Aminolysis and pyridinolysis of O-aryl S-(4-nitrophenyl) thiocarbonates in aqueous ethanol. Kinetics and mechanism

Article abstract of DOI:10.1002/poc.1312

The reactions of O-phenyl S-(4-nitrophenyl) thiocarbonate (PNPTC) and 0-(4-chlorophenyl) S-(4-nitrophenyl) thio-carbonate (CIPNPTC) with a series of secondary alicyclic (SA) amines and pyridines are subjected to a kinetic investigation in 44 wt% ethanol-water, at 25.0°C and an ionic strength of 0.2 M. The reactions are followed spectrophotometrically at 420 nm (4-nitrobenzenethiolate anion appearance). Under amine excess, pseudo-first-order rate coefficients (K_obs) are found. For all these reactions, plots of K_obs vs free amine concentration at constant pH are linear, the slope (K_n) being independent of pH. The Bronsted-type plots (log k_n vs pK_a of the conjugate acid of the amines) for the reactions of the series of SA amines with PNPTC and CIPNPTC are linear with slopes 0.59 and 0.54, respectively. The values of these slopes are in accordance with a concerted mechanism. The Bronsted-type plots for the pyridinolysis reactions are biphasic, suggesting a stepwise mechanism with a change in the rate-determining step, from breakdown to formation of a tetrahedral intermediate, as the basicity of the pyridines increases. Copyright

Full text of DOI:10.1002/poc.1312

Research Article
Received: 29 October 2007,
Revised: 27 November 2007,
Accepted: 28 November 2007,
Published online in Wiley InterScience: 24 January 2008
(www.interscience.wiley.com) DOI 10.1002/poc.1312
Aminolysis and pyridinolysis of O-aryl
S-(4-nitrophenyl) thiocarbonates in aqueous
ethanol. Kinetics and mechanism
a
a
a
*
´
Enrique A. Castro , Margarita Aliaga and Jose G. Santos
The reactions of O-phenyl S-(4-nitrophenyl) thiocarbonate (PNPTC) and O-(4-chlorophenyl) S-(4-nitrophenyl) thio-
carbonate (ClPNPTC) with a series of secondary alicyclic (SA) amines and pyridines are subjected to a kinetic investigation
in 44 wt% ethanol–water, at 25.0-C and an ionic strength of 0.2 M. The reactions are followed spectrophotometrically
at 420 nm (4-nitrobenzenethiolate anion appearance). Under amine excess, pseudo-first-order rate coefficients (kobs
)
are found. For all these reactions, plots of kobs vs free amine concentration at constant pH are linear, the slope (kN)
being independent of pH. The Brønsted-type plots (log kN vs pKa of the conjugate acid of the amines) for the reactions
of the series of SA amines with PNPTC and ClPNPTC are linear with slopes 0.59 and 0.54, respectively. The values of these
slopes are in accordance with a concerted mechanism. The Brønsted-type plots for the pyridinolysis reactions are
biphasic, suggesting a stepwise mechanism with a change in the rate-determining step, from breakdown to formation of
a tetrahedral intermediate, as the basicity of the pyridines increases. Copyright ß 2008 John Wiley & Sons, Ltd.
Keywords: aminolysis; pyridinolysis; diaryl thiocarbonates; kinetics; mechanism
With the aim to clarify the mechanism of the aminolysis of
INTRODUCTION
thiocarbonates, in this work we report a kinetic investigation of
the reactions of O-phenyl S-(4-nitrophenyl) thiocarbonate
(PNPTC) and O-(4-chlorophenyl) S-(4-nitrophenyl) thiocarbonate
(ClPNPTC) with a series of SA amines and pyridines. By a
comparison between the kinetic results obtained in this work and
those for the aminolysis of related compounds we evaluate the
effect of the amine nature, the non-leaving and the leaving
(S-nitrophenyl vs O-nitrophenyl) groups of the substrate on the
kinetics and mechanism. Also of interest is to assess the influence
of the electrophilic group (carbonyl vs thiocarbonyl), as the site of
nucleophilic attack by the amine, on the kinetics and mechanism
of these reactions.
The kinetics and mechanisms of the aminolysis of O-alkyl S-aryl
thiocarbonates[1–6] and S-alkyl O-aryl thiocarbonates[7–9] are well
documented. Nevertheless, to our knowledge, there have been
no reports on the kinetics and mechanism of the aminolysis of
O-aryl S-aryl thiocarbonates.
Some of the aminolysis reactions of O-ethyl S-aryl thiocarbo-
nates have been found to be concerted, such as those of O-ethyl
S-(2,4-dinitrophenyl) and O-ethyl S-(2,4,6-trinitrophenyl) thiocar-
bonates (EDNPTC and ETNPTC, respectively) with secondary
alicyclic (SA) amines[1] and quinuclidines[2] and those of the latter
substrate with anilines, all of them in water.[3] Other reactions in
water have been found to be stepwise, through a zwitterionic
tetrahedral intermediate. Among these are those of O-ethyl
S-(4-nitrophenyl) thiocarbonate (ENPTC) with pyridines,[1] SA
amines[1] and quinuclidines,[2] those of EDNPTC with pyridines[1]
and anilines,[3] those of ETNPTC with pyridines[1] and the
reactions of O-ethyl S-(4-X-phenyl) thiocarbonates (X ¼ MeO,
Me, H, Cl) with SA amines.[4]
On the other hand, the reactions of benzylamines with O-ethyl
S-aryl thiocarbonates in acetonitrile were claimed to be
concerted.[5] In contrast, the same reactions (except for O-methyl
instead of O-ethyl) in methanol were found to be stepwise,
through a zwitterionic tetrahedral intermediate.[6]
Concerning the aminolysis of S-methyl O-aryl thiocarbonates,
concerted as well as stepwise mechanisms have also been found.
For instance, the reactions in water of S-methyl O-(2,4-dinitrophenyl)
thiocarbonate (SMDNPTC) with quinuclidines[7] and SA amines[7]
and those of S-methyl O-(2,3,4,5,6-pentafluorophenyl) thiocarbo-
nate with SA amines[7] are concerted. In contrast, the reactions of
S-methyl O-(4-nitrophenyl) thiocarbonate with SA amines[7] and
pyridines[8] and those of SMDNPTC with pyridines[8] have been
claimed to be stepwise.
RESULTS AND DISCUSSION
For all the reactions, pseudo-first-order coefficients (kobs) were
obtained (under amine excess). These were determined by
means of the kinetics software for first-order reactions of the
spectrophotometer. The experimental conditions of the reactions
and the values of kobs are shown in Tables 1–4.
´
Facultad de Qu´ımica, Pontificia Universidad Catolica de Chile, Casilla 306,
*
Santiago 6094411, Chile.
E-mail: jgsantos@uc.cl
a
E. A. Castro, M. Aliaga, J. G. Santos
Facultad de Qu´ımica, Pontificia Universidad Catolica de Chile, Casilla 306,
Santiago 6094411, Chile
´
J. Phys. Org. Chem. 2008, 21 271–278
Copyright ß 2008 John Wiley & Sons, Ltd.

E. A. CASTRO, M. ALIAGA AND J. G. SANTOS
Table 1. Experimental conditions and kobs values for the reactions of SA amines with O-phenyl S-(4-nitrophenyl) thiocarbonate
(PNPTC)a
b
Amine
pH
FN
103 [N]tot (M)c
103 kobs (sꢂ1
)
No. of runs
Piperidine
10.65
10.82
11.05
6.80d
7.00d
7.25d
7.35d
7.55d
9.41
0.40
0.50
0.63
e
1.23–10.5
0.759–7.59
1.12–7.84
1.15–5.00
3.71–14.9
1.23–12.3
2.93–11.7
6.92–27.7
2.60–26.0
1.49–14.9
1.16–11.6
1.52–15.2
1.15–11.5
5.00–85.0
1.42–14.2
1.36–13.6
0.941–9.41
10.0–85.0
9.98–99.8
10.0–70.2
3.68–21.6
2.30–25.4
7.56–31.6
0.0142–0.0421
0.0143–0.102
0.0346–0.155
0.0531–0.189
0.0786–0.365
1.88–16.9
1.30–12.5
1.78–19.7
0.323–3.49
0.302–3.99
2.50–45.5
0.214–2.21
0.456–3.50
0.314–2.61
0.0676–1.59
0.214–2.48
0.345–3.01
6
7
5
6
5
5
6
6
7
7
7
7
6
7
7
7
7
6
7
6
Piperazine
f
g
h
i
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
9.71
10.01
8.79
9.09
9.39
8.19
8.49
8.78
7.33
7.63
1-(2-Hydroxyethyl)-piperazine
Morpholine
1-Formylpiperazine
7.93
a In 44 wt% ethanol–water, at 25.08C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
d Phosphate buffer 0.01 M.
e Free piperazine and piperazinium ion fractions are 0.001184 and 0.96303, respectively.
f Free piperazine and piperazinium ion fractions are 0.0019 and 0.7524, respectively.
g Free piperazine and piperazinium ion fractions are 0.00341 and 0.9836, respectively.
h Free piperazine and piperazinium ion fractions are 0.0043 and 0.9854, respectively.
i Free piperazine and piperazinium ion fractions are 0.00683 and 0.98665, respectively.
For all the reactions the pseudo-first-order rate constants (kobs),
obtained under amine excess, obey Eqn (1), where k0 and kN are
the rate coefficients for solvolysis and aminolysis of the subs-
trates, respectively. The values of k0 and kN show no dependence
on pH within the pH range employed. These values were
obtained as the intercept and slope, respectively, of linear plots of
kobs against free amine concentration at constant pH.
The Brønsted plots obtained for the reactions of the series of
SA amines with PNPTC and ClPNPTC (Fig. 1) are linear with slopes
b ¼ 0.59 ꢁ 0.03 and 0.54 ꢁ 0.06, respectively, suggesting con-
certed mechanisms for these reactions (Scheme 1), since these
slope values are in accordance with the b values found for the
concerted aminolysis of similar compounds. Examples of these
are the aminolysis of EDNPTC and ETNPTC with SA amines
(b ¼ 0.56 and 0.48, respectively)[1] and quinuclidines (b ¼ 0.54
and 0.47, respectively),[2] and those of the latter compound with
anilines (b ¼ 0.54),[3] all of them in water. The aminolyses of
some carbonates have also been proposed to be concerted, with
b values in the range 0.4–0.7, some of them in water[11,12] and
others in aqueous ethanol.[13,14]
The slope values of the Brønsted plots in Fig. 1 are also similar
to those obtained for the concerted reactions of thiocarbonates
in acetonitrile: The benzylaminolysis of O-ethyl S-aryl thiolcarbo-
nates[5] and dithiocarbonates[15] show b values in the range
0.6–0.7.
It is known that the b value alone is not enough to conclude
that a mechanism is concerted. It is also necessary to make sure
that the expected pKa value at the center of the Brønsted
curvature (pK0a) for a hypothetical stepwise mechanism is within
the pKa range used.[16] If the reactions of SA amines with the title
substrates are stepwise, a pK0a value greater than 11 can be
kobs ¼ k0 þ kN ½free amineꢀ
(1)
For the reactions studied the k0 values were much smaller than
the aminolysis term, kN [free amine] in Eqn (1). The values of kN
for the reactions of PNPTC and ClPNPTC with SA amines are
shown in Table 5 and those for the reaction with pyridines are
exhibited in Table 6.
For the reactions of SA amines the kN values, as well as those of
the pKa of the conjugate acids of these amines were statistically
corrected[10] with q ¼ 2 for piperazine (q ¼ 1 for all the other SA
amines) and p ¼ 2 for all the conjugate acids of the amines,
except that for piperazinium ion with p ¼ 4. The parameter q is
the number of equivalent basic sites in the free amine and p is the
number of equivalent dissociable protons in the conjugate acid of
the amine.[10] Figure 1 shows the statistically corrected Brønsted-
type plots.
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Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2008, 21 271–278

AMINOLYSIS AND PYRIDINOLYSIS OF O-ARYL S-(4-NITROPHENYL) THIOCARBONATES
Table 2. Experimental conditions and kobs values for the reactions of SA amines with O-(4-chlorophenyl) S-(4-nitrophenyl)
thiocarbonate (ClPNPTC)a
b
Amine
pH
FN
103 [N]tot (M)c
103 kobs (sꢂ1
)
No. of runs
Piperidine
10.65
10.82
11.05
7.25d
7.60d
7.85d
8.00d
9.41
0.40
0.50
0.63
e
1.23–12.3
1.90–7.59
1.12–7.84
2.93–11.7
2.93–9.97
2.79–23.7
2.54–25.4
2.60–26.0
2.43–24.3
1.16–11.6
1.52–15.2
1.15–11.5
5.00–85.2
1.42–12.1
1.36–13.6
0.941–9.41
25.0–85.0
24.9–99.8
10.0–70.2
4.21–46.9
3.62–28.5
6.43–32.8
0.227–0.510
0.442–0.817
0.153–1.83
0.235–2.60
2.77–33.8
5.88–67.6
2.63–35.0
0.567–7.41
0.737–8.04
4.38–86.2
0.196–2.37
0.756–5.64
0.960–5.16
0.333–2.52
1.05–4.05
0.553–3.49
6
7
5
6
5
6
6
7
7
6
6
7
7
6
7
6
5
6
6
Piperazine
f
g
h
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
9.71
10.01
8.79
9.09
9.39
8.19
8.49
8.78
7.33
7.63
1-(2-Hydroxyethyl)-piperazine
Morpholine
1-Formylpiperazine
7.93
a In 44 wt% ethanol–water, at 25.08C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
d Phosphate buffer 0.01 M.
e Free piperazine and piperazinium ion fractions are 0.00341 and 0.9836, respectively.
f Free piperazine and piperazinium ion fractions are 0.007657 and 0.9853, respectively.
g Free piperazine and piperazinium ion fractions are 0.01357 and 0.9832, respectively.
h Free piperazine and piperazinium ion fractions are 0.0191 and 0.9786, respectively.
estimated on the following grounds. (i) The reactions SA amines
with ENPTC in water show a pK0a value of 10.7;[1] the change of
ethoxy by phenoxy as the non-leaving group shifts the pK0a to a
greater value, since the latter group is more electron-
withdrawing than the former.[17–19] (ii) A change of solvent from
reactions of SA amines with the title substrates are 0.54 and 0.59,
which are too small for rate-limiting breakdown of Tꢁ in a
stepwise mechanism.
With the kN values found (Table 5), the corrected pKa values for
the nucleophiles and the pKa values for the non-leaving groups
(11.2 and 10.5 for phenol and 4-chlorophenol in 44 wt% aqueous
ethanol, respectively), Eqn (2) can be deduced by dual regression
analysis (n ¼ 12, R2 ¼ 0.975). In this expression N and nlg refer
to the nucleophile and the non-leaving group, respectively.
The pKa(N) and pKa(nlg) coefficients (bN and bnlg) are subject to
an error of ꢁ0.1 and ꢁ0.2, respectively.
water to aqueous ethanol or other less polar solvent also
[1,18]
increases the pK0a value
The simultaneous contribution of
these two effects can be seen by a comparison of the pK0a values
found in the reactions of SA amines with methyl 4-nitrophenyl
carbonate in water[11] and 4-methoxyphenyl and 4-chlorophenyl
4-nitrophenyl carbonates in ethanol–water:[20,21] the pKa0 values
are 9.3, 10.5 and 10.6, respectively. Therefore, the two changes,
MeO by ArO as non-leaving group and water by aqueous
ethanol as solvent increase the pK0a about 1.2 pKa units. If this
result can be extrapolated to the thiocarbonates of this study
a pK0a value of ca. 11.9 (10.7 þ 1.2) could be expected for the
reactions of SA amines with the title thiocarbonates, if these
reactions were stepwise.
log kN ¼ ꢂ1:0 þ 0:6 pKaðNÞ ꢂ 0:4 pKaðnlgÞ
(2)
A logarithmic plot (not shown) of the experimental kN vs that
calculated through Eqn (2) is linear with zero intercept and unity
slope. The values of bN and bnlg (0.6 and ꢂ0.4, respectively) are in
accordance with those expected for a concerted mechan-
ism.[1,5,13–15,22]
For the pyridinolysis of PNPTC and ClPNPTC the Brønsted-type
plots of Fig. 2 were obtained with the data in Table 6. As can be
observed, the Brønsted-type plots are biphasic. These curves
were calculated by means of a semi-empirical equation, Eqn (3),
based on the existence of a zwitterionic tetrahedral intermediate
(Tꢁ) on the reaction pathway (see Scheme 2).[23] A similar
equation has been reported by Gresser and Jencks.[24]
Although the expected center of curvature for a stepwise
mechanism is outside the pKa range studied (5.4–10.8), and
therefore, it is not possible to confirm the concerted mechanism
this way, we are more inclined to a concerted process because
if the mechanism were stepwise with pK0a about 12, the b
value observed should correspond to that for the breakdown of
the tetrahedral intermediate (Tꢁ) to products, which usually is
b ¼ 0.8–1.[1,18] Nevertheless, the observed b values for the
J. Phys. Org. Chem. 2008, 21 271–278
Copyright ß 2008 John Wiley & Sons, Ltd.
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E. A. CASTRO, M. ALIAGA AND J. G. SANTOS
Table 3. Experimental conditions and kobs values for the reactions of pyridines with O-phenyl S-(4-nitrophenyl) thiocarbonate
(PNPTC)a
b
Pyridine substituent
4-Oxy
pH
FN
103 [N]tot (M)c
103 kobs (sꢂ1
)
No. of runs
8.5d
9.1d
9.5d
9.14
9.45
9.76
8.83
9.14
9.45
8.67
8.98
9.29
6.6
0.000999
0.003979
0.0099
0.33
1.49–14.9
1.76–17.6
1.45–14.5
0.898–8.98
1.25–12.5
0.887–8.87
0.740–7.40
1.08–10.8
1.12–9.50
1.27–12.7
1.21–12.1
1.12–9.50
0.728–7.28
0.751–7.51
0.784–7.84
1.72–17.2
1.59–15.9
1.92–19.2
0.649–3.13
0.841–8.92
1.71–16.5
8.19–58.9
12.1–116
19.6–99.7
3.93–32.5
11.0–87.0
14.6–91.5
7.51–54.2
6.59–59.8
7.48–77.2
0.199–0.835
0.143–1.17
0.158–1.60
7
6
7
7
7
7
7
7
6
7
7
6
7
7
7
7
7
7
3,4-Diamino
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
4-Dimethylamino
4-Amino
4-Amino-3-bromo
3,4-Dimethyl
0.33
0.50
0.67
6.9
7.2
7.5e
8.0d
9.0d
0.986
0.995
0.9995
0.0523–0.240
0.0423–0.243
0.0343–0.292
a In 44 wt% ethanol–water, at 25.08C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
d Borate buffer 0.01 M.
e Phosphate buffer 0.01 M.
Table 4. Experimental conditions and kobs values for the reactions of pyridines with O-(4-chlorophenyl) S-(4-nitrophenyl)
thiocarbonate (ClPNPTC)a
b
Pyridine substituent
4-Oxy
pH
FN
103 [N]tot (M)c
103 kobs (sꢂ1
)
No. of runs
8.1d
8.5d
9.0d
9.14
9.45
9.76
8.83
9.14
9.45
8.6
0.000398
0.000999
0.00315
0.33
2.18–21.8
0.728–7.28
0.967–9.67
0.656–6.56
0.915–9.15
0.629–6.29
1.17–11.7
1.29–12.9
1.06–10.6
0.671–6.71
1.73–6.93
0.516–5.16
0.67–6.7
0.135–2.99
0.454–3.43
0.846–9.51
6.01–60.7
15.9–142
11.6–121
17.9–114
16.0–163
24.0–140
4.22–41.4
15.9–67.4
5.86–55.1
0.156–1.87
0.365–1.65
0.209–2.15
7
7
7
7
7
7
7
7
7
7
6
7
6
6
6
7
7
6
3,4-Diamino
0.50
0.67
0.33
0.50
4-Dimethylamino
4-Amino
0.67
0.294
0.454
0.624
0.9264
0.9755
0.9921
0.9952
0.9985
0.9995
8.9
9.2
4-Amino-3-bromo
3,4-Dimethyl
8.0d
8.5d
9.0d
8.0d
8.5d
9.0d
0.59–5.01
0.67–6.70
3.29–32.9
5.68–56.8
3.02–30.2
0.106–0.425
0.157–0.65
0.118–0.496
a In 44 wt% ethanol–water, at 25.08C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
d Borate buffer 0.01 M.
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Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2008, 21 271–278

AMINOLYSIS AND PYRIDINOLYSIS OF O-ARYL S-(4-NITROPHENYL) THIOCARBONATES
Table 5. Values of pKa for the conjugate acids of SA amines and kN values for the reactions of these amines with O-phenyl
S-(4-nitrophenyl) thiocarbonate (PNPTC) and O-(4-chlorophenyl) S-(4-nitrophenyl) thiocarbonate (ClPNPTC)a
kN (sꢂ1 Mꢂ1
)
Amine
pKa
PNPTC
ClPNPTC
Piperidine
Piperazine
Piperazine
1-(2-Hydroxyethyl)piperazine
Morpholine
10.82
9.71
9.71
9.09
8.48
7.63
5.37
6.2 ꢁ 0.5
7.8 ꢁ 0.6
5.3 ꢁ 0.3b
1.96 ꢁ 0.09b
1.6 ꢁ 0.5c
5.1 ꢁ 0.5c
0.797 ꢁ 0.005
0.45 ꢁ 0.02
1.52 ꢁ 0.02
0.78 ꢁ 0.05
0.081 ꢁ 0.004
0.015 ꢁ 0.002d
1-Formylpiperazine
Piperazinium ion
0.055 ꢁ 0.003
0.006 ꢁ 0.0006d
a Both the pKa and kN values were determined in 44 wt% ethanol–water, at 25.08C, ionic strength 0.2 M (KCl).
b Values for the 9.41–10.01 pH range.
c Values for piperazine, obtained from the kobs values at pH 6.8–8.0, where there is a mixture of piperazine and piperazinium ion (see
‘Experimental’).
d Values for piperazinium ion obtained from the kobs values at pH 6.8–8.0, where there is a mixture of piperazine and piperazinium ion
(see ‘Experimental’).
Equation (3) contains four parameters: b1 and b2, which are the
Brønsted slopes at high and low pKa, respectively, and k0N and pKa0,
which are the corresponding values at the center of the Brønsted
curvature.
hedral intermediate Tꢁ and a change in the rate-determining
step, from that for k2 in Scheme 2, to that for k1, as the amine
becomes more basic.[1,23,24]
The values of b1 and b2 are in accordance with those reported
for other aminolyses governed by stepwise mechanisms:
b1 ¼ 0.1ꢂ0.3 and b2 ¼ 0.8ꢂ1.1.[1,23–25]
log ðkN=k0 Þ ¼ b2 ðpKa ꢂ pKa0Þ ꢂ log ðð1 þ aÞ=2Þ
log a ¼ ðNb2 ꢂ b1Þ ðpKa ꢂ pK0Þ
(3)
a
Effect of the amine nature
The Brønsted curves were calculated by means of the following
parameters: log k0N ¼ 0.52, pKa0 ¼ 8.1, b1 ¼ 0.37 and b2 ¼ 1.1 (n ¼ 6,
R2 ¼ 0.9997) for the reactions of PNPTC and log k0N ¼ 0.53,
pK0a ¼ 7.9, b1 ¼ 0.46 and b2 ¼ 1.2 (n ¼ 6, R2 ¼ 0.9999) for the
reactions of ClPNPTC. The errors of the slopes are ꢁ0.1, and those
of pK0a and log k0N are ꢁ0.2 and ꢁ0.1, respectively. The curved
Brønsted plots can be explained by the existence of the tetra-
The reactions of the title substrates with SA amines are driven by
a concerted pathway; in contrast to the reactions of the same
substrates with pyridines, which are stepwise. These results
are consistent with those observed in the reactions of
2,4-dinitrophenyl and 2,4,6-trinitrophenyl O-ethyl thiolcarbo-
nates and their corresponding O-methyl carbonates with the
same amines in aqueous solution.[1,7,8,11] The change in
mechanism, from stepwise for pyridines to concerted for SA
amines, was explained by the destabilization of the putative
tetrahedral intermediate formed with the latter amines, due to a
Table 6. Values of pKa for the conjugate acids of pyridines
and kN values for the reactions of pyridines with O-phenyl
S-(4-nitrophenyl) thiocarbonate (PNPTC) and
O-(4-chlorophenyl) S-(4-nitrophenyl) thiocarbonate
(ClPNPTC)a
kN (sꢂ1 Mꢂ1
)
Pyridine substituent pKa
PNPTC
ClPNPTC
4-Oxy
11.5
9.45
9.14
8.98
6.9
121 ꢁ 5
17.1 ꢁ 0.4
14.8 ꢁ 0.5
11.2 ꢁ 0.5
0.262 ꢁ 0.02
302 ꢁ 9
3,4-Diamino
4-Dimethylamino
4-Amino
4-Amino 3-bromo
3,4-Dimethyl
30.1 ꢁ 0.7
23.0 ꢁ 0.8
18.8 ꢁ 0.8
0.31 ꢁ 0.02
5.68 0.0133 ꢁ 0.0005 0.0107 ꢁ .0006
a Both the pKa and kN values were determined in 44 wt%
ethanol–water, at 25.08C, ionic strength 0.2 M (KCl).
Figure 1. Brønsted-type plots (statistically corrected, see text) for the
reactions of SA amines with PNPTC (O) and ClPNPTC (*) in 44 wt%
ethanol–water, at 25.08C, ionic strength 0.2 M (KCl)
J. Phys. Org. Chem. 2008, 21 271–278
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E. A. CASTRO, M. ALIAGA AND J. G. SANTOS
Scheme 1.
at pK0a ¼ 10.6.[21] The fact that the reactions of the same amines
with the corresponding thiolcarbonate (ClPNPTC, this study) in
the same solvent are concerted shows that the tetrahedral
intermediate Tꢁ formed in the former reactions is greatly
destabilized by changing the nitrophenoxy group by 4-
nitrobenzenethio. This result is in accordance with the greater
leaving ability of 4-nitrobenzenethiolate, relative to 4-nitrophenoxide,
from the intermediate Tꢁ.[1] Although phenoxides are better
nucleofuges than isobasic benzenethiolates,[26] the above result
can be explained by the rather large difference in basicity of the
groups involved (pKa ¼ 4.5 and 7.5 in aqueous ethanol for
4-nitrobenzenethiol and 4-nitrophenol, respectively).
Effect of the non-leaving group
As seen in Figs. 1 and 2, ClPNPTC is more reactive than PNPTC
toward the title amines. This can be explained by the greater
electron-withdrawing effect of Cl than H, which leaves the
carbonyl carbon of ClPNPTC more positive, and therefore, more
prone to nucleophilic attack.
Figure 2. Brønsted-type plots for the reactions of pyridines with PNPTC
(O) and ClPNPTC (*) in 44 wt% ethanol–water, at 25.08C, ionic strength
0.2 M (KCl)
For the reactions with SA amines, the change of the
non-leaving group from phenyl in S-(4-nitrophenyl) thiobenzo-
ate[27] to phenoxy in PNPTC (this study), changes the mechanism
from stepwise to concerted. This result is in agreement with the
fact that the reactions of SA amines with S-(2,4-dinitrophenyl)
acetate are stepwise, in contrast to the reactions of the same
amines with O-ethyl S-(2,4-nitrophenyl) thiocarbonate, which are
concerted.[1] This has been explained by the greater electron
withdrawal (inductively) from ethoxy (or methoxy) than methyl in
faster leaving ability of these amines from the intermediate
compared with isobasic pyridines.[1,7,8,11]
Effect of the leaving group
The reactions of SA amines with 4-chlorophenyl 4-nitrophenyl
carbonate in aqueous ethanol were found to be stepwise,
showing a biphasic Brønsted plot with the curvature center
Scheme 2.
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AMINOLYSIS AND PYRIDINOLYSIS OF O-ARYL S-(4-NITROPHENYL) THIOCARBONATES
the corresponding intermediate Tꢁ.[17] This means that the
change of methyl to ethoxy (or methoxy) as the non-leaving
group increases the rate of expulsion of both the amine (k–1) and
the nucleofuge (k2) from Tꢁ, destabilizing, therefore, this
intermediate.[1]
The reactions of SA amines with ethyl S-(4-nitrophenyl) thio-
carbonate in water are stepwise,[1] whereas the reactions of the
same amines with PNPTC in aqueous ethanol are concerted (this
study). This means that the replacement of both ethoxy by
phenoxy as non-leaving group, and water by aqueous ethanol as
solvent, destabilize the intermediate Tꢁ in such a way that the
mechanism changes from stepwise to concerted. The destabi-
lization of Tꢁ caused by the change of non-leaving group can be
attributed to the greater inductive electron-withdrawing ability
of PhO (sI ¼ 0.37) than EtO. (sI ¼ 0.26).[17] The change of solvent,
from water to aqueous ethanol, should also destabilize the
intermediate in view of its zwitterionic nature.
change of the non-leaving group of the substrate, from phenyl in
S-(4-nitrophenyl) thiobenzoate to phenoxy (to give the corre-
sponding thiocarbonate) destabilizes the tetrahedral intermedi-
ate and changes the mechanism from stepwise to concerted. (iv)
For the pyridinolysis, the change of the non-leaving group of the
substrate, from phenoxy to ethoxy, increases the pK0a value. (v) For
the reactions with SA amines, the simultaneous change of ethoxy
in ethyl S-(4-nitrophenyl) thiocarbonate by phenoxy (to yield
phenyl S-(4-nitrophenyl) thiocarbonate) and water to aqueous
ethanol as solvent, destabilizes the tetrahedral intermediate,
changing the mechanism from stepwise to concerted. (vi) For the
SA aminolysis, the change of the electrophilic group, from
thiocarbonyl in O-phenyl S-(4-nitrophenyl) dithiocarbonate to
carbonyl (to yield PNPTC), destabilizes the tetrahedral intermedi-
ate and forces a mechanistic change, from stepwise to concerted.
The pyridinolysis of O-ethyl S-(4-nitrophenyl) thiocarbonate in
water shows a linear Brønsted plot of slope 0.8, with pK0a > 10,
consistent with a stepwise mechanism where breakdown of the
intermediate Tꢁ is rate limiting.[1] Instead, the stepwise pyri-
dinolysis of PNPTC shows a biphasic Brønsted plot with pK0a ¼ 8.1
(this work). Although the greater electron withdrawal of OPh than
OEt results in an increase in the values of both k–1 (rate constant
for amine leaving from Tꢁ) and k2 (rate constant for nucleofuge
expulsion from Tꢁ), see above, the fact that the pK0a value is larger
for the O-ethyl derivative means that the kꢂ1/k2 ratio is also larger
for the latter compound. This is because, according to the
hypothesis of the tetrahedral intermediate, an equation can be
deduced,[8] Eqn (4), that shows that a larger pK0a value means a
larger kꢂ1/k2 ratio.
EXPERIMENTAL
Materials
The substrates, PNPTC and ClPNPTC, were synthesized by the
reaction of the corresponding aryl chloroformate with
4-nitrobenzenethiolate in acetonitrile. The solid products showed
the following characteristics.
PNPTC: 1HNMR (400 MHz, CDCl3) 7.17–7.40 (m, 5H); 7.77 (d, 2H,
J ¼ 8.9Hz); 8.25(d 2H J ¼ 8.9Hz). 13CNMR (200 MHz,) dppm 126.78,
122.09, 143.28, 139.67, 119.45, 126.11, 142.2, 155.21, 156.9. MS
anal. Calc. for C13H9NO4S 275.02521; found 275.02537.
ClPNPTC: 1HNMR (400 MHz, CDCl3) d ppm 7.04 (d, 2H, J ¼
8.9Hz); 7.30(d, 2H, J ¼ 8.9Hz); 7.70(d, 2H, J ¼ 8.9Hz); 8.12 (d, 2H,
J ¼ 8.9Hz);13CNMR (200 MHz, CDCl3) d ppm 125.6, 130.1, 133.4,
150.3, 131.4, 120.8, 148.3, 140.4, 159.9. MS anal. Calc. for
C13H8ClNO4S 308.98627; found 308.98768.
log ðkꢂ1=k2Þ ¼ ðb2 ꢂ b1Þ ðpKa0 ꢂ pKaÞ
(4)
Effect of the electrophilic group
The reactions of SA amines with O-phenyl S-(4-nitrophenyl)
dithiocarbonate in aqueous ethanol are stepwise.[28] In contrast,
the reactions of the same amines with PNPTC in the same solvent
are concerted (this work). These results indicate that the change
of thiocarbonyl as the electrophilic group by carbonyl destabi-
lizes the tetrahedral intermediate (Tꢁ), changing the mechanism
from stepwise to concerted. This destabilization can be attributed
to the greater ability of Oꢂ than Sꢂ in Tꢁ to form the double bond
Kinetic measurements
The kinetics of the reactions were analyzed through a diode array
spectrophotometer in 44 wt% ethanol–water, at 25.0 ꢁ 0.18C and
an ionic strength of 0.2 M (maintained with KCl). The reactions
were followed at 420 nm (appearance of 4-nitrobenzenethiolate
anion).
The reactions were studied under at least 10-fold amine excess
over the substrate, the initial concentration of the latter being
2.5 ꢃ 10ꢂ5 M. Under these conditions pseudo-first-order rate
coefficients (kobs) were found throughout, the reactions being
followed for at least five half-lives. In order to prevent the
dimerization of 4-nitrobenzenethiolate,[30] the slower reactions
were studied by the initial rate method.[25,31]
For all the reactions the pH was maintained constant (three pH
values for each amine) either by the buffer formed by partial
protonation of the amine or by the addition of an external buffer.
The reactions of PNPTC and ClPNPTC with piperazine and
piperazinium ion were studied at pH 6.80–7.55 and 7.25–8.00,
respectively, where a mixture of both amines are present. In these
cases the kN values were obtained through Eqns (5) and (6). In
these equations kNobs is a global nucleophilic rate constant
(corresponding to the mixture of nucleophiles), [N]tot is the total
piperazine (piperazine þ piperazinium ion) concentration, FN
and FNH are the molar fractions of piperazine and piperazinium
ion, respectively, and kN and kNH are their corresponding
—
with carbon due to the stronger p-bonding energy of the C
O
—
group relative to C S.[29] This should increase the expulsion rate
—
—
of both the amine (kꢂ1) and the nucleofuge (k2) from the putative
tetrahedral intermediate.[1] The same effect of the electrophilic
group was found for the SA aminolyses of O-ethyl S-(2,4-dinitrophenyl)
dithiocarbonate and O-ethyl S-(2,4-dinitrophenyl) thiolcarbonate
in water: the former reactions are stepwise whereas the latter are
concerted.[1]
CONCLUDING REMARKS
From the results obtained in this work, several conclusions can be
drawn: (i) The mechanism of the aminolysis (SA amines) of PNPTC
and ClPNPTC is concerted, in contrast to the pyridinolysis of the
same substrates, which is stepwise. (ii) ClPNPTC is more reactive
than PNPTC toward SA amines. (iii) For the SA aminolysis, the
J. Phys. Org. Chem. 2008, 21 271–278
Copyright ß 2008 John Wiley & Sons, Ltd.
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E. A. CASTRO, M. ALIAGA AND J. G. SANTOS
nucleophilic rate constants. The values of kNobs were obtained as
the slopes of linear plots of kobs vs [N]tot at constant pH. The
nucleophilic rate constants for the reactions of the title
REFERENCES
[1] E. A. Castro, Chem. Rev. 1999, 99, 3505–3524.
˜
[2] E. A. Castro, P. Munoz, J. G. Santos, J. Org. Chem. 1999, 64, 8298–8301.
[3] E. A. Castro, L. Leandro, P. Millan, J. G. Santos, J. Org. Chem. 1999, 64,
1953–1957.
thiocarbonates with piperazine (kN) and piperazinium ion (kNH
)
were determined through Eqn (6), as described.[32]
[4] E. A. Castro, M. Cubillos, J. G. Santos, J. Org. Chem. 1999, 64,
6342–6346.
[5] H. K. Oh, Y. H. Lee, I. Lee, Int. J. Chem. Kinet. 2000, 32, 131–135.
[6] H. B. Song, M. H. Choi, I. S. Koo, H. K. Oh, I. Lee, Bull. Korean Chem. Soc.
2003, 24, 91–94.
[7] E. A. Castro, M. Aliaga, J. G. Santos, J. Org. Chem. 2005, 70, 2679–2685.
[8] E. A. Castro, M. Aliaga, J. G. Santos, J. Org. Chem. 2004, 68, 6711–6714.
[9] P. R. Campodonico, A. Aizman, R. Contreras, Chem. Phys Lett. 2006,
422, 204–209.
kobs ¼ k0 þ kNobs½Nꢀtot
kNobs ¼ FN kN þ FNH kNH
The experimental conditions of the reactions are shown in
Tables 1–4.
(5)
(6)
Product studies
[10] R. P. Bell, in The Proton in Chemistry, Methuen, London, 1959. 159.
[11] E. A. Castro, M. Aliaga, P. Campodonico, J. G. Santos, J. Org. Chem.
2002, 67, 8911–8916.
[12] E. A. Castro, P. R. Campodonico, R. Contreras, P. Fuentealba, J. G.
Santos, J. R. Leis, L. Garc´ıa-R´ıo, J. A. Saez, L. R. Domingo, Tetrahedron
2006, 62, 2555–2562.
4-Nitrobenzenethiolate ion was identified as one of the products
of the reactions of PNPTC and ClPNPTC. This was carried out by
comparison of the UV–Vis spectra after completion of these
reactions with that of an authentic sample of 4-nitrobenzenethiol,
under the same reactions conditions.
[13] E. A. Castro, P. Campodonico, A. Toro, J. G. Santos, J. Org. Chem. 2003,
68, 5930–5935.
A referee has pointed out that it is also possible that
some C—O cleavage concomitant with C—S breakage can take
place in the two substrates. This would result in a mixture of
4-nitrobenzenethiol (NPSH) and phenol (from PNPTC) or
4-chlorophenol (from ClPNPTC). Although 4-nitrobenzene-
thiolate (NPSꢂ) is a much better leaving group than phenoxide
or 4-chlorophenoxide, we looked for the presence of any phenol
arising from the reactions of SA amines. For this purpose we
chose the reaction of piperidine with PNPTC. For the reaction of
this very basic amine, the aminolysis (kN [amine]) is fast compared
with the hydrolysis of the substrate (k0) and, therefore, little or no
phenol arising from the latter reaction is expected (the hydrolysis
produces both NPSH and phenol). The presence of phenol was
determined by both spectrophotometric as well as HPLC
techniques. No significant amounts of phenol were found.
[14] E. A. Castro, M. Gazitu´a, J. G. Santos, J. Org. Chem. 2005, 70,
8088–8092.
[15] H. K. Oh, J. Y. Oh, D. D. Sung, I. Lee, Coll. Czech. Chem. Commun. 2004,
69, 2174–2182.
[16] A. Williams, Acc. Chem. Res. 1989, 22, 387–392.
[17] C. Hansch, A. Leo, R. W. Taft, Chem. Rev. 1991, 91, 165–195.
[18] M. J. Gresser, W. P. Jencks, J. Am. Chem. Soc. 1977, 99, 6970–6980.
[19] D. Lee, C. K. Kim, B. S. Lee, I. Lee, Bull. Korean Chem. Soc. 1995, 16,
1203–1208.
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[20] E. A. Castro, M. Andu´jar, P. Campodonico, J. G. Santos, Int. J. Chem.
Kinet. 2002, 34, 309–315.
[21] E. A. Castro, M. Andu´jar, A. Toro, J. G. Santos, J. Org. Chem. 2003, 68,
3608–3613.
[22] I. H. Um, S. E. Jeon, J. A. Seok, Eur. J. Chem. 2006, 12, 1237–1243.
[23] P. M. Bond, E. A. Castro, R. B. Moodie, J. Chem. Soc., Perkin Trans. 2
1976, 68–72.
[24] M. J. Gresser, W. P. Jencks, J. Am. Chem. Soc. 1977, 99, 6963–6970.
[25] A. C. Satterthwait, W. P. Jencks, J. Am. Chem. Soc. 1974, 96, 7018–7031.
[26] K. T. Douglas, Acc. Chem. Res. 1986, 19, 186–192.
[27] E. A. Castro, J. Bessolo, R. Aguayo, J. G. Santos, J. Org. Chem. 2003, 68,
8157–8161.
[28] E. A. Castro, L. Leandro, J. G. Santos, Int. J. Chem. Kinet. 1999, 31,
839–845.
Acknowledgements
[29] S. V. Hill, S. Thea, A. Williams, J. Chem. Soc., Perkin Trans. 2 1983,
437–446.
[30] D. J. Hupe, W. P. Jencks, J. Am. Chem. Soc. 1977, 99, 451–464.
[31] S. Ba-Saif, A. K. Luthra, A. Williams, J. Am. Chem. Soc. 1987, 109,
6362–6368.
We thank MECESUP of Chile (projects PUC-0004, UCH 0116 and
RED QUIMICA UCH-01) and FONDECYT of Chile (project 1060593)
for financial support. M.A. thanks CONICYT of Chile for a doctoral
˜
fellowship and project AT-2405019. We also thank Dr. A. Canete
and M. C. Zuniga for the MS and HPLC analyses, respectively.
[32] E. A. Castro, C. Ureta, J. Chem. Soc., Perkin Trans. 2 1991, 63–68.
˜
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Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2008, 21 271–278