Phenolysis and aminolysis of 4-nitrophenyl and 2,4-dinitrophenyl S-methyl thiocarbonates in aqueous ethanol

Article abstract of DOI:10.1002/kin.20562

The reactions of S-methyl O-(4-nitrophenyl) thiocarbonate (1) and S-methyl O-(2,4-dinitrophenyl) thiocarbonate (2) with a series of secondary alicyclic (SA) amines and phenols are subjected to a kinetic investigation. Under nucleophile excess, pseudo-first-order rate coefficients (k_obs) are obtained. Plots of k_obs against the free nucleophile concentration at constant pH are linear with slopes k_N. The Brnsted plots (log k_N vs. nucleophile pK_a) for the reactions are linear with slope (β) values in the 0.5-0.7 range, in accordance with concerted mechanisms. Comparison of the SA aminolysis of 1 with the same one carried out in water shows that the change of solvent from water to aqueous ethanol destabilizes the zwitterionic tetrahedral intermediate, changing the mechanism from stepwise to concerted. This destabilization is greater than that due to the change from SA amines to quinuclidines. For the phenolysis reactions, the k_N values in aqueous ethanol are smaller than those for the same reactions in water. Considering that the nucleophile is an anion, this result is unexpected because the anion should be more stabilized in the more polar solvent. This result is explained by the facts that the phenoxide reactant has a negative charge that is delocalized in the aromatic ring and the transition state is highly polar.

Full text of DOI:10.1002/kin.20562

Phenolysis and Aminolysis
of 4-Nitrophenyl and
2,4-Dinitrophenyl S-Methyl
Thiocarbonates in Aqueous
Ethanol
´
ENRIQUE A. CASTRO, MARGARITA E. ALIAGA, MARJORIE CEPEDA, JOSE G. SANTOS
Facultad de Qu´ımica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 6094411, Chile
Received 28 December 2010; revised 8 March 2011; accepted 9 March 2011
DOI 10.1002/kin.20562
Published online 27 April 2011 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: The reactions of S-methyl O-(4-nitrophenyl) thiocarbonate (1) and S-methyl O-
(2,4-dinitrophenyl) thiocarbonate (2) with a series of secondary alicyclic (SA) amines and
phenols are subjected to a kinetic investigation. Under nucleophile excess, pseudo-first-order
rate coefficients (kobs) are obtained. Plots of kobs against the free nucleophile concentration
at constant pH are linear with slopes kN. The Brønsted plots (log kN vs. nucleophile pKa)
for the reactions are linear with slope (β) values in the 0.5–0.7 range, in accordance with
concerted mechanisms. Comparison of the SA aminolysis of 1 with the same one carried out
in water shows that the change of solvent from water to aqueous ethanol destabilizes the
zwitterionic tetrahedral intermediate, changing the mechanism from stepwise to concerted.
This destabilization is greater than that due to the change from SA amines to quinuclidines.
For the phenolysis reactions, the kN values in aqueous ethanol are smaller than those for the
same reactions in water. Considering that the nucleophile is an anion, this result is unexpected
because the anion should be more stabilized in the more polar solvent. This result is explained
by the facts that the phenoxide reactant has a negative charge that is delocalized in the aromatic
ring and the transition state is highly polar. ꢀ 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43:
C
353–358, 2011
INTRODUCTION
The nucleophilic substitution reactions of carbonyl and
thiocarbonyl derivatives in a solution with reagents of
varying nucleophilicity have been studied by several
Correspondence to: J. G. Santos; e-mail: jgsantos@uc.cl.
Contract grant sponsor: MECESUP of Chile.
Contract grant number: UCH-06011.
groups. To date there is a suitable database since the
kinetics and mechanisms of these processes have been
fully described [1–18]. Taking into account these stud-
ies, several factors have been reported to affect the
Contract grant sponsor: FONDECYT of Chile.
Contract grant number: 1095145.
Supporting Information is available in the online issue at
www.wileyonlinelibrary.com.
c
ꢀ
2011 Wiley Periodicals, Inc.

354
CASTRO ET AL.
kinetics and mechanisms of these reactions: (i) nu-
cleophile nature and basicity, (ii) nonleaving group,
(iii) leaving group (nucleofuge), and (iv) electrophilic
group.
Pseudo-first-order rate coefficients (kobs) were
found throughout and determined by means of the ki-
netics software for first-order reactions of the spec-
trophotometer. Errors in the kobs values were less than
3%. The experimental conditions of the reactions and
the values of kobs are shown in Tables S1–S21 in the
Supporting Information.
In addition, other studies involving different nucle-
ophilic substitution reactions on carbonyl derivatives
show that the solvent plays an important role in con-
trolling the dynamics of a chemical reaction [19,20].
Nevertheless, there have been relatively few reports on
the effect of the solvent on the mechanisms of these
reactions. One of these is the reaction of O-ethyl S-
2,4,6-trinitrophenyl dithiocarbonate with secondary al-
icyclic (SA) amines, which changes from stepwise in
water [21] to concerted in aqueous 44 wt% ethanol
[22].
With the purpose to enhance the knowledge about
the solvent effect on these reactions, in this work
we study the aminolysis (SA amines) and phenoly-
sis of S-methyl O-(4-nitrophenyl) thiocarbonate (1)
and S-methyl O-(2,4-dinitrophenyl) thiocarbonate (2)
in aqueous 44 wt% ethanol. By comparison of these
reactions with the same ones carried out in water, the
effect of the solvent on the kinetics and mechanism
will be assessed.
Product Studies
For the aminolysis and phenolysis reactions of
thiocarbonates 1 and 2, 4-nitrophenoxide and 2,4-
dinitrophenoxide anions, respectively, were identified
as one of the products. This was achieved by com-
parison of the UV–vis spectra after completion of
these reactions with those of authentic samples of 4-
nitrophenol and 2,4-dinitrophenol under the same re-
action conditions.
RESULTS AND DISCUSSION
The kinetics of all the studied reactions is in accordance
with Eqs. (1) and (2), where [P] and [S] are the prod-
uct and substrate concentrations, respectively, and k0
and kN are the rate coefficients for solvolysis and phe-
nolysis or aminolysis of the substrates, respectively.
The values of k0 and kN showed no dependence on
pH within the pH range employed. These values were
obtained as the intercept and slope, respectively, of lin-
ear plots of kobs against the nucleophile concentration,
at constant pH. The pseudo-first-order rate constants
(kobs), obtained under an excess of phenol or secondary
alicyclic (SA) amine, and the experimental conditions
for the studied reactions are detailed in Tables S1–S21
in the Supporting Information.
EXPERIMENTAL
Materials
Phenols and secondary alicyclic (SA) amines were
purified by recrystallization or distillation. Thiocar-
bonates 1 and 2 were samples from previous studies
[23,24].
Kinetic Measurements
d[P]
The kinetics of the reactions were analyzed through
a diode array spectrophotometer in 44 wt% ethanol–
water at 25.0 0.1◦C and an ionic strength of 0.2 M
(maintained with KCl). The reactions were followed at
the 300–500 nm wavelength range.
= kobs[S]
(1)
(2)
dt
kobs = k0 + kN[nucleophile]
The k0 values were much smaller than the kN [nucle-
ophile] term in Eq. (2) for the studied reactions. The
values of kN for the reactions of thiocarbonates 1 and
2 with SA amines are shown in Table I, and those with
phenols are shown in Table II.
The reactions were studied under at least a 10-fold
excess of nucleophile over the substrate, the initial con-
centration of the latter being 2.5 × 10−5 M. Under these
conditions, pseudo-first-order rate coefficients (kobs
)
were found throughout, the kinetics being measured
for at least five half-lives at 400 and 360 nm following
4-nitrophenoxide and 2,4-dinitrophenoxide ions for-
mation, respectively. In most of the reactions, the pH
was maintained constant by the nucleophile, except
in some reactions where the pH was maintained by
0.01 M borate buffer.
The kN values, as well as those of the pKa of the
conjugate acids of these amines, in Table I, were statis-
tically corrected [21] with q = 2 for piperazine (q = 1
for all the other SA amines) and p = 2 for all the con-
jugate acids of the amines [21]. The parameter q is the
number of equivalent basic sites in the free amine, and
p is the number of equivalent dissociable protons in
International Journal of Chemical Kinetics DOI 10.1002/kin

PHENOLYSIS AND AMINOLYSIS OF THIOCARBONATES IN AQUEOUS ETHANOL
355
Table I Values of pKa for the Series of Secondary
Alicyclic (SA) Amines and Nucleophilic Rate Constants
(kN) for the SA Aminolysis of S-methyl
O-(4-nitrophenyl) Thiocarbonate (1) and S-methyl
O-(2,4-dinitrophenyl) Thiocarbonate (2)a,b
1.5
0.0
103kN (M−1 s−1
)
Amine
pK
1
2
a
q
k
Piperidine
Piperazine
1-(2-Hydroxyethyl)
piperazine
10.82
9.71
9.09
197
202
41
9
6
2
1030 50
590 20
152
6
Morpholine
1-Formylpiperazine
Piperazinium ion
8.48
7.63
5.57
11.8 0.4
14.0 0.4
0.25 0.01
124
75
6
5
6
8
10
12
pKa + log(p/q)
–
apKa and kN values were determined in aqueous 44 wt% ethanol.
bErrors shown are standard deviations.
Figure 1 Brønsted-type plots (statistically corrected, see
the text) obtained for the reactions of SA amines with thio-
carbonate 1 ( ) and thiocarbonate 2 ( ) in 44 wt% ethanol–
•
◦
water at 25.0◦C; ionic strength 0.2 M (KCl). Also shown
Table II Values of pKa for the Series of Phenols and
Nucleophilic Rate Constants (kN) for the Phenolysis of
S-methyl O-(4-nitrophenyl) Thiocarbonate (1) and
S-methyl O-(2,4-dinitrophenyl) Thiocarbonate (2)a,b
is the plot for the SA aminolysis of 2 ( , [23]) in water at
ꢀ
25.0◦C; ionic strength 0.2 M (KCl).
103kN (M−1 s−1
)
data in the literature to predict a good estimation of the
pKa0 for these reactions.
Phenol
pK
1
2
a
Nevertheless, the following argument can be useful
to decide about the mechanism: For the SA aminoly-
sis of thiocarbonate 1 in water, a linear Brønsted plot
with slope 0.9 was found [23]. This indicates the pres-
ence of a zwitterionic tetrahedral intermediate (T ) on
the reaction pathway, its breakdown to products being
the rate-determining step [3,4,8,9]. This means that the
pKa0 value for the SA aminolysis of 1 in water is larger
than 10.8 (the pKa for the most basic SA amine studied)
[3,4,8,9]. It is known that the change of solvent from
water to a less polar solvent fastens amine expulsion
from T (larger k−1), but does not affect significantly
the expulsion of aryloxide (similar k2) [9]. This is be-
cause the transition state (TS) for T formation is less
polar than T , but the TS for T breakdown is of sim-
ilar polarity as T [9]. A larger k−1/k2 ratio signifies
a larger pKa0 value [3,4,8,9]. Therefore, the pKa0 value
for the SA aminolysis of 1 in aqueous ethanol should
be much higher than 10.8 if this reaction were step-
wise, and the Brønsted plot for this reaction should be
linear with slope ca. 0.8–1 (the same rate-determining
step as that in water). In view that the actual Brønsted
slope is 0.57, one can safely conclude that the reaction
of 1 with SA amines in aqueous ethanol is concerted;
see Scheme 1 (X = H).
4-Methoxyphenol
Phenol
3-Chlorophenol
4-Cyanophenol
2,6-Difluorophenol
11.55
11.16
10.23
8.60
149
42
19.0 0.5
1.18 0.06
0.83 0.04
9
2
970 50
288
170
1
1
28.6 0.1
6.9 0.1
7.21
apKa and kN values were determined in aqueous 44 wt% ethanol.
bErrors shown are standard deviations.
the conjugate acid of the amine [25]. Figure 1 shows
the statistically corrected Brønsted-type plots for the
SA aminolysis of thiocarbonates 1 and 2 in aqueous
ethanol. This figure also includes the statistically cor-
rected Brønsted plot for the reactions of thiocarbonate
2 with SA amines in water [23].
The Brønsted-type plots for the reactions of SA
amines with thiocarbonates 1 and 2 in aqueous ethanol
are linear with slope values (β) 0.57 and 0.40, respec-
tively. These β values are in accordance with those re-
ported for other concerted reactions that show Brønsted
slopes within the range 0.5–0.7 [13,14,22,23].
Nonetheless, it is known that the β 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 (pKa0) for
a hypothetical stepwise mechanism is within the pKa
range used [26,27]. Unfortunately, there are no relevant
For the reactions of 2 with the same amine series
in water, a concerted mechanism was proposed [23].
These reactions are between neutral reactants that pro-
duce ionic products; therefore, if the mechanism were
International Journal of Chemical Kinetics DOI 10.1002/kin

356
CASTRO ET AL.
X
δ
-
O
δ
-
O
O2N
C S Me
δ+
NH
X
O
O
H+
N
C S Me -O
O2N
O C S Me
+
NO2
+
X
1 (X = H)
2 (X = NO2)
H+
NH
Fast
O
N
C S Me
Scheme 1
obtained for the reactions in aqueous ethanol are in ac-
cordance with those found in the concerted reactions
of the same reactants in water [24]. They also agree
with the β values found in other concerted processes,
which show Brønsted slopes within the range 0.5–0.7
[3,4,13,14,23].
0
As was mentioned above, the β value alone is not
enough to conclude that a mechanism is concerted. For
the phenolysis of 1, where 4-nitrophenoxide anion is
the leaving group, the absence of a break (pKa0) at 7.5
(the pKa of 4-nitrophenol in aqueous 44 wt% ethanol)
allows to rule out a stepwise process and confirms
the concerted mechanism. This is shown in Scheme 2
(X = H).
k
6
8
10
12
pKa
On the other hand, the hypothetical pKa0 for the
phenolysis of 2 is out of the pKa range studied (pKa
of 2,4-dinitrophenol is 4.0). Nevertheless, since 2,4-
dinitrophenoxide anion is a better nucleofuge than 4-
nitrophenoxide anion, the putative anionic tetrahedral
intermediate in the reaction of 2 would be even more
unstable than that in the phenolysis of 1, and there-
fore, the mechanism for the phenolysis of 2 in aqueous
ethanol should also be concerted as shown in Scheme
2 (X = NO2).
Figure 2 Brønsted-type plots for the reactions of phenoxide
ions with thiocarbonates 1 ( ) and 2 ( ), in 44 wt% ethanol–
ꢀ
•
◦
water, at 25.0◦C, ionic strength 0.2 M (KCl). Also included
are the same reactions of 1 ( ) and 2 ( ) in water, at 25.0◦C,
ꢁ
ionic strength 0.2 M (KCl), from [24].
stepwise, the putative tetrahedral intermediate would
have a charge separation. As this zwitterionic interme-
diate is unstable for the SA aminolysis of 2 in water,
then it would be even more unstable in aqueous ethanol.
According to this argument, it is highly probable that
the mechanism for the reactions of 2 with SA amines
in the less polar solvent is concerted, in accordance
with Scheme 1 (X = NO2).
From the kN values shown in Tables I and II and
from Figs. 1 and 2, it can be observed that thiocarbon-
ate 2 is more reactive than 1 toward amines and phe-
noxides. This result is in accordance with the greater
electron-withdrawing effect of the 2,4-dinitro group in
2, compared with 4-nitro in 1, which leads to a more
electrophilic carbonyl carbon in 2 and, therefore, more
prone to the nucleophilic attack.
With the kN values for the phenolysis of thiocar-
bonates 1 and 2, as well as those of the pKa of the
phenols in Table II, the Brønsted-type plots of Fig. 2
were obtained. The plots are linear with slope (β) val-
ues of 0.65 and 0.55, respectively. This figure also in-
cludes the plots for the same reactions in water, which
are concerted, with β = 0.51 and 0.66 for the phe-
nolysis of 1 and 2, respectively [24]. The β values
Solvent Effect on Mechanism
The aminolysis (SA amines) of 1 in aqueous ethanol
(this study) is in accordance with a concerted
International Journal of Chemical Kinetics DOI 10.1002/kin

PHENOLYSIS AND AMINOLYSIS OF THIOCARBONATES IN AQUEOUS ETHANOL
357
X
δ
δ
O
O2N
O
C S Me
O
δ-
X
Z
O
Z
O
O2N
O C S Me
O C S Me
+
+
O
X
1 (X = H)
O2N
O-
2 (X = NO2)
Z
Scheme 2
mechanism, as shown in Scheme 1 (X = H). It is
noteworthy that the same reaction in water proceeds
by a stepwise mechanism [23] (see above). Therefore,
the change of solvent from water to a less polar one,
such as aqueous ethanol, greatly destabilizes the zwit-
terionic tetrahedral intermediate. Two situations could
then be possible: (i) The intermediate could be destabi-
lized to the point of nonexistence (enforced concerted
mechanism) or (ii) the intermediate could still exist
but the free energy of activation of the stepwise pro-
cess could be larger than that of the concerted mecha-
nism [2,28,29]. The same behavior was described for
the reactions of SA amines with O-ethyl S-(2,4,6-
trinitrophenyl) dithiocarbonate, which shows a step-
wise mechanism in water [21] and a concerted process
in aqueous 44 wt% ethanol [22].
On the other hand, the reactions of 1 with quinu-
clidines in water are stepwise [23]; therefore, the cor-
responding tetrahedral intermediate exists. It is known
that quinuclidines destabilize the zwitterionic tetrahe-
dral intermediate relative to isobasic SA amines [30]. In
consequence, the solvent change from water to aqueous
44 wt% ethanol destabilizes this tetrahedral interme-
diate more than the change from SA amines to quinu-
clidines.
reactants are neutral and the transition state presents
charge dispersion, it is possible to expect a greater
stabilization of the transition state (relative to reactants)
in the more polar medium (water).
For the phenolysis reactions, the kN values in aque-
ous ethanol (this study) are smaller (about 15 times)
than those for the same reactions in water [24]. Con-
sidering that the nucleophile is an anion (phenoxide),
this result is unexpected because the anion should be
more stabilized in the more polar solvent.
A possible explanation is that the negative charge on
the TS is localized mainly in the leaving group (a late
TS) and, therefore, the TS would be more solvated by
water relative to aqueous ethanol. On the other hand,
it is necessary to consider that the phenoxide reactant
has a negative charge that is delocalized in the aro-
matic ring; therefore, it is less stabilized in a polar
solvent than could be expected for an anion with local-
ized charge, such as an alkoxide anion [24]. Because
of this, the delocalization of charge makes the nucle-
ophile a less anionic species, producing a decrease in
the total solvation energy, which is particularly strong
for a solvent such as water [24]. In accordance with
this, it is possible that the activation free energy for the
phenolysis of 1 and 2 in water be smaller than those in
44 wt% aqueous ethanol, therefore, being greater the
nucleophilic rate constants in the former solvent.
For the phenolysis reactions of thiocarbonates 1 and
2, and the SA aminolysis of 2, no changes in mech-
anism were found by the solvent change from water
[23,24] to aqueous 44 wt% ethanol.
CONCLUSIONS
Kinetic Solvent Effect
(i) The aminolysis (SA amines) and phenolysis reac-
tions of thiocarbonates 1 and 2 in aqueous 44 wt%
ethanol are concerted. (ii) For the aminolysis of 1, the
solvent change from water to aqueous 44 wt% ethanol
changes the mechanism from stepwise to concerted.
From Fig. 1, it can be observed that the kN values for
the reactions of 2 with SA amines are greater in water
[23] relative to aqueous ethanol (this study), both being
concerted mechanisms. Taking into account that the
International Journal of Chemical Kinetics DOI 10.1002/kin

358
CASTRO ET AL.
(iii) For the aminolysis of 1, the solvent change from
water to aqueous 44 wt% ethanol destabilizes the tetra-
hedral intermediate more than the change from SA
amines to quinuclidines in water. (iv) The concerted
phenolysis reactions of 1 and 2 are faster in water than
in aqueous 44 wt% ethanol; this is mainly attributed to
charge delocalization in the phenoxide reactant.
11. Um, I.-H.; Kim, K.-H.; Park, H.-R.; Fujio, M.; Tsuno,
Y. J Org Chem 2004, 69, 3937–3942.
12. Oh, H. K.; Ha, J. S.; Sung, D. D.; Lee, I. J Org Chem
2004, 69, 8219–8223.
13. Castro, E. A.; Ramos, M.; Santos, J. G. J Org Chem
2009, 74, 6374–6377.
14. Castro, E. A.; Aliaga, M.; Campodo´nico, P. R.; Cepeda,
M.; Contreras, R.; Santos, J. G. J Org Chem 2009, 74,
9173–9179.
15. Lee, I.; Koo, I. S. Tetrahedron 1983, 39, 1803–1807.
16. Lee, I.; Lee, W. H.; Sohn, S. C.; Kim, C. S. Koo, I. S.
Tetrahedron 1985, 41, 2635–2641.
17. Hong, S. W.; Koh, H. J.; Lee, H. W.; Lee, I. Bull Korean
Chem Soc 1999, 20, 1172–1176.
18. Lee, H. W.; Guha, A. K.; Lee, I. Int J Chem Kinet 2002,
34, 632–637.
19. Um, I.-H.; Yoon, H.-W; Lee, J.-S; Moon, H.-J, Kwon,
D.-S J Org Chem 1997, 62, 5939–5944.
We thank the program “Mejoramiento de la calidad y la
equidad de la Educacio´n Superior” (MECESUP) of Chile
(project UCH-06011) and Fondo Nacional de Desarrollo
Cient´ıfico y Tecnolo´gico (FONDECYT) of Chile (project
1095145) for financial support. M. C. thanks Comision Na-
cional de Investigacio´n Cient´ıfica y Tecnolo´gica (CONICYT)
of Chile for a doctoral fellowship and project AT-24080020.
20. Ghosh, K. K.; Satnami, M. L.; Sinha, D.; Vaidya, J. J
Mol Liq 2005, 116, 55–60.
BIBLIOGRAPHY
21. Castro, E. A.; Iba´n˜ez, F.; Salas, M.; Santos, J. G.;
1. Johnson, S. L. Adv Phys Org Chem 1967, 5, 237–330.
2. Williams, A. Chem Soc Rev 1994, 23, 93–100.
3. Castro, E. A. Chem Rev 1999, 99, 3505–3524.
4. Castro, E. A. J Sulfur Chem 2007, 28, 401–429.
5. Stefanidis D.; Cho S.; Dhe-Paganon S.; Jenks, W. P. J
Am Chem Soc 1993, 115, 1650–1656.
6. Jencks, W. P.; Gilchrist, M. J Am Chem Soc 1968, 90,
2622–2637.
7. Satterthwait, A. C.; Jencks, W. P. J Am Chem Soc 1974,
96, 7018–7031.
8. Gresser, M. J.; Jencks, W. P. J Am Chem Soc 1977, 99,
6963–6970.
Sepu´lveda. P. J Org Chem 1993, 58, 459–463.
22. Castro, E. A.; Cubillos, M.; Mu
n˜oz, G.; Santos, J. G. Int
J Chem Kinet 1994, 26, 571–575.
23. Castro, E. A.; Aliaga, M.; Santos, J. G. J Org Chem
2005, 70, 2679–2685.
24. Castro, E. A.; Aliaga, M.; Santos, J. G. J Phys Org Chem
2007, 20, 533–538.
25. Bell R. P. The Proton in Chemistry; Methuen: London,
1959; p 159.
26. Chystiuk, E.; Wiliams, A. J Am Chem Soc 1987, 109,
3040–3046.
27. Williams, A. Acc Chem Res 1989, 22, 387–392.
28. Jencks, W. P. Acc Chem Res 1980, 13, 161–169.
29. Jencks, W. P. Chem Soc Rev 1981, 10, 345–375.
9. Gresser, M. J.; Jencks, W. P. J Am Chem Soc 1977, 99,
6970–6980.
10. Neuvonen, H.; Neuvonen, K.; Pasanen, P. J Org Chem
2004, 69, 3794–3800.
30. Castro, E. A.; Mu
64, 8298–8301.
n˜oz, P.; Santos, J. G. J Org Chem 1999,
International Journal of Chemical Kinetics DOI 10.1002/kin