Structure-reactivity correlations in the aminolysis of aryl dithiomethyl- and dithiophenylacetates with anilines in acetonitrile

Article abstract of DOI:10.1039/b104295p

The kinetics and mechanism of the anilinolysis (XC6H4NH2) of dithio esters, RC(=S)SC6H4Z with R = C2H5 and C6H5CH2 are investigated in acetonitrile at 45.0 deg C. By application of various structure-reactivity correlations, selectivity parameters ρ_X, β_X, ρ_Z, β_Z and ρ_XZ are determined. The reactions are predicted to proceed stepwise with rate-limiting expulsion of the ArS^- group. The dithio ester with R = C2H5 exhibits the fastest rate and the largest positive ρ_XZ value; this is interpreted to result from the strongest electron donating ability of the ethyl group in the intermediate and a crowded tetrahedral intermediate and transition state in which the nucleophile (X) and leaving group (Z) are in close proximity due to the bulky C2H5 group. Much faster rates are observed for the thiocarbonyl (C=S) rather than carbonyl (C=O) esters in the stepwise nucleophilic substitution reactions, which may be ascribed to the lower ?*_C=S and ?*_C-LG levels than those of the corresponding antibonding levels in the carbonyl esters. The normal kinetic isotope effects, k_H/K_D > 1.0, involving deuterated anilines suggest concurrent proton transfer with the expulsion of the ArS^- leaving group in a four-center hydrogen bonded transition state.

Full text of DOI:10.1039/b104295p

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Structure–reactivity correlations in the aminolysis of aryl
dithiomethyl- and dithiophenylacetates with anilines in acetonitrile
a
a
b
b
Hyuck Keun Oh, Sun Kyung Kim, Hai Whang Lee and Ikchoon Lee*
2
a
Department of Chemistry, Chonbuk National University, Chonju, 560-756, Korea
Department of Chemistry, Inha University, Inchon, 402-751, Korea. E-mail: ilee@inha.ac.kr;
Fax: ϩ82-32-865-4855
b
Received (in Cambridge, UK) 16th May 2001, Accepted 28th June 2001
First published as an Advance Article on the web 14th August 2001
The kinetics and mechanism of the anilinolysis (XC H NH ) of dithio esters, RC(᎐S)SC H Z with R = C H and
C H CH are investigated in acetonitrile at 45.0 ЊC. By application of various structure–reactivity correlations,
selectivity parameters ρ , β , ρ , β and ρ are determined. The reactions are predicted to proceed stepwise with
rate-limiting expulsion of the ArS group. The dithio ester with R = C H exhibits the fastest rate and the largest
6
4
2
᎐
6
4
2
5
6
5
2
X
X
Z
Z
Ϫ
XZ
2
5
positive ρXZ value; this is interpreted to result from the strongest electron donating ability of the ethyl group in the
intermediate and a crowded tetrahedral intermediate and transition state in which the nucleophile (X) and leaving
group (Z) are in close proximity due to the bulky C H group. Much faster rates are observed for the thiocarbonyl
2
5
(
C᎐S) rather than carbonyl (C᎐O) esters in the stepwise nucleophilic substitution reactions, which may be ascribed
᎐ ᎐
to the lower π* and σ*C–LG levels than those of the corresponding antibonding levels in the carbonyl esters. The
C᎐S
᎐
normal kinetic isotope effects, k /k > 1.0, involving deuterated anilines suggest concurrent proton transfer with
H
D
Ϫ
the expulsion of the ArS leaving group in a four-center hydrogen bonded transition state.
Table 1. The aminolysis of all the carbonyl (I) series, except
for R = C H O (concerted, with ρ < 0), in Table 1 proceeds
through the stepwise path with rate-limiting expulsion of the
Introduction
2
5
XZ
The two common mechanisms for the aminolysis of carbonyl,
I, and thiocarbonyl, II, esters and carbonates are (i) concerted
through a tetrahedral transition state (TS) and (ii) stepwise
leaving group (with β = 1.36–2.11 and ρ > 0).
X
XZ
Another important aspect of the change of R is that the
1
through
a
tetrahedral intermediate. The latter reaction
6
cross-interaction constants, ρXZ in eqns. (2) where X and Z are
pathway can be described by eqn. (1), where R and L are non-
log (kXZ/kHH) = ρ σ ϩ ρ σ ϩ ρ σ σ
XZ X Z
(2a)
(2b)
X
X
Z
Z
(
1)
ρXZ = ∂ρ /∂σ = ∂ρ /∂σ
X
X
Z
Z
substituents in the nucleophile and leaving group, are
5
a
leaving and leaving groups, N represents an amine and Y is
either O (I) or S (II). A nonlinear Brønsted plot results from
a change in the rate-determining step, from that of kb at
exceptionally large with R = C H for the carbonyl as well as
2 5
5c
the thiocarbonyl series, which suggests that the interaction
between nucleophile (X) and leaving group (Z) is very strong in
a very tight TS structure for both carbonyl and thiocarbonyl
6
low amine basicity (with βnuc ≥ 0.8) to that of k at high amine
a
basicity (with β ≤ 0.3). Applying the steady-state condition
thio esters with R = C H only.
2 5
nuc
±
to T in eqn. (1), the equation k = k kb/(kϪa ϩ k ) ≅ (k /
This surprising result prompts us to test whether the similar
large ρXZ value persists with weakly basic amines (anilines) or
not, and to explore the possible cause for this large ρXZ value.
In this work, we performed kinetic studies on the anilinolysis
N
a
b
a
kϪa) × k = Kkb is obtained when the second step is rate-
b
limiting, and this accounts for the change in the rate-
determining step at pK Њ where k = k applies. The aminolysis
a
Ϫa
b
mechanisms naturally depend on Y, R, L, N in eqn. (1) and
of the two dithio esters with R = C H and C H CH , in
2 5 6 5 2
solvent. Fixing L (= SC H Z) and solvent (acetonitrile), we
acetonitrile at 45.0 ЊC, eqn. (3), and examined the aminolysis
mechanism applying various structure–reactivity correlations.
6
4
recently found an interesting mechanistic changeover due to
2
2,3
changes in Y (O or S), N (benzylamines or anilines) and
2–5
R (CH , C H , C H CH , C H or C H O). For example,
3
2
5
6
5
2
6
5
2
5
Results and discussion
change of Y from O to S resulted in lowering of pKaЊ
for R = CH3 and C H5 so that the rate-limiting step of the
The reactions studied in this work followed the rate law
described by eqns. (4) and (5), where S and N represent the
substrate and nucleophile, aniline, and kN is the rate constant
for anilinolysis of the substrate. The reactions were run under
pseudo-first-order conditions with a large excess of aniline
6
2a,b
aminolysis for carbonyl esters, I, with benzylamines changed
Ϫ
±
from expulsion of thiolate anion, ArS , from T (with
±
βnuc = β = 1.36 and 1.86, and ρ > 0) to formation of T (with
βX = 0.55 and 0.63 and ρXZ > 0) for thiocarbonyl esters, II,
X
XZ
2c,d
(
3)
DOI: 10.1039/b104295p
J. Chem. Soc., Perkin Trans. 2, 2001, 1753–1757
This journal is © The Royal Society of Chemistry 2001
1753

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3
Ϫ1 Ϫ1
Table 1 Rates (k /dm mol
s
) and selectivity parameters (ρ , β , ρ , β and ρ ) for the aminolysis of thiol esters, I [RC(᎐O)SC H Z], and dithio
N
X
X
Z
Z
XZ
6
4
esters, II [RC(᎐S)SC H Z], with benzylamines (XC H CH NH ) in acetonitrile
6
4
6
4
2
2
a
ρXb
βXb ρZc βZc
ρXZd
a
ρXb
βXb ρZc βZc
ρXZd Ref.
Entry
R
kN
Ref. kN
Ϫ3
1
2
3
4
5
CH3
3.93 × 10 (45.0 ЊC) Ϫ1.40 1.36 5.32 Ϫ2.21
0.90 2b
0.699 (20.0 ЊC)
9.84 (35.0 ЊC)
Ϫ0.56 0.55 1.19 Ϫ0.50 0.40 2d
Ϫ2.24 2.19 2.77 Ϫ1.15 3.51 5c
Ϫ2.21 2.03 3.51 Ϫ1.38 2.05 5d
Ϫ3
C H5
7.32 × 10 (45.0 ЊC) Ϫ2.09 2.11 2.74 Ϫ1.18
2.36 5a
0.92 5b
0.27 2a
2
Ϫ3
C H CH 4.94 × 10 (55.0 ЊC) Ϫ1.50 1.55 1.61 Ϫ1.66
11.6 (25.0 ЊC)
6
5
2
Ϫ3
Ϫ1
C H5
2.51 × 10 (55.0 ЊC) Ϫ1.88 1.86 3.84 Ϫ1.63
3.82 × 10 (30.0 ЊC) Ϫ0.65 0.24 0.56 Ϫ0.24 0.50 2c
6
Ϫ2
C H O
2.18 × 10 (45.0 ЊC) Ϫ0.63 0.63 1.51 Ϫ0.63 Ϫ0.47 4a
2
5
a
b
c
d
For X = Y = Z = H. For Z = H. For X = H. For Y = H when Y is varied.
4
3
Ϫ1 Ϫ1
Table 2 The second order rate constants, kN × 10 /dm mol
s
, for the reactions of Z-aryl dithiophenylacetates with X-anilines in acetonitrile at
4
5.0 ЊC
Z
X
p-Me
H
p-Cl
p-Br
ρZa
βZb
p-OMe
6.92
16.4
56.9
71.0c
54.6
41.2
2.43 ± 0.14
Ϫ0.98 ± 0.07
c
5
.34
.07
d
d
4
p-Me
H
p-Cl
m-Cl
3.16
1.06
0.251
7.80
2.76
0.781
0.271
28.7
11.2
3.67
36.1
14.1
5.05
2.00c
1.68
1.28
Ϫ2.34 ± 0.08
2.55 ± 0.14
2.72 ± 0.15
3.11 ± 0.19
3.31 ± 0.20
Ϫ1.03 ± 0.07
Ϫ1.10 ± 0.07
Ϫ1.25 ± 0.12
Ϫ1.33 ± 0.11
0.0810
1.43
c
0
0
.0610
.0459
d
d
ρXe
βXg
Ϫ2.95 ± 0.06
Ϫ2.64 ± 0.07
Ϫ2.42 ± 0.07
ρXZf = 1.41 ± 0.31
1.04 ± 0.02
0.93 ± 0.03
0.85 ± 0.03
0.82 ± 0.03
a
b
The σ values were taken from ref. 17. Correlation coefficients were better than 0.996 in all cases. The pK values were taken from ref. 18. Z = p-Br
a
c
was excluded from the Brønsted plot for β due to an unreliable pK value. Correlation coefficients were better than 0.996 in all cases. At 35.0 ЊC.
Z
a
d
e
f
At 25.0 ЊC. The source of σ is the same as for footnote a. Correlation coefficients were better than 0.998 in all cases. Correlation coefficient was
.998. The pK values were taken from ref. 19. Correlation coefficients were better than 0.998 in all cases.
g
0
a
3
3
Ϫ1 Ϫ1
Table 3 The second order rate constants, kN × 10 /dm mol
s , for the reactions of Z-aryl dithiomethylacetates with X-anilines in acetonitrile at
4
5.0 ЊC
Z
X
p-Me
H
p-Cl
p-Br
ρZa
βZb
p-OMe
9.72
19.8
81.2
89.5
175
46.5
39.8
14.6
2.42 ± 0.17
Ϫ1.00 ± 0.01
c
c
1
9.1
d
d
5
.05
p-Me
H
p-Cl
m-Cl
4.05
1.25
0.223
8.50
3.19
0.669
0.180
38.3
13.2
3.50
2.53 ± 0.17
2.64 ± 0.08
3.08 ± 0.08
3.73 ± 0.24
Ϫ1.06 ± 0.02
Ϫ1.10 ± 0.06
Ϫ1.29 ± 0.07
Ϫ1.51 ± 0.03
3.89
0.0551
1.38
1.83c
c
0
0
.128
.0242
3.97
d
d
0.842
Ϫ2.60 ± 0.09
ρXe
βXg
Ϫ3.42 ± 0.10
Ϫ3.08 ± 0.12
Ϫ2.72 ± 0.06
ρXZf = 1.90 ± 0.26
1.20 ± 0.03
1.09 ± 0.04
0.96 ± 0.03
0.91 ± 0.04
a
b
The source of σ is the same as that for a, Table 2. Correlation coefficients were better than 0.995 in all cases. The source of pK is the same as that
a
c
d
e
for footnote b, Table 2. Correlation coefficients were better than 0.998 in all cases. At 55.0 ЊC. At 35.0 ЊC. The source of σ is the same as for
footnote a. Correlation coefficients were better than 0.998 in all cases. Correlation coefficient was 0.998. The source of pK is the same as that for
f
g
a
footnote g, Table 2.
Rate = kobs[S]
(4)
(5)
In the determination of Brønsted coefficients, βX and β , the
Z
pK values in water are used; the pK (CH CN) values for
a
a
3
kobs = k [N]
structurally similar amines are known to change in parallel with
N
5a,7
the pK (H O) values. Although the absolute β values may
a
2
Z
nucleophiles. The values of kN were obtained as the slopes of
plots of kobs against [N], and are summarized in Tables 2 and
not be reliable, the comparison of β values for different series
Z
of substrates is justified since we have determined the β values
Z
3
for aryl dithiophenyl- (R = C H CH ) and dithiomethyl-
in the same reaction medium, acetonitrile. In order to facilitate
comparisons of rates and selectivity parameters between differ-
ent substrates, (for different R groups), we have summarized
them in Table 4. First of all, the anilinolysis of O-ethyl S-aryl
6
5
2
acetates (R = C H ), respectively. In these Tables, the selectivity
parameters obtained as σ and pK dependence of the composite
rate constant k = Kk , ρ , β , ρ , β and ρXZ, are also shown.
2
5
a
N
b
X
X
Z
Z
1
754
J. Chem. Soc., Perkin Trans. 2, 2001, 1753–1757

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3
Ϫ1 Ϫ1
Table 4 Rates (k /dm mol
s ) and selectivity parameters (ρ , β , ρ , β , and ρ ) for the aminolysis of dithioesters, II [RC(᎐S)SC H Z], with
X X Z Z XZ 6 4
N
anilines (XC H NH ) in acetonitrile
6
4
2
a
ρXb
βXb
ρZc
βZc
ρXZd
0.58
1.90
1.41
Entry
R
kN
Ref.
Ϫ4
1
2
3
4
5
CH3
9.46 × 10 (50.0 ЊC)
3.19 × 10 (45.0 ЊC)
2.76 × 10 (45.0 ЊC)
2.85 × 10 (55.0 ЊC)
Ϫ3.05
Ϫ3.08
Ϫ2.64
Ϫ2.86
Ϫ1.46
0.84
1.09
0.93
1.03
0.54
1.90
2.64
2.72
2.26
0.45
Ϫ0.81
Ϫ1.10
Ϫ1.10
Ϫ0.76
Ϫ0.19
2d
Ϫ3
C H
This work
This work
3
4b
2
5
Ϫ4
C H CH
6
5
2
Ϫ3
C H
0.60
Ϫ0.56
6
5
Ϫ2
C H O
1.71 × 10 (30.0 ЊC)
2
5
a
b
c
d
For X = Y = Z = H. For Z = H. For X = H. For Y = H when Y is varied.
4b
dithiocarbonates (R = C H O) has been reported to proceed
is expected as we found for R = C H O in Tables 1 and 4
2 5
2
5
concertedly based on (i) the small magnitude of β (= 0.54) and
(entry 5).
X
β (= Ϫ0.19) values relative to those reacting stepwise with large
We find a mechanistic difference between the carbonyl (I)
(Table 1) and thiocarbonyl (II) series (Tables 1 and 4): for the
Z
1,8
6c
β (≥ 0.8) and Ϫβ (≤ Ϫ0.8) and (ii) negative ρXZ (< 0). For
X
Z
the remaining Rs (entries 1–4), the same mechanism applies
with positive ρXZ, large magnitude of β and β , and adherence
former series (I) the rate-limiting expulsion (k ) applies even up
b
2a,b
to relatively strong basic amines (benzylamines),
whereas
X
Z
6,9
to the reactivity–selectivity principle (RSP), i.e., rate-limiting
for the latter dithio series, (II), the rate-limiting step changes
Ϫ
Ϫ
±
expulsion of thiolate anion (ArS ) leaving group from the
from rate-limiting expulsion of ArS from T with weakly
2d,3
±
tetrahedral intermediate, T . Reference to Table 1 reveals that
basic amines, anilines
with strongly basic amines, benzylamines
(Table 4), to rate-limiting formation
2c,d
the rate is the fastest (k is the greatest) with R = C H among
(Table 1). This
N
2
5
the four stepwise reaction series (entries 1–4). This is also true
for the aminolysis rates of carbonyl, I, and thiocarbonyl, II,
series with benzylamines shown in Table 1. Albeit exact com-
means that the center of the Brønsted curvature for the thio-
carbonyl series, II, shifted to a lower pKa value, i.e., from
pK Њ ≥ pK = 9.51 (for p-MeO-benzylamine in H O) for the
a
a
2
parison is difficult due to the k values determined at different
carbonyl to pK Њ ≤ pK = 9.14 (for p-Cl-benzylamine in H O)
N
a
a
2
temperatures, the approximate rate order is R = C H (σ* =
for the thiocarbonyl series. The smaller pK Њ value results from
a
11
2
5
Ϫ0.10) > CH (0.0) > C H CH (ϩ0.22) > C H (ϩ0.60), which
a smaller k /k ratio (for a given amine and leaving group) for
Ϫa b
3
6
4
2
6
5
is the order of decreasing electron donating ability of the R
group represented by the Taft σ* scale as shown in paren-
the thiocarbonyl compared to the carbonyl compound. It has
been shown that the change of carbonyl to thiocarbonyl
10
11
theses. This is quite reasonable in view of the rate-limiting
decreases both kϪa and k but the decrease in k is greater.
b
Ϫ
a
Ϫ
±
expulsion of the ArS group from T , since in the tetrahedral
A similar effect has been found in the aminolysis of
p-nitrophenyl benzoate and thionobenzoate in aqueous solu-
structure only the inductive effect is expected to apply and the
greater the electron donation by R, the greater will be the
tion. The pK Њ value of greater than 11 was obtained for the
a
Ϫ
leaving ability of the ArS group (k ). If the electronic effect of
former reactions, whereas pK Њ = 9.2 was found with the latter
b
a
12
R were predominant in the bond formation step (k ), then the
reactions. Again pK Њ = 7.8 for the pyridinolysis of methyl
a
a
rate sequence should have been in the reverse order since a
stronger electron acceptor R will lead to a stronger positive
charge on the carbonyl carbon in the substrate.
2,4-dinitrophenyl carbonate shifted to pK Њ = 6.8 for the same
a
reactions with ethyl 2,4-dinitrophenyl thionocarbonate in
11
aqueous solution.
Thus, the fastest rates for aminolyses of carbonyl as well as
thiocarbonyl esters with R = C H are in line with the stepwise
mechanism with rate-limiting expulsion of ArS . The concerted
It has been shown by MO calculation that the possibility of
an acyl transfer reaction through a tetrahedral intermediate is
the greater, the lower the π* (or π* ) level and the higher the
2
5
Ϫ
C᎐O
C᎐S
᎐
᎐
13
reaction pathway predicted for R = C H O (σ* = Ϫ0.18) both
σ*C–LG level, i.e., the greater the level gap, ∆ε = ε(σ*) Ϫ ε(π*).
2
5
4b
4a
with anilines (Table 4) and benzylamines (Table 1, entry 5)
can also be explained in a similar vein: substitution of ethoxy
group destabilizes the tetrahedral intermediate so much as to
prevent the existence of the putative intermediate, and there-
fore, the mechanism changes from stepwise to enforced con-
certed. This destabilization is mainly due to a strong electron
donating effect of the ethoxy group in the TS leading to a
greater nucleofugality and faster leaving from the tetrahedral
For CH C(᎐O)Cl and CH C(᎐S)Cl at the RHF/6-31ϩG*//
3
3
14
B3LYP/6-31ϩG* level, the π* level is much lower (by ca. 1.9
C᎐S
᎐
eV) but the σ*C–Cl level is slightly lower (by ca. 0.3 eV) than the
corresponding levels of the carbonyl compound so that the
level gap, ∆ε, is much greater for the thiocarbonyl transfers.
This means that the thiocarbonyl transfer is more prone to
proceed through a tetrahedral intermediate than the carb-
onyl transfers. Since both the π* and σ*C–LG levels of thio-
C᎐S
᎐
Ϫ
intermediate of the ArS group.
carbonyl compounds are lower than the corresponding levels of
carbonyl compounds, both the initial attack on the thiocarb-
For R = CH and C H (entries 1 and 4) groups, a biphasic rate
3
6
5
dependence on the amine basicity is observed; the aminolysis
onyl π bond, C᎐S, by a nucleophile, e.g., amines, (i.e., k is
greater) and the leaving group expulsion due to electron flow
into the σ*C–LG orbital in a stepwise mechanism are more facile
᎐
a
Ϫ
proceeds stepwise with rate-limiting expulsion of ArS with
2
d,3
weakly basic anilines
(entries 1 and 4 in Table 4) but with
±
rate-limiting formation of T with strongly basic benzyl-
amines (entries 1 and 4 for the dithio series in Table 1). The
change of the rate-determining step is apparent from (i)
(i.e., k is greater) for the thiocarbonyl than the carbonyl deriv-
b
2c,d
atives. However, since the π*–σ* level gap is much narrower for
the carbonyl compound, the concerted carbonyl transfer will be
more facile for the carbonyl than the thiocarbonyl due to greater
π*–σ* mixing. Theoretically, the carbonyl transfer through a
the change in βX (and β ) from large to smaller magnitude
Z
6c
and (ii) positive ρXZ throughout. Although β ≈ 0.6 (entries
X
14
1
and 4 in Table 1) may be considered rather high for the
tetrahedral TS is found to have a lower energy barrier.
±
rate-limiting formation of T , for which β values of less
than 0.3 (β ≥ 0.3) are common and a concerted pathway
Although predictions from MO theory are applicable strictly
in the gas phase, our experimental results in acetonitrile shown
in Table 1 are in excellent agreement. Indeed, the rates for the
thiocarbonyl series are seen to be much faster than those for the
corresponding carbonyl series (comparisons are valid only for
entries 2 and 3 which have a common mechanism of the rate-
X
8
X
may seem more appropriate, we nevertheless found that βX
values come out rather high in general for the aminolysis
with benzylamines as the comparison of βX values in Table 1
with those in Table 4 shows. This prediction of rate-limiting
6c
±
formation is also based on the positive ρXZ value, since in
the concerted nucleophilic substitution reactions a negative ρXZ
limiting breakdown of T ; for entries 1 and 4, the thiocarbonyl
and carbonyl compounds have different reaction mechanisms).
J. Chem. Soc., Perkin Trans. 2, 2001, 1753–1757
1755

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An important aspect we note in Tables 1 and 4 is that the
greater than unity, i.e., primary kinetic isotope effects are
operative and the amine proton shift in the TS is implicated.
6b
magnitude of ρXZ is unusually large for R = C H (entry 2 in
2
5
both Tables). The size of ρXZ is considered to represent the
intensity of interaction in the TS between the two substituents
This means that deprotonation of the amine hydrogen takes
6
place concurrently with the expulsion (k ) of the leaving group,
b
Ϫ
in the nucleophile (X) and leaving group (Z), and hence the
larger the ρXZ, the stronger is the interaction, i.e., the closer are
the two fragments, the nucleophile and leaving group, in the TS.
In order to see whether this interpretation is correct or not and
whether the size of ρXZ is indeed inversely related to the distance
ArS . In this proposed TS structure (Scheme 2), the leaving
(
rXZ in Scheme 1) between the two, we attempted to optimize
Scheme 2
Ϫ
group departure is facilitated by a partial protonation of ArS
and therefore the activation energy required for the C–S bond
scission and reformation of the C᎐S bond may be partially
᎐
lowered. Even though the proton is transferred to thiolate
anion partially in the TS, the aniline, which is in large excess,
will become protonated eventually and the reaction proceeds as
represented by eqn. (3). The proposed TS structure (Scheme 2)
Scheme 1
≠
should lead to relatively low activation enthalpies (∆H ) and
±
≠
the MO theoretical structures of the intermediate, T , and the
substrate. This was a rather difficult endeavour since the
systems are so large that ab initio calculations, even at a
relatively low level, require extremely long computational
times and hence are very expensive. The intermediate structure
at the RHF/6-31G* level revealed that the amine, aniline, and
the leaving group, thiolate anion, are located nearer due to the
bulky ethyl group in T , especially when the ethyl group rotates
freely around the C–C bond, so that the TS structure corre-
sponding to the k step should also be crowded and the closer
distance between the two fragments, nucleophile (X) and
leaving group (Z), can be explained. For other R groups, e.g.,
with R = CH or C H CH , the structures of the intermediates
are less crowded, and hence the distance, rXZ, is greater than
that for R = C H .
large negative activation entropies (∆S ), as we have found for
all the reactions listed in Tables 1 and 4 (except for entry 5,
R = C H O). The activation parameters determined in the
2
5
15
present work by the Eyring equation are shown in Table 6. We
note that the ∆H values for the reactions of dithio compounds
≠
with R = C H are somewhat higher than the other correspond-
2
5
ing values. In addition the k /k values for this series tend to be
H
D
±
somewhat smaller than the other corresponding values. This
could be related to the relatively tight TS in which the nucleo-
phile (X) and the thiophenolate leaving group (Z) are in rather
close proximity, as the large magnitude of ρXZ suggested, so that
the protonation (on deprotonation) has progressed very little
and hydrogen bonding assistance for bond cleavage is low.
The magnitudes of the selectivity parameters in Tables 2 and
3 decrease as the rates become faster so that the reactivity–
b
3
6
5
2
2
5
9
The kinetic isotope effects, k /k , involving deuterated amine
selectivity principle (RSP) holds. This adherence to the RSP is
H
D
6b
nucleophiles (XC H ND ) have been determined in aceto-
considered another necessary condition for a stepwise acyl
transfer reaction with rate-limiting breakdown of the tetra-
6
4
2
nitrile as shown in Table 5. The k /kD values are significantly
H
6a–c
hedral intermediate.
Table 5 Kinetic isotope effects for the reactions of dithioesters, II [RC
(
᎐S)SC H Z] with deuterated X-anilines in acetonitrile at 45.0 ЊC
6 4
Conclusions
X
Z
R = C H k /k
R = C H CH k /k
6 5 2 H D
2
5
H
D
We conclude that: (i) the stepwise aminolysis reaction of carb-
onyl or thiocarbonyl esters or carbonates exhibits a positive
ρXZ, irrespective of whether the rate-determining step is form-
ation or breakdown of the tetrahedral intermediate, T . (ii)
The concerted aminolysis mechanism, on the other hand, is
a
a
p-OMe
p-OMe
p-OMe
p-OMe
p-Cl
p-Cl
p-Cl
p-Me
H
p-Cl
p-Br
p-Me
H
1.64 ± 0.02
1.47 ± 0.02
1.30 ± 0.03
1.13 ± 0.03
1.24 ± 0.02
1.13 ± 0.02
1.08 ± 0.03
1.04 ± 0.02
1.53 ± 0.02
1.39 ± 0.02
1.32 ± 0.03
1.19 ± 0.03
1.74 ± 0.02
1.66 ± 0.03
1.51 ± 0.02
1.42 ± 0.02
±
characterized by a negative ρXZ. (iii) The stepwise mechanism
is more likely to be obtained, the lower the π*C ᎐᎐ O or π*C᎐S level
᎐
p-Cl
p-Br
and the higher the σ*C–LG level, i.e., the wider the level gap
p-Cl
∆
ε = ε(σ*) Ϫ ε(π*). (iv) Since both the π* and σ* levels of the
thiocarbonyl (C᎐S) compound are lower than the correspond-
ing levels of the carbonyl (C᎐O) compound, the reactivity of
a
Standard deviations.
᎐
a
Table 6 Activation parameters for the reactions of dithioesters, II [RC(᎐S)SC H Z], with X-anilines in acetonitrile
6
4
≠
Ϫ1
≠
Ϫ1
Ϫ1
R
X
Z
∆H /kcal mol
Ϫ∆S /cal mol
K
C H
p-OMe
p-OMe
m-Cl
p-Me
p-Br
p-Me
p-Br
p-Me
p-Br
p-Me
p-Br
12.7
12.7
16.0
14.9
4.4
4.5
4.7
28
24
28
24
59
54
67
64
2
5
m-Cl
C H CH
2
p-OMe
p-OMe
m-Cl
6
5
m-Cl
4.0
a
Ϫ1
≠
≠
Calculated by the Eyring equation. The maximum errors calculated (by the method in ref. 20) are ±0.6 kcal mol and ±2 e.u. for ∆H and ∆S ,
respectively.
1
756
J. Chem. Soc., Perkin Trans. 2, 2001, 1753–1757

View Article Online
the stepwise reaction is faster for the thiocarbonyl than for
the carbonyl esters. (v) The reactivity order for the stepwise
aminolysis follows roughly the order of the electron donating
ability of the R group as represented by the Taft σ* scale with
the fastest rate for R = C H . (vi) The largest ρ value of
(400 MHz, CDCl ) δ 2.42 (3H, s, CH ), 3.12 (1H, s, NH), 3.17
3
3
13
(2H, q, CH ), 7.51–7.68 (4H, m, aromatic ring); C NMR
2
(100.4 MHz, CDCl ) δ 224.4 (C᎐S), 134.6, 133.1, 131.8, 130.2,
3
58.0, 44.6.
2
5
XZ
R = C H for the stepwise aminolysis among four R groups
Acknowledgements
2
5
(
R = CH , C H , C H CH and C H ) appears to result from
3 2 5 6 5 2 6 5
This work was supported by a Korea Research Foundation
Grant (KRF-2000-015-DP0209).
the close proximity of nucleophile (X) and leaving group (Z) in
the TS due to the steric crowding of the bulky C H group in the
2
5
±
tetrahedral intermediate T .
References
Experimental
1
(a) M. I. Page and A. Williams, Organic and Bio-organic
Mechanisms, Longman, Harlow, 1997; (b) A. Williams, Concerted
Organic and Bio-organic Mechanisms, CRC Press, Boca Raton, 2000.
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J. H. Yang, H. W. Lee and I. Lee, Bull. Korean Chem. Soc., 1999, 20,
Materials
2
Merck GR acetonitrile was used after three distillations. The
Aldrich anilines were used without further purification.
1
1
418; (c) H. K. Oh, C. H. Shin and I. Lee, Bull. Korean Chem. Soc.,
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(a) H. K. Oh, Y. H. Lee and I. Lee, Int. J. Chem. Kinet., 2000, 32,
31; (b) H. K. Oh, J. Y. Lee, J. H. Yun, Y. S. Park and I. Lee,
5c,d
Preparations and analytical data are reported elsewhere.
1
4
5
Kinetic measurements
1
Int. J. Chem. Kinet., 1998, 30, 419.
Rates were measured conductometrically in acetonitrile. Since
the anilines were in large excess, [S] ≈ 10 M and [N] = 0.02–
(a) H. K. Oh, J. H. Yang, I. H. Cho, H. W. Lee and I. Lee,
Int. J. Chem. Kinet., 2000, 32, 485; (b) H. K. Oh, S. K. Kim and
I. Lee, Bull. Korean Chem. Soc., 1999, 20, 1017; (c) H. K. Oh, S. K.
Kim, H. W. Lee and I. Lee, New J. Chem., 2001, 25, 313; (d ) H. K.
Oh, S. K. Kim, I. H. Cho, H. W. Lee and I. Lee, J. Chem. Soc.,
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(a) I. Lee, Adv. Phys. Org. Chem., 1992, 27, 57; (b) I. Lee, Chem. Soc.
Rev., 1994, 24, 223; (c) I. Lee and H. W. Lee, Collect. Czech. Chem.
Commun., 1999, 64, 1529; (d ) N. S. Isaacs, Physical Organic
Chemistry, 2nd edn., Longman, Harlow, 1995, Ch. 4.
Ϫ3
0
.45 M in eqns. (4) and (5), the proton transfer can be con-
sidered to occur to aniline, instead of thiolate anion, and the
conductivity of the medium increases with the progress of the
reaction as expressed by eqn. (3). The conductivity bridge used
in this work was a laboratory-made computer-automatic A/D
converter conductivity bridge. Pseudo-first-order rate con-
6
16
stants, kobs, were determined by the Guggenheim method.
More than 4 concentrations of aniline were used in the
determination of kN [eqn. (5)] and the kN values reported are
averages of at least two determinations with reproducibility of
7 (a) I. Lee, C. K. Kim, I. S. Han, H. W. Lee, W. K. Kim and Y. B.
Kim, J. Phys. Chem. B, 1999, 103, 7302; (b) W. J. Spillane, G. Hogan,
P. McGroth, J. King and C. Brack, J. Chem. Soc., Perkin Trans. 2,
1
996, 2099.
M. J. Gresser and W. P. Jencks, J. Am. Chem. Soc., 1977, 99, 6963,
970.
±
3ꢀ.
8
6
Product analysis
9 (a) A. Pross, Adv. Phys. Org. Chem., 1997, 14, 69; (b) E. Buncel and
H. Wilson, J. Chem. Educ., 1987, 64, 475.
0 (a) R. W. Taft, in Steric Effects in Organic Chemistry, M. S.
Newman, Ed., Wiley, New York, 1956; (b) F. Ruff and I. G.
Csizmadia, Organic Reactions, Equilibria, Kinetics and Mechanism,
Elsevier, Amsterdam, 1994, p. 191.
Substrate, phenyl dithiophenylacetate (0.05 mol) (and phenyl
dithiomethylacetate (0.05 mol)), was reacted with excess aniline
1
(
0.5 mol) with stirring for more than 15 half-lives at 45.0 ЊC in
acetonitrile, and the products were isolated by evaporating the
solvent under reduced pressure. The product mixture was
treated with column chromatography (silica gel, 20ꢀ ethyl
acetate–n-hexane). Analysis of the products gave the following
1
1 E. A. Castro, M. Cufillos, J. G. Santos and J. Tellez, J. Org. Chem.,
1
997, 62, 2512.
2 P. Campbell and B. A. Lapinskas, J. Am. Chem. Soc., 1977, 99,
378.
1
5
Ϫ1
results. IR absorptions are given in cm and NMR shifts in
13 (a) S. Yamabe and T. Minato, J. Org. Chem., 1983, 48, 2972; (b) C. K.
Kim, H. G. Li, H. W. Lee, C. K. Sohn, Y. I. Chun and I. Lee, J. Phys.
Chem. A, 2000, 104, 4069.
4 I. Lee, C. K. Kim, H. G. Li, C. K. Sohn, C. K. Kim, H. W. Lee and
B. S. Lee, J. Am. Chem. Soc., 2000, 112, 11162.
5 F. Ruff and I. G. Csizmadia, Organic Reactions, Equilibria, Kinetics
and Mechanism, Elsevier, Amsterdam, 1994, p. 141.
16 E. A. Guggenheim, Philos. Mag., 1926, 2, 538.
17 C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 91, 165.
8 Dictionary of Organic Chemistry, 5th edn., J. Buckingham, Ed.,
Chapman and Hall, New York, 1982.
9 A. Streitwieser, Jr. and C. H. Heathcock, Introduction to Organic
Chemistry, 3rd edn., Macmillan, New York, 1989, p. 693.
ppm.
1
C H CH C(᎐S)NHC H . Liquid, IR (KBr) 1606 (N–H), 1512
6
5
2
᎐
6
5
(
(
C–C, aromatic), 1492 (C᎐C, aromatic), 1461 (C–H, CH ), 1209
᎐
2
1
1
C᎐S), 705 (C–H, aromatic); H NMR (400 MHz, CDCl3)
᎐
δ 3.14 (1H, s, NH), 4.14 (2H, s, CH ), 7.36–7.51 (10H, m,
2
13
aromatic ring); C NMR (100.4 MHz, CDCl ) δ 214.2 (C᎐S),
3
1
1
1
34.6, 132.7, 131.4, 129.0, 127.4, 126.5, 124.3, 122.7, 58.1.
CH CH C(᎐S)NHC H . Liquid, IR (KBr) 2989 (C–H, CH ),
3
2
᎐
6
5
2
2
938 (C–H, CH ), 1607 (N–H), 1504 (C–C, aromatic), 1463
3
20 K. B. Wiberg, Physical Organic Chemistry, Wiley, New York, 1964,
1
(
C᎐C, aromatic), 1279 (C᎐S), 701 (C–H, aromatic); H NMR
p. 378.
᎐
᎐
J. Chem. Soc., Perkin Trans. 2, 2001, 1753–1757
1757