Modification of both the electrophilic center and substituents on the nonleaving group in pyridinolysis of O-4-nitrophenyl benzoate and thionobenzoates

Article abstract of DOI:10.1021/jo061682x

(Chemical Equation Presented) A kinetic study is reported for reactions of 4-nitrophenyl benzoate (1c) and O-4-nitrophenyl X-substituted thionobenzoates (2a-e) with a series of pyridines in 80 mol % H₂O/20 mol % dimethyl sulfoxide (DMSO) at 25.0 ± 0.1°C. O-4-Nitrophenyl thionobenzoate (2c) is more reactive than its oxygen analogue 1c toward all the pyridines studied. The Bronsted-type plot is linear with β_nuc = 1.06 for reactions of 1c but curved for the corresponding reactions of 2c with β_nuc decreasing from 1.38 to 0.38 as the pyridine basicity increases, indicating that the reaction mechanism is also influenced on changing the electrophilic center from C=O to C=S. The curvature center of the curved Bronsted-type plots (defined as pK_a^o) occurs at pK_a = 9.3 regardless of the electronic nature of the substituent X in the nonleaving group. The Hammett plot for reactions of 2a-e with 4-aminopyridine is nonlinear, i.e., the substrates having an electron-donating substituent exhibit negative deviations from the Hammett plot. However, the Yukawa-Tsuno plot for the same reactions exhibits good linear correlation, indicating that the negative deviations shown by these substrates arise from stabilization of the ground state through resonance interaction between the electron-donating substituent X and the C=S bond.

Full text of DOI:10.1021/jo061682x

Modification of Both the Electrophilic Center and Substituents on
the Nonleaving Group in Pyridinolysis of O-4-Nitrophenyl Benzoate
and Thionobenzoates
Ik-Hwan Um,* So-Jeong Hwang, Mi-Hwa Baek, and Eun Ji Park†
DiVision of Nano Sciences & Department of Chemistry, Ewha Womans UniVersity, Seoul 120-750, Korea
ihum@ewha.ac.kr
ReceiVed August 13, 2006
A kinetic study is reported for reactions of 4-nitrophenyl benzoate (1c) and O-4-nitrophenyl X-substituted
thionobenzoates (2a-e) with a series of pyridines in 80 mol % H O/20 mol % dimethyl sulfoxide (DMSO)
2
at 25.0 ( 0.1 °C. O-4-Nitrophenyl thionobenzoate (2c) is more reactive than its oxygen analogue 1c
toward all the pyridines studied. The Brønsted-type plot is linear with ânuc ) 1.06 for reactions of 1c but
curved for the corresponding reactions of 2c with ânuc decreasing from 1.38 to 0.38 as the pyridine
basicity increases, indicating that the reaction mechanism is also influenced on changing the electrophilic
o
center from CdO to CdS. The curvature center of the curved Brønsted-type plots (defined as pK
occurs at pK
a
)
a
) 9.3 regardless of the electronic nature of the substituent X in the nonleaving group. The
Hammett plot for reactions of 2a-e with 4-aminopyridine is nonlinear, i.e., the substrates having an
electron-donating substituent exhibit negative deviations from the Hammett plot. However, the Yukawa-
Tsuno plot for the same reactions exhibits good linear correlation, indicating that the negative deviations
shown by these substrates arise from stabilization of the ground state through resonance interaction between
the electron-donating substituent X and the CdS bond.
Introduction
SCHEME 1
Acyl group transfer reactions have been the subject of
extensive experimental and theoretical studies due to their
importance in biological processes as well as utility in synthetic
1-9
applications. Reactions of carboxylic esters with amines have
generally been understood to proceed through a zwitterionic
tetrahedral intermediate (T as shown in Scheme 1); curved
Brønsted-type plots have often been observed for reactions of
esters that contain a good leaving group, and this behavior has
(
been taken to be diagnostic of a change in the rate-determining
1
-5
step (RDS).
Recent computational studies also favor a
(2) (a) Castro, E. A.; Aliaga, M.; Gazitua, M.; Santos, J. G. Tetrahedron
2006, 62, 4863-4869. (b) Castro, E. A.; Campodonico, P. R.; Contreras,
*
To whom correspondence should be addressed. Phone: 82-2-3277-2349.
Fax: 82-2-3277-2844.
Present Address: Department of Microbiology, University of Michigan, Ann
Arbor Michigan 48109.
R.; Fuentealba, P.; Santos, J. G.; Leis, J. R.; Garcia-Rio, L.; Saez, J. A.;
Domingo, L. R. Tetrahedron 2006, 62, 2555 - 2562. (c) Castro, E. A.;
Gazitua, M.; Santos, J. G. J. Org. Chem. 2005, 70, 8088-8092. (d)
Campodonico, P. R.; Fuentealba, P.; Castro, E. A.; Santos, J. G.; Contreras,
R. J. Org. Chem. 2005, 70, 1754-1760. (e) Castro, E. A.; Aliaga, M.;
Evangelisti, S.; Santos, J. G. J. Org. Chem. 2004, 69, 2411-2416.
†
(
1) (a) Jencks, W. P. Chem. ReV. 1985, 85, 511-527. (b) Castro, E. A.
Chem. ReV. 1999, 99, 3505-3524. (c) Page, M. I.; Williams, A. Organic
and Bio-organic Mechanisms; Longman: Harlow, U.K., 1997; Chapter 7.
1
0.1021/jo061682x CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/24/2006
J. Org. Chem. 2006, 71, 9191 9191

Um et al.
stepwise mechanism over a concerted pathway, although some
SCHEME 2
(
studies failed to identify the transition state and T for
aminolysis of various carboxylic esters.6
-9
The curvature center of curved Brønsted plots indicates a
1
0-12
change in RDS, and this center was defined as pKa°.
Gresser
o
and Jencks reported that the pKa increases as the substituent
in the nonleaving group changes from an electron-donating
group (EDG) to an electron-withdrawing group (EWG) for
1
0
reactions of diaryl carbonates with a series of quinuclidines.
This has been rationalized on the basis that departure of the
(
amine from T (i.e., k-1 step; Scheme 1) is favored, over that
of the leaving group (i.e., k2 step; Scheme 1), as the substituent
in the nonleaving group becomes a stronger EWG.1 Castro et
al. found a comparable result in pyridinolysis of 2,4-dinitro-
0
o
pKa and the k2/k-1 ratio both remain nearly constant even as
the substituent X in the benzoyl moiety is progressively modified
from an EWG to an EDG.
The electronic nature of the substituent X in the nonleaving
group would be anticipated to influence both the k2 and k-1
values, i.e., an EWG in the nonleaving group would retard the
departure of the leaving group (decrease k2) as well as the amine
also decrease k-1) from T , while an EDG in the nonleaving
group would accelerate both k2 and k-1 processes since the
nucleofuge departs with the bonding electron pair from T .
Accordingly, one can predict that the k2/k-1 ratio should be
independent of the substituent X in the nonleaving group. This
argument is consistent with our finding that pKa and the k2/
k-1 ratio remain nearly constant on changing the electronic
nature of the substituent X for the reactions mentioned above.
To obtain further information about the pKa , we extended
o
phenyl X-substituted benzoates; hence, pKa ) 9.5 when X )
13-15
The explanation is as follows.
o
11
H but pKa > 9.5 when X ) 4-Cl, 4-CN, or 4-NO2 and
similarly for S-2,4-dinitrophenyl X-substituted thiobenzoates in
o
aqueous ethanol, where pKa increases from 8.5 to 8.9 and 9.9
1
2
as X is changed from 4-CH3 to H and 4-NO2, in turn. Thus,
it has been concluded that changing the substituent in the
nonleaving group from an EDG to an EWG results in an increase
(
(
o
10-12
in pKa by decreasing the k2/k-1 ratio.
(
o
However, we have shown that the pKa value is independent
of the electronic nature of the substituent X in the nonleaving
group for aminolysis of 2,4-dinitrophenyl X-substituted ben-
zoates and benzenesulfonates.1 A similar result has recently
been found for reactions of Y-substituted phenyl X-substituted
benzoates with piperidine.15 Further, we have shown that the
o
3,14
o
our study to reactions of 4-nitrophenyl benzoate (1c) and O-4-
nitrophenyl X-substituted thionobenzoates (2a-e) using a series
of pyridines whose pKa values range from 5.09 to 11.30 (Scheme
(
3) (a) Oh, H. K.; Oh, J. Y.; Sung, D. D.; Lee, I. J. Org. Chem. 2005,
7
0, 5624-5629. (b) Oh, H. K.; Jin, Y. C.; Sung, D. D.; Lee, I. Org. Biomol.
Chem. 2005, 3, 1240-1244. (c) Oh, H. K.; Park, J. E.; Sung, D. D.; Lee,
I. J. Org. Chem. 2004, 69, 9285-9288. (d) Oh, H. K.; Park, J. E.; Sung, D.
D.; Lee, I. J. Org. Chem. 2004, 69, 3150-3153. (e) Oh, H. K.; Ku, M. H.;
Lee, H. W.; Lee, I. J. Org. Chem. 2002, 67, 3874-3877.
2
). Replacement of O by a polarizable S atom in the carbonyl
bond of 1c should provide insights into both the reactivity and
the comparative reaction mechanism. We probed the effect of
modification of the electrophilic center (CdO to CdS) on
(4) (a) Baxter, N. J.; Rigoreau, L. J. M.; Laws, A. P.; Page. M. I. J. Am.
Chem. Soc. 2000, 122, 3375-3385. (b) Spillane, W. J.; McGrath, P.; Brack,
C.; O’Byrne, A. B. J. Org. Chem. 2001, 66, 6313-6316. (c) Gordon, I.
M.; Maskill, H.; Ruasse, M. F. Chem. Soc. ReV. 1989, 18, 123-151.
o
reactivity, reaction mechanism, and, notably, pKa and report
the kinetic results herein. In addition to our Brønsted analysis
we analyzed the substituent effects according to the dual-
parameter Yukawa-Tsuno equation. This combined approach
has previously proven effective in elucidating mechanistic
ambiguities in acyl group transfer reactions.
(
5) (a) Um, I. H.; Jeon, S. E.; Seok, J. A. Chem. Eur. J. 2006, 12, 1237-
1
2
243. (b) Um, I. H.; Kim, E. J; Park, H. R.; Jeon, S. E. J. Org. Chem.
006, 71, 2302-2306. (c) Um, I. H.; Lee, J. Y.; Lee, H. W.; Nagano, Y.;
Fujio, M.; Tsuno, Y. J. Org. Chem. 2005, 70, 4980-4987. (d) Um, I. H.;
Han, H. J.; Baek, M. H.; Bae, S. K. J. Org. Chem. 2004, 69, 6365-6370.
(
e) Um, I. H.; Lee, J. Y.; Kim, H. T.; Bae, S. K. J. Org. Chem. 2004, 69,
2
436-2441. (f) Um, I. H.; Seok, J. A.; Kim, H. T.; Bae, S. K. J. Org.
Chem. 2003, 68, 7742-7746.
6) (a) Galabov, B.; Atanasov, Y; Ilieva, S.; Schaefer, H. F., III. J. Phys.
Results and Discussion
(
Chem. A 2005, 109, 11470-11474. (b) Ilieva, S.; Galabov, B.; Musaev, D.
Reactions of O-4-nitrophenyl X-substituted thionobenzoates
with pyridines proceeded with quantitative liberation of 4-ni-
trophenoxide (and/or its conjugate acid). The reactions were
followed by monitoring the appearance of 4-nitrophenoxide at
410 nm. Kinetic study was performed under pseudo-first-order
conditions; the pyridine concentration was always in excess over
that of substrate. All reactions obeyed first-order kinetics over
90% of the total reaction. Pseudo-first-order rate constants (kobsd)
were determined from the equation ln(A∞ - At) ) -kobsdt + C.
The plots of kobsd vs the pyridine concentration showed excellent
linearity (see Supporting Information for detailed kinetic data).
The plots had only small intercept values, indicating that the
G.; Morokuma, K.; Schaefer, H. F., III. J. Org. Chem. 2003, 68, 1496-
1
502.
(
(
(
7) Yang, W.; Drueckhammer, Org. Lett. 2000, 2, 4133-4136.
8) Zipse, H.; Wang, L.; Houk, K. N. Liebigs Ann. 1996, 1511-1522.
9) (a) Lee, I.; Sung, D. D. Curr. Org. Chem. 2004, 8, 557-567. (b)
Lee, I.; Lee, H. W.; Lee, B. C.; Choi, J. H. Bull. Korean Chem. Soc. 2002,
2
3, 201-204. (c) Lee, H. W.; Guha, A. K.; Kim, C. K.; Lee, I. J. Org.
Chem. 2002, 67, 2215-2222.
(10) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6970-
6
980.
(
11) (a) Castro, E. A.; Santander, C. L. J. Org. Chem. 1985, 50, 3595-
3
1
2
600. (b) Castro, E. A.; Valdivia, J. L. J. Org. Chem. 1986, 51, 1668-
672. (c) Castro, E. A.; Steinfort, G. B. J. Chem. Soc., Perkin Trans. 1983,
, 453-457.
(12) (a) Castro, E. A.; Aguayo, R.; Bessolo, J.; Santos, J. G. J. Org.
-
contribution of H2O or OH ion from the hydrolysis of pyridines
Chem. 2005, 70, 7788-7791. (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,
(14) (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.
(15) Um, I. H.; Lee, J. Y.; Ko, S. H.; Bae, S. K. J. Org. Chem. 2006,
71, 5800-5803.
6
2
9, 5399-5404. (d) Castro, E. A.; Aguayo, R.; Santos, J. G. J. Org. Chem.
003, 68, 8157-8161.
(13) (a) Um, I. H.; Kim, K. H.; Park, H. R.; Fujio, M.; Tsuno, Y. J.
Org. Chem. 2004, 69, 3937-3942. (b) Um, I. H.; Min, J. S.; Ahn, J. A.;
Hahn, H. J. J. Org. Chem. 2000, 65, 5659-5663.
9192 J. Org. Chem., Vol. 71, No. 24, 2006

Pyridinolysis of O-4-Nitrophenyl Benzoate
TABLE 1. Summary of Second-Order Rate Constants for Reactions of 4-Nitrophenyl Benzoate, 1c (X ) H), and O-4-Nitrophenyl
X-Substituted Thionobenzoates, 2a (X ) 3-Cl), 2c (X ) H), and 2e (X ) 4-MeO), with Pyridines in 20 mol % DMSO at 25.0 ( 0.1 °C
kN/M-1s-1
Z-pyridine
pKa
1c
2a
2c
2e
1
2
3
4
5
6
Z ) 4-O-
11.30
9.12
8.93
5.78
5.53
5.09
32.7
0.347
0.193
8.36 × 10
4.19 × 10
8.98 × 10
942
67.1
26.3
1.91 × 10
9.03 × 10
1.66 × 10
296.0
19.2
9.23
7.45 × 10
3.50 × 10
7.66 × 10
70.4
3.61
1.68
1.82 × 10
5.58 × 10
1.50 × 10
Z ) 4-NMe2
Z ) 4-NH2
Z ) 3,4-Me2
Z ) 4-Me
-
-
-
5
5
6
-3
-4
-4
-4
-4
-5
-4
-5
-5
Z ) 3-Me
TABLE 2. Summary of Microscopic Rate Constants for Reactions of O-4-Nitrophenyl X-Substituted Thionobenzoates, 2a (X ) 3-Cl), 2c (X )
H), and 2e (X ) 4-MeO), with Pyridines in 20 mol % DMSO at 25.0 ( 0.1 °C
k1/M- s-1
1
k2/k-1
Z-pyridine
2a
2c
2e
2a
951
170
89.0
7.44
2c
2e
71
9.14
5.72
0.769
0.426
0.325
1
2
3
4
5
6
Z ) 4-O-
110
100
115
299
Z ) 4-NMe2
Z ) 4-NH2
Z ) 3,4-Me2
Z ) 4-Me
0.655
0.419
2.57 × 10
1.43 × 10
5.08 × 10
0.661
0.427
3.02 × 10
1.70 × 10
6.17 × 10
0.653
0.416
2.37 × 10
1.31 × 10
4.61 × 10
48.3
30.9
2.47
2.06
1.24
-
-
-
4
4
5
-4
-4
-5
-4
-4
-5
6.33
3.27
Z ) 3-Me
TABLE 3. Summary of Second-Order Rate Constants (kN) for
Reactions of O-4-Nitrophenyl X-Substituted Thionobenzoates (2a-e)
with 4-Aminopyridine in 20 mol % DMSO at 25.0 ( 0.1 °C
chemical shift for the carbon atom of the CdO and CdS bonds
in compounds 1c and 2c has been reported to be 163.8 and
18
209.8 ppm, respectively. Such a large downfield shift suggests
1
entry
X
kN/M- s-1
that the carbon atom of the CdS bond bears greater positive
charge than that of the CdO bond. Besides, it is well known
that the overlap between 2p and 3p orbitals that make up the
π-bond component of the CdS bond is weaker than that between
2
2
2
2
2
a
b
c
d
e
3-Cl
3-MeO
H
4-Me
4-MeO
26.3
11.5
9.23
4.07
1.68
1
9
2
p orbitals in a CdO bond. Thus, the fact that 2c is more
reactive than 1c is consistent with the argument that the former
would be more electrophilic than the latter.
to kobsd is negligible. The second-order rate constants (kN) were
determined from the slope of these linear plots. Generally five
different pyridine concentrations were used to determine kN
values. It is estimated from replicate runs that the uncertainty
in the rate constants is less than 3%. Kinetic data are summarized
in Tables 1-3.
However, 2c has been reported to be less reactive than 1c
-
-
18,20
toward strongly basic OH and EtO ions.
et al. reported that 4-nitrophenyl chlorothionoformate and bis-
4-nitrophenyl) thionocarbonate are less reactive than their
Similarly, Castro
(
oxygen analogues toward aryloxides and alicyclic secondary
21
amines, respectively, indicating that the reactivity of thiono
One of the initial products (i.e., 1-thionobenzoylpyridinium
ion or its oxygen analogue) was not isolated but hydrolyzed to
yield thiobenzoate (or benzoate for reactions of 1c). Similar
pyridinium intermediates have been reported in pyridinolyses
of 2,4-dinitrophenyl methyl thionocarbonate, methyl chlorofor-
mate, and acetic anhydride.1 Since the pyridinium intermedi-
ate in the current reactions does not absorb at 410 nm, where
the reactions were monitored, the kN values obtained are the
rate constants for formation of the intermediate and 4-nitro-
phenoxide ion.
compounds is, at least partly, dependent on the nature of
nucleophiles. The contrasting reactivity order is consistent with
a hard and soft acids and bases (HSAB) analysis since the
22
softer thiocarbonyl group (relative to carbonyl) would exhibit
-
-
-
lower reactivity toward hard bases such as OH , EtO , ArO ,
and alicyclic secondary amines. On the contrary, pyridines have
been suggested to be relatively soft nucleophiles compared to
6,17
16a
isobasic alicyclic secondary amines. Thus, the current result
that 2c is more reactive than 1c toward pyridines is also in
accordance with the HSAB principle.
Effect of Replacing CdO by CdS on Reactivity and
Mechanism. Table 1 shows that O-4-nitrophenyl thionobenzoate
As shown in Table 1, the kN value for reactions of 2c with
pyridines decreases as the basicity of pyridines decreases, i.e.,
(2c) is more reactive than its oxygen analogue 1c. One might
-
5
-1 -1
it decreases from 296 to 9.23 and 7.66 × 10
pKa of the conjugate acid of pyridines decreases from 11.30 to
.93 and 5.09. A similar result has been shown for the
M
s
as the
expect that replacement of the O atom in the CdO bond of 1c
by a polarizable S atom would enhance the electrophilicity of
the reactive center by increasing polarizability. This argument
is supported by 13C NMR spectra as well as the difference in
the bond energy between CdO and CdS bonds. Hence, the
8
(
18) Um, I. H.; Lee, J. Y.; Bae, S. Y.; Buncel, E. Can. J. Chem. 2005,
3, 1365-1371.
19) Hill, S. V.; Thea, S.; Williams, A. J. Chem. Soc., Perkin Trans.
8
(
(
16) (a) Castro, E. A.; Cubillos, M.; Santos, J. G.; Tellez, J. J. Org. Chem.
1983, 2, 437-446.
1
997, 62, 2512-2517. (b) Bond, P. M.; Moodie, R. B. J. Chem. Soc., Perkin
(20) Kwon, D. S.; Park, H. S.; Um, I. H. Bull. Korean Chem. Soc. 1991,
12, 93-97.
Trans. 2 1976, 679-682. (c) Bond, P. M.; Castro, E. A.; Moodie, R. B. J.
Chem. Soc., Perkin Trans. 2 1976, 68-72. (d) Guillot-Edelheit, G.; Laloi-
Diard, M.; Guibe-Jampel, E.; Wakselman, M. J. Chem. Soc., Perkin Trans.
(21) (a) Castro, E. A.; Angel, M.; Arellano, D.; Santos, J. G. J. Org.
Chem. 2001, 66, 6571-6575. (b) Castro, E. A.; Ruiz, M. G.; Salinas, S.;
Santos, J. G. J. Org. Chem. 1999, 64, 4817-4820. (c) Castro, E. A.;
Cubillos, M.; Santos, J. G. J. Org. Chem. 1997, 62, 4395-4397.
(22) Pearson, R. G. J. Chem. Educ. 1968, 45, 581-587.
2
1979, 1123-1127.
17) Fersht, A. R.; Jencks, W. P. J. Am. Chem. Soc. 1970, 92, 5432-
442.
(
5
J. Org. Chem, Vol. 71, No. 24, 2006 9193

Um et al.
FIGURE 1. Brønsted plots for reactions of O-4-nitrophenyl thion-
obenzoate (2c, O) and 4-nitrophenyl benzoate (1c, 9) with pyridines
in 20 mol % DMSO at 25.0 ( 0.1 °C. The assignment of numbers is
given in Table 1.
FIGURE 2. Brønsted plots for reactions of O-4-nitrophenyl X-
substituted thionobenzoates, 2a (9), 2c (O), and 2e(b), with pyridines
in 20 mol % DMSO at 25.0 ( 0.1 °C. The assignment of numbers is
given in Table 1.
using a semiempirical equation (eq 1)10,24 on the basis of the
proposed mechanism shown in Scheme 2. The parameters â1
and â2 represent the slope of the curved Brønsted plots in Figure
corresponding reactions of 1c. The effect of pyridine basicity
on reactivity has been illustrated in Figure 1. The Brønsted plot
for reactions of 2c is curved. Such a nonlinear Brønsted plot is
typical for reactions which proceed through a stepwise mech-
2
for reactions with strongly basic and weakly basic pyridines,
anism with a change in the RDS.1 Thus, one can suggest that
-5
N N a 2 -1
respectively. Here k refers to the k value at pK where k /k
)
1.
the pyridinolysis of 2c proceeds through a zwitterionic tetra-
(
hedral intermediate (T ) in which the RDS is dependent on the
log(k /k °) ) â (pK - pK °) - log(1 + R)/2
basicity of pyridines as shown in Scheme 2. On the other hand,
the Brønsted plot for the corresponding reactions of 1c is linear
with a ânuc value of 1.06. Such a linear Brønsted plot with a
large ânuc value indicates that the pyridinolysis of 1c proceeds
N
N
2
a
a
where
(
through an addition intermediate (T ) with its breakdown being
log R ) (â - â )(pK - pK °)
(1)
2
1
a
a
the RDS.
The RDS for aminolyses of carboxylic esters has been
reported to change from breakdown of T (the k2 step) to its
The â1 and â2 values determined for reactions of 2a, 2c, and
2e are shown in Figure 2. Note that the pKa determined is 9.3
(
o
formation (the k1 step) as the amine nucleophile becomes more
basic than the leaving group by 4-5 pKa units.1 Given that
the pKa of 4-nitrophenol in 20 mol % DMSO has been reported
regardless of the nature of the substituent X in the thionobenzoyl
-5
moiety, indicating that the electronic character of the substituent
o
X in the nonleaving group does not influence the pKa value.
2
3
o
to be ca. 7.8, the pKa for the pyridinolysis of 1c would be
expected to occur at a pKa value between 11.8 and 12.8. Lack
of such a strongly basic pyridine precludes observation of a
curved Brønsted-type plot for reactions of 1c with pyridines.
This contrasts with the finding of Jencks and Castro that an
o
EWG in the nonleaving group increases the pKa value for
1
0-12
aminolyses of various esters.
However, the current result
o
is consistent with our previous report that the pKa and k2/k-1
ratio are independent of the nature of the substituent X in the
nonleaving group for aminolysis of aryl X-substituted benzoates
o
On the other hand, the pKa found here in the pyridinolysis of
2
c is 9.3 (Figure 1), only 1.5 pKa units more basic than the
1
3,14
leaving 4-nitrophenoxide ion. Clearly, the generalization that
an amine nucleophile be 4-5 pKa units more basic than the
leaving group to effect a change in RDS must be revised for
aminolysis of thionobenzoate esters.
and benzenesulfonates.
The kN values for reactions of 2a, 2c, and 2e have been
dissected into their microscopic rate constants to further support
the argument that the k2/k-1 ratio is independent of the nature
of the substituent X. The apparent second-order rate constant
kN can be expressed as eq 2 by applying the steady-state
conditions to the intermediate on the basis of the proposed
mechanism shown in Scheme 2.
Effect of Substituent X on pKa°. To investigate the effect
o
of the substituent X in the thionobenzoyl moiety on pKa ,
Brønsted-type plots have been constructed for reactions of 2a
(X ) 3-Cl), 2c (X ) H), and 2e (X ) 4-MeO) with pyridines.
Figure 2 shows that all the Brønsted plots are curved with a
similar shape. The curved Brønsted plots have been analyzed
k ) k k /(k + k2)
(2)
N
1
2
-1
(
75.
23) Buncel, E.; Um, I. H.; Hoz, S. J. Am. Chem. Soc. 1989, 111, 971-
(24) Castro, E. A.; Moodie, R. B. J. Chem. Soc., Chem. Commun. 1973,
828-829.
9
9194 J. Org. Chem., Vol. 71, No. 24, 2006

Pyridinolysis of O-4-Nitrophenyl Benzoate
The k2/k-1 ratios associated with the pyridinolysis of 2a, 2c,
and 2e have been determined using eqs 3-8. Equation 2 can
be simplified to eq 3 or 4. Then, â1 and â2 can be expressed as
eqs 5 and 6, respectively.
k ) k k /k , when k , k
-1
(3)
(4)
(5)
N
1
2
-1
2
k ) k , when k . k
-1
N
1
2
â ) d(log k )/d(pK )
1
1
a
â ) d(log k k /k )/d(pK ) ) â + d(log k /k )/d(pK ) (6)
2
1
2
-1
a
1
2
-1
a
Equation 6 can be rearranged as eq 7. Integration of eq 7 from
o
o
pKa results in eq 8. Since k2 ) k-1 at pKa , the term (log k2/
k-1)pKa° is zero. Therefore, one can calculate the k2/k-1 ratios
o
for the pyridinolysis of 2a, 2c, and 2e from eq 8 using pKa )
9
.3, â1 ) 0.39, 0.38, and 0.36, and â2 ) 1.41, 1.38, and 1.39,
respectively.
â - â ) d(log k /k )/d(pK )
(7)
(8)
2
1
2
-1
a
2 a
FIGURE 3. Plots of log k /k-1 vs pK for reactions of O-4-nitrophenyl
(
log k /k ) ) (â - â )(pK - pK °)
2 -1 pKa 2 1 a a
X-substituted thionobenzoates, 2a (9), 2c (O), and 2e(b), with pyridines
in 20 mol % DMSO at 25.0 ( 0.1 °C. The assignment of numbers is
given Table 2.
The k1 values have been determined from eq 9 using the kN
values in Table 1 and the k2/k-1 ratios determined above. The
k2/k-1 ratios and k1 values derived are summarized in Table 2.
k ) k k /(k + k ) ) k /(k /k + 1)
(9)
N
1
2
-1
2
1
-1
2
As shown in Table 2, the k2/k-1 ratio for reactions of 2a, 2c,
and 2e is highly sensitive to the basicity of pyridines, i.e., it
decreases significantly as the basicity of pyridines decreases.
However, the k2/k-1 ratio is independent of the electronic nature
of the substituent X in the nonleaving group, i.e., it remains
nearly constant on changing the substituent X from 3-Cl (2a)
to H (2c) or 4-MeO (2e) for reaction with a given pyridine.
The effect of the substituent X and pyridine basicity on the k2/
k-1 ratio is illustrated in Figure 3. The plots of log k2/k-1 vs
the pKa of the conjugate acid of pyridines are linear with a â-1
value of ca. 1.0, indicating that the k2/k-1 ratio is highly sensitive
to the pyridine basicity. Furthermore, the plots are nearly
o
identical and the pKa where k2/k-1 ) 1 (pKa ) is 9.3 regardless
of the nature of the substituent X. Thus, this result clearly
o
supports our preceding proposal that the pKa and the k2/k-1
ratio are independent of the electronic nature of the substituent
X in the nonleaving group.
Table 2 and Figure 4 show that k1 increases in tandem with
increases in pyridine basicity. The â1 value is ca. 0.38, which
is much smaller than the â-1 value of ca. 1.0, indicating that k1
is much less sensitive than the k2/k-1 ratio to the pyridine
basicity. Also, the k1 value increases as the substituent X changes
from an EDG to an EWG. This contrasts with the fact that the
k2/k-1 ratio remains nearly constant on changing the substituent
X for the reactions with a given pyridine. Thus, one can
conclude that the k1 value determines the reactivity of 2a-e
toward pyridines.
1
FIGURE 4. Brønsted plots for k for reactions of O-4-nitrophenyl
X-substituted thionobenzoates, 2a (9), 2c (O), and 2e(b), with pyridines
in 20 mol % DMSO at 25.0 ( 0.1 °C. The assignment of numbers is
given Table 2.
to an EWG. Recently, Neuvonen et al. reported a similar result,
i.e., an EWG in the leaving or nonleaving group of aryl acetates
or alkyl benzoates increases the reactivity of the esters along
1
3
with upfield C NMR chemical shifts of the carbonyl carbon
and higher frequencies of the CdO stretching vibration. The
increased reactivity of esters with a strong EWG, therefore, has
been attributed to destabilization of the ground state due to
decreased resonance stabilization of the esters as illustrated by
resonance structures I T II T III on the basis of the upfield
Effect of Nonleaving Group Substituent on Mechanism.
To investigate the effect of the substituent X in the thionoben-
zoyl moiety on the reaction mechanism, reactions of 2a-e with
4-aminopyridine have been performed. The kN values determined
are summarized in Table 3.
It can be seen in Table 3 that the kN value increases as the
substituent X in the thionobenzoyl group changes from an EDG
1
3
C NMR chemical shifts and higher frequencies of the CdO
2
5
stretching vibration. Thus, one might attribute the higher
J. Org. Chem, Vol. 71, No. 24, 2006 9195

Um et al.
equation (eq 10) represents the resonance demand of the reaction
center or the extent of the resonance contribution, while the
+
term (σ - σ°) is the resonance substituent constant that
measures the capacity for π-delocalization of a given π-electron
2
6,27
donor substituent.
X
H
+
log(k /k ) ) F [σ° + r (σ - σ°)]
(10)
The Yukawa-Tsuno equation transforms into the Hammett
equation when r ) 0 or into the Brown-Okamoto equation
when r )1. Since the r value determined (i.e., 0.75) is neither
0
nor 1, the Yukawa-Tsuno plot exhibits much better linear
correlation than the Hammett or the Brown-Okamoto plot in
which σ or σ constants alone are used. The linear Yukawa-
+
Tsuno plot shown in the inset of Figure 5 yields a relatively
large r value of 0.75 which indicates that stabilization of the
ground state through the resonance interactions (IV T V) is
responsible for the negative deviation shown by substrates 2d
and 2e from the Hammett plot. Therefore, one can conclude
that stabilization of the ground state by an EDG through
resonance interaction is more important than destabilization of
the ground state through decreased resonance interaction by an
EWG in governing reactivity of esters. A similar conclusion
has been drawn for solvolysis of methyl chloroformate and
acetyl chloride in aqueous acetone. The former has been reported
FIGURE 5. Hammett and Yukawa-Tsuno (inset) plots for reactions
of O-4-nitrophenyl X-substituted thionobenzoates (2a-e) with 4-ami-
nopyridine in 20 mol % DMSO at 25.0 ( 0.1 °C. The identity of points
is given in Table 3.
3
28
to be 9 × 10 times less reactive than the latter. Kevill recently
concluded that ground-state stabilization through resonance
interaction (e.g., VI T V), analogous to that suggested in the
current systems, is responsible for the decreased reactivity of
methyl chloroformate since such resonance interaction is not
reactivity of 2a compared to 2e to destabilization of the ground
state of 2a as a result of decreased resonance stabilization.
2
9
possible for acetyl chloride.
To examine this interpretation, a Hammett plot was con-
structed for reactions of 2a-e with 4-aminopyridine. If desta-
bilization of the ground state through decreased resonance
interaction were responsible for the high reactivity shown by
substrates having an EWG in the thionobenzoyl moiety (e.g.,
Conclusions
2
a and 2b), these substrates should give rise to positive
The present study leads to the following conclusions. (1)
Modification of the electrophilic center from CdO to CdS (1c
f 2c) results in an increase in the reactivity toward pyridines
deviations from the Hammett plot. As shown in Figure 5, the
Hammett plot is nonlinear. Notably, substrates 2a and 2b do
not exhibit positive deviations, but rather 2a, 2b, and 2c define
the Hammett correlation and 2d and 2e exhibit negative
deviations from this Hammett line. Moreover, the degree of the
negative deviation is more significant for the substrate having
a stronger EDG (i.e., 2e). This finding alone suggests that the
negative deviation shown by 2d and 2e arises from stabilization
of the ground state through resonance interaction between the
EDG and the thiocarbonyl group as illustrated in the resonance
structures IV T V.
o
but a significant decrease in the pKa value. (2) The k2/k-1 ratio
is highly sensitive to the basicity of pyridines but independent
of the electronic nature of the substituent X in the nonleaving
group, i.e., the k2/k-1 ratio remains nearly constant on changing
the substituent X for reactions with a given pyridine. Accord-
o
ingly, the pKa value is not influenced by the electronic nature
of the substituent X in the thionobenzoyl moiety. (3) The
Hammett plot for reactions of 2a-e with 4-aminopyridine is
not linear, i.e., substrates bearing an EDG (e.g., 2d and 2e)
exhibit negative deviations from the Hammett plot. On the other
hand, the Yukawa-Tsuno plot for the same reaction exhibits
(
26) (a) Tsuno, Y.; Fujio, M. AdV. Phys. Org. Chem. 1999, 32, 267-
85. (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.
27) (a) Fujio, M.; Rappoport, Z.; Uddin, M. K.; Kim, H. J.; Tsuno, Y.
3
(
Furthermore, the above argument can be clearly supported
from the linear Yukawa-Tsuno plot shown in the inset of Figure
for the same reactions. The r value in the Yukawa-Tsuno
Bull. Chem. Soc. Jpn. 2003, 76, 163-169. (b) Nakata, K.; Fujio, M.;
Nishimoto, K.; Tsuno, Y. J. Phys. Org. Chem. 2003, 16, 323-335. (c)
Uddin, M. K.; Fujio, M.; Kim, H. J.; Rappoport, Z.; Tsuno, Y. Bull. Chem.
Soc. Jpn. 2002, 75, 1371-1379.
5
(28) Ugi, I.; Beck, F. Chem. Ber. 1961, 94, 1839.
(
25) (a) Neuvonen, H.; Neuvonen, K.; Pasanen, P. J. Org. Chem. 2004,
(29) (a) Kevill, D. N.; D’Souza, M. J. J. Org. Chem. 2004, 69, 7044-
7050. (b) Kevill, D. N. In The Chemistry of the Functional Groups. The
Chemistry of Acyl Halrides; Patai, S., Ed.; Wiley: New York, 1972; Chapter
12.
6
9, 3794-3800. (b) Neuvonen, H.; Neuvonen, K.; Koch, A.; Kleinpeter,
E.; Pasanen, P. J. Org. Chem. 2002, 67, 6995-7003. (c) Neuvonen, H.;
Neuvonen, K. J. Chem. Soc., Perkin Trans. 2 1999, 1497-1502.
9196 J. Org. Chem., Vol. 71, No. 24, 2006

Pyridinolysis of O-4-Nitrophenyl Benzoate
excellent linear correlation with an r value of 0.75. Thus,
stabilization of the ground state through resonance interaction
is responsible for the negative deviation shown by 2d and 2e.
Typically, the reaction was initiated by adding 5 µL of a 0.02
M substrate solution in MeCN by a 10 µL syringe into a 10 mm
UV cell containing 2.50 mL of the reaction medium and pyridine.
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 pyridine
to 1 equiv of standardized HCl solution in order to obtain a self-
buffered solution. All transfers of reaction solutions were carried
out by means of gastight syringes. The kinetic conditions and results
are shown in the Supporting Information.
Experimental Section
Materials. Substrates 2a-e were readily prepared from the
reaction of 4-nitrophenol and X-substituted thionobenzoyl chloride
in the presence of triethylamine in anhydrous ether as reported
5
d-f,30
previously.
Their purity was confirmed by their melting points
1
Products Analysis. The amount of 4-nitrophenoxide (and/or
and H NMR spectra. Pyridines and other chemicals were of the
highest quality available and generally recrystallized or distilled
4-nitrophenol) was determined quantitatively by comparison of the
UV-vis spectra after completion of the reactions with those of the
authentic samples under the same reaction conditions. Other
products, such as 1-thionobenzoylpyridinium ion, were not isolated,
but its hydrolyzed product, thiobenzoate, was identified by HPLC.
before use. Due to the low solubility of 2a-e in pure H
DMSO was used as the reaction medium (i.e., 20 mol % DMSO/
0 mol % H O). Doubly glass distilled water was further boiled
2
O, aqueous
8
2
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 circulating bath for slow reactions (e.g., t1/2 g 10 s)
or with a stopped-flow spectrophotometer for fast reactions (e.g.,
Acknowledgment. This work was supported by a grant from
KOSEF of Korea (R01-2004-000-10279-0). S.J.H. is also
grateful for the BK 21 scholarship.
t
1/2 < 10 s). The reactions were followed by monitoring the
appearance of 4-nitrophenoxide ion at 410 nm (or 4-nitrophenol at
40 nm for reactions with weakly basic pyridines). All reactions
were carried out under pseudo-first-order conditions in which the
pyridine concentration was at least 20 times greater than that of
substrate.
Supporting Information Available: Tables S1-S18 for the
kinetic conditions and data for reactions of 2a, 2c, and 2e with six
different pyridines, Tables S19 and S20 for the kinetic data for
reactions of 2b and 2d with 4-aminopyridine, and Table S21 for
the kinetic result for the reaction of 1c with 4-oxidopyridine. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
3
(
30) Campbell, P.; Lapinskas, B. A. J. Am. Chem. Soc. 1977, 99, 5378-
5
382.
JO061682X
J. Org. Chem, Vol. 71, No. 24, 2006 9197