Structure-Reactivity Correlations in the Aminolysis and Pyridinolysis of Bis(phenyl) and Bis(4-nitrophenyl) Thionocarbonates

Article abstract of DOI:10.1021/jo970624w

The reactions of a series of secondary alicyclic amines with bis(phenyl) and bis(4-nitrophenyl) thionocarbonates (BPTOC and BNPTOC, respectively), and a series of pyridines with the latter substrate, are subjected to a kinetic investigation in water, 25.0

Full text of DOI:10.1021/jo970624w

6568
J . Org. Chem. 1997, 62, 6568-6574
Str u ctu r e-Rea ctivity Cor r ela tion s in th e Am in olysis a n d
P yr id in olysis of Bis(p h en yl) a n d Bis(4-n itr op h en yl)
Th ion oca r bon a tes
Enrique A. Castro,* J ose´ G. Santos,* J imena Te´llez, and Mar´ıa I. Uman˜a
Facultad de Quı´mica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 22, Chile
Received April 7, 1997X
The reactions of a series of secondary alicyclic amines with bis(phenyl) and bis(4-nitrophenyl)
thionocarbonates (BPTOC and BNPTOC, respectively), and a series of pyridines with the latter
substrate, are subjected to a kinetic investigation in water, 25.0 °C, ionic strength 0.2 M (KCl).
All the reactions obey pseudo-first-order kinetics under amine excess over the substrate. The
reactions of piperidine with BPTOC are first order in amine, but those of the same substrate with
the other secondary alicyclic amines exhibit a complex order, consistent with the existence of both
a zwitterionic (T() and an anionic (T-) tetrahedral intermediates on the reaction pathway.
Deprotonation of T( by a secondary amine to give T- (rate coefficient k3) competes with expulsion
of the amine moiety from T( (k-1), except in the reactions of 1-formylpiperazine whereby k-1 . k3
[1-formylpiperazine], and a kinetics second order in amine is observed. The reactions of secondary
alicyclic amines with BNPTOC are all first order in amine and show a nonlinear Bro¨nsted-type
plot with limiting slopes â ) 0.1 (high amine pKa) and â ) 0.5 (low amine pKa). This slight curvature
is consistent with a concerted mechanism (one step). The intermediate T( is not formed because
of its high kinetic instability due to a large k-1 value. The pyridinolysis of BNPTOC exhibits a
first order in amine kinetics and a linear Bro¨nsted-type plot of slope â ) 1.0, which is consistent
with the existence of T( whereby the expulsion of the leaving group from T( is the rate-determining
step. This intermediate is less unstable than that with a secondary amine due to the fact that k-1
is smaller for a pyridine compared to an isobasic secondary alicyclic amine.
In tr od u ction
Exp er im en ta l Section
Lately, we have been interested on the mechanisms of
the aminolysis of thiono derivatives and particularly
thionocarbonates. We have kinetically studied the reac-
tions of phenyl and 4-nitrophenyl ethyl thionocarbonates
with secondary alicyclic amines, where a stepwise mech-
anism through two tetrahedral intermediates on the
reaction pathway was found.1
Recently we have performed a kinetic study on the
pyridinolysis of methyl and ethyl 4-nitrophenyl thiono-
carbonates and ethyl 2,4-dinitrophenyl thionocarbonate.2
In this work a biphasic Bro¨nsted-type plot was obtained
for the latter reactions whereas linear plots were found
for those of the alkyl 4-nitrophenyl derivatives. These
Bro¨nsted plots were interpreted through a zwitterionic
tetrahedral intermediate (T() on the reaction path,
whereby there is a change in the rate-determining step
depending on the pyridine basicity (for the dinitro deriva-
tive) and whereby the expulsion of 4-nitrophenoxide ion
from T( is rate determining (for the two mononitro
thionocarbonates).2
In order to extend our mechanistic investigations we
perform in the present work a kinetic study on the
reactions of secondary alicyclic amines with bis(phenyl)
and bis(4-nitrophenyl) thionocarbonates, and the reac-
tions of pyridines with the latter substrate. The object
is to assess the influence of the nonleaving and leaving
groups of the substrate and the amine nature on these
mechanisms by comparing these reactions among them
and with those of alkyl aryl thionocarbonates.1,2
Ma ter ia ls. The secondary alicyclic amines and pyridines
were purified as reported.3,4 Bis(4-nitrophenyl) thionocarbon-
ate (BNPTOC) was synthesized as follows: To a solution of
4-nitrophenol (3.62 g, 26 mmol) dissolved in THF (20 mL) in
a Schlenk round-bottomed flask was added slowly a solution
(16.3 mL) of 1.6 M butyllithium (Aldrich) under nitrogen
atmosphere. The product, lithium 4-nitrophenoxide, was
rapidly transferred to a compensation funnel, under nitrogen.
In another Schlenk round-bottomed flask, thiophosgene (1 mL,
Aldrich) was dissolved in anhydrous THF (20 mL) under
nitrogen and the flask placed in an ethanol-liquid nitrogen
bath. The compensation funnel was attached to the flask and
the lithium 4-nitrophenoxide solution added dropwise with
stirring during 2 h. The mixture was left overnight with
stirring under nitrogen at ambient temperature. Chloroform
(50 mL) was added to this mixture and the solution washed
with water. The organic layer was dried with MgSO4 and
filtered under vacuum and the solvent evaporated off. The
crystallized BNPTOC melted at 195-196 °C (lit.5 mp 196-
197 °C) and was identified as follows:
BNPTOC: 1H NMR (200 MHz, CDCl3) δ 7.40 (sd, 2H, J )
7.0 Hz), 8.36 (sd, 2H, J ) 7.0 Hz); 13C NMR (50 MHz, CDCl3)
δ 123.09 (C-2/6), 125.60 (C-3/5), 146.35 (C-4), 157.19 (C-1),
192.02 (CdS); IR (KBr) 1532 and 1351 (CsNO2), 1209 (CdS),
1192 (CsO), 865 (CH, arom) cm-1
.
Bis(phenyl) thionocarbonate (BPTOC) was prepared in the
same way but using phenol (2.47 g) and sodium (0.6 g) in order
to obtain sodium phenoxide. The product BPTOC melted at
103-104 °C (lit.6 mp 105-106 °C) and was identified as
follows:
(3) Castro, E. A.; Ureta, C. J . Org. Chem. 1989, 54, 2153.
(4) Bond, P. M.; Castro, E. A.; Moodie, R. B. J . Chem. Soc., Perkin
Trans. 2 1976, 68.
(5) Al-Kazimi H. R.; Tarbell, D. S.; Plant, D. J . Am. Chem. Soc. 1955,
77, 2479.
X Abstract published in Advance ACS Abstracts, August 15, 1997.
(1) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org. Chem. 1996,
61, 3501.
(2) Castro, E. A.; Cubillos, M.; Santos, J . G.; Te´llez, J . J . Org. Chem.
1997, 62, 2512.
(6) Narasimhamurthy, N.; Samuelson, A. G. Tetrahedron Lett. 1988,
29, 827.
S0022-3263(97)00624-5 CCC: $14.00 © 1997 American Chemical Society

Bis(phenyl) Thionocarbonate Aminolysis and Pyridinolysis
J . Org. Chem., Vol. 62, No. 19, 1997 6569
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 Bis(p h en yl) Th ion oca r bon a te (BP TOC)a
102[N]tot,c M
103kobsd, s-1
no. of runs
b
amine
pH
FN
piperidine
piperazine
10.94
11.24
11.54
9.64
9.94
10.24
9.08
9.38
9.68
8.48
8.78
9.08
7.68
7.98
8.28
0.33
0.50
0.66
0.33
0.50
0.66
0.33
0.50
0.66
0.33
0.50
0.66
0.33
0.50
0.66
0.50-5.0
0.50-5.0
0.50-5.0
0.90-9.0
1.0-7.0
0.40-4.0
0.30-3.0
0.20-1.8
0.30-1.5
1.5-30.0
2.5-19.0
0.75-15.0
7.5-30.0
5.0-35.0
3.75-30.0
1.10-39.0
4.80-72.1
4.86-108
2.81-99.7
10.8-106
1.92-87.5
0.37-8.53
0.26-6.60
0.72-9.07
0.99-148
2.02-112
0.86-126
0.014-0.23
0.019-0.77
0.017-1.12
7
7
7
7
7
7
6
6
6
9
7
10
4
7
1-(2-hydroxyethyl)piperazine
morpholine
1-formylpiperazine
8
a
b
In aqueous solution at 25.0 °C, ionic strength 0.2 M (KCl). Free amine fraction. c Concentration of total amine (free base plus
protonated forms).
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 Bis(4-n itr op h en yl) Th ion oca r bon a te
(BNP TOC)a
102[N]tot,c M
103kobsd, s-1
no. of runs
b
amine
pH
FN
piperidine
piperazine
10.94
11.24
11.54
9.64
9.94
10.24
9.08
9.38
9.68
8.48
8.78
9.08
7.68
7.98
8.28
5.51
5.81
6.11
0.33
0.50
0.66
0.33
0.50
0.66
0.33
0.50
0.66
0.33
0.50
0.66
0.33
0.50
0.66
0.33
0.50
0.66
0.30-2.4
0.20-1.6
0.30-1.2
0.05-1.5
0.05-1.0
0.05-1.0
0.15-3.0
0.10-2.0
0.075-1.5
0.30-3.0
0.20-2.0
0.15-1.5
3.0-30.0
2.0-19.0
1.5-15.0
1.5-7.5
6.25-46.7
11.7-54.8
18.8-66.6
0.89-29.2
1.22-26.0
1.76-31.5
2.07-32.9
1.21-28.7
1.52-40.6
3.69-27.1
3.64-25.8
3.10-30.0
11.0-82.0
9.22-77.4
9.34-90.0
2.13-6.75
1.80-11.0
2.26-15.7
7
7
6
9
9
9
9
9
9
7
7
7
8
7
7
6
5
7
1-(2-hydroxyethyl)piperazine
morpholine
1-formylpiperazine
piperazinium ion
1.0-10.0
7.5-9.76
a
b
In aqueous solution at 25.0 °C, ionic strength 0.2 M (KCl). Free amine fraction. c Concentration of total amine (free base plus
protonated forms).
BPTOC: 1H NMR (200 MHz, CDCl3) δ 7.21-7.51 (m); 13C
NMR (50 MHz, CDCl3) δ 121.86 (C-2/6), 126.86 (C-4), 129.70
(C-3/5), 153.59 (C-1), 194.85 (CdS); IR (KBr) 1252 (CdS), 1158
fied as the other reaction product by comparison of the UV-
vis spectra after completion of these reactions with those of
authentic samples of phenol in the same reaction conditions.
(C-O), 775 and 693 (CH, arom) cm-1
.
The identification of 4-nitrophenol and the 4-nitrophenyl
thionocarbamates of some secondary alicyclic amines and
pyridines as the products of the reactions of BNPTOC with
these amines was carried out by comparison of the UV-vis
spectra after completion of these reactions with those of
authentic samples of 4-nitrophenol under the same experi-
mental conditions and also with those at the end of the
reactions of 4-nitrophenyl chlorothionoformate with the sec-
ondary amines.
Kin etic Mea su r em en ts. These were performed spectro-
photometrically by following the production of phenoxide and
4-nitrophenoxide ions at 250 and 400 nm, respectively, for the
aminolyses of BPTOC and BNPTOC, respectively. The reac-
tions were measured using a Perkin-Elmer Lambda-3 spec-
trophotometer. The reactions were studied in aqueous solu-
tions, 25.0 ( 0.1 °C, ionic strength 0.2 M (maintained with
KCl), and at least a 10-fold excess of total amine over the
substrate.
Pseudo-first-order rate coefficients (kobsd) were found through-
out, by means of the method described.3 The experimental
conditions of the reactions and the kobsd values obtained are
shown in Tables 1-3. The initial concentration of BPTOC and
BNPTOC was 3 × 10-5 M in all the reactions.
Resu lts a n d Discu ssion
The rate law obtained for all the reactions under study
is given by eq 1, where Ar is either phenyl or 4-nitro-
phenyl, S represents the substrate (either BPTOC or
P r od u ct Stu d ies. The phenyl thionocarbamates of pip-
eridine and morpholine, 1-(phenoxythiocarbonyl)piperidine,
and 1-(phenoxythiocarbonyl)morpholine, were identified as the
final products of the reactions of BPTOC with these two
amines. This 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. The UV-
vis spectra after completion of the reactions of BPTOC with
all the amines were also compared with those at the end of
the reactions of phenyl chlorothionoformate with the same
amines. It was deduced from these comparisons that the
phenyl thionocarbamates derivatives of these amines are one
of the products of these reactions. Phenoxide ion was identi-
d[ArO-]
) kobsd[S]
(1)
dt
BNPTOC) and kobsd is the pseudo-first-order rate coef-
ficient (excess of amine over the substrate was used
throughout).
The dependence of kobsd on the concentration of the free
amine varied according to the nature of both the sub-
strate and the amine.

6570 J . Org. Chem., Vol. 62, No. 19, 1997
Castro et al.
Ta ble 3. Exp er im en ta l Con d ition s a n d kobsd Va lu es for th e P yr id in olysis of Bis(4-n itr op h en yl) Th ion oca r bon a te
(BNP TOC)a
b
pyridine substituent
4-dimethylaminod
pH
FN
102[N]tot,c M
103kobsd, s-1
no. of runs
8.2
8.5
9.0
8.2
8.5
9.0
8.0
8.2
8.5
8.2
8.5
8.8
8.5
8.8
9.0
0.021
0.041
0.119
0.057
0.107
0.275
0.946
0.964
0.982
0.995
0.997
0.999
0.999
0.999
0.999
0.15-0.60
0.04-0.09
0.03-0.08
0.10-0.425
0.08-0.25
0.03-0.08
5.0-9.0
4.0-18.0
5.0-15.0
5.0-15.0
4.0-13.5
3.0-13.0
7.0-15
6.8-10.1
2.3-4.34
6
6
6
7
7
6
4
5
7
5
5
6
5
6
7
3.98-8.24
3.33-11.2
4.03-11.9
4.49-9.77
1.78-2.69
1.57-7.49
1.91-5.77
0.60-1.66
0.37-1.56
0.19-1.49
0.13-0.25
0.12-0.32
0.24-0.35
4-aminod
3,4-dimethyle
3-methyle
nonee
6.0-21
10.0-25
a
b
In aqueous solution at 25.0 °C, ionic strength 0.2 M (KCl). Fraction of amine free base. c Concentration of total amine (free base +
protonated forms). In the presence of carbonate buffer 5 × 10-2 M. e In the presence of borate buffer 5 × 10-3 M.
d
Ta ble 4. Va lu es of th e Ra te Micr ocoefficien ts for th e
Sch em e 1
Rea ction s of Secon d a r y Alicyclic Am in es w ith BP TOC
a n d Va lu es of kN for th e Rea ction s of th e Sa m e Am in es
w ith BNP TOCa
BPTOC
BNPTOC
k1,
pKa s-1 M-1
10-8k-1
,
kN,
a
amine
s-1
s-1 M-1
piperidine
piperazine
1-(2-hydroxyethyl)piperazine 9.38
morpholine
1-formylpiperazine
piperazinium ion
11.24
9.94
3.2
4.2
2.6
2.0
1.8c
0.02b
1.0
2.3
7.0
6.4
3.5
2.6
0.85
0.22
8.78
7.98
5.81
3.0
65d
a
The reactions and pKa determinations were carried out in
b
aqueous solution, 25.0 °C, ionic strength 0.2 M (KCl). Value
obtained by extrapolation of the Bro¨nsted-type plot for k-1.
c Value
d
obtained by extrapolation of the Bro¨nsted-type plot for k1. Value
obtained from the values of K1 and k1 (k-1 ) k1/K1). The value of
K1 was determined from the slope of a kobsd vs [NH]2 plot (see text).
k1(k2 + k3[NH])[NH]
kobsd
)
(2)
k-1 + k2 + k3[NH]
For the reactions BPTOC with piperidine, it is reason-
able that k2 + k3[NH] . k-1, since this amine is by far
the most basic of the series of secondary amines and
Linear plots of kobsd vs [NH], where NH represents a
free secondary alicyclic amine, at constant pH were found
for the reactions of these amines with BNPTOC and in
the reactions of piperidine with BPTOC. For the reac-
tions of the secondary amines (except piperidine) with
BPTOC, the plots of kobsd vs [NH] were concave upward,
indicating a kinetic order greater than unity in the
amine. The reaction of 1-formylpiperazine with this
substrate was the only one showing a clear second-order
dependence on [NH].
therefore should show the smallest leaving ability (k-1
)
from 1 compared to the other amines of the series (see
below the values of the rate microefficients involved).
This fact leads to the kinetic law shown in eq 3 for these
reactions, which explains the linear kobsd vs [NH] plots
kobsd ) k1[NH]
(3)
observed. The value of k1 was obtained as the slope of
this plot and is shown in Table 4.
On the other hand the above plots for the pyridinolysis
of BNPTOC were linear for the reactions of all the series
of pyridines.
For the reactions of 1-formylpiperazine with BPTOC,
a kinetics second-order in amine was found. The only
way to achieve this in eq 2 is by assuming k-1 . k3 [NH]
. k2, which leads to eq 4. These inequalities are
reasonable in view of the magnitude of the rate micro-
The reactions of secondary alicyclic amines with BP-
TOC can be described by the mechanism depicted in
Scheme 1. This was arrived at by taking into account
the kinetic results, the product studies, and the shape of
the Bro¨nsted-type plots obtained (see below). In this
scheme the k3 step is deprotonation of the zwitterionic
tetrahedral intermediate 1 by an amine to yield the
anionic intermediate 2.
k1k3
kobsd
)
[NH]2 ) K1k3[NH]2
(4)
k-1
Applying the steady state condition to both tetrahedral
intermediates of Scheme 1, eq 2 can be obtained.
coefficients found (Table 4) and the concentration range
of free amine employed (see Table 1). From the slope of

Bis(phenyl) Thionocarbonate Aminolysis and Pyridinolysis
J . Org. Chem., Vol. 62, No. 19, 1997 6571
In order to determine the value of k3 it is necessary to
estimate the pKa value of the tetrahedral intermediate
1 of Scheme 1.
It has been determined that the pKa value of interme-
diate 3 is 5.5 pKa units lower than that of the corre-
sponding aminium ion.1
The above was carried out by J encks’s procedure,
which assumes that the inductive effects are the most
important ones for tetrahedral compounds.8 The pKa
value of 1 of Scheme 1 can be found by replacing EtO (σI
) 0.28)9 by PhO (σI ) 0.37)10 and using FI ) -9.2 for the
pKa of substituents at the central carbon atom of tetra-
hedral intermediates such as 3.9
This procedure gives pKa (1) - pKa (3) ) -9.2(0.37-
0.28) ) -0.8. Namely, the pKa value of 1 of Scheme 1
should be 5.5 + 0.8 ) 6.3 pKa units lower than that of
the corresponding aminium ion.
It follows from above that the proton transfer from 1
to the corresponding amine is thermodynamically favor-
able, and therefore a k3 value of ca 1010 s-1 M-1 (see
Scheme 1) can be assumed.11 This value should be
independent of the amine basicity since the proton
transfer is from the aminium ion moiety of 1 to the
corresponding free amine.1
The k-1 values found for the reactions of BPTOC with
the secondary amines (Table 4) are smaller than the
corresponding values for the reactions of ethyl phenyl
thionocarbonate with the same amines.1 This could be
due to the σI values involved,10 which should result in a
weaker push provided by PhO in 1 than EtO in 3 to expel
the amine.
F igu r e 1. Plots of [NH]/kobsd against 1/[NH] for the reactions
of BPTOC with piperazine (b) and morpholine (O) in aqueous
solution, at 25 °C, ionic strength 0.2 M.
the plot of kobsd vs [NH]2, and by knowledge of k3 and k1
(see below), the value of k-1 was found (shown in Table
4).
For the reactions of BPTOC with the other secondary
amines, complex kinetics were found. Assuming k2
,
k3[NH] (see below), eq 2 leads to eq 5. Rearranging this
equation, eq 6 is obtained. Through linear plots of [NH]/
kobsd against 1/[NH] the values of k1 and k-1/k3 were
The rate of expulsion of phenoxide anion from 3 (k2)
has been estimated as ca. 107 s-1 1
. The rate of expulsion
of the same group from 1 of Scheme 1 should be of the
same order of magnitude in view of the larger push
exerted by EtO in 3 to expel phenoxide anion compared
to PhO in 1, which is counterbalanced by the fact that
there are two PhO leaving groups in 1.
k1k3[NH]2
kobsd
)
)
(5)
(6)
k-1 + k3[NH]
k-1
[NH]
kobsd
1
1
+
An upper limit to the value of k2 of Scheme 1 is set by
the fact that for the reactions of BPTOC with piperazine,
1-(2-hydroxyethyl)piperazine, and morpholine, the best
fittings were obtained through eq 5, and not eq 2, i.e.,
assuming k3[NH] . k2. Since the lowest value of [NH]
for these reactions is 1 × 10-3 M (Table 1), and therefore
the lowest value for k3[NH] is 1 × 107 s-1 (k3 ) 1010 s-1
k1 k1k3
[NH]
found, from the intercept and the slope, respectively. As
examples, Figure 1 shows the linear plots of eq 6 for the
reactions of BPTOC with piperazine and morpholine.
Since the value of k3 can be estimated and it is the
same for all the reactions (see below), the values of k-1
for each amine can be determined. With these and those
of k1 taken as initial values, the best k1 and k-1 values
were found by nonlinear least squares fitting of eq 5 to
the experimental kobsd vs [HN] points. These best values
are shown in Table 4.
M-1, see above), the value of k2 should be e107 s-1
.
A lower limit to k2 of Scheme 1 is given by the
nucleofugality rate of PhO from 4, which is k2 ) 106 s-1 12
,
since the push provided by PhO in 1 should be stronger
than that of Me in 4.13 Therefore, the value of k2 in
Scheme 1 should be 107 s-1 > k2 > 106 s-1
.
The values of k1 for the reaction of BPTOC with
1-formylpiperazine and k-1 for the reaction of this
substrate with piperidine were found by extrapolation
of the linear Bro¨nsted-type plots involved (statistically
corrected,1,7 Figures 2 and 3), and are shown in Table 4.
(8) Sayer, J . M.; J encks, W. P. J . Am. Chem. Soc. 1973, 95, 5637.
Fox, J . P.; J encks, W. P. J . Am. Chem. Soc. 1974, 96, 1436.
(9) Taylor, P. J . J . Chem. Soc., Perkin Trans. 2 1993, 1423.
(10) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(11) Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1.
(12) Castro E. A.; Iba´n˜ez, F.; Santos, J . G.; Ureta, C. J . Org. Chem.
1993, 58, 4908.
(7) Bell, R. P. The Proton in Chemistry; Methuen: London, 1959; p
159.
(13) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963,
6970.

6572 J . Org. Chem., Vol. 62, No. 19, 1997
Castro et al.
F igu r e 4. Free energy (arbitrary units) reaction profiles for
the aminolysis of BPTOC when the formation of T( (A) or the
breakdown of T( to products (B) is the rate-determining step.
F igu r e 2. Bro¨nsted-type plot for k1 (statistically corrected7)
obtained in the reactions of BPTOC with secondary alicyclic
amines. The value of the slope is â1 ) 0.1.
reactant to the transition state for the formation of the
intermediate (structure 5 for the aminolysis of BPTOC).13
On the other hand, the Bro¨nsted slope for k-1 in Figure
3 is â-1 ) -1.0. Since the Bro¨nsted slope when break-
down of the intermediate is rate determining (â2) is â1 -
â-1,
1,13 it follows that â2 ) 0.1 - (-1.0) ) 1.1. This value
is in accord with the Bro¨nsted-type slopes at low amine
pKa for numerous aminolyses of carbonyl and thiocar-
bonyl compounds.1-4,12-16 The larger value of â2 com-
pared to â1 arises from the fact that there is a large
effective charge development on the amine nitrogen from
reactant to the transition state for breakdown to products
of the intermediate (see Figure 4B and structure 6 for
the aminolysis of BPTOC), since there is a full bond
formation between amine and the carbonyl or thiocar-
bonyl carbon in this transition state.13
For the reactions of BNPTOC with secondary alicyclic
amines, linear plots of kobsd vs [HN] at constant pH were
found. The nucleophilic rate constant (kN) were obtained
as the slopes of these plots, and the values are shown in
Table 4. After statistical correction of the kN and pKa
values of the conjugate acids of the amines,7 the Bro¨n-
sted-type plot shown in Figure 5 was obtained. The line
in this figure was calculated by an equation based on the
existence of a tetrahedral intermediate on the reaction
path and a change in the rate-determining step from
F igu r e 3. Bro¨nsted-type plot for k-1 (statistically corrected7)
obtained in the reactions of BPTOC with secondary alicyclic
amines. The value of the slope is â-1 ) -1.0.
We believe the reactions of BPTOC with secondary
amines are stepwise not only because satisfactory fittings
were found through eq 5, but also because of the
magnitudes of the Bro¨nsted slopes for k1 and k-1 (Figures
2 and 3). The former value (â1 ) 0.1) is in agreement
with the Bro¨nsted slopes obtained in many aminolyses
of carbonyl and thiocarbonyl derivatives when formation
of the zwitterionic tetrahedral intermediate (T() is the
rate-determining step (see Figure 4A).1,3,12-16 This low
value is due to the little effective charge development on
the amine nitrogen atom in going from the amine
(14) Satterthwait, A. C.; J encks, W. P. J . Am. Chem. Soc. 1974, 96,
7018.
(15) Castro, E. A.; Iba´n˜ez, F.; Salas, M.; Santos, J . G.; Sepu´lveda,
P. J . Org. Chem. 1993, 58, 459.
(16) Campbell, P; Lapinskas, B. A. J . Am. Chem. Soc. 1977, 99, 5378.
Kwon, D. S.; Choi, K. E.; Um I. H. Bull. Korean Chem. Soc. 1989, 10,
610.

Bis(phenyl) Thionocarbonate Aminolysis and Pyridinolysis
J . Org. Chem., Vol. 62, No. 19, 1997 6573
Ta ble 5. Va lu es of kN for th e P yr id in olysis of BNP TOC
a n d p Ka Va lu es for th e Con ju ga te Acid s of P yr id in esa
pyridine substituent
pKa
kN, s-1 M-1
4-dimethylamino
4-amino
3,4-dimethyl
3-methyl
H
9.87
9.42
6.77
5.80
5.37
74
44
3.5 × 10-2
1.2 × 10-2
1.4 × 10-3
a
Both the kN and pKa values were obtained in aqueous solution,
25.0 °C, ionic strength 0.2 M (KCl).
The Bro¨nsted-type plot in Figure 5 can be explained
by a gradual decrease of â with increasing amine pKa in
a single step. This represents a normal Hammond effect
for a concerted reaction, with an earlier transition state
for more reactive nucleophiles.20,21
Although for the reactions of the alicyclic amines with
BNPTOC the concerted mechanism seems preferable to
the stepwise process, the latter cannot be rigorously
excluded, although if this were the case, the tetrahedral
intermediate formed would be extremely unstable.
The instability of the hypothetical zwitterionic tetra-
hedral intermediate formed in the reactions of secondary
amines with BNPTOC should be extremely high in view
of the two 4-nitrophenoxy groups attached to the central
carbon of the intermediate. Therefore, this intermediate
should have a lifetime comparable to a vibration period
(ca.10-13 s), and therefore the intermediate would not be
formed (would be too unstable to exist) and the concerted
mechanism is enforced.20,22
F igu r e 5. Bro¨nsted-type plot for kN (statistically corrected7)
found in the reactions of BNPTOC with secondary alicyclic
amines. The line is calculated (see text) and the points are
experimental. The values of the limiting slopes are â ) 0.1
(high pKa) and 0.45 (low pKa).
For the pyridinolysis of BNPTOC, the nucleophilic rate
constants (kN) were found as the slopes of the linear kobsd
vs [N] plots at constant pH, where N is the substituted
pyridine free base. The values of kN obtained and the
pKa values of the conjugate acids of the pyridines are
shown in Table 5. The corresponding Bro¨nsted type plot
is shown in Figure 6.
breakdown to formation of this intermediate as the amine
gets more basic.4 An analogous equation was derived by
J encks.13 By nonlinear least-squares fitting,4 the follow-
ing parameters were found: â1 ) 0.1 (slope at high pKa),
â2 ) 0.45 (slope at low pKa) and pKa° ) 9.5 (pKa value at
the curvature center).
The slope of the linear Bro¨nsted-type plot in Figure 6
has a value of â ) 1.0, which is in accord with the values
shown by the Bro¨nsted slopes in numerous aminolysis
reactions of carbonyl and thiocarbonyl derivatives when
breakdown of a tetrahedral intermediate is the rate-
determining step.1-4,12-16
Although the value of â1 ) 0.1 is in agreement with
previous ones when the k1 step is rate determining (see
above), the value of â2 ) 0.45 is not in line with the
Bro¨nsted slopes when the k2 step is rate limiting. The
latter values are usually 0.8-1.0.1-4,12-16
On the other hand, in the concerted reactions of
secondary alicyclic amines with S-(2,4-dinitrophenyl) and
S-(2,4,6-trinitrophenyl) O-ethyl thiolcarbonates, linear
Bro¨nsted plots with slopes â ≈ 0.5-0.6 were found.17
The fact that the reactions of BNPTOC with alicyclic
amines seem to be concerted while those of the same
substrate with pyridines are stepwise is in line with
previous findings: The reactions of the above secondary
alicyclic amines with S-(2,4-dinitrophenyl) and S-(2,4,6-
trinitrophenyl) O-ethyl thiolcarbonates are concerted,17
while the pyridinolysis of these substrates are stepwise.23
The above results have been explained by a high
instability of the putative tetrahedral intermediate formed
by the alicyclic amines due to a large nucleofugality rate
of these amines from the intermediate. This kinetic
instability prevents the intermediate to be formed, and
the mechanism is enforced concerted.17 Substitution of
an alicyclic amine by an isobasic pyridine as the amine
moiety of the tetrahedral intermediate decreases the
kinetic instability of the latter species since pyridines are
worse nucleofuges than isobasic secondary alicyclic amines
from a tetrahedral intermediate.24 This makes possible
the existence of the intermediate formed by pyridines.
Also a linear Bro¨nsted plot with â ≈ 0.5 was exhibited
in the concerted reactions of the above amines with 2,4,6-
trinitrophenyl O-ethyl dithiocarbonate in aqueous etha-
nol.18 Methoxycarbonyl transfer between isoquinoline
and pyridines is also believed to be concerted as indicated
by the linear Bro¨nsted plot of â ≈ 0.58 found.19
In some concerted aminolysis such as those of benzoyl
fluorides, slightly curved Bro¨nsted-type plots were ob-
tained, with slopes â ≈ 0.23 and 0.67 at high and low
pKa values, respectively.20 The difference between these
extremes â values is small compared to that of typical
stepwise aminolyses.1-4,12-16 These type of Bro¨nsted plots
are not usually biphasic, as those for stepwise reactions,
but rather show a continuous curvature.20
(17) Castro, E. A.; Iba´n˜ez, F.; Salas, M.; Santos, J . G. J . Org. Chem.
1991, 56, 4819. Castro, E. A.; Salas, M.; Santos, J . G. J . Org. Chem.
1994, 59, 30.
(18) Castro, E. A.; Cubillos, M.; Mun˜oz, G.; Santos, J . G. Int. J .
Chem. Kinet. 1994, 26, 571.
(19) Chrystiuk, E.; Williams, A. J . Am. Chem. Soc. 1987, 109, 3040.
(20) Song, B. D.; J encks, W. P. J . Am. Chem. Soc. 1989, 111, 8479.
(21) Hammond, G. S. J . Am. Chem. Soc. 1955, 77, 334.
(22) J encks, W. P. Chem. Soc. Rev. 1981, 10, 345. Williams, A. Chem.
Soc. Rev. 1994, 23, 93.
(23) Castro, E. A.; Pizarro, M. I.; Santos, J . G. J . Org. Chem. 1996,
61, 5982.
(24) Castro, E. A.; Ureta, C. J . Org. Chem. 1990, 55, 1676.

6574 J . Org. Chem., Vol. 62, No. 19, 1997
Castro et al.
F igu r e 7. Bro¨nsted-type plot for kN found in the reactions of
pyridines with BNPTOC (O, this work) and ENPTOC (b, ref
1).
F igu r e 6. Bro¨nsted-type plot for kN (statistically corrected7)
found in the reactions of BNPTOC with secondary alicyclic
amines (b) and pyridines (2).
On the other hand, the value of k-1 (expulsion of the
pyridine from 7 or 8) should be greater for 8 than for 7
in view of the stronger push exerted by EtO in 8 than
Our results are also in line with the work of Gresser
and J encks.13 They found that in the aminolysis of
phenyl 4-nitrophenyl carbonate, pyridines are expelled
more slowly from the tetrahedral addition intermediate
formed in these reactions than isobasic quinuclidines (the
latter are tertiary alicyclic amines).13
From a comparison of the Bro¨nsted-type plots obtained
in the pyridinolyses of BNPTOC and ethyl 4-nitrophenyl
thionocarbonate (ENPTOC),2 shown in Figure 7, it can
be observed that the former substrate is more reactive
toward pyridines than the latter. Since breakdown to
products of the corresponding tetrahedral intermediate
is the rate-determining step for both reactions, it means
that kN ) K1k2 is greater for BNPTOC (K1 ) k1/k-1 and
k2 are defined in Scheme 1). The value of k1 should be
larger for the reactions of BNPTOC in view of the larger
electron-withdrawing effect of the nitro group in this
substrate compared to the ethoxy group in ENPTOC.
This effect should leave the thiocarbonyl carbon atom of
BNPTOC more positively charged than that of ENPTOC,
which should result in a faster attack of the amine on
the former substrate.
that of 4-nitrophenoxy in 7 to expel the amine.13 The
value of k2 (expulsion of 4-nitrophenoxide ion) should be
similar for 7 and 8 since the stronger push by EtO in 8
is compensated by the fact that there are two leaving
groups in 7 (see above). Therefore, the larger value of
K1k2 for the pyridinolysis of BNPTOC relative to that of
ENPTOC (Figure 7) can be explained by a larger K1
(larger k1 and smaller k-1) value for BNPTOC and similar
k2 for the reactions of both substrates.
Ack n ow led gm en t. We thank FONDECYT of Chile
for financial support to this work.
J O970624W