The effect of medium on rate and mechanism: Aminolysis of O-4-nitrophenyl thionobenzoate in MeCN and H2O

Article abstract of DOI:10.1021/jo034637n

Pseudo-first-order rate constants (k_obs) have been measured spectrophotometrically for reactions of O-4-nitrophenyl thionobenzoate (1) with a series of alicyclic secondary amines in MeCN and H₂O at 25.0 ± 0.1 °C. The plot of k_obs vs amine concentration exhibits an upward curvature in all cases, indicating that the reactions proceed through two tetrahedral intermediates (a zwitterionic T ^± and its deprotonated anionic T^-) regardless of the amine basicity and the nature of the reaction medium. However, all the amines investigated have been found to be much less reactive in MeCN than in H₂O, although the amines are more basic in the former medium by 7-9 pK_a units.

Full text of DOI:10.1021/jo034637n

Th e Effect of Med iu m on Ra te a n d Mech a n ism : Am in olysis of
O-4-Nitr op h en yl Th ion oben zoa te in MeCN a n d H
2
O
†
†
Ik-Hwan Um,* J in-A Seok, Han-Tae Kim, and Sun-Kun Bae
Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea, and Department of
Chemistry, Kunsan National University, Kunsan 573-701, Korea
ihum@mm.ewha.ac.kr
Received May 13, 2003
Pseudo-first-order rate constants (kobs) have been measured spectrophotometrically for reactions
of O-4-nitrophenyl thionobenzoate (1) with a series of alicyclic secondary amines in MeCN and
H
2
O at 25.0 ( 0.1 °C. The plot of kobs vs amine concentration exhibits an upward curvature in all
cases, indicating that the reactions proceed through two tetrahedral intermediates (a zwitterionic
(
-
T and its deprotonated anionic T ) regardless of the amine basicity and the nature of the reaction
medium. However, all the amines investigated have been found to be much less reactive in MeCN
than in H
2
a
O, although the amines are more basic in the former medium by 7-9 pK units.
In tr od u ction
reaction with primary amines proceeds through one
intermediate (T ) while the corresponding reaction with
secondary amines proceeds through two intermediates
(
Since aminolyses of thiono compounds (e.g., 1, 3, 5)
have been much less investigated compared with those
of the oxygen analogues (e.g., 2, 4, 6), their reaction
(
- 2a
(
T
and T ). More systematic studies have been per-
formed by Castro et al. for aminolyses of various thiono
and dithio esters (e.g., 3 and 5) in H O or in aqueous
2
3
ethanol. The reactions of 3 and 5 with weakly basic
amines have been found to proceed through two tetra-
hedral intermediates, while the corresponding reactions
with strongly basic amines proceed without the depro-
(
3
tonation process from the zwitterionic T .
On the contrary, Lee et al. have studied the reactions
of 5 with a series of aniline and benzylamine derivatives
in pure MeCN and found that the reaction mechanism
changes from rate-determining expulsion of the leaving
mechanisms are not fully understood.1 An intriguing
-4
(
group from T for the reactions with weakly basic
question is whether the reaction proceeds through one
anilines to rate-determining nucleophilic attack for the
(
4a
or two tetrahedral intermediates, a zwitterionic T and
reactions with more basic benzylamines. The deproto-
-
1-4
(
its deprotonated anionic T .
We have recently per-
nation process from T , which has often been observed
formed the reaction of O-4-nitrophenyl thionobenzoate
as the rate-determining step for the reactions performed
(
1) with a series of primary and secondary amines in H
2
O
2
in H O, has been found to be absent regardless of the
(containing 20 mol % of DMSO) and found that the
amine basicity. On the other hand, Hanna et al. have
found that reactions of various acetate esters with
butylamine and pyrrolidine in MeCN proceed through the
deprotonation process, while the corresponding reaction
with piperidine proceeds without the deprotonation
*
Address correspondence to this author at Ewha Womans Univer-
Kunsan National University.
sity† .
(
1) Campbell, P.; Lapinskas, B. A. J . Am. Chem. Soc. 1977, 99,
378-5382.
2) (a) Um, I. H.; Lee, S. E.; Kwon, H. J . J . Org. Chem. 2002, 67,
999-9005. (b) Um, I. H.; Kwon, H. J .; Kwon, D. S.; Park, J . Y. J .
5
5
8
pathway although the basicity of these amines is similar.
(
2
Since most studies have been performed only in H O
Chem. Res., Synop. 1995, 301; J . Chem. Res., Miniprint 1995, 1801-
817.
3) (a) Castro, E. A. Chem. Rev. 1999, 99, 3505-3524. (b) Castro,
E. A.; Galvez, A.; Leandro, L.; Santos, J . G. J . Org. Chem. 2002, 67,
or in an organic solvent separately, the effect of medium
on rate and mechanism (particularly factors influencing
the deprotonation process from T ) cannot be compared
1
(
(
4
309-4315. (c) Castro, E. A.; Leandro, L.; Quesieh, N.; Santos, J . G.
directly. Therefore, we have performed the reaction of 1
with a series of alicyclic secondary amines in MeCN as
J . Org. Chem. 2001, 66, 6130-6135. (d) Castro, E. A.; Garcia, P.;
Leandro, L.; Quesieh, N.; Rebolledo, A.; Santos, J . G. J . Org. Chem.
2
000, 65, 9047-9053. (e) Castro, E. A.; Saavedra, C.; Santos, J . G.;
Umana, M. I. J . Org. Chem. 1999, 64, 5401-5407.
4) (a) Oh, H. K.; Woo, S. Y.; Shin, C. H.; Park, Y. S.; Lee, I. J . Org.
well as H
determined the microscopic rate constants associated
with the aminolysis reaction in both MeCN and H O. We
2
O (containing 20 mol % of DMSO). We have
(
2
Chem. 1997, 62, 5780-5784. (b) Oh, H. K.; Ku, M. H.; Lee, H. W.;
Lee, I. J . Org. Chem. 2002, 67, 8995-8998. (c) Lee, I.; Lee, H. W.; Lee,
B. C.; Choi, J . H. Bull. Korean Chem. Soc. 2002, 23, 201-205. (d) Oh,
H. K.; Kim, K. S.; Lee, H. W.; Lee, I. New J . Chem. 2001, 25, 313-
report here the effect of medium on rate and mechanism
3
17.
(5) Pfeiffer, M. J .; Hanna, S. B. J . Org. Chem. 1993, 58, 735-740.
1
0.1021/jo034637n CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/14/2003
7
742
J . Org. Chem. 2003, 68, 7742-7746

Effect of Medium on Rate and Mechanism
SCHEME 1
As shown in Figure 1, the plots of kobs vs amine
concentration exhibit an upward curvature for the reac-
tions of 1 with 1-formylpieprazine performed in MeCN
and H
than that in H
the reactions of 1 with all the other amines studied
figure not shown). Such an upward curvature is typical
2
O. However, the reaction in MeCN is much slower
2
O. A similar result has been obtained for
(
of the reaction that proceeds through two tetrahedral
(
intermediates, a zwitterionic T and its deprotonated
-
2,3
form T , as shown in Scheme 1. One can derive a rate
equation as eq 1 under the assumption of a steady-state
(
condition for the zwitterionic intermediate T . Then the
pseudo-first-order rate constant (kobs) can be expressed
(
as eq 2, in which [P], [T ], [1], and [NH] represent the
concentration of 4-nitrophenoxide (one of the products),
(
the zwitterionic intermediate T , the substrate 1, and the
amine, respectively. 2
,3
(
(
d[P]/dt ) k [T ] + k [T ][NH] ) {(k k [NH] +
2
3
1 2
2
k k [NH] )[1]}/(k + k + k [NH]) (1)
1
3
-1
2
3
2
kobs ) (k k [NH] + k k [NH] )/(k + k + k [NH])
1
2
1
3
-1
2
3
(2)
The further assumption of k-1 . k
2
+ k
3
[NH] simplifies
F IGURE 1. Plots of kobs vs amine concentration for the
reaction of 1 with 1-formylpiperazine in MeCN (O) and in H O
2
containing 20 mol % of DMSO (b) at 25.0 ( 0.1 °C. The solid
line was calculated through eq 2 with the parameters listed
in Table S2.
eq 2 to eq 3.
kobs/[NH] ) k k /k + k k [NH]/k
-1
(3)
1
2
-1
1
3
As shown in Figure 2, the plot of kobs/[NH] vs [NH] is
linear for the reaction of 1 with 1-formylpiperazine
regardless of the nature of the reaction medium. A
similar result has been obtained for the reactions with
weakly basic amines such as morpholine and 1-(2-
hydroxyethyl)piperazine (figure not shown), indicating
together with factors which govern the presence or
absence of the deprotonation process based on a quan-
titative analysis of the microscopic rate constants associ-
ated with the aminolysis reactions.
that the assumption k-1 . k
valid for the reactions with these weakly basic amines.
Therefore, the k /k-1 and k /k-1 values have been
2
+ k
3
[NH] appears to be
Resu lts a n d Discu ssion
1
k
2
1 3
k
Reactions of 1 with all the amines studied proceeded
with quantitative liberation of 4-nitrophenoxide and/or
its conjugate acid. All the reactions in the present study
obeyed first-order kinetics over 90% of the total reaction.
Pseudo-first-order rate constants (kobs) were calculated
determined from the intercept and the slope of the linear
plot, respectively. However, the corresponding plot for the
reactions with strongly basic amines (e.g., piperazine and
piperidine) is linear only at a low amine concentration
region but exhibits negative deviations as the amine
concentration is greatly increased (Figure S1 in Support-
from the equation ln(A
values obtained in this way are summarized in Table S1
Supporting Information) along with the kinetic condi-
tions.
∞
- A
t
) ) -kobst + C. The kobs
ing Information). Therefore, the assumption k-1 . k
3
2
+
(
k [NH] is valid only at a low amine concentration region
for the reactions with the strongly basic amines (both in
J . Org. Chem, Vol. 68, No. 20, 2003 7743

Um et al.
MeCN and in H
[NH] + k
concentration is significantly high, especially for the
reactions with highly basic amines run in H O. This
argument is consistent with the fact that Figure S1
Supporting Information) exhibits negative deviations
2
O, respectively. Therefore, the inequality
k
-1 . k
3
2
appears not to be valid when the amine
2
(
when the amine concentration is greatly increased, and
the deviation is more significant for the reaction run in
H
2
O than for that run in MeCN.
The k /k ratios have been determined from the k
and k /k-1 ratios. Since the magnitude of k and k values
has been suggested to be insensitive to the amine
3
2
2
/k-1
3
2
3
basicity,2 one might expect that the k
constant upon changing the amine basicity. However, as
shown in Table S2, the k /k ratio for the reactions with
,8,9
3
2
/k ratio is nearly
3
2
piperazine and morpholine is definitively larger than that
for the reactions with the other amines. One can attribute
the large k /k ratio obtained from the reaction with
3 2
piperazine to the fact that piperazine possesses two basic
(
sites to deprotonate from T . Similarly, the oxygen atom
(
of morpholine appears to deprotonate from T based on
the large k
of morpholine is much lower than that of the N site.
Since the k /k ratio is in the range of 136-482 and
744-1610 M for the reaction in MeCN and in H O,
respectively, the assumption k , k [NH] is valid only
when the amine concentration is significantly high,
especially for the reaction run in MeCN. This argument
accounts for the result that the plot of [NH]/kobs vs 1/[NH]
is linear at a high [NH] region, but exhibits negative
deviations at a low [NH] region, and such a negative
deviation is more significant for the reaction run in
3 2
/k ratio, although the basicity of the O site
3
2
-
1
F IGURE 2. Plots of kobs/[amine] vs [amine] for the reaction
2
of 1 with 1-formylpiperazine in MeCN (O) and in H
ing 20 mol % of DMSO (b) at 25.0 ( 0.1 °C.
2
O contain-
2
3
MeCN and in H
1) The k-1 value would decrease with increasing amine
basicity. (2) The term k [NH] increases with increasing
NH], although k and k values have been suggested to
be insensitive to the amine basicity.
2
O). One can explain this result as below:
(
3
[
2
3
2
,8,9
2
MeCN than in H O, as shown in Figure S2 (Supporting
[
NH]/kobs ) 1/k + k /k k [NH]
(4)
Information). Therefore, the microscopic rate constants
determined through the nonlinear least-squares fitting
of eq 2 are considered to be reliable, and support the
proposed reaction mechanism.
1
-1
1 3
One can reduce eq 2 to eq 4 under the assumption k
2
,
k
3
[NH] at a high amine concentration region. As shown
in Figure S2 (Supporting Information), the plot of [NH]/
obs vs 1/[NH] is linear for the reaction of 1 with
piperidine at a high amine concentration region but
exhibits negative deviations at a low concentration
region. A similar result has been obtained for the
reactions with all the other amines studied, indicating
that the assumption k
amine concentration region. Therefore, the 1/k
been estimated from the intercept of the linear part of
the plot. The values of k , k /k-1, and k /k-1 have been
determined through the nonlinear least-squares fitting
of eq 2 to the experimental data by using the estimated
Many studies have been performed to investigate
k
factors influencing reaction mechanism, particularly the
2-7,10-12
presence or absence of the k
3
pathway.
J encks et
al. have suggested that the aminolysis of esters proceeds
through the k pathway when the ester possesses a
strongly basic leaving group but without the k process
3
3
2
, k
3
[NH] is valid only at a high
when the leaving group is weakly basic, indicating that
7a
1
value has
the basicity of the leaving group is an important factor.
Gresser et al. have reported that the aminolysis of diaryl
7b
1
2
3
3
carbonates (e.g., 4) proceeds without the k process.
However, Castro et al. have found that the reaction of
diaryl thionocarbonates (e.g., 3) with weakly basic amines
1
k values, and summarized in Table S2 (Supporting
Information).
As shown in Table S2, the k /k-1 ratio is in the range
3
of 1.17-7.94 and 4.89-104 M for the reaction run in
proceeds through the k
strongly basic amines proceeds without the k
3
pathway, while the one with
3b-d
3
process.
Therefore, the basicity of amines and the structure of the
electrophilic center (e.g., CdS vs CdO) have been sug-
gested to be important to determine the reaction mech-
-
1
(
6) Kwon, D. S.; Park, H. S.; Um, I. H. Bull. Korean Chem. Soc. 1991,
2, 93-97.
7) (a) Satterthwait, A. C.; J encks, W. P. J . Am. Chem. Soc. 1974,
1
(
(10) (a) Maude, A. B.; Williams, A. J . Chem. Soc., Perkin Trans. 2
1997, 179-183. (b) Maude, A. B.; Williams, A. J . Chem. Soc., Perkin
Trans. 2 1995, 691-696. (c) Talvik, A. T.; Tuulmets, A.; Vanino, E. J .
Phys. Org. Chem. 1999, 12, 747-750. (d) J edrzejczak, M.; Motie, R.
E.; Satchell, D. J . Chem. Soc., Perkin Trans. 2 1993, 599-600.
(11) (a) Haberfield, P.; Cincotta, J . J . J . Org. Chem. 1990, 55, 1334-
1338. (b) Hogan, J . C.; Grandour, R. D. J . Org. Chem. 1991, 56, 2821-
2826. (c) Hogan, J . C.; Grandour, R. D. J . Org. Chem. 1992, 57, 55-
61.
9
1
6, 7018-7031. (b) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc.
977, 99, 6963-6970. (c) J encks, W. P.; Brant, S. R.; Gandler, J . R.;
Fendrich, G.; Nakamura, C. J . Am. Chem. Soc. 1982, 104, 7045-7051.
(
d) Stefanidis, D.; Cho, S.; Dhe-Paganon, S.; J encks, W. P. J . Am. Chem.
Soc. 1993, 115, 1650-1656.
8) Oh, H. K.; Kim, K. S.; Lee, H. W.; Lee, I. J . Chem. Soc., Perkin
Trans. 2 2000, 2306-2310.
9) (a) Castro, E. A.; Ibanez, F.; Santos, J . G.; Ureta, C. J . Org. Chem.
993, 58, 4908-4912. (b) Castro, E. A.; Ibanez, F.; Santos, J . G.; Ureta,
C. J . Chem. Soc., Perkin Trans. 2 1991, 1919-1924.
(
(
1
(12) Menger, F. M.; Smith, J . H. J . Am. Chem. Soc. 1972, 94, 3824-
3829.
7
744 J . Org. Chem., Vol. 68, No. 20, 2003

Effect of Medium on Rate and Mechanism
3
anism. We have recently shown that the amine nature
as follows. The k
ate T as shown in Scheme 1. Since MeCN cannot
1
process yields a zwitterionic intermedi-
(
is also an important factor, since the reaction of 1 with
various secondary amines (both cyclic and acyclic second-
ary amines) proceeds through the k
corresponding reaction with primary amines proceeds
without the k
Lee et al. have reported that the k
in the aminolysis of aryl dithiobenzoates (5) performed
in MeCN.4 The absence of the k
process has been
attributed to a greatly reduced mobility of proton in such
an aprotic solvent. However, the present aminolysis of
1
4
stabilize such an ionic species, the k
to be smaller in MeCN than in H O. In fact, the k
shown in Table S2 for the reactions run in MeCN is
slightly smaller than that for the reactions run in H
(except for the reaction with 1-formylpiperazine), al-
though the amines are more basic in MeCN than in H
units. On the other hand, the breakdown
1
value is expected
3
pathway while the
2
1
value
2
a
3
process regardless of the amine basicity.
2
O
3
pathway is absent
2
O
by ca. 7-9 pK
a
3
(
of the intermediate T to the reactants (the k-1 process)
4
(
would be faster in MeCN than in H
2
O, since T would
1
performed in MeCN proceeds through the k
3
pathway
be more unstable in the former medium. However, the
(
as mentioned in the preceding section. Therefore, one can
suggest that the reduced rate of proton transfer in MeCN
is not an important factor in determining the presence
medium effect on the rate of the decomposition of T to
-
T
3 2
(the k process) or to the products (the k process) is
expected to be insignificant, since both processes yield
(
or absence of the k
3
process. This argument can be further
another ionic species from the zwitterionic T . Therefore,
supported from the previous reports that aminolyses
the k
MeCN than in H
/k-1 and k /k-1 ratios have been determined to be much
smaller for the reactions performed in MeCN than for
those in H O.
3
Lee et al. have recently proposed that the k value
2
/k-1 and k
3
/k-1 ratios are expected to be smaller in
performed in various aprotic solvents including MeCN
2
O. In fact, as shown in Table S2, the
,10-12
proceed through the k
3
pathway.5
k
2
3
It is interesting that the aminolysis that proceeds
through the k pathway has a small k /k-1 ratio either
by deceasing the k value or by increasing the k-1 value.
The introduction of a poor leaving group as in the
2
3
2
2
+
would be diminished greatly in MeCN since the H
J encks’system7 decreases the k
a
value. Similarly, the
4a
mobility decreases in the aprotic solvent. Such a solvent
2
replacement of the CdO bond in the substrate by the
effect on the k
the k /k-1 ratio for the reacion run in MeCN. This
argument is consistent with the fact that the k /k-1 ratio
decreases much more significantly than the k /k-1 ratio
upon the medium change from H O to MeCN. Therefore,
one can suggest that the decreased k /k-1 ratio is the most
responsible contributor to the decreased reaction rate
upon the medium change from H O to MeCN. To the best
3
value would cause a further decrease in
CdS bond as in Castro’s system would also decrease the
3
-
k
2
value due to the decreased ability of C-S to form a
3
-
CdS bond compared with the ability of C-O to form a
2
3
CdO bond. On the other hand, the k
2
/k-1 ratio also can
2
be decreased by using weakly basic amines, since the k-1
value increases with decreasing amine basicity. Besides,
we have recently shown that the k-1 value is much larger
3
2
for the reactions of 1 with secondary amines than those
of our knowledge, the effect of medium on the microscopic
rate constants for ester aminolyses has never been
analyzed quantitatively.
with primary amines.2 As shown in Table S2, the k
a
/k-1
2
-
3
ratio is in the range of (4.90-31.7) × 10 and (6.58-
-
3
9
7.1) × 10 for the reactions run in MeCN and in H
2
O,
To investigate the effect of medium on rate and
H O
MeCN
respectively. These values are much smaller than those
reported in the literature for the reactions proceeding
basicity, the plot of log k
1
2
/k
1
vs ∆pK
a
has been
a
represent
H O
MeCN
constructed, in which k
the k values in H
the pK of the conjugate acid of amine in the two solvents
(i.e., ∆pK ) pK in MeCN - pK in H O), respectively.
1
2
, k
1
, and ∆pK
without the k
of 1 with various primary amines. Therefore, the small
/k-1 ratio is considered to be a common feature for the
3
pathway, i.e., ca. 1-25 for the reactions
1
2
O and in MeCN, and the difference in
2
a
a
k
2
a
a
a
2
aminolysis reaction that proceeds through the k
way.
3
path-
As shown in Figure S5 (Supporting Information), the plot
is linear with a slope of 0.30. One can also see a linear
H O
MeCN
-1)
/k-1) 2
/(k k /k
1 2
and
Figure S3 (Supporting Information), which is statisti-
correlation between log(k
1
k
2
cally corrected by using p and q,13 exhibits a linear
a
∆pK
with a slope of 0.62 (Figure S6 in the Supporting
Brønsted-type plot with a â
1
value of 0.45 for the
Information). The linearity shown in Figures S5 and S6
suggests that the effect of medium on the amine basicity
aminolysis of 1 performed in MeCN. A similar result has
been shown in the inset of Figure S3 for the correspond-
ing reactions performed in the aqueous medium with a
(∆pK
as well as the equilibrium (k
effect appears to be more significant on the basicity
(∆pK ) than on the k value or on the k /k-1 ratio, since
a
) is reflected in the effect of medium on the k
1
value
1
/k-1). However, the medium
â
1
value of 0.39. Figure S4 (Supporting Information)
demonstrates that the plot of log k /k-1 vs pK is also
linear for reactions performed both in MeCN and in H
2
a
a
1
1
O
the slopes of Figures S5 and S6 are much smaller than
unity.
2
with a -â-1 value of 0.29 and 0.39, respectively. Since
there is little difference in the âeq value for the reactions
In conclusion, we have found the following. (1) The
aminolysis of 1 proceeds through rate-limiting deproto-
in MeCN (âeq ) 0.74) and H O (âeq ) 0.78), one can
2
(
-
suggest that the effect of the medium on the structure of
the transition state is insignificant in the present ami-
nolysis.
2
nation from T to give T both in MeCN and in H O. (2)
(14) (a) Parker, A. J . Chem. Rev. 1969, 69, 1-32. (b) Buncel, E.;
Wilson, H. Adv. Phys. Org. Chem. 1977, 14, 133-202. (c) Um, I. H.;
Buncel, E. J . Org. Chem. 2000, 65, 577-582. (d) Um, I. H.; Lee, E. J .;
Buncel, E. J . Org. Chem. 2001, 66, 4859-4864. (e) Um, I. H.; Buncel,
E. J . Am. Chem. Soc. 2001, 123, 11111-11112.
As mentioned in the preceding section, the reaction
performed in MeCN is much slower than that run in H
One can explain the effect of medium on the reaction rate
2
O.
(15) Spillane, W. J .; McGrath, P.; Brack, C.; O’Byrne, A. B. J . Org.
Chem. 2001, 66, 6313-6316.
(16) Um, I. M.; Min, J . S.; Ahn J . A.; Hahn, H. J . J . Org. Chem.
2000, 65, 5659-5663.
(
13) Bell. R. P. The Proton in Chemistry; Methuen: London, UK,
1
959; p159.
J . Org. Chem, Vol. 68, No. 20, 2003 7745

Um et al.
The reaction is much slower in MeCN than in H
although the amines studied are more basic in the former
medium by ca. 7-9 pK units. (3) The k /k-1 ratio
decreases more significantly than the k value or the k
-1 ratio upon the medium change from H O to MeCN,
2
O,
with a constant temperature circulating bath to keep the
reaction temperature at 25.0 ( 0.1 °C. The amine stock
solution of ca. 0.2 M was prepared by dissolving 2 equiv of
free amine and 1 equiv of standardized HCl solution to keep
the pH constant by making a self-buffered solution for the
a
3
1
2
/
k
2
2
reactions run in H O. However, for the reactions run in MeCN,
which is most responsible for the slower reaction rate in
MeCN.
the amine stock solutions were prepared only with free amines.
All the solutions were prepared fresh just before use under
nitrogen and transferred by gastight syringes.
Exp er im en ta l Section
P r od u ct An a lysis. 4-Nitrophenoxide (and/or its conjugate
acid) was identified as one of the products of the aminolysis
of 1 by comparison of the UV-vis spectrum at the end of
reaction with the authentic sample under the same kinetic
conditions. Other products (e.g., N-thiobenzoylpiperidine) were
analyzed by HPLC by comparison with the authentic sample.
The flow rate was 1 mL/min, and the eluent was 50% MeCN
in MeOH (v/v).
Ma ter ia ls. O-4-Nitrophenyl thionobenzoate (1) was syn-
thesized as reported previously. The purity of 1 was checked
1
,6
by means of the melting point and spectral data such as IR
1
and H NMR characteristics. Amines and other chemicals used
were of the highest quality available. MeCN was distilled over
P O . DMSO was treated with CaH overnight and distilled
2 5 2
at a reduced pressure (bp 64-66 °C at 6-7 mmHg) and stored
under nitrogen. Doubly glass distilled water was further boiled
and cooled under nitrogen just before use. When the reactions
were performed in aqueous medium, 20 mol % of DMSO was
Ack n ow led gm en t. This work was supported by a
grant (KRF-2002-015-CP0223) from Korea Research
Foundation.
2 2
added to H O due to the low solubility of 1 in pure H O.
Kin etics. All the reactions were carried out under pseudo-
first-order conditions in which the amine concentrations were
at least 30 times greater than the substrate concentration. The
reaction was followed by monitoring the appearance of the
leaving 4-nitrophenoxide at 400 nm with a UV-vis spectro-
photometer for slow reactions (t1/2 g 10 s) or with a stopped-
flow spectrophotometer for fast reactions (t1/2 < 10 s) equipped
Su p p or tin g In for m a tion Ava ila ble: Tables S1 and S2
giving reaction conditions and the kinetic results and Figures
S1-S6 showing kinetic results. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O034637N
7
746 J . Org. Chem., Vol. 68, No. 20, 2003