Kinetics and mechanism of the pyridinolysis of S-2,4-dinitrophenyl 4-substituted thiobenzoates

Article abstract of DOI:10.1021/jo050119w

(Chemical Equation Presented) The reactions of S-2,4-dinitrophenyl 4-methyl (1), S-2,4-dinitrophenyl 4-H (2), S-2,4-dinitrophenyl 4-chloro (3), and S-2,4-dinitrophenyl 4-nitro (4) thiobenzoates with a structurally homogeneous series of pyridines are subjected to a kinetic investigation in 44 wt % ethanol-water, at 25.0°C and an ionic strength of 0.2 M (KCl). The reactions are studied spectrophotometrically (420 nm) by monitoring the appearance of 2,4-dinitrobenzenethiolate anion. Pseudo-first-order rate coefficients (k _obsd) are obtained for all the reactions, employing excess of amine. The plots of k_obsd vs [free pyridine] at constant pH are linear with the slopes (k_N) independent of pH. The Bronsted-type plots (log k_N vs pK_a, of the conjugate acid of the pyridines) are curved for all the reactions. The Bronsted curves are in accordance with stepwise mechanisms, through a zwitterionic tetrahedral intermediate (T^±), and a change in the rate-limiting step. An equation based on this hypothesis accounts well for the experimental points. The Bronsted lines were calculated with the following parameters: Reactions of thiolbenzoate 1: β₁ 0.33 (slope at high pK_a), β₂ 0.95 (slope at low pK_a), and pK_a ⁰ = 8.5 (pK_a at the curvature center); thiolbenzoate 2: β₁ 0.30, β₂ 0.88, and pK_a⁰ = 8.9; thiolbenzoate 3: β₁ 0.33, β₂ 0.89, and pK_a⁰ = 9.5; thiolbenzoate 4: β₁ 0.21, β₂ 0.97, and pK_a⁰ = 9.9. The increase of the pK_a⁰ value with the increase of the electron-withdrawing effect of the acyl substituent is explained by the argument that the rate of pyridine expulsion from T^± (k_-1) is favored over that of 2,4-dinitrobenzenethiolate leaving (k₂), i.e., k_-1/k₂ increases, as the acyl group becomes more electron withdrawing. The pK_a⁰ values for the title reactions are smaller than those for the reactions of the corresponding 4-nitrophenyl 4-substituted thiolbenzoates with the same pyridine series. This is explained by the larger k₂ value for 2,4-dinitrobenzenethiolate leaving from T^± compared with 4-nitrobenzenethiolate, which results in lower k_-1/k₂ ratios for the dinitro derivatives. The pK_a⁰ value obtained for the pyridinolysis of thiolbenzoate 2 (pK_a⁰ = 8.9) is smaller than that found for the same aminolysis of 2,4-dinitrophenyl benzoate (pK_a ⁰ = 9.5). This is attributed to the greater nucleofugality from T^± of 2,4-dinitrobenzenethiolate (pK_a of conjugate acid 3.4) relative to 2,4-dinitrophenoxide (pK_a of conjugate acid 4.1). The title reactions are also compared with the aminolysis of similar esters to assess the effect of the amine nature and leaving and acyl groups on the kinetics and mechanism.

Full text of DOI:10.1021/jo050119w

Kinetics and Mechanism of the Pyridinolysis of
S-2,4-Dinitrophenyl 4-Substituted Thiobenzoates
Enrique A. Castro,* Raul Aguayo, Jorge Bessolo, and Jose´ G. Santos
Facultad de Quı´mica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 22, Chile
ecastro@puc.cl
Received January 20, 2005
The reactions of S-2,4-dinitrophenyl 4-methyl (1), S-2,4-dinitrophenyl 4-H (2), S-2,4-dinitrophenyl
4-chloro (3), and S-2,4-dinitrophenyl 4-nitro (4) thiobenzoates with a structurally homogeneous
series of pyridines are subjected to a kinetic investigation in 44 wt % ethanol-water, at 25.0 °C
and an ionic strength of 0.2 M (KCl). The reactions are studied spectrophotometrically (420 nm) by
monitoring the appearance of 2,4-dinitrobenzenethiolate anion. Pseudo-first-order rate coefficients
(kobsd) are obtained for all the reactions, employing excess of amine. The plots of kobsd vs [free pyridine]
at constant pH are linear with the slopes (kN) independent of pH. The Brønsted-type plots (log kN
vs pKa of the conjugate acid of the pyridines) are curved for all the reactions. The Brønsted curves
are in accordance with stepwise mechanisms, through a zwitterionic tetrahedral intermediate (T(),
and a change in the rate-limiting step. An equation based on this hypothesis accounts well for the
experimental points. The Brønsted lines were calculated with the following parameters: Reactions
of thiolbenzoate 1: â1 0.33 (slope at high pKa), â2 0.95 (slope at low pKa), and pKa0 ) 8.5 (pKa at the
0
curvature center); thiolbenzoate 2: â1 0.30, â2 0.88, and pKa ) 8.9; thiolbenzoate 3: â1 0.33, â2
0
0
0
0.89, and pKa ) 9.5; thiolbenzoate 4: â1 0.21, â2 0.97, and pKa ) 9.9. The increase of the pKa
value with the increase of the electron-withdrawing effect of the acyl substituent is explained by
the argument that the rate of pyridine expulsion from T( (k-1) is favored over that of 2,4-
dinitrobenzenethiolate leaving (k2), i.e., k-1/k2 increases, as the acyl group becomes more electron
withdrawing. The pKa0 values for the title reactions are smaller than those for the reactions of the
corresponding 4-nitrophenyl 4-substituted thiolbenzoates with the same pyridine series. This is
explained by the larger k2 value for 2,4-dinitrobenzenethiolate leaving from T( compared with
0
4-nitrobenzenethiolate, which results in lower k-1/k2 ratios for the dinitro derivatives. The pKa
0
value obtained for the pyridinolysis of thiolbenzoate 2 (pKa ) 8.9) is smaller than that found for
0
the same aminolysis of 2,4-dinitrophenyl benzoate (pKa ) 9.5). This is attributed to the greater
nucleofugality from T( of 2,4-dinitrobenzenethiolate (pKa of conjugate acid 3.4) relative to 2,4-
dinitrophenoxide (pKa of conjugate acid 4.1). The title reactions are also compared with the
aminolysis of similar esters to assess the effect of the amine nature and leaving and acyl groups on
the kinetics and mechanism.
Introduction
The reactions of secondary alicyclic amines with S-4-
nitrophenyl 4-Y-substituted thiobenzoates (Y ) H, Cl,
NO2) in aqueous ethanol are governed by a stepwise
mechanism, through a zwitterionic tetrahedral interme-
diate (T(), as shown by the nonlinear Brønsted-type plots
obtained for the unsubstituted and 4-chloro-substituted
derivatives.4a The Brønsted curves are consistent with a
change in the rate-determining step, from T( breakdown
to its formation, as the amine becomes more basic.4a The
Although the kinetics and mechanisms of the aminoly-
sis of alkyl aryl and diaryl thiocarbonates have been
extensively investigated,1,2 the kinetics of the aminolyses
(various types of amines) of thiobenzoates have attracted
less attention.3,4
(1) Castro, E. A. Chem. Rev. 1999, 99, 3505 and references therein.
10.1021/jo050119w CCC: $30.25 © 2005 American Chemical Society
Published on Web 03/25/2005
3530
J. Org. Chem. 2005, 70, 3530-3536

Pyridinolysis of Dinitrophenyl Thiobenzoates
0
pKa values at the center of the Brønsted curvature (pKa )
To shed more light on the kinetics and mechanisms of
the aminolysis of aryl thiolbenzoates and to clarify the
effect of the substituent in the nonleaving group on the
0
obtained for Y ) H and Cl are pKa ) 10.0 and 10.4,
respectively. For the reactions of the 4-nitro derivative
0
0
the Brønsted-type plot is linear, indicating that pKa
>
pKa value, in the present work we undertake a kinetic
11. Namely, these results suggest that pKa0 increases as
investigation of the pyridinolysis of 2,4-dinitrphenyl
Y-substituted thiolbenzoates 1-4. We have increased the
range of electronic abilities of the substituents, relative
to that in our previous studies,4 by adding a thiolbenzoate
with Y ) Me. We have also extended the pKa range of
the series of pyridines by including a very basic one with
pKa ) 11.5. By introducing a very good leaving group in
the electron-withdrawing effect of substituent
Y
increases.4a
The pyridinolysis of the above thiolbenzoates in the
same solvent shows a nonlinear Brønsted-type plot for
0
Y ) H, with pKa ) 9.7, and linear Brønsted-type plots
for Y ) Cl and NO2 (pKa0 > 9.7).4b These results are not
conclusive in view that quantification of the pKa0 values
was not possible for the reactions of thiolbenzoates with
chloro and nitro substituents, due to the lack of pyridines
with pKa > 9.5.4b
0
the thiolbenzoates, quantification of the pKa value will
0
be easier in view that smaller pKa values are expected
for these reactions compared with those for the corre-
sponding 4-nitrophenyl derivatives.6
The pyridinolysis of 2,4-dinitrophenyl benzoate in
aqueous ethanol exhibits a nonlinear Brønsted-type plot
0
with pKa ) 9.5.5a The corresponding plots for the
pyridinolyses of 2,4-dinitrophenyl 4-Y-substituted ben-
zoates (Y ) Cl, CN, NO2) in the same solvent are linear,
indicating that for these reactions pKa0 > 9.5.5b-d Again,
no firm conclusions regarding the effect of the acyl
substituent on the pKa0 value can be derived due to lack
0
of very basic pyridines for pKa quantification.
For the quinuclidinolysis of diaryl carbonates in water
Gresser and Jencks found that the pKa0 value increases
as the electron-withdrawing ability of the substituent (Y)
in the nonleaving group increases.6 This was explained
through the argument that amine leaving from the
zwitterionic tetrahedral intermediate is favored, over that
of the nucleofuge of the substrate, as Y becomes more
electron withdrawing.6
By comparison of the title reactions with the pyridi-
nolysis of S-4-nitrophenyl 4-substituted thiolbenzoates
5-7 in the same solvent (aqueous ethanol),4b the effect
of the nucleofuge basicity will be examined. Another
objective of the present work is to assess the influence
of the sulfur atom in the nucleofuge on the kinetics and
mechanism. This will be achieved by comparison of the
title reactions in aqueous ethanol with the pyridinolysis
of the corresponding 2,4-dinitrophenyl 4-Y-substituted
benzoates in the same solvent.5
In contrast, for the aminolysis of 2,4-dinitrophenyl 4-Y-
substituted benzoates (Y ) MeO, Me, H, Cl, NO2) in
aqueous solution (20 mol % DMSO) it was concluded that
0
the pKa value does not change by the change of sub-
stituent Y in the benzoyl group.7,8 This conclusion was
Experimental Section
0
achieved by pKa quantification of the nonlinear Brøn-
Materials. The series of pyridines were purified as
reported.5a,11 Thiolbenzoates 1-4 were synthesized by the same
method used for the synthesis of S-4-nitrophenyl 4-substituted
thiolbenzoates.12 The procedure described for the synthesis of
thiolbenzoates 1-4 gave low yields.13 Previously, 2,4-dini-
trobenzenethiol was prepared as reported.14 The IR spectra of
thiolbenzoates 1-4 agreed with those in the literature,15 and
sted-type plots obtained for these reactions.7,8 The same
conclusion was drawn by these authors for the aminoly-
ses of 4-nitrophenyl Y-benzoates9 and 2,4-dinitrophenyl
Y-benzenesulfonates in the same solvent.10
1
their H and 13C NMR spectra and elemental analyses were
(2) (a) Oh, H. K.; Lee, J. Y.; Yun, J. H.; Park, Y. S.; Lee, I. Int. J.
Chem. Kinet. 1998, 30, 419. (b) Humeres, E.; Soldi, V.; Klug, M.; Nunes,
M.; Oliveira, C. M. S.; Barrie, P. J. Can. J. Chem. 1999, 77, 1050. (c)
Oh, H. K.; Lee, Y. H.; Lee, I. Int. J. Chem. Kinet. 2000, 32, 131. (d)
Castro, E. A.; Leandro, L.; Quesieh, N.; Santos, J. G. J. Org. Chem.
2001, 66, 6130. (e) Faissat, L.; Chavis, C.; Montero, J.-L.; Lucas, M. J.
Chem. Soc., Perkin Trans. 1 2002, 1253. (f) Castro, E. A.; Cubillos,
M.; Aliaga, M.; Evangelisti, S.; Santos, J. G. J. Org. Chem. 2004, 69,
2411. (g) Castro, E. A.; Aliaga, M.; Santos, J. G. J. Org. Chem. 2004,
69, 6711.
in accordance with their structures.
Kinetic Measurements. The reactions were followed spec-
trophotometrically through diode array equipment, monitoring
the release of 2,4-dinitrobenzenethiolate anion at 420 nm. The
reactions were carried out in 44 wt % ethanol-water solutions,
at 25.0 ( 0.1 °C, and an ionic strength of 0.2 M (maintained
(3) (a) Campbell, P.; Lapinskas, B. A. J. Am. Chem. Soc. 1977, 99,
5378. (b) Lee, I.; Shim, C. S.; Lee, H. W. J. Chem. Res., Synop. 1992,
90. (c) Oh, H. K.; Shin, C. H.; Lee, I. J. Chem. Soc., Perkin Trans. 2
1995, 1169. (d) Lee, I.; Koh, H. J. New J. Chem. 1996, 20, 131. (e)
Koh, H. J.; Han, K. L.; Lee, I. J. Org. Chem. 1999, 64, 4783. (f) Um,
I.-H.; Seok, J.-A.; Kim, H.-T.; Bae, S.-K. J. Org. Chem. 2003, 68, 7742.
(g) Um, I.-H.; Han, H.-J.; Baek, M.-H.; Bae, S.-Y. J. Org. Chem. 2004,
69, 6365. (h) Oh, H. K.; Lee, J. M.; Lee, H. W.; Lee, I. Int. J. Chem.
Kinet. 2004, 36, 434.
(7) Um, I.-H.; Min, J.-S.; Lee, H.-W. Can. J. Chem. 1999, 77, 659.
(8) Um, I.-H.; Kim, K.-H.; Park, H.-R.; Fujio, M.; Tsuno, Y. J. Org.
Chem. 2004, 69, 3937.
(9) Um, I.-H.; Min, J.-S.; Ahn, J.-A.; Hahn, H.-J. J. Org. Chem. 2000,
65, 5659.
(10) (a) Um, I.-H.; Hong, J.-Y.; Kim, J.-J.; Chae, O.-M.; Bae, S.-K.
J. Org. Chem. 2003, 68, 5180. (b) Um, I.-H.; Chun, S.-M.; Chae, O.-
M.; Fujio, M.; Tsuno, Y. J. Org. Chem. 2004, 69, 3166.
(11) Bond, P. M.; Castro, E. A.; Moodie, R. B. J. Chem. Soc., Perkin
Trans. 2 1976, 68.
(12) Bunton, C. A.; Foroudian, H. J.; Kumar, A. J. Chem. Soc.,
Perkin Trans. 2 1995, 33.
(4) (a) Castro, E. A.; Bessolo, J.; Aguayo, R.; Santos, J. G. J. Org.
Chem. 2003, 68, 8157. (b) Castro, E. A.; Vivanco, M.; Aguayo, R.;
Santos, J. G. J. Org. Chem. 2004, 69, 5399.
(5) (a) Castro, E. A.; Santander, C. L. J. Org. Chem. 1985, 50, 3595.
(b) Castro, E. A.; Steinfort, G. B. J. Chem. Soc., Perkin Trans. 2 1983,
453. (c) Castro, E. A.; Valdivia, J. L. J. Org. Chem. 1986, 51, 1668. (d)
Castro, E. A.; Becerra, M. C. Bol. Soc. Chil. Quim. 1988, 33, 67.
(6) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6970.
(13) Prangova, L. S.; Kvitko, I. Y.; Efros, L. S. Dokl. Bolg. Akad.
Nauk 1971, 24, 1349; Chem. Abstr. 1972, 76, 112332.
(14) Kharasch, N.; Parker, A. J. J. Org. Chem. 1959, 24, 1029.
(15) Prangova, L. S.; Fradkina, S. P.; Vasileva, I. N. Zh. Obsch.
Khim. 1987, 57, 1853; Chem. Abstr. 1988, 108, 185902.
J. Org. Chem, Vol. 70, No. 9, 2005 3531

Castro et al.
TABLE 1. Experimental Conditions and kobsd Values for
the Pyridinolysis of S-2,4-Dinitrophenyl
4-Methylthiobenzoate (1)a
TABLE 3. Experimental Conditions and kobsd Values for
the Pyridinolysis of S-4-Nitrophenyl
4-Chlorothiobenzoate (3)a
no.
no.
103[N]tot
M
/
103kobsd
/
of
pyridine
substituent
103[N]tot
M
/
103kobsd
/
of
c
c
pyridine
substituent
s-1
runs
pH
FN
s-1
runs
b
b
pH
FN
4-oxy
11.2
11.5
0.333 0.55-5.5 39.4-584
0.500 0.55-5.5 105-898
9
9
4-oxy
7.25d 0.000056 1.5-15
0.237-1.86 10
0.805-6.67 10
7.85d 0.00024 1.5-15
3.4-diamino
4-dimethylamino
4-amino
9.15 0.333 0.50-5.0 10.3-105
9.45 0.500 0.50-5.0 13.1-140
8.84 0.333 0.50-5.0 7.22-77.3
9.14 0.500 0.50-5.0 8.54-94.4
8.98 0.500 0.99-9.9 12.3-125
9.28 0.667 0.50-5.0 8.80-93.3
9
3,4-diamino
9.15 0.333
9.45 0.500
9.75 0.667
0.25-2.5 14.2-172
0.25-2.5 22.5-213
0.25-2.5 22.1-278
0.25-2.5 7.36-133
0.25-2.5 7.09-174
0.54-3.4 14.4-109
0.99-5.0 51.8-246
0.50-5.0 0.746-5.36
0.99-5.0 1.31-6.39
10
10
9
9
10
9
4-dimethylamino 8.84 0.333
9.14 0.500
4-amino
10
10
10
9
10
10
10
10
9
8.68 0.333
8.98 0.500
4-amino-3-bromo
3,4-dimethyl
4-methyl
6.90 0.500 2.0-20
7.20 0.667 2.0-20
0.720-9.21
0.853-12.8
4-amino-3-bromo 6.90 0.500
7.20 0.667
3,4-dimethyl
8
5.68 0.500 16.5-165 0.585-5.50
5.98 0.667 16.5-165 0.815-7.43
5.35 0.500 39.6-396 0.681-6.26
5.65 0.667 49.5-495 1.18-9.92
4.92 0.500 39.6-356 0.402-2.73
5.22 0.667 49.5-446 0.503-4.12
8
7
5.68 0.500
5.98 0.667
5.35 0.500
5.65 0.667
4.92 0.500
5.22 0.667
66-330
33-165
5.99-32.5
4.04-21.6
7
10
10
9
8
9
10
4-methyl
39.6-396 1.56-16.9
49.5-495 2.71-28.5
3-methyl
9
3-methyl
39.6-396 0.959-8.84 10
99-495
2.00-13.6
9
a In 44 wt % ethanol-water, at 25.0 °C, ionic strength 0.2 M
(KCl). b Fraction of free amine. c Concentration of total amine (free
amine plus its conjugate acid).
a In 44 wt % ethanol-water, at 25.0 °C, ionic strength 0.2 M
(KCl). b Fraction of free amine. c Concentration of total amine (free
amine plus its conjugate acid). d Under the presence of phosphate
buffer 0.01 M.
TABLE 2. Experimental Conditions and kobsd Values for
the Pyridinolysis of S-2,4-Dinitrophenyl Thiobenzoate
(2)a
TABLE 4. Experimental Conditions and kobsd Values for
the Pyridinolysis of S-4-Nitrophenyl 4-Nitrothiobenzoate
(4)a
no.
of
runs
c
pyridine
substituent
103[N]tot
M
/
103kobsd
/
pH
FN
s-1
no.
b
c
pyridine
substituent
103[N]tot
M
/
103kobsd
/
of
pH
FN
s-1
runs
b
4-oxy
11.2 0.333 0.55-5.5 51.1-890
11.5 0.500 0.55-5.5 167-1450
9.15 0.333 0.10-1.0 2.83-25.8
9.45 0.500 0.20-0.90 3.72-30.0
9.75 0.667 0.10-1.0 3.49-47.2
9
9
10
8
4-oxy
7.25d 0.000056 5.0-50
3.37-43.8
10
9
3.4-diamino
7.85d 0.00024 0.50-5.0 0.745-7.24
7.25d 0.00627 0.50-5.0 6.52-681
3.4-diamino
10
9
10
7
7.55d 0.0124
0.50-4.5 12.1-123
0.50-5.0 5.78-68.7
0.50-5.0 10.0-124
0.50-4.5 5.90-54.8
0.50-4.0 10.3-95.8
0.50-5.0 2.38-25.6
0.50-5.0 3.61-32.3
4.13-41.3 1.58-14.0
4.13-41.3 2.45-18.2
4.13-41.3 0.743-4.72
4-dimethylamino 8.84 0.333 0.10-1.0 2.33-20.3
9.14 0.500 0.10-0.90 3.36-27.6
4-dimethylamino 7.25d 0.0127
7.55d 0.0251
4-amino
9
8
9
9.44 0.667 0.10-1.0 4.25-38.7
9
7.25d 0.0182
7.55d 0.0358
9
4-amino
8.68 0.333 0.10-1.0 0.516-16.0
8.98 0.500 0.10-1.0 1.61-22.8
9.28 0.667 0.10-0.9 1.03-27.4
9
8
9
4-amino-3-bromo 6.90 0.500
7.20 0.667
3,4-dimethyl
10
10
10
10
9
8
4-amino-3-bromo 6.60 0.333 1.0-10
6.90 0.500 1.0-9.0
0.934-5.69
0.828-7.41
1.18-8.89
8
5.68 0.500
5.98 0.667
5.35 0.500
5.65 0.667
4.92 0.500
5.22 0.667
9
7.20 0.667 1.0-10
8
4-methyl
3,4-dimethyl
5.38 0.333 1.0-10
5.68 0.500 1.0-10
5.98 0.667 1.0-10
5.05 0.333 1.0-10
5.35 0.500 1.0-10
5.65 0.667 1.0-10
4.62 0.333 1.0-9.0
4.92 0.500 1.0-10
5.22 0.667 1.0-10
4.33 0.333 10-90
4.63 0.500 10-100
4.93 0.667 10-100
0.110-0.435
0.135-0.635
0.123-0.753
0.0635-0.241
8
4.13-41.3 0.810-7.31 10
8
3-methyl
2.5-25
2.5-25
0.472-1.73
0.362-2.14
6
9
7
4-methyl
8
a In 44 wt % ethanol-water, at 25.0 °C, ionic strength 0.2 M
(KCl). b Fraction of free amine. c Concentration of total amine (free
amine plus its conjugate acid). d Under the presence of phosphate
buffer 0.01 M.
0.0706-0.368 10
0.0918-0.416
0.0506-0.139
0.0502-0.207
0.0365-0.238
0.101-0.533
0.120-0.820
0.130-0.928
8
7
8
8
8
7
7
3-methyl
unsubstituted
tometer. The experimental conditions of the reactions and kobsd
values are shown in Tables 1-4.
Determination of pKa. The pKa value of the conjugate acid
of 4-oxypyridine anion was determined by a spectrophotometric
method,16 in 44 wt % ethanol-water, at 25.0 ( 0.1 °C, and an
ionic strength of 0.2 M (maintained with KCl). The value found
is 11.5 ( 0.1. A similar value (pKa ) 11.3) was obtained by
Um and co-workers in 80 mol % water/20 mol % DMSO at the
same temperature.3g
Product Studies. One of the products of the title reactions
was identified as 2,4-dinitrobenzenethiolate anion. The other
final product is the corresponding benzoate anion. This was
concluded by comparison of the UV-vis spectra after comple-
tion of the reactions with those of an equimolar mixture of
a In 44 wt % ethanol-water, at 25.0 °C, ionic strength 0.2 M
(KCl). b Fraction of free amine. c Concentration of total amine (free
amine plus its conjugate acid).
with KCl). Two or three pH values were employed for the
reactions of each pyridine. For most reactions the pH was kept
constant by partial protonation of the pyridines. For the very
fast reactions of thiolbenzoate 3 with the most basic pyridine
and thiolbenzoate 4 with the four more basic pyridines,
phosphate was employed as buffer. At least a 10-fold excess
of total amine over the substrate was used throughout. The
initial substrate concentration was (2-5) × 10-5 M in all runs.
Pseudo-first-order rate coefficients (kobsd) were obtained in
all cases by means of the kinetic software of the spectropho-
(16) Albert, A.; Serjeant, E. P. The Determination of Ionization
Constants; Chapman and Hall: London, UK, 1971; p 44.
3532 J. Org. Chem., Vol. 70, No. 9, 2005

Pyridinolysis of Dinitrophenyl Thiobenzoates
TABLE 5. Values of pKa for the Conjugate Acids of Pyridines and Those of kN for the Pyridinolysis of
S-2,4-Dinitrophenyl 4-Methylhiobenzoate (1), S-2,4-Dinitrophenyl Thiobenzoate (2), S-2,4-Dinitrophenyl
4-Chlorothiobenzoate (3), and S-2,4-Dinitrophenyl 4-Nitrothiobenzoate (4)a
kN/s-1 M-1
pyridine
substituent
pKa
1
2
3
4
4-oxy
11.5
9.45
9.14
8.98
6.90
5.68
5.35
4.92
4.63
320 ( 20
59 ( 4
500 ( 30
79 ( 6
2100 ( 150
190 ( 14
15000 ( 1000
2200 ( 140
1050 ( 70
680 ( 40
3,4-diamino
4-dimethylamino
4-amino
43 ( 2
60 ( 4
160 ( 12
27 ( 2
1.0 ( 0.1
0.068 ( 0.004
0.031 ( 0.002
0.014 ( 0.001
49 ( 3
1.5 ( 0.1
0.11 ( 0.01
0.060 ( 0.004
0.033 ( 0.002
0.015 ( 0.001
100 ( 7
2.0 ( 0.1
0.20 ( 0.01
0.089 ( 0.006
0.044 ( 0.003
4-amino-3-bromo
3,4-dimethyl
4-methyl
3-methyl
none
14 ( 1
0.65 ( 0.04
0.26 ( 0.02
0.12 ( 0.01
a Both the pKa and kN values were determined in 44 wt % ethanol-water, at 25.0 °C, ionic strength 0.2 M (KCl).
authentic samples of 2,4-dinitrobenzenethiolate and the cor-
responding benzoate anion, under the same experimental
conditions of the kinetic measurements.
An intermediate was detected spectrophotometrically (300-
302 nm) in some reactions. This is presumably the amidic
cation, 1-(4-substituted-benzoyl)pyridinium, as described for
the pyridinolysis of thiolbenzoates 5-7.4b
For some of the slowest reactions studied a slow decrease
of absorbance at 420 nm was observed This is presumably due
to dimerization of 2,4-dinitrobenzenethiolate anion to form bis-
(2,4-dinitrophenyl) disulfide, as found for 4-nitrobenzenethi-
olate anion.4b This reaction was not a problem for the deter-
mination of the kobsd values for the title reactions (as was for
the pyridinolysis of thiolbenzoates 5-7),4b since the title
reactions are much faster than those involving the mononi-
trophenyl derivatives (5-7).
Results and Discussion
The kinetic behavior shown by the reactions under the
present investigation is given by eqs 1 and 2, where
DNPS-, S, and N represent 2,4-dinitrobenzenethiolate
anion, the corresponding thiolbenzoate, and the free
pyridine, respectively. The rate coefficients k0 and kN are
those for solvolysis and pyridinolysis of the substrates,
FIGURE 1. Brønsted-type plots obtained for the pyridinolysis
of 1 (O) and 3 (b) in 44 wt % ethanol-water, at 25.0 °C, and
an ionic strength of 0.2 M (KCl).
respectively.
d[DNPS-]
) kobsd[S]
(1)
(2)
Figures 1 and 2 show the Brønsted-type plots obtained
with the data in Table 5. According to the shape and slope
values of these plots the most likely mechanism for these
reactions is the stepwise process (Scheme 1), through a
zwitterionic tetrahedral intermediate (T() and a change
in the rate-determining step, from breakdown of T( to
products (k2 step) to formation of T( (k1 step), as the
amine becomes more basic.1-8,11,17
dt
kobsd ) k0 + kN[N]
For all reactions the value of k0 was much lower than
that of kN[N] in eq 2. The values of kN were obtained as
the slopes of linear plots of kobsd against [N], and found
to be pH independent. The values of kN are shown in
Table 5, together with the pKa values of the conjugate
acids of the pyridines.
As seen in Table 5 the kN values increase as both amine
basicity and electron withdrawal from the benzoyl sub-
stituent increases, as was found for the aminolysis of
similar esters and carbonates.1,3-9,17 The kN values in
Table 5 are larger than the corresponding ones obtained
for the pyridinolysis of thiolbenzoates 5-7.4b This is
reasonable taking into account the two nitro groups in
the nucleofuge of substrates 1-4 (compared to only one
in thiolbenzoates 5-7), which increases both amine
attack toward the former compounds and the nucleofu-
gality of 2,4-dinitrobenzenethiolate, compared to that of
4-nitrobenzenethiolate.
On the basis of the hypothesis of the intermediate T(
on the reaction pathway a semiempirical equation (eq 3)
can be derived that involves four parameters:1,4-6,11,17 kN
0
0
and pKa , which are the values of kN and pKa at the
curvature center (where k-1 ) k2), and â1 and â2, which
are the slopes at high and low pKa values, respectively.
The best fitting parameters of this equation to the
experimental points are shown in Table 6. The curved
lines exhibited in Figures 1 and 2 were calculated by this
equation with the parameters shown in Table 6.
0
log(kN/kN0) ) â2(pKa - pKa ) - log((1 + a)/2)
0
log a ) (â2 - â1)(pKa - pKa )
(3)
J. Org. Chem, Vol. 70, No. 9, 2005 3533

Castro et al.
For the reactions of quinuclidines (tertiary alicyclic
amines) with Y-substituted-phenyl 3,4-dinitrophenyl car-
bonates (Y ) H, 4-acetyl, and pentafluoro) in water it
was found that the pKa0 value increases with the increas-
ing electron withdrawal of the Y substituent in the
nonleaving group of the carbonate.6
In accordance with the results above, Lee and co-
0
workers have reported a larger pKa value for the
aminolysis of a dithioester possessing 2-furyl as the
substituent in the acyl group relative to the correspond-
ing values for the same aminolysis of the corresponding
dithioesters with Me and Ph as acyl substituents.18 The
larger pKa0 for the former reactions was attributed to the
stronger electron-withdrawing effect exerted by 2-furyl
compared to those by the other substituents.18
The effect of the substituent in the nonleaving group
of a diaryl carbonate or in the acyl group of a thiolester
0
upon the pKa value has been explained as follows:4b,6,19
as the substituent increases its electron attraction the
central carbon of the zwitterionic tetrahedral intermedi-
ate (T() becomes more positive and favors the push
provided by the oxygen or sulfur atom in the leaving
group of T( to expel the amine. The cationic amino moiety
in T( cannot exert its push to expel the nucleofuge due
to the lack of an electron pair. Therefore, electron-
withdrawing substituents in the nonleaving or acyl group
favor amine expulsion from T( relative to that of the
nucleofuge, increasing therefore the ratio k-1/k2 (see
Scheme 1).4b,6,19 By applying the steady-state treatment
to the tetrahedral intermediate in a stepwise reaction,
eq 4 can be deduced.20 Since the values of â1 and â2 do
not change significantly with the nature of the sub-
FIGURE 2. Brønsted-type plots obtained for the pyridinolysis
of 2 (O) and 4 (b) in 44 wt % ethanol-water, at 25.0 °C, and
an ionic strength of 0.2 M (KCl).
SCHEME 1
strate,1,3-5,11,17 eq 4 shows that pKa increases with the
0
increase of the k-1/k2 ratio.
log(k-1/k2) ) (â2 - â1)(pKa0 - pKa)
(4)
TABLE 6. Values of the Fitting Parameters of the
Equation Based on the Stepwise Mechanism for the
Pyridinolysis of Thiolbenzoates 1-4
0
The same effect of Y on pKa was suggested for the
reactions of secondary alicyclic amines with thiolben-
zoates 5-7, where the pKa0 values are 10.0 and 10.4 for
the reactions of the substrates with Y ) H (5) and Cl
(6), respectively.4a The reactions of the thiolbenzoate with
Y ) NO2 (7) exhibit a linear Brønsted-type plot of slope
parameter
1
2
3
4
0
log kN
1.23 ( 0.20 1.63 ( 0.25 2.36 ( 0.44 3.56 ( 0.47
0
pKa
8.5 ( 0.3
8.9 ( 0.4
9.5 ( 0.6
9.9 ( 0.7
â1
0.33 ( 0.04 0.30 ( 0.05 0.33 ( 0.07 0.21 ( 0.09
0.95 ( 0.04 0.88 ( 0.04 0.89 ( 0.04 0.97 ( 0.07
â2
R2 a
0.9995
0.9994
0.9995
0.9985
0.81, indicating that pKa > 11.4a
0
The pyridinolysis of thiolbenzoate 5 in 44 wt % ethan-
a R is the correlation coefficient.
0
ol-water shows a nonlinear Brønsted-type plot with pKa
) 9.7, whereas thiolbenzoates 6 and 7 exhibit linear plots
of slopes 0.94 and 1.0, respectively, indicating pKa0 > 9.7
for Y ) Cl and NO2.4b These results also suggest the
The values of â1 and â2 in Table 6 are in accordance
with those obtained in the aminolysis of similar esters
and carbonates, and their thio analogues, when formation
and breakdown of the tetrahedral intermediate (T(),
respectively, is the rate-determining step.1-6,11,17 The
usual â values are 0.1-0.3 for rate-limiting formation of
T(, and â ) 0.8-1 for decomposition to products of this
intermediate.1-6,11,17
0
above effect of the Y substituent on the pKa value,
although these results are not conclusive due to the lack
0
of quantification of the pKa values for the two latter
thiolbenzoates. This quantification was not possible since
pyridines more basic than 9.7 were not employed in the
kinetic study.4b It is noteworthy that, for the title reac-
tions, quantification of the pKa0 values for thiolbenzoates
with Y ) Cl and NO2 was possible due to the inclusion
Table 6 shows that the pKa values at the curvature
0
center of the Brønsted-type plots (pKa ) increase as the
Y substituent in the benzoyl moiety becomes more
electron withdrawing. This effect is in accordance with
the results found in the quinuclidinolysis of diaryl
carbonates6 and in the aminolysis of dithioesters.18 The
(17) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6963.
(18) Oh, H. K.; Ku, M. H.; Lee, H. W.; Lee, I. J. Org. Chem. 2002,
67, 8995.
(19) Koh, H. J.; Lee, H. C.; Lee, H. W.; Lee, I. Bull. Korean Chem.
Soc. 1995, 16, 839.
(20) Castro, E. A.; Araneda, C. A.; Santos, J. G. J. Org. Chem. 1997,
62, 126.
0
same influence of substituent Y on pKa was suggested
for the aminolyses of thiolbenzoates 5-7 and 2,4-dini-
trophenyl benzoate.4,5
3534 J. Org. Chem., Vol. 70, No. 9, 2005

Pyridinolysis of Dinitrophenyl Thiobenzoates
of a much more basic pyridine (4-oxypyridine) and a
better leaving group, compared to those used in the
pyridinolysis of thiolbenzoates 5-7.
more in agreement with those found in some concerted
reactions.23
Song and Jencks have studied kinetically the reactions
of primary amines with substituted benzoyl fluorides in
water and found slightly curved (â1 ) 0.23, â2 ) 0.67)
Brønsted-type plots, with the pKa value at the curvature
0
The smaller pKa value obtained in the pyridinolysis
0
of thiolbenzoate 2 (pKa ) 8.9, Table 6), relative to that
0
found in the same aminolysis of thiolbenzoate 5 (pKa
)
9.7),4b can be explained by the superior leaving ability
from T( of 2,4-dinitrobenzenethiolate, relative to that of
4-nitrobenzenethiolate, as reflected by the lower basicity
of the former: the pKa values of conjugate acids are 3.4
and 4.6, respectively.21 This means a larger k2 value for
the reactions of thiolbenzoate 2, and therefore, a smaller
center (pKa ) 9.1) independent of the benzoyl sub-
0
stituent.23a This independence is typical of concerted
reactions.23a The slight Brønsted curvature represents a
normal Hammond effect for a concerted reaction, with
an earlier transition state for a more reactive nucleo-
phile.23a,24 Brønsted-type plots slightly curved (â1 ) 0.10,
â2 ) ca. 0.5) were also obtained in the concerted reactions
of secondary alicyclic amines with bis(4-nitrophenyl)
thionocarbonate23b and 2,4-dinitrophenyl 4-methylphenyl
carbonate.23c
0
pKa value, according to eq 4.
A curved Brønsted-type plot has been found for the
pyridinolysis of 2,4-dinitrophenyl benzoate in 44 wt %
ethanol-water, with pKa ) 9.5.5a The corresponding
0
plots for the pyridinolysis of analogous 4-substituted
benzoates with 4-Cl-, 4-CN-, and 4-NO2-substituents are
linear with slopes ca. 0.9, indicating pKa0 > 9.5.5b-d Again,
Another kinetic result that suggests that the reactions
of secondary alicyclic amines with 2,4-dinitrophenyl 4-Y-
substituted benzoates in water-20 mol % DMSO are
concerted is the linear Brønsted-type plot of slope 0.6
obtained for the reactions of the same amines with 2,4-
dinitrophenyl 4-cyanobenzoate in aqueous ethanol.25 The
value of the Brønsted slope for the latter reactions is
within the typical range (â ) 0.4-0.7) of those found in
the concerted aminolysis of esters and carbonates and
their thio derivatives.1,26
If the reactions of secondary alicyclic amines with 2,4-
dinitrophenyl 4-Y-substituted benzoates are concerted it
is more likely that those of the same amines with
thiolbenzoates 1-4 be concerted in view of the better
leaving group involved in the latter reactions.
The reason for the stepwise pyridinolysis of the title
thiolbenzoates in contrast to the probable concerted
reactions of secondary alicyclic amines with these sub-
strates can be found in the superior nucleofugality from
the tetrahedral intermediate (T() of the latter amines
compared to isobasic pyridines.1,4,18,20,25 Therefore, the
change of a pyridino moiety in T( by an isobasic second-
ary alicyclic amino destabilizes T(, in some cases to the
point of nonexistence, and the mechanism becomes
enforced concerted.27 There are many examples in the
literature of reactions of reactive esters and carbonates
and their thio analogues with pyridines that are stepwise,
in contrast to those of the same substrates with secondary
alicyclic amines which are concerted.1,25,26b,c,28
0
it was not possible to quantify the pKa values for the
latter reactions, preventing, therefore, a clear conclusion
regarding the influence of the acyl substituents on the
pKa position at the center of the Brønsted curvature. The
0
smaller pKa value found in the pyridinolysis of thiol-
0
benzoate 2 in the same solvent (pKa ) 8.9, this work)
can be explained by the greater nucleofugality of 2,4-
dinitrobenzenethiolate (pKa ) 3.4)21 from T( than 2,4-
dinitrophenoxide (pKa 4.1).22 According to eq 4, a larger
0
k2 implies a lower pKa value, as found.
In contrast to the results obtained in the title reactions,
and others,6,18 concerning the influence of the substituent
0
in the acyl or nonleaving groups upon the pKa values,
Um and co-workers have claimed that for the aminolysis
of 2,4-dinitrophenyl and 4-nitrophenyl 4-substituted
benzoates7-9 and 2,4-dinitrophenyl substituted benzene-
sulfonates,10 all in water-20 mol % DMSO, there is no
0
effect of the acyl substituents on the pKa values.
For the reactions of a series of secondary alicyclic
amines with 2,4-dinitrophenyl 4-Y-substituted benzoates,
Um and co-workers found curved Brønsted-type plots for
Y ) MeO, Me, H, Cl, and NO2, with the center of the
plots located at pKa ) 9.1 for all substituents.7 The
Brønsted curves were attributed to a stepwise mechanism
and a change in the rate-determining step, and it was
0
claimed that no change in the pKa value was observed
with the change of substituents.7 Nevertheless, for the
reactions of the benzoates with Y ) MeO, H, and NO2
the values of the Brønsted slopes obtained at high pKa
(â1) are 0.48, 0.38, and 0.55, respectively, which are too
large compared to those normally found (â1 ) 0.1-0.3)
for rate-determining formation of the zwitterionic tetra-
hedral intermediate (T().1,4-6,11,17-20 On the other hand,
for the reactions of the benzoates with Y ) MeO and H,
the slope values found at low pKa (â2) are 0.64 and 0.66,
respectively, which are too small relative to those usually
obtained (â2 ) 0.8-1.1) for rate-limiting breakdown of
T( to products.1,4-6,11,17-20 Therefore, for all these reac-
tions the Brønsted curvatures are too slight (the differ-
ence of â2 - â1 values are too small) compared to those
observed in stepwise aminolysis; these Brønsted plots are
For the reactions of secondary alicyclic amines with
4-nitrophenyl Y-substituted benzoates in water-20 mol
% DMSO, linear Brønsted-type plots of slope 0.8-0.9
were obtained, which are in accordance with stepwise
mechanisms where breakdown to products of the inter-
mediate T( is rate determining.9 The pKa value of the
(23) (a) Song, B. D.; Jencks, W. P. J. Am. Chem. Soc. 1989, 111,
8479. (b) Castro, E. A.; Santos, J. G.; Tellez, J.; Uman˜a, M. I. J. Org.
Chem. 1997, 62, 6568. (c) Castro, E. A.; Andujar, M.; Campodonico,
P.; Santos, J. G. Int. J. Chem. Kinet. 2002, 34, 309.
(24) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334.
(25) Castro, E. A.; Hormazabal, A.; Santos, J. G. Int. J. Chem. Kinet.
1998, 30, 267.
(26) (a) Chrystiuk, E.; Williams, A. J. Am. Chem. Soc. 1987, 109,
3040. (b) Castro, E. A.; Cubillos, M.; Santos, J. G. J. Org. Chem. 2001,
66, 6000. (c) Castro, E. A.; Aliaga, M.; Campodonico, P.; Santos, J. G.
J. Org. Chem. 2002, 67, 8911. (d) Castro, E. A.; Campodonico, P.; Toro,
A.; Santos, J. G. J. Org. Chem. 2003, 68, 5930.
(27) Jencks, W. P. Chem. Soc. Rev. 1981, 10, 345. Williams, A. Chem.
Soc. Rev. 1994, 23, 93.
(28) Castro, E. A.; Pizarro, M. I.; Santos, J. G. J. Org. Chem. 1996,
61, 5982.
(21) Castro, E. A.; Ureta, C. J. Chem. Soc., Perkin Trans. 2 1991,
63.
(22) Reference 16, p 87.
J. Org. Chem, Vol. 70, No. 9, 2005 3535

Castro et al.
conjugate acid of the most basic amine employed (pip-
eridine) is ca. 11; therefore, for all these reactions the
Brønsted break is centered at pKa0 > 11. It was claimed
in this work that since no change in the rate-determining
step with the change of Y substituents was observed,
Brønsted break are all consistent with a stepwise mech-
anism.21 The kN values obtained in these reactions are
larger than those found in the reactions of the same
amines with thiolbenzoate 2 (this work, Table 5),21 both
when formation and breakdown of the tetrahedral inter-
mediate is rate limiting. For the reactions of 4-(dimethyl-
amino)pyridine, for which the first step of Scheme 1 is
rate determining, the kN (k1 in Scheme 1) value is 10-
fold larger for thiolacetate 8, whereas for the reactions
of 4-methylpyridine, 3-methylpyridine, and pyridine (sec-
ond step rate limiting) the kN values are 480-, 520-, and
400-fold larger for the thiolacetate. The former result can
be explained by steric hindrance toward amine attack by
phenyl in the acyl group of thiolbenzoate 2, compared to
the methyl group in thiolacetate 8. The larger kN values
for the reactions of the thiolacetate when the second step
of Scheme 1 is rate determining (kN ) k1k2/k-1) can be
attributed to a greater k1 and a much greater k2/k-1 ratio
for thiolacetate 8. The latter is due to a greater electron-
0
there is no influence of Y on the pKa value.9 We think
this is not the right conclusion from the kinetic results.
It must be taken into account that it is very likely that
0
the pKa value for these reactions be much larger than
11. This is because of the following: (i) 4-Nitrophenoxide
is a relatively poor nucleofuge (for instance compared to
2,4-dinitrophenoxide), which means a relatively small k2
0
and, according to eq 4, high pKa . This is why almost
always the Brønsted-type plots involving 4-nitrophenox-
ide as leaving group are linear with high slopes and
0
quantification of pKa is not possible. (ii) Secondary
alicyclic amines are relatively good leaving groups (for
instance compared to isobasic pyridines, see above),
which means large k-1 values (relative to those for
isobasic pyridines). According to eq 4 this means larger
pKa0 values. Therefore, it is very unlikely that the change
of a Y substituent, even from 4-NO2 to 4-MeO, could be
so drastic as to change the rate-limiting step, from the
k2 step for NO2 to the k1 step for MeO. According to Um
and co-workers to produce such a change in rate-
determining step a Y substituent of σ ) -6.4 would be
needed, which does not exist.9
donating effect by Me compared to Ph.29 The larger pKa
0
value found for the pyridinolysis of thiolbenzoate 2 (8.9,
this work), relative to that obtained in the same ami-
nolysis of thiolacetate 8 (6.6),21 can also be explained by
the greater electron-withdrawing ability of phenyl in the
former compound compared to that of methyl in thiol-
acetate 8. This results in a larger k-1/k2 ratio for thiol-
0
benzoate 2 and, according to eq 4, a larger value of pKa
for the latter reactions, as found.
For the pyridinolysis of 2,4-dinitrophenyl thiolacetate
(8) a curved Brønsted-type plot centered at pKa ) 6.6 was
Acknowledgment. We thank FONDECYT of Chile
(project 1020524) for financial assistance to this work.
R.A. thanks “Direccio´n de Investigacio´n y Postgrado de
Pontificia Universidad Cato´lica de Chile” (DIPUC) for
a Doctoral scholarship.
JO050119W
found.21 The values of the slopes at high and low pKa (â1
) 0.2 and â2 ) 0.85, respectively) and the value of the
(29) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
3536 J. Org. Chem., Vol. 70, No. 9, 2005