Kinetics and mechanisms of the pyridinolysis of phenyl and 4-nitrophenyl chlorothionoformates formation and hydrolysis of 1-(aryloxythiocarbonyl) pyridinium cations

Article abstract of DOI:10.1021/jo049559y

The title reactions are subjected to a kinetic study in water, at 25.0 °C, and an ionic strength of 0.2 M (KCl). By following the reactions spectrophotometrically two consecutive reactions are observed: the first is formation of the corresponding thionocarbamates (1-(aryloxythiocarbonyl)- pyridinium cations) and the second is their decomposition to the corresponding phenol and pyridine, and COS. Pseudo-first-order rate coefficients (k _obsd1 and k_obsd2, respectively) are found under excess amine. Plots of k_obsd1 vs free pyridine concentration at constant pH are linear, with the slope (k_N) independent of pH. The Bronsted-type plots (log k_N vs pK_a of the conjugate acids of the pyridines) are linear with slopes β = 0.07 and 0.11 for the reactions of phenyl and 4-nitrophenyl chlorothionoformates, respectively. These Bronsted slopes are in agreement with those found in other stepwise reactions of the same pyridines in water, where the formation of a tetrahedral intermediate is the rate-determining step. In contrast to the stepwise mechanism of the title reactions that for the reactions of the same substrates with phenols is concerted, which means that substitution of a pyridino moiety in a tetrahedral intermediate by a phenoxy group destabilizes the intermediate. The second reaction corresponds to the pyridine-catalyzed hydrolysis of the corresponding 1-(aryloxythiocarbonyl)pyridinium cation. Plots of k _obsd2 VS free pyridine concentration at constant pH are linear, with the slope (k_H) independent of pH. The Bronsted plots for k_H are linear with slopes β = 0.19 and 0.26 for the reactions of the phenyl and 4-nitrophenyl derivatives, respectively. These low values are explained by the fact that as pK_a increases the effect of a better pyridine catalyst is compensated by a worse leaving pyridine from the corresponding thionocarbamate.

Full text of DOI:10.1021/jo049559y

Kin etics a n d Mech a n ism s of th e P yr id in olysis of P h en yl a n d
4-Nitr op h en yl Ch lor oth ion ofor m a tes. F or m a tion a n d Hyd r olysis of
1-(Ar yloxyth ioca r bon yl)p yr id in iu m Ca tion s
Enrique A. Castro,* Mar´ıa Cubillos, and J ose´ G. Santos*
Facultad de Qu´ımica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 22, Chile
ecastro@puc.cl
Received March 17, 2004
The title reactions are subjected to a kinetic study in water, at 25.0 °C, and an ionic strength of 0.2
M (KCl). By following the reactions spectrophotometrically two consecutive reactions are ob-
served: the first is formation of the corresponding thionocarbamates (1-(aryloxythiocarbonyl)-
pyridinium cations) and the second is their decomposition to the corresponding phenol and pyridine,
and COS. Pseudo-first-order rate coefficients (kobsd1 and kobsd2, respectively) are found under excess
amine. Plots of kobsd1 vs free pyridine concentration at constant pH are linear, with the slope (kN)
independent of pH. The Brønsted-type plots (log kN vs pKa of the conjugate acids of the pyridines)
are linear with slopes â ) 0.07 and 0.11 for the reactions of phenyl and 4-nitrophenyl chlorothiono-
formates, respectively. These Brønsted slopes are in agreement with those found in other stepwise
reactions of the same pyridines in water, where the formation of a tetrahedral intermediate is the
rate-determining step. In contrast to the stepwise mechanism of the title reactions that for the
reactions of the same substrates with phenols is concerted, which means that substitution of a
pyridino moiety in a tetrahedral intermediate by a phenoxy group destabilizes the intermediate.
The second reaction corresponds to the pyridine-catalyzed hydrolysis of the corresponding
1-(aryloxythiocarbonyl)pyridinium cation. Plots of kobsd2 vs free pyridine concentration at constant
pH are linear, with the slope (kH) independent of pH. The Brønsted plots for kH are linear with
slopes â ) 0.19 and 0.26 for the reactions of the phenyl and 4-nitrophenyl derivatives, respectively.
These low values are explained by the fact that as pKa increases the effect of a better pyridine
catalyst is compensated by a worse leaving pyridine from the corresponding thionocarbamate
In tr od u ction
a stepwise mechanism where the formation of a zwitte-
rionic tetrahedral intermediate (T() is the rate-determin-
ing step.2d
The solvolysis of phenyl chlorothionoformate (PClTF)
in aqueous ethanol and aqueous acetone mixtures was
found to be driven by an addition-elimination reaction
at the trigonal carbon.3a In contrast, the solvolysis
(methanol, ethanol, and their aqueous mixtures) of the
same substrate was found to be subjected to a general-
base-catalyzed SN2 pathway.3b
Although much attention has been focused on the
kinetics and mechanisms of the solvolysis1 and aminoly-
sis2 of chloroformates, much less is known on the mech-
anisms of the solvolysis,3 phenolysis,4 and aminolysis5 of
chlorothionoformates.
The pyridinolysis of phenyl and 4-nitrophenyl chloro-
formates in acetonitrile exhibits linear Brønsted-type
plots with slopes (â) of ca. 0.3, which were attributed to
The reactions of PClTF and 4-nitrophenyl chlorothion-
oformate (NPCITF) with substituted phenolates in water
are governed by a concerted mechanism, as shown by the
linear Brønsted-type plots obtained, with slopes (â) of
0.55 and 0.47, respectively.4
On the other hand, the aminolysis (secondary alicyclic
amines) of PCITF and NPCITF in water exhibits linear
Brønsted-type plots with the same slope, â 0.26, consis-
tent with a stepwise process, where the formation of the
intermediate T( is rate limiting.5
(1) Moodie, R. B.; Towill, R. J . Chem. Soc., Perkin Trans. 2 1972,
184. Butler, A. R.; Robertson, I. H.; Bacaloglu, R. J . Chem. Soc., Perkin
Trans. 2 1974, 1733. Kevill, D. N.; Kyong, J . B.; Weitl, F. L. J . Org
Chem. 1990, 55, 4304. Koo, I. S.; Yang, K.; Kang, K.; Oh, H. K.; Lee,
I. Bull. Korean Chem. Soc. 1996, 17, 520. Koo, I. S.; Yang, K.; Koo, J .
C.; Park, J . K.; Lee, I. Bull. Korean Chem. Soc. 1997, 18, 1017. Kevill,
D. N.; D’Souza, M. J . J . Chem. Soc., Perkin Trans. 2 1997, 1721. Kevill,
D. N.; Bond, M. W.; D’Souza, M. J . J . Org. Chem. 1997, 62, 7869. Kevill,
D. N.; D’Souza, M. J . J . Org. Chem. 1998, 63, 2120. Kevill, D. N.; Kim,
J . C.; Kyong, J . B. J . Chem. Res., Synop. 1999, 150. Koo, I. S.; Lee, J .
S.; Yang, K.; Kang, K.; Lee, I. Bull. Korean Chem. Soc. 1999, 20, 573.
Possidonio, S.; Siviero, F.; El Seoud, O. A. J . Phys. Org. Chem. 1999,
12, 325. Kyong, J . B.; Kim, Y. G.; Kim, D. K.; Kevill, D. N. Bull. Korean
Chem. Soc. 2000, 21, 662. Kyong, J . B.; Park, B. C.; Kim, C. B.; Kevill,
D. N. J . Org. Chem. 2000, 65, 8051.
In the present work, we undergo a kinetic and mecha-
nistic study of the reactions of pyridines with the title
(2) (a) Castro, E. A.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2
1974, 658. (b) Bond, P. M.; Castro, E. A.; Moodie, R. B. J . Chem. Soc.,
Perkin Trans. 2 1976, 68. (c) Yew, K. H.; Koh, H. J .; Lee, H. W.; Lee,
I. J . Chem. Soc., Perkin Trans. 2 1995, 2263. (d) Koh, H. J .; Han, K.
L.; Lee, H. W.; Lee, I. J . Org. Chem. 1998, 63, 9834. (e) Castro, E. A.;
Ruiz, M. G.; Salinas, S.; Santos, J . G. J . Org. Chem. 1999, 64, 4817.
(f) Castro, E. A.; Ruiz, M. G.; Santos, J . G. Int. J . Chem. Kinet. 2001,
33, 281.
(3) (a) Kevill, D. N.; D’Souza, M. J . Can. J . Chem. 1999, 77, 1118.
(b) Koo, I. S.; Yang, K.; Kang, D. H.; Park, H. J .; Kang, K.; Lee, I.
Bull. Korean Chem. Soc. 1999, 20, 577.
(4) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org Chem. 1998, 63,
6820.
(5) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org Chem. 1997, 62,
4395.
10.1021/jo049559y CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/17/2004
4802
J . Org. Chem. 2004, 69, 4802-4807

Pyridinolysis of Chlorothionoformates
TABLE 1. Exp er im en ta l Con d ition s a n d Va lu es of kobsd 1
(fa st p r ocess) a n d kobsd 2 (Slow P r ocess) for th e
P yr id in olysis of P CITF a
TABLE 2. Exp er im en ta l Con d ition s a n d Va lu es of kobsd 1
(F a st P r ocess) a n d kobsd 2 (Slow P r ocess) for th e
P yr id in olysis of NP CITF a
pyridine
substituent pH
103[N]tot
(M)
103kobsd1
(s-1
103kobsd2
(s-1
no. of
runs
pyridine
substituent pH
103[N]tot
(M)
103kobsd1
(s-1
103kobsd2
(s-1
no. of
runs
)
)
)
)
4-N(CH3)2 6.50 1.0-10.0
6.80 0.70-10.0
0.11-0.27
0.96-3.96
1.35-5.21
2.90-25.8
2.11-24.3
6.36-58.7
7
9
7
7
7
7
7
6
6
6
7
6
7
7
6
6
7
6
2
5
7
7
6
7
7
7
4-N(CH3)2 6.50 1.0-10.0
6.80 1.0-10.0
2.44-4.95
3.49-8.27
3.10-10.1
6.90-61.0
7.55-62.4
17.4-133
7
7
7
7
7
7
6
6
5
6
7
7
6
6
6
2
6
7
7
6
4
5
4
7
7
7
7.10 0.70-7.0
7.10 0.70-7.0
4-NH2
6.50 9.0-90
6.80 1.0-50
7.10 5.0-50
4-NH2
6.50 9.0-90
6.80 5.5-50
7.10 5.0-50
3.4-(CH3)2 6.50 0.15-1.05
6.80 0.15-0.90 29-101
1.61-8.00
1.69-9.90
2.86-11.7
6.90-35.9
6.44-27.5
7.65-30.3
2.30-9.40
4.71-17.3
3.4-(CH3)2 6.50 0.15-0.90
6.80 0.15-0.90
21.6-41.5
20.9-48.9
22.1-49.8
32.9-93.8
20.6-75.2
16.9-85.7
12.2-35.0
11.8-35.5
16.2-40.2
7.10 0.15-0.90 29.5-111
6.50 0.40-3.40 46-370
6.80 0.20-2.00 35.5-234
7.10 0.40-4.00 40.1-319
5.00b 0.15-1.00
7.10 0.15-0.75
4-CH3
4-CH3
6.50 0.40-3.40
6.80 0.20-2.20
7.10 0.40-4.00
6.50 0.35-1.10
6.80 0.25-1.00
7.10 0.30-1.05
H
H
6.50 0.20-1.10 27.3-156
6.80 0.25-1.00 41.8-144
7.10 0.30-1.50 50.1-227
6.80 0.10-1.00
3-CONH2
3.40b 0.20-0.32 44.2-53.0
5.00c 0.30-1.20 62.3-169
6.50 0.20-1.10
4.17-15.4
4.60-18.1
7.10 0.15-1.05
2.27-10.5
2.18-9.85
3.47-9.50
3-CONH2
3.40b 0.20-0.32 16.0-23.0
5.00c 0.30-1.20 37.4-118
6.50 0.20-1.10
6.80 0.15-1.00
7.10 0.25-0.90
2.22-9.45
1.88-8.68
2.60-7.62
16.4-129
17.4-176
8.45-81.2
4-CN
1.90b 0.30-0.70 27.2-37.7
2.20b 0.30-0.70 30.9-51.7
2.50b 0.30-0.70 32.0-64.0
6.50 6.0-60.0
6.80 0.15-1.00
7.10 0.25-0.90
4-CN
6.50 4.0-60.0
24.1-221
33.6-329
15.8-142
6.80 8.0-80.0
6.80 8.0-80.0
7.10 4.0-40.0
7.10 4.0-40.0
a
a
In aqueous solution, at 25.0 °C, an ionic strength of 0.2 M,
and under the presence of phosphate buffer 0.005 M, unless
In aqueous solution, at 25.0 °C, an ionic strength of 0.2 M,
and under the presence of phosphate buffer 0.005 M, unless
otherwise stated. Without external buffer. c Under the presence
otherwise stated. Without external buffer. c Under the presence
b
b
of citrate buffer 0.005 M.
of citrate buffer 0.005 M.
In some cases, consecutive reactions were observed: initial
fast absorbance increase (kobsd1), followed by a slow further
increase of absorbance (kobsd2), Depending on the experimental
conditions, in some reactions the formation and/or hydrolysis
of an intermediate could be studied kinetically (see below).
The experimental conditions of the reactions and the values
of kobsd1 and kobsd2 are shown in Tables 1 and 2 and in Tables
S1-S4 in Supporting Information.
substrates (PCITF and NPCITF) in water with the aim
of extending our investigations on the aminolysis of
chlorothionoformates. Specific aims are the comparisons
of these reactions with the following: the pyridinolysis
of aryl chloroformates in acetonitrile,2d the solvolysis of
PCITF,3 and the phenolysis4 and aminolysis (secondary
alicyclic amines)5 of the title substrates in water.
P r od u ct Stu d ies. Phenol and 4-nitrophenol (and/or their
corresponding anions) were identified as one of the final
products of the pyridinolysis of PClTF and NPClTF. This was
achieved by comparison of the UV-vis spectra at the end of
the reactions with those of authentic samples under the same
experimental conditions. For some reactions, the appearance
and disappearance of an intermediate was also detected
spectrophotometrically at 270-320 nm. As an example, Figure
1 shows a plot of absorbance at 295 nm vs time obtained for
the reaction of pyridine with PClTF. We identify this inter-
mediate as the corresponding 1-(aryloxythiocarbonyl)pyri-
dinium cation (intermediate 1 in Scheme 1). Similar interme-
diates have been detected spectrophotometrically or isolated
in the pyridinolysis of methyl chloroformate and other re-
agents.7
A reviewer has pointed out that some catalysis by pyridine
of the hydrolysis of the substrates could also take place.
Nevertheless, one proof that this catalysis is not important
comes from the fact that the final phenol (or 4-nitrophenol,
depending on the substrate) concentration for the fast step was
never more than 10% of the substrate initial concentration.
This was found for the reactions of 4-cyanopyridine, which is
the least basic of all the pyridines studied, and therefore this
is the most favorable reaction to observe general base catalysis.
Exp er im en ta l Section
Ma ter ia ls. The series of pyridines were purified either by
distillation or recrystallization. PClTF was used as purchased.
NPClTF was synthesized as described.5
Kin etic Mea su r em en ts. These were carried out by means
of a diode array spectrophotometer, in aqueous solution, at
25.0 ( 0.1 °C, an ionic strength of 0.2 M (KCl), and usually
under the presence of phosphate buffer 0.005 M. In a few cases,
the pH was maintained by the corresponding pyridine/pyri-
dinium pair or by the use of citrate buffer 0.005 M. The pH
values of some reaction solutions were also measured after
completion of these reactions; no significant pH variations were
observed within 0.01 pH unit. The reactions were followed at
220-500 nm and carried out under an excess (10-fold at least)
of the pyridine over the substrate. The initial substrate
concentration was (1-2) × 10-5 M. Pseudo-first-order rate
coefficients (kobsd) were found for all the reactions by means of
the method described.6
(7) (a) Guillot-Edelheit, G.; Laloi-Diard, M.; Guibe´-J ampel, E.;
Wakselman, M. J . Chem. Soc., Perkin Trans. 2 1979, 1123. (b) Battye,
P. J .; Ihsan, E. M.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2 1980,
741. (c) Chryistiuk, E.; Williams, A. J . Am. Chem. Soc. 1987, 109, 3040.
(6) Castro, E. A.; Ureta, C. J . Org Chem. 1989, 54, 2153.
J . Org. Chem, Vol. 69, No. 14, 2004 4803

Castro et al.
F IGURE 1. Plot of absorbance at 295 nm (1-cm cell) against
time obtained in the reaction of PClTF with pyridine in
aqueous solution at 25.0 °C, ionic strength 0.2 (KCl), [N]tot
)
F IGURE 2. Plot of kobsd1 and kobsd2 against free amine
concentration for the reaction of 3,4-dimethylpyridine with
PClTF, in aqueous solution, at 25.0 °C, ionic strength 0.2 (KCl)
(O, kobsd1 pH 7.1; b, kobsd1 pH 6.8; 2, kobsd2 pH 7.1; 0, kobsd2 pH
6.8; 9, kobsd2 pH 6.5).
4 × 10-4 M, pH ) 6.8 (0.005 M phosphate buffer).
SCHEME 1
TABLE 3. Va lu es of p Ka of P yr id in iu m Ion s a n d of kN
a n d kH for th e P yr id in olysis of P ClTF a n d NP ClTF a
PCITF
NPCITF
b
c
b
c
pyridine
kN
kH
kN
(s-1 M-1
kH
substituent pKa (s-1 M-1
)
(s-1 M-1
)
)
(s-1 M-1
)
4-N(CH3)2 9.87
4-NH2 9.42
3,4-(CH3)2 6.77
330
222
181
168
91
673
519
20
15
14
8
75
35
32
9
The above percentage was obtained by comparison of the final
absorbance of phenol (before decomposition of intermediate 1)
with an authentic sample of phenol at the same initial
substrate concentration, under the same experimental condi-
tions. Namely, the sum of the uncatalyzed term (k0) and the
general base-catalyzed term (kgb[N]) was at most 10% of the
kobsd1 value.
4-CH3
H
3-CONH2
4-CN
6.25
5.37
3.4
123
100
2.2
2
4
a
In aqueous solution, at 25.0 °C, and an ionic strength of 0.2
b
M. Nucleophilic rate constant for the formation of intermediate
1. c General base-catalyzed (by the corresponding pyridine) rate
constant for hydrolysis of intermediate 1.
Resu lts a n d Discu ssion
the values of k0 were negligible compared to those of the
pyridinolysis term in eq 2
Sp ectr op h otom etr ic Stu d y. The reactions of PCITF
and NPCITF with the series of pyridines were followed
spectrophotometrically (220-500 nm), showing, in many
cases, a fast absorbance increase, followed by a slower
increase. The former increase is attributed to the forma-
tion of the corresponding phenol/phenoxide pair (k0 step
in Scheme 1) and the latter to the slow hydrolysis of the
corresponding thionocarbamate 1 (kobsd2 step in Scheme
1), which also produces the corresponding phenol/phen-
oxide pair. However, the values of kobsd1 were obtained
by measuring the formation of the thionocarbamate 1 (see
below).
d[1]
dt
) kN[N][S] ) kN[N][S]0 e-(kobsd1 t)
kobsd1 ) k0 + kN[N]
(1)
(2)
The second-order rate coefficients for aminolysis (kN)
were obtained as the slopes of plots of eq 2 at constant
pH and were pH independent. Figure 2 shows an
example of such plots, for kobsd1 as well as kobsd2. The
values of kN found, together with the pKa values of the
conjugate acids of the pyridines, are shown in Table 3.
With these data the Brønsted-type plots of Figure 3 were
obtained. Table 3 also shows the values of kH (obtained
from the kobsd2 values), which were obtained as explained
below.
The slopes of the lines (â) are 0.07 ( 0.05 and 0.11 (
0.05 for the reactions of PCITF and NPCITF, respec-
tively. The magnitude of â is in agreement with the
values of Brønsted slopes found in stepwise mechanisms
of similar reactions when the formation of the zwitteri-
onic tetrahedral intermediate (T() is the rate-determining
step (Scheme 2).2b,d-f,5,6,8-10
In some cases, depending on the pyridine nature and
its concentration used, it was possible to obtain kinetic
values for the fast reaction (kobsd1) or the slow one (kobsd2
)
or both.
P yr id in olysis of Ch lor oth ion ofor m a tes. The ki-
netic results obtained for these reactions are in ac-
cordance with eqs 1 and 2, where 1, S, and N represent
the corresponding 1-(aryloxythiocarbonyl)pyridinium, the
substrate, and the free pyridine, respectively; [S]0 is the
initial substrate concentration and t is time. The rate
constants k0 and kN are those for the hydrolysis and
pyridinolysis, respectively, of the chlorothionoformates.
For all the reactions (except those of both substrates with
nicotinamide and that of NPCITF with 4-cyanopyridine),
By applying the steady-state treatment to the inter-
mediate T( and assuming that the hydrolysis of com-
4804 J . Org. Chem., Vol. 69, No. 14, 2004

Pyridinolysis of Chlorothionoformates
F IGUR E 4. Double-logarithmic plot of experimental kN vs
calculated kN (through eq 3) for the reactions of pyridines with
PClTF (O) and NPClTF (b), in aqueous solution, 25.0 °C, ionic
strength 0.2 (KCl).
F IGURE 3. Bro¨nsted plots for kN, obtained in the reactions
of pyridines with PClTF (b) and NPClTF (O), in aqueous
solution, 25.0 °C, ionic strength 0.2 (KCl).
SCHEME 2
Brønsted plots exhibiting low slopes for the nucleophiles
(e.g., â ≈ 0.3).2d On the other hand, it seems that for these
reactions there is little influence of the change of O- to
S
- in the intermediate T(, as judged by the fact that the
same step is rate limiting for the aminolyses (secondary
alicyclic amines) in water of PCIF and NPCIF2e and their
corresponding thiono derivatives.5 Therefore, it is sur-
prising that the same step be rate determining for these
reactions in water and acetonitrile, since it is known that
amine expulsion from T( (k-1 in Scheme 2) is accelerated
in less polar solvents10 and nucleofuge expulsion (k2) is
little affected by the solvent.10 Therefore, comparison of
the pyridinolyses of the title substrates in water with
those of PCIF and NPCIF in acetonitrile indicates that
the change of solvent from water to acetonitrile does not
sufficiently increase the value of k-1 as to change the rate
determining step from formation of T( (k1 step) to its
decomposition (k2 step).
On the other hand, substitution of S- by O- in the
zwitterionic tetrahedral intermediates formed in the
aminolysis of phenyl and 4-nitrophenyl 2,4-dinitrophenyl
thionocarbonates does affect their stability, due to a
faster amine expulsion from the oxy intermediate.11
Similarly, the zwitterionic intermediate formed in the
aminolysis of 3-methyl-7â-(phenylacetamido)thioxoceph-
3-em-4-carboxylic acid expels the amine slower than that
from the corresponding oxy intermediate (with O-).12
pound 1 is negligible, the following equation results: kN
) k1k2/(k-1 + k2), where kN is the macroscopic nucleophilic
rate constant. Since the first step is limiting, it follows
that in this scheme, k2 . k-1, and therefore, kN ) k1.
As shown in Table 3 and Figure 3, the kN values for
the reactions of NPCITF are greater than those of PCITF.
This is reasonable due to the presence of the powerful
electron withdrawing 4-nitro group in NPCITF that
leaves the thiocarbonyl group of this substrate more
reactive than that in PCITF.
For the reactions of the present work, a correlation of
log kN as a function of the pKa of the conjugate acids of
the nucleophile (pKN) and nonleaving group (pKnlg) can
be achieved by dual regression analysis. This is shown
in eq 3 (R2 ) 0.944, n ) 10). Figure 4 shows a double-
logarithmic plot of the experimental kN vs that calculated
through eq 3. The slope is unity and the intercept is zero,
within experimental errors. The good correlation and
unity slope of this plot indicates that the pyridinolysis
of PClTF and NPClTF are driven by the same mechanism
and the same rate-determining step.
The pyridinolysis of bis(4-nitrophenyl) thionocarbonate
(BNPTOC) in water exhibits a linear Brønsted-type plot
of slope â ) 1.0, which is consistent with a mechanism
through an intermediate T(, where its decomposition to
products is the rate-determining step.13 Comparison with
the Brønsted plot obtained for the pyridinolysis of
NPCITF (this work), which differs from BNPTOC only
in the leaving group, shows that 4-nitrophenoxide is a
worse nucleofuge than Cl- from the tetrahedral inter-
mediate.
log kN ) (2.4 ( 0.2) + (0.1 ( 0.01)pKN -
(0.08 ( 0.02)pKnlg (3)
The pyridinolysis of phenyl and 4-nitrophenyl chloro-
formates (PCIF and NPCIF, respectively) in acetonitrile
obeys a stepwise mechanism, where the formation of a
zwitterionic tetrahedral intermediate (T() is rate deter-
mining.2d This was shown on the basis of Hammett and
(11) Castro, E. A.; Cubillos, M.; Aliaga, M.; Evangelisti, S.; Santos,
J . G. J . Org Chem. 2004, 69, 2411.
(8) Castro, E. A. Chem. Rev. 1999, 99, 3505 and references therein.
(9) Satterthwait, A. C.; J encks, W. P. J . Am. Chem. Soc. 1974, 96,
7018.
(12) Tsang, W. Y.; Dhanda, A.; Schofield, C. J .; Page, M. I. J . Org
Chem. 2004, 69, 339.
(13) Castro, E. A.; Santos, J . G.; Tellez, J .; Uman˜a, M. I. J . Org
Chem. 1997, 62, 6568.
(10) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963.
J . Org. Chem, Vol. 69, No. 14, 2004 4805

Castro et al.
SCHEME 3
We have recently found that the pyridinolysis of 2,4-
dinitrophenyl phenyl thionocarbonate in water is driven
by a stepwise mechanism, with rate-determining forma-
tion of a T( intermediate at high pyridine basicity (â )
0.1) and rate-limiting elimination of 2,4-dinitrophenoxide
at low pyridine basicity (â ) 1.0).11 The fact that for the
pyridinolysis of PClTF the rate-determining step is the
formation of T( (this work) indicates that Cl- is a better
nucleofuge from T( than 2,4-dinitrophenoxide anion.
The reactions of secondary alicyclic (SA) amines with
PCITF and NPCITF show linear Brønsted-type plots with
identical slopes, â 0.26, indicating that formation of the
intermediate T( is rate limiting.5 These results are
consistent with the fact that the same step is rate
determining for the pyridinolysis of the same substrates
(this work), for the following reasons: SA amines are
known to be better nucleofuges from the intermediate T(
than isobasic pyridines.14 Since for the reactions of these
substrates with SA amines k-1 , k2, this inequality is
even more certain for the reactions with isobasic py-
ridines because the latter are worse leaving groups. This
explains why the first step of Scheme 2 is rate limiting
for the reactions of PCITF and NPCITF with pyridines.
The rate constants kN obtained for the pyridinolysis of
PCITF and NPCITF (Table 3) are larger than those found
for the reactions of these substrates with isobasic SA
amines.5 This is in accordance with the concept of
Pearson’s hard and soft acids and bases:15 relatively soft
bases such as pyridines would preferably bind to a
relatively soft thiocarbonyl group, compared with isobasic
SA amines which are relatively harder bases.
F IGURE 5. Bronsted-type plots for the hydrolysis of 1-(phen-
yloxythiocarbonyl)pyridinium (b) and 1-(4-nitrophenyloxythio-
carbonyl)pyridinium (O) cations catalyzed by the corresponding
pyridine, in aqueous solution at 25.0 °C, ionic strength 0.2 M
(KCl).
The solvolysis of PClTF in water, methanol, ethanol,
and aqueous mixtures of the two latter solvents has been
subjected to a kinetic investigation.3b It was found that
these reactions are of SN2 character, especially in water;
i.e., a tetrahedral intermediate is not formed.3b Compari-
son with the pyridinolysis of the same substrate (this
work) indicates that substitution of a pyridino moiety by
OH, MeO, or EtO in the intermediate T( of Scheme 2
destabilizes the intermediate. This is in line with the
discussion above on the destabilization of the intermedi-
ate by the change of a pyridino group by phenoxy. On
the other hand, an addition-elimination pathway was
proposed for the solvolysis of PClTF in aqueous mixtures
of ethanol, methanol, and acetone.3a Nevertheless, an SN1
mechanism was claimed to govern the solvolysis of this
substrate in aqueous trifluoroethanol mixtures.3a
Hyd r olysis of 1-(Ar yloxyth ioca r bon yl)p yr id in iu m
(1). The rate constants for decomposition of these cationic
thionocarbamates (kobsd2, Tables 1 and 2) show a linear
dependence on the corresponding free pyridine (N) con-
centration, according to eq 4, by analogy to the behavior
displayed by chlorothionoformates. The rate constants k02
and kH were obtained as intercept and slope, respectively,
of the linear plots of kobsd2 vs free amine concentration.
For the reactions of phenoxide anions with PClTF and
NPCITF in aqueous solution, linear Brønsted-type plots
with slopes â ) 0.55 and 0.47, respectively, were found.4
The values of these slopes and other results were
explained by concerted mechanisms, without the forma-
tion of a tetrahedral intermediate.4 This means that
substitution of the pyridino moiety in the intermediate
T( of Scheme 2 by a phenoxy group greatly destabilizes
the intermediate. This is consistent with the facts that
the pyridinolyses of aryl acetates,9,16 carbonates,10,17 and
thiolcarbonates18 are stepwise, whereas the phenolyses
of the same substrates are concerted.19-21
kobsd2 ) k02 + kH[N]
(4)
A probable mechanism for the kH path is water attack
to the thiocarbonyl moiety of the thionocarbamate 1,
catalyzed by a pyridine molecule (general base catalysis,
rate constant kH), as shown in Scheme 3. The same type
of catalysis was reported for the hydrolysis of ring-
substituted 1-(methoxycarbonyl)pyridinium cations.7b
Buffer-catalyzed hydrolysis (rate constant k02) can also
occur, as shown in Scheme 3 where B is the buffer. The
(14) Castro, E. A.; Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991,
63.
(15) Pearson, R. G. J . Chem. Educ. 1968, 45, 581. Pearson, R. G. J .
Org. Chem. 1989, 54, 1423.
(16) Castro, E. A.; Freudenberg, M. J . Org. Chem. 1980, 45, 906.
Castro, E. A.; Iba´n˜ez, F.; Lagos, S.; Schick, M.; Santos, J . G. J . Org.
Chem. 1992, 57, 2691.
(17) Bond, P. M.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2 1976,
679. Castro, E. A.; Gil, F. J . J . Am. Chem. Soc. 1977, 99, 7611.
(18) Castro, E. A.; Pizarro, M. I.; Santos, J . G. J . Org Chem. 1996,
61, 5982.
(19) Ba-Saif, S.; Luthra, A. K.; Williams, A. J . Am. Chem. Soc. 1989,
111, 2647. Ba-Saif, S.; Colthurst, M.; Waring, M. A.; Williams, A. J .
Chem. Soc., Perkin Trans. 2 1991, 1901. Stefanidis, D.; Cho, S.; Dhe-
Paganon, S.; J encks, W. P. J . Am. Chem. Soc. 1993, 115, 1650.
(20) Castro, E. A.; Pavez, P.; Santos, J . G. J . Org Chem. 2001, 66,
3129.
(21) Castro, E. A.; Pavez, P.; Santos, J . G. J . Org Chem. 1999, 64,
2310.
4806 J . Org. Chem., Vol. 69, No. 14, 2004

Pyridinolysis of Chlorothionoformates
latter mechanism would be similar to that for pyridine
as catalyst.
slopes (â ) 0.19 and 0.26, respectively) can be explained
by the fact that as pKa increases the effect of a better
pyridine catalyst is compensated by a worse leaving
pyridine from the corresponding thionocarbamate.
Table 3 shows the values of kH found for the hydrolysis
of the various cationic thionocarbamates (1). It can be
seen that the value of kH increases as pyridine basicity
increases, as expected from general base catalysis. Nev-
ertheless, taking into account that the thionocarbamates
studied are obtained “in situ”, the kinetic study corre-
sponds to a simultaneous change of the pyridine group
of the thionocarbamate and the pyridine catalyst. Figure
5 shows the Brønsted plots for the hydrolysis of the
cationic thionocarbamates 1 formed in the pyridinolysis
of PClTF and NPClTF. The linear behavior with low
Ack n ow led gm en t. We thank FONDECYT of Chile
for financial assistance to this work.
Su p p or tin g In for m a tion Ava ila ble: Pages S2-S14 con-
taining Tables S1-S4. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O049559Y
J . Org. Chem, Vol. 69, No. 14, 2004 4807