Aminolysis of aryl chlorothionoformates with anilines in acetonitrile: Effects of amine nature and solvent on the mechanism

Article abstract of DOI:10.1021/jo0487247

The aminolysis of aryl chlorothionoformates (7, YC₆H ₄OC(=S)Cl) with anilines (XC₆H₄NH₂) in acetonitrile at 5.0 °C has been investigated. The rates are slower than those for the corresponding reactions of aryl chloroformates (6, YC ₆H₄OC(=O)Cl). This rate sequence is a reverse of that for alkyl chloroformates (1 4) in water, for which rate-limiting formation of a tetrahedral intermediate, T^±, is predicted. On the basis of the large negative cross-interaction constant, ρ_XY = -0.77, failure of the reactivity-selectivity principle, normal k_H/k _D values involving deuterated nucleophiles (XC₆H ₄ND₂), and low ΔH^≠ with large negative ΔS^≠ values, a concerted mechanism with a four-membered hydrogen bonded cyclic transition state (11) is proposed for the title reaction series. It has been shown that the solvent change from water to acetonitrile for the aminolysis of 6 and 7 causes a mechanistic change from stepwise to concerted.

Full text of DOI:10.1021/jo0487247

Aminolysis of Aryl Chlorothionoformates with Anilines in
Acetonitrile: Effects of Amine Nature and Solvent on the
Mechanism
Hyuck Keun Oh,† Joo Suk Ha,† Dae Dong Sung,‡ and Ikchoon Lee*,‡,§
Department of Chemistry, Chonbuk National University, Chonju 560-756, Korea,
Department of Chemistry, Dong-A University, Busan 604-714, Korea, and Department of Chemistry,
Inha University, Inchon 402-751, Korea
ilee@inha.ac.kr
Received July 25, 2004
The aminolysis of aryl chlorothionoformates (7, YC6H4OC(dS)Cl) with anilines (XC6H4NH2) in
acetonitrile at 5.0 °C has been investigated. The rates are slower than those for the corresponding
reactions of aryl chloroformates (6, YC6H4OC(dO)Cl). This rate sequence is a reverse of that for
alkyl chloroformates (1-4) in water, for which rate-limiting formation of a tetrahedral intermediate,
T(, is predicted. On the basis of the large negative cross-interaction constant, FXY ) -0.77, failure
of the reactivity-selectivity principle, normal kH/kD values involving deuterated nucleophiles
(XC6H4ND2), and low ∆H* with large negative ∆S* values, a concerted mechanism with a four-
membered hydrogen bonded cyclic transition state (11) is proposed for the title reaction series. It
has been shown that the solvent change from water to acetonitrile for the aminolysis of 6 and 7
causes a mechanistic change from stepwise to concerted.
Introduction
in the rate-determining step from breakdown to forma-
tion of a zwitterionic tetrahedral intermediate, T(, with
increasing basicity of the pyridines. In contrast, the
aminolysis of phenyl chloroformate (1 with R ) Ph) with
secondary alicyclic amines in water was reported to
proceed by rate limiting formation of T(.3
The aminolysis of aryl chlorothionoformates (3 with R
) YC6H4) with secondary alicyclic amines4a as well as
with pyridines4b in water was also found to proceed by
rate-limiting formation of T(. This shows that the change
of CdO to CdS in the aryl chloroformates does not cause
a mechanistic change for the aminolysis in water. How-
ever, this is contrasted with a concerted process found
for the aminolysis of aryl chloroformates (6; 1 with R )
YC6H4) in acetonitrile.5
The aminolysis of carbonyl and thiocarbonyl deriva-
tives has shown interesting mechanistic changes depend-
ing on the nonleaving acyl group and the solvent medium.
For example, the rate sequence for the solvolysis of
chloroformates (1-4) is reported to depend on the initial
state stabilization of type 51 (shown for the thiono
analogue). The extent of delocalization of the lone pair
To shed more light on the mechanistic changes de-
pending on the nonleaving RO group and on the reaction
medium, we carried out kinetic studies on the aminolysis
of aryl chlorothionoformates (7; 3 with R ) YC6H4) with
anilines in acetonitrile, eq 1.
electrons (n) on RO¨ (or RS) toward CdO (or CdS) has
been shown to decrease in the order, 1 > 4 > 3 > 2, and
accordingly the solvolysis rates in water were found to
increase in the reverse order (1 < 4 < 3 < 2), which was
attributed to the initial state stabilization of the reac-
tions.1
On the other hand, the aminolysis of methyl chloro-
formate2 (1 with R ) Me) with pyridines in water was
found to proceed by a stepwise mechanism with a change
* Address correspondence to this author. Phone: +82-32-860-7681.
FAX: +82-32-865-4855.
In this work we varied substituents in the nucleophile
(X) and in the nonleaving group (Y), and subjected the
† Chonbuk National University.
‡ Dong-A University.
§ Inha University.
(3) Castro, E. A.; Ruiz, M. G.; Santos, J. G. Int. J. Chem. Kinet. 2001,
33, 281.
(4) (a) Castro, E. A.; Cubillos, M.; Santos, J. G. J. Org. Chem. 1997,
62, 4395. (b) Castro, E. A.; Cubillos, M.; Santos, J. G. J. Org. Chem.
2004, 69, 4802.
(1) McKinnon, D. M.; Queen, A. Can. J. Chem. 1972, 50, 1401.
(2) (a) Palling, D. J.; Jencks, W. P. J. Am. Chem. Soc. 1984, 106,
4869. (b) Bond, P. M.; Castro, E. A.; Moodie, R. B. J. Chem. Soc., Perkin
Trans. 2 1976, 68.
10.1021/jo0487247 CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/30/2004
J. Org. Chem. 2004, 69, 8219-8223
8219

Oh et al.
TABLE 1. The Second Order Rate Constants, k2 (×10 M-1 s-1) for the Reactions of Y-Phenyl Chlorothionoformates
(YC6H4OC(dS)Cl) with X-Anilines (XC6H4NH2) in Acetonitrile at 5.0°C
Y
a
X
p-OMe
p-Me
13.1
H
p-Cl
86.8b
FY
p-OMe
11.2b
8.41
28.5
64.7
48.0c
34.8
10.3
3.61b
2.68
1.98c
0.780
1.79 ( 0.08
6.35c
4.61
p-Me
H
p-Cl
7.16
2.46
13.3
4.38
1.75 ( 0.04
1.60 ( 0.03
1.63
0.669b
0.502
0.378c
0.181
0.698
0.231
1.17
1.46 ( 0.04
m-Cl
0.391
1.29 ( 0.03
d
FX
-2.55 ( 0.06
0.90 ( 0.02
-2.69 ( 0.07
0.95 ( 0.02
-2.84 ( 0.07
1.00 ( 0.03
-2.94 ( 0.09
1.04 ( 0.02
FXYe ) -0.77
f
âX
a The σ values were taken from ref 7. Correlation coefficients were better than 0.998 in all cases. b At 15 °C. c At -5 °C. d The σ values
were taken from ref 7. Correlation coefficients were better than 0.999 in all cases. e Correlation coefficient was 0.999. f The pKa values
were taken from the following: Fischer, A.; Galloway, W. J.; Vaughan, J. J. Chem. Soc. 1964, 3588. Correlation coefficients were better
than 0.999 in all cases. X ) p-CH3O were excluded from the Bro¨nsted plot for âX(benzylamine) due to an unreliable pKa value listed.
second-order rate constants, kXY, to a multiple regression
analysis to obtain the cross-interaction constant, FXY in
eq 2.6 The sign and magnitude of FXY provide mechanistic
criteria for the nucleophilic substitution reactions.
methoxy group (σp ) -0.27; σp+ ) -0.78),7 and hence the
effect of the initial state stabilization will be much weaker
for PhO than for alkoxy group. Thus the solvolysis rate
sequence for phenyl chloroformates (1-4 with R ) Ph)
is no longer determined by the initial state stabilization,
but is determined largely by the strength of push
provided by the carbonyl (CdO or CdS) and nonleaving
groups (RO- or RS-) to expel the leaving group, Cl-, in
the tetrahedral structure, which can be either an inter-
mediate, 8a, or a TS, 8b. The change of S- (in 3 and 4)
log(kXY/kHH) ) FXσX + FYσY + FXYσXσY
FXY ) ∂FY/∂σX ) ∂FX/∂σY
(2a)
(2b)
Results and Discussion
The second-order rate constants, k2, are summarized
in Table 1. These values were determined from the kobs
kobs ) k2[AN]
(3)
values of at least five aniline concentrations, [AN], under
pseudo-first-order conditions, [AN] ) 0.02-0.05 mol
dm-3, for [substrate] ) 1 × 10-4 mol dm-3. The aminolysis
rates are found to follow good second-order kinetics and
no complications by side reaction are found. The rates
are ca. 10 times slower than those for the corresponding
aminolysis of aryl chloroformate (6; R ) YC6H4 in 1) in
acetonitrile.5 For example, the k2 values for 7 are 0.120
and 0.390 s-1 M-1 in MeCN at 25. 0°C (estimated by
using activation parameters) for Y ) p-OMe and p-Cl
with X ) p-Cl, respectively, and the corresponding values
for 6 are 1.13 and 3.87 s-1 M-1. Thus the aminolysis rate
decreases by substitution of O (in 6) by S (7). This is in
contrast to the solvolysis rate increase observed for the
same replacement of O by S, from methyl chloroformate
(1 with R ) Me; k ) 0.674 × 10-4 s-1) to methyl
chlorothionoformate (3 with R ) Me; k ) 1.73 × 10-4 s-1),
in water at 4.62 and 4.96 °C, respectively.1 As has been
pointed out by the original authors1 of the solvolysis
studies, the initial state stabilization should be important
in determining the rate sequence in water for chlorofor-
mates (1-4) with alkoxy nonleaving groups (R ) Me, Et,
and 2-Pr). In the rate-determining step, it is expected
that, the greater the initial state (reactant) stabilization,
the slower will become the bond formation. In contrast,
by O- (in 1 and 2) and that of RS- (in 2 and 4) by RO-
(in 1 and 3) are known to increase the nucleofugality of
the leaving group,8 Cl-, the effect of the former being
greater. This could be the reason for the solvolysis rate
sequence for the R ) Ph series, 1 > 2 > 3 > 4, being
quite different from the rate sequence for the R ) alkyl
series as noted in the Introduction.
The aminolysis of both aryl chloroformates,3,9 6, and
aryl chlorothionoformates,4a 7, with secondary alicyclic
amines in water is reported to proceed by rate-limiting
formation of T(. Since the expulsion rates of amines from
T( increases in the order pyridines < anilines < second-
ary alicyclic amines < quinuclidines < benzylamines,10
it is reasonable to expect that the same mechanism, i.e.,
rate-limiting formation of T(, applies to the aminolysis
of both 6 and 7 with anilines in water. This is because,
(6) (a) Lee, I. Chem. Soc. Rev. 1990, 19, 317. (b) Lee, I. Adv. Phys.
Org. Chem. 1992, 27, 57.
(7) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(8) (a) Castro, E. A.; Araneda, C. A.; Santos, J. G. J. Org. Chem.
1997, 62, 126. (b) Castro, E. A.; Ibanez, F.; Santos, J. G.; Ureta, C. J.
Org. Chem. 1993, 58, 4908. (c) Castro, E. A. Chem. Rev. 1999, 99, 3505.
(9) Castro, E. A.; Ruiz, M. G.; Salinas, S.; Santos, J. G. J. Org. Chem.
1999, 64, 4817.
the electron donor ability of the phenoxy group (σp
)
-0.03; σp ) -0.50)7 is much lower than that of the
+
(5) Yew, K. H.; Koh, H.-J.; Lee, H. W.; Lee, I. J. Chem. Soc., Perkin
Trans. 2 1995, 2263.
(10) (a) Castro, E. A.; Munoz, P.; Santos, J. G. J. Org. Chem. 1999,
64, 8298. (b) Lee, I.; Sumg, D. D. Curr. Org. Chem. 2004, 8, 557.
8220 J. Org. Chem., Vol. 69, No. 24, 2004

Aminolysis of Aryl Chlorothionoformates
as the expulsion rate from T( decreases, the intermedi-
ate, T(, becomes more stable (stability of T( with anilines
is reported to be greater than that with secondary
alicyclic amines)11 and the possibility of a stepwise
mechanism increases, i.e., the aminolysis with anilines
is more likely to proceed by the stepwise mechanism than
with the secondary alicyclic amines under the same
reaction conditions.10 For example, the aminolyses of
O-ethyl S-(2,4-dinitrophenyl)- (9a: EtO-C(dO)‚SC6H3‚
2,4-(NO2)2) and O-ethyl S-(2,4,6-trinitrophenyl)carbon-
ates (9b: EtO-C(dO)‚SC6H2‚2,4,6-(NO2)3) have been
studied in water at 25 °C with amines of the increasing
order of expulsion rate from T(, pyridines12 < anilines11
of T( (to formation of T() to concerted with increasing
nucleofugality of the amines from T( is generally fol-
lowed, and an inversion of the sequence has rarely been
observed.
The stepwise mechanism predicted for 6 and 7 with
anilines in water is, however, in contrast to the concerted
mechanism found for the aminolysis of 6 with anilines
in acetonitrile.5 The solvent change from water to a less
polar solvent, MeCN, thus causes a mechanistic change
for 6 from stepwise in water to concerted in MeCN. The
change of solvent from water to acetonitrile destabilizes
the zwitterionic intermediate resulting in an increase in
the rate of expulsion of amines from T(. The lower
stability of T( leading to the higher expulsion rate of a
given amine from T( in a less polar solvent compared to
a more polar one is due to the zwitterionic nature of T(.
Mechanistic changes from stepwise to concerted incurred
by a solvent change from water to acetonitrile are often
observed. An example is the aminolysis of O-ethyl aryl
dithiocarbonate (EtO-C(dS)‚SAr), which proceeds by a
stepwise mechanism with pyridines8 and secondary ali-
cyclic amines21 in water but concertedly with anilines14
and benzylamines22 in acetonitrile. As noted above,
anilines should also react by the stepwise mechanism in
water since the expulsion rate of aniline is less than that
of the secondary alicyclic amines. Similarly, the aminoly-
sis of O-ethyl 2,4,6-trinitrophenyl dithiocarbonate is
stepwise with a biphasic plot in water, but is concerted
(âX ) 0.53) in a less polar solvent (44 wt % EtOH-H2O).23
This was attributed to the enhanced expulsion rate of
the amine from T( in the less polar solvent while the
nucleofugality of the leaving group remains practically
unaffected by the solvent nature resulting in the more
destabilized T( kinetically in the less polar solvent.23
It is therefore highly likely that the aminolysis of 7
with anilines in acetonitrile also proceeds by a concerted
mechanism.
We propose a concerted mechanism for the aminolysis
of aryl chlorothionoformate, 7, in acetonitrile on the
following grounds: (i) The rate sequence for the phenoxy
series, k2 (6 with CdO) > k2 (7 with CdS) in acetonitrile,
is a reverse of that for the alkoxy series, k2 (1 with CdO)
< k2 (3 with CdS) in water, reflecting a mechanistic
change from a rate-limiting formation of T( for the alkoxy
series in water to a concerted mechanism for the phenoxy
series in acetonitrile. A change of CdO to CdS leads to
a decrease in push provided to expel the leaving group,
Cl-, in the tetrahedral TS (8b), and this will result in a
decrease in the rate of the concerted process for 7 relative
to 6.4,8 Of course, the same rate decrease may be expected
from the intermediate, T( (8a), in a rate-limiting break-
down of T(. However, the stepwise mechanism with rate-
limiting breakdown of T( has never been found, either
for 6 or for 7 in water or in acetonitrile with any type of
amines. The stepwise mechanism with rate-limiting
formation of T( has been reported for 7 with pyridines
in water.4b Pyridines are known to have a stronger ability
to stabilize the intermediate, T(, than anilines,11 and
< secondary alicyclic amines13 < quinuclidines10a
<
(benzylamines).14 A gradual shift of mechanism was
observed from stepwise to concerted as the expulsion rate
of amine from T( increased: For the aminolyses with
pyridines both 9a and 9b were found to react by a
stepwise mechanism,11 whereas those with secondary
alicyclic amines13 and quinuclidines10a proceed by a
concerted mechanism. Quite interestingly, the aminolysis
with anilines12 is stepwise with 9a but is concerted with
9b, which should form a less stable intermediate than
9a due to the stronger nucleofugality of the trini-
trothiophenolate in 9b than the dinitrothiophenolate
leaving group in 9a. The aminolysis with benzylamines14
is also concerted (in acetonitrile). Similarly, the aminoly-
sis of aryl dithioacetates, 10, in acetonitrile is stepwise
with pyridines15 (with a change of the rate-limiting step
from breakdown, âX ) 0.9, to formation, âX ) 0.4, of T()
and anilines16 (with rate-limiting breakdown of T(, âX )
0.84), but is concerted with benzylamines16 (âX ) 0.55).
The aminolysis of 10 with secondary alicyclic amines17
was found to proceed by rate-limiting formation of T( in
water. Another interesting case is the aminolysis of aryl
dithiobenzoates (YC6H4C(dS)‚SC6H4Z) in acetonitrile.18-20
The intermediates, T(, are so stable that the reactions
are stepwise all the way from pyridines through anilines
to benzylamines in the increasing order of nucleofugality
of amines from T(. However, there is a subtle shift of
the rate-limiting step from biphasic plots with a change
of the rate-determining step from breakdown (âX ) 0.8)
to formation (âX ) 0.2) of T( with pyridines,18 to the
simple rate limiting breakdown of T( with anilines (âX
) 0.8),19 and to the rate-limiting formation of T( with
benzylamines (âX ) 0.24).20 Thus, the shift of aminolysis
mechanism from stepwise with rate-limiting breakdown
(11) Castro, E. A.; Leandro, L.; Millan, P.; Santos, J. G. J. Org.
Chem. 1999, 64, 1953.
(12) Castro, E. A.; Pizarro, M. I.; Santos, J. G. J. Org. Chem. 1996,
61, 5982.
(13) (a) Castro, E. A.; Ibanez, F.; Salas, M.; Santos, J. G. J. Org.
Chem. 1991, 56 4819. (b) Castro, E. A.; Salas, M.; Santos, J. G. J. Org.
Chem. 1994, 59, 30.
(14) (a) Oh, H. K.; Lee, Y. H.; Lee, I. Int. J. Chem. Kinet. 2000, 32,
131. (b) Oh, H. K.; Lee, J.-Y.; Park, Y. S.; Lee, I. Int. J. Chem. Kinet.
1998, 30, 419.
(15) Oh, H. K.; Ku, M. H.; Lee, H. W.; Lee, I. J. Org. Chem. 2002,
67, 3874.
(16) Oh, H. K.; Woo, S. Y.; Shin, C. H.; Park, Y. S.; Lee, I. J. Org.
Chem. 1997, 62, 5780.
(17) Castro, E. A.; Ibanez, F.; Santos, J. G.; Ureta, C. J. Chem. Soc.,
Perkin Trans. 2 1991, 1919.
(18) Oh, H. K.; Lee, J. M.; Lee, H. W.; Lee, I. Int. J. Chem. Kinet.
2004, 36, 434.
(21) Castro, E. A.; Ibanez, F.; Salas, M.; Santos, J. G.; Sepulveda,
P. J. Org. Chem. 1993, 58, 459.
(19) Oh, H. K.; Shin, C. H.; Lee, I. J. Chem. Soc., Perkin Trans. 2
1995, 1169.
(22) Oh, H. K.; Oh, J. Y.; Sung, D. D.; Lee, I. Collet. Czech. Chem.
Commun. In press.
(20) Oh, H. K.; Shin, C. H.; Lee, I. Bull. Korean Chem. Soc. 1995,
16, 657.
(23) Castro, E. A.; Cubillos, M.; Munoz, G.; Santos, J. G. Int. J.
Chem. Kinet. 1994, 26, 571.
J. Org. Chem, Vol. 69, No. 24, 2004 8221

Oh et al.
TABLE 2. The Secondary Kinetic Isotope Effects for
the Reactions of Y-Phenyl Chlorothionoformates with
Deuterated X-Anilines (XC6H4ND2) in Acetonitrile at 5.0
°C
TABLE 3. Activation Parametersa for the Reactions of
Y-Phenyl Chlorothionoformates with X-Anilines in
Acetonitrile
X
Y
∆H*/kcal mol-1
-∆S*/cal mol-1 K-1
X
Y
kH (×10 M-1s-1
)
kD (×10 M-1s-1
5.68 ((0.05)
8.45 ((0.07)
17.7 ((0.2)
38.3 ((0.5)
0.332 ((0.002) 1.51 ( 0.02
0.442 ((0.005) 1.58 ( 0.02
0.791 ((0.006) 1.67 ( 0.02
)
kH/kD
p-OMe
p-OMe
p-Cl
p-OMe
p-Cl
p-OMe
p-Cl
3.9
4.1
3.8
4.0
45
47
50
47
p-OMe p-OMe 8.41 ((0.07)
1.48 ( 0.02a
1.55 ( 0.02
1.61 ( 0.03
1.69 ( 0.03
p-OMe p-Me
p-OMe
p-OMe p-Cl
p-Cl
p-Cl
p-Cl
p-Cl
13.1 ((0.1)
28.5 ((0.3)
64.7 ((0.1)
H
p-Cl
a Calculated by the Eyring equation. The maximum errors
calculated (by the method of Wiberg: Wiberg, K. B. Physical
Organic Chemistry; Wiley, New York, 1964; p 378) are (0.9 kcal
mol-1 and (3 eu for ∆H* and ∆S*, respectively.
p-OMe 0.502 ((0.005)
p-Me
H
0.698 ((0.007)
1.17 ((0.02)
2.68 ((0.06)
p-Cl
1.57 ((0.02)
1.71 ( 0.04
a Standard deviations.
(7) has a greater degree of bond formation (larger
magnitude of FX and âX) with a lower degree of leaving
many of the aminolyses of esters and carbonates (but not
phenyl chloroformates) with pyridines are reported to be
the stepwise mechanism with rate-limiting breakdown
group expulsion (larger FY) so that overall the TS is
6
tighter (larger magnitude of FXY
)
than the carbonyl
series, 6. (v) The activation parameters, ∆H* and ∆S*
in Table 3, are consistent with the proposed mechanism.
The ∆H* values are small due to the assistance in the
C-Cl bond cleavage by the hydrogen bonding in 11, and
the ∆S* values are large negatives due to the strained
hydrogen bonded cyclic TS structure.
of T( 10b. (ii) The sign of FXY for 7 is negative (FXY
)
-0.77), which is a necessary condition for the concerted
reactions10b,24 as it was found for the concerted reaction
with 6 (FXY ) -0.04).5 A further increase of push provided
to expel Cl- by the nonleaving acyl group with PhN(CH3)
(σp ) -0.56, σp+ ) -1.40 for PhNH)7 in PhN(CH3)C(dO)Cl
Reference to Table 1 reveals that the âX values are 0.9-
1.0, which are rather larger compared to the values
normally expected for the concerted aminolysis reactions,
âX ) 0.4-0.7.10a However, âX values smaller than 0.427
and larger than 0.728 have also been reported for the
concerted aminolysis reactions. Especially in solvents less
polar than water, larger âX values (1.3-1.6) are often
observed for the concerted processes.29 Therefore the
large âX values obtained in the present work may well
be due to the less polar solvent used, MeCN. The
relatively large âX values are, however, consistent with
the rather tight TS structure predicted with a tighter
bond formation.
We conclude that the aminolysis of aryl chlorothionofor-
mates, 7, with anilines in acetonitrile proceeds by a con-
certed mechanism with a four-membered hydrogen bonded
cyclic TS structure. The mechanism is the same as that
of the carbonyl analogue, 6, but the thiono series, 7, lacks
a strong push to expel the leaving group in the TS, unlike
with 6, and the TS structure differs between the two
series, 8b for 6, but 11 for 7. It is noteworthy that while
the aminolyses of both 6 and 7 with secondary alicyclic
amines (and also with anilines) in water are stepwise,
those of 6 and 7 with anilines are concerted in acetonitrile.
25
also leads to a concerted process in acetonitrile with
FXY ) -0.14. (iii) The rate (k2) and selectivity data (FX,
âX, and FY) show that a faster rate is accompanied by a
stronger selectivity, i.e., the reactivity-selectivity prin-
ciple (RSP) does not hold.10b,24 This type of anti-RSP is
considered as another criterion for the concerted mech-
anism.10b,24 (iv) The kinetic isotope effects (KIEs), kH/kD,
involving deuterated nucleophiles26 (XC6H4ND2) are nor-
mal, i.e., kH/kD > 1.0 in Table 2. This is not consistent
with the rate-limiting bond formation in a stepwise
mechanism, since in such cases inverse KIEs are ex-
pected due to the increased N-H(D) vibrational frequen-
cies in the more crowded TS.26 Such inverse KIEs were
indeed found for 6 in acetonitrile.5 For the thiono
analogue (7; CdS) the push provided to expel the leaving
group (Cl-) is weaker than that for the carbonyl com-
pounds (6; CdO), and hence the hydrogen bonding by the
N-H(D) proton toward the Cl- ion to assist the leaving
group expulsion may be needed. We therefore propose a
four-membered cyclic TS structure in a concerted process
for the present reaction series, 11. The TS proposed is
Experimental Section
Materials. GR grade acetonitrile was used after three
distillations. GR grade aniline nucleophiles were used after
recrystallization.
Preparation of Phenyl Chlorothionoformates. Phenyl
chlorothionoformates were prepared by the literature method
of Hill, Thea, and Williams.30 A solution of phenol (67 mmol)
in 5% NaOH (60 mL) was added to a solution of thiophosgene
(67 mmol) in chloroform (40 mL). The reaction was stirred for
1 h at 0-5 °C and the chloroform layer washed with dilute
supported by larger magnitudes of FX (-2.55 to -2.94),
âX (0.90 to 1.04), FY (1.29 to 1.79), and FXY (-0.77) for 7
(Table 1) than the corresponding values for 6, FX (-2.27
to -2.30), âX (0.79 to 0.80), FY (1.20 to 1.26), and FXY
(-0.04), indicating that the TS with 7 (11) has a much
tighter structure than that with 6 (8b); the thiono series
(27) (a) Skoog, M. T.; Jencks, W. P. J. Am. Chem. Soc. 1984, 106,
7597. (b) Bourne, N.; Williams, A. J. Am. Chem. Soc. 1984, 106, 7591.
(28) (a) Ba-Saif, S.; Luthra, A. K.; Williams, A. J. Am. Chem. Soc.
1989, 111, 2647. (b) Colthurst, M. J.; Nanni, M.; Williams, A. J. Chem.
Soc., Perkin Trans. 2 1996, 2285.
(29) (a) Maude, A. B.; Williams, A. J. Chem. Soc., Perkin Trans. 2
1997, 179. (b) Castro, E. A.; Cubillos, M.; Santos, J. G. J. Org. Chem.
1998, 63, 6820.
(24) Lee, I.; Lee, H. W. Collect. Czech. Chem. Commun. 1999, 64,
1529.
(25) Koh, H. J.; Lee, H. C.; Lee, H. W.; Lee, I. Bull. Korean Chem.
Soc. 1996, 17, 712.
(26) Lee, I. Chem. Soc. Rev. 1995, 24, 223.
8222 J. Org. Chem., Vol. 69, No. 24, 2004

Aminolysis of Aryl Chlorothionoformates
HCl and water. Solvent was removed under reduced pressure
and product was separated by column chromatography (silica
gel, 10% ethyl acetate-n-hexane) (yield >85%). IR (Nicolet
5BX FT-IR) and 1H and 13C NMR (JEOL 400 MHz) data were
found to agree well with the literature value.30
Kinetic Measurement. Rates were measured conductome-
trically in acetonitrile. The conductivity bridge used in this
work was a homemade computer-automatic A/D converter con-
ductivity bridge. Pseudo-first-order rate constants, kobs, were
determined by the Guggenheim method with a large excess of
aniline. Second-order rate constants, kN, were obtained from
the slope of a plot of kobs vs [AN] with more than five concen-
trations of aniline. The kN values in Table 1 are the averages
of more than three runs and were reproducible within (3%.
Product Analysis. The substrate p-methoxyphenyl chlo-
rothionoformate (0.05 mol) was reacted with excess aniline (0.5
mole) with stirring for more than 15 half-lives at 5.0 °C in
acetonitrile and the products were isolated by evaporating the
solvent under reduced pressure. The product mixture was sub-
jected to column chromatography (silica gel, 20% ethyl acetate-
n-hexene). Analysis of the product gave the following results.
p-MeO-C6H4OC(dS)NHC6H5: liquid; 1H NMR(400 MHz,
CDCl3) δ 3.80 (3H, s, CH3), 6.51 (1H, s, NH), 7.05-7.54 (9H,
m, C6H4, C6H5); 13C NMR (100.4 MHz, CDCl3) δ 192.1, 157.7,
147.3, 143.3, 129.5, 127.9, 122.4, 114.5, 114.2, 55.6; νmax(KBr)
3255 (NH), 3056 (CH, aromatic), 2836 (CH, CH3), 1598 (CdC,
aromatic), 1382 (C-N), 1241 (CdS), 1130 (C-O); MS m/z 259
(M+). Anal. Calcd for C14H13NO2S: C, 64.8; H, 5.11. Found; C,
64.6; H, 5.12.
Acknowledgment. This work was supported by a
Korea Research Foundation grant (KRF-2002-070-
C00061).
(30) Hill, S. V.; Thea, S.; Williams, A. J. Chem. Soc., Perkin Trans.
2 1983, 437.
JO0487247
J. Org. Chem, Vol. 69, No. 24, 2004 8223