Kinetic Study of the Aminolysis and Pyridinolysis of O-Phenyl and O-Ethyl O-(2,4-Dinitrophenyl) Thiocarbonates. A Remarkable Leaving Group Effect

Article abstract of DOI:10.1021/jo035451r

The reactions of a series of secondary alicyclic (SA) amines with O-phenyl and O-ethyl O-(2,4-dinitrophenyl) thiocarbonates (1 and 2, respectively) and of a series of pyridines with the former substrate are subjected to a kinetic investigation in water, at 25.0 °C, ionic strength 0.2 M (KCl). Under amine excess over the substrate, all the reactions obey pseudo-first-order kinetics and are first-order in amine. The Broensted-type plots are biphasic, with slopes (at high pK_a) of β₁ = 0.20 for the reactions of SA amines with 1 and 2 and β₁ = 0.10 for the pyridinolysis of 1 and with slopes (at low pK_a) of β₂ = 0.80 for the reactions of SA amines with 1 and 2 and β₂ = 1.0 for the pyridinolysis of 1. The pK_a values at the curvature center (pK _a⁰) are 7.7, 7.0, and 7.0, respectively. These results are consistent with the existence of a zwitterionic tetrahedral intermediate (T?) and a change in the rate-determining step with the variation of amine basicity. The larger pK_a⁰ value for the pyridinolysis of 1 compared to that for 2 (pK_a⁰ = 6.8) and the larger pK_a⁰ value for the reactions of SA amines with 1 relative to 2 are explained by the greater inductive electron withdrawal of PhO compared to EtO. The larger pK_a⁰ values for the reactions of SA amines with 1 and 2, relative to their corresponding pyridinolysis, are attributed to the greater nucleofugalities of SA amines compared to isobasic pyridines. The smaller pK_a⁰ value for the reactions of SA amines with 2 than with O-ethyl S-(2,4-dinitrophenyl) dithiocarbonate (pK_a⁰ = 9.2) is explained by the greater nucleofugality from T? of 2,4-dinitrophenoxide (DNPO^-) relative to the thio derivative. The stepwise reactions of SA amines with 1 and 2, in contrast to the concerted mechanisms for the reactions of the same amines with the corresponding carbonates, is attributed to stabilization of T? by the change of O^- to S^-. The simple mechanism for the SA aminolysis of 2 (only one tetrahedral intermediate, T?) is in contrast to the more complex mechanism (two tetrahedral intermediates, T? and T^-, the latter formed by deprotonation of T? by the amine) for the same aminolysis of the analogous thionocarbonate with 4-nitrophenoxide (NPO^-) as nucleofuge. To our knowledge, this is the first example of a remarkable change in the decomposition path of a tetrahedral intermediate T? by replacement of NPO^- with DNPO^- as the leaving group of the substrate. This is explained by (i) the greater leaving ability from T? of DNPO^- than NPO^- and (ii) the similar rates of deprotonation of both T? (formed with DNPO and NPO).

Full text of DOI:10.1021/jo035451r

Kin etic Stu d y of th e Am in olysis a n d P yr id in olysis of O-P h en yl a n d
O-Eth yl O-(2,4-Din itr op h en yl) Th ioca r bon a tes. A Rem a r k a ble
Lea vin g Gr ou p Effect
Enrique A. Castro,* Mar´ıa Cubillos, Margarita Aliaga, Sandra Evangelisti, and
J ose´ G. Santos*
Facultad de Qu´ımica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 22, Chile
ecastro@puc.cl
Received October 2, 2003
The reactions of a series of secondary alicyclic (SA) amines with O-phenyl and O-ethyl O-(2,4-
dinitrophenyl) thiocarbonates (1 and 2, respectively) and of a series of pyridines with the former
substrate are subjected to a kinetic investigation in water, at 25.0 °C, ionic strength 0.2 M (KCl).
Under amine excess over the substrate, all the reactions obey pseudo-first-order kinetics and are
first-order in amine. The Bro¨nsted-type plots are biphasic, with slopes (at high pKa) of â1 ) 0.20
for the reactions of SA amines with 1 and 2 and â1 ) 0.10 for the pyridinolysis of 1 and with slopes
(at low pKa) of â2 ) 0.80 for the reactions of SA amines with 1 and 2 and â2 ) 1.0 for the pyridinolysis
0
of 1. The pKa values at the curvature center (pKa ) are 7.7, 7.0, and 7.0, respectively. These results
are consistent with the existence of a zwitterionic tetrahedral intermediate (Tq) and a change in
0
the rate-determining step with the variation of amine basicity. The larger pKa value for the
0
0
pyridinolysis of 1 compared to that for 2 (pKa ) 6.8) and the larger pKa value for the reactions of
SA amines with 1 relative to 2 are explained by the greater inductive electron withdrawal of PhO
0
compared to EtO. The larger pKa values for the reactions of SA amines with 1 and 2, relative to
their corresponding pyridinolysis, are attributed to the greater nucleofugalities of SA amines
0
compared to isobasic pyridines. The smaller pKa value for the reactions of SA amines with 2 than
0
with O-ethyl S-(2,4-dinitrophenyl) dithiocarbonate (pKa ) 9.2) is explained by the greater
nucleofugality from Tq of 2,4-dinitrophenoxide (DNPO-) relative to the thio derivative. The stepwise
reactions of SA amines with 1 and 2, in contrast to the concerted mechanisms for the reactions of
the same amines with the corresponding carbonates, is attributed to stabilization of Tq by the change
of O- to S-. The simple mechanism for the SA aminolysis of 2 (only one tetrahedral intermediate,
Tq) is in contrast to the more complex mechanism (two tetrahedral intermediates, Tq and T-, the
latter formed by deprotonation of Tq by the amine) for the same aminolysis of the analogous
thionocarbonate with 4-nitrophenoxide (NPO-) as nucleofuge. To our knowledge, this is the first
example of a remarkable change in the decomposition path of a tetrahedral intermediate Tq by
replacement of NPO- with DNPO- as the leaving group of the substrate. This is explained by (i)
the greater leaving ability from Tq of DNPO- than NPO- and (ii) the similar rates of deprotonation
of both Tq (formed with DNPO and NPO).
In tr od u ction
We have also carried out a kinetic study on the
pyridinolysis of O-methyl and O-ethyl O-(4-nitrophenyl)
thiocarbonates and O-ethyl O-(2,4-dinitrophenyl) thio-
carbonate.3 For the reactions of the two former sub-
strates, linear Bro¨nsted-type plots of slopes â ) 1.0 were
found. These were interpreted by a stepwise mechanism
through an intermediate Tq on the reaction path, whereby
decomposition of Tq to products is rate-determining.3 In
the pyridinolysis of O-ethyl O-(2,4-dinitrophenyl) thio-
carbonate, a biphasic Bro¨nsted-type plot was obtained,
with limiting slopes â ) 0.1 (high pyridine pKa) and â )
In recent years we have been interested in the mech-
anisms of the aminolysis of thionocarbonates. We have
studied kinetically the reactions of O-phenyl and O-(4-
nitrophenyl) O-ethyl thiocarbonates (EtO-CS-OC6H4X,
X ) H, NO2) with secondary alicyclic (SA) amines, where
we found a mechanism through two tetrahedral inter-
mediates on the reaction pathway, one zwitterionic (Tq)
and the other anionic.1 A similar behavior was found for
the aminolysis (SA amines) of O-methyl O-(4-nitrophenyl)
thiocarbonate (MeO-CS-OC6H4NO2).2
(2) Castro, E. A.; Saavedra, C.; Santos, J . G. Uman˜a, M. I. J . Org
Chem. 1999, 64, 5401.
(3) Castro, E. A.; Cubillos, M.; Santos, J . G.; Te´llez, J . J . Org. Chem.
1997, 62, 2512.
* Corresponding author.
(1) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org Chem. 1996, 61,
3501.
10.1021/jo035451r CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/06/2004
J . Org. Chem. 2004, 69, 2411-2416
2411

Castro et al.
1.0 (low pyridine pKa). This Bro¨nsted plot was explained
by a stepwise mechanism through an intermediate Tq,
with a change in the rate-determining step according to
the pyridine basicity.3
nature on these mechanisms by comparing these reac-
tions between them and with thoseofalkylarylthionocarbon-
ates,1-4 diaryl thionocarbonates,5 O-ethyl 2,4-dinitrophen-
yl dithiocarbonate,6 and phenyl and methyl 2,4-dinitro-
phenyl carbonates.7
Also a kinetic study has been carried out on the
reactions of SA amines with bis(phenyl) and bis(4-
nitrophenyl) thionocarbonates and the reactions of py-
ridines with the latter substrate.4 The reactions of the
SA amines (except piperidine) with the former substrate
exhibit a complex order in amine, consistent with the
existence of both a zwitterionic (Tq) and an anionic (T-)
tetrahedral intermediate on the reaction pathway,
whereby Tq is deprotonated by an amine to give T-.4 On
the other hand, the pyridinolysis of the nitro derivative
shows first-order kinetics in pyridine and the Bro¨nsted
plot is linear, with slope â ) 1.0, consistent with a
stepwise mechanism where Tq breakdown to products is
the rate-determining step.4 The reactions of the SA
amines with this substrate 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 Tq is not formed
because of its high kinetic instability due to the large
nucleofugality of both leaving groups.4
The reactions of asymmetric diaryl thionocarbonates
with SA amines in 44 wt % ethanol-water show curved
upward plots of the pseudo-first-order rate constant vs
amine concentration, in agreement with the formation
of the tetrahedral intermediates Tq, which transfers a
proton to an amine to yield T-.5
The reactions of SA amines with O-ethyl 2,4-dinitro-
phenyl dithiocarbonate exhibit a biphasic Bro¨nsted plot
with limiting slopes â ) 0.2 and 0.8, in accordance with
an intermediate Tq on the reaction path and a change in
the rate-limiting step, from Tq breakdown to products to
Tq formation, as the amine basicity increases.6
According to our results, there is a remarkably differ-
ent mechanism between the SA aminolysis of thionocar-
bonate 2 (only one tetrahedral intermediate, Tq, on the
reaction path) and the same aminolysis of the analogous
thionocarbonate possessing 4-nitrophenoxide as leaving
group (tetrahedral intermediates Tq and T-).1,2 Namely,
this remarkable mechanistic change takes place by
substitution of 2,4-dinitrophenoxy by 4-nitrophenoxy as
the nucleofuge in Tq. According to our records, this is the
first report on this change in mechanism by the above
change in the leaving group.
Exp er im en ta l Section
Ma ter ia ls. The SA amines and pyridines were purified as
reported.8 The thionocarbonates 1 and 2 were prepared as
described elsewere.3,9,10
O-Ethyl thiocarbamates of piperidine and morpholine (one
of the products of the reactions of these amines with thiono-
carbonate 2) were prepared as described elsewere;11 O-phenyl
thiocarbamates of piperidine and morpholine (products in the
reactions of 1) were synthesized by the reaction of O-phenyl
chlorothioformate with the corresponding amines, as re-
ported.12
Kin etic Mea su r em en ts. These were carried out spectro-
photometrically by following the production of 2,4-dinitrophen-
oxide ion at 400 nm. The reactions were studied in aqueous
solutions, at 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 spectrophotometer kinetic software for
first-order reactions. The experimental conditions of the reac-
tions and the kobsd values obtained are shown in Tables S1-
S3 (pages S2-S4 in the Supporting Information). The initial
substrate concentration was 3 × 10-5 M in all the reactions.
P r od u ct Stu d ies. In the reactions of thionocarbonates 1
and 2, 2,4-dinitrophenoxide anion was identified as one of the
reaction products, by comparison of the UV-vis spectra after
completion of these reactions with that of an authentic sample
of 2,4-dinitrophenol under the same reaction conditions.
In the reactions of thionocarbonate 2 with piperidine and
morpholine, the presence of the corresponding O-ethyl thio-
carbamates in the reaction media was determined by HPLC,
as reported previously.13
On the other hand, the aminolysis (SA) of phenyl and
methyl 2,4-dinitrophenyl carbonates were found to be
concerted, on the basis of the linear Bro¨nsted-type plots
obtained with slopes ca. 0.4.7
To extend our mechanistic investigations on the ami-
nolysis of thionocarbonates, in the present work we
undertake a kinetic study of the reactions of SA amines
with the thionocarbonates O-phenyl O-(2,4-dinitrophenyl)
thiocarbonate (1) and O-ethyl O-(2,4-dinitrophenyl) thio-
The O-phenyl thiocarbamates of piperidine and morpholine
were identified as the final products of the reactions of 1 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.2,4
Resu lts a n d Discu ssion
carbonate (2) and of the reactions of pyridines with the
former substrate. The object is to assess the influence of
the different groups of the substrate and the amine
The rate law obtained for all the reactions under study
is given by eqs 1 and 2, where DNP is 2,4-dinitrophenyl
(4) Castro, E. A.; Santos, J . G.; Te´llez, J .; Uman˜a, M. I. J . Org. Chem.
1997, 62, 6568.
(8) (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.
(9) Castro, E. A.; Pavez, P.; Santos, J . G. J . Org. Chem. 2003, 68,
6192.
(10) Al-Kazimi, H. R.; Tarbell, D. S.; Plant, D. J . Am. Chem. Soc.
1955, 77, 2479.
(11) Herrera, M.; Ruiz, V. M.; Valderrama, J . A.; Vega, J . C. An.
Quim., Ser. C 1980, 76, 183.
(5) Castro, E. A.; Garc´ıa, P.; Leandro, L.; Quesieh, N.; Rebolledo,
A.; Santos, J . G. J . Org. Chem. 2000, 65, 9047. Castro, E. A.; Leandro,
L.; Quesieh, N.; Santos, J . G. J . Org. Chem. 2001, 66, 6130. Castro, E.
A.; Ga´lvez, A.; Leandro, L.; Santos, J . G. J . Org. Chem. 2002, 67, 4309.
(6) Castro, E. A.; Iba´n˜ez, F.; Salas, M.; Santos, J . G.; Sepu´lveda, P.
J . Org. Chem. 1993, 58, 459.
(7) Castro, E. A.; Aliaga, M.; Campodonico, P.; Santos, J . G. J . Org.
Chem. 2002, 67, 8911.
(12) Newman, M. S.; Karnes, H. A. J . Org. Chem. 1966, 31, 3980.
2412 J . Org. Chem., Vol. 69, No. 7, 2004

Aminolysis of Thiocarbonates
TABLE 1. Va lu es of p Ka for th e Con ju ga te Acid s of
P yr id in es a n d kN for th e P yr id in olysis of
Th ion oca r bon a te 1a
pyridine substituent
pKa
kN/s-1 M-1
4-(dimethylamino)
4-amino
3,4-dimethyl
4-methyl
3-methyl
H-
9.87
9.37
6.77
6.25
5.86
5.37
3.43
160 ( 16
48 ( 7
19 ( 3
6.7 ( 1
2.9 ( 0.5
1.1 ( 0.1
0.013 ( 0.002
3-carbamoyl
a
Both the kN and pKa values were obtained in aqueous solution,
at 25.0 °C, ionic strength 0.2 M (KCl).
TABLE 2. Va lu es of p Ka for th e Con ju ga te Acid s of SA
Am in es a n d kN for th e Rea ction s of SA Am in es w ith
Th ion oca r bon a tes 1 a n d 2a
F IGURE 1. Bro¨nsted-type plots for the reactions of pyridines
with 1 (b, this work) and 2 (O, ref 3) in aqueous solution, at
25.0 °C and an ionic strength of 0.2 M (KCl).
kN/s-1 M-1
SA amine
piperidine
piperazine
1-(2-hydroxyethyl)piperazine
morpholine
pKa
1
2
11.24 6.2 ( 0.3
9.94 6.4 ( 0.2
9.38 2.9 ( 0.1
8.78 1.8 ( 0.1
9.5 ( 0.4
8.3 ( 0.3
4.0 ( 0.1
3.4 ( 0.1
SCHEME 1
1-formylpiperazine
piperazinium ion
7.98 0.75 ( 0.08 1.8 ( 0.1
5.81 0.10 ( 0.01 0.27 ( 0.01
a
The rate constants and pKa determinations were carried out
in aqueous solution, at 25.0 °C, ionic strength 0.2 M (KCl).
) 0.1 ( 0.1 (slope at high pKa), â2 ) 1.0 ( 0.1 (slope at
low pKa) and pKa0 ) 7.0 ( 0.2 (pKa value at the curvature
center).
and S and N represent the substrate and an amine,
respectively.
The value of â1 ) 0.1 is in agreement with previous
ones obtained for similar aminolyses when the k1 step of
Scheme 1 is rate-determining (typical values are 0.1-
0.3),1-8,14 and the value of â2 ) 1.0 is in line with the
Bro¨nsted slopes for analogous reactions when the k2 step
is rate-limiting (typical values are 0.8-1.1).2,6-8,13,14
From a comparison of the Bro¨nsted-type plots obtained
in the pyridinolysis of 1 and 2,3 shown in Figure 1, three
observations can be made: (i) The values of k1 (kN values
at high pKa) are larger for the reactions of 1; this can be
attributed to a greater electron-withdrawing effect of
phenoxy in 1, compared to ethoxy in 2, which would leave
the former thiocarbonyl carbon more prone to a nucleo-
philic attack by the amine. (ii) The thionocarbonate 1 is
also more reactive toward pyridines than 2 when the
breakdown to products of the corresponding tetrahedral
intermediate (Tq) is the rate-determining step. In this
case kN ) k1k2/k-1. It is known that inductive electron
withdrawal by the nonleaving substituent in Tq decreases
the k2/k-1 ratio.14,15 This means that this ratio should be
smaller for the reactions of 1, since PhO in the tetrahe-
dral intermediate 3 is more electron withdrawing induc-
d[DNPO-]
) kobsd[S]
(1)
(2)
dt
kobsd ) kN[N]
Linear plots of kobsd vs [N] at constant pH were found
for the reactions of all amines with both substrates, with
the slopes (kN) independent of pH. The kN values are
shown in Table 1 for the reactions of pyridines and in
Table 2 for the reactions of SA amines. The linear plots
for the SA aminolysis of thionocarbonate 2 are in marked
contrast to the nonlinear upward kobsd vs [N] plots found
for the SA aminolysis of ethyl and methyl 4-nitrophenyl
thionocarbonates.1,2
With the pKa values of the conjugate acids of pyridines
and the kN values for the pyridinolysis of 1 (Table 1), the
Bro¨nsted-type plot shown in Figure 1 was obtained. For
comparison, this figure also includes the corresponding
plot for the pyridinolysis of 2.3 The Bro¨nsted line for the
reactions of 1 with pyridines was calculated by eq 38a
0
log(kN/kN0) ) â2(pKa - pKa ) - log[(1 + a)/2] (3)
0
log a ) (â2 - â1) (pKa - pKa )
based on the existence of a zwitterionic tetrahedral
intermediate (Tq) on the reaction path and a change in
the rate-determining step, from breakdown to formation
of Tq, as the amine becomes more basic.8 This mechanism
is shown in Scheme 1, where DNP is 2,4-dinitrophenyl
and N represents a pyridine. An analogous equation was
derived by Gresser and J encks.14 By nonlinear least-
squares fitting, the following parameters were found: â1
tively than EtO in intermediate 4 (σI ) 0.37 and 0.26,
(13) Cabrera, M.; Castro, E. A.; Salas, M.; Santos, J . G.; Sepu´lveda,
P. J . Org. Chem. 1991, 56, 5324.
(14) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963,
6970.
(15) 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.
J . Org. Chem, Vol. 69, No. 7, 2004 2413

Castro et al.
F IGURE 2. Brønsted-type plots (statistically corrected) for
the reactions of SA amines with 1 (b) and 2 (O) in aqueous
solution, at 25.0 °C and an ionic strength of 0.2 M (KCl).
F IGURE 3. Bro¨nsted-type plots for the reactions of SA amines
with 2 (O, this work) and EDNPDTC (b, ref 6) in aqueous
solution, at 25.0 °C and an ionic strength of 0.2 M (KCl).
and 6 than for an isobasic pyridine from intermediates
respectively).16 Therefore, the greater kN values for the
pyridinolysis of 1 (compared to 2) should be due to the
much larger k1 values for 1, which are only partially
counterbalanced by the smaller values of the k2/k-1 ratio
for the reactions of 1. (iii) The center of the Bro¨nsted
0
0
curvature (pKa ) for the pyridinolysis of 1 (pKa ) 7.0) is
larger than that for the reactions of the same amines with
2 (pKa0 ) 6.8).3 This result can be explained by the larger
k-1/k2 ratio for intermediate 3 (relative to that for 4), since
it is known that log(k-1/k2) is linearly dependent on
3 and 4, respectively. Since the amine basicity and nature
should not affect the rate of expulsion of the leaving
group (k2) from the zwitterionic tetrahedral intermedi-
ate,14 the k-1/k2 ratios for SA amines from 5 and 6 should
be larger than those for isobasic pyridines from 3 and 4,
0 17
pKa .
Figure 2 shows the Brønsted-type plots (statistically
corrected) for the reactions of SA amines with thiono-
carbonates 1 and 2. The statistical parameter q is the
number of equivalent basic sites in the free amine and p
is the number of equivalent protons in the conjugate acid
of the amine.8b,18 The statistical corrections are q ) 2 for
piperazine, p ) 4 for the conjugate acid of piperazinium
cation, and p ) 2 for the conjugate acids of the other SA
amines.8b,18
0
respectively. As discussed above, this means larger pKa
values for the SA aminolysis of 1 and 2 compared with
their corresponding pyridinolysis.
Contrary to what is observed for the pyridinolysis of
thionocarbonates 1 and 2, the latter substrate is more
reactive than 1 toward SA amines. This could be ex-
plained by assuming that the phenyl group in 1 offers
steric hindrance to SA attack, which may not be so
important for pyridine attack. This could be due to the
fact that pyridines are planar structures and SA amines
are not. In other words, steric effects may be more
important than electronic effects for SA aminolysis,
whereas the opposite seems to be true for pyridinolysis.
The stepwise mechanisms found for the reactions of
SA amines with thionocarbonates 1 and 2 are in agree-
ment with the stepwise phenolysis of 1 and O-methyl
O-(2,4-dinitrophenyl) thiocarbonate.9,20 This is because
the change of an amino moiety in a tetrahedral inter-
mediate by an aryloxy group destabilizes the intermedi-
ate.9 If the phenolysis of the above thionocarbonates is
stepwise, it is more likely that the aminolysis of these
substrates be driven by a stepwise mechanism.
For the reactions of SA amines with O-ethyl 2,4-
dinitrophenyl dithiocarbonate (EDNPDTC),6 a nonlinear
biphasic Brønsted-type plot has been found, with the
following parameters: â1 ) 0.2, â2 ) 0.8, and pKa0 ) 9.2.
This has been attributed to a stepwise mechanism
through a zwitterionic tetrahedral intermediate.6 Figure
3 shows the Brønsted-type plot obtained for the reactions
of SA amines with EDNPDTC.6 For comparison reasons,
the corresponding plot for the reactions of the same
amines with 2 is also shown in Figure 3.
The curved lines in Figure 2 were obtained as for the
reactions of pyridines (see above), with â1 ) 0.2 ( 0.1
0
and â2 ) 0.8 ( 0.1 for both reaction series and pKa
)
7.7 ( 0.3 and 7.0 ( 0.2 for the reactions of 1 and 2,
respectively. As discussed above, the â1 and â2 values are
in accordance with the corresponding ones obtained for
the stepwise aminolysis of similar compounds.1-8,13,14
0
The larger pKa value for the reactions of SA amines
with 1, compared with that for the reactions of 2, is in
agreement with the larger σI value for PhO than EtO,
0
as discussed above. The larger pKa values for the
reactions of SA amines with 1 and 2, compared with those
0
for the pyridinolysis of the corresponding substrates (pKa
) 7.0 and 6.8, respectively) can be attributed to the
greater nucleofugality from the intermediate Tq of SA
amines relative to isobasic pyridines.19 This means a
larger k-1 value for an SA amine from intermediates 5
(16) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(17) Castro, E. A.; Araneda, C. A.; Santos, J . G. J . Org. Chem. 1997,
62, 126.
(18) Bell, R. P. The Proton in Chemistry; Methuen: London, 1959;
p 159.
(19) Castro, E. A.; Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991,
63.
2414 J . Org. Chem., Vol. 69, No. 7, 2004

Aminolysis of Thiocarbonates
SCHEME 2
From Figure 3 three observations can be made:
(i) The pKa value at the curvature center (pKa ) is
0
larger for the SA aminolysis of the dithiocarbonate
0
(EDNPDTC) than the thionocarbonate (pKa ) 9.2 and
7.0, respectively). This means that for a given SA amine
the ratio k-1/k2 should be larger for tetrahedral interme-
diate 7 than for intermediate 6 (see above). This fact
The above result is in agreement with the fact that the
reactions of SA amines with S-(2,4-dinitrophenyl) and
S-(2,4,6-trinitrophenyl) O-ethyl thiolcarbonates are con-
certed,22 whereas the reactions of the same amines with
S-(2,4-dinitrophenyl) and S-(2,4,6-trinitrophenyl) O-ethyl
dithiocarbonates are stepwise.6 The destabilization of a
tetrahedral intermediate by substitution of S- by O- has
been explained by the greater ability of O- in the
intermediate to form a double bond and expel a nucle-
ofuge, compared to S-, due to the stronger π-bonding
energy of the carbonyl group relative to thiocarbonyl.23
The higher stability of a tetrahedral intermediate with
S- compared with O- is in agreement with the greater
stabilization of S,S-acetals relative to O,S- and O,O-
acetals24 and the fact that the stability of other similar
tetrahedral intermediates increases as the number of
sulfur atoms attached to the central carbon increases.25
For the reactions of SA amines with O-alkyl O-aryl
thiocarbonates1,2 and O,O-diaryl thiocarbonates,2,4,5 where
the leaving groups are 3- or 4-nitrophenoxide (NPO-), a
complex kinetic order in amine (between 1 and 2) was
found. This behavior was explained by a mechanistic
scheme (Scheme 2) involving two tetrahedral intermedi-
ates, one zwitterionic (Tq), formed by the attack of the
amine at thiocarbonyl group, and the other anionic (T-),
resulting from the deprotonation of Tq by the correspond-
ing parent amine.
suggests that 2,4-dinitrophenoxide (DNPO-) leaves faster
from intermediate 6 than 2,4-dinitrobenzenethiolate
(DNPS-) from 7 (k2 larger for 6). This result is surprising
on the basis of the basicity of the leaving groups involved
(pKa values of DNPOH and DNPSH are 4.1 and 3.4,
respectively).19 Nonetheless, it is known that ArO is a
better leaving group than an isobasic Ar′S;21 therefore,
it is possible that DNPO leaves faster from 6 than DNPS
from 7. In contrast, DNPO leaves at similar rates than
DNPS from intermediates 8 and 9, respectively, formed
in the phenolysis of 2 and EDNPDTC, respectively,9 and
DNPO leaves slower than DNPS from intermediates 10
and 11, respectively, formed in the pyridinolysis of the
corresponding acetates.9,19 These contrasting results il-
lustrate the influence on the k-1/k2 ratio of the other
groups of an intermediate, as discussed by Gresser and
J encks.14
(ii) The kN values are similar for the reactions of the
two substrates with piperidine. Since the pKa value for
0
this amine is larger than that of pKa , the formation of
the zwitterionic tetrahedral intermediate (Tq) is rate-
limiting for these reactions, and kN ) k1. The similar rate
constants for formation of Tq is in line with the similar
structures of the substrates involved.
0
(iii) For SA amines whose pKa are lower than pKa , the
decomposition of Tq to products (k2 step) is rate-determin-
ing and kN ) K1k2. It can be seen in Figure 3 that the kN
values for the reactions of these amines with 2 are larger
than those for EDNPDTC. Since the k1 values are similar
for both reactions, it follows that the k2/k-1 ratio for
intermediate 6 is larger than that for intermediate 7,
which agrees with the conclusions concerning point i.
It has been found that the reactions of SA amines with
phenyl and methyl 2,4-dinitrophenyl carbonates are
driven by a concerted mechanism,7 in contrast to the
same aminolysis of 1 and 2, which shows a stepwise path
(this work). This indicates that substitution of S- in the
tetrahedral intermediate 5 or 6 by O- destabilizes this
intermediate to the point of a mechanistic change.20
This complex mechanism for the reactions of SA
amines with alkyl nitrophenyl thionocarbonates is in
marked contrast to the simpler scheme (without the k3
step in Scheme 2) for the same aminolysis of thionocar-
bonates 1 and 2. The difference of these mechanisms
should be due to the superior leaving ability from the
intermediate Tq of DNPO (larger k2) relative to NPO. On
the other hand, it is known that the proton transfer from
the intermediate Tq to the amine is thermodynamically
(22) 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.
(23) Hill, S. V.; Thea, S.; Williams, A. J . Chem. Soc., Perkin Trans.
2 1983, 437.
(24) Satchell, D. P. N.; Satchell, R. S. Chem. Soc. Rev. 1990, 19, 55,
and references therein.
(25) Capon, B.; Ghosh, A. K.; Grieve, D. M. A. Acc. Chem. Res. 1981,
14, 306. Capon, B.; Dosunumu, M. I.; de Matus-Sanchez, M. N. Adv.
Phys. Org. Chem. 1985, 21, 37, and references therein.
(20) It has been shown that the change of methoxy to ethoxy in a
zwitterionic tetrahedral intermediate does not affect either the k-1 or
the k2 values or the stability of the intermediate in a significant
manner.3
(21) Douglas, K. T.; Alborz, M. J . Chem. Soc., Chem. Commun. 1981,
551. Douglas, K. T. Acc. Chem. Res. 1986, 19, 186.
J . Org. Chem, Vol. 69, No. 7, 2004 2415

Castro et al.
favorable, and therefore, the k3 value for these reactions
is diffusion-controlled (k3 ) 1010 s-1 M-1).1,2,4,5,26 The
change of NPO to DNPO should render the intermediate
Tq more acidic still, and therefore, the k3 value should
remain the same. In conclusion, the reason for this
remarkably different mechanisms should be due to the
fact that for the aminolysis of thionocarbonates 1 and 2
the inequality k2 . k3[NH] applies, whereas for the
reactions of the thionocarbonates with NPO as nucleo-
fuge, k2 is similar to k3[NH].
Ack n ow led gm en t. We thank FONDECYT of Chile
(project 1990561) for financial assistance to this work.
Su p p or tin g In for m a tion Ava ila ble: Pages S2-S4 con-
taining Tables S1-S3. This material is available free of charge
via the Internet at http://pubs.acs.org.
(26) Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1. Ahrens, M.
L.; Maass, G. Angew. Chem., Int. Ed. Engl. 1968, 7, 818.
J O035451R
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