Kinetics and Mechanism of the Aminolysis of Phenyl Dithioacetates in Acetonitrile

Article abstract of DOI:10.1021/jo970413r

The aminolysis reactions of phenyl dithioacetates with anilines (AN), N,N-dimethylanilines (DMA), and benzylamines (BA) in acetonitrile are investigated. The mechanism is relatively simple, involving a zwitterionic tetrahedral intermediate, T^±, and is uncomplicated by the fast proton transfer step which may become rate limiting in the aminolysis of thiono and dithio esters and carbonates with poor leaving groups in water. The mechanism changes from rate-limiting expulsion of the leaving group with β_X = 0.80-0.86 and β_Z = -0.71 to -0.84 for ANs and DMAs to rate-limiting attack by the nucleophile with much smaller magnitudes of β_X and β_Z for BAs. The relatively large β_XZ values for the former series and a smaller β_XZ for the latter series support the proposed mechanistic change.

Full text of DOI:10.1021/jo970413r

5780
J . Org. Chem. 1997, 62, 5780-5784
Kin etics a n d Mech a n ism of th e Am in olysis of P h en yl
Dith ioa ceta tes in Aceton itr ile
Hyuck Keun Oh,† So Young Woo,† Chul Ho Shin,† Young Sook Park,‡ and Ikchoon Lee*,‡
Departments of Chemistry, Chonbuk National University, Chonju 560-756, Korea, and
Inha University, Inchon 402-751, Korea
Received March 5, 1997X
The aminolysis reactions of phenyl dithioacetates with anilines (AN), N,N-dimethylanilines (DMA),
and benzylamines (BA) in acetonitrile are investigated. The mechanism is relatively simple,
involving a zwitterionic tetrahedral intermediate, T(, and is uncomplicated by the fast proton
transfer step which may become rate limiting in the aminolysis of thiono and dithio esters and
carbonates with poor leaving groups in water. The mechanism changes from rate-limiting expulsion
of the leaving group with âX ) 0.80-0.86 and âZ ) -0.71 to -0.84 for ANs and DMAs to rate-
limiting attack by the nucleophile with much smaller magnitudes of âX and âZ for BAs. The
relatively large âXZ values for the former series and a smaller âXZ for the latter series support the
proposed mechanistic change.
In tr od u ction
been reported lately. The aminolysis reactions of thiol
esters (RCOSR′, IIE) and carbonates (ROCOSR′, IIC)
have been found to proceed according to eq 1 with rate-
limiting expulsion of the leaving group, R′S-, for weakly
The mechanism of aminolysis of oxyesters, IE, and
oxycarbonates, IC, has been extensively studied and is
relatively well established.1,2 In contrast only a few
works devoted to the investigation of the mechanism of
O
C
O–
C
NH+
T±
O
ka
kb
+ R′S–
R
SR′
R
C
NH+
R
SR′ +
NH
k–a
O
O
IIE
R
C
OR′
RO
C
OR′
–H+
fast
IE
IC
–H+
kd[N]
(1)
k–d
the aminolysis of their thio analogues, thiol (-SR′),1c,3
IIE and IIC, thiono4 (-C(dS)-), IIIE and IIIC, and
dithio5 (-C(dS)SR′), IVE and IVC, compounds, have
O–
O
C
fast
R
C
SR′
R
N
–SR′
N
T–
† Chonbuk National University.
‡ Inha University.
X Abstract published in Advance ACS Abstracts, August 1, 1997.
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basic nucleophiles and basic leaving groups, with large
values of ânuc (0.8-1.4) and âlg (ca. 1.0), and rate-limiting
attack of the nucleophile for basic nucleophiles and good
leaving group with small values of ânuc (0.1-0.7) and âlg
(ca. 0.3).1c,3 In this mechanism, the deprotonation of T(
(kd[N]) is slow and negligible compared to kb. Thus, the
aminolysis mechanism of the thiol derivatives is in
general similar to that of their oxy analogues, IE and
IC.1,2
However, the mechanistic behavior for the aminolysis
of thiono analogues, IIIE and IIIC, has been found to
deviate from that of oxy and thiol derivatives when the
reactions are conducted in water involving substrates
with a poor leaving group.4c,d In these latter reactions,
the kb becomes sufficiently lower to enable a competition
between the expulsion of the leaving group (OR′) from
the zwitterionic tetrahedral intermediate, T(, and the
deprotonation of T( by the amine, kd[N], leading to T-,
i.e., kb = kd[N]. The importance of the deprotonation step
(3) (a) Castro, E. A.; Ureta, C. J . Org. Chem. 1989, 54, 2153-2159.
(b) Castro, E. A.; Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991, 63-
68. (c) Castro, E. A.; Iba`n˜ez, F. ; Salas, M.; Santos, J . G. J . Org. Chem.
1991, 56, 4819-4821. (d) Lee, I.; Shin, C. S.; Lee, H. W. J . Chem.
Res. 1992, (S) 90-91, (M) 0769-0773. (e) Castro, E. A.; Salas, M.;
Santos, J . G. J . Org. Chem. 1994, 59, 30-32. (f) Castro, E. A.; Pizarro,
M. I.; Santos, J . G. J . Org. Chem. 1996, 61, 5982-5985.
(4) Campbell, P.; Lapinskas, B. A.; J . Am. Chem. Soc. 1977, 99,
5378-5382. (b) Um, I.-H.; Choi, K.-E.; Kwon, D.-S. Bull. Korean.
Chem. Soc. 1990, 11, 362-364. (c) Castro, E. A.; Iba`n˜ez, F.; Santos,
J . G.; Ureta, C. J . Org. Chem. 1993, 58, 4908-4912. (d) Castro, E. A.;
Cubillos, M.; Santos, J . G. J . Org. Chem. 1996, 61, 3501-3505.
(5) (a) Cabrera, M.; Castro, E. A.; Salas, M.; Santos, J . G.; Sepu´lveda,
P. J . Org. Chem. 1991, 56, 5324-5328. (b) Castro, E. A.; Iba`n˜ez, F.;
Santos, J . G.; Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991, 1919-
1924. (c) Castro, E. A.; Iba`n˜ez, F.; Santos, J . G.; Ureta, C. J . Org.
Chem. 1992, 57, 7024-7028. (d) Castro, E. A.; Iba`n˜ez, F.; Salas, M.;
Santos, J . G.; Sepu´lveda, P. J . Org. Chem. 1993, 58, 459-463. (e)
Castro, E. A. ; Cubillos, M.; Iba`n˜ez, F.; Moraga, I.; Santos, J . G. J .
Org. Chem. 1993, 58, 5400-5404. (f) Oh, H. K.; Shin, C. H.; Lee, I. J .
Chem. Soc., Perkin Trans. 2 1995, 1169-1173. (g) Oh, H. K.; Shin, C.
H.; Lee, I. Bull. Korean Chem. Soc. 1995, 16, 657-661. (h) Castro, E.
A.; Araneda, C. A. J . Org. Chem. 1997, 62, 126-129.
S0022-3263(97)00413-1 CCC: $14.00 © 1997 American Chemical Society

Aminolysis of Phenyl Dithioacetates in Acetonitrile
J . Org. Chem., Vol. 62, No. 17, 1997 5781
Ta ble 1. Secon d -Or d er Ra te Con sta n ts, k2 (×104 d m 3
m ol-1 s-1), for th e Rea ction s of Z-Su bstitu ted P h en yl
Dith ioa ceta tes w ith X-Su bstitu ted An ilin es a n d
N,N-Dim eth yla n ilin es in Aceton itr ile a t 50.0 °C
was also found in the aminolysis of dithio derivatives,
IVE and IVC.5a,b,c,e For example, Castro et al. reported
in the aminolysis of phenyl dithioacetate,5b CH3C-
(dS)SC6H5, and phenyl O-ethyl dithiocarbonates,5a
EtOC(dS)SC6H5, in water at 25.0 °C a general reaction
scheme, eq 1 (where -C(dO)- is replaced by -C(dS)-
and R ) CH3 and EtO, respectively, with R′ ) C6H5), with
T( and T-. Depending on the basicities of the amine,
the relative importance of the three competing steps of
T( decomposition, k-1, kb, and kd[N], varies and different
rate equations hold. When the amine is strongly basic
(pKa ) 11.24), a simple expression, eq 2, was obtained,
Z
Nu
AN
X
p-Me
H
p-Cl
153
74.6
27.4
6.42
279
146
45.8
9.65
2.72
2.45
2.03
1.58
p-Br
159
75.9
28.4
5.65
284
149
47.9
10.4
2.81
2.54
2.12
1.66
p-OMe
p-Me
H
p-Cl
p-OMe
p-Me
H
p-Cl
p-OMe
p-Me
H
33.8
14.7
4.99
0.923
57.4
27.6
7.83
1.55
1.03
0.898
0.699
0.503
64.8
30.9
9.46
1.97
118
56.9
16.0
3.47
1.50
1.33
1.06
0.795
DMA
BAa
kobs ) ka[N]
(2)
whereas when the nucleofugality of the leaving group,
SR′, is sufficiently strong, first-order dependence of kobs
on the nucleophile (amine) concentration [N], eq 3, where
p-Cl
a
At -20.0 °C.
examine whether the use of an aprotic solvent really
results in a simple reaction scheme with negligible
contribution of the deprotonation step, kd[N], in the rate-
determining step. In addition, we have determined and
compared the cross-interaction constants, FXZ and âXZ in
eqs 5 and 6,7 where X and Z refer to the substituents in
the nucleophile and leaving group, respectively, and ∆pKi
) pKi - pKH. Previous works in our laboratories have
ka
kN
)
kb ) Kkb
k-a
was observed. In other reactions,5a,b,c,e however, the
competition of the deprotonation step, kd[N], with the
leaving group expulsion, kb, becomes possible since the
kobs ) k0 + kN[N]
(3)
log(kXZ/ kHH) ) FXσX + FZσZ + FXZσXσZ
(5)
mobility of the proton in water is anomalously high, kd
= 1010 dm3 mol-1 s-1 6a
Due to the involvement of the
.
log(kXZ/kHH) ) âX ∆pKX + âZ ∆pKZ + âXZ ∆pKX ∆pKZ
proton transfer step in the rate expression, the original
simple dependence of kobs on [N], eq 3, disappears and
the simple biphasic dependence of log kobs vs pKa of the
amine basicity, i.e., either kb or ka as rate-limiting, no
longer holds. One way of circumventing the complication
incurred by the competition of the fast proton transfer
step may be to use an aprotic solvent instead of water
as a reaction medium.5f,g It is expected that the mobility
of the proton will be reduced greatly in aprotic media,
and we can disregard the kd[N] term. We therefore
conducted studies on the aminolysis mechanism of phen-
yl dithioacetates in acetonitrile varying both the leav-
ing group, -SC6H4Z, and the nucleophiles, XC6H4NH2
(AN), XC6H4N(CH3)2 (DMA), and XC6H4CH2NH2 (BA),
eq 4.
(6)
indicated that the FXZ and âXZ are both positive and the
magnitude is relatively large for the stepwise mechanism
of acyl transfer reactions involving rate-limiting break-
down of the zwitterionic tetrahedral intermediate com-
pared to that for rate-limiting formation of T(.1i,5f,g,8
Furthermore, by varying substitutents in both the nu-
cleophile and leaving group, it will be possible to examine
the effects of nucleophilicity on the magnitude of âlg (or
âZ in eq 6) and of nucleofugality on the ânuc (or âX in eq
6) value.
Resu lts a n d Discu ssion
All reactions studied obeyed the kinetic law shown in
eqs 7 and 8, where [N] is amine concentration. Plots of
2XC6H4NH2 + CH3C(dS)SC6H4Z MeCN8
also with XC6H4N(CH3)2
and XC6H4CH2NH2
CH3C(dS)NHC6H4X + +NH3C6H4X + -SC6H4Z (4)
d[P]
) kobs[Substrate]
kobs ) kN[N]
(7)
(8)
dt
X ) p-OMe, p-Me, H, or p-Cl
Z ) p-Me, H, p-Cl, or p-Br
kobs vs [N] were linear, and the kN values were obtained
from the slopes of these plots. The kN values determined
are summarized in Table 1. The rates are faster with
DMAs than with the corresponding ANs, and also are
faster with a stronger nucleophile (X ) p-OMe) and a
better nucleofuge (Z ) p-Br). These trends are in accord
with those for typical nucleophilic substitution reactions.
The Hammett FX and FZ and the Bro¨nsted âX and âZ
values are shown in Table 2. Here, FX and âX correspond
to Fnuc and ânuc, and FZ and âZ to Flg and âlg. First of all,
we note that the correlation is good for all the linear plots
The object of this work is to shed more light on the
mechanism of the aminolysis of dithioacetates by inves-
tigating the effects of substitutents in the nucleophile and
leaving group and the nature of the amine (primary vs
tertiary) on the mechanism. It is also of interest to
(6) (a) Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1. (b) Ando.
K.; Hynes, J . T. In Structure and Reactivity in Aqueous Solution.
Characterization of Chemical and Biological Systems; Cramer, C. J .;
Truhlar, D. G., Eds.; ACS Symposium Series 568; American Chemical
Society: Washington, DC, 1994; Chapter 10. (c) Robinson, B. H. In
Proton-Transfer Reactions; Caldin, E., Gold, V., Eds.; Chapman and
Hall: London, 1975; Chapter 5.
(7) (a) Lee, I. Adv. Phys. Org. Chem. 1992, 27, 57-117. (b) Lee, I.
Chem. Soc. Rev. 1994, 24, 223-229.
(8) Lee, I. Bull. Korean Chem. Soc. 1994, 15, 985-990.

5782 J . Org. Chem., Vol. 62, No. 17, 1997
Oh et al.
Ta ble 2. Ha m m ett (GX a n d GZ)a a n d Br o1n sted (âX a n d âZ)a
Coefficien ts for th e Rea ction s of P h en yl Dith ioa ceta tes
w ith An ilin es a n d N,N-Dim eth yla n ilin es in Aceton itr ile
a t 50.0 °C
and the other without the deprotonation step, clearly
shows that in aprotic solvent, MeCN, the mechanism
becomes simple with no complications arising from
participation of the rate-limiting deprotonation step.5f,g
The complex mechanism found in water is indeed due to
the anomalously fast rate of proton transfer (kd) in water.6
Another notable aspect concerning the magnitudes of âX
and âZ found in this work is that the use of the pKa values
determined in water instead of in MeCN9 seems to have
little effect on the magnitudes, since in our plots we used
the rate data in MeCN but the pKa values in water. This
suggests that although the absolute values may differ9
the relative values remain constant in H2O and CH3CN.
Nu
AN
Z
FX
âX
X
FZ
âZ
p-Me
H
p-Cl
p-Br
p-Me
H
p-Cl
p-Br
p-Me
H
p-Cl
p-Br
-3.11
-3.05
-2.90
-2.89
-3.17
-3.09
-2.96
-2.90
-0.63
-0.56
-0.48
-0.46
0.85
0.84
0.80
0.79
0.87
0.85
0.82
0.80
0.63
0.55
0.48
0.46
p-OMe
p-Me
H
p-Cl
p-OMe
p-Me
H
p-Cl
p-OMe
p-Me
H
1.66
1.76
1.90
1.95
1.73
1.82
1.94
2.00
1.09
1.12
1.19
1.28
-0.71
-0.76
-0.81
-0.82
-0.73
-0.77
-0.82
-0.84
-0.45
-0.47
-0.50
-0.55
DMA
BAb
Such a constant ∆pKa () pKCH
- pKH = 7.5) was
3CN
2O
indeed found for various amines.9b-d The values of âZ
may be significantly smaller than the values reported on
the basis of on aqueous acidities. However, we are
comparing the âZ values determined under similar
conditions.5f,g Overall, variations in the magnitudes of
both F and â (Table 2) with substituents show that a
stronger nucleophile (δσX < 0) and/or nucleofuge (δσZ >
0) lead to a decrease in the magnitude.1k,l This trend is
in accord with that observed for the aminolyses of O-ethyl
S-aryl dithiocarbonates5h (IVC with R ) Et and R′ ) Ar)
and other aryl acetates3b and carbonates.3c,e,4d In the
former reaction series for 2,4-dinitro (DN) and 2,4,6-
trinitro (TN) substituents in the S-aryl leaving group,
the observed âX values were 1.0 and 0.9, respectively.5h
In the aminolysis of CH3C(dO)SAr with Ar ) 4-nitro; 2,4-
dinitro, and 2,4,6-trinitrophenyl, the âX values observed
were 0.86, 0.85, and 0.80, respectively,3b and in the
aminolysis of EtOC(dS)OAr with Ar ) 2,4-dinitro- and
2,4,6-trinitrophenyl, the âX obtained were 0.9 and 0.8,
respectively.3f There are also some examples in the
literature of a stronger nucleophile leading to a smaller
magnitude of âZ.2b,3a,b
p-Cl
a
b
Correlation coefficents > 0.995 in all cases. At -20.0 °C,
correlation coefficents > 0.998 in all cases.
(not shown) both for the AN and DMA nucleophiles. The
straight line for DMA is parallel to that for AN and shows
a higher intercept, i.e., the tertiary amines react faster
than the primary amines toward aryl dithioacetates.
These types of behavior are well-known.1d,g,3b,f The âX
values range from 0.80 to 0.86, and the âZ values vary
from -0.71 to -0.84. The magnitudes of âX and âZ are
large and are similar to those obtained for the rate-
limiting expulsion of the leaving group from T( in the
aminolysis of phenyl dithiobenzoates (IVE with R ) C6H5
and R′ ) ZC6H4) in MeCN5f (âX ) 1.0, âZ ) -0.8), O-ethyl
S-aryl dithiocarbonates (IVC with R ) Et and R′ ) 2,4-
(NO2)2C6H3 and R′ ) 2,4,6-(NO2)3C6H2) in water (âX
)
0.9-1.0)5h and other reactive acetates (IE-IIIE)1a-g and
carbonates (IC-IIIC).2a-c For these series of reactions
with AN and DMA, there are no complications arising
from competition of the fast proton transfer from T(
leading to T-, kd[N] in eq 1, in the rate-determining step,
and the mechanism of the reactions can be described
completely by eq 9, where Ar ) C6H4Z and XN represents
amines with substitutent X. The rate-determining step
is the breakdown of T(, kb, and hence kN in eq 8 is a
complex quantity with
For the reactions with BAs, we were unable to measure
rates at the same temperature of 50.0 °C used in the
reactions with ANs and DMAs. Since the reaction
temperature was -20.0 °C, there is 70.0° temperature
difference between the two reaction series. The magni-
tudes of FX (âX) and FZ (âZ) in Table 2 are smaller than
those with the ANs and DMAs; the size should be in fact
much smaller than those at -20.0 °C if we compare them
at the same temperature of 50.0 °C, since numerical
values of all susceptibility factors decrease with increas-
ing temperature.10 Thus, the much smaller sizes of âX
and âZ suggest that the reactions with BAs proceed by
rate-limiting attack of the nucleophile, the step repre-
sented by ka in eqs 1 and 9, or by a concerted SN2 type
mechanism. This is reasonable since the basicities of the
BAs (for X ) H, pKa ) 9.35 in water) are much stronger
than those of the ANs (for X ) H, pKa ) 4.60 in water)
and DMAs (for X ) H, pKa ) 5.07 in water), ∆pK > 4. A
rough estimate of temperature dependence indicated that
at the same temperature of 50 °C âX and âZ should be
ca. 0.1-0.3 and -0.2 to -0.3, respectively.11 These
values are well within the range of values reported for
ka
kN
)
kb ) Kkb
k-a
S–
S
C
S
ka
kb
CH3 C + ArS–
CH3
SAr + XN
CH3 C SAr
(9)
k–a
+NX
+NX
T±
This conclusion is based on the following. (i) A simple
rate law, eq 8, is obeyed in all cases. (ii) The two classes
of amines, primary (AN) and tertiary (DMA), exhibit the
same behavior. If the deprotonation step, kd[N] in eq 1,
were important in the rate-determining step, the primary
amines (AN) would have followed different kinetic law
from that of the tertiary (DMA) since the latter bases
cannot form an acidic T(, and therefore there is no
deprotonation step for their reactions. (iii) The large
magnitudes of both âX and âZ.
The rate-limiting breakdown mechanism proposed
above for the aminolysis of phenyl dithioacetates in
MeCN is in sharp contrast to the complex mechanism
involving the rate-limiting deprotonation step, kd[N] in
eq 1, proposed for the aminolysis of the same substrates
in water.5b,c This difference in the mechanism, one with
(9) See for example: (a) Popovych, O.; Tomkins, R. P. T. Nonaqueous
Solution Chemistry; Wiley: New York, 1981; pp 60-65. (b) Ritchie,
C. D. In Solute-Solvent Interactions; Coetzee, J . F., Ritchie, C. D., Eds.;
Marcel Dekker: New York, 1969; Chapter 4. (c) Coetzee, J . F. Progress
in Physical. Organic Chemistry; Streitwieser, A., Taft, R. W., Eds.;
Wiley: New York, 1967; Vol. 4. pp 54-92. (d) Spillane, W. J .; Hogan,
G.; McGrath, P.; King, J .; Brack, C. J . Chem. Soc., Perkin Trans. 2
1996, 2099-2104.
(10) Klumpp, G. W. Reactivity in Organic Chmistry; Wiley: New
York, 1982; p 224.

Aminolysis of Phenyl Dithioacetates in Acetonitrile
J . Org. Chem., Vol. 62, No. 17, 1997 5783
Ta ble 3. Secon d a r y Kin etic Isotop e Effects for th e Rea ction s of P h en yl Dith ioa ceta tes w ith Deu ter a ted An ilin es
(XC6H4ND2) a t 50.0 °C a n d Ben zyla m in es (XC6H4CH2ND2) a t -20.0 °C in Aceton itr ile
Nu
AN
X
Z
kH (dm3 mol-1 s-1
)
kD (dm3 mol-1 s-1
)
kH/kD
p-OMe
p-Cl
p-OMe
p-Cl
p-OMe
p-Cl
p-OMe
p-Cl
p-Me
p-Me
p-Br
p-Br
p-Me
p-Me
p-Br
p-Br
(3.38 ( 0.21a) × 10-3
(9.23 ( 0.25) × 10-5
(1.59 ( 0.06) × 10-2
(5.65 ( 0.41) × 10-4
1.03 ( 0.02
(3.21 ( 0.21) × 10-3
(8.55 ( 0.24) × 10-5
(1.45 ( 0.06) × 10-2
(4.96 ( 0.49) × 10-4
0.93 ( 0.02
1.05 ( 0.09b
1.08 ( 0.04
1.10 ( 0.06
1.14 ( 0.14
1.11 ( 0.03
1.20 ( 0.01
1.31 ( 0.02
1.36 ( 0.03
BA
(5.03 ( 0.04) × 10-1
(4.20 ( 0.03) × 10-1
2.81 ( 0.02
2.14 ( 0.03
1.66 ( 0.02
1.22 ( 0.02
a
b
Standard deviation. Standard error.
such mechanism, i.e., the rate-limiting attack in the
stepwise mechanism or concerted.1h-m
four-center type hydrogen bond strucutre, V, in which
δ–
S
We therefore conclude that the aminolysis of phenyl
dithioacetes with anilines and N,N-dimethylanilines in
acetonitrile at 50.0 °C proceed by a stepwise mechanism
involving rate-limiting breakdown of the zwitterionic
intermediate, T(, whereas that with benzylamines in
acetonitrile changes to a mechanism with rate-limiting
attack of the substrate. This mechanistic changeover is
quite similar to the corresponding mechanistic change
observed with phenyl dithiobenzoates in acetonitrile; for
the aminolysis with ANs, the magnitudes of âX (0.8-1.1)
and âZ (-0.5 to -0.8) were large5f and with BAs they were
smaller with âX ) 0.5-0.7 and âZ ) -0.2 to -0.3.5g Thus
substitution of methyl for phenyl group in dithio com-
pounds does not cause any change in the aminolysis
mechanism. This is also true for the aminolysis of other
esters and carbonates. However, it is well-known that
substitution of ethoxy for methyl can sometimes cause
change of the aminolysis mechanism to a concerted
reaction which is enforced by the high instability caused
to T( by ethoxy (or methoxy) group.3c,e
The cross-interaction constants, FXZ and âXZ, calculated
by subjecting the rate data in Table 1 to multiple
regression analysis using eqs 5 and 6 gave FXZ (âXZ) of
0.58 (0.13) and 0.61 (0.10) for the AN and DMA series,
respectively. For the BA series the values are smaller
with 0.40 (0.08) at -20.0 °C; as noted above these values
are expected to decrease to much smaller values at 50.0
°C. The larger âXZ (and FXZ) for the rate-limiting expul-
sion of the leaving group (-SAr) compared to the âXZ (and
δ–
CH3
C
S
C6H4Z
N
H
CH2
C6H4X
V
partial proton transfer takes place leading to a relatively
large normal primary kinetic isotope effect, kH/kD
>
1.0.7b,14 It is well-known that formation of the double
CdS bond in V to expel the nucleofuge is more difficult
compared to the formation of the CdO double bond due
to a weaker π-bonding energy of the thiocarbonyl (a dπ-
pπ bond) compared to the carbonyl group (a pπ-pπ
bond).4d,15 As a result, the zwitterionic tetrahedral
intermediate, T(, becomes relatively more stable and
causes a lowering of the nucleofugality of the leaving
group. This is why there is a mechanistic change for the
aminolysis of thiono and dithio derivatives to a competi-
tive proton transfer from T(, i.e., kd[N] g kb. Thus, in
the bond-making step in V, extra push is provided by the
BA to expel the leaving group. This is supported by the
larger kH/kD values for an acceptor X (facile deprotona-
tion) and a stronger nucleofuge (greater negative charge
on S) in Table 3.
Con clu sion
F
XZ) for the rate-limiting attack of the nucleophile is
consistent with our earlier results.1i,5f,g,8 Finally we have
determined the secondary kinetic isotope effects with
deuterated nucleophiles, XC6H4ND2, and XC6H4CH2ND2,
and the results are shown in Table 3. The kH/kD values
(1.05-1.14) for the reactions with deuterated ANs are
consistent with the mechanism proposed.1h,i,5f,12 We note
that for the reactions with deuterated BAs the kH/kD
values are somewhat larger than those for the reactions
with ANs. Since in the rate-determing step the benzyl-
amine approaches to the substrate and vibrational
frequencies are expected to increase due to steric crowd-
ing in the TS, the secondary kinetic isotope effect should
be of inverse type, kH/kD < 1.0,5g,7b,13 rather than the
normal effect (kH/kD > 1.0) observed. It may be possible
that the TS in the rate-limiting attack by BA involves a
In summary, the mechanism of aminolysis of phenyl
dithioacetates in acetonitrile is relatively simple, involv-
ing only one tetrahedral intermediate, T(, and being
uncomplicated by the fast proton transfer step which may
become rate determining in the aminolysis of thiono and
dithio esters and carbonates with poorer leaving groups,
and especially when the reactions are conducted in
aqueous solution. The mechanism changes from rate-
limiting expulsion of the leaving group for anilines and
N,N-dimethylanilines to a rate-limiting attack by the
nucleophile or concerted for the more basic nucleophiles
(benzylamines).
In the stepwise (or less likely concerted) process of the
reactions with benzylamine, a four-center type TS involv-
ing a hydrogen-bonded bridged structure is suggested in
view of the relatively large deuterium kinetic isotope
effects observed with deuterated amines, XC6H4CH2ND2.
(11) Temperature coefficient of FX obtained for 10° was calculated
to be ca. 0.20 (Lee, B. C.; Yoon, J . H.; Lee, C. G.; Lee, I. J . Phys. Org.
1
1
Chem. 1994, 7, 273-279). Since the âX values are ca.
/ to / of FX,
3 4
∆âX/∆T = 0.05 for ∆T ) 10°.
(14) (a) Lee, I.; Kim, H. Y.; Kang, H. K.; Lee, H. W. J . Org. Chem.
1988, 53, 678-2683. (b) Lee, I.; Choi, Y. H.; Lee, H. W.; Lee, B. C. J .
Chem. Soc., Perkin Trans. 2 1988, 1537-1540.
(15) Hill, S. V.; Thea, S.; Williams, A. J . Chem. Soc., Perkin Trans.
2 1983, 437-446.
(12) Kim, T.-H.; Huh, C.; Lee, B.-S.; Lee, I. J . Chem. Soc., Perkin
Trans. 2 1995, 2257-2261.
(13) Yew, K. H.; Koh, H. J .; Lee, H. W.; Lee, I. J . Chem. Soc., Perkin
Trans. 2 1995, 2263-2268.

5784 J . Org. Chem., Vol. 62, No. 17, 1997
Oh et al.
CH3C(dS)SC6H4-p-Br : mp 49-50 °C; IR (cm-1, KBr), 1209
(SdO), 1071 (CO-S), 852 (phenyl); δH (CDCl3) 2.879 (3H, s,
CH3), 7.26 (2H, d, J ) 8.06 Hz), 7.61 (2H, d, J ) 8.79 Hz); δC
38.86, 125.19, 130.66, 132.84, 136.26, 232.85.
Exp er im en ta l Section
Ma ter ia ls. Anilines were Tokyo Kasei G. R. grade, and
N,N-dimethylanilines were prepared and purified by the
known method.16 Benzylamines, thiophenol, acetyl chloride,
and the Lawesson’s reagent17 used for the preparation of
substrates were Aldrich G. R. grade. Merck G. R. grade
acetonitrile was distilled three times before use. S-Phenyl
thioacetates were prepared by reacting corresponding thiophe-
nols with acetyl chloride in ether at 0-5 °C. The products
were confirmed by NMR analysis. S-Phenyl thioacetates were
dissolved in toluene and refluxed with the Lawesson’s re-
agent.17 The mixture was extracted with dichloromethane and
distilled under reduced pressure after drying. The products
Kin etic Mea su r em en ts. The reactions were followed
conductometrically under pseudo-first-order condition with
excess amounts of amine, [S] = 10-3 M, and [N] = 0.02-0.45
M. The rate constants, kN in eq 8, were obtained as described
previously.5f,g The rate constants reported were averages of
more than two determinations and were reproducible to (5%.
P r od u ct An a lysis. Phenyl dithioacetate (0.05 mol) was
reacted with aniline (0.5 M) in acetonitrile at 50.0 °C for more
than 15 half-lives. After the solvent was evaporated under
reduced pressure, anilides were separated by column chroma-
tography (hexane:ethyl acetate ) 10:1). Products for the
reactions with benzylamine were similarly obtained. Analyti-
cal data are as follows.
CH3C(dS)NHC6H5: liquid; δH (CDCl3) 2.33 (3H, s, CH3),
7.11-7.62 (5H, m, aromatic ring); δC 31.04, 128.50, 129.16,
133.15, 195.73.
CH3C(dS)NHCH2C6H5: liquid; δH (CDCl3) 2.55 (3H, s,
CH3), 3.62 (1H, br, NH), 6.00 (2H, d, CH2, J ) 5.13 Hz) 7.15-
7.65 (5H, m, aromatic ring); δC 21.35, 51.05, 127.10, 127.44,
129.05, 137.00, 198.89.
1
were identified by their H NMR, 13C NMR, and IR spectra as
follows.5b,c
CH3C(dS)SC6H5: as reported in the literature.5b
CH3C(dS)SC6H4-p -CH3: liquid; IR (cm-1, KBr), 1196
(SdO), 1098 (CO-S), 1012 (CH3), 853 (phenyl); δH (CDCl3),
2.41 (3H, s, CH3), 2.86 (3H, s, CH3), 7.28-7.33 (4H, m, aromatic
ring); δC 21.42, 38.79, 128.48, 130.36, 134.51, 140.71, 234.86.
CH3C(dS)SC6H4-p-Cl: liquid; IR (cm-1, KBr), 1209 (SdO),
1087(CO-S), 852 (phenyl); δH (CDCl3), 2.88 (3H, s, CH3), 7.33
(2H, d, J ) 8.06 Hz), 7.45 (2H, d, J ) 8.79H Hz); δC 38.77,
129.86, 132.37, 136.05, 136.78, 232.94.
Ack n ow led gm en t. We thank the Ministry of Edu-
cation of Korea for a Basic Science Research Grant
(BSRI-96-3431) and Inha University for support of this
work.
(16) Bordwell, F. G.; Boutan, P. J . J . Am. Chem. Soc., 1956, 78, 87-
91.
(17) Perderson, B. S.; Scheibye, S.; Clausen, K.; Lawesson, S. O. Bull.
Soc. Chim. Belg. 1978, 87, 293.
J O970413R