Kinetics and mechanism of the reactions of S-4-nitrophenyl 4-methylthiobenzoate with secondary alicyclic amines and pyridines

Article abstract of DOI:10.1002/poc.1055

The reactions of the title substrate with a series of six secondary alicyclic amines and a series of eight pyridines are subjected to a kinetic investigation in 44 wt% ethanol-water, at 25.0°C, and an ionic strength of 0.2 mol · dm^-3. Under amine excess pseudo first-order rate coefficients (k_obs) are obtained. Plots of k_obs against free amine concentration at constant pH are linear, with the slope (k _N) independent of pH. The Bronsted-type plots (log k _N against pK_a of the conjugate acids of the amines) are non-linear, with the curvature center located at pK_a (pX _a⁰) 9.7 and 9.4, for the reactions of secondary alicyclic amines and pyridines, respectively. The plots are consistent with a zwitterionic tetrahedral intermediate (T^±) on the reaction path and a change in rate-determining step. The greater pK_a⁰ value for secondary alicyclic amines than pyridines is explained by the greater nucleofugality from T^± of secondary alicyclic amines compared to isobasic pyridines. These pK_a⁰ values are lower than those found for the reactions of S-4-nitrophenyl 4-Y-substituted thiolbenzoates (Y = H, Cl, NO₂) with the corresponding amine series. These results indicate that electron donation from the non-leaving group in T ^± favors leaving group expulsion from T^± relative to amine expulsion. Copyright

Full text of DOI:10.1002/poc.1055

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2006; 19: 555–561
Published online 5 June 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.1055
Kinetics and mechanism of the reactions of
S-4-nitrophenyl 4-methylthiobenzoate with
secondary alicyclic amines and pyridinesy
*
´
Enrique A. Castro, Raul Aguayo, Jorge Bessolo and Jose G. Santos
´
´
Facultad de Quımica, Pontificia Universidad Catolica de Chile, Casilla 306, Santiago 6094411, Chile
Received 24 July 2005; revised 23 December 2005; accepted 10 January 2006
ABSTRACT: The reactions of the title substrate with a series of six secondary alicyclic amines and a series of eight
pyridines are subjected to a kinetic investigation in 44 wt% ethanol-water, at 25.08C, and an ionic strength of
0.2 mol ꢀ dmꢁ3. Under amine excess pseudo first-order rate coefficients (kobs) are obtained. Plots of kobs against free
amine concentration at constant pH are linear, with the slope (kN) independent of pH. The Brønsted-type plots (log kN
against pKa of the conjugate acids of the amines) are non-linear, with the curvature center located at pKa (pK0a) 9.7 and
9.4, for the reactions of secondary alicyclic amines and pyridines, respectively. The plots are consistent with a
zwitterionic tetrahedral intermediate (Tꢂ) on the reaction path and a change in rate-determining step. The greater pKa0
value for secondary alicyclic amines than pyridines is explained by the greater nucleofugality from Tꢂ of secondary
alicyclic amines compared to isobasic pyridines. These pK0a values are lower than those found for the reactions of S-4-
nitrophenyl 4-Y-substituted thiolbenzoates (Y ¼ H, Cl, NO2) with the corresponding amine series. These results
indicate that electron donation from the non-leaving group in Tꢂ favors leaving group expulsion from Tꢂ relative to
amine expulsion. Copyright # 2006 John Wiley & Sons, Ltd.
KEYWORDS: kinetics and mechanism; thiobenzoate; aminolysis; pyridinolysis; Brønsted plot; tetrahedral intermediate
INTRODUCTION
results suggest that the pK0a value increases as Y becomes
more electron withdrawing.5
The kinetics and mechanisms of the aminolyses (several
types of amines) of aryl benzoates has been the subject
of many reports.1–5 In contrast, the aminolyses of
aryl thionobenzoates (ArCSOAr),6,7 dithiobenzoates
(ArCSSAr)6,8, and thiolbenzoates (ArCOSAr)9,10 have
received little attention.
The pyridinolysis of 2,4-dinitrophenyl 4-Y-substituted
benzoates in aqueous ethanol shows a curved Brønsted-
type plot for Y ¼ H,5a and linear plots for Y ¼ Cl and
NO2.5b,c The curvature of the former plot is centered at a
pKa value (pK0a) of 9.5. This curve was explained by the
presence of a zwitterionic tetrahedral intermediate (Tꢂ,
Scheme 1) on the reaction pathway and a change in the
rate-determining step, from breaking to products of Tꢂ to
its formation, as basicity of the pyridine increases.5a The
linear Brønsted-type plots for Y ¼ Cl and NO2 show slope
values of ca. 0.9, which indicates that breaking to
products of Tꢂ is rate limiting.5b,c This means that the pKa0
values for these reactions are greater than 9.5. These
The above findings are in accordance with the results
obtained by Gresser and Jencks for the quinuclidinolysis
of diaryl carbonates in water:11 the pKa0 value increases as
the substituent in the non-leaving aryloxy group of the
intermediate increases its electron withdrawing ability.11
Also in agreement are the results obtained for the
benzylaminolysis of 4-nitrophenyl Y-benzoates in aceto-
nitrile:2 the ratio of rate coefficients for amine (kꢁ1) and
4-nitrophenoxide (k2) expulsion from the intermediate Tꢂ
increases with the increasing electron attraction of Y.2
Since it is known that log (kꢁ1/k2) depends linearly on
pKa0,10,12 the above means that the pK0a value increases as
Y becomes more electron withdrawing.
A similar trend was found for the reactions of S-4-
nitrophenyl 4-Y-substituted thiobenzoates (thiolbenzo-
ates) with secondary alicyclic amines in aqueous ethanol:
the pK0a values obtained are 10.0, 10.4, and >10.8 for
Y ¼ H, Cl, and NO2, respectively.10a Also in accordance
is the fact that for the pyridinolysis of the same
thiolbenzoates in the same solvent, the pK0a values are
9.7 for Y ¼ H and >9.9 for Y ¼ Cl and NO2.10b Moreover,
for the pyridinolysis of S-2,4-dinitrophenyl 4-Y-substi-
tuted thiobenzoates (Y ¼ Me, H, Cl, and NO2) in aqueous
ethanol the pK0a values obtained are 8.5, 8.9, 9.5, and 9.9,
respectively.10c
´
*Correspondence to: E. A. Castro, Facultad de Quımica, Pontificia
Universidad Catolica de Chile, Casilla 306, Santiago 6094411, Chile.
´
E-mail: ecastro@puc.cl
ySelected paper presented at the 10th European Symposium on Organic
Reactivity, 25–30 July 2005, Rome, Italy.
Contract/grant sponsor: FONDECYT (Chile); contract/grant number:
1020524.
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 555–561

556
E. A. CASTRO ET AL.
O
C
+
O–
C
O
C
N
thiobenzoates 2, 3, and 4,10a,b in order to confirm or reject
the hypothesis of the increase of pK0a with the electron
+
Ar'O–
Ar
OAr'
Ar
OAr'
Ar
attraction from the Y substituent.2,5,10,11
+
+
N
N
T
EXPERIMENTAL
Materials
Scheme 1
In contrast to the above findings Um et al. have found
that for the reactions of secondary alicyclic amines
with 2,4-dinitrophenyl and 4-nitrophenyl Y-substituted
benzoates in aqueous dimethyl sulfoxide the pK0a value is
independent of the Y substituent.3
The series of secondary alicyclic amines and pyridines
were purified as reported.5,13 4-Hydroxypyridine was
purified by recrystallization in acetone. Thiolbenzoate 1
was synthesized as described.14 Its melting point agreed
with that reported,15 and its 1H and 13C NMR spectra and
elemental analysis were in accordance to its structure.
Thiolbenzoates 2–4 were synthesized as reported.10a
To try to solve the above controversy and to extend our
investigations on the mechanisms of the aminolysis of aryl
thiolbenzoates, in this work we study kinetically the
reactions of secondary alicyclic amines and pyridines with
S-4-nitrophenyl 4-methylthiobenzoate (1) in aqueous
ethanol. To quantify more precisely the pK0a values for
these reactions we have added a new pyridine (4-
oxypyridine) with pKa ¼ 11.5 in order to extend the amine
pKa range previously employed.10b In this work we also
determine the rate coefficients (kN) for the reactions of this
pyridine with the other S-4-nitrophenyl 4-Y-substituted
thiobenzoates (Y¼ H, Cl, and NO2, 2, 3, and 4) previously
studied. This is to obtain more accurate pK0a values for these
reactions than those previously reported.10b The main goal
of this work is to compare the pK0a values for the title
reactions with those obtained for the same aminolyses of
Kinetics
The reactions were followed spectrophotometrically by
monitoring the appearance of 4-nitrobenzenethiolate
anion at 425 nm by means of a Hewlett-Packard 8453
instrument. The reactions were studied in 44 wt%
ethanol-water solution, at 25.0 ꢂ 0.18C and an ionic
strength of 0.2 mol ꢀ dmꢁ3 (maintained with KCl). All
reactions were carried out under excess amine over
thiolbenzoate 1; the initial concentration of the latter was
ca. 5 ꢃ 10ꢁ5 mol ꢀ dmꢁ3
.
Most of the reactions were followed for at least three half-
lives, where pseudo first-order rate coefficients (kobs) were
found. The kobs values for the slow reactions of
piperazinium ion and the four less basic pyridines with
substrate 1 were obtained by the initial rate method.16 This
procedure was used due to the slow reactions and also to
avoid kinetic interference with the very slow oxidation of 4-
nitrobenzenethiolate to yield bis(4-nitrophenyl) disulfide.10b
X
O
C
X
N
H
N
Y
S
NO2
1 (Y = Me)
2 (Y = H)
3 (Y = Cl)
4 (Y = NO2)
sec. alicyclic
amines
pyridines
Table 1. Values of kobs and experimental conditions for the reactions of thiolbenzoate 1 with secondary alicyclic aminesa
b
Amine
pH
FN
102 [N]totc/mol ꢀ dmꢁ3
103kobs/sꢁ1
Number of runs
Piperidine
10.52
10.82
11.12
9.41
9.71
10.01
8.79
9.09
9.39
8.48
8.78
7.63
7.93
5.37
5.67
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
0.50
0.67
0.50
0.67
0.50
0.67
0.50–5.0
0.50–5.0
1.0–5.0
0.50–1.7
0.25–2.2
0.25–2.2
1.0–10
1.0–10
1.0–10
2.5–20
2.5–17
2.1–22
3.8–38
13–61
0.99–4.0
0.92–7.4
1.9–11
0.70–7.4
1.1–11
1.4–14
1.6–13
3.7–14
8
10
8
6
9
7
9
8
8
8
7
7
6
7
8
Piperazine
1-(2-Hydroxyethyl)piperazine
Morpholine
1-Formylpiperazine
Piperaziniun cation
4.0–32
7.9–32
1.0–9.9
1.0–9.9
0.31–2.3
0.81–2.9
0.0001–0.011
0.0008–0.020
a In 44 wt% ethanol-water, at 25.08C, and an ionic strength of 0.2 mol ꢀ dmꢁ3
c Concentration of total amine (free amine plus its conjugate acid).
.
b Free amine fraction.
Copyright # 2006 John Wiley & Sons, Ltd.
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KINETICS OF REACTIONS OF 4-NITROPHENYL 4-METHYLTHIOBENZOATE WITH AMINES
557
Table 2. Values of kobs and experimental conditions for the reactions of thiolbenzoate 1 with pyridinesa
b
Pyridine substituent
4-Oxypyridine
pH
FN
102 [N]totc/mol ꢀ dmꢁ3
103kobs/sꢁ1
Number of runs
11.20
11.50
11.80
9.15
9.45
9.75
8.84
9.14
9.44
8.68
8.98
9.28
7.55
7.85
7.55
7.85
7.55
7.85
7.55
7.85
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
0.817
0.899
0.987
0.993
0.994
0.997
0.998
0.999
0.10–1.0
0.10–0.90
0.10–1.0
0.50–4.5
0.50–4.0
0.50–4.5
1.0–8.9
1.0–8.9
1.0–10
3.0–13
3.0–13
1.5–15
0.25–2.5
0.17–1.2
15–50
5.2–41
22–57
18–90
3.6–28
4.8–32
9.1–40
4.0–35
6.3–46
8.7–76
7
8
7
8
7
7
6
7
8
7
7
8
7
5
8
9
7
6
7
7
3,4-Diamino
4-Dimethylamino
4-Amino
6.4–36
9.8–52
8.9–83
4-Amino-3-bromod
3,4-Dimethyld
4-Methyld
0.027–0.13
0.020–0.076
0.095–0.24
0.030–0.19
0.0070–0.036
0.00082–0.020
0.00081–0.026
0.0045–0.031
9.9–50
8.9–27
1.5–13
9.9–45
9.9–45
3-Methyld
a In 44 wt% ethanol-water, at 25.08C, and an ionic strength of 0.2 mol ꢀ dmꢁ3
b Free amine fraction.
.
c Concentration of total amine (free amine plus its conjugate acid).
d In the presence of phosphate buffer 0.01 mol ꢀ dmꢁ3
.
Table 3. Values of kobs and experimental conditions for the reactions of thiolbenzoates 2–4 with 4-oxypyridinea
b
Thiolbenzoate
pH
FN
102 [N]totc/mol ꢀ dmꢁ3
103kobs/sꢁ1
Number of runs
2
3
4
11.50
11.80
11.20
11.50
11.50
11.80
0.50
0.67
0.33
0.50
0.50
0.67
0.10–0.80
0.10–0.80
0.10–0.90
0.10–1.0
0.01–0.10
0.01–0.10
4.4–50
12–106
17–159
23–253
45–340
6.6-452
8
8
8
8
10
10
a In 44 wt% ethanol-water, at 25.08C, and an ionic strength of 0.2 mol ꢀ dmꢁ3
c Concentration of total amine (free amine plus its conjugate acid).
.
b Free amine fraction.
The values of kobs and the experimental conditions for
the reactions of thiolbenzoate 1 are shown in Tables 1 and
2; those for the reactions of thiolbenzoates 2–4 with 4-
oxypyridine are shown in Table 3.
RESULTS AND DISCUSSION
Under amine excess the rate law obtained for the
reactions of thiolbenzoate 1 is given by Eqns (1) and (2),
where NPSꢁ and N represent 4-nitrobenzenethiolate
anion and the free amine, respectively, and k0 and kN are
the rate coefficients for solvolysis and aminolysis,
respectively, of thiolbenzoate 1. Similar rate equations
were found for the reactions of thiolbenzoates 2–4 with
4-oxypyridine.
Product studies
The products of the reactions of secondary alicyclic
amines with the title thiolbenzoate (1) are 4-nitrobenze-
nethiolate anion and the corresponding 4-methylbenza-
mide. The same benzenethiolate and 4-methylbenzoate
anions were found as products of the reactions with
pyridines. The latter product is due to rapid hydrolysis of
the cationic benzamides formed with pyridines, as found
in the pyridinolysis of thiolbenzoates 2–4.10b
The identification of the above products was carried out
by comparison of the UV-Vis spectra of the kinetic samples
at the end of the reactions (but before the slow oxidation of
4-nitrobenzenethiolate)10b with those of the authentic
products under identical experimental conditions.
d½NPSꢁꢄ
¼ kobs½1ꢄ
(1)
(2)
dt
kobs ¼ k0 þ kN½Nꢄ
Plots of kobs against [N] at constant pH are linear, with
the slopes (kN) independent of pH. The kN values are
shown in Table 4. With the kN values and the pKa of the
conjugate acids of the amines, the Brønsted-type plots for
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 555–561

558
E. A. CASTRO ET AL.
2
1
Table 4. Values of pKa for the conjugate acids of secondary
alicyclic amines and pyridines, and kN values for the reactions
of thiolbenzoate 1 with secondary alicyclic amines and
pyridinesa
Amine
pKa
kN/sꢁ1 ꢀ molꢁ1 ꢀ dm3
0
Piperidine
Piperazine
1-(2-Hydroxyethyl)piperazine
Morpholine
1-Formylpiperazine
Piperaziniun cation
4-Oxypyridineb
3,4-Diaminopyridine
4-(Dimethylamino)pyridine
4-Aminopyridine
10.82
9.71
9.09
8.48
7.63
5.37
11.50
9.45
9.14
8.98
6.90
5.68
5.35
4.92
1.6 ꢂ 0.1
0.70 ꢂ 0.04
0.22 ꢂ 0.01
0.11 ꢂ 0.01
0.014 ꢂ 0.001ꢁ4
(2.7 ꢂ 0.2) ꢃ 10
11 ꢂ 1
-1
-2
-3
-4
-5
1.5 ꢂ 0.1
1.1 ꢂ 0.1
0.84 ꢂ 0.05
ꢁ3
4-Amino-3-bromopyridine
3,4-Dimethylpyridine
4-Methylpyridine
3-Methylpyridine
(5.8 ꢂ 0.3) ꢃ 10
ꢁ4
(4.2 ꢂ 0.3) ꢃ 10
ꢁ4
ꢁ5
(1.6 ꢂ 0.2) ꢃ 10
(7.5 ꢂ 0.5) ꢃ 10
a Both the pKa and kN values were obtained in 44 wt% ethanol-water, at
4
6
8
10
12
25.08C, and an ionic strength of 0.2 mol ꢀ dmꢁ3
.
pKa + log(p/q)
b The kN values obtained for the reactions of 4-oxypyridine with thiol-
benzoates 2, 3, and 4 are 16, 53, and 650 sꢁ1 ꢀ molꢁ1 ꢀ dm3, respectively.
Figure 1. Brønsted-type plots (statistically corrected) for the
reactions of thiolbenzoate 1 with secondary alicyclic amines
(*) and pyridines (*) in 44 wt% ethanol-water, at 25.08C,
ionic strength 0.2 mol ꢀ dmS3
the reactions of thiolbenzoate 1 with secondary alicyclic
amines and pyridines were obtained. These are shown in
Figure 1. The plot for secondary alicyclic amines was
statistically corrected,13b,17 using the values of q ¼ 2 for
piperazine, p ¼ 4 for piperazinium dication and p ¼ 2 for
the conjugate acids of the other secondary alicyclic
amines. The parameter q is the number of equivalent basic
sites in the free amine and p is the number of equivalent
protons in the conjugate acid.13b,17
linear least-squares fitting of Eqn (3) to the experimental
points are: log kN0 ¼ ꢁ0.43 ꢂ 0.05, pK0a ¼ 9.7 ꢂ 0.1,
b2 ¼ 0.92 ꢂ 0.05, and b1 ¼ 0.26 ꢂ 0.05 for the reactions
of secondary alicyclic amines, and log k0N ¼ 0.18 ꢂ 0.05,
pK0a ¼ 9.4 ꢂ 0.1, b2 ¼ 1.05 ꢂ 0.05 and b1 ¼ 0.27 ꢂ 0.08
for the reactions of pyridines.
The curved lines in Figure 1 were calculated through
a semi-empirical equation, Eqn (3), derived on the basis
of the existence of a zwitterionic tetrahedral intermedi-
ate (Tꢂ) on the reaction pathway and a change in the
rate-determining step, from breakdown to products of
Tꢂ to its formation, as the basicity of the amine
increases.13 In this equation, kN0 and pKa0 are the
corresponding parameters at the curvature center and b2
and b1 are the Brønsted slopes at low and high pKa
values, respectively. The best parameters for the non-
logðkN=kN0 Þ ¼ b2ðpKa ꢁ pKa0Þ ꢁ log½ð1 þ aÞ=2ꢄ (3)
where
log a ¼ ðb2 ꢁ b1ÞðpKa ꢁ pKa0Þ
According to the rate law, the product studies and the
Brønsted-type plots obtained for the reactions under
scrutiny, the most likely mechanism for these reactions is
that described in Scheme 2 for secondary alicyclic amines
and Scheme 3 for pyridines. As found for the
O-
O
C
O
k1
k2
Me
S
NO2
Me
C
+
O2N
S-
Me
C
N
S
NO2
H
H
k-1
+
+
N
+
X
H
X
T
N
X
-H+
fast
N
O
Me
C
X
Scheme 2
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 555–561

KINETICS OF REACTIONS OF 4-NITROPHENYL 4-METHYLTHIOBENZOATE WITH AMINES
559
-
O
k
1
O
C
O
C
k
2
-
Me
C
S
+
NO
2
Me
S
NO
Me
+
O N
2
S
2
+
k
-1
N
N
+
X
X
N
T
fast
N
X
H O
2
X
-
+
+
2H+
Me
COO
Scheme 3
pyridinolysis of thiolbenzoates 2–4,10b a good isosbestic
point was obtained for the same aminolysis of thiol-
benzoate 1 (except for the reactions of the three more
basic pyridines), indicating, therefore, that the hydrolysis
of the cationic amidinium intermediate is fast. For the
reactions with the three more basic pyridines, a small
increase and fast decrease of absorbance was observed at
300 nm, which indicates that these intermediates are also
rapidly hydrolyzed, but not as fast as the cationic
intermediates formed from the less basic pyridines.
The larger pK0a value obtained for the reactions of
thiolbenzoate 1 with secondary alicyclic amines in
aqueous ethanol (pK0a ¼ 9.7) relative to that with pyridines
(pK0a ¼ 9.4) is in accordance with the results found for the
reactions of these series of amines with thiolbenzoate 2 in
the same solvent.10a,b For the pyridinolysis of thiolbenzo-
ates 3 and 4, linear Brønsted-type plots up to a pKa value of
9.45 were obtained.10b Quantification of the pK0a value for
these reactions was not possible due to the fact that the
most basic pyridine employed was 3,4-diaminopyridine, of
pKa 9.45.10b
ized in Table 5. The pK0a value found for the pyridinolysis
of 2 including the new pyridine (4-oxypyridine) is the
same (pK0a ¼ 9.7) as that obtained previously without this
amine.10b Due to this new pyridine, quantification of the
pK0a value for the pyridinolysis of 3 and 4 is now possible.
As seen in Table 5, the pKa0 value for the reactions of a
given thiolbenzoate with secondary alicyclic amines is
larger than that with pyridines. This can be attributed to
the greater nucleofugality from the intermediate Tꢂ
(larger k in Schemes 2 and 3) of secondary alicyclic
ꢁ1
amines relative to isobasic pyridines.18 This means a
larger kꢁ1/k2 ratio for former amines since k2 should be
independent of the amine basicity and nature.19 A larger
k
ꢁ1/k2 ratio means a larger pK0a, according to Eqn (4),
4
3
2
In order to quantify the pK0a value for the pyridinolysis
of thiolbenzoates 3 and 4 and to obtain a more precise
value for the same aminolysis of thiolbenzoate 2, we have
determined in this work the kN values for the reactions of
4-oxypyridine (pKa 11.5) with these three thiolbenzoates.
These kN values are shown in Table 4.
1
0
With the values of kN reported for the reactions of
thiolbenzoates 2–4 with seven pyridines,10b and those
found in this work for the reactions of these substrates
with 4-oxypyridine, the Brønsted-type plots shown in
Figures 2 and 3 were obtained. The best fitting
parameters of Eqn (3) to the experimental points are:
log k0N ¼ 0.54 ꢂ 0.04, pKa0 ¼ 9.7 ꢂ 0.1, b2 ¼ 0.94 ꢂ 0.04,
and b1 ¼ 0.22 ꢂ 0.03 for the reactions thiolbenzoate 2;
log k0N ¼ 1.11 ꢂ 0.06, pKa0 ¼ 10.1 ꢂ 0.1, b2 ¼ 0.96 ꢂ 0.04,
and b1 ¼ 0.25 ꢂ 0.04 for the reactions of thiolbenzoate
3; and log k0N ¼ 2.43 ꢂ 0.07, pKa0 ¼ 10.7 ꢂ 0.2, b2 ¼
1.01 ꢂ 0.06, and b1 ¼ 0.22 ꢂ 0.03 for the reactions of
thiolbenzoate 4. The pK0a values obtained for these
reactions, together with those found in the secondary
alicyclic aminolysis of thiolbenzoates 1–4 are summar-
-1
-2
-3
-4
-5
4
6
8
pKa
10
12
Figure 2. Brønsted-type plots for the pyridinolysis of thiol-
benzoates 2 (*) and 4 (*) in 44 wt% ethanol-water, at
25.08C, ionic strength 0.2 mol ꢀ dmS3
Copyright # 2006 John Wiley & Sons, Ltd.
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560
E. A. CASTRO ET AL.
the carbonate favors amine (relative to leaving group)
expulsion from the zwitterionic tetrahedral intermediate,
increasing, therefore, the pK0a value.11 The same trend
was obtained for the reactions of benzylamines with 4-
nitrophenyl Y-benzoates in acetonitrile:2 the ratio of rate
coefficients arising from the intermediate Tꢂ (kꢁ1/k2)
increases with the increasing electron attraction of Y.2
This means that the pK0a value increases as Y becomes
more electron withdrawing.
2
1
0
The above effect has been explained as follows:10,11 as
electron attraction from Y in the intermediate Tꢂ
increases, the central carbon of this intermediate becomes
more positively charged and this enhances the push
provided by the oxygen (or sulfur) atom in the leaving
group to expel the amine (larger kꢁ1). The amine nitrogen
atom in Tꢂ lacks an electron pair to exert its push to expel
the leaving group. Therefore, electron withdrawal from Y
favors amine leaving from Tꢂ, compared to leaving group
expulsion, enlarging the kꢁ1/k2 ratio and, according to
Eqn (4), increasing the pK0a value.
In contrast to the above results, Um et al. have found
that in some aminolysis reactions, the substituents in the
acyl group of aryl benzoates do not affect the pKa0
value.3 For instance, for the reactions of 2,4-dinitro-
phenyl 4-Y-substituted benzoates with secondary ali-
cyclic amines in aqueous DMSO, these workers found
curved Brønsted-type plots centered at pKa ¼ pK0a ¼ 9.1
for Y ¼ MeO, H, and NO2.3a Nonetheless, these plots
exhibit slope values of b1 ¼ 0.40–0.55 (at high pKa) and
b2 ¼ 0.63–0.76 (at low pKa).3a These slopes are not
typical of stepwise mechanisms through a tetrahedral
intermediate. For a two-step mechanism in aqueous
solution the usual slopes are b1 ¼ 0.10–0.3 and
b2 ¼ 0.80–1.1.5a–c,6,10,13,16,18,19 The magnitude of the
Brønsted slopes obtained in the secondary alicyclic
aminolysis of 2,4-dinitrophenyl benzoates in aqueous
DMSO, together with the small Brønsted curvatures
suggests that a concerted mechanism, rather than a
stepwise, governs these reactions. This is based on the
following grounds.
-1
-2
-3
-4
-5
4
6
8
10
12
pKa
Figure 3. Brønsted-type plot for the pyridinolysis of thiol-
benzoate 3 in 44 wt% ethanol-water, at 25.08C, ionic
strength 0.2 mol ꢀ dmS3
which was derived from the hypothesis of the tetrahedral
intermediate.10,12
logðkꢁ1=k2Þ ¼ ðb2 ꢁ b1ÞðpKa0 ꢁ pKaÞ
(4)
As seen in Table 5 for the reactions of a given series of
amines, the pK0a value increases as the substituent Y in the
benzoyl group becomes more electron withdrawing.
The same effect was found by Gresser and Jencks for
the aminolysis of diaryl carbonates in water.11 Electron
attraction from the substituent in the non-leaving group of
(1) We have found that the reactions of secondary ali-
cyclic amines with 2,4-dinitrophenyl 4-cyanobenzo-
ate in aqueous ethanol are ruled by a concerted
mechanism, on the basis of the linear Brønsted-type
plot of slope 0.6 obtained.5d
Table 5. Values of pKa for the center of the Brønsted
curvature (pK0a) for the reactions of 4-nitrophenyl 4-Y-thiol-
benzoates (1–4) with secondary alicyclic (SA) amines and
pyridinesa
(2) Song and Jencks obtained slightly curved Brønsted
plots in the aminolysis of substituted benzoyl fluor-
ides.20 The values of the slopes at low and high pKa
are ca. 0.67 and 0.23, respectively.20 The magnitude
of these slopes and the small difference between their
values at low and high pKa (i.e., small curvatures)
were interpreted as concerted mechanisms.20 Further-
more, the fact that the center of the Brønsted curva-
ture (pKa0) is the same for all the benzoyl fluorides
investigated indicates that these mechanisms are
concerted.20
Thiolbenzoate
SA amines
Pyridines
1 (Y ¼ Me)
2 (Y ¼ H)
9.7 ꢂ 0.1b
10.0 ꢂ 0.2c
10.4 ꢂ 0.2c
>10.8c
9.4 ꢂ 0.1b
9.7 ꢂ 0.1d
10.1 ꢂ 0.1d
10.7 ꢂ 0.2d
3 (Y ¼ Cl)
4 (Y ¼ NO2)
a Reactions carried out in 44 wt% ethanol-water, at 25.08C, and an ionic
strength of 0.2 mol ꢀ dmꢁ3
b Data from this work.
c Data from Ref. 10a.
.
d Values of pK0a obtained from the Brønsted data for seven pyridines
(Ref. 10b) and the data for 4-oxypyridine (this work).
Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 555–561

KINETICS OF REACTIONS OF 4-NITROPHENYL 4-METHYLTHIOBENZOATE WITH AMINES
561
2003; 24: 1251; (c) Um IH, Kim KH, Park HR, Fujio M, Tsuno Y.
J. Org. Chem. 2004; 69: 3937.
The gradual decrease of the Brønsted slope with
increasing amine pKa in a single step has been explained
by a manifestation of a normal Hammond effect, with an
earlier transition state for the more reactive nucleo-
philes.20,21
5. (a) Castro EA, Santander CL. J. Org. Chem. 1985; 50: 3595; (b)
Castro EA, Valdivia JL. J. Org. Chem. 1986; 51: 1668; (c) Castro
EA, Steinfort GB. J. Chem. Soc. Perkin Trans. 2 1983; 453; (d)
Castro EA, Hormazabal A, Santos JG. Int. J. Chem. Kinet. 1998;
30: 267.
6. Castro EA. Chem. Rev. 1999; 19: 3505, and references therein.
7. (a) Um IH, Lee S-E, Kwon HJ. J. Org. Chem. 2002; 67: 8999;
(b) Um IH, Seok JA, Kim HT, Bae S-K. J. Org. Chem. 2003; 68:
7742.
8. Oh HK, Ku MH, Lee HW, Lee I. J. Org. Chem. 2002; 67: 8995.
9. (a) Lee I, Shim CS, Lee HW. J. Chem. Res. (S) 1992; 90; (b) Lee I,
Koo HJ. New J. Chem. 1996; 20: 131; (c) Koo HJ, Han KL, Lee I. J.
Org. Chem. 1999; 64: 4783.
10. (a) Castro EA, Bessolo J, Aguayo R, Santos JG. J. Org. Chem.
2003; 68: 8157; (b) Castro EA, Vivanco M, Aguayo R, Santos JG.
J. Org. Chem. 2004; 69: 5399; (c) Castro EA, Aguayo R, Bessolo J,
Santos JG. J. Org. Chem. 2005; 70: 3530.
Acknowledgements
This work was financially supported by FONDECYT of
Chile, through project 1020524. R.A. thanks DIPUC of
Pontificia Universidad Catolica de Chile for a Doctoral
scholarship.
11. Gresser MJ, Jencks WP. J. Am. Chem. Soc. 1977; 99: 6970.
12. Castro EA, Araneda CA, Santos JG. J. Org. Chem. 1997; 62:
126.
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Copyright # 2006 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2006; 19: 555–561