Further-
more, the rX values for both processes are nearly the same (Fig.
3), indicating that the hydrolysis of 2a–i proceeds through the
same mechanism for both the pyridine-catalyzed and uncatalyzed
processes. However, one might exclude the possibility that the
reaction proceeds through TS3, since OH- is significantly more
basic and a poorer nucleofuge than 4-aminopyridine. Accordingly,
it is concluded that the hydrolysis of 2a–i proceeds through a
stepwise mechanism with a TS structure similar to TS2.
Acknowledgements
This research was supported by Basic Science Research Pro-
gram through National Research Foundation of Korea (NRF)
funded by Ministry of Education, Science and Technology (2009-
0075488). E. H. Kim and J. S. Kang are grateful for the BK 21
Scholarship.
Conclusions
The current study has allowed us to conclude the following:
(1) Hydrolysis of 2a–i proceeds through pyridine-catalyzed and
uncatalyzed pathways. (2) The Hammett plots for the pyridine-
catalyzed and uncatalyzed reactions of 2a–i consist of two
intersecting straight lines, while the corresponding Yukawa–Tsuno
plots exhibit excellent linear correlations with rX = 1.39 ~ 1.45 and
r = 0.72 ~ 0.76. (3) The nonlinear Hammett plots are not due to
a change in the RDS but are caused by stabilization of 2a–i in
the GS through the resonance interaction between the p-electron
donor substituent and the carbonyl functionality in the GS. (4) The
possibility that the reactions of 2a–i proceed through a concerted
mechanism has been ruled out on the basis of the large rX values.
(5) The hydrolysis of 2a–i proceeds through a stepwise mechanism,
in which the first step (i.e., attack of OH- ion to the carbonyl
carbon atom of 2a–i) is the RDS, since OH- ion is significantly
more basic and a poorer nucleofuge than 4-aminopyridine.
References
1 (a) Y. Tsuno and M. Fujio, Adv. Phys. Org. Chem., 32, 267–385; (b) Y.
Tsuno and M. Fujio, Chem. Soc. Rev., 1996, 25, 129–139; (c) Y. Yukawa
and Y. Tsuno, Bull. Chem. Soc. Jpn., 1959, 32, 960–965.
2 (a) K. Nakata, M. Fujio, K. Nishimoto and Y. Tsuno, J. Phys. Org.
Chem., 2010, 23, 1057–1065; (b) R. Fujiyama, M. A. Alam, A. Aiko,
T. Munechika, M Fujio and Y. Tsuno, J. Phys. Org. Chem., 2010, 23,
819–827; (c) S. Than, M. M. R. Badal, S. Itoh and M. Mishima, J.
Phys. Org. Chem., 2010, 23, 411–417; (d) S. Toh, M. M. R. Badal and
M. Mishima, J. Phys. Chem. A, 2009, 113, 10075–10080.
3 (a) S. Than, H. Maeda, M. Irie, K. Kikukawa and M. Mishima, Int. J.
Mass Spectrom., 2007, 267, 205–214; (b) H. Maeda, M. Irie, S. Than, K.
Kikukawa and M. Mishima, Bull. Chem. Soc. Jpn., 2007, 80, 195–203;
(c) M. Fujio, M. A. Alam, Y. Umezaki, K. Kikukawa, R. Fujiyama
and Y. Tsuno, Bull. Chem. Soc. Jpn., 2007, 80, 2378–2383.
4 (a) I. H. Um, L. R. Im, E. H. Kim and J. H. shin, Org. Biomol. Chem.,
2010, 8, 3801–3806; (b) I. H. Um, Y. M. Park, M. Fujio, M. Mishima
and Y. Tsuno, J. Org. Chem., 2007, 72, 4816–4821; (c) I. H. Um, J. Y.
Lee, S. H. Ko and S. K. Bae, J. Org. Chem., 2006, 71, 5800–5803; (d) I.
H. Um, S. E. Jeon and J. A. Seok, Chem.–Eur. J., 2006, 12, 1237–1243;
(e) I. H. Um, S. J. Hwang, M. H. Baek and E. J. Park, J. Org. Chem.,
2006, 71, 9191–9197.
5 (a) I. H. Um, E. H. Kim and J. Y. Lee, J. Org. Chem., 2009, 74, 1212–
1217; (b) I. H. Um, S. J. Hwang, S. Yoon, S. E. Jeon and S. K. Bae, J.
Org. Chem., 2008, 73, 7671–7677; (c) I. H. Um, S. Yoon, H. R. Park
and H. J. Han, Org. Biomol. Chem., 2008, 6, 1618–1624.
6 (a) I. H. Um, J. Y. Hong and J. A. Seok, J. Org. Chem., 2005, 70, 1438–
1444; (b) I. H. Um, S. M. Chun, O. M. Chae, M. Fujio and Y. Tsuno,
J. Org. Chem., 2004, 69, 3166–3172; (c) I. H. Um, J. Y. Hong, J. J. Kim,
O. M. Chae and S. K. Bae, J. Org. Chem., 2003, 68, 5180–5185.
7 (a) I. H. Um, Y. H. Shin, J. Y. Han and M. Mishima, J. Org. Chem.,
2006, 71, 7715–7720; (b) I. H. Um, J. Y. Han and Y. H. Shin, J. Org.
Chem., 2009, 74, 3073–3078; (c) I. H. Um, J. Y. Han and S. J. Hwang,
Experimental
Materials
2,4-Dinitrophenyl X-substituted benzoates 1a–i were prepared
readily from the reactions of 2,4-dinitrophenol and X-substituted
benzoyl chlorides in anhydrous ether in the presence of triethy-
lamine as reported previously.8d,e The crude products were purified
through column chromatography. The purity of 1a–i was checked
1
by means of their melting points and H NMR characteristics.
8066 | Org. Biomol. Chem., 2011, 9, 8062–8067
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
Chem.–Eur. J., 2008, 14, 7324–7330; (d) I. H. Um, K. Akhtar, Y. H.
Shin and J. Y. Han, J. Org. Chem., 2007, 72, 3823–3829.
15 (a) H. K. Oh, Bull. Korean Chem. Soc., 2010, 31, 2357–2360; (b) H. K.
Oh, M. H. Ku, H. W. Lee and I. Lee, J. Org. Chem., 2002, 67, 8995–
8998; (c) H. K. Oh, M. H. Ku, H. W. Lee and I. Lee, J. Org. Chem.,
2002, 67, 3874–3877.
16 (a) F. A. Carroll, Perspectives on Structure and Mechanism in
Organic Chemistry, Brooks/Cole, New York, 1998, pp. 371–
386; (b) W. P. Jencks, Catalysis in Chemistry and Enzymology,
McGraw-Hill, New York, 1969, pp. 480–483; (c) T. H. Lowry,
K. S. Richardson, Mechanism and Theory in Organic Chemistry,
3rd ed., Harper Collins Publishers, New York, 1987, pp. 143–
151.
8 (a) W. P. Jencks, Chem. Rev., 1985, 85, 511–527; (b) E. A. Castro, Chem.
Rev., 1999, 99, 3505–3524; (c) M. I. Page, A. Williams, Organic and Bio-
organic Mechanisms, Longman, Singapore, 1997, Chapter 7; (d) F. M.
Menger and J. H. Smith, J. Am. Chem. Soc., 1972, 94, 3824–3829;
(e) A. B. Maude and A. Williams, J. Chem. Soc., Perkin Trans. 2, 1997,
179–183.
9 (a) E. A. Castro, M. Aliaga and J. G. Santos, J. Org. Chem., 2005, 70,
2679–2685; (b) E. A. Castro, M. Gazitua and J. G. Santos, J. Org. Chem.,
2005, 70, 8088–8092; (c) B. Galabov, S. Ilieva, B. Hadjieva, Y. Atanasov
and H. F. Schaefer III, J. Phys. Chem. A, 2008, 112, 6700–6707.
10 (a) H. K. Oh, J. Y. Oh, D. D. Sung and I. Lee, J. Org. Chem., 2005,
70, 5624–5629; (b) I. Lee and D. D. Sung, Curr. Org. Chem., 2004, 8,
557–567; (c) H. K. Oh, J. E. Park, D. D Sung and I. Lee, J. Org. Chem.,
2004, 69, 9285–9288; (d) H. K. Oh, J. S. Ha, D. D. Sung and I. Lee, J.
Org. Chem., 2004, 69, 8219–8223; (e) H. K. Oh, J. E. Park, D. D. Sung
and I. Lee, J. Org. Chem., 2004, 69, 3150–3153.
11 (a) B. J. Lumbiny and H. W. Lee, Bull. Korean Chem. Soc., 2008, 29,
2065–2068; (b) H. K. Oh, J. M. Lee, H. W. Lee and I. C. Lee, Int. J.
Chem. Kinet., 2004, 36, 434–440; (c) H. K. Oh, I. K. Kim, H. W. Lee
and I. Lee, J. Org. Chem., 2004, 69, 3806–3810.
12 A. R. Fersht and W. P. Jencks, J. Am. Chem. Soc., 1970, 92, 5432–5442.
13 P. J. Battye, E. M. Ihsan and R. B. Moodie, J. Chem. Soc., Perkin Trans.
2, 1980, 741–748.
17 Methyl chloroformate was reported to be 9 ¥ 103 times less reactive
than acetyl chloride due to GS stabilization through resonance
interactions. D. N. Kevill, in The Chemistry of the Functional Groups.
The Chemistry of Acyl Halides, ed. S. Patai, Wiley, New York, 1972,
Chapter 12.
18 A reviewer has suggested that H2O could be a nucleophilic species as
well as a general base catalyst in the reaction of 2e in the absence of
pyridine/pyridinium-ion buffer, as reported previously for hydrolyses
of 4-methoxyphenyl-2,2-dichloroethanoate and 1-benzoyl-3-phenyl-
1,2,4-triazole. (a) T. Rispens, C. Cabaleiro-Lago and J. B. F. N.
Engberts, Org. Biomol. Chem., 2005, 3, 597–602; (b) N. J. Buurma,
M. J. Blandamer and J. B. F. N. Engberts, J. Phys. Org. Chem., 2003,
16, 438–449.
19 (a) M. Fujio, K. Funatsu, M. Goto, Y. Seki, M. Mishima and Y. Tsuno,
Bull. Chem. Soc. Jpn., 1987, 60, 1091–1096; (b) M. Fujio, M. Goto, T.
Susuki, I. Akasaka, M. Mishima and Y. Tsuno, Bull. Chem. Soc. Jpn.,
1990, 63, 1146–1151.
20 H. W. Lee, A. K. Guha and I. Lee, Int. J. Chem. Kinet., 2002, 34,
632–637.
14 (a) E. A. Castro, M. Cubillos and J. G. Santos, J. Org. Chem., 2004,
69, 4802–4807; (b) E. A. Castro, M. Ramos and J. G. Santos, J. Org.
Chem., 2009, 74, 6374–6377; (c) E. A. Castro, M. Acuna, C. Soto, D.
Trujillo, B. Vasquez and J. G. Santos, J. Phys. Org. Chem., 2008, 21,
816–822.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 8062–8067 | 8067
©