Reactions of O-aryl S-aryl dithiocarbonates with secondary alicyclic amines in aqueous ethanol. Kinetics and mechanism

Article abstract of DOI:10.1002/poc.1787

The reactions of O-(4-methylphenyl) S-(4-nitrophenyl), O-(4-chlorophenyl) (4-nitrophenyl), O-(4-chlorophenyl) S-phenyl, and O-(4-methylphenyl) S-phenyl dithiocarbonates (1, 2, 3, and 4, respectively) with a series of secondary alicyclic (SA) amines 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. Under amine excess, pseudo-first-order rate coefficients (k_obs) are found. For some of the reactions, plots of k_obs vs. free amine concentration at constant pH are linear but others are nonlinear upwards. This kinetic behavior is in accordance with a stepwise mechanism with two tetrahedral intermediates, one zwitterionic (T ^±) and the other anionic (T^-). In some cases, there is a kinetically significant proton transfer from T^± to an amine to yield T^-. Values of the rate micro constants k₁ (amine attack to form T^±), k_-1 (its back step), k₂ (nucleofuge expulsion from T^±), and k ₃ (proton transfer from T^± to the amine) are determined for some reactions. The Bronsted plots for k₁ are linear with slopes β₁ = 0.2-0.4 in accordance with the slope values found when T^± formation is the rate-determining step. The sensitivity of log k₁ and log k_-1 to the pK _a of the amine, leaving and non-leaving groups are determined by a multiparametric equation. For the reactions of 1-4 with 1-formylpiperazine and those of 3 and 4 with morpholine the k₂ and k₃ steps are rate determining. Copyright

Full text of DOI:10.1002/poc.1787

Research Article
Received: 14 May 2010,
Revised: 9 July 2010,
Accepted: 19 July 2010,
Published online in Wiley Online Library: 28 September 2010
(wileyonlinelibrary.com) DOI 10.1002/poc.1787
Reactions of O-aryl S-aryl dithiocarbonates
with secondary alicyclic amines in aqueous
ethanol. Kinetics and mechanism
a
a
a
*
´
Enrique A. Castro , Marcela Gazitu´a and Jose G. Santos
The reactions of O-(4-methylphenyl) S-(4-nitrophenyl), O-(4-chlorophenyl) (4-nitrophenyl), O-(4-chlorophenyl)
S-phenyl, and O-(4-methylphenyl) S-phenyl dithiocarbonates (1, 2, 3, and 4, respectively) with a series of secondary
alicyclic (SA) amines 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. Under amine excess, pseudo-first-order rate coefficients
(kobs) are found. For some of the reactions, plots of kobs vs. free amine concentration at constant pH are linear
but others are nonlinear upwards. This kinetic behavior is in accordance with a stepwise mechanism with two
tetrahedral intermediates, one zwitterionic (TW) and the other anionic (TS). In some cases, there is a kinetically
significant proton transfer from TW to an amine to yield TS. Values of the rate micro constants k1 (amine attack to form
TW), kS1 (its back step), k2 (nucleofuge expulsion from TW), and k3 (proton transfer from TW to the amine) are
determined for some reactions. The Brønsted plots for k1 are linear with slopes b1 ¼ 0.2–0.4 in accordance with the
slope values found when TW formation is the rate-determining step. The sensitivity of log k1 and log kS1 to the pKa of
the amine, leaving and non-leaving groups are determined by a multiparametric equation. For the reactions of 1–4
with 1-formylpiperazine and those of 3 and 4 with morpholine the k2 and k3 steps are rate determining. Copyright ß
2010 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this paper.
Keywords: Brønsted plots; dithiocarbonates; kinetics; mechanisms; secondary alicyclic amines
ethanol, showing that these reactions are stepwise and occur
INTRODUCTION
through a Tꢀ intermediate.[6] Also, a kinetic and mechanistic
study of the reactions of dithiocarbonates 1 and 2 with anilines
has demonstrated the presence of the above two (Tꢀ and Tꢁ)
intermediates.[7]
The kinetics and mechanisms of the aminolysis of O-alkyl S-aryl
dithiocarbonates are well documented.[1–4] Among these reports
are those of the reactions of S-(2,4-dinitrophenyl) and
S-(2,4,6-trinitrophenyl) O-ethyl dithiocarbonates with pyridines
and secondary alicyclic (SA) amines in water, which proceed by a
stepwise mechanism, through a zwitterionic tetrahedral inter-
mediate (Tꢀ).[1] On the other hand, the reactions of S-(4-X-phenyl)
O-ethyl dithiocarbonates (X ¼ H, MeO, Me, and Cl) with SA amines
have been found to take place through two tetrahedral
intermediates, one zwitterionic (Tꢀ), and the other anionic
(Tꢁ).[1] In contrast, the reactions of S-(2,4-dinitrophenyl) and
S-(2,4,6-trinitrophenyl) O-ethyl dithiocarbonates with quinucli-
dines are driven by a concerted mechanism (single step, with no
intermediate).[2]
In order to shed more light on the mechanisms of the
aminolysis of diaryl dithiocarbonates, in this work we report a
kinetic study of the reactions of dithiocarbonates 1, 2, 3 and
O-(4-methylphenyl) S-phenyl dithiocarbonate (4) with a series of
SA amines. By a comparison between the kinetic results obtained
in this work and those in the pyridinolysis and anilinolysis of the
same substrates and the aminolysis (SA amines) of related
compounds, we evaluate the effect of the amine nature, the
On the other hand, the aminolysis of diaryl dithiocarbonates
has received less attention.[5–8] The reactions of SA amines with
O-phenyl S-(4-nitrophenyl) dithiocarbonate in aqueous ethanol
have been shown to proceed through Tꢀ and Tꢁ inter-
mediates.[8] We have recently described the pyridinolysis of
O-(4-methylphenyl) S-(4-nitrophenyl) dithiocarbonate (1),
O-(4-chlorophenyl) S-(4-nitrophenyl) dithiocarbonate (2), and
O-(4-chlorophenyl) S-phenyl dithiocarbonate (3) in aqueous
*
Correspondence to: J. G. Santos, Facultad de Qu´ımica, Pontificia Universidad
´
Catolica de Chile, Casilla 306, Santiago 6094411, Chile.
E-mail: jgsantos@uc.cl
a
E. A. Castro, M. Gazitu´a, J. G. Santos
Facultad de Qu´ımica, Pontificia Universidad Catolica de Chile, Casilla 306,
Santiago 6094411, Chile
´
J. Phys. Org. Chem. 2011, 24 466–473
Copyright ß 2010 John Wiley & Sons, Ltd.

REACTIONS OF O-ARYL S-ARYLDITHIOCARBONATES
electrophile moiety, and the non-leaving and leaving groups of
the substrates on the kinetics and mechanism.
The reactions of 3 and 4 with piperazine and 1-(2-hydroxyethyl)-
piperazine, and those of 1 and 2 with morpholine, show nonlinear
upwards plots of kobs against [N]. The plots [N]/kobs vs. 1/[N] exhibit
linear portions at high amine concentrations.
The different behavior exhibited by all these reactions can be
explained by the mechanism shown in Scheme 1. A similar
reaction mechanism has been obtained for the aminolysis (SA
amines) of some O-alkyl S-aryl dithiocarbonates,[1] O-phenyl
S-4-nitrophenyl dithiocarbonate,[8] alkyl aryl[1] and diaryl thio-
nocarbonates,[5] and for the reactions of 1 and 2 with anilines.[7]
By application of the steady state condition to the tetrahedral
intermediates Tꢀ and Tꢁ in Scheme 1, Eqn (1) can be derived.
k1ðk2þk3½NꢂÞ½Nꢂ
kobs
¼
(1)
k
ꢁ1þk2þk3½Nꢂ
If kꢁ1 >> k2 þ k3[N], Eqn (1) can be reduced to Eqn (2), where
K1 ¼ k1/kꢁ1. In this case, the plots correspond to a second order
polynomial behavior, as was found in the reactions of 1, 2, and 3
with 1-formylpiperazine and those of 3 and 4 with morpholine.
This is because these two amines are the least basic of the series
andtheirnucleofugalityfromtheintermediateTꢀ (kꢁ1)isverylarge.
In the particular case of the reaction of 4 with 1-formylpiperazine,
the second order in amine term is much larger than that first
order in amine, i.e., k3[N] >> k2 and kobs ¼ K1k3[N]2.
RESULTS AND DISCUSSION
For all the reactions studied, under amine excess, pseudo-
first-order rate constants (kobs) were found. These were obtained
by means of the kinetic software for first-order reactions of the
spectrophotometer. The experimental conditions of the reactions
and the values of kobs are detailed in Supplementary Materials.
The ranges of amine concentration and kobs values are
summarized in Tables 1–4.
Plots of kobs against free amine concentration ([N]) show
different behaviors depending on the amine basicity and the
dithiocarbonate:
2
kobs¼K1k2½NꢂþK1k3½Nꢂ
(2)
On the other hand, if in Eqn (1) k2 þ k3[N] >> kꢁ1, then Eqn (3)
is obtained.
The reactions of 1, 2, and 3 with piperidine, those of 1 and 2
with piperazine and that of 2 with 1-(2-hydroxyethylpiperazine)
show linear plots of kobs against free amine concentration.
The reaction of 4 with 1-formylpiperazine shows a linear plot of
kobs against [N]2.
For the reactions of 1, 2, and 3 with 1-formylpiperazine and
those of 3 and 4 with morpholine, the plots of kobs vs. [N] are in
accordance with a second order polynomial equation.
kobs¼k1 ½Nꢂ
(3)
This is the case of the reactions of 2 with piperidine, piperazine,
and 1-(2-hydroxyethyl)piperazine and those of 1 and 3 with
piperidine. These amines are highly basic and it is reasonable that
their nucleofugality from the intermediate Tꢀ (kꢁ1) is very low.
This is why linear plots of kobs vs. [N] were found for these
reactions.
Table 1. Experimental conditions and kobs values for the reactions of SA amines with O-(4-methylphenyl) 4-nitrophenyl dithio-
carbonate (1)a
b
pH
FN
103[N]tot (M)c
103kobs (sꢁ1
)
No. of runs
Piperidine
10.52
10.82
11.12
9.41
9.71
8.79
9.09
9.39
8.48
8.78
9.08
7.33
7.63
7.93
0.33
0.50
0.67
0.33
0.50
0.33
0.50
0.67
0.50
0.67
0.81
0.33
0.50
0.67
3.43–34.3
2.90–29.0
2.47–24.7
4.58–38.9
3.67–25.7
4.72–47.2
4.34–80.6
3.82–146
3.63–26.3
3.50–121
3.80–38.0
5.71–57.1
6.39–160
5.79–160
1.22–9.56
1.50–15.9
2.20–18.5
0.926–9.72
1.15–9.84
0.276–4.20
0.277–9.66
0.373–24.3
0.142–2.60
0.230–15.2
0.26–15.2
6
7
7
6
5
Piperazine
1-(2-Hydroxyethyl) piperazine
7
10
12
7
11
7
7
12
12
Morpholine
1-Formylpiperazine
0.0240–0.411
0.0376–2.34
0.0507–4.23
a In 44 wt% ethanol–water, at 25.0 8C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
J. Phys. Org. Chem. 2011, 24 466–473
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´
E. A. CASTRO, M. GAZITUA AND J. G. SANTOS
Table 2. Experimental conditions and kobs values for the reactions of SA amines with O-(4-chlorophenyl) 4-nitrophenyl dithio-
carbonate (2)a
b
pH
FN
103[N]tot (M)c
103kobs (sꢁ1
)
No. 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
9.08
7.33
7.63
7.93
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
0.50
0.67
0.81
0.33
0.50
0.67
3.43–34.3
2.92–29.2
2.47–24.7
4.58–45.8
3.67–36.7
6.00–24.0
4.72–47.2
4.34–80.6
3.82–146
3.63–36.3
3.50–143
3.80–38.0
5.71–57.1
6.40–53.9
5.45–170
2.16–18.2
2.62–27.6
3.34–31.3
1.53–21.0
1.93–27.2
5.31–24.8
0.623–8.63
0.661–20.7
0.862–45.9
0.357–5.86
0.546–46.6
0.654–11.9
7
7
7
7
7
Piperazine
3
7
1-(2-Hydroxyethyl) piperazine
Morpholine
10
12
7
11
7
7
7
12
1-Formylpiperazine
0.0970–1.17
0.122–1.56
0.144–11.2
a In 44 wt% ethanol–water, at 25.0 8C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
Table 3. Experimental conditions and kobs values for the reactions of SA amines with O-(4-chlorophenyl) phenyl dithiocarbonate (3)a
103[N]tot (M)c
103kobs (sꢁ1
)
No. of runs
b
pH
FN
Piperidine
Piperazine
10.52
10.82
11.12
9.41
9.71
10.01
9.09
9.39
8.48
8.78
9.08
7.33
7.63
7.93
0.33
0.50
0.67
0.33
0.50
0.67
0.50
0.67
0.50
0.67
0.81
0.33
0.50
0.67
3.92–39.2
4.18–41.8
3.63–36.3
3.63–36.3
4.71–47.1
3.52–35.2
6.05–60.5
5.79–57.9
5.95–50.6
5.19–36.3
5.50–46.8
20.3–44.6
7.28–72.8
19.9–67.8
0.675–8.29
1.56–15.8
1.48–16.1
0.221–4.96
1.72–12.6
0.660–13.8
0.189–3.84
0.373–5.43
0.138–3.21
0.186–2.79
0.283–5.67
7
7
7
7
6
7
7
7
6
5
6
3
7
5
1-(2-Hydroxyethyl) piperazine
Morpholine
1-Formylpiperazine
0.0680–0.215
0.0364–0.680
0.168–0.899
a In 44 wt% ethanol–water, at 25.0 8C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
If experimentally the amine concentration is high enough, then
k3[N] >> k2 and Eqn (1) can be simplified to Eqn (4), which by
morpholine, Eqn (1) holds at low amine concentrations but at
higher amine concentrations, the reaction conditions are
described by Eqns (4) and (5). In accordance with Eqn (5), plots
of [N]/kobs vs. 1/[N] are linear in the region where the amine
concentration is high enough, but the plots exhibit a downward
curvature as amine concentration decreases. Therefore, from the
linear parts of the curved plots, the values of 1/k1 and kꢁ1/k1k3
were obtained from the intercept and slope, respectively.
In Scheme 1, the k3 step corresponds to the proton
transfer from the zwitterionic tetrahedral intermediate Tꢀ to
the corresponding amine to give the anionic tetrahedral
intermediate Tꢁ. In order to determine the value of k3, it is
rearrangement leads to Eqn (5). If also k3[N] >> k Eqn (4)
ꢁ1
transforms into Eqn (3).
2
k1k3½Nꢂ
kobs
¼
¼
(4)
(5)
ðkꢁ1þk3½NꢂÞ
½Nꢂ
k
1
ꢁ1
þ
kobs k1 k3½Nꢂ k1
For the reactions of 1, 3, and 4 with piperazine and
1-(2-hydroxyethyl)piperazine, and those of 1 and 2 with
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Copyright ß 2010 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2011, 24 466–473

REACTIONS OF O-ARYL S-ARYLDITHIOCARBONATES
Table 4. Experimental conditions and kobs values for the reactions of SA amines with O-(4-methylphenyl) phenyl dithiocarbonate
(4)a
b
pH
FN
103[N]tot (M)c
103kobs (sꢁ1
)
No. of runs
Piperidine
10.52
10.82
11.12
9.41
9.71
10.01
8.79
9.09
9.39
8.18
8.48
8.78
7.33
7.63
7.93
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
9.70–97.0
9.83–98.3
9.68–96.8
8.50–85.0
8.60–86.0
8.47–84.7
6.43–64.3
6.75–67.5
6.43–64.3
11.9–119
11.1–94.3
10.9–109
49.1–196
18.1–181
18.1–181
0.652–11.2
1.25–19.4
1.93–27.9
7
7
7
7
7
7
7
7
7
7
6
7
6
7
7
Piperazine
0.233–6.81
0.314–12.2
0.607–16.5
0.0285–1.03
0.0486–2.08
0.0584–2.66
0.0564–2.41
0.0899–2.73
0.112–5.05
1-(2-Hydroxyethyl) piperazine
Morpholine
1-Formylpiperazine
0.0306–0.392
0.0263–0.521
0.0301–1.15
a In 44 wt% ethanol–water, at 25.0 8C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
necessary to estimate the pKa values of the corresponding Tꢀ
intermediates.
larger than those of 5 and 6, respectively, can be estimated.
Therefore, the pKa of intermediates 8 and 7 are 4.8 and 5.4 units
lower, respectively, than those of the corresponding amine.
For the tetrahedral intermediates Tꢀ derived from the
reactions of 1 and 2 with anilines a pKa value 5.4 and 6.0 units,
respectively, lower than that of the respective amine has been
estimated.[7] Since these values should be independent of the
amine basicity and nature,[1] it means that the pKa of the
tetrahedral intermediates formed with SA amines (intermediates
5 and 6) should also be 5.4 and 6.0 units, respectively, lower than
that of the respective amine. Substitution of S-(4-nitrophenyl) in
the intermediates 5 and 6 by the S-phenyl group yield the
intermediates 8 and 7, respectively. The pKa of these species can
be estimated by Jencks’ method, which considers the Hammett
inductive sI values for the substituents attached to the central
carbon of a tetrahedral intermediate.[9,10] The sI values for
S-phenyl and S-(4-nitrophenyl) are 0.30 and 0.36, respectively.[11]
Using rI ¼ –9.2 for the Hammett inductive constant for the pKa of
the tetrahedral intermediates,[12] a pKa for 8 and 7 of ca. 0.6 units
According to this estimation, the proton transfer from Tꢀ to the
amine (k3) must be thermodynamically favorable and, therefore,
S-
k2
S
S
k1
+ Ar'S-
ArO C
ArO C SAr'
ArO C SAr'
NH+
NH+
k-1
+
T
NH
- H+
fast
k3[NH]
S-
S
fast
- Ar'S-
ArO C
ArO C SAr'
N
N
T-
Scheme 1.
J. Phys. Org. Chem. 2011, 24 466–473
Copyright ß 2010 John Wiley & Sons, Ltd.
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´
E. A. CASTRO, M. GAZITUA AND J. G. SANTOS
Table 5. Values of k1 obtained for the reactions of O-(4-methylphenyl) S-(4-nitrophenyl) dithiocarbonate (1), O-(4-chlorophenyl)
S-(4-nitrophenyl) dithiocarbonate (2), O-(4-chlorophenyl) S-phenyl dithiocarbonate (3), and O-(4-methylphenyl) S-phenyl dithio-
carbonate (4) with SA aminesa
k1 (sꢁ1 Mꢁ1
)
b
Amine
pKa
1
2
3
4
Piperidine
Piperazine
1-(2-Hydroxyethyl) piperazine
Morpholine
10.82
9.71
9.09
8.48
1.11c
1.86c
1.51c
0.481c
0.50d
0.716c
0.660d
0.180d
—
0.528d
0.375d
0.0785d
—
0.794c
0.260d
0.210d
a Values determined in 44 wt% ethanol–water, at 25.0 8C, ionic strength 0.2 M (KCl).
b Values of pKa of the conjugate acid of the amine under the reaction conditions.
c Values of the slope of linear kobs vs. [N] plots (Eqn (3)).
d Values of the reciprocal of the intercept of the linear portion of the [N]/kobs vs. 1/[N] plots (Eqn (5)).
diffusion controlled.[8] A value of ca. 4 ꢃ 109 sꢁ1 Mꢁ1 has been
estimated for k3 in 44 wt% ethanol–water.[7,8,13] It is noteworthy
that this value is independent of the amine basicity and nature
because the same amine that acts as a base is in the
corresponding intermediate.[1]
Tables 5 and 6 summarize the k1 and kꢁ1 values obtained from
Eqns (3) and (5) for some of the reactions studied.
Figure 1 shows the Brønsted plots for the k1 values obtained for
the reactions of the series of SA amines with dithiocarbonates
1–4 (Table 5). These plots are linear with slopes b ¼ 0.2–0.4. The
k1 values, as well as those of the pKa of the conjugate acids of
these amines, were statistically corrected[1,14] 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.[1] 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.[14]
The b values obtained for k1 (Fig. 1) are in accordance with
those found for similar stepwise reactions where the formation of
Figure 1. Brønsted-type plots (statistically corrected, see text) for the k1
values obtained in the reactions of secondary alicyclic aminess with (*)
O-(4-methylphenyl) S-(4-nitrophenyl) dithiocarbonate (1), (*) O-(4-
chlorophenyl) S-(4-nitrophenyl) dithiocarbonate (2), (&) O-(4-chlorophenyl)
S-phenyl dithiocarbonate (3), and (&) O-(4-methylphenyl) S-phenyl dithio-
carbonate (4) in 44 wt% ethanol–water, at 25.0 8C, ionic strength 0.2 M (KCl)
Tꢀ is the rate determining step.[1,5]
With the k1 corrected values obtained for the SA aminolysis of
dithiocarbonates 1–4 (Table 5) and those for the same aminolysis
of phenyl S-4-nitrophenyl dithiocarbonate,[8] and the corrected
pKa of the conjugate acid of the amines (pKNcorr), those of the
Table 6. Values of k obtained for the reactions of O-(4-methylphenyl) S-(4-nitrophenyl) dithiocarbonate (1), O-(4-chlorophenyl)
ꢁ1
S-(4-nitrophenyl) dithiocarbonate (2), O-(4-chlorophenyl) S-phenyl dithiocarbonate (3), and O-(4-methylphenyl) S-phenyl dithio-
carbonate (4) with SA aminesa
10ꢁ8k (sꢁ1
)
ꢁ1
b
Amine
pKa
1
2
3
4
Piperidine
Piperazine
1-(2-Hydroxyethylpiperazine
Morpholine
10.82
9.71
9.09
8.48
—
—
0.72
1.5
—
—
—
0.70
—
0.314
2.62
—
1.05
1.9
7.22
—
a Values of kꢁ1determined in 44 wt% ethanol–water, at 25.0 8C, ionic strength 0.2 M (KCl). These were determined from the slopes of
the linear portion of [N]/kobs vs. 1/[N] plots (Eqn (5)), with k3 ¼ 4 ꢃ 109 sꢁ1 Mꢁ1(see text) and k values in Table 5.
ꢁ1
b Values of pKa of the conjugate acid of the amine under the reactions conditions.
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REACTIONS OF O-ARYL S-ARYLDITHIOCARBONATES
leaving (pKlg) and the non-leaving (pKnlg) groups, the multi-
parametric relationship shown in Eqn (6) (n ¼ 19, R2 ¼ 0.917) was
obtained. The bN value (0.27) is in accordance with those found
for stepwise mechanisms where the formation of the Tꢀ
intermediate is the rate-determining step.
could be due to the large errors involved in the determination of
K1k2 and K1k3 for the reaction of 4 with morpholine. Another
possibility, as one of the referees suggested, is that it could be due
to ‘perhaps some small changes in local solvation of some
centers’.
logk1corr ¼ ð0:6ꢀ0:6Þ þ ð0:27ꢀ0:03ÞpKNcorrꢁð0:22ꢀ0:05Þ
pKnlgꢁð0:23ꢀ0:03Þ pKlg
(6)
Effect of the amine nature
The reactions of dithiocarbonates 1 and 2 with pyridines,[6]
anilines,[7] and SA amines (this work) under the same
experimental conditions were found to be stepwise, albeit with
an important difference: the reactions with pyridines proceed
through only one tetrahedral intermediate (Tꢀ), while in the
reactions with SA amines and anilines two tetrahedral inter-
mediates, the zwitterionic (Tꢀ) and the anionic (Tꢁ), are formed.
The absence of the intermediate Tꢁ in the reactions with
pyridines is obvious since these tertiary amines lack a proton and,
therefore, the proton transfer from Tꢀ to the amine is impossible.
In the studied reactions of 1–3 with 1-formylpiperazine and of
3 and 4 with morpholine, the formation of Tꢀ is an equilibrium
step, as is in the anilinolysis of 1 and 2.[7] This should be due to the
weak basicity of these amines (pKa for 1-formylpiperazine and
morpholine are 7.63 and 8.48, respectively, and for anilines the
pKa range covered was 4.3–6.5), which means high nucleofugality
With the kꢁ1 values of Table 6 and those for the SA aminolysis
of phenyl S-4-nitrophenyl dithiocarbonate,[8] and the corrected
pKa of the conjugate acid of the SA amines and those of the
leaving and non-leaving groups, Eqn (7) (n ¼ 13, R2 ¼ 0.815) can
be obtained.
logk ¼ ð6:3ꢀ1:8Þꢁð0:66ꢀ0:11ÞpKNcorr
ꢁ1
þ ð0:47ꢀ0:16ÞpKnlg þ ð0:49ꢀ0:1ÞpKlg
(7)
The negative value of bN (ꢁ0.66) is in agreement with the fact
that the more basic is the amine (higher pKa) the lower is its
nucleofugality from the Tꢀ intermediate. The positive b values for
the non-leaving and leaving groups (0.47 and 0.49, respectively)
are in accordance with the results of Gresser and Jencks: the
leaving ability of the amine from Tꢀ increases with electron
donation (higher basicity) from these two groups.[15,16]
from the Tꢀ intermediate (large k
value). Therefore, the
ꢁ1
condition kꢁ1 >> k2 þ k3[N] is satisfied and Eqn (1) reduces to
Eqn (2), which implies an equilibrium between reactants and Tꢀ.
Exceptions to this are the reactions carried out at very high amine
concentrations, where both terms are comparable.
By nonlinear least-squares fitting to Eqn (2) of the kinetic
results for the reactions of 1–3 with 1-formylpiperazine and 3 and
4 with morpholine, the values for the coefficients for first and
second order in amine, K1k2 and K1k3, respectively, were obtained.
These are summarized in Table 7.
The k2 values obtained from the reactions of 1 and 2 with
1-formylpiperazine are similar to those obtained for their
anilinolysis under the same experimental conditions:
(3 ꢀ 2) ꢃ 108 sꢁ1 and (4 ꢀ 2) ꢃ 108 sꢁ1 for 1 and 2, respectively.[7]
This is in accordance with the finding that the nucleofugality of
the leaving group from the Tꢀ intermediate is independent of the
amine basicity and nature.[15] This is because the cationic amino
moiety in Tꢀ cannot exert a push to expel the leaving group since
it lacks an electron pair.[15] On the other hand, the k2 values
obtained for 4-nitrobenzenethiolate expulsion should be larger
than those for benzenethiolate. As seen in Table 7, the k2 values
for 2 are larger than those for 3. Nonetheless, the k2 value for 1 is
smaller than that for 4 (morpholine), which is not reasonable and
Effect of the leaving and non-leaving groups
The k1 values are larger for the reactions of 1 and 2 than those of
4 and 3, respectively. These results are reasonable in the light of
the larger electron withdrawing effect of the 4-nitrobenzenethio
group in the two former dithiocarbonates compared with the
benzenethio group in the latter compounds. This leaves more
positive the thiocarbonyl carbon atom of 1 and 2, and, therefore,
more prone to the amine attack.
On the other hand, the negative values for the sensitivity of the
non-leaving and leaving groups on k1 obtained (bnlg ¼ ꢁ0.22 and
blg ¼ ꢁ0.23) are reasonable since as the pKa of the leaving and
non-leaving groups increases, there is less electron-withdrawal
Table 7. Values of K1k2, K1k3, K1, and k2 obtained for some of the reactions of O-4-methylphenyl S-4-nitrophenyl dithiocarbonate (1),
O-4-chlorophenyl S-4-nitrophenyl dithiocarbonate (2), O-(4-chlorophenyl) S-phenyl dithiocarbonate (3), and O-(4-methylphenyl)
S-phenyl dithiocarbonate (4) with some SA aminesa,b,c
Amine
Substrate
103K1k2 (sꢁ1 Mꢁ1
)
102K1k3 (sꢁ1 Mꢁ2
)
1011K1 (Mꢁ1
)
10ꢁ8k2 (sꢁ1
)
Morpholine
Morpholine
1-Formylpiperazine
1-Formylpiperazine
1-Formylpiperazine
1-Formylpiperazine
4
3
1
2
3
4
38 ꢀ 6
80 ꢀ 10
10 ꢀ 2
40 ꢀ 2
12 ꢀ 2
—
45 ꢀ 8
200 ꢀ 30
26 ꢀ 2
11.3
50
6.5
13
4.5
1.9
3.4
1.6
1.5
3.2
2.7
—
50 ꢀ 2
18 ꢀ 5
7.5 ꢀ 0.2
a The values of K1k2 and K1k3 were determined in 44 wt% ethanol–water, at 25 8C and ionic strength 0.2 M (KCl), by fitting of the
experimental data to Eqn (2).
b The values of K1 were calculated by dividing K1k3 by k3 ¼ 4 ꢃ 109 sꢁ1 Mꢁ1 (see text).
c The values of k2 were calculated by dividing K1k2 by K1.
J. Phys. Org. Chem. 2011, 24 466–473
Copyright ß 2010 John Wiley & Sons, Ltd.
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´
E. A. CASTRO, M. GAZITUA AND J. G. SANTOS
from them and the thiocarbonyl carbon of the substrate becomes
less positive and less susceptible to the amine attack. It is
noteworthy that the values of bnlg and blg are very similar. This
means that the electronic abilities from these two groups in the
substrate have a similar effect on the charge of the thiocarbonyl
carbon.
the nucleofuge (k2) from the putative tetrahedral intermediate.[1]
The same effect of the electrophilic group was found for the SA
aminolysis of O-ethyl S-(2,4-dinitrophenyl) dithiocarbonate[21]
and O-ethyl S-(2,4-dinitrophenyl) thiolcarbonate,[22] both in
water: the former reactions are stepwise whereas the latter are
concerted.
The reactions of SA amines with 1 show the same mechanism
as that exhibited by the same aminolysis of 4-methylphenyl
4-nitrophenyl thionocarbonate, under the same experimental
conditions.[17] In fact, in both reactions the corresponding
zwitterionic tetrahedral intermediate (Tꢀ) transfers a proton to
the amine to form the anionic intermediate (Tꢁ). For both
reactions, the k3[N] values are comparable with those of k2
despite the larger value of the rate constant k2 for expulsion of
4-nitrobenzenethiolate, relative to 4-nitrophenoxide, from the
corresponding intermediate Tꢀ (the k2 values are 1.5 ꢃ 108 sꢁ1
(this work) and ca. 1 ꢃ 107 sꢁ1, respectively).[17]
CONCLUDING REMARKS
From the results obtained in this work, several conclusions can be
drawn: (i) The mechanism of the aminolysis (SA amines) of
dithiocarbonates 1–4 is stepwise, with two tetrahedral inter-
mediates, one zwitterionic (Tꢀ) and other anionic (Tꢁ). (ii)
Multiparametric equations are determined for the dependence of
k1 and kꢁ1 on the pKa of the conjugate acids of the nucleophile
(pKN) and the non-leaving (pKnlg) and leaving (pKlg) groups. (iii)
Dithiocarbonates 2 and 3 are more reactive toward SA amines
than 1 and 4, respectively, due to the larger electron withdrawal
of 4-chloro than 4-methyl in the non-leaving group. (iv) The
reactions of SA amines with 1 show the same mechanism as that
exhibited by the same aminolysis of 4-methylphenyl
4-nitrophenyl thionocarbonate, under the same experimental
conditions. The larger value of the rate constant k2 for expulsion
of 4-nitrobenzenethiolate, relative to 4-nitrophenoxide, from the
corresponding intermediate Tꢀ should be due to the lower
basicity of the former. (v) The k1 values for the SA aminolysis of 1
are 2–6 times smaller than those of the corresponding
thionocarbonate due to the smaller electron withdrawal of
4-nitrobenzenethio than 4-nitrophenoxy. (vi) The reactions of 2
with SA amines in aqueous ethanol are stepwise (this work). In
contrast, the reactions of the same amines with
O-(4-chlorophenyl) S-(4-nitrophenyl) thiolcarbonate, under the
same experimental conditions, are concerted. These results
indicate that the change of thiocarbonyl as the electrophilic
group by carbonyl destabilizes the tetrahedral intermediate Tꢀ,
changing the mechanism from stepwise to concerted. (vii) The
reactions of ethyl S-(4-nitrophenyl) dithiocarbonate with SA
amines proceed by a stepwise mechanism with formation of the
intermediate Tꢀ only. The change of O-ethyl by O-aryl as the
non-leaving group diminishes the push exerted by this group to
expel the nucleofuge. Therefore, the rate constant k2 becomes
smaller and comparable with the rate constant for deprotonation
of the Tꢀ intermediate (k3). (viii) The k2 values obtained for the
reactions of 1 and 2 with 1-formylpiperazine are similar to those
obtained for their anilinolysis under the same experimental
conditions, in accordance with the finding that the nucleofugality
of the leaving group from the Tꢀ intermediate is independent of
the amine basicity and nature.
The k1 values for the reactions of 4-methylphenyl 4-nitrophenyl
thionocarbonate with a given SA amine are 2 to 6 times larger
than those of 1 with the same amine, probably due to the larger
electron withdrawing effect of 4-nitrophenoxy relative to
4-nitrobenzenethio.[11]
From Table 5 and Fig. 1 it can be observed that the k1 values
obtained for the reactions of SA amines with 2 and 3 are larger
than those for 1 and 4, respectively. These results can be
explained by the larger electron-withdrawing effect of Cl than
CH3 from the non-leaving group, which leads to a more positive
thiocarbonyl carbon in 2 and 3, which in turn facilitates the
nucleophilic attack by the amine.
The positive values for the sensitivity of logk on the pKa of
ꢁ1
both the non-leaving and leaving groups (bnlg ¼ 0.47 and
blg ¼ 0.49 in Eqn (7)) can be attributed to the fact that as the
basicity (i.e., pKa) of both groups in the intermediate Tꢀ increase,
they can exert a better push to expel the amine from this
intermediate.[15,16]
The reactions of SA amines with O-ethyl S-(4-nitrophenyl)
dithiocarbonate in aqueous ethanol are driven by a stepwise
mechanism, with the formation of only one tetrahedral
intermediate (Tꢀ).[18] Namely, there is no competition between
leaving group expulsion from Tꢀ (k2 step) and proton transfer
from Tꢀ to the amine to give Tꢁ (k3 step). The former step is faster
than the latter. The difference with the SA aminolysis of 1 and 2
(this work, where both Tꢀ and Tꢁ are kinetically significant) can
be explained by the superior push provided by EtO in the
corresponding Tꢀ,[16] compared with that by 4-MePhO or
4-ClPhO in the respective intermediates Tꢀ, to expel the leaving
group. Therefore, it is reasonable that for the reactions of the
O-ethyl derivative, k2 >> k3[N].
Effect of the electrophilic group
The reactions of 2 with SA amines in aqueous ethanol are
stepwise (this work). In contrast, the reactions of the same amines
with O-(4-chlorophenyl) S-(4-nitrophenyl) thiolcarbonate, in the
same experimental conditions, are concerted.[19] These results
indicate that the change of thiocarbonyl as the electrophilic
group by carbonyl destabilizes the tetrahedral intermediate Tꢀ,
changing the mechanism from stepwise to concerted. This
destabilization can be attributed to the larger ability of Oꢁ than
EXPERIMENTAL
Materials
Dithiocarbonates 1, 2, and 3 were synthesized as described.[6]
O-(4-methylphenyl) S-phenyl dithiocarbonate (4) was synthes-
ized by the reaction of phenyl chlorodithioformate with
4-methylphenoxide, as previously described for the preparation
of dithiocarbonate 3.[6] The solid product 4 showed the following
characteristics: m.p. 62–63 8C (lit[23] 59.5–60.5 8C); 1H NMR
(400 MHz, CDCl3) dH 7.60 (m, 2H), 7.50 (m, 3H), 7.30 (d, J ¼ 8.2 Hz,
Sꢁ in Tꢀ to form the double bond with carbon due to the stronger
[20]
—
—
p-bonding energy of the C O group relative to C S.
This
—
—
should increase the expulsion rates of both the amine (kꢁ1) and
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Copyright ß 2010 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2011, 24 466–473

REACTIONS OF O-ARYL S-ARYLDITHIOCARBONATES
Hz, 2H), 6.96 (d, J ¼ 8.5 Hz, 2H), 2.30 (s, 3H); 13C NMR (100 MHz,
CDCl3) dC 21.0, 117.9, 121.6, 129.5, 130.1, 130.3, 135.2, 136.5, 152.4,
214.5.
Acknowledgements
We thank MECESUP of Chile (projects PUC-0004, UCH 0116, and
RED QUIMICA UCH-01) and FONDECYTof Chile (projects 1060593,
and 1095145) for financial support. M.G. thanks CONICYT of Chile
for a doctoral fellowship.
Kinetic measurements
The kinetics of the reactions were analyzed through a diode array
spectrophotometer in 44 wt% ethanol–water, at 25.0 ꢀ 0.1 8C and
an ionic strength of 0.2 M (maintained with KCl). The reactions of
dithiocarbonates 1 and 2 were followed at 420 nm (appearance
of 4-nitrobenzenethiolate anion), and those of 3 and 4 at 260 nm
(appearance of the corresponding aryl thionocarbamate).
The reactions were studied under at least 10-fold amine excess
over the substrate, the initial concentration of the latter being
2.5 ꢃ 10ꢁ5 M. Under these conditions pseudo-first-order rate
coefficients (kobs) were found throughout, the reactions being
followed for at least five half-lives.
For all the reactions, the pH was maintained constant (two or
three pH values for each amine) by the buffer formed by partial
protonation of the amine. The experimental conditions of the
reactions and the values of kobs are detailed in Supplementary
Materials. The ranges of amine concentration and kobs values are
summarized in Tables 1–4.
REFERENCES
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[3] H. K. Oh, J. Y. Lee, J. W. Yun, Y. S. Park, I. Lee, Int. J. Chem. Kinet. 1998,
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[9] J. M. Sayer, W. P. Jencks, J. Am. Chem. Soc. 1973, 95, 5637–5649.
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[12] P. J. Taylor, J. Chem. Soc. Perkin Trans. 2 1993, 1423–1427.
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Product studies
In the reactions of dithiocarbonates 1 and 4 with morpholine and
piperazine, the corresponding 4-methylphenyl thionocarbamates
were found as final products. Also, 4-nitrobenzenethiolate ion
was identified as one of the products of the reactions of 1 and 2.
These identifications were carried out by comparison of the
UV-vis spectra after completion of these reactions with those of
authentic samples, under the same reaction conditions.
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bamates were identified as one of the products by comparing
the final UV-vis spectra of the reactions with those of the
product of the reactions of 4-chlorophenyl chlorothionoformate
with the same amines under the same experimental conditions
(lmax ¼ 260 nm).
[14] R. P. Bell, The Proton in Chemistry, Methuen, London, 1959. p 159.
[15] M. J. Gresser, W. P. Jencks, J. Am. Chem. Soc. 1977, 99, 6963–6970.
[16] M. J. Gresser, W. P. Jencks, J. Am. Chem. Soc. 1977, 99, 6970–6980.
[17] E. A. Castro, P. Garcia, L. Leandro, N. Quesieh, A. Rebolledo, J. G.
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[18] E. A. Castro, G. Munoz, M. Salas, J. G. Santos, Int. J. Chem. Kinet. 1995,
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[19] E. A. Castro, M. Aliaga, J. G. Santos, J. Phys. Org. Chem. 2008, 21,
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[20] S. V. Hill, S. Thea, A. Williams, J. Chem. Soc. Perkin Trans. 2 1983,
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[22] E. A. Castro, F. Ibanez, M. Salas, J. G. Santos, J. Org. Chem. 1991, 56,
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[23] Y. Araki, Bull. Chem. Soc. Jpn. 1970, 43, 252–257.
J. Phys. Org. Chem. 2011, 24 466–473
Copyright ß 2010 John Wiley & Sons, Ltd.
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