Kinetics and mechanisms of the reactions of 4-nitro- and 3-nitrophenyl 4-methylphenyl thionocarbonates with alicyclic amines and pyridines

Article abstract of DOI:10.1021/jo005587e

The reactions of the title thionocarbonates (1 and 2, respectively) with a series of secondary alicyclic amines and pyridines are subjected to a kinetic investigation in 44 wt % ethanol-water, 25.0 °C, ionic strength 0.2 M (KCl). Under amine excess over the substrates pseudo-first-order rate coefficients (k_obsd) are obtained for all the reactions. Those of the alicyclic amines with the two substrates show nonlinear upward plots of k_obsd vs [amine], except the reactions of piperidine, which exhibit linear plots. For these reactions a reaction scheme is proposed with two tetrahedral intermediates, one zwitterionic (T^±) and the other anionic (T^-), with a kinetically significant proton transfer from T^± to an amine to give T^-. From an equation derived from the scheme the rate microcoefficients are obtained through fitting. The rate coefficient for formation of T^± (k₁) is larger for 1 compared to 2, which can be explained by a stronger electron-withdrawal of 4-nitro in 1 than 3-nitro in 2, which leaves the thiocarbonyl carbon of 1 more positive and, therefore, more susceptible to nucleophilic attack. For the pyridinolyses of both thionocarbonates the plots of k_obsd vs [amine] are linear, with the slope (k_N) independent of pH. The Broensted plots (log k_N vs pyridine pK_a) for these reactions are linear with slopes β = 0.9 and 1.2 for the pyridinolysis of 1 and 2, respectively. These slopes are consistent with a mechanism through a T^± intermediate on the reaction path, whereby decomposition of T^± to products is the rate-determining step. The k_N values are larger for the reactions of 1 than those of 2. This is attributed to a larger equilibrium formation of T^± and a larger expulsion rate of the nucleofuge from T^± in the reactions of 1 compared to those of 2.

Full text of DOI:10.1021/jo005587e

J . Org. Chem. 2000, 65, 9047-9053
9047
Kin etics a n d Mech a n ism s of th e Rea ction s of 4-Nitr o- a n d
3-Nitr op h en yl 4-Meth ylp h en yl Th ion oca r bon a tes w ith Alicyclic
Am in es a n d P yr id in es
Enrique A. Castro,* Paula Garcia, Leonardo Leandro, Nicolas Quesieh,
Aquiles Rebolledo, 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 uly 24, 2000
The reactions of the title thionocarbonates (1 and 2, respectively) with a series of secondary alicyclic
amines and pyridines are subjected to a kinetic investigation in 44 wt % ethanol-water, 25.0 °C,
ionic strength 0.2 M (KCl). Under amine excess over the substrates pseudo-first-order rate
coefficients (kobsd) are obtained for all the reactions. Those of the alicyclic amines with the two
substrates show nonlinear upward plots of kobsd vs [amine], except the reactions of piperidine, which
exhibit linear plots. For these reactions a reaction scheme is proposed with two tetrahedral
intermediates, one zwitterionic (T() and the other anionic (T-), with a kinetically significant proton
transfer from T( to an amine to give T-. From an equation derived from the scheme the rate
microcoefficients are obtained through fitting. The rate coefficient for formation of T( (k1) is larger
for 1 compared to 2, which can be explained by a stronger electron-withdrawal of 4-nitro in 1
than 3-nitro in 2, which leaves the thiocarbonyl carbon of 1 more positive and, therefore, more
susceptible to nucleophilic attack. For the pyridinolyses of both thionocarbonates the plots of
kobsd vs [amine] are linear, with the slope (kN) independent of pH. The Bro¨nsted plots (log kN vs
pyridine pKa) for these reactions are linear with slopes â ) 0.9 and 1.2 for the pyridinolysis of 1
and 2, respectively. These slopes are consistent with a mechanism through a T( intermediate on
the reaction path, whereby decomposition of T( to products is the rate-determining step. The kN
values are larger for the reactions of 1 than those of 2. This is attributed to a larger equilibrium
formation of T( and a larger expulsion rate of the nucleofuge from T( in the reactions of 1 compared
to those of 2.
In tr od u ction
study in this work the kinetics of the aminolysis (second-
ary alicyclic amines) and pyridinolysis of 4-nitro- and
3-nitro-phenyl 4-methylphenyl thionocarbonates (1 and
2, respectively). The aim is to compare these reactions
between them and with the other thionocarbonates
described above.
Although the mechanisms of the aminolysis of alkyl
aryl and diaryl carbonates1 and aryl acetates2 are well
understood, much less is known on the mechanisms of
the aminolysis of thiocarbonates3 and thioacetates,4
particularly thionocarbonates.5
Recently, we have investigated kinetically the reac-
tions of alkyl aryl thionocarbonates,5a,b bis(aryl) thiono-
carbonates,5c and phenyl 4-nitrophenyl thionocarbonate5d
with a series of secondary alicyclic amines and pyridines.
To evaluate the effects of the leaving and nonleaving
groups and the amine nature on these mechanisms, we
Exp er im en ta l Section
(1) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963,
6970.
(2) Satterthwait, A. C.; J encks, W. P. J . Am. Chem. Soc. 1974, 96,
7018.
(3) Oh, H. K.; Lee, J . Y.; Yun, L. H.; Park, Y. S. Int. J . Chem. Kinet.
1998, 30, 419. Humeres, E.; Soldi, V.; Klug, M.; Nunes, M.; Oliveira,
C. M. S.; Barrie, P. J . Can. J . Chem. 1999, 77, 1050. Castro, E. A.;
Cubillos, M.; Santos, J . G. J . Org. Chem. 1999, 64, 6342.
(4) Oh, H. K.; Shin, C. H.; Lee, I. J . Chem. Soc., Perkin Trans. 2
1995, 1169. Oh, H. K.; Woo, S. Y.; Shin, C. H.; Park, Y. S.; Lee, I. J .
Org. Chem. 1997, 62, 5780. Oh, H. K.; Lee, J .-Y.; Lee, I. Bull. Korean
Chem. Soc. 1998, 19, 1198. Koh, H. J .; Han, K. L.; Lee, I. J . Org. Chem.
1999, 64, 4783.
Ma ter ia ls. The secondary alicyclic amines and pyridines
were purified as reported.6 4-Nitrophenyl 4-methylphenyl
thionocarbonate (1) was synthesized by a modification of a
standard procedure,7 as follows: To a solution of 4-nitrophenol
(4.17 g, 30 mmol) dissolved in THF (20 mL) in a Schlenk flask
in an ethanol-liquid nitrogen bath, a solution (12.5 mL, 30
mmol) of 1.6 M butyllithium (Aldrich) dissolved in THF (20
mL) was added slowly under nitrogen atmosphere. This
lithium 4-nitrophenoxide solution was added dropwise, with
(5) (a) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org. Chem. 1996,
61, 3501. (b) Castro, E. A.; Cubillos, M.; Santos, J . G.; Tellez, J . J .
Org. Chem. 1997, 62, 2512. (c) Castro, E. A.; Santos, J . G.; Tellez, J .;
Uman˜a, M. I. J . Org. Chem. 1997, 62, 6568. (d) Castro, E. A.; Saavedra,
C.; Santos, J . G.; Uman˜a, M. I. J . Org. Chem. 1999, 64, 5401.
(6) (a) Bond, P. M.; Castro, E. A.; Moodie, R. B. J . Chem. Soc., Perkin
Trans. 2 1976, 68. (b) Castro, E. A.; Ureta, C. J . Org. Chem. 1989, 54,
2153.
(7) Al-Kazimi H. R.; Tarbell, D. S.; Plant, D. J . Am. Chem. Soc. 1955,
77, 2479.
10.1021/jo005587e CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/28/2000

9048 J . Org. Chem., Vol. 65, No. 26, 2000
Castro et al.
Ta ble 1. Exp er im en ta l Con d ition s a n d kobsd Va lu es
Obta in ed in th e Rea ction s of 4-Nitr op h en yl
4-Meth ylp h en yl Th ion oca r bon a te (1) w ith Alicyclic
Am in esa
Ta ble 2. Exp er im en ta l Con d ition s a n d kobsd Va lu es
Obta in ed in th e Rea ction s of 3-Nitr op h en yl
4-Meth ylp h en yl Th ion oca r bon a te (2) w ith Alicyclic
Am in esa
c
102 [N]tot
M
,
103kobsd
,
no. of
runs
102 [N]tot
Mc
,
103kobsd
,
no. of
runs
s-1
amine
piperidine
pH
FN
s-1
b
b
amine
piperidine
pH
FN
10.62 0.39 0.20-2.0 1.4-21.1
10.82 0.50 0.20-2.0 2.8-31.3
11.12 0.67 0.20-2.0 4.2-53.1
6
6
6
8
8
8
8
8
8
10.52 0.33 0.25-2.5 1.54-24.1
10.82 0.50 0.25-2.5 2.73-30.1
11.12 0.67 0.25-2.5 7.91-49.6
9.41 0.33 0.50-5.0 0.96-21.3
9.71 0.50 0.50-5.0 4.51-38.7
10.01 0.67 0.50-5.0 4.95-70.3
10
10
10
10
10
10
10
10
10
8
8
9
9
10
8
piperazine
9.41 0.33 0.20-2.0 0.98-15.2
9.71 0.50 0.20-2.0 1.60-26.3
10.01 0.67 0.20-2.0 3.0-36.7
piperazine
1-(2-hydroxyethyl)- 8.79 0.33 0.20-2.0 0.30-4.8
1-(2-hydroxyethyl)- 8.79 0.33 0.50-5.0 1.12-13
piperazine
9.09 0.50 0.20-6.0 0.46-29.3
9.39 0.67 0.20-2.0 0.62-10.3
8.18 0.33 0.60-6.0 0.42-11.7
8.48 0.50 0.60-6.0 0.64-20.6
8.78 0.67 0.60-6.0 1.4-35
piperazine
9.09 0.50 0.50-5.0 1.31-20.1
9.39 0.67 0.50-4.5 1.69-23.9
8.18 0.33 3.0-13.5 3.52-25.4
8.48 0.50 3.0-13.5 7.60-46.3
8.78 0.67 2.0-10
7.33 0.33 2.0-20
7.63 0.50 1.0-10
7.93 0.67 1.0-8.0
5.07 0.33 1.0-8.0
5.37 0.50 1.0-10
5.67 0.67 1.0-8.0
morpholine
9
morpholine
10
10
6
5
6
6
6
6
6.12-45.2
1-formylpiperazine
piperazinium ion
7.33 0.33 1.0-10
7.63 0.50 1.0-10
7.93 0.67 1.0-10
5.07 0.33 3.0-12
5.37 0.50 3.0-12
5.67 0.67 3.0-12
0.32-5.7
0.36-8.2
0.50-11.0
0.077-0.44
0.19-0.79
0.24-1.20
1-formylpiperazine
piperazinium ion
0.447-11.9
0.109-9.45
0.423-10.0
0.429-1.27
0.195-3.65
0.464-4.09
8
10
8
a
In 44 wt % ethanol-water, 25.0 °C, ionic strength 0.2 M
a
In 44 wt % ethanol-water, 25.0 °C, ionic strength 0.2 M
(KCl). Free amine fraction. c Concentration of total amine (free
b
(KCl). Free amine fraction. c Concentration of total amine (free
b
amine + protonated forms).
amine + protonated forms).
stirring under nitrogen during 2 h, to a solution of 4-methyl
thionochloroformate8 (5.6 g, 30 mmol) dissolved in THF (40
mL), placed in a Schlenk flask in an ethanol-liquid nitrogen
bath. After the addition, the mixture was left at ambient
temperature for 2 h with stirring under nitrogen. After
evaporation of the solvent, chloroform was added to this
mixture and the solution washed with cold water. The organic
layer was dried with MgSO4 and filtered under vacuum and
the solvent evaporated off. The crystallized (n-hexane-
chloroform) thionocarbonate 1 melted at 129-130 °C and was
identified as follows: 1H NMR (200 MHz, CDCl3) δ 2.40 (s,
3H), 7.12 (d, 2H J ) 8.0 Hz), 7.27 (d, 2H, J ) 7.7 Hz), 7.40 (d,
2H J ) 8.7 Hz), 8.35 (d, 2H, J ) 8.7 Hz); 13C NMR (50 MHz,
CDCl3) δ 21.01 (CH3), 121.20 (C-3′/5′), 123.29 (C-2/6), 125.46
(C-3/5), 130.35 (C-2′/6′), 137.03 (C-4′),146.11 (C-4), 151.33 (C-
1′), 157.56 (C-1), 193.66 (CdS). Anal. Calcd for C14H11O4NS:
C, 58.18; H, 3.84; N, 4.85; S, 11.09. Found: C, 58.56; H, 4.33;
N, 4.55; S, 11.29.
3-Nitr op h en yl 4-m eth ylp h en yl th ion oca r bon a te (2)
was synthesized in the same way but using 3-nitrophenol. This
compound melted at 179-180 °C and was identified as
follows: 1H NMR (200 MHz, CDCl3) ∂ 2.40 (s, 3H), 7.12 (d, 2H
J ) 8.6 Hz), 7.28 (d, 2H, J ) 8.6 Hz), 7.58 (d, 1H, J ) 8.1 Hz),
7.66 (t, 1H J ) 8.1 Hz), 8.13 (d, 1H J ) 8.1 Hz), 8.22 (d, 1H,
J ) 8.1 Hz); 13C NMR (50 MHz, CDCl3) ∂ 21.03 (CH3), 118.09
(C-2), 120.65 (C-4), 121.24 (C-3′/5′), 121.77 (C-6), 128.64 (C-
5), 130.37 (C-2′/6′), 136.99 (C-4′),148.94 (C-3), 151.41 (C-1′),
153.53 (C-1), 194.22 (CdS). Anal. Calcd for C14H11O4NS: C,
58.18; H, 3.84; N, 4.85; S, 11.09. Found: C, 58.21; H, 3.88; N,
4.64; S, 10.90.
Ta ble 3. Exp er im en ta l Con d ition s a n d kobsd Va lu es
Obta in ed in th e P yr id in olysis of 4-Nitr op h en yl
4-Meth ylp h en yl Th ion oca r bon a te (1)a
pyridine
substituent
103 [N]tot
Mc
,
103kobsd
,
no. of
runs
b
pH
FN
s-1
4-(dimethylamino)d 7.25 0.013 5.0-50
7.55 0.025 5.0-50
2.0-20
3.8-40
6.6-65.8
1.8-15.8
3.0-32.6
4.9-57.3
11
11
11
11
11
11
8
7.85 0.049 5.0-50
4-aminod
3,4-dimethyl
4-methyl
3-methyl
H
7.25 0.018 5.0-50
7.55 0.036 5.0-50
7.85 0.069 5.0-50
5.68 0.50
5.98 0.67
6.28 0.80
5.35 0.50
5.65 0.67
5.95 0.80
4.92 0.50
5.22 0.67
5.52 0.80
4.63 0.50
4.93 0.67
5.23 0.80
120-400 1.75-4.75
120-400 2.81-6.41
120-400 3.56-8.02
120-400 1.21-3.01
120-400 1.87-4.26
120-400 2.20-5.25
120-400 0.49-1.49
120-400 0.72-2.21
120-400 0.91-2.40
120-400 0.54-1.30
120-400 0.74-1.97
120-400 0.64-1.84
8
8
8
8
8
8
8
8
8
8
8
a
In 44 wt % ethanol-water, 25.0 °C, ionic strength 0.2 M
b
(KCl). Free amine fraction. c Concentration of total amine (free
d
amine + protonated forms). In the presence of phosphate buffer
0.005 M.
Kin etic Mea su r em en ts. These were performed spectro-
photometrically (Hewlett-Packard 8453) by following the
production of 4-phenol and 3-nitrophenol (and/or their conju-
gate bases) for the reactions of 1 and 2, respectively. The
reactions of 1 were followed at 400 nm, except those at pH
lower than 7, which were studied at 325-330 nm. The
reactions of 2 were followed at 320-330 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 concentra-
tion of the substrates was (3-6) × 10-5 M., and at least a 10-
fold excess of total amine over the substrates was employed.
Pseudo-first-order rate coefficients (kobsd) were found through-
out. The experimental conditions of the reactions and the kobsd
values obtained are shown in Tables 1-4.
P r od u ct Stu d ies. In the reactions of 1 and 2 with mor-
pholine and piperazine, the corresponding 4-methylphenyl
thionocarbamates and 4-nitrophenol or 3-nitrophenol, respec-
tively, were found as final products. 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. In the reactions of 1 and 2 with 4-aminopyridine a
thionocarbamate cation intermediate was detected; a similar
intermediate was found in the reaction of this amine with
methyl 4-nitrophenyl thionocarbonate.5b For the reactions of
1 and 2 with 4-aminopyridine and 4-methylpyridine, 4-methyl-
phenol and 4-nitrophenol or 3-nitrophenol were found as
final products. All these products were identified by compari-
son of the UV-vis spectra at the end of the reactions with
those of authentic samples under the same experimental
conditions.
(8) 4-Methylphenyl thionochloroformate was synthesized from 4-me-
thylphenol and thiophosgene, as previously described.7

Reactions of Thionocarbonates with Alicyclic Amines
J . Org. Chem., Vol. 65, No. 26, 2000 9049
Ta ble 4. Exp er im en ta l Con d ition s a n d kObsd Va lu es
Obta in ed in th e P yr id in olysis of 3-Nitr op h en yl
4-Meth ylp h en yl Th ion oca r bon a te (2)a
pyridine
substituent
102 [N]tot
Mc
,
103kobsd
s-1
,
no. of
runs
b
pH
FN
4-(dimethylamine) 8.84 0.33 0.25-2.50
9.14 0.50 0.25-2.50
20.0-70.3
20.9-96.9
10
9
9.44 0.67 0.125-1.25 20.3-68.8
8.68 0.33 0.25-2.50
8.98 0.50 0.25-2.50
10
10
10
10
8
8
8
8
9
10
8
10
10
4-amino
11.3-27.9
12.2-37.3
9.28 0.67 0.125-1.25 11.1-27.8
3,4-dimethyl
4-methyl
3-methyl
5.85 0.60 6.0-48.0
6.04 0.70 12.0-54.0
6.28 0.80 6.0-60.0
5.53 0.60 6.0-48.0
5.72 0.70 6.0-54.0
5.96 0.80 6.0-60.0
5.10 0.60 6.0-48.0
5.29 0.70 6.0-54.0
5.52 0.80 6.0-60.0
0.018-0.080
0.038-0.113
0.027-0.137
0.0041-0.029
0.0061-0.037
0.0057-0.042
0.0017-0.015
0.0020-0.020
0.0019-0.023
a
In 44 wt % ethanol-water, 25.0 °C, ionic strength 0.2 M (KCl).
Free amine fraction. c Concentration of total amine (free amine
b
+ protonated forms).
Sch em e 1
F igu r e 1. Plot of kobs vs [piperazinium] for the reaction of 2.
For the reactions of 1 and 2 with piperazinium ion, the
plot kobsd vs [NH] can be fitted by eq 3, where K1 () k1/
k-1) is the equilibrium constant for the first step in
Scheme 1.
kobsd ) ko + K1k2[NH] + K1k3[NH]2
(3)
This amine is the least basic of the series; therefore, it
is reasonable that the C-NH bond in T( be the weakest
of the series, and thus, k-1 . k2 + k3[NH], and eq 2
reduces to eq 3. By fitting this equation to the experi-
mental data, the values of ko, K1, and k2 were obtained,
k3 being estimated previously (see below). The values of
K1, k2, and k3 are shown in Table 5. The plot of kobsd vs
[NH] for the reaction of this amine with thionocarbonate
2 is shown in Figure 1. A similar plot was obtained for
the reaction of piperazinium ion with 1.
Resu lts a n d Discu ssion
Rea ction s of Secon d a r y Alicyclic Am in es w ith
Th ion oca r bon a tes 1 a n d 2. The rate law obtained for
these reactions is given by eq 1, where P represents
4-nitrophenol or 3-nitrophenol (and/or their conjugate
bases), S is the substrate (1 or 2), and kobsd is the pseudo-
first-order rate coefficient (amine was in excess over the
substrate).
For the reactions of thionocarbonates 1 and 2 with the
other secondary alicyclic amines (except piperidine) the
plots kobsd vs [NH] are in accord with eq 2. By dividing
numerator and denominator of this equation by k3, eq 4
results, where A ) k1k2/k3, B ) k1, and C ) (k-1 + k2)/k3.
By fitting this equation to the experimental points, the
values of ko, k1, k-1, and k2 were found, with k3 previously
estimated (see below). As an example, Figure 2 shows
the plot of kobsd vs [NH] for the reaction of 1 with
morpholine. The values of the rate microcoefficients found
for the reactions of 1 and 2 with these amines are shown
in Table 5.
d[P]
dt
) kobsd[S]
(1)
Plots of kobsd vs [NH] are nonlinear upward (NH
represents a secondary amine), except that for piperidine,
which is linear. This kinetic behavior is consistent with
the mechanism described in Scheme 1. In this scheme,
the k3 step is the deprotonation of the zwitterionic
tetrahedral intermediate T( by an amine to give the
anionic intermediate T-. Applying the steady-state condi-
tion to the tetrahedral intermediates in Scheme 1, eq 2
is obtained. In this equation ko is the rate coefficient for
solvolysis of the substrate, and the rate coefficients k1,
k-1, k2, and k3 are defined in Scheme 1. In all cases
the value of ko was much smaller than the second term
of eq 2.
(A + B[NH])[NH]
kobsd ) ko +
(4)
C + [NH]
For the reactions of thionocarbonates 1 and 2 with
piperidine, linear plots of kobsd vs [NH] were obtained
(plots not shown). For this very basic amine, k-1 , k2 +
k3[NH]; thus, eq 2 reduces to eq 5. From this plot the
values of ko and k1 were obtained. The ko values were
k1(k2 + k3[NH])[NH]
kobsd ) ko +
(2)
k-1 + k2 + k3[NH]

9050 J . Org. Chem., Vol. 65, No. 26, 2000
Castro et al.
Ta ble 5. Va lu es for th e Ra te Micr ocoefficien ts F ou n d in th e Rea ction s of Th ion oca r bon a tes 1 a n d 2 w ith Secon d a r y
Alicyclic Am in esa
k1/s-1 M-1
10-7 k-1/s-1
amine
pKa
1
2
1
2
piperidine
piperazine
1-(2-hydroxyethyl)piperazine
morpholine
1-formylpiperazine
piperazinium ion
10.82
9.71
9.09
8.48
7.63
5.37
3.4
3.8
1.5
1.3
0.51
3.0
2.2
1.0
1.9
4.7
10
2.9
4.0
8.1
0.87
0.45
44
30
9 × 10-11 b
5 × 10-11 b
other rate microcoefficients:
k2 ) (0.9-1.5) × 107 s-1 (1) and (4-6) × 106 s-1 (2)
k3 ) 2 × 109 s-1 M-1 (piperazinium ion)
k3 ) 4 × 109 s-1 M-1 (other sec. alicyclic amines)
a
Both the rate microcoefficients and pKa values were determined in 44 wt % ethanol-water, 25.0 °C, ionic strength 0.2 M (KCl).
Values of K1 () k1/k-1) in M-1
.
b
F igu r e 3. Bro¨nsted plots for k1 for the aminolyses of thiono-
carbonates 1 and 2.
F igu r e 2. Plot of kobs vs [morpholine] for the reaction of 1.
larger reactivity of compound 1 than 2 can be explained
by the stronger electron-withdrawing effect of the 4-nitro
group in 1 than 3-nitro in 2, which leaves the thiocar-
bonyl carbon of 1 more positively charged and therefore
more susceptible to nucleophilic attack.
The Bro¨nsted plots for k-1 (pKa values statistically
corrected)5,9 for the reactions of thionocarbonates 1 and
2 are linear with slopes â-1 ) -0.72 and -0.57, respec-
tively (Figure 4). For the first step of Scheme 1, the
negligible compared to those of k1[NH]. The k1 values are
shown in Table 5.
kobsd ) ko + k1[NH]
(5)
With the values of k1 obtained either through fitting
of eq 2 or as the slopes of the linear plots of eq 5, the
Bro¨nsted plots for the reactions of 1 and 2 with secondary
alicyclic amines (except piperazinium ion) were obtained.
These plots are statistically corrected9 with p ) 2 for all
the conjugate acids of the amines and q ) 1 for all
amines, except piperazine with q ) 2.5,6b The Bro¨nsted
plots are linear with slopes â1 ) 0.25 for the reactions of
both substrates (Figure 3); the magnitudes of the slopes
are in accord with those of Bro¨nsted slopes for similar
reactions when T( formation is rate determining.1,2 This
indicates that the k1 values obtained are reasonable.
According to the Bro¨nsted plots in Figure 3, thiono-
carbonate 1 is more reactive than thionocarbonate 2. The
Bro¨nsted slope for the equilibrium constant K1 is âeq
)
â1 - â-1, which gives âeq ) 0.25 - (-0.72) ) ca. 1.0 for
the reactions of 1. A similar calculation gives âeq ca. 0.8
for the reactions of 2. Since the Bro¨nsted slope for the k2
step of Scheme 1 is zero or near zero, namely the k2 value
is independent of amine basicity,1,2 it follows that the
Bro¨nsted slopes for the equilibrium formation of T( (âeq)
should be the same as those when the k1 step of Scheme
1 is at equilibrium and the k2 step is rate determining
(with k3 ) 0). In fact the values of âeq obtained above for
the aminolyses of 1 and 2 are similar to those of the
Bro¨nsted slopes found in analogous aminolyses when
decomposition of a zwitterionic tetrahedral intermediate
to products is the rate-limiting step.1,2,5,6 This indicates
(9) Bell, R. P. The Proton in Chemistry; Methuen: London, 1959; p
159.

Reactions of Thionocarbonates with Alicyclic Amines
J . Org. Chem., Vol. 65, No. 26, 2000 9051
F igu r e 5. Bro¨nsted plots for k1 for the pyridinolyses of
thionocarbonates 1 and 2.
F igu r e 4. Bro¨nsted plots for k1 for the aminolyses of thiono-
carbonates 1 and 2. The ordinate values for 1 are increased
by 0.5 units.
sion controlled.10 Therefore, the k3 value should be ca.
1010 s-1 M-1 in water,5,14 and 4 × 109 s-1 M-1 in 44 wt %
ethanol-water.15,16 In the particular case of the proton
transfer from T( of Scheme 1 to piperazinium cation, the
value of k3 in 44 wt % ethanol-water has been estimated
as 2 × 109 s-1 M-1, due to repulsion of the positive
charges involved.16
that the k1 and k-1 values obtained as stated above for
the reactions of 1 and 2 with alicyclic amines are
reasonable.
Estim a tion of th e p Ka Va lu e of T( of Sch em e 1.
To determine the value of k3 in Scheme 1, we must first
estimate the pKa value of the intermediate T( in this
scheme. On the basis of J encks' procedure, which involves
the use of Hammett inductive parameters,10 it was
estimated that the pKa of the tetrahedral intermediate
3 is 6.4 units lower than that of the corresponding
aminium ion.5a That is, the proton transfer from 3 to
the corresponding amine is thermodynamically favorable
and should be diffusion controlled.5,10 Employing the
Hammett inductive reaction constant FI ) -9.2 for the
pKa of intermediates similar to 3,11 and the values of
Hammett inductive substituent constants σI ) 0.26 and
0.37 for EtO and PhO, respectively,12 it can be determined
that pKa (4) - pKa (3) ) -9.2(0.37-0.26) ) -1.0.
Therefore, the pKa of 4 should be 6.4 + 1.0 ) 7.4 pKa
units lower than that of the corresponding aminium
ion. Since σI for phenyl is the same as that for 4-methyl-
phenyl,12 the pKa of 5 should be the same as that
of 4. Taking into account that σI ) 0.47 for 4-nitro-
phenoxy12 and σI ) 0.44 for 3-nitrophenoxy,13 replacement
of the 4-nitro group by 3-nitro should change the pKa by
-9.3(0.44 - 0.47) ) 0.3 unit. Therefore, the pKa of 6
should be 7.1 units lower than that of the aminium ion.
Namely, the proton transfers from either 5 or 6, which
are the intermediates T( in Scheme 1, to the correspond-
ing amines are thermodynamically favorable and diffu-
R ea ct ion s of P yr id in es w it h Th ion oca r b on a t es
1 a n d 2. The rate law found for these reactions is
described by eqs 1 and 6, where N represents a pyridine,
and ko and kN are the rate constants for solvolysis and
pyridinolysis, respectively.
kobsd ) ko + kN[N]
(6)
For these reactions, the plots of kobsd vs [N] at different
pH values are linear (plots not shown), with the slopes
(kN) independent of pH. In all cases the ko values were
much smaller than those of the second term of eq 6. The
kN values obtained for the pyridinolysis of thionocarbon-
ates 1 and 2 are summarized in Table 6.
With the kN data determined for these reactions the
Bro¨nsted plots shown in Figure 5 were obtained. The
Bro¨nsted slopes for the pyridinolysis of 1 and 2 are
â ) 0.9 and 1.2, respectively. According to their slope
values the reactions of pyridines with both substrates
follow the mechanism depicted in Scheme 2, where the
(10) 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.
(11) Taylor, P. J . J . Chem. Soc., Perkin Trans. 2 1993, 1423.
(12) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(13) The σI value for 3-nitrophenoxy is unknown but it can be
deduced from that for 4-nitrophenoxy ()0.47)12 and assuming there is
the same σI difference than that between 3-nitrophenyl and 4-nitro-
phenyl (σI ) 0.23 and 0.26, respectively).12
(14) Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1.
(15) Value estimated knowing that the viscosity coefficient of 44 wt
% ethanol-water is 2.5-fold higher than that of water at 25 °C.
(16) Castro, E. A.; Leandro, L.; Santos, J . G. Int. J . Chem. Kinet.
1999, 31, 839.

9052 J . Org. Chem., Vol. 65, No. 26, 2000
Castro et al.
Ta ble 6. Va lu es for th e Nu cleop h ilic Ra te Coefficien ts
(kN) a n d th e Equ ilibr iu m Con sta n ts K1 of Sch em e 2 for
th e P yr id in olysis of Th ion oca r bon a tes 1 a n d 2a
kN, s-1 M-1
109K1, M-1
pyridine
substituent
pKa
1
2
1
2
4-(dimethylamino) 9.14 30
6.7
2.3
3000 1340
1800 460
4-amino
3,4-dimethyl
4-methyl
3-methyl
H
8.98 18
5.68 0.019
5.35 0.013
2.8 × 10-4 1.9
0.056
0.018
0.010
9.2 × 10-5 1.3
4.92 0.0070 4.9 × 10-5 0.7
4.63 0.0060
0.6
a
Both the rate coefficients and pKa values were determined in
44 wt % ethanol-water, 25.0 °C, ionic strength 0.2 M (KCl).
Sch em e 2
first step is at equilibrium (K1) and the k2 step is rate
limiting.1,2,5,6
F igu r e 6. Bro¨nsted plots for K1 for the reactions of thiono-
carbonate 1 with pyridines and alicyclic amines.
Since for these reactions kN ) K1k2, and assuming the
k2 values are independent of the amine basicity and
nature,1,2 the K1 values can be determined from the k2
values found in the reactions of 1 and 2 with secondary
alicyclic amines (k2 values in Table 5 and K1 values in
Table 6). The larger K1 values for the pyridinolysis of
thionocarbonate 1 than thionocarbonate 2, are reason-
able, in view of the stronger electron-withdrawing effect
of 4-nitro in 1 compared to 3-nitro in 2, which should
favor the nucleophilic attack by a pyridine and also the
equilibrium formation of the zwitterionic tetrahedral
intermediate (T( in Scheme 2).
The larger kN values for the pyridinolysis of 1 relative
to those for 2 (Figure 5 and Table 6) should be due to
larger K1 values for the reactions of 1 than 2, and also to
a larger k2 value for the former reactions. The latter is
reasonable on the grounds of the better nucleofugality
of 4-nitrophenoxide anion than 3-nitrophenoxide from the
intermediate T(.1,2,5
Com p a r ison betw een th e Am in olysis a n d P yr i-
d in olysis of 1 a n d 2. This comparison is not straight-
forward since the mechanisms are different. Neverthe-
less, we can compare the K1 values for these reactions.
Those for the pyridinolysis of thionocarbonates 1 and 2
can be calculated as K1 ) kN/k2. The K1 values for the
reactions of thionocarbonates 1 and 2 with secondary
alicyclic amines can be determined as k1/k-1 (Table 5).
Figure 6 shows the Bro¨nsted plots (statistically corrected)
obtained for the reactions of thionocarbonate 1 with the
two amine series. As seen in this figure, the K1 values
are larger for the reactions of pyridines compared to
isobasic alicyclic amines. The same situation occurs for
the reactions of thionocarbonate 2. This indicates that
pyridines favor the equilibrium formation of T( more
than isobasic secondary alicyclic amines. This could be
due in part to larger k1 values for pyridines toward these
types of substrates, as found in the reactions of ethyl
4-nitrophenyl thionocarbonate with these two amine
series.5b This could also be due to smaller k-1 values for
pyridines relative to isobasic alicyclic. amine, since it is
well-known that pyridines can leave a zwitterionic tetra-
hedral intermediate slower than isobasic quinuclidines
(tertiary alicyclic amines)1,17 and isobasic alicyclic
amines.5b,c,18
Com p a r ison of th e Title Rea ction s w th th e Am i-
n olysis of Oth er Su bstr a tes. The reactions of second-
ary alicyclic amines with ethyl 4-nitrophenyl thionocar-
bonate (7) in water5a are governed by the same mechanism
(Scheme 1) as that for the reactions of the same amines
with substrate 1 in ethanol-water (this work). In both
cases, the order in amine is one for piperidine and
between one and two for the other amines. Nevertheless,
the k1 values for the reactions of thionocarbonate 7 are
larger than those of 1.5a This fact cannot be explained
by electronic effects since EtO is probably as electron
donating as 4-MePhO by resonance and the former group
should possess a smaller inductive electron-withdrawing
ability than the latter.19 These effects should leave the
thiocarbonyl carbon of 1 more positively charged than
that of 7, which would result in a faster amine attack to
1. The larger k1 values for the aminolysis of thionocar-
bonate 7 in water than those of 1 in aqueous ethanol
could be explained by the more polar solvent used in the
former reactions. It can also be explained by a larger
steric hindrance caused by the 4-methylphenyl group of
1, compared with the Et group of 7. A similar situation
was found in the same aminolyses of methyl and phenyl
4-nitrophenyl thionocarbonates in water,5d whereby the
values of k1 for the reactions of the former substrate are
(17) Castro, E. A.; Mun˜oz, P.; Santos, J . G. J . Org. Chem. 1999, 64,
8298.
(18) Castro, E. A.; Ureta, C. J . Org. Chem. 1990, 55, 1676. Castro,
E. A.; Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991, 63. Castro, E. A.;
Araneda, C. A.; Santos, J . G. J . Org. Chem. 1997, 62, 126. Castro, E.
A.; Pizarro, M. I.; Santos, J . G. J . Org. Chem. 1996, 61, 5982.
(19) The σR and σI values for the 4-methylphenoxy group are
unknown, but we can compare the groups Et with 4-methylphenyl.
The value of σR is -0.15 for both and those for σI are 0.0 and 0.12,
respectively.12

Reactions of Thionocarbonates with Alicyclic Amines
J . Org. Chem., Vol. 65, No. 26, 2000 9053
larger than those for the latter, despite the electronic
effects, which should favor amine attack on the phenyl
derivative.5d
unstable, and perhaps nonexistent (if the mechanism is
enforced concerted).20 The change of 4-nitrophenoxy to
4-methylphenoxy should stabilize this intermediate since
4-methylphenoxy is a much worse leaving group. This
could be the reason for the shift in mechanism from
concerted to stepwise by the above change. On the other
hand, the intermediate T( should be more stable in water
than aqueous ethanol. Therefore, the stabilization of T(
brought about by the change of 4-nitro to 4-methyl should
be more important than the destabilization caused by the
solvent change.
The mechanism found in the pyridinolysis of thiono-
carbonate 1 in aqueous ethanol (Scheme 2) is the same
as that for the same reactions of thionocarbonate 7,5b and
bis(4-nitrophenyl) thionocarbonate (8) in water.5c In all
these reactions linear Bro¨nsted plots were obtained, with
slopes (â ) 1.0 for the two latter reactions) compatible
with a stepwise mechanism whereby expulsion of the
leaving group is rate limiting. The kN () K1k2) values for
the pyridinolysis of 8 are larger5c than those for the same
reactions of 1 (Table 6). This can be explained by the
larger K1 values for the former reactions, and probably,
by similar k2 values for these reactions. The larger K1
values for the pyridinolysis of 8 are reasonable on the
basis of the stronger electron-withdrawing effect of the
4-nitro group in 8 compared to 4-methyl in 1, which
should favor amine attack and also equilibrium formation
of the zwitterionic tetrahedral intermediate (T() in the
former reactions. Moreover, the solvent should also play
a role here: the K1 values in water (reactions of 8) should
be greater than those in aqueous ethanol (reactions of
1), due to the zwitterionic nature of T(.1 The value of k2
should be larger for the pyridinolysis of 1, in view of the
stronger push by 4-methoxy than 4-nitrophenoxy in T(
to expel the leaving 4-nitrophenoxide group from this
intermediate. Nevertheless, this can be compensated by
the fact that 8 possesses two identical leaving groups,
which should favor statistically the nucleofugality of
4-nitrophenoxide from the intermediate T( formed in this
reaction. On the other hand, there should be little
influence of the solvent on the k2 value since both the
transition state for T( breakdown and T( are highly
polar.1
The reactions of secondary alicyclic amines with phenyl
4-nitrophenyl thionocarbonate (9) in water are ruled by
the stepwise mechanism of Scheme 1, whereby the k1 step
is rate determining for the reactions of most amines
(except piperazinium ion).5d The plots of kobsd vs [NH] are
linear for these reactions, in contrast to the nonlinear
upward plots found in the same aminolysis (except
piperidine) of 1 in aqueous ethanol (Figure 2). The reason
for the k1 step being rate limiting in the aminolysis of 9
5d
is that k3[NH] + k2 . k-1
,
therefore, eq 2 reduces to eq
5. It was also found that in this reaction k3[NH] > k2.
For the reactions of 1 there is no clear rate-determining
step, i.e., the three terms in the denominator of eq 2 are
of the same order of magnitude. The reasons for the
different behavior between these reactions can be found
in both the addition of 4-methyl in the nonleaving group
and the change of solvent. Addition of 4-methyl to the
T( intermediate formed in the aminolysis of 9 should
increase both k-1 and k2 and also the ratio k2/k-1, since
it is known that electron donation from the nonleaving
group favors aryloxide expulsion (relative to amine
expulsion) from T(.1 The value of k3 should be the
approximately the same for both reactions due to the fact
that the proton transfers from both T( to the correspond-
ing amine are diffusion controlled.5d Also the range of
amine concentration is about the same for the reactions
of 1 and 9. On the other hand, the change of solvent from
water to aqueous ethanol should increase the value of
k-1 and hardly affect the value of k2.1 Therefore, the
different kinetic behavior between these reactions should
be due to the larger values of both k2 and k-1 (but much
larger k-1 due to solvent effect) for the reactions of 1 in
aqueous ethanol than those for the same reactions of 9
in water.
The reactions of 8 with secondary alicyclic amines in
water are concerted, as evidenced by a the slightly curved
Bro¨nsted plot found in these reactions.5c This is in great
contrast to the stepwise process exhibited by the reac-
tions of the same amines with 1 in aqueous ethanol
(Scheme 1). The difference in mechanism must be due
to the different stability of the putative tetrahedral
intermediates (T() in these reactions. The hypothetical
T( in the reactions of 8 would possess three very good
nucleofuges (two 4-nitrophenoxy groups and the amino
moiety), which should render this intermediate highly
Ack n ow led gm en t. We thank FONDECYT (project
1990561) of Chile for financial assistance. L.L. thanks
FONDECYT (project 2990101) for financial support to
this work and CONICYT for a scholarship.
J O005587E
(20) J encks, W. P. Chem. Soc. Rev. 1981, 10, 345. Williams, A. Chem.
Soc. Rev. 1994, 23, 93.