Kinetic and mechanistic investigation of the aminolysis of 3-methoxyphenyl 3-nitrophenyl thionocarbonate, 3-chlorophenyl 3-nitrophenyl thionocarbonate, and bis(3-nitrophenyl) thionocarbonate

Article abstract of DOI:10.1021/jo025562a

The reactions of the title thionocarbonates (6, 7, and 8, respectively) with a series of secondary alicyclic amines are subjected to a kinetic investigation in 44 wt % ethanol-water, 25.0 °C, ionic strength 0.2 M (KCl). Under excess amine, pseudo-first-order rate coefficients (k_obsd) are obtained for all reactions. Reactions of substrates 6 and 7 with piperidine and of thionocarbonate 8 with the same amine and piperazine, 1-(2-hydroxyethyl)piperazine, and morpholine show linear k_obsd vs [amine] plots, with slopes (k₁) independent of pH. On the other hand, these plots are nonlinear upward for the reactions of substrates 6 and 7 with all the amines, except piperidine, and also for the reactions of compound 8 with 1-formylpiperazine and piperazinium ion. For all these reactions a mechanistic scheme is proposed with the formation of a zwitterionic tetrahedral intermediate (T^±), which can transfer a proton to an amine to give an anionic intermediate (T^-). Rate and equilibrium microcoefficients of this scheme, K₁, k_-1, K₁, (= k₁/k_-1), and k₂, are obtained by fitting the nonlinear plots through an equation derived from the scheme. The Broensted-type plots for k₁ are linear with slopes β₁ = 0.19, 0.21, and 0.26 for the aminolysis of 6, 7, and 8, respectively. This is consistent with the hypothesis that the formation of T^± (k₁ (k₁ step) is the rate-determining step. The k₁ values for these reactions follow the sequence 8 > 7 > 6, consistent with the sequence of the electron-withdrawing effects from the substituents on the nonleaving group of the substrates. The k₁ values for the aminolysis of 6, 7, and 8 are smaller than those for the same aminolysis of 3-methoxyphenyl, 3-chlorophenyl, and 4-cyanophenyl 4-nitrophenyl thionocarbonates (2, 3, and 4, respectively). The k₂ values (expulsion of the nucleofuge from T^±) increase as the electron withdrawal from the nonleaving group increases. These values are smaller for the aminolysis of 6, 7, and 8 compared to those for the same aminolysis of 2, 3, and 4, respectively.

Full text of DOI:10.1021/jo025562a

J . Org. Chem. 2002, 67, 4309-4315
4309
Kin etic a n d Mech a n istic In vestiga tion of th e Am in olysis of
3-Meth oxyp h en yl 3-Nitr op h en yl Th ion oca r bon a te, 3-Ch lor op h en yl
3-Nitr op h en yl Th ion oca r bon a te, a n d Bis(3-n itr op h en yl)
Th ion oca r bon a te
Enrique A. Castro,* Angelique Galvez, Leonardo Leandro, and J ose´ G. Santos*
Facultad de Quı´mica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 22, Chile
ecastro@puc.cl
Received J anuary 28, 2002
The reactions of the title thionocarbonates (6, 7, and 8, respectively) with a series of secondary
alicyclic amines are subjected to a kinetic investigation in 44 wt % ethanol-water, 25.0 °C, ionic
strength 0.2 M (KCl). Under excess amine, pseudo-first-order rate coefficients (kobsd) are obtained
for all reactions. Reactions of substrates 6 and 7 with piperidine and of thionocarbonate 8 with the
same amine and piperazine, 1-(2-hydroxyethyl)piperazine, and morpholine show linear kobsd vs
[amine] plots, with slopes (k1) independent of pH. On the other hand, these plots are nonlinear
upward for the reactions of substrates 6 and 7 with all the amines, except piperidine, and also for
the reactions of compound 8 with 1-formylpiperazine and piperazinium ion. For all these reactions
a mechanistic scheme is proposed with the formation of a zwitterionic tetrahedral intermediate
(T(), which can transfer a proton to an amine to give an anionic intermediate (T-). Rate and
equilibrium microcoefficients of this scheme, k1, k-1, K1 () k1/k-1), and k2, are obtained by fitting
the nonlinear plots through an equation derived from the scheme. The Bro¨nsted-type plots for k1
are linear with slopes â1 ) 0.19, 0.21, and 0.26 for the aminolysis of 6, 7, and 8, respectively. This
is consistent with the hypothesis that the formation of T( (k1 step) is the rate-determining step.
The k1 values for these reactions follow the sequence 8 > 7 > 6, consistent with the sequence of the
electron-withdrawing effects from the substituents on the “nonleaving” group of the substrates.
The k1 values for the aminolysis of 6, 7, and 8 are smaller than those for the same aminolysis of
3-methoxyphenyl, 3-chlorophenyl, and 4-cyanophenyl 4-nitrophenyl thionocarbonates (2, 3, and 4,
respectively). The k2 values (expulsion of the nucleofuge from T() increase as the electron withdrawal
from the nonleaving group increases. These values are smaller for the aminolysis of 6, 7, and 8
compared to those for the same aminolysis of 2, 3, and 4, respectively.
In tr od u ction
4-methylphenyl,5a 3-methoxyphenyl, 3-chlorophenyl, and
4-cyanophenyl 4-nitrophenyl thionocarbonates (1-4, re-
spectively) in 44 wt % ethanol-water.5b We have chosen
these thionocarbonates in view of the wide span of
electron-withdrawing abilities of the substituents at-
tached to the “nonleaving” group of the substrates. We
have also studied kinetically the same aminolysis of
4-methylphenyl 3-nitrophenyl thionocarbonate (5) in the
same solvent.5a
To extend our investigations on the mechanisms of the
aminolysis of diaryl thionocarbonates, in this work, we
study the reactions of sec alicyclic amines with 3-meth-
oxyphenyl and 3-chlorophenyl 3-nitrophenyl thionocar-
bonates (6 and 7, respectively) and bis(3-nitrophenyl
thionocarbonate) (8) in 44 wt % ethanol-water. These
reactions will be compared with those of the thionocar-
bonates 1-5 with the aim of assessing the effect of both
the leaving and “nonleaving” groups of the substrates on
the kinetics and mechanisms of these reactions.
Although much work has been devoted to the study of
the kinetics of reactions involving dithiocarbonates and
thiolcarbonates,1,2 especially their aminolysis,2,3 less is
known on the kinetics of the aminolysis of thionocarbon-
ates.4,5 Among the latter studies, there are only a few
(as far as we are aware) on diaryl thionocarbonates.4c,5
To shed light on the mechanism of the aminolysis of
diaryl thionocarbonates, we have reported a kinetic
investigation on the reactions of sec alicyclic amines with
* To whom correspondence should be addressed. Fax: (56-2) 6864744.
(1) Eto, M.; Tajiri, O.; Nakagawa, H.; Harano, K. Tetrahedron 1998,
54, 8009-8014. Humeres, E.; Sequinel, L. F.; Nunes, M.; Oliveira, C.
M. S.; Barrie, P. J . Can. J . Chem. 1998, 76, 960-965. Humeres, E.;
Soldi, V.; Klug, M.; Nunes, M.; Oliveira, C. M. S.; Barrie, P. J . Can. J .
Chem. 1999, 77, 1050-1056. Castro, E. A.; Cubillos, M.; Santos, J . G.;
Buja´n, E. I.; Remedi, M. V.; Ferna´ndez, M. A.; de Rossi, R. H. J . Chem.
Soc., Perkin Trans. 2 1999, 2603-2607.
(2) Castro, E. A. Chem. Rev. 1999, 99, 3505-3524 and references
therein.
(3) Oh, H. K.; Lee, Y. H.; Lee, I. Int. J . Chem. Kinet. 2000, 32, 131-
135. Castro, E. A.; Leandro, L.; Millan, P.; Santos, J . G. J . Org. Chem.
1999, 64, 1953-1957. Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org.
Chem. 1999, 64, 6342-6346. Castro, E. A.; Mun˜oz, P.; Santos, J . G. J .
Org. Chem. 1999, 64, 8298-8301.
(4) (a) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org. Chem. 1996,
61, 3501-3505. (b) Castro, E. A.; Cubillos, M.; Santos, J . G.; Tellez, J .
J . Org. Chem. 1997, 62, 2512-2517. (c) Castro, E. A.; Santos, J . G.;
Tellez, J .; Uman˜a, M. I. J . Org. Chem. 1997, 62, 6568-6574. (d) Castro,
E. A.; Saavedra, C.; Santos, J . G.; Uman˜a, M. I. J . Org. Chem. 1999,
64, 4, 5401-5407.
Exp er im en ta l Section
Ma ter ia ls. The secondary alicyclic amines were purified as
reported.6 Thionocarbonates 6-8 have not been previously
prepared, to our knowledge. They were synthesized according
(5) (a) Castro, E. A.; Garcia, P.; Leandro, L.; Quesieh, N.; Rebolledo,
A.; Santos, J . G. J . Org. Chem. 2000, 65, 9047-9053. (b) Castro, E.
A.; Leandro, L.; Quesieh, N.; Santos, J . G. J . Org. Chem. 2001, 66,
6130-6135.
10.1021/jo025562a CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/09/2002

4310 J . Org. Chem., Vol. 67, No. 12, 2002
Castro et al.
Ta ble 1. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Am in olysis of 3-Meth oxyp h en yl 3-Nitr op h en yl
Th ion oca r bon a te (6)a
103[N]tot
Mc
,
103kobsd
,
no. of
runs
b
amine
piperidine
pH
FN
s-1
10.51 0.33 4.0-20
10.82 0.50 1.9-18
11.13 0.67 1.8-18
9.40 0.33 1.9-13
9.71 0.50 1.8-14
10.02 0.67 1.8-15
7.9-29
8.1-29
9
9
10
7
7
8
8
9
8
10
8
7.1-41
piperazine
1.0-12
0.84-19
3.0-32
1-(2-hydroxyethyl)- 8.79 0.33 1.1-11
0.18-2.3
0.34-4.5
0.34-4.7
0.64-11
0.66-19
0.88-8.1
0.19-1.8
0.33-3.8
0.34-8.5
0.051-0.24
0.10-0.56
0.11-0.97
piperazine
9.09 0.50 1.1-11
9.37 0.66 1.2-9.5
8.18 0.33 4.2-42
8.48 0.50 5.0-45
8.78 0.67 2.1-19
7.33 0.33 4.3-43
7.63 0.50 4.9-49
7.93 0.67 5.3-53
5.06 0.33 8.1-81
morpholine
9
1-formylpiperazine
piperazinium ion
10
10
10
10
10
10
to a reported procedure4c,5,7 by the reactions of 3-methoxyphen-
yl, 3-chlorophenyl, or 3-nitrophenyl thionochloroformates with
3-nitrophenol. The thionochloroformates were synthesized as
described.7
5.37 0.50 10-100
5.68 0.67 10-100
Thionocarbonate 6 melted at 109.1-109.8 °C and was
characterized by 1H and 13C NMR (page S2 in Supporting
Information) and elemental analyses. Anal. Calcd for C14H11O5-
NS: C, 55.08; H, 3.63; N, 4.59; S, 10.50. Found: C, 54.54; H,
3.46; N, 4.74; S, 10.12.
Thionocarbonate 7 melted at 129.4-130.2 °C and was
characterized by 1H and 13C NMR (page S2 in Supporting
Information) and elemental analyses. Anal. Calcd for C13H8O4-
ClNS: C, 50.41; H, 2.60; N, 4.52; S, 10.35. Found: C, 50.88;
H, 2.55; N, 4.49; S, 10.67.
a
In 44 wt % ethanol-water at 25.0 °C and an ionic strength of
0.2 M (KCl). Free-amine fraction. c Concentration of total amine
(free-base and protonated forms).
b
Ta ble 2. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Am in olysis of 3-Ch lor op h en yl 3-Nitr op h en yl
Th ion oca r bon a te (7)a
103[N]tot
Mc
,
103kobsd
,
no. of
runs
b
amine
piperidine
pH
FN
s-1
Thionocarbonate 8 melted at 184-185 °C and was charac-
10.52 0.33 4.0-18
10.82 0.50 4.8-24
11.12 0.67 1.9-15
9.40 0.33 1.9-19
9.71 0.50 1.9-19
10.02 0.67 2.0-20
13-39
22-82
8
8
8
1
terized by H and 13C NMR (page S2 in Supporting Informa-
tion) and elemental analyses. Anal. Calcd for C13H8O6N2S: C,
48.75; H, 2.52; N, 8.75; S, 10.01. Found: C, 48.79; H, 2.60; N,
8.76; S, 9.91.
10-71
piperazine
4.0-27
4.4-39
8.0-64
0.91-11
3.9-18
1.5-25
1.1-23
2.1-29
7.9-41
0.21-4.3
0.24-6.0
0.32-9.8
9
10
10
8
9
8
9
9
7
10
10
10
8
10
10
Kin etic Mea su r em en ts. Reactions were studied spectro-
photometrically by monitoring the appearance of 3-nitrophe-
noxide anion and/or its conjugate acid at 336 nm. All reactions
were carried out in 44 wt % ethanol-water, 25.0 ( 0.1 °C,
ionic strength 0.2 M (maintained with KCl). The initial
concentration of the substrates was (4-6) × 10-5 M.
Three pH values were employed for the reactions of each
amine. The preparation of the kinetic samples as well as the
pH adjustments were carried out as reported.8
Pseudo-first-order rate coefficients (kobsd) were found in all
reactions (at least a 20-fold excess of the total amine over the
substrates was employed). The experimental conditions of the
reactions and the kobsd values obtained are shown in Tables
1-3.
P r od u ct Stu d ies. In the reactions of the thionocarbonates
6-8 with morpholine and piperidine, the final products
obtained were the corresponding 3-methoxyphenyl, 3-chlo-
rophenyl, and 3-nitrophenyl thionocarbamates, respectively,
and 3-nitrophenol (and/or its conjugate base). The identifica-
tion of the final products was carried out by comparison of the
UV-vis spectra at the end of these reactions with those of
authentic samples under the same experimental conditions.
1-(2-hydroxyethyl)- 8.78 0.33 2.5-22
piperazine
9.09 0.50 3.7-18
9.40 0.67 1.9-19
8.17 0.33 4.9-50
8.48 0.50 4.3-43
8.79 0.67 8.5-43
7.32 0.33 4.9-49
7.63 0.50 3.8-38
7.94 0.67 4.2-42
morpholine
1-formylpiperazine
piperazinium ion
5.07 0.33 10-100 0.020-0.88
5.37 0.50 9.8-98
5.67 0.67 9.4-94
0.10-1.8
0.13-2.6
a
In 44 wt % ethanol-water at 25.0 °C and an ionic strength of
0.2 M (KCl). Free-amine fraction. c Concentration of total amine
(free-base and protonated forms).
b
7 with piperazine, 1-(2-hydroxyethyl)piperazine, and
morpholine and in the reactions of compound 8 with
1-formylpiperazine. The reactions of thionocarbonates 6
and 7 with 1-formylpiperazine and piperazinium ion and
that of substrate 8 with the latter amine showed a kinetic
behavior in accordance with a second-order polynomial
equation. On the other hand, first-order kinetics with
respect to amine were obtained for the reactions of
compounds 6 and 7 with piperidine and those of thiono-
carbonate 8 with the four more basic amines.
Resu lts a n d Discu ssion
The pseudo-first-order rate coefficient (kobsd) was found
to vary with the concentration of free amine in different
ways, depending on the substrates and on the amine
basicity.
A complex kinetic order in amine (between 1 and 2)
was exhibited by the reactions of thionocarbonates 6 and
According to these kinetic results, the product analysis,
and the Bro¨nsted-type plots obtained (see below), a
mechanistic scheme is proposed for these reactions
(Scheme 1). This reaction scheme is the same as that
found in the aminolysis of similar thionocarbonates (1-
4) with a better leaving group (4-nitrophenoxide anion
instead of 3-nitrophenoxide anion).5 In this scheme, the
k3 step is the deprotonation of the aminium moiety of a
(6) Castro, E. A.; Ureta, C. J . Org. Chem. 1989, 54, 2153-2159.
(7) Al-Kazimi, H. R.; Tarbell, D. S.; Plant, D. J . Am. Chem. Soc.
1955, 77, 2479-2482.
(8) Castro, E. A.; Angel, M.; Pavez, P.; Santos, J . G. J . Chem. Soc.,
Perkin Trans. 2 2001, 2351-2354.

Investigation of Aminolysis of Thionocarbonates
J . Org. Chem., Vol. 67, No. 12, 2002 4311
Ta ble 3. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Am in olysis of Bis(3-n itr op h en yl) Th ion oca r bon a te
(8)a
103[N]tot
Mc
,
103kobsd
,
no. of
runs
b
amine
piperidine
pH
FN
s-1
10.51 0.33
10.82 0.50
11.13 0.67
9.40 0.33
9.71 0.50
10.02 0.67
8.78 0.33
9.09 0.50
9.40 0.67
8.17 0.33
8.48 0.50
8.79 0.67
7.32 0.33
7.63 0.50
7.94 0.67
5.06 0.33
5.37 0.50
5.68 0.67
1.0-10
1.0-10
3.0-10
1.6-16
3.1-14
1.5-15
4.9-49
4.0-40
3.2-32
5.0-45
5.0-50
5.0-50
3.6-36
4.8-48
9.4-94
10-80
10-90
9.9-99
2.6-26
6.5-54
18-61
3.4-49
11-57
10
10
8
10
7
10
9
10
10
8
piperazine
3.8-65
4.0-51
4.7-49
5.6-59
3.5-35
5.5-61
5.4-92
1.8-36
3.4-53
4.0-71
0.37-3.0
0.55-5.9
0.82-11
1-(2-hydroxyethyl)-
piperazine
morpholine
8
11
10
10
10
8
1-formylpiperazine
piperazinium ion
9
10
a
In 44 wt % ethanol-water at 25.0 °C and an ionic strength of
0.2 M (KCl). Free-amine fraction. c Concentration of total amine
b
(free-base and protonated forms).
F igu r e 1. Plot of kobsd against the free-amine concentration
for the reaction of thionocarbonate 8 with piperazinium ion
in 44 wt % ethanol-water, at 25.0 °C and an ionic strength of
0.2 M. The line was calculated using eq 2 with the micro-
coefficients shown in Table 4.
Sch em e 1
k2 + k3[NH], which is reasonable for weakly basic amines.
This inequality reduces eq 1 to eq 2, where K1 () k1/k-1
)
is the equilibrium constant for the formation of the
intermediate T( in Scheme 1. An example of this type of
plot is shown in Figure 1.
kobsd ) k0 + K1k2[NH] + K1k3[NH]2
(2)
The line in Figure 1 was calculated through eq 2 with
the values of the equilibrium and rate coefficients shown
in Table 4. These values were obtained by nonlinear
least-squares fitting of eq 2 to the experimental points,
introducing into this equation a known and constant
value of k3 (also shown in Table 4). The determination of
the k3 value is discussed below.
The reaction of 1-formylpiperazine with substrate 8
exhibits kobsd vs [NH] plots that are best fitted with the
general equation (eq 1) instead of the restricted one (eq
2). The values of the best fitting parameters, k1, k2, and
k-1, as well as the k3 value, are shown in Table 4. The
adherence of this reaction to eq 1, and not to eq 2, is
presumably due to the fact that for this reaction k-1 is
smaller and k2 is larger than the corresponding values
for the reactions of this amine with compounds 6 and 7
(see Table 4). This is why for the reaction of 1-formylpip-
erazine with 8, k-1 ≈ k2 + k3[NH], and eq 1 applies.
The kobsd vs [NH] plots found in the reactions of
piperazine, 1-(2-hydroxyethyl)piperazine, and morpholine
with thionocarbonates 6 and 7 were best adjusted to the
general equation (eq 1). The best fitting parameters k1,
k-1, and k2 are shown in Table 4. The constant k3 value
used for the fittings was the same as that determined
for the reactions of 1-formylpiperazine and that for the
reaction of 1-formylpiperazine with thionocarbonate 8.
Figure 2 shows an example of the plots of kobsd vs [NH]
fitted through eq 1.
zwitterionic tetrahedral intermediate T( by the corre-
sponding amine to give an anionic tetrahedral intermedi-
ate T-.
Since the tetrahedral intermediates in Scheme 1 are
highly reactive, the steady-state condition can be applied
to them, whereby eq 1 can be obtained. In this equation,
k0 is the solvolytic rate constant and NH represents a
free secondary alicyclic amine.
k1(k2 + k3[NH])[NH]
kobsd ) k0 +
(1)
k-1 + k2 + k3[NH]
In the reactions of the two least basic amines,
1-formylpiperazine and piperazinium cation, with 6 and
7 and in those of the least basic amine, piperazinium
cation, with compound 8, the kobsd vs [NH] plots are best
fitted through a polynomial equation of second order in
The reactions of the most basic amine of the series,
piperidine, with the three substrates of this work show
amine. This can be accounted for by assuming k-1
.

4312 J . Org. Chem., Vol. 67, No. 12, 2002
Castro et al.
Ta ble 4. Va lu es of th e Ra te a n d Equ ilibr iu m Micr ocoefficien ts Obta in ed in th e Am in olysis of 4-Meth ylp h en yl,
3-Meth oxyp h en yl, 3-Ch lor op h en yl, a n d 3-Nitr op h en yl 3-Nitr op h en yl Th ion oca r bon a tes (5-8, Resp ectively)a
k1/s-1 M-1
10-7k-1/s-1
amine
pKa
5b
6
7
8
5b
6
7
8
piperidine
piperazine
1-(2-hydroxyethyl)piperazine
morpholine
1-formylpiperazine
piperazinium cation
10.82
9.71
9.09
8.48
7.63
5.37
3.0
2.2
1.0
0.9
0.45
3.2
3.8
1.3
1.2
5.8
5.2
2.3
2.0
9.4
8.0
2.8
2.5
1.4
2.9
4.0
8.1
1.9
2.9
5.6
1.5
2.2
5.3
30
10
other rate microcoefficients:
10-7k2/s-1 ) 0.5 ( 0.1 (5),b 2.0 ( 0.5 (6), 4 ( 1 (7), and 11 ( 1 (8)c
k3 ) 2 × 109 s-1 M-1 (piperazinium ion)
k3 ) 4 × 109 s-1 M-1 (other amines)
equilibrium microcoefficients:
K1 ) 8.5 × 10-10 M-1 (1-formylpiperazine + 6)
K1 ) 2.2 × 10-9 M-1 (1-formylpiperazine + 7)
K1 ) 6.0 × 10-11 M-1 (piperazinium + 6)
K1 ) 3.0 × 10-10 M-1 (piperazinium + 7)
K1 ) 5.0 × 10-10 M-1 (piperazinium + 8)
a
b
Values of both the pKa and microcoefficients were determined in 44 wt % ethanol-water, 25.0 °C, ionic strength 0.2 M (KCl). Values
were taken from ref 5a, obtained under the same experimental conditions as those of this work. c For reactions of 8, k2 ) 5.5 × 107 s-1
after statistical correction.
F igu r e 2. Plot of kobsd against the free-amine concentration
for the reaction of thionocarbonate 6 with morpholine in 44
wt % ethanol-water, at 25.0 °C and an ionic strength of 0.2
M. The line was calculated using eq 1 with the rate micro-
coefficients shown in Table 4.
F igu r e 3. Plot of kobsd against the free-amine concentration
for the reaction of thionocarbonate 7 with piperidine in 44 wt
% ethanol-water, at 25.0 °C and an ionic strength of 0.2 M.
linear kobsd vs [NH] plots, with a pH-independent slope.
This behavior can be explained by the poor leaving ability
of this amine from the zwitterionic tetrahedral interme-
diate (T( in Scheme 1), which means k-1 , k2 + k3[NH]
in eq 1. This reduces this general equation to a linear
dependence of kobsd on [NH], with a slope k1. The values
of k1 obtained are shown in Table 4. An example of these
plots is exhibited in Figure 3.
The reactions of piperazine, 1-(2-hydroxyethyl)pipera-
zine, and morpholine with thionocarbonate 8 also show
linear kobsd vs [NH] plots, with a pH-independent slope.
These results can be accounted for by a larger value of
k2 and a smaller value of k-1 for the reactions of
thionocarbonate 8 than the corresponding ones for the
reactions of these amines with substrates 6 and 7 (see
Table 4). The k1 values obtained for these reactions are
also included in Table 4.
Deter m in a tion of k3 Va lu es. Since this rate coef-
ficient measures the proton transfer from the aminium
moiety of the zwitterionic tetrahedral intermediate (T()
to the corresponding free amine, knowledge of the pKa
values of both T( and the conjugate acid of the free amine
is requisite for the determination of the k3 values.
The pKa of the tetrahedral intermediates T( in Scheme
1 can be estimated following the method of J encks and
co-workers,9 which assumes that the inductive effect is
the most important for assessing ionization constants of
tetrahedral structures. By this method, the pKa of
intermediates similar to T( can be estimated by the use
of eq 3. In this equation, pKa(ref) is the known pKa of a
(9) Sayer, J . M.; J encks, W. P. J . Am. Chem. Soc. 1973, 95, 5637-
5649. Fox, J . P.; J encks, W. P. J . Am. Chem. Soc. 1974, 96, 1436-
1449.

Investigation of Aminolysis of Thionocarbonates
J . Org. Chem., Vol. 67, No. 12, 2002 4313
tetrahedral reference, FI is the inductive reaction constant
(- 9.2 for intermediates similar to T( in Scheme 1),10 and
σI and σI(ref) are the inductive substituent constants for
groups (variable and reference) attached to the central
carbon atom of the intermediate.
pKa - pKa(ref) ) FI(σI - σI(ref))
(3)
The pKa of structure 9 has been found to be 7.1 pKa
units lower than that of the corresponding aminium
cation.5a The pKa of intermediate 10 can be estimated
through eq 3 with the σI values of 4-methylphenoxy and
3-methoxyphenoxy, σI ) 0.37 and 0.39, respectively.5b
This gives pKa(10) - pKa(9) ) - 9.2 (0.39-0.37) ) ca.
-0.2. Namely, the pKa of 10 is 7.3 pKa units lower than
that of the corresponding aminium cation.
F igu r e 4. Bro¨nsted-type plots (statistically corrected) for k1
for the aminolysis of thionocarbonates 6 (b), 7 (O), and 8 (2)
in 44 wt % ethanol-water, at 25.0 °C and an ionic strength of
0.2 M. Slopes (â) are 0.19 ( 0.03, 0.21 ( 0.03, and 0.26 ( 0.02,
respectively.
The pKa of 11 and 12 can be determined with the σI
values of 3-chlorophenoxy and 3-nitrophenoxy, respec-
tively. These values have been estimated as ca. σI )
0.44.5a,b Obviously, these are rough estimations because
the σI value of 3-nitrophenoxy should be larger than that
of 3-chlorophenoxy, judging by the higher acidity of
3-nitrophenol than 3-chlorophenol (pKa values in water
at 25 °C are 8.4 and 9.0, respectively).11 Taking compound
9 as a reference and assuming σI ) 0.44 for 3-chlorophe-
noxy, eq 3 gives pKa(11) - pKa(9) ) -9.2 (0.44-0.37) )
ca. -0.6. This means that the pKa of 11 is roughly 7.7
pKa units lower than that of the corresponding conjugate
acid of the amine. The pKa of 12 should be lower than
that of 11 for the reasons stated above.
Due to the fact that all the tetrahedral intermediates
(T() formed in the reactions under the present investiga-
tion exhibit pKa values lower than those of the corre-
sponding conjugate acid of the amine, the proton transfer
from T( to the corresponding amine is thermodynami-
cally favorable. Therefore, these transfers are diffusion
controlled, and according to Eigen, the value of k3 should
be ca. 1010 s-1 M-1 in water.12,13 In 44 wt % ethanol-
water, the value of k3 has been reported as 4 × 109 s-1
M-1 in view of the 2.5 times larger viscosity coefficient
of this medium compared to that of water.14 This value
should be independent of the amine since the amine
moiety in T( and the free amine are the same.14 Never-
theless, for the proton transfer from the intermediate T(
formed in the reactions with piperazinium ion to this
amine, the value of k3 has been estimated as 2 × 109 s-1
M-1 in 44 wt % ethanol-water due to electrostatic
repulsion of the positive charges involved.14
Br o1n sted -Typ e P lots. Figure 4 shows the Bro¨nsted-
type plots obtained (statistically corrected) with the k1
values (shown in Table 4) found in the reactions of some
secondary alicyclic amines with substrates 6-8. The
values of k1 for the reactions of piperazine were corrected
statistically by dividing them by q ) 2, since this amine
possesses two equivalent basic sites.6,15 Similarly, the Ka
values of the conjugate acid of the amines were corrected
statistically by multiplying them by q/p, where p is the
number of equivalent protons of the conjugate acid of the
amine. The value of p is 2 for all amines, except
piperazinium ion, whose p value is 4.6,15
The slopes (â) of the Bro¨nsted plots in Figure 4 for the
aminolysis of substrates 6, 7, and 8 are 0.19 ( 0.03, 0.21
( 0.03, and 0.26 ( 0.02, respectively. The magnitudes of
these slopes are consistent with a stepwise mechanism
through a zwitterionic tetrahedral intermediate whereby
its formation is the rate-determining step.2-6,13,14,16 The
order of reactivities toward these amines shown by the
substrates is a consequence of the order of electron-
withdrawing effects of the substituents in the nonleaving
group of the substrates. As shown in Table 4, thionocar-
bonate 5 exhibits the lowest reactivity toward a given
amine due to the slight electron-donating effect of the
4-methyl substituent. This leaves the thionocarbonyl
carbon of 5 less positive relative to that of the other
substrates and, therefore, less prone to nucleophilic
attack by the amine.
The k1 values found in the aminolysis of thionocarbon-
ates 5-7 (Table 4) are smaller than those obtained in
the same aminolysis of thionocarbonates 1-3, respec-
tively. This is understandable in terms of the lesser
electron-withdrawing ability of 3-nitrophenoxy in the
(10) Taylor, P. J . J . Chem. Soc., Perkin Trans. 2 1993, 1423-1427.
(11) Albert, A.; Serjeant, E. P. The Determination of Ionization
Constants; Chapman and Hall: London, 1971; p 87.
(12) Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1-19.
(13) Castro, E. A.; Iban˜ez, F.; Santos, J . G.; Ureta, C. J . Chem. Soc.,
Perkin Trans. 2 1991, 1919-1924.
(14) Castro, E. A.; Leandro, L.; Santos, J . G. Int. J . Chem. Kinet.
1999, 31, 839-845.
(15) Bell, R. P. The Proton in Chemistry; Methuen: London, 1959;
p 159.

4314 J . Org. Chem., Vol. 67, No. 12, 2002
Castro et al.
former substrates relative to that of 4-nitrophenoxy in
the latter thionocarbonates. This leaves the thiocarbonyl
carbon of compounds 5-7 less positive than that of 1-3,
decreasing, therefore, the rate of nucleophilic attack by
the amine.
the greater basicity of the 3-nitrophenoxide anion relative
to that of 4-nitrophenoxide (pKa values of the respective
phenols are 8.4 and 7.2 in water at 25 °C),11 which makes
the former a worse nucleofuge from the zwitterionic
intermediate compared to the latter.
For the aminolysis of thionocarbonates 6 and 7, no
significant amounts of 3-methoxyphenol and 3-chlorophe-
nol were found, respectively. These results can be ex-
plained by the greater basicity of 3-methoxyphenoxide
and 3-chlorophenoxide compared to that of 3-nitrophe-
noxide (pKa values of the corresponding phenols in water
at 25 °C are 9.7, 9.0, and 8.4, respectively).11 This
suggests a greater nucleofugality from the zwitterionic
intermediate of the latter relative to that of the two other
groups.17
The aminolysis of 8 also exhibits values of k1 (Table 4)
lower than those obtained in the same aminolysis of
thionocarbonate 4.5b This should be due to the lower
electron withdrawal of 3-nitro in 8 than that of both
groups, 4-cyano and 4-nitro, in 4, as reflected by the pKa
values of the corresponding phenols (pKa ) 8.4, 8.0, and
7.2, respectively, in water at 25 °C).11
Table 4 also shows the values of k-1 obtained by the
fittings through eq 1. As expected, these values increase
as the basicity of the amine decreases for the reactions
of a given thionocarbonate. This is in accordance with
the strength of the C-N bond between the central carbon
atom and the amine in the zwitterionic tetrahedral
intermediate. As the amine basicity decreases, this bond
becomes weaker and the rate constant for amine expul-
sion (k-1) becomes larger.
As seen in Table 4, the k-1 values increase slightly for
the reactions of a given amine, as the substituent on the
nonleaving group of the substrate becomes less electron
withdrawing. Although this effect is small and just
outside experimental error (ca. 30%), one could argue that
this effect could be due to a greater “push” exerted by
the oxygen atom of the nonleaving group (to expel the
amine from the zwitterionic intermediate) as the sub-
stituent becomes less electron withdrawing. The same
small effect was found in the reactions of 1-formylpip-
erazine with substrates 2-4.5b The relatively long dis-
tance from these substituents in the zwitterionic inter-
mediate to the central carbon and leaving amine has been
claimed to be responsible for this small effect.5b
Table 4 shows the values of k2 obtained in the ami-
nolysis of thionocarbonates 5-8. As seen in this table,
these values are independent of the amine basicity but
show dependence on the substituents in the nonleaving
groups. The independence of these values on amine
basicity can be explained by the lack of an electron pair
on the aminium moiety of the zwitterionic tetrahedral
intermediate, which prevents its push to expel the
nucleofuge.16
For a comparison between the k2 values in Table 4, k2
for the reaction of substrate 8 must be divided by 2 due
to the two identical nucleofuges in the corresponding
tetrahedral intermediate (12). As seen in this table, the
value of k2 increases steadily in going from 4-methyl, the
substituent in the nonleaving group of thionocarbonate
5, to 3-methoxy, 3-chloro, and 3-nitro in thionocarbonates
6, 7, and 8, respectively. This could be attributed to the
greatest electron-withdrawal from the 3-nitro group
(compared to the other groups), which leaves the central
carbon atom of intermediate 12 the most positive. This
facilitates the push provided by S- in this intermediate
to expel the nucleofuge.
The fact that neither 3-methoxyphenol nor 3-chlo-
rophenol was found in the aminolysis of thionocarbonates
6 or 7, respectively, indicates that the corresponding
thionocarbamates are stable under the experimental
conditions. This is in agreement with the fact that the
4-nitrophenyl thionocarbamate derived from morpholine
(Mo-CS-OPNp, where Mo is morpholine and PNp is
4-nitrophenyl) at pH 8.5 did not show any signs of
decomposition after 2 days at room temperature.18
The values of the equilibrium constant for formation
of the zwitterionic tetrahedral intermediate (K1), obtained
by a fitting using eq 2, increase as the electron with-
drawal from the substituent in the nonleaving group
becomes greater (Table 4). This is a reflection of the
larger k1 and smaller k-1 values in going from 3-methoxy
to 3-nitro as the above substituent. On the other hand,
for the reactions of a given substrate, the value of K1
increases with the increase of the amine basicity, as
expected on the basis of a faster attack on the substrate
(larger k1) and a slower expulsion from the zwitterionic
intermediate (smaller k-1) for the more basic amines.
The reactions of piperazine and 1-(2-hydroxyethyl)-
piperazine with thionocarbonates 2 and 3 show linear
plots of kobsd vs [NH].5b The Bro¨nsted plots obtained with
the slopes of these plots show â values in accord with
the rate-determining formation (k1 step) of a zwitterionic
tetrahedral intermediate.5b These results are in great
contrast to the nonlinear upward plots of kobsd vs [NH],
obeying eq 1, found in the reactions of the same amines
with thionocarbonates 6 and 7 (this work). This apparent
inconsistency can be explained by the larger k2 values
for the reactions of substrates 2 and 35b relative to those
for 6 and 7 (6- and 4-fold, respectively) and the larger
[NH] values employed in the reactions of the former
substrates (from 4- to 9-fold). This makes k2 + k3[NH] .
k-1 for the reactions of thionocarbonates 2 and 3, reduc-
ing eq 1 to kobsd ) k0 + k1[NH].
Gresser and J encks did not find any amine catalysis
in the aminolysis of diaryl carbonates, including phenyl
3-nitrophenyl carbonate.16b Namely, the kobs vs [amine]
plots they obtained are linear for the reactions of all
amines. The reaction mechanism proposed by these
authors lacks the k3 step found in the aminolysis of diaryl
As expected, the values of k2 for the aminolysis of
thionocarbonates 5-8, with 3-nitrophenoxide as the
leaving group (Table 4), are smaller than those for the
same aminolysis of the similar thionocarbonates 1-4,
with 4-nitrophenoxide as the nucleofuge.5a,b This reflects
(17) A referee has commented that if the log of the relative
nucleofugalities of 3-nitrophenoxide (NPO-) and 3-chlorophenoxide
ClPO
(ClPO-) is in direct proportion to their pKa values, then k2NPO/k2
≈
4 and 20% of the 3-phenolic product should be ClPO-. Unfortunately,
the UV-vis technique does not allow us to detect this. Therefore, it
could be possible that the k2 value for the reaction of 7 (Table 4) could
be slightly overestimated. In any case, the error in the determination
in this value of k2 is 25% (Table 4).
(16) (a) Satterthwait, A. C.; J encks, W. P. J . Am. Chem. Soc. 1974,
96, 6, 7018-7031. (b) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc.
1977, 99, 6963-6980.
(18) Unpublished results from this laboratory.

Investigation of Aminolysis of Thionocarbonates
J . Org. Chem., Vol. 67, No. 12, 2002 4315
thionocarbonates (Scheme 1). The difference in mecha-
nism can be attributed to the faster nucleofugality of the
leaving groups from the T( intermediate formed with
diaryl carbonates than that formed with diaryl thiono-
carbonates. The k3 value is about the same for both
systems since the proton transfer from T( to the corre-
sponding amine is diffusion controlled in both cases. This
means that for diaryl thionocarbonates, k2 ≈ k3[NH] in
Scheme 1, whereas k2 . k3[NH] for diaryl carbonates.
The faster k2 value for the T( formed with carbonates
relative to that formed with thionocarbonates has been
explained by the greater ability of O- in the former
intermediate (compared to that of S- in the latter
intermediate) to form a double bond and expel the
nucleofuge. This is consistent with the higher polariz-
ability of the CdS bond compared to that of the CdO
bond, which hinders the formation of the CdS bond from
the thio T( compared to the CdO bond from the oxy T(,
thus decreasing the nucleofugality of the leaving group
(and also the amine) from the former T(.19,20
Ack n ow led gm en t. We thank Dr. Florencia Gonza´-
lez for the synthesis of thionocarbonate 7. We also thank
the financial assistance by “Fondo Nacional de Desar-
rollo Cientifico y Tecnologico” of Chile (FONDECYT),
project 1990561. L. L. thanks FONDECYT (project
2990101) for financial support to this work and CONI-
CYT for a scholarship.
(19) Castro, E. A.; Iban˜ez, F.; Santos, J . G.; Ureta, C. J . Org. Chem.
1993, 58, 4908-4912.
(20) Hill, S. V.; Thea, S.; Williams, A. J . Chem. Soc., Perkin Trans.
2 1983, 437-446. Cottrell, T. L. The Strengths of Chemical Bonds, 2nd
ed.; Butterworth: London, 1959; pp 275, 276. Kwon, D. S.; Park, H.
S.; Um, I. H. Bull. Korean Chem. Soc. 1991, 12, 93-97.
Su p p or tin g In for m a tion Ava ila ble: Page S2 containing
1H NMR and 13C NMR data for compounds 6-8. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O025562A