Kinetics and mechanism of the aminolysis of aryl N-ethyl thiocarbamates in acetonitrile

Article abstract of DOI:10.1021/jo0484676

The aminolysis of aryl N-ethyl thiocarbamates (EtNHC(=O)SC ₆H₄Z) with benzylamines (XC₆H ₄-CN₂NH₂) in acetonitrile at 30.0 °C is investigated. The rates are faster than the corresponding values for aryl N-phenyl thiocarbamates (PhNHC(=O)SC₆H₄Z), reflecting a stronger push to expel the leaving group by EtNH than the PhNH nonleaving group in a concerted process. The negative ρ_XZ (-0.86) and failure of the reactivity-selectivity principle found are consistent with the concerted mechanism. The kinetic isotope effects involving deuterated nucleophiles (k _H/k_D = 1-5-1.7) and low ΔH? with large negative ΔS? values suggest a hydrogen bond cyclic transition state.

Full text of DOI:10.1021/jo0484676

Kinetics and Mechanism of the Aminolysis of Aryl N-Ethyl
Thiocarbamates in Acetonitrile
Hyuck Keun Oh,† Jie Eun Park,† Dae Dong Sung,‡ and Ikchoon Lee*,‡,§
Departments of Chemistry, Chonbuk National University, Chonju 560-756, Dong-A University,
Busan 604-714, and Inha University, Inchon 402-751, Korea
ilee@inha.ac.kr
Received August 31, 2004
The aminolysis of aryl N-ethyl thiocarbamates (EtNHC(dO)SC6H4Z) with benzylamines (XC6H4-
CN2NH2) in acetonitrile at 30.0 °C is investigated. The rates are faster than the corresponding
values for aryl N-phenyl thiocarbamates (PhNHC(dO)SC6H4Z), reflecting a stronger push to expel
the leaving group by EtNH than the PhNH nonleaving group in a concerted process. The negative
F
XZ (-0.86) and failure of the reactivity-selectivity principle found are consistent with the concerted
mechanism. The kinetic isotope effects involving deuterated nucleophiles (kH/kD ) 1.5-1.7) and
low ∆Hq with large negative ∆Sq values suggest a hydrogen bond cyclic transition state.
Introduction
The aminolysis mechanism of aryl carbamates 1 is
quite similar to that of aryl carbonates 2 and aryl esters
3. A change in the mechanism of the aminolysis with
Although there is abundant literature on the kinetics
and mechanism of the aminolysis of aryl carbonates1 and
esters,2 the aminolysis reactions of aryl carbamates3 have
been less studied kinetically. The mechanism of the
aminolysis of substituted diphenyl carbonates has been
studied, and structure-reactivity relationships have been
examined in detail by Gresser and Jencks.1a. Castro and
co-workers have reported a number of mechanistic stud-
ies on the aminolysis of aryl carbonates1c-f and esters.2h-l
These and other studies showed that most of the ami-
nolysis of aryl carbonates and esters proceed by either a
stepwise mechanism through a zwitterionic tetrahedral
intermediate, T(, or concertedly, depending on the amine,
substrate, and solvent involved.
benzylamines in acetonitrile has been observed from
stepwise through a tetrahedral intermediate, T(, to
concerted for the carbamates3a,b 1 (with R ) Ph) as well
as for the carbonates4 2 (with R ) Et) when the leaving
group is changed from phenoxide (a, -OAr) to thio-
phenoxide (b, -SAr). This suggests that the strength of
* To whom correspondence should be addressed. Phone: +82-32-
860-7681. Fax: +82-32-865-4855.
† Chonbuk National University.
‡ Dong-A University.
§ Inha University.
(1) (a) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99,
6963. (b) Castro, E. A.; Gil, F. J. J. Am. Chem. Soc. 1977, 99, 7611. (c)
Castro, E. A.; Aliaga, M.; Campodonico, P.; Santos, J. G. J. Org. Chem.
2002, 67, 8911. (d) Castro, E. A.; Andujar, M.; Toro, A.; Santos, J. G.
J. Org. Chem. 2003, 68, 3608, 5930. (e) Castro, E. A.; Cubillos, M.;
Santos, J. G. J. Org. Chem. 2001, 66, 6000. (f) Bond, P. M.; Moodie, R.
B. J. Chem. Soc., Perkin Trans. 2 1976, 679. (g) Shawali, A. S.;
Harhash, A.; Sidky, M. M.; Hassanen, H. M.; Elkaabi S. S. J. Org.
Chem. 1986, 51, 3498.
(2) (a) Satterthwait, A. C.; Jencks, W. P. J. Am. Chem. Soc. 1974,
96, 7018. (b) Campbell, P.; Lapinskas, B. A. J. Am. Chem. Soc. 1977,
99, 5378. (c) Oh, H. K.; Shin, C. H.; Lee, I. Bull. Korean Chem. Soc.
1995, 16, 657. (d) Oh, H. K.; Woo, S. Y.; Shin, C. H.; Park, Y. S.; Lee,
I. J. Org. Chem. 1997, 62, 5780. (e) Um, I.-H.; Kwon, H.-J.; Kwon,
D.-S.; Park, J.-Y. J. Chem. Res., Synop. 1995, 301; J. Chem. Res.,
Miniprint 1995, 1801. (f) Um, I.-H.; Choi, K.-E.; Kwon, D.-S. Bull.
Korean Chem. Soc. 1990, 11, 362. (g) Castro, E. A.; Ureta, C. J. Chem.
Soc., Perkin Trans. 2 1991, 63. (h) Castro, E. A.; Araneda, C. A.; Santos,
J. G. J. Org. Chem. 1997, 62, 126. (i) Castro, E. A.; Ureta, C. J. Org.
Chem. 1990, 55, 1676. (j) Castro, E. A.; Ureta, C. J. Org. Chem. 1989,
54, 2153. (k) Castro, E. A.; Santander, C. L. J. Org. Chem. 1985, 50,
3595. (l) Neuvonen, H. J. Chem. Soc., Perkin Trans. 2 1995, 951.
(3) (a) Koh, H. J.; Kim, O. K.; Lee, H. W.; Lee, I. J. Phys. Org. Chem.
1997, 10, 725. (b) Oh, H. K.; Park, J. E,; Sung, D. D.; Lee, I. J. Org.
Chem. 2004, 69, 3150. (c) Menger, F. M.; Glass, L. E. J. Org. Chem.
1974, 39, 2469.
push provided to expel the leaving group from T( by
PhNH is similar to that by EtO, and the destabilization
of T( due to this push is strong enough for -SAr but is
too weak for -OAr to lead the aminolysis to a concerted
process.
To pursue further the mechanistic similarities be-
tween carbamates and carbonates, we carried out
kinetic studies on the aminolysis of aryl N-ethyl thio-
carbamates (AETC, EtNHC(dO)SC6H4Z) with benzyl-
amines in acetonitrile, eq 1. The primary purpose of this
(4) (a) Koh, H. J.; Lee, J.-W.; Lee, H. W.; Lee, I. Can. J. Chem. 1998,
76, 710. (b) Oh, H. K.; Lee, Y. H.; Lee, I. Int. J. Chem. Kinet. 2000, 32,
131.
10.1021/jo0484676 CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/23/2004
J. Org. Chem. 2004, 69, 9285-9288
9285

Oh et al.
TABLE 1. Second-Order Rate Constants, k2 (103 dm3 mol-1 s-1 ) for the Reactions of Z-Phenyl N-Ethyl Thiocarbamates
with X-Benzylamines in Acetonitrile at 30.0 °C
a
b
X
Z ) p-Me
Z ) H
Z ) p-Cl
Z ) p-Br
FZ
âZ
p-OMe
10.1c
41.0c
6.96
11.2
26.3
39.4
1.53 ( 0.08
-0.45 ( 0.06
4.94d
20.6d
p-Me
H
p-Cl
5.99
9.79
7.36
19.9
13.9
22.2
1.38 ( 0.07
1.24 ( 0.08
-0.35 ( 0.02
-0.32 ( 0.02
4.77
15.7
4.21c
11.1c
3.06
4.23
7.51
7.74
1.01 ( 0.05
0.98 ( 0.05
-0.26 ( 0.02
-0.25 ( 0.02
2.17d
5.34d
m-Cl
2.39
3.31
-0.88 ( 0.03
0.87 ( 0.04
5.66
-1.05 ( 0.03
1.06 ( 0.02
6.01
e
FXg
-0.73 ( 0.03
0.74 ( 0.03
-1.10 ( 0.05
1.25 ( 0.11
FXZf ) -0.86
âX
a The σ values were taken from ref 8.Correlation coefficients were better than 0.997 in all cases. b The pKa values were taken from
Buckingham, J., Ed.. Dictionary of Organic Chemistry, 5th ed.; Chapman and Hall: New York, 1982. These values of âZ (in MeCN) are
estimated by multiplying âZ (in H2O) by 0.62: See footnote 13 of Oh, H. K.; Ku, M. H.; Lee, H. W.; Lee, I. J. Org. Chem. 2002, 67, 3874.
Correlation coefficients were better than 0.983 in all cases. c At 40 °C. d At 20 °C. e The σ values were taken from ref 6. Correlation
coefficients were better than 0.996 in all cases. f The correlation coefficient was 0.997. g The pKa values were taken from Fischer, A.;
Galloway,W. J.; Vaughan, J. J. Chem. Soc. 1964, 3588. Correlation coefficients were better than 0.989 in all cases. For X ) p-CH3O an
extrapolared value of 9.64 was used.
TABLE 2. Substituent Constants for RO and RNH (R )
work is to establish the aminolysis mechanism for eq 1
and to examine the effect of the nonleaving group,
EtNH-, on the mechanism. It is of much interest to
examine whether the concerted mechanism observed for
the aminolysis of aryl N-phenyl thiocarbamates (APTC,
PhNHC(dO)SC6H4Z) with benzylamines in acetonitrile3b
also applies to the corresponding reactions of AETC,
which has a stronger electron donor group, EtNH. We
varied substituents in the nucleophile (X) and leaving
group (Z), and the rate constants, k2, are subjected to a
multiple regression analysis to determine the cross-
Me, Et, and Ph) Groups6
+
σm
σp
σp
MeO
0.12
0.10
-0.27
-0.24
-0.03
-0.70
-0.61
-0.56
-0.78
-0.81
EtO
PhO
0.25
-0.50
MeNH
EtNH
PhNH
-0.21
-0.24
-0.02
-1.81
(∼-1.8)
-1.40
state (TS). Electron donor abilities (σ < 0) of the RO and
RNH groups are compared in Table 2. Since the lone pair
electrons on O (nO) and N (nN) atoms are donated to the
lowest unoccupied MO (LUMO) of the C-S bond orbital
(σ*C-S) by nO f σ*C-S and nN f σ*C-S type vicinal charge-
transfer interactions within the T( structures,6,9 the
higher the nonbonding orbital (ꢀn < ꢀn ) (and the lower
interaction constant,5
FXZ, in eq 2. For a concerted
mechanism, the sign of FXZ was found to be negative5,6
and the reactivity-selectivity principle (RSP) failed.6
log(kXZ/kHH) ) FXσX + FZσZ + FXZσXσZ
XZ ) ∂FZ/∂σX ) ∂FX/∂σZ
Results and Discussion
(2a)
(2b)
O
N
F
the σ*C-S level) the stronger the charge-transfer interac-
tion, ∆E, in eq 5, where ∆ꢀ ) ꢀσ* - ꢀn and Fnσ* is the Fock
∆E ) -2Fnσ*2/∆ꢀ
(5)
The reactions of Z-phenyl N-ethyl thiocarbamates with
X-benzylamines in acetonitrile at 30.0 °C obey a clean
second-order rate law, eqs 3 and 4, where [AETC] and
[BA] are the concentrations of aryl N-ethyl thiocarbamate
and benzylamine, respectively. The second-order rate
constants, k2, summarized in Table 1 are obtained from
a straight line plot of kobs vs [BA].
matrix element which is proportional to the overlap
integral between the two interacting orbitals, Snσ*, and
hence the stronger will become the push provided by the
RNH than the RO group to expel the leaving group. The
resonance electron donor ability (σp+) listed8 in Table 2
should roughly parallel ∆E in eq 5, since the lone pair
electrons on N or O are delocalized through the π* orbital
of the benzene ring by n f π* interaction with the
electron-deficient functional center on the σp+ scale.9 We
note that in general RNH groups are stronger electron
donors than the corresponding RO groups, and the two
alkyl groups (R ) Me and Et) have similar electron-
releasing effects, which are stronger than that for the
phenyl (R ) Ph) group. The order of increasing electron
donor ability can be given as shown in eq 6.
rate ) kobs[AETC]
kobs ) k2[BA]
(3)
(4)
The rates are ca. 2-8 times faster than the corre-
sponding aminolysis values for the APTCs.3b This rate
enhancement found with N-ethyl (AETC) relative to
N-phenyl (APTC) analogues can be attributed to the
lower steric effect and the stronger push provided by the
ethylamino (EtNH) than phenylamino (PhNH) group to
expel the leaving group from a tetrahedral structure,7
which may be either an intermediate T( or a transition
PhO < MeO = EtO , PhNH < MeNH = EtNH (6)
(8) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(9) (a) Epiotis, N. D.; Cherry, W. R.; Shaik, S.; Yates, R. L.; Bernardi,
F. Structural Theory of Organic Chemistry; Springer-Verlag: Berlin,
1977; Part 1. (b) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev.
1988, 88, 899.
(5) (a) Lee, I. Chem. Soc. Rev. 1990, 19, 317. (b) Lee, I. Adv. Phys.
Org. Chem. 1992, 27, 57.
(6) Lee, I.; Sung, D. D. Curr. Org. Chem. 2004, 8, 557.
(7) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6970.
9286 J. Org. Chem., Vol. 69, No. 26, 2004

Aryl N-Ethyl Thiocarbamate Aminolysis in Acetonitrile
TABLE 3. Kinetic Isotope Effects Involving Deuterated
Benzylamines (XC6H4CH2ND2) for the Reactions of
Z-Phenyl N-Ethyl Thiocarbamates with X-Benzylamines
in Acetonitrile at 30.0 °C
The stronger electron donor ability of the EtNH than
the PhNH group is thus reflected in the faster aminolysis
rates for AETC than for the corresponding reactions of
APTC. The alkyl and phenyl groups (R ) alkyl and Ph
in 3 lack lone pair electrons) are weak electron donors
compared to RNH and RO in 1 and 2. Thus, the push to
expel the leaving group from T( by them (3) should be
much weaker than those by RNH (1) and RO (2), and
the aminolyses were found to proceed by the stepwise
mechanism with rate-limiting breakdown of T(.10 The
electron donor ability of a phenoxy group (R ) Ph in 2)
is stronger than that of R ) alkyl and phenyl in 3, but is
lower than that of EtO (R ) Et in 2), and is much lower
than that of PhNH and/or EtNH in 1. The results of
Gresser and Jencks1a show that the aminolysis of aryl
phenyl carbonates, R ) Ph in 2, with quinuclidines in
water proceeds by a stepwise mechanism. No correspond-
ing aminolysis data with benzylamines are available for
the diaryl carbonate series, R ) Ph in 2, in water nor in
acetonitrile.
X
Z
kH (103 M-1 s-1
)
kD (103 M-1 s-1
)
kH/kD
p-OMe p-Me
p-OMe
p-OMe p-Cl
p-OMe p-Br
6.70 ((0.06)
11.2 ((0.1)
26.3 ((0.5)
29.4 ((0.6)
3.06 ((0.02)
4.23 ((0.04)
7.51 ((0.08)
7.74 ((0.06)
4.70 ((0.05)
7.32 ((0.04)
16.6 ((0.2)
17.7 ((0.2)
2.00 ((0.02)
2.63 ((0.04)
4.49 ((0.05)
4.45 ((0.04)
1.48 ( 0.02a
1.53 ( 0.02
1.58 ( 0.04
1.66 ( 0.04
1.53 ( 0.02
1.61 ( 0.03
1.67 ( 0.03
1.74 ( 0.02
H
p-Cl
p-Cl
p-Cl
p-Cl
p-Me
H
p-Cl
p-Br
a Standard deviations.
a less polar solvent destabilizes the zwitterionic inter-
mediate, resulting in an increase in the rate of expulsion
of the amines from T(, and rendering the intermediate
more unstable kinetically.11c,14
It is also known that the carbonyl group (CdO) has a
greater proclivity for the concerted mechanism than the
thiocarbonyl group (CdS)15 due to a narrower energy gap
between the π* and σ* levels, ∆ꢀ ) ꢀ(π*CdO) - ꢀ(σ*C-S) <
∆ꢀ ) ꢀ(π*CdS) - ꢀ(σ*C-S), enabling efficient mixing of the
two orbitals.6,16 For example, concerted mechanisms are
found for the aminolyses of S-(2,4-dinitrophenyl)15 and
S-(2,4,6-trinitrophenyl)18 O-ethyl thiocarbonates in con-
trast to the stepwise mechanisms for the corresponding
dithiocarbonates.13
Benzylamines are reported to strongly destabilize the
intermediate,6 T(, due to their powerful nucleofugality
from T(, as the order of the increasing rate of expulsion
shows:6,19 pyridines < anilines < secondary alicyclic
amines < quinuclidines < benzylamines. These three
factors, the less polar solvent, MeCN, than water, a
carbonyl rather than a thiocarbonyl compound, and
benzylamines used in the present work, are all conducive
to the concerted mechanism.
Note that the sign of FXZ is invariably positive for
stepwise but is negative for concerted reactions.6 Since
the aminolysis of N-ethyl aryl thiocarbamates involves
a still stronger electron donor (PhNH < EtNH in Table
2) than in the corresponding concerted aminolysis reac-
tions of N-phenyl aryl thiocarbamates, it is reasonable
to expect a concerted mechanism for the present series
of reactions. Further support for the concerted mecha-
nism is provided by the negative FXZ (-0.86) obtained,5,6
and failure of the RSP.6 The selectivities (the magnitudes
of F, â, and kH/kD values in Tables 1 and 3) are greater
for the faster reactions.This type of anti-RSP is consid-
ered another criterion for the concerted aminolysis.6
Examination of Table 1 shows that the âX values are 0.7-
1.,3 which are rather larger than the values normally
Interestingly, as we move up to the stronger electron-
donating groups in the sequence shown in eq 6, EtO and
PhNH, a mechanistic change occurs from stepwise with
phenoxide (a, -OAr)3a,4a to concerted with thiophenoxide
(b, -SAr)3b,4b leaving groups. This is because the thio-
phenoxides are better leaving groups than phenoxides,
since the σ*C-S orbital is lower than the σ*C-O level and
hence is a better electron acceptor, ∆ꢀ in eq 5 is smaller,9a
and is readily broken compared to the C-O bond. For
example, the aminolysis of O-ethyl aryl carbonates (R )
Et in 2a) with benzylamines4a in MeCN is stepwise with
rate-limiting breakdown of T( (âX ) 2.4 for Z ) 4-NO2,
and FXZ ) 1.35), but the corresponding reaction of O-ethyl
aryl thiolcarbonate4b (R ) Et in 2b) is concerted (âX
)
0.6 for Z ) 4-NO2 and FXZ ) -0.47). Likewise, the
aminolysis of N-phenyl aryl carbamates (R ) Ph in 1a)
with benzylamines3a in MeCN is stepwise (âX ) 1.3, FXZ
) +1.10), but that of thiocarbamate3b analogues (R ) Ph
in 1b) proceeds by a concerted mechanism (âX ) 1.3, FXZ
) -0.63).
Mechanistic changes are often observed for the ami-
nolysis of carbonates from stepwise in water to concerted
in acetonitrile.11,12 For example, the aminolyses of aryl
chloroformates in water (with secondary alicyclic amines)
are stepwise,11c whereas the corresponding reactions in
acetonitrile (with anilines) are concerted.11b Likewise, the
aminolysis of 2,4,6-trinitrophenyl O-ethyl dithiocarbon-
ates is stepwise13 (biphasic Brønsted plot) in water, but
is concerted (âX ) 0.53) in a less polar solvent (44 wt %
aqueous ethanol).14 The change of solvent from water to
(10) (a) Koh, H. J.; Kim, S. I.; Lee, B. S.; Lee, I. J. Chem. Soc., Perkin
Trans 2 1996, 1353. (b) Oh, H. K.; Yang, J. H.; Lee, H. W.; Lee, I.
Bull. Korean Chem. Soc. 1999, 20, 1418. (c) Oh, H. K.; Yang, J. H.;
Cho, I. H.; Lee, H. W.; Lee, I. Int. J. Chem. Kinet. 2000, 32, 485. (d)
Koh, H. J.; Lee, H. C.; Lee, H. W.; Lee, I. Bull. Korean Chem. Soc.
1995, 16, 839. (e) Lee, I.; Koh, H. J. New J. Chem. 1996, 20, 131.
(11) (a) Castro, E. A.; Ruiz, M. G.; Santos, J. G. Int. J. Chem. Kinet.
2001, 33, 281. (b) Yew, K. H.; Koh, H. J.; Lee, H. W.; Lee, I. J. Chem.
Soc., Perkin Trans. 2 1995, 2263. (c) Castro, E. A.; Ruiz, M. G.; Salinas,
S.; Santos, J. G. J. Org. Chem. 1999, 64, 4817.
(15) (a) Castro, E. A. Chem. Rev. 1999, 99, 3505. (b) Castro, E. A.;
Cubillos, M.; Santos, J. G. J. Org. Chem. 1996, 61, 3501
(16) (a) Yamabe, S.; Minato, T. J. Org. Chem. 1983, 48, 2972. (b)
Lee, I.; Lee, D.; Kim, C. K. J. Phys. Chem. A 1997, 101, 879. (c) Lee,
I.; Kim, C. K.; Li, H. G.; Sohn, C. K.; Kim, C. K.; Lee, H. W.; Lee, B.-S.
J. Am. Chem. Soc. 2000, 122, 11162. (d) Lee, I. Int. Rev. Phys. Chem.
2003, 22, 263.
(17) Castro, E. A.; Ibanez, F.; Salas, M.; Santos, J. G. J. Org. Chem.
1991, 56, 4819.
(18) Castro, E. A.; Salas, M.; Santos, J. G. J. Org. Chem. 1994, 59,
30
(12) (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.
(13) Castro, E. A.; Ibanez, F.; Salas, M.; Santos, J. G.; Sepulveda,
P. J. Org. Chem. 1993, 58, 459.
(19) (a) Castro, E. A.; Munoz, P.; Santos, J. G. J. Org. Chem. 1999,
64, 8298. (b) Lee, K. S.; Adhikary, K. K.; Lee, H. W.; Lee, B.-S.; Lee, I.
Org. Biomol. Chem. 2003, 1, 1989.
(14) Castro, E. A.; Cubillos, M.; Munoz, G.; Santos, J. G. Int. J.
Chem. Kinet. 1994, 26, 571.
J. Org. Chem, Vol. 69, No. 26, 2004 9287

Oh et al.
TABLE 4. Activation Parametersa for the Reactions of
Z-Phenyl N-Ethyl Thiocarbamates with X-Benzylamines
in Acetonitrile
nolysis of aryl N-ethyl thiocarbamates with benzylamines
in acetonitrile on the basis of the negative cross-interac-
tion constant, failure of RSP, kinetic isotope effects
greater than unity, and relatively low ∆Hq values with
large negative ∆Sq values. The five conducive factors for
the concerted aminolysis mechanism for the present
reaction series are (i) a strong (strongest) push provided
to expel ArS- by the nonleaving group, EtNH, (ii)
destabilization of the intermediate, T(, by a powerful
expulsion rate of the benzylamine from T(, (iii) the
greater leaving ability of -SAr than -OAr due to the
greater electron acceptor ability of the σ*C-S than the
σ*C-O bond orbital, (iv) the instability of the intermediate,
T(, in a less polar solvent, MeCN, than in water due to
the ionic nature of T(, and (v) the greater proclivity of
the carbonyl (CdO) than the thiocarbonyl (CdS) group
for the concerted mechanism due to a relatively narrow
energy gap between the π*CdO and σ*C-S orbitals, ∆ꢀ )
ꢀπ* - ꢀσ* ) small.
X
Z
∆Hq (kcal mol-1
)
-∆Sq (cal mol-1 K-1
)
p-OMe
p-OMe
p-Cl
p-Me
p-Br
p-Me
p-Br
5.8
5.6
5.4
5.8
49
47
52
48
p-Cl
a Calculated by the Eyring equation. The maximum errors
calculated (by the method of Wiberg, K. B. Physical Organic
Chemistry; Wiley: New York, 1964; p 378) are (1.0 kcal mol-1
and (4 eu for ∆Hq and ∆Sq, respectively.
expected for the concerted aminolysis reactions, âX ) 0.4-
0.7.17,20 However, âX values smaller than 0.421 and larger
than 0.722 have also been obtained for the concerted
aminolysis reactions. Especially in solvents less polar
than water, larger âX values (1.3-1.6) are often obtained
for the concerted processes.23 Thus, the large âX values
in the present work may be due to the less polar solvent
used, MeCN. The relatively large âX values are however
consistent with the rather tight TS structure with a
tighter bond formation. The âZ values in Table 1 are
within the range of values that are expected for a
concerted aminolysis reaction.20b,24
Experimental Section
Materials. GR-grade acetonitrile was used after three
distillations. GR-grade benzylamine nucleophiles were used
after distillation.
Substrates. Phenyl N-Ethyl Thiocarbamate. A solution
of thiophenol (0.01 mol) in dry toluene (10 mL) was added to
a solution of ethyl isocyanate (0.01 mol). A catalytic quantity
(0.5 mL) of pyridine was added and the solution refluxed for
1 h. On evaporation of the solvent in vacuo, the thiocarbamate
precipitated and was recrystallized from chloroform-pentane.
The other substituted phenyl N-ethyl thiocarbamates were
prepared in an analogous manner and recrystallized from
chloroform-pentane. The substrates synthesized were con-
firmed by spectral and elemental analysis (Supporting Infor-
mation).
The kinetic isotope effects, kH/kD, involving deuterated
benzylamines25 (XC6H4CH2ND2) in
Table 3 are larger than 1.0 (1.5-1.7), suggesting a
proton transfer in the TS, which in turn suggests a
hydrogen-bonded cyclic TS structure, 4.
Kinetic Measurement. Rates were measured conducto-
metrically in acetonitrile. The conductivity bridge used in this
work was a homemade computer automatic A/D converter
conductivity bridge.26 Pseudo-first-order rate constants, kobs
,
were determined by the Guggenheim method27 with a large
excess of benzylamine. Second-order rate constants, k2, were
obtained from the slope of a plot of kobs vs [BA] with more than
five concentrations of benzylamine. The k2 values in Table 1
are the averages of more than three runs and were reproduc-
ible to within (3%.
The relatively small ∆Hq values with large negative
∆Sq values in Table 4 are consistent with this pro-
posed TS structure. The ∆Hq values are small due to a
larger energy gain in C-N bond formation relative to
energy loss in C-S bond cleavage in the TS and the
assistance in the C-S bond cleavage by the hydrogen
bonding, and the ∆Sq values are large negative due to
the strained hydrogen-bonded four-membered cyclic TS
structure.
Product Analysis. The substrate phenyl N-ethyl thiocar-
bamate (0.01 mol) was reacted with excess p-chlorobenzyl-
amine (0.1 mol) with stirring for more than 15 half-lives
at 30.0 °C in acetonitrile (ca. 200 mL), and the products
were isolated by evaporating the solvent under reduced
pressure. The product mixture was subjected to column
chromatography (silica gel, 20% ethyl acetate-n-hexene).
Analysis of the product gave the results shown in the Sup-
porting Information.
In summary, we propose a concerted mechanism with
a hydrogen-bonded cyclic transition state for the ami-
Acknowledgment. This work was supported by
Korea Research Foundation Grant KRF-2002-070-
C00061.
(20) (a) Castro, E. A.; Leandro, L.; Millan, P.; Santos, J. G. J. Org.
Chem. 1999, 64, 1953. (b) Castro, E. A.; Pavez, P.; Santos, J. G. J.
Org. Chem. 2001, 66, 3129.
(21) Skoog, M. T.; Jencks, W. P. J. Am. Chem. Soc. 1984, 106, 7597.
(b) Bourne, N.; Williams, A. J. Am. Chem. Soc. 1984, 106, 7597.
(22) (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.
Supporting Information Available: Spectral, melting
point, and elemental analysis data for substrates and product
analysis data. This material is available free of charge via the
Internet at http://pubs.acs.org.
(23) (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.
JO0484676
(24) Stefanidas, D.; Cho, S.; Dhe-Paganon, S.; Jencks, W. P. J. Am.
Chem. Soc. 1993, 115, 1650.
(25) (a) Lee, I.; Koh, H. J.; Lee, B.-S.; Lee, H. W.; Choi, J. H. Bull.
Korean Chem. Soc. 1990, 11, 435. (b) Lee, I. Chem. Soc. Rev. 1995, 24,
223.
(26) Lee, I.; Shin, C. S.; Chung, S. Y.; Kim, H. Y.; Lee, H. W. J.
Chem. Soc., Perkin Trans. 2 1988, 1919.
(27) (a) Guggenheim, E. A. Philos. Mag. 1926, 2, 538. (b) Moor, J.
W.; Pearson, R. G. Kinetics and Mechanism, 3rd. ed.; Wiley: New York,
1981; p 71.
9288 J. Org. Chem., Vol. 69, No. 26, 2004