Aminolyses of 4-nitrophenyl phenyl carbonate and thionocarbonate: Effect of modification of electrophilic center from C=O to C=S on reactivity and mechanism

Article abstract of DOI:10.1021/jo052417z

A kinetic study is reported for nucleophilic substitution reactions of 4-nitrophenyl phenyl carbonate (5) and 4-nitrophenyl phenyl thionocarbonate (6) with a series of primary amines. The thiono compound 6 is less reactive than its oxygen analogue 5 toward strongly basic amines but is more reactive toward weakly basic CF₃CH₂NH₂. The Bronsted-type plots obtained from the aminolyses of 5 and 6 are curved downwardly. The reactions are proposed to proceed through a stepwise mechanism with a change in the RDS on the basis of the curved Bronsted-type plots. The microscopic rate constants (k₁ and k₂/k_-1 ratio) associated with the current aminolyses are consistent with the proposed reaction mechanism. The replacement of the C=O bond in 5 by a polarizable C=S group results in a decrease in the k₁ value but an increase in the k₂/k_-1 ratio. Besides, such a modification of the electrophilic center causes a decrease in pK_a^c, defined as the pK_a at the curvature center of curved Bronsted-type plots, but does not alter the reaction mechanism. The larger k ₂/k_-1 ratio for the reactions of 6 compared to those of 5 is proposed to be responsible for the decreased pK_a^c value.

Full text of DOI:10.1021/jo052417z

Aminolyses of 4-Nitrophenyl Phenyl Carbonate and
Thionocarbonate: Effect of Modification of Electrophilic Center
from CdO to CdS on Reactivity and Mechanism
Ik-Hwan Um,* Eun Young Kim, Hye-Ran Park, and Sang-Eun Jeon
Department of Chemistry, Ewha Womans UniVersity, Seoul 120-750, Korea
ihum@mm.ewha.ac.kr
ReceiVed NoVember 22, 2005
A kinetic study is reported for nucleophilic substitution reactions of 4-nitrophenyl phenyl carbonate (5)
and 4-nitrophenyl phenyl thionocarbonate (6) with a series of primary amines. The thiono compound 6
is less reactive than its oxygen analogue 5 toward strongly basic amines but is more reactive toward
weakly basic CF3CH2NH2. The Brønsted-type plots obtained from the aminolyses of 5 and 6 are curved
downwardly. The reactions are proposed to proceed through a stepwise mechanism with a change in the
RDS on the basis of the curved Brønsted-type plots. The microscopic rate constants (k1 and k2/k-1 ratio)
associated with the current aminolyses are consistent with the proposed reaction mechanism. The
replacement of the CdO bond in 5 by a polarizable CdS group results in a decrease in the k1 value but
an increase in the k2/k-1 ratio. Besides, such a modification of the electrophilic center causes a decrease
in pKa°, defined as the pKa at the curvature center of curved Brønsted-type plots, but does not alter the
reaction mechanism. The larger k2/k-1 ratio for the reactions of 6 compared to those of 5 is proposed to
be responsible for the decreased pKa° value.
Introduction
intermediate T(, and 2 is up to 200 times more reactive than
its oxygen analogue 4-nitrophenyl benzoate (1).2 We have
recently shown that the reaction of 2 with secondary amines
proceeds through two intermediates, T( and its deprotonated
Nucleophilic substitution reactions of thionocarbonyl and
thionophosphoryl compounds have received considerable at-
tention due to their importance in biological processes as well
as synthetic applications.1-10 The first kinetic study on thionester
has been performed by Campbell et al.2 They have found that
the reaction of O-4-nitrophenyl thionobenzoate (2) with a series
of primary amines proceeds through a zwitterionic tetrahedral
(5) (a) Balakrishnan, V.; Buncel, E.; VanLoon, G. W. EnViron. Sci.
Technol. 2005, 39, 5824-5830. (b) Onyido, I.; Albright, K.; Buncel, E.
Org. Biomol. Chem. 2005, 3, 1468-1475. (c) Balakrishnan, V.; Han, X.;
VanLoon, G. W.; Dust, J. M.; Toullec, J.; Buncel, E. Langmuir, 2004, 20,
6586-6593. (d) Buncel, E.; Albright, K.; Onyido, I. Org. Biomol. Chem.
2004, 2, 601-610. (e) Buncel, E.; Nagelkerke, R.; Thatcher, G. R. J. Can.
J. Chem. 2003, 81, 53-63.
(6) (a) Thatcher, G. R. J.; Kluger, R. AdV. Phys. Org. Chem. 1989, 25,
99-265. (b) Moss, R. A.; Kanamathareddy, S.; Vijayaraghavan, S. Langmuir
2001, 17, 6108-6112. (c) Toullec, J.; Moukawim. M. Chem. Commun.
1996, 221-222. (d) Lavey, B.; Janda, K. D. J. Org. Chem. 1996, 61, 7633-
7636. (e) Kevill, D. N.; D’Souza, M. J. Can. J. Chem. 1999, 77, 1118-
1122. (f) Kevill, D. N.; Carver, J. S. Org. Biomol. Chem. 2004, 2, 2040-
2043.
* To whom correspondence should be addressed. Fax: 822-3277-2844.
(1) (a) Castro, E. A. Chem. ReV. 1999, 99, 3505-3524. (b) Campodonico,
P. R.; Fuentealba, P.; Castro, E. A.; Santos, J. G. J. Org. Chem. 2005, 70,
1754-1760. (c) Castro, E. A.; Cubillos, M.; Santos, J. G. J. Org. Chem.
2004, 69, 4802-4807.
(2) Campbell, P.; Lapinskas, B. A. J. Am. Chem. Soc. 1977, 99, 5378-
5382.
(3) (a) Um, I. H.; Seok, J. A.; Kim, H. T.; Bae, S. K. J. Org. Chem.
2003, 68, 7742-7746. (b) Um, I. H.; Lee, S. E.; Kwon, H. J. J. Org. Chem.
2002, 67, 8999-9005. (c) Um, I. H.; Kwon, H. J.; Kwon, D. S.; Park, J. Y.
J. Chem. Res., Synop. 1995, 301.
(7) (a) Oh, H. K.; Oh, J. Y.; Sung, D. D.; Lee, I. J. Org. Chem. 2005,
70, 5624-5629. (b) Oh, H. K.; Oh, J. Y.; Sung, D. D.; Lee, I. Collect.
Czech. Chem. Commun. 2004, 69, 2174-2182. (c) Oh, H. K.; Park, J. E.;
Sung, D. D.; Lee, I. J. Org. Chem. 2004, 69, 9285-9288. (d) Oh, H. K.;
Ha, J. S.; Sung, D. D.; Lee, I. J. Org. Chem. 2004, 69, 8219-8223.
(4) Um, I. H.; Jeon, S. E.; Baek, M. H.; Park, H. R. Chem. Commun.
2003, 3016-3017.
10.1021/jo052417z CCC: $33.50 © 2006 American Chemical Society
Published on Web 02/16/2006
2302
J. Org. Chem. 2006, 71, 2302-2306

ReactiVity of Carbonate Vs Thionocarbonate
TABLE 1. Summary of Apparent Second-Order Rate Constants
SCHEME 1
(kN, M-1 s-1) for the Reaction of 4-Nitrophenyl Phenyl Carbonate
(5) and Thionocarbonate (6) with Primary Amines, OH-, and N3 in
-
H2O Containing 20 mol % DMSO at 25.0 ( 0.1 °C
k
N (M-1 s-1
)
entry
nucleophile
pKa
5
6
1
2
3
4
5
6
7
8
9
trifluoroethylamine
gylcine ethyl ester
glycylglycine
benzylamine
ethanolamine
ethylamine
5.70a
7.68
8.31
9.46
9.67
10.67
10.89
15.7
4.0
0.00495
0.620
2.30
0.0335
0.576
1.24
2.22
2.98
4.45
4.86
5.14
6.78
14.5
form T-, whereas the corresponding reaction of 1 proceeds
through T( only.3
18.8
63.9
61.0
160
0.258
propylamine
Modification of the electrophilic center from a PdO to a
PdS bond has also been reported to cause a remarkable effect
on reactivity and reaction mechanism.4-6 In the nucleophilic
substitution reaction of diethyl 4-nitrophenyl phosphate (3) and
its thiono analogue diethyl 4-nitrophenyl thionophosphate (4)
with alkali metal ethoxides (EtO-M+) in anhydrous ethanol,
we have shown that 3 is up to ca. 2 × 103 times more reactive
than 4 and alkali metal ions catalyze the reactions with 3, with
the catalytic effect increasing in the order of K+ < Na+ < Li+.4
In contrast, alkali metal ions have been found to inhibit the
reactions with 4, and the inhibitory effect increases in the order
of K+ < Na+ < Li+.4
OH-
-
N3
a The pKa data for amines in 20 mol % DMSO were taken from ref 3b.
origin, indicating that general base catalysis by a second amine
molecule is absent and the contribution of OH- and/or water
to kobsd is negligible. Thus, one can derive eqs 1 and 2, where
[S] and [RNH2] represent the concentration of the substrate and
amines used, respectively. The apparent second-order rate
constants (kN) were determined from the slope of the linear plots
of kobsd vs amine concentration and are summarized in Table 1.
It is estimated from replicate runs that the uncertainty in the
rate constants is less than 3%.
rate )kN[RNH2][S] ) kobsd[S] where kobsd ) kN[RNH2]
(1)
We have extended our study to aminolyses of 4-nitrophenyl
phenyl carbonate (5) and 4-nitrophenyl phenyl thionocarbonate
(6), a carbonate and its thiono analogue, respectively (Scheme
1). Although scattered information about the reactivity and
mechanism for aminolysis of carbonate and thionocarbonate
compounds is available,1,7,8 the effect of such a modification
of the electrophilic center (e.g., 5 f 6) on reactivity and reaction
mechanism has not been systematically investigated. In the
current study, we have determined the apparent second-order
rate constants (kN) and the microscopic rate constants (k1 and
k2/k-1 ratio) associated with the reactions of 5 and 6 with a
series of primary amines and report the effect of replacing the
oxygen by a polarizable sulfur in the CdO bond of 5 on
reactivity and reaction mechanism.
k1k2
kN )
(2)
k-1 + k2
Effect of Replacing CdO by CdS on Reactivity: HSAB
Principle. It is generally considered that a CdS bond is more
polarizable than a CdO bond, since the overlap between 2p
and 3p orbitals in a CdS bond is not as strong as that between
2p and 2p orbitals in a CdO bond. Thus, the contribution of
6a is expected to be more significant than that of 5a. This
argument is consistent with the 13C NMR spectra for 5 and 6
shown in Supporting Information. The chemical shifts for the
carbon atoms of the CdO in 5 and the CdS bond in 6 are 150.7
and 193.4 ppm, respectively. Such a large downfield shift (42.7
ppm) suggests that the carbon atom of the CdS bond in 6 has
a greater positive charge than that of the CdO bond in 5,
supporting the preceding argument that the contribution of 6a
outweighs that of 5a. Thus, one might expect that 6 is more
electrophilic and more reactive than 5.
Results and Discussion
Reactions of 5 and 6 with primary amines proceeded with
quantitative liberation of 4-nitrophenoxide ion and/or its con-
jugate acid. The kinetic study was performed under pseudo-
first-order conditions, i.e., the amine concentration in excess
over the substrate concentration. All the reactions obeyed first-
order kinetics over 90% of the reaction. Pseudo-first-order rate
constants (kobsd) were calculated from the equation ln(A∞ - At)
) -kobsdt + C. The kobsd values obtained are summarized in
Tables S1-S14 in Supporting Information. The plots of kobsd
vs nucleophile concentration are linear and pass through the
However, Table 1 shows that 6 is less reactive than 5 except
for the reaction with the least basic CF3CH2NH2. A similar
reactivity trend has recently been reported, i.e., O-2,4-dinitro-
phenyl thionobenzoate is less reactive than its oxygen analogue,
2,4-dinitrophenyl benzoate, toward strongly basic pyridines but
more reactive toward weakly basic pyridines.9 Besides, 2 has
been reported to be less reactive than its oxygen analogue 1 in
the reactions with strongly basic hydroxide and ethoxide ions.10
Castro et al. have also demonstrated that bis(4-nitrophenyl)
thionocarbonate is less reactive than its oxygen analogue, bis-
(4-nitrophenyl) carbonate, toward aryloxides.8b A common
(8) (a) Hill, S. V.; Thea, S.; Williams, A. J. Chem. Soc., Perkin Trans.
2 1983, 437-446. (b) Castro, E. A.; Angel, M.; Arellano, D.; Santos, J. G.
J. Org. Chem. 2001, 66, 6571-6575. (c) Castro, E. A.; Pavez, P.; Santos,
J. G. J. Org. Chem. 2003, 68, 3640-3645.
(9) Um, I. H.; Han, H. J.; Baek, M. H.; Bae, S. Y. J. Org. Chem. 2004,
69, 6365-6370.
(10) Kwon, D. S.; Park, H. S.; Um, I. H. Bull. Korean Chem. Soc. 1991,
12, 93-97.
J. Org. Chem, Vol. 71, No. 6, 2006 2303

Um et al.
feature for the reactivity of these compounds is that the
thionocarbonyl compounds are less reactive than their oxygen
analogues toward strongly basic amines or oxy anions.
The CdS bond in 6 is considered to be a soft electrophilic
center due to the high poarizability of S, whereas the CdO bond
in 5 is a hard electrophilic center. The primary amines used in
this study have been classified as hard bases on the basis of
their strong proton basicity.11 Thus, the hard amine bases would
not exhibit high reactivity toward the soft electrophile 6 on the
basis of the hard-soft acids and bases (HSAB) principle. Since
the hardness of amines increases with increase in their basicity,
one might expect that the rate enhancement accompanied by
increasing amine basicity is much less significant for the
reactions of the soft electrophile 6 than for those of the hard
electrophile 5. This argument can be supported by the present
kinetic results. Table 1 demonstrates that as the amine changes
from the least basic CF3CH2NH2 (pKa ) 5.70) to the most basic
C3H7NH2 (pKa ) 10.89), the kN value increases from 4.95 ×
10-3 to 61.0 M-1 s-1 for the reactions of 5 and from 3.35 ×
10-2 to 4.86 M-1 s-1 for the reactions of 6. The increase in the
C3H7NH2
CF3CH2NH2
second-order rate constant (kN
/kN
) on increasing
the amine basicity (e.g., from 5.70 to 10.89) is 1.2 × 104 for
the reaction of 5 but only 1.3 × 102 for the reactions of 6, i.e.,
ca. 2 orders of magnitude smaller.
FIGURE 1. Brønsted-type plots for the reactions of 5 (O) and 6 (b)
with primary amines in H2O containing 20 mol % DMSO at 25.0 (
0.1 °C. The numbers refer to the amines in Table 1. The solid line was
calculated by eq 3.
To get further evidence for the preceding argument that 6
would not exhibit high reactivity toward hard nucleophiles, the
second-order rate constants have been determined for the
-
reactions of 5 and 6 with OH- and N3 ions, a strongly hard
As shown in Figure 1, the Brønsted-type plot for the reaction
of 6 is also nonlinear, i.e., ânuc decreases from 0.68 to 0.11 as
the amine basicity increases. Since it has often been suggested
that the ânuc value should be larger than 0.8 for reactions that
proceed through a stepwise mechanism,15-17 one might insist
that the aminolysis of 6 does not proceed through a stepwise
mechanism, although the Brønsted-type plot is nonlinear. In fact,
Jencks and Castro et al. have attributed such a nonlinear
Brønsted-type plot to a normal Hammond effect for a concerted
reaction with an earlier transition-state for a more reactive
nucleophile.15,16
However, the above argument is inconsistent with the stability
of the tetrahedral intermediate T(. It has generally been reported
that T( is less unstable for reactions of thionocarbonyl
compounds than for those of carbonyl compounds. This has been
attributed to the weaker ability of the C-S- moiety in T( to
form a CdS bond and expel the nucleofuge, when compared
to the C-O- moiety, due to a weaker π-bonding energy of
the thionocarbonyl group relative to the carbonyl group.8 This
argument implies that the lifetime of the tetrahedral intermediate
T( is longer for the reactions of 6 than for those of 5. Thus, the
curved Brønsted-type plot obtained for the aminolysis of 6 can
be interpreted as a change in the RDS, although ânuc is smaller
than 0.8.
base and a borderline one, respectively. As shown in Table 1,
the second-order rate constants for the reactions of OH- ion
with 5 and 6 are 160 and 5.14 M-1 s-1, respectively, whereas
-
those for the reactions of N3 ion with 5 and 6 are 0.258 and
6.78 M-1 s-1, respectively. It is noted that 6 is ca. 30 times
less reactive than 5 toward the hard base OH- ion but ca. 25
times more reactive toward the borderline base N3- ion. More
-
interestingly, N3 is more reactive than the strongly basic
propylamine and OH- in the reaction with 6, although N3 is
-
over 6 and 11 pKa units less basic than propylamine and OH-,
respectively. It follows from the evidence presented here that
the weak interaction between the soft electrophile and the hard
amine nucleophiles might be a plausible cause for the current
result that 6 exhibits lower reactivity than 5 in the reaction with
highly basic amines.
Effect of Replacing CdO by CdS on Mechanism. The
effect of amine basicity on the second-order rate constant kN is
illustrated in Figure 1. The Brønsted-type plot for the reaction
of 5 exhibits a downward curvature, i.e., ânuc decreases from
0.99 to 0.27 as the amine basicity increases. Such a nonlinear
Brønsted-type plot is typical for aminolyses of esters with a
good leaving group and has been interpreted as a change in the
rate-determining step (RDS) of stepwise reactions, i.e., from
breakdown of T( (the k2 step) to its formation (the k1 step) as
the amine basicity increases.1,12-14 Thus, one can suggest that
the current aminolysis of 5 proceeds through T( with a change
in the RDS.
(14) (a) Um, I. H.; Hong, J. Y.; Seok, J. A. J. Org. Chem. 2005, 70,
1438-1444. (b) Um, I. H.; Lee, J. Y.; Lee, H. W.; Nagano, Y.; Fujio, M.;
Tsuno, Y. J. Org. Chem. 2005, 70, 4980-4987. (c) Um, I. H.; Kim, K. H.;
Park, H. R.; Fujio, M.; Tsuno, Y. J. Org. Chem. 2004, 69, 3937-3942. (d)
Um, I. H.; Chun, S. M.; Chae, O. M.; Fujio, M.; Tsuno, Y. J. Org. Chem.
2004, 69, 3166-3172. (e) Um, I. H.; Lee, J. Y.; Kim, H. T.; Bae, S. K. J.
Org. Chem. 2004, 69, 2436-2441.
(15) Song, B. D.; Jencks, W. P. J. Am. Chem. Soc. 1989, 111, 8479-
8484. (b) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334-338.
(16) (a) Castro, E. A.; Aguayo, R.; Besselo, J.; Santos, J. G. J. Org.
Chem. 2005, 70, 7788-7791. (b) Castro, E. A.; Santos, J. G.; Tellez, J.;
Umana, M. I. J. Org. Chem. 1997, 62, 6568-6574.
(17) Oh, H. K.; Ku, M. H.; Lee, H. W.; Lee, I. J. Org. Chem. 2002, 67,
8995-8998.
(11) (a) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in
Organic Chemistry, 3rd ed; Harper: New York, 1987; pp 318-320. (b)
Pearson, R. G. J. Am. Chem. Soc. 1963, 85, 3533-3539.
(12) (a) Jencks, W. P. Chem. ReV. 1985, 85, 511-527. (b) Page, M. I.;
Williams, A. Organic and Bio-organic Mechanisms; Longman: Harlow,
U.K. 1997; Chapter 7.
(13) (a) Lee, I.; Sung, D. D. Curr. Org. Chem. 2004, 8, 557-567. (b)
Oh, H. K.; Lee, J. M.; Sung, D. D.; Lee, I. Bull. Korean Chem. Soc. 2004,
25, 557-559.
2304 J. Org. Chem., Vol. 71, No. 6, 2006

ReactiVity of Carbonate Vs Thionocarbonate
TABLE 2. Summary of Microscopic Rate Constant (k1, M-1 s-1
Associated with Reaction of 4-Nitrophenyl Phenyl Carbonate (5) and
Thionocarbonate (6) with Primary Amines in H2O Containing 20
mol % DMSO at 25.0 ( 0.1 °C
)
To support the above argument that the aminolysis of 6
proceeds through T(, we have performed the reaction of 6 with
morpholine, an alicyclic secondary amine. As shown in Figure
S1 in Supporting Information, the plot of kobsd vs amine
concentration exhibits an upward curvature. Such an upward
curvature is definitive evidence for a reaction that proceeds
through two intermediates, T( and its deprotonated form T-.3,18
It has been reported that the rate of amine expulsion from T(
is slower for the reactions with primary amines than for those
with isobasic secondary amines.3b Accordingly, one can expect
that T( is more stable for the reaction of 6 with primary amines
than for that with morpholine, being consistent with our
preceding proposal that the reaction of 6 with primary amines
proceeds through T( with a change in the RDS.
k1 (M-1 s-1
)
entry
RNH2
pKa
5
6
1
2
3
4
5
6
7
trifluoroethylamine
gylcine ethyl ester
glycylglycine
benzylamine
ethanolamine
ethylamine
5.70
7.68
8.31
9.46
9.67
2.70
13.3
1.35
2.27
2.83
2.85
3.62
4.71
5.07
18.8
30.0
33.0
73.1
67.1
10.67
10.89
propylamine
TABLE 3. Summary of k2/k-1 Ratios for Reaction of
4-Nitrophenyl Phenyl Carbonate (5) and Thionocarbonate (6) with
Primary Amines in H2O Containing 20 mol % DMSO at 25.0 ( 0.1
°C
Microscopic Rate Constants. The nonlinear Brønsted-type
plots shown in Figure 1 have been analyzed using a semi-
empirical equation (eq 3) in which â1 and â2 represent the slope
of the Brønsted-type plot at the high and low pKa region,
respectively.19 The curvature center of curved Brønsted-type
plots has been defined as pKa°, where k-1 ) k2.19 The kN° refers
the kN value at pKa°. The parameters determined from the fitting
of eq 3 to the experimental points are â1 ) 0.27, â2 ) 0.99,
and pKa° ) 9.5 for the reactions of 5, whereas â1 ) 0.11, â2 )
0.68, and pKa° ) 8.5 for the reactions of 6.
k2/k-1
entry
RNH2
pKa
5
6
1
2
3
4
5
6
7
trifluoroethylamine
gylcine ethyl ester
glycylglycine
benzylamine
ethanolamine
ethylamine
5.70
7.68
8.31
9.46
9.67
0.00184
0.0489
0.139
0.936
1.33
0.0254
0.341
0.779
3.53
4.64
17.3
23.0
10.67
10.89
6.96
10.0
propylamine
kN
a
2
log
) â2(pKa - pKa°) - log 1 +
(
[
)
(
)
]
kN°
reactions of 5, and â1 ) 0.11, â2 ) 0.68, and pKa° ) 8.5 for
the reactions of 6.
where log a ) (â2 - â1)(pKa - pKa°) (3)
d(log k2/k-1)
To obtain more information about the reaction mechanism,
the microscopic rate constants involved in the present system
have been determined. As discussed above, the RDS of the
reactions of 5 and 6 with RNH2 is considered to change from
the k2 to the k1 step as the basicity of RNH2 increases. Therefore,
eq 2 can be simplified to eq 4 or 5. Then, â1 and â2 can be
expressed as eqs 6 and 7, respectively.
â2 - â1 )
(8)
(9)
d(pKa)
(log k2/k-1)pKa ) (â2 - â1)(pKa - pKa°)
k
k1 ) kN -1 +1
(10)
(
)
k2
k1k2
kN )
,
when k2 , k-1
(4)
(5)
k-1
Equation 2 can be rewritten as eq 10, which allows one to
calculate the k1 value using the kN values in Table 1 and the
k2/k-1 ratios determined above. The k1 values and the k2/k-1
ratios calculated in this way are summarized in Tables 2 and 3,
respectively.
kN ) k1, when k2 . k-1
d(log k1)
â1 )
Table 2 shows that k1 values are smaller for the reactions of
6 than for those of 5. This is consistent with the preceding
argument that 6 would exhibit a weaker interaction than 5
toward the hard amine bases on the basis of the HSAB principle.
As shown in Figure 2, the Brønsted-type plots for the k1 values
are linear. The slope of the linear plots (â1) is smaller for the
reactions of 6 than for those of 5. This result is also in accord
with the argument that the rate enhancement on increasing amine
basicity would be much less significant for the reactions of 6
than for those of 5.
(6)
(7)
d(pKa)
d(log k1k2/k-1)
d(pKa)
d(log k2/k-1)
â2 )
) â1 +
d(pKa)
Equation 7 can be rearranged as eq 8. Integral of eq 8 from
pKa° to pKa results in eq 9. Since k2 ) k-1 at pKa°, the term
(log k2/k-1 pK ° is zero. Thus, one can calculate the k2/k-1 ratio
for the reactions of 5 and 6 with all the primary amines studied
from eq 9 using â1 ) 0.27, â2 ) 0.99, and pKa° ) 9.5 for the
)
a
Table 3 shows that the k2/k-1 ratio increases with increasing
the amine basicity, i.e., k2/k-1 < 1 when pKa e 9.46 but k2/k-1
> 1 when pKa g 9.67 for the reactions of 5, whereas k2/k-1
<
1 when pKa e 8.31 but k2/k-1 > 1 when pKa g 9.46 for the
reactions of 6. Since a change in the RDS occurs at pKa° where
k2/k-1 ) 1, the k2/k-1 ratios shown in Table 3 are consistent
with the proposed mechanism that the RDS of the aminolyses
of 5 and 6 changes at pKa 9.5 and 8.5, respectively.
(18) Castro, E. A.; Leandro, L.; Quesieh, N.; Santos, J. G. J. Org. Chem.
2001, 66, 6130-6135.
(19) (a) Castro, E. A.; Moodie, R. B. J. Chem. Soc., Chem. Commun.
1973, 828-829. (b) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977,
99, 6963-6970.
J. Org. Chem, Vol. 71, No. 6, 2006 2305

Um et al.
group in 5 by a CdS bond causes a decrease in pKa° by
increasing the k2/k-1 ratio but does not alter the reaction
mechanism.
Conclusions
The present study has allowed us to conclude the following:
(1) The reactivity of 5 and 6 is greatly influenced by the basicity
and hardness of nucleophiles, i.e., 6 is less reactive than 5 toward
strongly basic primary amines and OH- ion but is more reactive
-
toward the weakly basic trifluoroethylamine and N3 ion. (2)
The curved Brønsted-type plots obtained from the aminolyses
of 5 and 6 indicate that these reactions proceed through a
stepwise mechanism with a change in the RDS. (3) The
replacement of the CdO bond in 5 by a polarizable CdS group
affects the reactivity by decreasing the k1 value and increasing
the k2/k-1 ratio. (4) Such a modification of the electrophilic
center does not alter the reaction mechanism but decreases the
pKa° value by increasing the k2/k-1 ratio. (5) The larger k2/k-1
ratio for the reactions of 6 than for those of 5 is responsible for
the decreased pKa° value.
Experimental Section
FIGURE 2. Brønsted-type plots for the reactions of 5 (O) and 6 (b)
with primary amines in H2O containing 20 mol % DMSO at 25.0 (
0.1 °C. The numbers refer to the amines in Table 2.
Materials. 4-Nitrophenyl phenyl carbonate (5) and thionocar-
bonate (6) were prepared as reported.8b,16b,18 Their purity was
checked by their melting points and NMR spectra. Amines and
other chemicals were of the highest quality available. The reaction
medium was H2O containing 20 mol % dimethyl sulfoxide (DMSO)
to eliminate solubility problems. DMSO was distilled over calcium
hydride at a reduced pressure and was stored under nitrogen. Doubly
glass-distilled water was further boiled and cooled under nitrogen
just before use.
Kinetics. The kinetic study was performed using a UV-vis
spectrophotometer equipped with a constant-temperature circulating
bath for slow reactions (t1/2 > 10 s) or a stopped-flow spectro-
photometer for fast reactions (t1/2 e 10 s). The reactions were
followed by monitoring the appearance of 4-nitrophenoxide ion at
405 nm. Typically, the reaction was initiated by adding 5 µL of a
0.02 M substrate stock solution in MeCN by a 10 µL syringe to a
10 mm UV cell containing 2.50 mL of the reaction medium and
nucleophile. The amine stock solution of ca. 0.2 M was prepared
in a 25.0 mL volumetric flask under nitrogen by adding 2 equiv of
amine hydrochloride to 1 equiv of standardized NaOH solution to
obtain a self-buffered solution. All transfers of solutions were carried
out by means of gastight syringes. Concentrations and pseudo-
first-order rate constants are summarized in Tables S1-S18 in
Supporting Information.
Product Analysis. 4-Nitrophenoxide ion was liberated quanti-
tatively and was identified as one of the products by comparison
of the UV-vis spectra after completion of the reactions with those
of the authentic sample under the same kinetic conditions.
FIGURE 3. Plots of log k2/k-1 vs pKa of the conjugate acids of amines
for the reactions of 5 (O) and 6 (b) with primary amines in H2O
containing 20 mol % DMSO at 25.0 ( 0.1 °C. The numbers refer to
the amines in Table 3.
Acknowledgment. This work was supported by a grant from
KOSEF of Korea (R01-2004-000-10279-0).
Supporting Information Available: 13C NMR spectra for 5
and 6; kinetic data for reactions of 5 and 6 with seven primary
It is noted that the dotted lines in Figure 3 exhibit that the
pKa, where log k2/k-1 ) 0, is smaller by ca. 1 pKa unit for the
reactions of 6 than for those of 5. Figure 3 also demonstrates
that the k2/k-1 ratio for a given amine is larger for the reaction
of 6 than for that of 5, which is responsible for the smaller
pKa° value determined for the aminolysis of 6 compared to that
of 5. Thus, one can suggest that the replacement of the CdO
-
amines and two anionic nucleophiles OH- and N3 ions (Table
S1-S18); a plot of kobsd vs amine concentration for the reaction of
6 with morpholine (Figure S1). This material is available free of
charge via the Internet at http://pubs.acs.org.
JO052417Z
2306 J. Org. Chem., Vol. 71, No. 6, 2006