Kinetic studies on nucleophilic substitution reactions of O-Aryl thionobenzoates with azide, cyanide, and hydroxide: Contrasting reactivity and mechanism

Article abstract of DOI:10.1021/jo802446y

A kinetic study is reported for nucleophilic substitution reactions of O-Y-substituted phenyl thionobenzoates (1a-h) and O-4-nitrophenyl X-substituted thionobenzoates (2a-f) with N₃^- and CN^- in 80 mol % H₂O-2O m

Full text of DOI:10.1021/jo802446y

Kinetic Studies on Nucleophilic Substitution Reactions of O-Aryl
Thionobenzoates with Azide, Cyanide, and Hydroxide: Contrasting
Reactivity and Mechanism
Ik-Hwan Um,* Eun-Hee Kim, and Ji-Youn Lee
Department of Chemistry and Nano Science, Ewha Womans UniVersity, Seoul 120-750, Korea
ihum@ewha.ac.kr
ReceiVed NoVember 3, 2008
A kinetic study is reported for nucleophilic substitution reactions of O-Y-substituted phenyl thionobenzoates
-
(1a-h) and O-4-nitrophenyl X-substituted thionobenzoates (2a-f) with N3 and CN- in 80 mol %
-
H2O-20 mol % DMSO at 25.0 ( 0.1 °C. The Brønsted-type plot for the reactions of 1a-h with N3
exhibits a downward curvature, i.e., the slope (ꢀlg) changes from -1.10 to -0.33 as the leaving group
basicity decreases, indicating that the reactions proceed through a stepwise mechanism with a change in
rate-determining step (RDS). In contrast, the Brønsted-type plot for the corresponding reactions with
CN- is linear with a ꢀlg value of -0.33. This value is similar to that found previously for the reactions
of 1a-h with OH- (-0.35). Besides, σo constants result in much better Hammett correlation than σ-
constants. Thus, the reactions with CN- and OH- have been concluded to proceed through a stepwise
-
mechanism in which departure of the leaving group occurs after RDS. Reactions of 2a-f with N3 and
CN- result in nonlinear Hammett plots. However, the Yukawa-Tsuno plots for the same reactions exhibit
excellent linearity with r ) 0.5 ( 0.1, indicating that the nonlinear Hammett plots are not due to a
change in RDS but are caused by ground state stabilization through resonance interactions between the
electron-donating substituent and the thio carbonyl functionality. Calculation of the k1 values (nucleophile
-
attack as RDS) for the reactions of 1a-h with N3 indicates that azide ion is more reactive than OH-
toward the thione esters, although the former is over 11 pKa units less basic than the latter. The high
polarizability of N3- has been suggested to be responsible for its great affinity for the polarizable thione
esters 1a-h and 2a-f.
Introduction
been suggested to proceed through a concerted mechanism.2-7
However, reactions of carboxylic esters have been reported to
proceed through a concerted or stepwise mechanism depending
Acyl-group transfer reactions have been the subject of
intensive experimental and theoretical studies due to their
importance in biological processes as well as synthetic
applications.1-16 Reactions of acid chlorides or anhydrides have
(3) Kevill, D. N.; Kim, C. B. J. Chem. Soc., Perkin Trans. 2 1988, 7, 1353–
1358.
* Corresponding author. Fax: 82-2-3277-2844. Phone: 82-2-3277-2349.
(1) (a) March, J. AdVanced Organic Chemistry, 4th ed.; Wiley: New York,
1992; pp 330-335. (b) Lowry, T. H.; Richardson, K. S. Mechanism and Theory
in Organic Chemistry, 3rd ed.; Harper and Row: New York, 1987; pp 710-
723.
(2) (a) Bentley, T. W.; Llewellyn, G.; McAlister, J. A. J. Org. Chem. 1996,
61, 7927–7932. (b) Bentley, T. W.; Harris, H. C. J. Chem. Soc., Perkin Trans.
2 1986, 619–624.
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B. S. J. Am. Chem. Soc. 2000, 122, 11162–11172.
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1212 J. Org. Chem. 2009, 74, 1212–1217
10.1021/jo802446y CCC: $40.75 2009 American Chemical Society
Published on Web 01/02/2009

Substitution Reactions of O-Aryl Thionobenzoates
on the nature of nucleophiles (e.g., neutral amines and anionic
nucleophiles).8-16
analysis of the free energy profile in alkaline hydrolysis of
methyl formate.19
It has been reported that the effect of replacing the O atom
of the CdO bond in 4-nitrophenyl benzoate (PNPB) by
polarizableSonreactivityandreactionmechanismissignificant.20-25
We have shown that O-4-nitrophenyl thionobenzoate (PNPTB)
is 1.4 × 104 times more reactive than PNPB toward 4-chlo-
rothiophenoxide.20 In contrast, Campbell et al. have reported
that PNPTB is 8 times less reactive than PNPB toward OH-.21
The effect of changing the electrophilic center from CdO to
CdS on reaction mechanism has also been investigated. We
have found that reactions of PNPTB with a series of alicyclic
secondary amines proceed through two intermediates, a zwit-
terionic tetrahedral intermediate T ( and its deprotonated form
T-, while the corresponding reactions of its oxygen analogue
Reactions of esters with amines have generally been reported
to proceed through an addition-elimination mechanism, in
which the rate-determining step (RDS) is dependent on the
basicity of the entering amine and the leaving group.12-15
Evidence provided is nonlinear Brønsted-type plots that have
often been observed for reactions of esters possessing a weakly
basic aryloxide (e.g., 2,4-dinitrophenoxide).12-15 Theoretical
studies have also favored a stepwise mechanism although the
difference in activation energies between the two pathways was
calculated to be insignificant.16
However, reactions of carboxylic esters with anionic nucleo-
philes have not been completely understood. Williams et al.
have concluded that nucleophilic substitution reactions of
4-nitrophenyl acetate with a series of aryloxides proceed through
a concerted mechanism. The evidence consisted mainly of the
absence of a break (or curvature) in the Brønsted-type plot when
the pKa of the incoming aryloxide corresponded to that of the
leaving 4-nitrophenoxide.10 The concerted mechanism has been
supported by Hengge et al. from heavy atom kinetic isotope
effects (KIEs)11 and by Xie et al. from computational studies.9a
On the contrary, we have concluded that reactions of phenoxide
with a series of substituted phenyl acetates proceed through a
stepwise mechanism on the basis of the kinetic results that σo
constants exhibit better Hammett correlation than σ- constants.17
A similar conclusion has been drawn from kinetic studies of
alkaline hydrolysis of aryl benzoates18 as well as from theoretical
22
(
PNPB proceed without the deprotonation process from T
.
Similar results have been reported for aminolyses of aryl
carbonates and thionocarbonates.23,24
Recently, we performed a systematic study for alkaline
hydrolysis of O-Y-substituted phenyl thionobenzoates (1a-h)
and O-4-nitrophenyl X-substituted thionobenzoates (2a-f). The
reactions were concluded to proceed through an anionic
tetrahedral intermediate T-, in which departure of the leaving
group from T- occurs after the RDS.25 To get more information
on reactivity and mechanism, our kinetic study has been
-
extended to reactions of 1a-h and 2a-f with N3 and CN-
(i.e., representing an anionic nitrogen and carbon nucleophile,
respectively). The kinetic results obtained from the current
-
reactions with N3 and CN- have been compared with those
reported previously for the corresponding reactions with OH-
to investigate the effect of the nucleophile nature on reactivity
and mechanism.
(9) (a) Xie, D.; Zhou, Y.; Xu, D.; Guo, H. Org. Lett. 2005, 7, 2093–2095.
(b) Chong, L. T.; Bandyopadhyay, P.; Scanlan, T. S.; Kuntz, I. D.; Kollman,
P. A. J. Comput. Chem. 2003, 24, 1371–1377. (c) Tantillo, D. J.; Houk, K. N.
J. Org. Chem. 1999, 64, 3066–3076.
(10) (a) Williams, A. Acc. Chem. Res. 1989, 22, 387–392. (b) Ba-Saif, S.;
Luthra, A. K.; Williams, A. J. Am. Chem. Soc. 1989, 111, 2647–2652. (c) Ba-
Saif, S.; Luthra, A. K.; Williams, A. J. Am. Chem. Soc. 1987, 109, 6362–6368.
(11) (a) Hess, R. A.; Hengge, A. C.; Cleland, W. W. J. Am. Chem. Soc.
1997, 119, 6980–6983. (b) Hengge, A. C.; Hess, R. A. J. Am. Chem. Soc. 1994,
116, 11256–11263. (c) Hengge, A. C. J. Am. Chem. Soc. 1992, 114, 2747–
2748.
(12) (a) Jencks, W. P. Catalysis in Chemistry and Enzymology; McGraw-
Hill: New York, 1969; pp 480-483. (b) Jencks, W. P. Chem. Soc. ReV. 1981,
10, 345–375. (c) Jencks, W. P.; Gilchrist, M. J. Am. Chem. Soc. 1968, 90, 2622–
2637. (d) Menger, F. M.; Smith, J. H. J. Am. Chem. Soc. 1972, 94, 3824–3829.
(13) (a) Castro, E. A.; Echevarria, G. R.; Opazo, A.; Robert, P.; Santos, J. G.
J. Phys. Org. Chem. 2006, 19, 129–135. (b) Castro, E. A.; Campodonico, P. R.;
Contreras, 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.;
Aliaga, M.; Gazitua, M.; Santos, J. G. Tetrahedron 2006, 62, 4863–4869. (d)
Castro, E. A.; Aguayo, R.; Bessolo, J.; Santos, J. G. J. Org. Chem. 2005, 70,
7788–7791. (e) Castro, E. A.; Aliaga, M.; Santos, J. G. J. Org. Chem. 2005, 70,
2679–2685. (f) Castro, E. A.; Gazitua, M.; Santos, J. G. J. Org. Chem. 2005,
70, 8088–8092. (g) Castro, E. A.; Aliaga, M.; Santos, J. G. J. Org. Chem. 2004,
69, 6711–6714. (h) Castro, E. A.; Andujar, M.; Toro, A.; Santos, J. G. J. Org.
Chem. 2003, 68, 3608–3613. (i) Castro, E. A.; Aliaga, M.; Campodonico, P.;
Santos, J. G. J. Org. Chem. 2002, 67, 8911–8916.
Results and Discussion
The kinetic study was performed under pseudo-first-order
conditions with the concentration of nucleophile in excess over
the substrate concentration. All reactions obeyed first-order
kinetics with quantitative liberation of Y-substituted phenoxide
ion and/or its conjugate acid. Pseudo-first-order rate constants
(kobsd) were calculated from the equation ln(A∞ - At) ) -kobsd
t
+ C. The plots of kobsd vs nucleophile concentration were linear
passing through the origin. Thus, the rate equation can be given
as eq 1. Second-order rate constants (kNu) have been determined
from the slope of the linear plots and summarized in Table 1
for reactions of 1a-h and in Table 3 for those of 2a-f. It is
(19) Pliego, J. R., Jr.; Riveros, J. M. Chem. Eur. J. 2002, 8, 1945–1953.
(20) Um, I. H.; Lee, J. Y.; Bae, S. Y.; Buncel, E. Can. J. Chem. 2005, 83,
1365–1371.
(21) Campbell, P.; Lapinskas, B. A. J. Am. Chem. Soc. 1977, 99, 5378–
5382.
(14) (a) Lee, I.; Lee, H. W.; Yu, Y. K. Bull. Korean Chem. Soc. 2003, 24,
993–998. (b) Oh, H. K.; Park, C. Y.; Lee, J. M.; Lee, I. Bull. Korean Chem.
Soc. 2001, 22, 383–387. (c) Koh, H. J.; Han, K. L.; Lee, H. W.; Lee, I. J. Org.
Chem. 2000, 65, 4706–4711.
(15) (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.; Lee, H. W. Can. J. Chem.
1999, 77, 659–666.
(16) (a) Galabov, B.; Atanasov, Y.; Ilieva, S., III. J. Phys. Chem. A 2005,
109, 11470–11474. (b) Ilieva, S.; Galabov, B.; Musaev, D. G.; Morokuma, K.;
Schaefer, H. F., III. J. Org. Chem. 2003, 68, 1496–1502. (c) Yang, W.;
Drueckhammer, D. G. Org. Lett. 2000, 2, 4133–4136.
(17) (a) Buncel, E.; Um, I. H.; Hoz, S. J. Am. Chem. Soc. 1989, 111, 971–
975. (b) Um, I. H.; Hwang, S. J.; Buncel, E. J. Org. Chem. 2006, 71, 915–920.
(18) (a) Um, I. H.; Han, H. J.; Ahn, J. A.; Kang, S.; Buncel, E. J. Org.
Chem. 2002, 67, 8475–8480. (b) Um, I. H.; Lee, J. Y.; Fujio, M.; Tsuno, Y.
Org. Biomol. Chem. 2006, 4, 2979–2985.
(22) (a) Um, I. H.; Hwang, S. J.; Yoon, S. R.; Jeon, S. E.; Bae, S. K. J. Org.
Chem. 2008, 73, 7671–7677. (b) Um, I. H.; Seok, J. A.; Kim, H. T.; Bae, S. K.
J. Org. Chem. 2003, 68, 7742–7746. (c) Um, I. H.; Lee, S. E.; Kwon, H. J. J.
Org. Chem. 2002, 67, 8999–9005.
(23) (a) Castro, E. A.; Cubillos, M.; Aliaga, M.; Evangelisti, S.; Santos, J. G.
J. Org. Chem. 2004, 69, 2411–2416. (b) Castro, E. A.; Andujar, M.; Camp-
odonico, P.; Santos, J. G. Int. J. Chem. Kinet. 2002, 34, 309–315. (c) Castro,
E. A.; Galvez, A.; Leandro, L.; Santos, J. G. J. Org. Chem. 2002, 67, 4309–
4315. (d) Castro, E. A.; Leandro, L.; Quesieh, N.; Santos, J. G. J. Org. Chem.
2001, 66, 6130–6135.
(24) Um, I. H.; Yoon, S. R.; Park, H. R.; Han, H. J. Org. Biomol. Chem.
2008, 6, 1618–1624.
(25) Um, I. H.; Lee, J. Y.; Kim, H. T.; Bae, S. K. J. Org. Chem. 2004, 69,
2436–2441.
(26) Um, I. H.; Kim, E. H.; Han, H. J. Bull. Korean Chem. Soc. 2008, 29,
580–584.
J. Org. Chem. Vol. 74, No. 3, 2009 1213

Um et al.
TABLE 1. Summary of Second-Order Rate Constants for
Reactions of O-Y-Substituted Phenyl Thionobenzoates (1a-h) with
N3-, CN-, and OH- in 80 mol % H2O-20 mol % DMSO at 25.0 (
0.1 °Ca
102kN
/
102kCN
/
kOH /
-
-
-
3
pKaY-C H OH
M-1 s-1
M-1 s-1
M-1 s-1
6
4
Y
1a: 4-MeO
1b: 4-Me
1c: H
1d: 3-COMe
1e: 4-COMe
1f: 4-CHO
1g: 4-NO2
1h: 3,4-(NO2)2
10.20
10.19
9.95
9.19
8.05
7.66
7.14
5.42
0.544((0.045)
0.509((0.010)
1.22((0.01)
2.13((0.02)
1.89((0.04)
2.75((0.03)
5.52((0.08)
7.88((0.04)
9.26((0.09)
19.7((0.2)
93.5((0.5)
0.172
0.161
0.210
0.489
0.650
0.846
1.87
139((1)
250((1)
1100((10)
18300((200)
10.5
a pKa of phenols and the kNu values for reactions of 1a-h with OH-
were taken from ref 25.
TABLE 2. Summary of Microscopic Rate Constants for Reactions
-
of O-Y-Substituted Phenyl Thionobenzoates (1a-h) with N3 in 80
mol % H2O- 0 mol % DMSO at 25.0 ( 0.1°C
pKaY-C H OH
k1/M-1 s-1
k2/k-1
6
4
Y
1a: 4-MeO
1b: 4-Me
1c: H
1d: 3-COMe
1e: 4-COMe
1f: 4-CHO
1g: 4-NO2
1h: 3,4-(NO2)2
10.20
10.19
9.95
9.19
8.05
7.66
7.14
5.42
5.48
5.84
7.90
9.93 × 10-4
FIGURE 1. Brønsted-type plots for reactions of O-Y-substituted phenyl
thionobenzoates (1a-h) with N3- (0), CN- (O), and OH- (b)25 in 80
mol % H2O-20 mol % DMSO at 25.0 ( 0.1 °C. The identity of
numbers is given in Table 1.
0.00101
0.00155
32.3
30.4
59.8
221
0.0449
0.0897
0.226
4.76
estimated from replicate runs that the uncertainty in the rate
constants is less than (3%.
rate ) kobsd[substrate], where kobsd ) kNu[Nu-] (1)
Effect of Leaving-Group Substituent Y on Reaction
Mechanism. As shown in Table 1, the second-order rate
constant (kNu) increases as the substituent Y in the leaving group
changes from an electron-donating substituent (EDS) to a strong
electron-withdrawing substituent (EWS). It is noted that the
effect of substituent on reactivity is more significant for the
reactions with N3 than for those with CN- and OH-, e.g., as
-
the substituent Y changes from 4-MeO to 3,4-(NO2)2, the kNu
value for reactions with N3- increases from 5.44 × 10-3 to 183
M-1 s-1, over a 104-fold increase in reactivity. In contrast, the
kNu value increases from 0.0213 to 0.935 M-1 s-1 for the reac-
tions with CN- and from 0.172 to 10.5 M-1 s-1 for the reactions
with OH-, only a 40- to 60-fold increase in reactivity as the
substituent Y changes from 4-MeO to 3,4-(NO2)2. More
interestingly, Table 1 shows that N3- is more reactive than OH-
toward 1e-h, although the former is over 11 pKa units less basic
than the latter.
FIGURE 2. Hammett correlations with σ- (A) and σo (B) constants
for reactions of O-Y-substituted phenyl thionobenzoates (1a-h) with
OH- (b) and CN- (O) in 80 mol % H2O-20 mol % DMSO at 25.0 (
0.1 °C. The identity of numbers is given in Table 1.
for reactions that proceed through a stepwise mechanism with
formation of an intermediate being the RDS.12-15 Thus, one
can suggest that the reactions of 1a-h with OH- and CN-
proceed through a stepwise mechanism, in which leaving-group
departure occurs after the RDS.
The effect of leaving-group basicity on reactivity is illustrated
in Figure 1. The Brønsted-type plot for the reactions with N3
To examine the above argument, Hammett plots have been
constructed with use of σ- and σo constants. If the leaving-
group departure occurs at the RDS, a partial negative charge
would develop on the oxygen atom of the leaving aryloxide.
Such a partial negative charge can be delocalized on the
substituent Y through resonance. Thus, one can expect that σ-
constants should result in a good Hammett correlation if the
leaving group departs at the RDS. As shown in Figure 2A, the
Hammett correlation with σ- constants exhibits many scattered
points for reactions with both OH- and CN-. On the contrary,
σo constants result in excellent linear correlations (Figure 2B),
indicating that no negative charge is developing on the oxygen
atom of the leaving aryloxides at the rate-determining transition
state. Thus, one can conclude that the reactions of 1a-h with
-
exhibits a downward curvature, i.e., the slope (ꢀlg) changes from
-1.10 to -0.33 as the leaving-group basicity decreases. Such
a curved Brønsted-type plot has often been reported for reactions
which proceed through a stepwise mechanism with a change in
the RDS (e.g., aminolysis of esters possessing a good
nucleofuge).12-15 Thus, one can suggest that the reactions of
1a-h with N3- proceed through a stepwise mechanism with a
change in the RDS upon changing the leaving-group basicity
as shown in Scheme 1.
On the other hand, the Brønsted-type plots for the reactions
with OH- and CN- are linear with ꢀlg values of -0.35 and
-0.33, respectively. Such linear Brønsted-type plots are typical
1214 J. Org. Chem. Vol. 74, No. 3, 2009

Substitution Reactions of O-Aryl Thionobenzoates
SCHEME 1
increase from 5.48 to 221 M-1 s-1 and from 9.93 × 10-4 to
4.76, respectively. The k1 value increases only ca. 40-fold while
the k2/k-1 ratio increases ca. (5 × 103)-fold, indicating that the
effect of leaving group substituent is more significant on the
k2/k-1 ratios than on the k1 values. It is noted that the k2/k-1
ratio is 4.76 for the reaction of 1h with N3-, indicating that
N3- is a poorer nucleofuge than 3,4-dinitrophenoxide although
the former is less basic than the latter. Thus, one can suggest
TABLE 3. Summary of Second-Order Rate Constants for
Reactions of O-4-Nitrophenyl X-Substituted Thionobenzoates (2a-f)
with N3-, CN-, and OH- in 80 mol % H2O-20 mol % DMSO at
25.0 ( 0.1 °C
-1
-1
-1
-
-
-
X
kN /M s-1
103kCN /M s-1
102kOH /M s-1
3
2a: 4-NMe2
2b: 4-MeO
2c: 4-Me
2d: H
2e: 3-MeO
2f: 3-Cl
0.0460
1.78
4.77
11.0
17.3
1.30
36.4
88.0
197
262
822
1.44
40.8a
83.0a
187a
-
271a
that N3 has greater affinity than an isobasic aryloxide for the
81.6
797a
thio carbonyl carbon. This is in contrast to what is found in
aminolysis: amines leave the zwitterionic tetrahedral intermedi-
ate faster than an isobasic aryloxide.13 This must be due to the
a The kOH values for reactions of 2b-f were taken from ref 25.
-
-
fact that N3 in the anionic tetrahedral intermediate can exert
OH- and CN- proceed through a stepwise mechanism, in which
leaving group departure occurs rapidly after the RDS (i.e., kNu
) k1).
its push and enforce its bond to the central C, whereas the
cationic amino moiety in the zwitterionic tetrahedral intermedi-
ate cannot.
Dissection of Macroscopic Rate Constants into Micro-
scopic Rate Constants. The nonlinear Brønsted-type plot shown
The effect of leaving-group basicity on k1 is illustrated in
Figure 3 together with the Brønsted-type plots for the reactions
with OH- and CN- for comparison purposes. The plot of log
-
in Figure 1 for the reactions of 1a-h with N3 has been
analyzed by using a semiempirical equation (eq 2)27 on the basis
of the proposed mechanism. In eq 2, ꢀlg1 and ꢀlg2 represent the
slope of the Brønsted-type plots for the weakly basic and
strongly basic leaving groups, respectively. The pKa at the
curvature center of the nonlinear Brønsted-type plot has been
defined as pKao, where a change in RDS occurs (i.e., k-1 ) k2
k1 vs pKa for the reactions of 1a-h with N3 exhibits an
-
excellent linearity with ꢀlg1 ) -0.33. It is noted that the ꢀlg1
-
value for the reactions with N3 is practically identical with
the ꢀlg values for the corresponding reactions with OH- and
-
CN-, although the k1 values for reactions with N3 and the
macroscopic rate constant kNu values for reactions with OH-
and CN- are employed to construct the Brønsted-type plots.
This result is consistent with the preceding conclusion that kNu
) k1 for the reactions of 1a-h with OH- and CN-.
27
o
at pKao). The kNu refers to the kNu value at pKao. The
parameters determined from the fitting of eq 2 to the experi-
mental points are ꢀlg1 ) -0.33, ꢀlg2 ) -1.10, kNuo ) 50.1, and
pKao ) 6.3.
log(kNu/kNuo) ) ꢀlg1(pKa - pKao) - log[(1 + R)/2],
where log R ) (ꢀlg1 - ꢀ ) pK - pK o (2)
(
)
lg2
a
a
To get further information on reaction mechanism, the macro-
scopic rate constants (kNu) have been dissected into the
microscopic rate constants (i.e., k1 and k2/k-1 ratios) associated
with the reactions of 1a-h with N3-. The k2/k-1 ratios have
been calculated from eq 3,27c using ꢀlg1, ꢀlg2, and pKao values
obtained above. The k1 values have been calculated from eq
4,27c using the kNu values in Table 1 and the k2/k-1 ratios
calculated above, and summarized in Table 2.
(log k2/k-1) ) (ꢀlg2 - ꢀlg1)(pKa - pKao)
kNu ) k1k2/(k-1 + k2) ) k1/(k-1/k2 + 1)
(3)
(4)
As shown in Table 2, k1 and k2/k-1 ratios increase as the
substituent Y in the leaving group changes from an EDS to a
strong EWS, e.g., as the substituent Y in the leaving group
changes from 4-MeO to 3,4-(NO2)2, the k1 value and k2/k-1 ratio
FIGURE 3. Plots of log k1 (or log kNu) vs pKaY-C H OH for reactions of
6
4
(27) (a) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6970–
6980. (b) Castro, E. A.; Moodie, R. B. J. Chem. Soc., Chem. Commun. 1973,
828–829. (c) Castro, E. A.; Araneda, C. A.; Santos, J. G. J. Org. Chem. 1997,
62, 126–129.
-
O-Y-substituted phenyl thionobenzoates (1a-h) with N3 (0), CN-
(O), and OH- (b) in 80 mol % H2O-20 mol % DMSO at 25.0 ( 0.1
°C. The identity of numbers is given in Tables 1 and 2.
J. Org. Chem. Vol. 74, No. 3, 2009 1215

Um et al.
FIGURE 5. Hammett plots for reactions of O-4-nitrophenyl X-
FIGURE 4. Plot of log k2/k-1 vs pKaY-C H OH for reactions of O-Y-
6
4
substituted thionobenzoates (2a-f) with N3 (0), CN- (O), and OH-
-
-
substituted phenyl thionobenzoates (1a-h) with N3 in 80 mol %
H2O-20 mol % DMSO at 25.0 ( 0.1 °C. The identity of numbers is
(b) in 80 mol % H2O-20 mol % DMSO at 25.0 ( 0.1 °C. The identity
of numbers is given in Table 3.
given in Table 2.
k-1 ratio should be independent of the electronic nature of
substituent X in the nonleaving group.
The effect of leaving-group basicity on the k2/k-1 ratios is
illustrated in Figure 4 for the reactions of 1a-h with N3-. The
plot exhibits an excellent linearity with a slope of -0.77, which
is much steeper than those shown in Figure 3. However, such
a large negative slope is not unexpected for reactions which
proceed through a stepwise mechanism. This is because the k2
value increases significantly as the leaving group becomes less
basic. On the contrary, the k-1 value would decrease as the
substituent Y in the leaving aryloxide becomes a stronger EWS,
although the effect of the substituent Y on the k-1 value would
not be significant due to the long distance between the reaction
center and the substituent. Thus, one can expect a large slope
in the plot of log k2/k-1 vs leaving group basicity due to the
contrasting substituent effect on the k2 and k-1 values.
A careful examination of Figure 5 reveals that the substrates
with an EDS exhibit negative deviations from the Hammett plots
and the degree of deviation is more significant for the substrate
with a stronger EDS, e.g., X ) 4-NMe2 (2a). Thus, one can
suggest that the origin of the nonlinear Hammett plots is
stabilization of the ground state (GS) through resonance
interaction between the EDS on the thionobenzoyl moiety and
the thio carbonyl functionality as illustrated by resonance
structures I and II.
Effect of Nonleaving-Group Substituent X on Reacti-
vity and Mechanism. To investigate the effect of nonleaving-
group substituent on mechanism, we have performed reactions
of O-4-nitrophenyl X-substituted thionobenzoates (2a-f) with
To confirm the above argument, Yukawa-Tsuno plots have
been constructed in Figure 6. The r value in the Yukawa-Tsuno
equation (eq 5) represents the resonance demand of the reaction
center or the extent of resonance contribution, while the term
(σ+ - σo) is the resonance substituent constant that measures
the capacity for π-delocalization of the π-electron donor
substituent.29
-
N3 and CN-. The second-order rate constants, together with
those for the reactions with OH-,25 are summarized in Table 3.
It is seen that the kNu value increases as the substituent X changes
from a strong EDS to an EWS.
The effect of substituent X on reactivity is illustrated in Figure
5. Each Hammett plot consists of two intersecting straight lines.
Such a nonlinear Hammett plot has traditionally been interpreted
as a change in RDS.28 Thus, at a first sight, one might suggest
that a change in RDS occurs as the substituent X changes from
EDSs to EWSs. However, we propose that the nonlinear
Hammett plots are not due to a change in RDS on the basis of
the following argument. The RDS is determined by the k2/k-1
ratio. Since the leaving aryloxide and nucleophile leave from
the anionic intermediate T- with the bonding electron pair, both
k2 and k-1 processes would be accelerated by an EDS in the
thionobenzoyl moiety but retarded by an EWS. Thus, the k2/
log(kX/kH) ) F[σo + r(σ+-σo)]
(5)
As shown in Figure 6, the Yukawa-Tsuno plots exhibit
excellent linear correlations with r values of 0.46, 0.56, and
0.62 for the reactions with N3-, OH-, and CN-, in turn. Since
the r value is neither 0 nor 1, the Yukawa-Tsuno plots result
in much better linear correlations than the Hammett plot using
σ or σ+ constants alone. It is apparent that the nonlinear
Hammett plots shown in Figure 5 are not due to a change in
(29) (a) Yukawa, Y.; Tsuno, Y. Bull. Chem. Soc. Jpn. 1959, 32, 965–970.
(b) Tsuno, Y.; Fujio, M. AdV. Phys. Org. Chem. 1999, 32, 267–385. (c) Tsuno,
Y.; Fujio, M. Chem. Soc. ReV. 1996, 25, 129–139. (d) Fujio, M.; Alam, M. A.;
Umezaki, Y.; Kikukawa, K.; Fujiyama, R.; Tsuno, Y. Bull. Chem. Soc. Jpn.
2007, 80, 2378–2383. (e) Fujio, M.; Umezaki, Y.; Alam, M. A.; Kikukawa, K.;
Fujiyama, R.; Tsuno, Y. Bull. Chem. Soc. Jpn. 2006, 79, 1091–1099.
(28) Carrol, F. A. PerspectiVes on Structure and Mechanism in Organic
Chemistry; Brooks/Cole: New York, 1998; pp 371-386.
1216 J. Org. Chem. Vol. 74, No. 3, 2009

Substitution Reactions of O-Aryl Thionobenzoates
(3) Dissection of the macroscopic rate constants (kNu) into the
microscopic rate constants for the reactions of 1a-h has
revealed that N3- exhibits larger k1 values than OH-, although
the former is over 11 pKa units less basic than the latter. The
-
high polarizability of N3 is responsible for the great affinity
-
of N3 for the polarizable thione esters. (4) The reactions of
2a-f with N3-, CN-, and OH- result in nonlinear Hammett
plots. In contrast, the Yukawa-Tsuno plots for the same
reactions are linear with r ) 0.5 ( 0.1, indicating that the
nonlinear Hammett plots are not due to a change in RDS but
are caused by GS stabilization through resonance interactions
between the EDS in the thionobenzoyl moiety and the thio
carbonyl functionality.
Experimental Section
Materials. Compounds 1a-h and 2a-f were prepared as
reported previously.22a,25 Other chemicals used were of the highest
quality available. The reaction medium was H2O containing 20 mol
% DMSO due to low solubility of the substrates in pure H2O.
Doubly glass distilled water was further boiled and cooled under
nitrogen just before use.
Kinetics. The kinetic study was performed with a UV-vis
spectrophotometer for slow reactions (t1/2 g 10 s) or with a stopped-
flow spectrophotometer for fast reactions (t1/2 < 10 s) equipped
with a constant temperature circulating bath to maintain the
temperature in the reaction cell at 25.0 ( 0.1 °C. The reaction was
followed by monitoring the appearance of the leaving Y-substituted
phenoxide ion or its conjugate acid. All the reactions were carried
out under pseudo-first-order conditions in which nucleophile
concentrations were at least 20 times greater than the substrate
concentration. All solutions were prepared freshly just before use
under nitrogen, and transferred by gas-tight syringes. Typically,
reactions were initiated by adding 5 µL of a 0.02 M solution of the
substrate in CH3CN by a 10 µL 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 the nucleophile stock solution.
Product Analysis. Y-Substituted phenoxide (and/or its conjugate
acid) was liberated quantitatively and identified as one of the
products by comparison of the UV-vis spectrum at the end of
reaction with that of the authentic sample under the experimental
condition.
FIGURE 6. Yukawa-Tsuno plots for reactions of O-4-nitrophenyl
X-substituted thionobenzoates (2a-f) with N3- (0), CN- (O), and OH-
(b) in 80 mol % H2O-20 mol % DMSO at 25.0 ( 0.1 °C. The identity
of numbers is given in Table 3.
RDS but are caused by the GS stabilization through resonance
interactions as mentioned above. Thus, one can conclude that
the nature of substituent X in the nonleaving group does not
influence the reaction mechanism in the current system.
-
Figure 6 shows that N3 is more reactive than OH- toward
thione esters 2a-f, although the former is over 11 pKa units
less basic than the latter. A similar result is demonstrated in
-
Figure 3, i.e., N3 exhibits larger k1 values than OH- in the
reactions of 1a-h. It is apparent that the current results are in
accordance with the hard-soft acid and base principle, since
OH- is a typical hard base while N3- has been suggested to be
a highly polarizable nucleophile.30 Thus, one can suggest that
the high polarizability of N3- is responsible for the great affinity
-
of N3 for the polarizable thione esters.
Acknowledgment. This work was supported by a grant from
Korea Research Foundation (KRF-2005-015-C00256). E.H.K.
is also grateful for the BK 21 scholarship.
Conclusions
The present study has allowed us to conclude the following:
(1) The reactions of 1a-h with N3- proceed through a stepwise
mechanism with a change in RDS at pKao ) 6.3. (2) The
corresponding reactions with OH- and CN- proceed also
through a stepwise mechanism in which departure of the leaving
group occurs after RDS regardless of the leaving-group basicity.
Supporting Information Available: Kinetic conditions and
results for the reactions of 1a-h with N3 and CN- and for
-
those of 2a-f with N3-, CN-, and OH- in 80 mol %
DMSO-20 mol % DMSO at 25.0 ( 0.1 °C. This material is
available free of charge via the Internet at http://pubs.acs.org.
(30) Jencks, W. P.; Carriuolo, J. J. Am. Chem. Soc. 1960, 82, 1778–1786.
JO802446Y
J. Org. Chem. Vol. 74, No. 3, 2009 1217