Reactions of 2,4-Dinitrophenyl 5-substituted-2-thiophenecarboxylates with R2NH/R2NH2 + in 20 Mol % DMSO(aq). Effects of 5-Thienyl Substituent and Leaving Group on the Reaction Mechanism

Article abstract of DOI:10.1002/bkcs.11857

Reactions of 2,4-dinitrophenyl 2-thiophenecarboxylate (2a–d) with R₂NH/R₂NH₂ ⁺ in 20 mol % DMSO(aq) have been studied. The reactions are overall second order, first order to the substrates, and first order to th

Full text of DOI:10.1002/bkcs.11857

Article
DOI: 10.1002/bkcs.11857
BULLETIN OF THE
S. Y. Pyun et al.
KOREAN CHEMICAL SOCIETY
Reactions of 2,4-Dinitrophenyl 5-substituted-2-thiophenecarboxylates
+
with R NH/R NH in 20 Mol % DMSO(aq). Effects of 5-Thienyl
2
2
2
Substituent and Leaving Group on the Reaction Mechanism
†,*
‡
‡
§,*
Sang Yong Pyun, Kyu Cheol Paik, Man So Han, and Bong Rae Cho
†Department of Chemistry, Pukyong National University, Pusan 608-737, South Korea.
*
E-mail: sypyun@pknu.ac.kr
‡
Department of Chemistry, Daejin University, Gyeonggi-do 11159, South Korea
§
Department of Chemistry, Korea University, Seoul 136-713, South Korea. *E-mail: chobr@korea.ac.kr
Received July 8, 2019, Accepted July 29, 2019, Published online September 5, 2019
+
Reactions of 2,4-dinitrophenyl 2-thiophenecarboxylate (2a–d) with R NH/R NH
2
in 20 mol %
2
2
DMSO(aq) have been studied. The reactions are overall second order, first order to the substrates, and first
0
order to the nucleophiles. The Brönsted plots showed downward curves with pKa = 9.5, β = 0.22–0.34,
1
and β = 0.85–0.92. The k values increased with a stronger electron-withdrawing 5-thienyl substituent
and a stronger nucleophile, whereas the k /k values remained nearly the same for all 5-thienyl substitu-
2
1
2
−1
ents. The influence of 5-thienyl substituent on the reaction rates showed excellent correlations on the
Yukawa-Tsuno plots with ρ = 1.28–2.16 and r = 0.20–0.60. The ρ value increased and r value decreased
with a stronger nucleophile, indicating an increase in the electron density at the carbonyl carbon and a
decrease in the resonance demand. From these results, a stepwise mechanism with a change in the rate-
determining step has been proposed.
Keywords: Aminolysis, Bronsted-plot, Hammett plot, Yukawa-Tsuno plot
Introduction
the aminolysis for 2,4-dinitrophenyl 2-thiophenecarboxylate
17
under the same condition. This result has been attributed to
9–11
Acyl transfer reactions from XC H C(O)OC H Y have
a change in the rds.
It was noted that the rds changed
6
4
6 4
been the subject of intensive investigation because of their
from the second to the first step when the pK of the amine
a
1–7
mechanistic diversity.
The most important question is
nucleophile was higher than that of the leaving group by
whether the reaction proceeds through a stepwise or a con-
12–15
4–5 units.
However, the electronic effect on the transi-
1–8
certed mechanism.
For example, the acyl transfer reac-
tion state on this reaction was not studied.
In this work, we have studied the reactions of
tions of aryl phenyl carbonates and 4-nitrophenyl acetate
with
mechanism.
aryloxides
proceed
through
a
concerted
2
,4-dinitrophenyl 5-substituted-2-thiophenecarboxylates
9
–11
When amine was used as the nucleophile,
+
(
(
2a–d) with R NH/R NH in 20 mol % DMSO(aq)
Equation 1). We have introduced different 5-thienyl
2
2
2
the reaction proceeded through a stepwise mechanism via a
1
2–15
Zwitterionic tetrahedral intermediate.
A change in the
substituents (2a–d) to study the electronic effect and
rate-determining step (rds) from the second to the first step
was noted by the change in the nucleophile from weakly
basic amines to strongly basic ones. Compared with large
diversity of mechanism studies on the acyl transfer reac-
tions of aryl acetates, little is known about the reactions of
heterocyclic aromatic compounds.
+
employed R NH/R NH buffer as the nucleophile to
2
2
2
keep the pH constant. All reactions proceeded through a
stepwise mechanism with a change in the rds. Compari-
son with existing data for 1a–d revealed the origin of
the change in the rds wrought by the change in the
basicity of the nucleophile.
Earlier, we reported the mechanism of the reactions of
4
-nitrophenyl 5-substituted 2-thiophenecarboxylates (1a–d)
+
16
with R NH/R NH in 20 mol % DMSO(aq). The Brön-
2
2
2
sted plots were linear with reasonable correlations. The
results have been interpreted with an addition-elimination
mechanism in which the break-down of the intermediate
(second step) is the rds. On the other hand, Um et al.
reported curved Brönsted plots with downward curvature in
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a
+b
2
Table 1. Rate constants for the aminolysis of 5-XC
at 25.0 C
4
H
2
(S)C(O)OC
6
H
3
–2,4-(NO
2
)
2
promoted by R
2
NH/R
2
NH
in 20 mol % DMSO(aq)
ꢁ
, M−
1
s
-1e,f
When X is
K
N
c
d
Amine
pKa
H (2a)
OCH (2b)
CH (2c)
Cl (2d)
3
3
1
-Formylpiperazine
7.98
8.65
9.38
9.85
10.8
11.02
3.14
14.4
15.9
74.2
143
0.710
2.43
3.69
13.3
23.1
24.5
1.90
7.0
31.2
40.8
180
389
448
Morpholine
N-(2-hydroxylethyl)-piperazine
Piperazine
7.39
10.9
38.9
53.0
62.2
3
-Methylpiperidine
Piperidine
151
a
−5
[
[
Substrate] = 5.0 × 10 M.
b
c
d
e
f
+
R
2
NH]/[R
NH] = (5.0 × 10 ) M.
a
data in 20 mol % DMSO(aq) taken from Ref. 8d.
2 2
NH ] = 1.0.
−4
[R
2
pK
Average of three or more rate constants.
Estimated uncertainty, ꢂ3%.
0
a
Results
For the aminolysis of 2a–d, the calculated pK value is 9.5,
while the values of β and β are in the range of 0.22–0.34
1
2
2
,4-Dinitrophenyl 2-thiophenecarboxylates (2a–d) were pre-
and 0.85–0.92, respectively (Figure 1 and Figure S8). The k2/
k−1 values increased with a stronger nucleophile and remained
nearly the same for all 5-thienyl substituent (Table 2).
pared by the reaction 5-substituted-2-thiophenecarboxylic
acid chloride with 2,4-dinitrophenol in the presence of Et N
in CH Cl as described. The yields of 2,4-dinitrophenoxide
3
1
8
The k values increased with a stronger nucleophile and a
2
2
1
determined by comparing the absorbance of the infinity sam-
ples from the kinetic studies with those of the authentic
aryloxides were in the range of 96–98%.
stronger the electron-withdrawing 5-thienyl substituent
(Table 3). The Brönsted plots of log k /k and log k1
2
−1
vs. pK + log(p/q) values of R NH are straight lines with
a
2
Rates of aminolysis were determined by monitoring the
increase in the absorption at the λmax = 426 nm of
2,4-dinitrophenoxide. Excellent pseudo-first order kinetics
excellent correlations (Figures 2 and 3). Their slopes (β−1 and
β1) are in the ranges of 0.58–0.63 and 0.21–0.34, respectively.
Similar β values calculated from the data in Tables 1 and 3
1
plots, which covered at least three half-lives were obtained.
Pseudo-first order rate constants (kobs) are summarized in
Tables S1–S6 (File S1, Supporting Information). The plots of
kobs vs. amine concentration are straight lines passing through
the origin, indicating that the reactions are second order, first
order to the ester and 1st order to the amine (Figures S1–S7).
The rate equation can be expressed as Equation 2. The
second-order rate constants kN were obtained either
from the slopes of straight lines or by dividing the kobs by
nucleophile concentration. The kN values for the reactions
of 2a–d are summarized in Table 1.
demonstrates the reliability of these analysis (Figures 1 and 3).
The Hammett plots for the aminolysis from 2a–d are
shown in Figure 4. The influence of the 5-thienyl substitu-
ents on the aminolysis rates could be correlated with the
Rate = kobs½2ꢀ,wherekobs = k ½nucleophileꢀ
ð2Þ
N
The rate increased with increasing in the electron-
withdrawing ability of the 5-thienyl substituent and the pKa
value of the amine (Table 1). The Brönsted plots for the
aminolysis from 2a–d showed downward curvature
0
(
Figure 1). The values of pK , β , and β that best fit with
a
1
2
Equation 3 have been calculated using a nonlinear regres-
sion analysis program.8b,19,25
À
Á
À
Á
log kN=kN0 = β pKa – pKa – logð1 + αÞ=2
0
Figure 1. Brönsted plots for the reactions of 5-XC
4
H
2
(S)C(O)
in 20 mol % DMSO(aq)
(2b, ), Cl (2d, )].
2
+
À
Á
ð3Þ
OC
6
H
3
–2,4-(NO
2
)
2
with R
2
NH/R
2
NH
2
0
ꢁ
where logα = ðβ – β Þ pKa – pKa
2
1
at 25.0 C [X = H (2a, ), OCH
3
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2,4-Dinitrophenyl 5-substituted-2-thiophenecarboxylates
KOREAN CHEMICAL SOCIETY
a
+b
2
ꢁ
Table 2. k
2
/k−1 values for the reactions of 5-XC
4
H
2
(S)C(O)OC
6
H
3
–2,4-(NO
2
)
2
with R
2
NH/R
2
NH
in 20 mol % DMSO(aq) at 25.0 C.
e,f
2
k /k−1
c
d
Amine
pKa
H (2a)
OCH (2b)
CH (2c)
Cl (2d)
3
3
1
-Formylpiperazine
7.98
8.65
9.38
9.85
10.8
11.02
0.170
0.450
1.30
1.66
10.2
14.0
0.185
0.467
1.28
1.62
9.12
12.4
0.17
0.450
1.30
1.66
10.2
14.0
0.196
0.479
1.27
1.60
8.47
11.4
Morpholine
N-(2-hydroxylethyl)-piperazine
Piperazine
3
-Methylpiperidine
Piperidine
a
−5
[
[
Substrate] = 5.0 × 10 M.
b
c
d
e
f
+
R
2
NH]/[R
N] = 7.0 × 10 to 2.0 × 10−2 M.
a
data in 20 mol % DMSO(aq) taken from Ref. 8d.
2 2
NH ] = 1.0.
−4
[R
2
pK
Average of three or more rate constants.
Estimated uncertainty, ꢂ3%.
a
+ b
ꢁ
Table 3. k
1
values for the reactions of 5-XC
4
H
2
(S)C(O)OC
6
H
3
–2,4-(NO
H (2a)
)
2 2
with R
2
NH/R
2
NH
2
in 20 mol % DMSO(aq) at 25.0 C.
k1/ M−
(2b)
1 -1e,f
s
c
d
a
Amine
pK
OCH
3
CH
3
(2c)
Cl (2d)
1
-formylpiperazine
7.98
8.65
9.38
9.85
10.8
11.02
21.6
46.4
53.5
119
157
162
4.55
7.63
10.0
23.0
25.6
26.5
13.1
23.8
25.0
62.5
58.2
66.6
42.7
96.3
127
293
435
487
morpholine
N-(2-hydroxylethyl)- piperazine
piperazine
3
-methylpiperidine
piperidine
a
−5
[
[
Substrate] = 5.0 × 10 M.
b
c
d
e
f
+
R
2
NH]/[R
N] = 7.0 × 10 to 2.0 × 10−2 M.
a
data in 20 mol % DMSO(aq) taken from Ref. 8d.
2 2
NH ] = 1.0.
−4
[R
2
pK
Average of three or more rate constants.
Estimated uncertainty, ꢂ 3%.
Figure 2. Plots of log(k
reactions of 5-XC
NH/R
, OCH
2
/k−1) vs. pK
a
+ log(p/q) values for the
Figure 3. Plots of log(k
1 a
) vs. pK + log(p/q) values for the reac-
+
4
H
2
(S)C(O)OC
6
H
3
–2,4-(NO
2
)
2
with
tions of 5-XC (S)C(O)OC
4
H
2
6
H
3
–2,4-(NO
2
)
2
with R
2
NH/R
2
NH
2
+
ꢁ
ꢁ
R
)
2
2
NH
2
in 20 mol % DMSO(aq) at 25.0 C [X = H (2a,
in 20 mol % DMSO(aq) at 25.0 C [X = H (2a, ), OCH
), CH (2c, ), Cl (2d, ).
3
3
(2b,
3
(2b, ), CH
3
(2c, ), Cl (2d, ).
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2,4-Dinitrophenyl 5-substituted-2-thiophenecarboxylates
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4 2
Table 4. The ρ and r values for the reactions of 5-XC H (S)C(O)
+
2
OC
at 25.0 C.
6
H
3
–2,4-(NO
2
)
2
with R
2
NH/R
2
NH
in 20 mol % DMSO(aq)
ꢁ
a
a
Entry
Amine
pK
ρ
r
1
2
3
4
Piperidine
3-Methyl piperidine
Piperazine
1-(2-Hydroxyethyl)
piperazine
11.02 2.16 ꢂ 0.05 0.20
10.80 2.06 ꢂ 0.04 0.25
9.85 1.63 ꢂ 0.10 0.40
9.38 1.59 ꢂ 0.09 0.45
5
6
a
Morpholine
1-Formylpiperazine
8.65 1.50 ꢂ 0.09 0.55
7.98 1.28 ꢂ 0.13 0.60
a
pK data in 20 mol % DMSO(aq) taken from Ref. 8d.
Figure 4. Hammett plots of log(kN/q) vs. σ values for the reactions
are overall second order, first order to 2a–d and first order
to the amine nucleophiles. This result is consistent with
both concerted and stepwise mechanisms. However, Brön-
sted plots exhibit downward curvature. Since the Brönsted
plots for the concerted reactions are linear with
βnuc = 0.5–0.6, the curved Brönsted plots observed in this
study can be most reasonably attributed to the stepwise
+
of 5-XC
4
H
2
(S)C(O)OC
6
H
3
–2,4-(NO
2
)
2
with R
2
NH/R
2
NH
2
in
ꢁ
2
0 mol % DMSO(aq) at 25.0 C. [R
zine ( ), 1-formylpiperazine ( )]. Inset: Plots of log(kN/q) vs. σ
2
N = piperidine ( ), pipera-
+
values for the same reaction.
9–11
mechanism with change in the rds (Scheme 1).
To provide additional evidence for the stepwise mecha-
0
nism, the pK , β , and β values have been calculated. The
a
1
2
o
pKa was defined as the pK at the midpoint of the curved
a
Brönsted plot, while the β and β values represent the
1
2
slopes of the curved Brönsted plots for the reactions with
strongly and weakly basic nucleophiles, respectively, that
is, the β values when the second and first step is the rds,
o
respectively (Figure 1). For reactions of 2a–d, pKa = 9.5,
β = 0.22–0.34, and β = 0.85–0.92 have been calculated.
1
2
The β1 and β2 values are in the same range as those
reported for acyl transfer reactions of 3,4-dinitrophenyl aryl
20
carbonate with quinuclidines and of 2,4-dinitrophenyl
benzonates with pyridine in aqueous ethanol,4a-4c both of
9–11
which have been interpreted with a change in the rds.
We also calculated the k1 and k /k values using
Eqs. (4)–(10). If the reaction proceeds as shown in
Figure 5. Yukawa-Tsuno plots for the reactions of 5-XC
4
H
2
(S)C
%
2
−1
+
(
O)OC
DMSO(aq) at 25.0 C [R
-formylpiperazine ( )].
6
H
3
–2,4-(NO
2
)
2
ꢁ
with
R
2
NH/R
2
NH
2
in 20 mol
19
2
N = piperidine ( ), piperazine ( ),
Scheme 1, one can apply steady-state approximation with
1
ꢂ
respect to T . The rate equation can be expressed as Eq. (4).
k = k k =ðk + k Þ = k ðk =k + 1Þ
ð4Þ
Hammett σ values, if the data for 2b is excluded. It showed
negative deviation when plotted against σ (Figure 4). How-
ever, all of the data showed excellent correlations on the
Yukawa-Tsuno plots (Figure 5). The ρ and r values calculated
from these plots are in the range of 1.28–2.16 and 0.20–0.60,
respectively (Table 4). The ρ value decreased and r value
increased as the nucleophile was less basic.
N
1
2
−1
2
1
−1
2
Discussion
Mechanism of Aminolysis. The reactions of 2a–d with
+
2
R NH/R NH
in 20 mol
%
DMSO(aq) produced
2
2
2
,4-dinitrophenoxide almost quantitatively. The reactions
Scheme 1. Stepwise mechanism for the acyl transfer reaction.
986
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2,4-Dinitrophenyl 5-substituted-2-thiophenecarboxylates
KOREAN CHEMICAL SOCIETY
If k << k , Eq. (4) reduces to Eq. (5).
results have been reported for the aminolysis from
2
−1
2
2
,4-dinitrophenyl
X-substituted
benzonates7j
and
k = k k /k , when k < < k
−1
(5)
(6)
20
N
1 2 −1
2
,4-dinitrophenyl X-substituted benzene sulfonates.
0
(3) The pKa values, pK of the nucleophile when k = k ,
a 2 −1
(
second step is rds)
If k >> k , the rate expression becomes Eq. (6).
are the same for all 5-thienyl substituents (Figure 1). Since
the k values for the departure of the common leaving
group should be identical, the basicity of the nucleophiles
2
−1
2
k = k , when k > > k
−1
N
1
2
0
(pK ) required to keep k a constant should also be the
a
−1
same. (4) The k increased as the nucleophile becomes a
1
(
first step is rds)
On the other hand, the β and β can be expressed by the
stronger base, while the 5-thienyl substituent changes from
an electron donating group to an electron withdrawing
group. This is because the reactivity of the nucleophile and
the carbonyl carbon are increased by these changes.
1
2
Eqs. (7) and (8), respectively.4e
β = dðlogk Þ=dðpK Þ
ð7Þ
ð8Þ
1
1
a
(
5) The β values are in the range of 0.25–0.34, indicating
1
β2 = d½logðk1k2=k−1Þꢀ=dðpKaÞ
β + dðlogk =k−1Þ=dðpKaÞ
modest sensitivity of the k1 to the amine basicity. The
values are smaller by about 2-fold than the β−1 values of
=
1
2
0
.58–0.63 (Figures 1 and 2). Since k and k are reversible
1 −1
steps involving common transition states, the moderate
Rearrangement of Eq. (8) provides an expression
for β –β .
values of the β predict that k should be more sensitive
1
−1
2
1
than k to the amine basicity. On the other hand, the k2
1
value should be relatively insensitive to the amine basicity
β −β = dðlogk =k−1Þ=dðpKaÞ
ð9Þ
2
1
2
(
see above). This would predict that the k /k
values
2
−1
should be more sensitive than k to the amine basicity and
1
Integration of Eq. (9) yields Eq. (10),
a larger β−1 than β values.
1
À
Á
0
logðk =k Þ = ðβ −β Þ pK −pK
ð10Þ
Effect of 5-Thienyl Substituent. The rate of the reaction
increased as the 5-thienyl substituent changes from an elec-
tron donating group to an electron withdrawing group
(Table 1). The rate data could be correlated with the Ham-
mett plots, if the data for 2b is excluded. It showed nega-
tive deviation when plotted against σ (Figure 4). In sharp
contrast, all of the rate data showed excellent correlations
on the Yukawa-Tsuno plots when plotted against [σ + r
2
−1
2
1
a
a
0
where pK = pK when k = k .
a
a
2
−1
The k /k values can be calculated from Eq. (10) using
the β , β , and pK values. The k values can then be calcu-
lated from Eq. (5) using the values of k and k /k calcu-
2
−1
1
2
a
1
N
2 −1
lated as above.
The values of pK , k , and k /k provide strong support
0
a
1
2 −1
+
for a stepwise mechanism; (1) the k /k value increased
with a stronger nucleophile (Table 2). This outcome is as
expected because k−1 should decrease with a stronger base
(σ − σ)] values (Figure 5). The extra resonance stabiliza-
2
−1
tion by the π donor substituents can be evaluated with
21
Eq. (10) using the Yukawa-Tsuno equation.
and k should remain constant. More importantly, values of
2
+
k2/k−1 << 1, k /k ≈ 1, and k /k >> 1 have been calcu-
logðk=k0Þ = ρfσ + r ðσ −σÞg
ð10Þ
2
−1
2 −1
lated for nucleophiles with pK < 9.0, pK = 9.38–9.85, and
a
a
pK > 10.8, respectively (Table 2). As stated above, an
The ρ value indicates the extent of negative charge
a
+
increase in the pK value of the nucleophile should increase
development at the reaction site, (σ − σ) is the resonance
a
the k /k value, thereby resulting in a gradual shift of the
substituent constant measuring the π-delocalization capabil-
ity of the donor group, and r is a parameter characteristic
of the given reaction, measuring the extent of resonance
demand, i.e., the degree of resonance interaction between
2
−1
rds from the second (k /k << 1) to the first step (k /k
2 −1
2
−1
>
> 1). This outcome is consistent with that of Um except
that the change in the rds occurs when the pK of the amine
a
21
nucleophile is larger than that of the leaving group by
the aryl group and the reaction site in the rds. This equa-
tion is identical to the Hammett equation when r = 0 and
Brown equation when r = 1. The much better correlation of
the rate data with Eq. (10) than with Hammett and Brown
equations indicates that the extra resonance stabilization by
the π-donor substituent in 2b can be represented by the res-
onance hybrid (III) of I and II, not by I (Hammett σ) or II
1
2–15
6–7 units rather than 4–5 units.
(2) The k /k values
2 −1
are nearly the same for all 5-thienyl substituents (Table 2).
Also, the β−1 values, the slopes of the plots of log k /k
2
−1
vs. pK of the amines, are very similar (Figure 2). A step-
a
wise mechanism predicts that the electron density at the
ꢂ
carbonyl carbon should decrease as the intermediate (T ) is
+
22
converted to either reactant (k ) or product (k )
(Brown σ ) alone (Scheme 2).
−1
2
(
Scheme 1). Hence, an electron withdrawing 5-thienyl sub-
For the aminolysis of 2a–d, the ρ value increased from
1.28 to 2.16 and r value decreased from 0.60 to 0.20 as the
amine was changed to a stronger base (Table 4). This
stituent should decrease both of k−1 and k values, thereby
keeping the k /k value more or less a constant. Similar
2
2
−1
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2,4-Dinitrophenyl 5-substituted-2-thiophenecarboxylates
KOREAN CHEMICAL SOCIETY
the enhanced leaving group ability. (3) The βnuc = 0.89 for
1
a is very similar to β = 0.91 for 2a measured using weak
2
nucleophiles (Figure 1). Since the reactions of 1a and 2a
Scheme 2. Extra resonance stabilization by the π-donor substituent.
Table 5. Transition state parameters for reactions of C H (S)C(O)
with weakly basic nucleophiles proceed through the same
mechanism in which the k step is the rds, the extent of
2
N─C bond formation in the transition state should be simi-
lar. This would predict similar Brönsted β values, as
observed. (4) The ρ value increased from 0.89 to 1.50 while
the r values decreased from 0.90 to 0.55 by the change in
the leaving group from 4-nitrophenoxide (1a) to
4
3
ꢁ
+
OY with R NH/R NH in 20 mol % DMSO(aq) at 25.0 C.
2
2
2
1
4
6
Y = 4-NO C H
Y = 2,4-(NO ) C H
2 2 6 3
2
6
2
3
pK
a
7.14
1
4.11
260
—
a
Relative rate
βnuc
2
,4-dinitrophenoxide (2a). This result can be attributed to
0.89 ꢂ 0.05
the different extent of participation of the first step to the
rds. As stated above, the electron density at the carbonyl
carbon increases in the first step and decreases in the sec-
ond step, thereby resulting in a larger ρ value when the first
step is rds than when the second step is rds. For the
aminolysis from 1a, the second step is always rds for all
nucleophiles. On the other hand, the rds in the aminolysis
from 2a changes from the second step to the first step as
the basicity of the nucleophile is increased (see above).
Therefore, the larger ρ value determined for 2a can be
attributed to the partial involvement of the first step in the
rds. The smaller r value reflects the reduced resonance
demand caused by the enhanced electron density at the car-
bonyl carbon. All of these results are in excellent agreement
with the stepwise mechanism with the change in the rds.
β
1
—
—
—
0.28 ꢂ 0.04
0.91 ꢂ 0.08
0.63
1.50 ꢂ 0.09
0.55
β2
β
ρ
−
1
a
a
0.89 ꢂ 0.05
0.90
r
Brönsted plot
Linear
Downward curve
a
2
R NH = morpholine.
indicates an increase in the electron density at the carbonyl
carbon and a decrease in the resonance demand. Since the
electron density at the carbonyl carbon increases in the first
step and decreases in the second step, the ρ value for the
acyl transfer reaction should be larger when the first step is
rds than when the second step is rds due to the opposite
substituent effect. Therefore, the increase in the ρ value
with a stronger nucleophile provides additional support for
the change in the rds from the second to the first step. The
decrease in the r value is also consistent because the reso-
nance demand should decrease as the electron density is
increased.
Conclusions
In this work, we have studied the aminolysis reactions of
2
,4-dinitrophenyl 5-substituted-2-thiophene carboxylate
+
(
2a–d) with R NH/R NH in 20 mol % DMSO(aq). The
2 2 2
0
curved Brönsted plots with identical pKa = 9.5,
β = 0.22–0.34, β = 0.85–0.92, gradual increase in the k
Effect of Leaving Group. Comparison of the kinetic data
for the aminolysis of 1a–d and 2a–d provides additional
evidence for the proposed mechanism; (1) the rate of
morpholine-promoted aminolysis from 2a is faster than that
from 1a by 270-fold (Table 5). Since the second step is the
rds for both reactions, the rate equation should be
1
2
1
values with electron-withdrawing 5-thienyl substituents and
stronger nucleophiles, and values of k /k << 1, k2/
2
−1
k−1 ≈ 1, and k /k >> 1 for nucleophiles with pK < 9.0,
2
−1
a
pKa = 9.38–9.85, and pKa > 10.8, respectively, provide
strong evidence for the stepwise mechanism with the
change in rds. Moreover, the excellent correlation of the
rate data on the Yukawa-Tsuno plots, the gradual increase
in the ρ values with concomitant decrease in the r value
with a stronger nucleophile indicated the gradual increase
in the N─C bond formation in the transition state. Compari-
son with the previously reported data for 1a–d revealed that
the change in the rds in the reactions of 2a–d from the sec-
ond to the first step with a stronger nucleophile originated
from the increased leaving group ability of
2,4-dinitrophenoxide.
kN = k k /k . For a given nucleophile, k and k values
1 2
−1
1
−1
should remain almost the same regardless of the leaving
group. Therefore, the 270-fold faster rate of 2a is undoubt-
edly due to the enhanced leaving group ability. (2) For the
aminolysis of 1a–d, the second step is rds (k /k << 1) for
2
−1
all nucleophiles, whereas those of 2a–d proceed by the
stepwise mechanism with the change in the rds (Table 2).
Since the k step of 2a is much faster than that of 1a, and
2
k−1 decreases as the nucleophile becomes more basic, the
k2/k−1 value of 2a could become greater than 1 with a
strong nucleophile, thereby changing the rds to the first
step. On the other hand, the k step of 1a should be slower
Experimental Section
2
than that of 2a by more than 270-fold in order for the first
step to become rds. However, this is not possible because
the k−1 values for the two compounds should be same for a
given nucleophile. Therefore, the stepwise mechanism with
a change in the rds observed for 2a–d can be attributed to
Materials.
All of the 2,4-dinitrophenyl 5-substituted-
2-thiophenecarboxylates 2a-d were prepared by the reactions
of 2,4-dinitrophenol with 5-substituted-2-thiophenecarboxyl
chloride in the presence of Et N in methylene chloride.
18
3
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2,4-Dinitrophenyl 5-substituted-2-thiophenecarboxylates
KOREAN CHEMICAL SOCIETY
The spectral and analytical data of the compounds were con-
sistent with the proposed structures. The yield (%), IR (KBr,
origin, indicating that the reactions are second-order, first-
order to the substrate and first-order to the base. The
−1
1
C═O, cm ), H NMR (400 MHz, CDCl , J values are in
second-order rate constants k were obtained either from
3
2
13
Hz), and C NMR (100 MHz), and mass spectral data for
the new compounds are as follows.
the slopes of straight lines or by dividing the kobs by the
base concentration.
C H (S)C(O)OC H –2,4-(NO ) (2a): Yield 83%; IR
Product Studies. The products were identified by periodi-
cally monitoring the UV absorption of the reactions mix-
tures under the reaction condition. The yields of aryloxides
determined by comparing the UV absorptions of the infinity
samples with those for the authentic aryloxides were in the
range of 96–98%.
4
3
6
3
2 2
−
1 1
1
(
710 cm ; H NMR δ 7.24 (dd,1H, J = 3.68, 8.8), 7.67
d, 1H, J = 9.14), 7.79 (d, 1H, J = 1.44), 8.06 (dd, 1H,
J = 1.44, 3.68), 8.56 (dd, 1H, J = 2.74, 9.14), 9.01 (d, 1H,
13
J = 2.74); C NMR δ 121.8, 126.7, 128.6, 128.9, 130,3,
1
2
3
35.6, 136.7, 141.9, 145.1, 148.3, 158.2.; LRMS(EI); m/z
+
94[M ] (3), 112(100), 111(92), 83(32), 63(16),
Control Experiments. The stabilities of 2a–d were deter-
16
9(77), 30(14).
mined as reported earlier. The solutions of 2a–d in
MeCN were stable for at least 2 days when stored in the
refrigerator.
5
-MeOC H (S)C(O)OC H –2,4-(NO ) (2b): Yield
4 2 6 3 2
−
1 1
7
9%; IR 1716 cm ; H NMR δ 4.03 (s, 3H), 6.37 (d, 1H,
J = 4.11), 7.65 (d, 1H, J = 8.96), 7.82 (d, 1H, J = 4.11),
Acknowledgment. This work was supported by the
Pukyong National University Research Fund in 2019.
8
.53–8.56 (dd, J = 3.26, 8.96, 1H), 8.97 (d, 1H, J = 3.26);
1
3
C NMR δ 60.9, 101.1, 115.1, 121.9, 126.9, 129.0, 137.5,
+
1
(
6
42.2, 145.1148.8, 158.7, 175.7. LRMS(EI); m/z 324[M ]
Supporting Information. Observed rate constants for
6), 141(100), 126(15), 98(48), 85(8), 70(26),
9(14), 30(12).
-MeC H (S)C(O)OC H –2,4-(NO ) (2c): Yield 81%;
+
elimination from 2a–d promoted by R N/R NH in 20 mol
2
2
%
DMSO(aq), plots of kobs vs. base concentration, and
5
4
2
−
6
3
2 2
NMR spectra for all compounds are available on request
from the correspondence author (14 pages).
1
1
IR 1715 cm ; H NMR δ 2.61 (s, 3H), 6.90 (d, 1H,
J = 3.48), 7.65 (d, 1H, J = 8.98), 7.87 (d, 1H, J = 3.48),
.55 (dd, 1H,J = 2.76, 8.8), 8.98 (d, 1H, J = 2.76);
13
8
C
NMR δ 160.0, 121.7, 127.3, 121.4, 128.8, 137.2, 141.9,
+
1
44.9, 148.5, 152.0, 158.3.; LRMS(EI); m/z 308[M ] (9),
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Bull. Korean Chem. Soc. 2019, Vol. 40, 983–990
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989

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2,4-Dinitrophenyl 5-substituted-2-thiophenecarboxylates
KOREAN CHEMICAL SOCIETY
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Bull. Korean Chem. Soc. 2019, Vol. 40, 983–990
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990