Oh et al.
M- s-1 for X ) H and Z ) 3-NO
1
at 45.0 °C and k
)
TABLE 2. Kin etic Isotop e Effects for th e Rea ction s of
2
2
-
2
-1 -1
Z-P h en yl N-P h en yl Th ioca r ba m a tes w ith X-Ben zyla m in es
in Aceton itr ile a t 30.0 °C
6
(
.30 × 10
M
s
2
for X ) H and Z ) 3-NO at 45.0 °C
1
estimated) , for 2b and 2a , respectively. The rate
1
kD (M-1 s-1
X
Z
kH (M- s-1
)
)
kH/kD
enhancement due to an increased nucleofugality with SAr
compared to OAr is ca. 7 times for R ) EtO, while it is
much greater, at least 50 times for R ) PhNH. This
suggests that the rate increase is not completely due to
the substitution of SAr for OAr, but the mechanistic
change from stepwise to concerted is partly responsible.
In fact, the substitution of SAr for OAr was found to
result in only ca. 2-3 times the rate increase when there
is no mechanistic change. The aminolysis of 2,4-dinitro-
p-OMe p-Me
p-OMe
p-OMe p-Cl 13.0 ((0.1)
P-OMe p-Me 15.1 ((0.2)
2.18 ((0.05)
3.97 ((0.06)
1.70 ((0.02)
2.96 ((0.06)
9.35 ((0.08)
10.6 ((0.09)
1.28 ( 0.03a
1.34 ( 0.08
1.39 ( 0.02
1.43 ( 0.02
H
p-Cl
p-Cl
p-Cl
p-Cl
p-Br
H
p-Cl
p-Br
0.451 ((0.004)
0.805 ((0.008)
2.03 ((0.04)
2.33 ((0.05)
0.364 ((0.002) 1.24 ( 0.01
0.615 ((0.005) 1.31 ( 0.02
1.48 ((0.02)
1.65 ((0.02)
1.37 ( 0.03
1.41 ( 0.03
a Standard deviations.
phenyl thioacetate,14 CH
C(dO)SC H (NO ) , with alicy-
3 6 3 2 2
clic secondary amines is only ca. 2-3 times faster than
TABLE 3. Activa tion P a r a m eter sa for th e Rea ction s of
those corresponding rates of 2,4-dinitrophenyl acetate,15
Z-P h en yl N-P h en yl Th ioca r ba m a tes w ith X-Ben zyla m in es
in Aceton itr ile
3 6 3 2 2
CH C(dO)OC H (NO ) , in aqueous solution at 25.0 °C.
These two reactions were found to proceed stepwise with
X
Z
∆Hq/kcal mol-1 b
-∆Sq/cal mol-1 K-1
-
rate-limiting expulsion of the leaving group, SAr in the
p-OMe
p-OMe
p-Cl
p-Me
p-Br
p-Me
p-Br
10.5
10.1
9.4
22
20
29
22
-
former and OAr in the latter. The unusually large
aminolysis rate increase from 3a to 3b is therefore most
likely caused partly by a change of mechanism from a
stepwise (for 3a ) to a concerted (for 3b), similar to the
rate increase accompanied by a mechanistic change
observed from 2a to 2b.
p-Cl
10.5
a
Calculated by use of the Eyring equation with the k2 values
at three temperatures: 20, 30, and 40 °C. The maximum errors
calculated (by the method of: Wiberg, K. B. Physical Organic
-
1
Chemistry; Wiley: New York, 1964; p 378) are (1.0 kcal mol
Further important mechanistic criteria for the con-
certed reaction with 3b rather than the stepwise reaction
and (4 eu for ∆Hq and ∆Sq, respectively. b Correlation coefficients
were better than 0.9996 in all cases.
(as with 3a ) is that the sign of cross-interaction constant
F
XZ is negative for 3b (rather than positive as with 3a )
taken as an indicative of a stepwise mechanism but
cannot provide conclusive evidence for a stepwise mech-
anism.
and the reactivity-selectivity principle (a stronger reac-
tivity is accompanied by a lower selectivity; RSP) fails
with 3b.5 The stepwise mechanism is not favored for
the present reactions, since for the stepwise aminolysis
of esters, carbonates and carbamates, the sign of FXZ (and
d,6
The kinetic isotope effects (k /k ) involving deuterated
H
D
benzylamines5 (XC H CH ND ) are presented in Table
c
6
4
2
2
2. We note that the isotope effects are normal with k /kD
H
F
XY) is positive and the RSP holds.5d,6
The magnitude of â is, however, large (â
which is normally considered to indicate a stepwise
> 1.0 suggesting there is a hydrogen bond formed by the
amino proton (N-H or N-D) in the TS, most probably
X
X
= 1.3-1.5),
with the negatively charged S atom in the leaving group.
reaction.16 For concerted aminolysis reactions, the â
Since the large â and â values suggest that the TS is a
X
Z
X
1
7
late type with a large degree of bond formation and bond
cleavage, the hydrogen bonding seems to be rather strong
values were found to range from 0.4-0.8. It is, however,
well-known that the large magnitude of the Br o¨ nsted
slope alone is not sufficient to decide the aminolysis
mechanism as stepwise. J encks and co-workers reported
with relatively large values of k
supported by a larger k /k value for a stronger nucleo-
philie (δσ < 0) and a stronger nucleofuge (δσ > 0),
which will lead to a later TS in accordance with the
negative FXZ; a stronger nucleophile, δσ < 0, gave a
larger F value δF > 0 so that FXZ ) δF /δσ < 0, while
a stronger nucleofuge, δσ > 0, gave a larger negative F
value (δF < 0) leading to FXZ < 0.
H
/k
D
> 1.0. This is
H
D
X
Z
concerted acyl-transfer reactions with large â
X
values, â
X
)
0.6-0.9 for the reactions of phenyl formates with
1
8
X
substituted O-chlorophenolate anions and â
X
) 0.7-
Z
Z
Z
X
1
.0 for the reactions of a series of nucleophilic reagents
1
9
Z
X
with substituted N-acetylpyridinium ions. Williams and
co-workers20 reported even larger â
values (â ) 1.3 and
.6) for the concerted acyl-transfer reactions. Thus, the
X
X
X
The activation parameters determined with the rate
data at three temperatures are summarized in Table 3.
The values are well within the ranges obtained for the
concerted reactions. However, it is difficult to distinguish
by the magnitude of the activation parameters a stepwise
1
X
large â values observed in the present work may be
(14) Castro, E. A.; Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991,
6
6
3.
q
q
from a concerted process. For example, the ∆H and -∆S
(
15) Castro, E. A.; Ureta, C. J . Org. Chem. 1990, 55, 1676.
1
(16) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963,
values for the aminolysis reactions of 2a (stepwise) and
977.
17) (a) Castro, E. A.; Angel, M.; Arellano, D.; Santos, J . G. J . Org.
4
-1
2
1
b (concerted) are 14.4-15.0 kcal mol , 17-21 eu and
(
-1
2.5-16.3 kcal mol , 15-28 2 eu, respectively.
In summary, the nucleophilic substitution reactions of
Chem. 2001, 66, 6571. (b) Castro, E. A.; Leandro, L.; Millan, P.; Santos,
J . G. J . Org. Chem. 1999, 64, 1953. (c) Castro, E. A.; Munoz, P.; Santos,
J . G. J . Org. Chem. 1999, 64, 8298.
aryl N-phenylthiocarbamates (3b) with benzylamines in
acetonitrile proceed by a concerted mechanism, which is
in contrast to the stepwise mechanism of the correspond-
ing reactions of aryl N-phenylcarbamates (3a ). The
mechanistic change occurred by substitution of SAr (3b)
for OAr (3a ) is quite similar to the mechanistic change
(
18) Stefanidas, D.; Cho, S.; Dhe-Paganon, S.; J encks, W. P. J . Am.
Chem. Soc. 1993, 115, 1650.
19) Fersht, A. R.; J encks, W. P. J . Am. Chem. Soc. 1970, 92, 6963,
442.
(
5
(20) (a) Ba-Saif, S.; Luthra, A. K.; Williams, A. J . Am. Chem. Soc.
1
989, 111, 2647. (b) Maude, A. B.; Williams, A.. J . Chem. Soc., Perkin
Trans. 2, 1997, 179.
3
152 J . Org. Chem., Vol. 69, No. 9, 2004