Elimination Reactions of Aryl Furylacetates Promoted by R2NH in MeCN: Effects of Base Solvent and β-Aryl Group on the Ketene-forming Transition State

Article abstract of DOI:10.1002/bkcs.11285

Ketene-forming elimination from C₄H₃(O)CH₂C(O)OC₆H₃-2-X-4-NO₂ (1) promoted by R₂NH in MeCN has been studied. The reactions produced elimination products and exhibited second-orde

Full text of DOI:10.1002/bkcs.11285

Article
DOI: 10.1002/bkcs.11285
BULLETIN OF THE
S. Y. Pyun et al.
KOREAN CHEMICAL SOCIETY
Elimination Reactions of Aryl Furylacetates Promoted by R2NH
in MeCN: Effects of Base Solvent and β-Aryl Group on the
Ketene-forming Transition State
‡
‡
§
¶,
Sang Yong Pyun,†, Kyu Cheol Paik, Man So Han, Byung Tae Kim, and Bong Rae Cho
*
*
†Department of Chemistry, Pukyong National University, Pusan 608-737, Korea.
*E-mail: sypyun@pknu.ac.kr
‡Department of Chemistry, Daejin University, Gyeonggi-do 11159, Korea
§Division of Energy and Environmental Engineering, Daejin University, Gyeonggi-do 11159, Korea
¶Department of Chemistry, Korea University, Seoul 136-713, Korea. *E-mail: chobr@korea.ac.kr
Received July 27, 2017, Accepted August 28, 2017, Published online October 9, 2017
Ketene-forming elimination from C4H3(O)CH2C(O)OC6H3-2-X-4-NO2 (1) promoted by R2NH in MeCN
has been studied. The reactions produced elimination products and exhibited second-order kinetics with
Brönsted β = 0.51, and |βlg| = 0.47–0.53, indicating that the reaction proceeds by the E2 mechanism via
¼
¼
an E2-central transition state. Comparison of β, |βlg|, ΔH , and ΔS values for R2NH-promoted elimina-
tions from ArCH2C(O)OC6H3-2-X-4-NO2 reveals that the transition-state structures for Ar = furyl and
thienyl are similar and more symmetrical than that for Ar = Ph. This outcome has been attributed to the
greater double bond stabilizing ability of the former than that of the latter.
Keywords: Elimination, Ketene, E2 mechanism, Base solvent, β-Aryl group
Introduction
invalidated by the experimental results demonstrating that
the E2 mechanism changes to a competing E2 and E1cb and
then to E1cb by the change in the reactant structure in the
reactions of ArCH2C(O)OC6H3-2-X-4-NO2 (Ar = aryl, 3)
Base-promoted eliminations from 2-alkyl halides produce
1-alkene, cis- and trans-2-alkenes. The C C bond pro-
duced by this reaction is an important conjugation bridge in
organic materials including organic light-emitting diode,
organic semiconductors, and nonlinear optical materials.1
Due to the lack of selectivity, however, Wittig reaction
rather than the elimination reaction is usually employed to
introduce the C C bonds. Understanding the detailed
mechanism of the elimination reactions might lead to a new
synthetic method for the C C bond formation. More
importantly, the E2 transition state involving two partially
broken bonds and two partially formed bonds is one of the
most complex transition states in organic reactions. Under-
standing the E2 transition state would thus enhance our
insight into the mechanistic organic chemistry. In fact, the
three-dimensional reaction coordinate diagram,2 which is
useful to explain the structure–reactivity relationship of
elimination, substitution, and carbonyl addition reactions
relevant to bio-organic chemistry, has been evolved from
the study of the E2 reaction.
with R2NH/R2NH2 in 70 mol% MeCN(aq).4 Additional
+
examples of such mechanistic changes were reported for
eliminations from aryl thienylacetates (Ar = thienyl, 2) and
aryl furylacetates (Ar = furyl, 1) under the same
condition.5,6
When R2NH in MeCN was used as the base solvent sys-
tem; however, the reactions of 2 and 3 proceeded by the E2
mechanism via the E2-central transition state.4a,7,8 This out-
come has been ascribed to the poorly anion solvating
MeCN. Since MeCN cannot stabilize the partial negative
charge at the β-carbon as effectively as 70 mol %
MeCN(aq), the charge should be distributed as much as
possible throughout the transition state. This can be
achieved by forming a symmetrical transition state with
increased partial double bond. The observation of more
symmetrical transition state for 2 than 3 underlined the
importance of the partial double bond character under this
condition.
There was a long standing controversy on the borderline
mechanism between E2 and E1cb in the elimination reac-
tions. Earlier, Jencks proposed that the change in the mecha-
nism from E2 to E1cb occurs by the “merging of the
transition states.”3 He argued that the E1cb-like and E1cb
transition states are so closely located in the reaction coordi-
nate diagram that they cannot coexist, i.e., the concurrent E2
and E1cb mechanisms are not possible. The proposal was
Since the aromatic resonance energy of furan (16 kcal/
mol) is smaller than those of thiophene (29 kcal/mol) and
benzene (36 kcal/mol),9 the furyl group is expected to sta-
bilize the developing double bond character more than thie-
nyl and phenyl groups. In order to understand the effect of
aromaticity on the ketene-forming transition state, we have
now studied the elimination reactions of aryl furylacetates
promoted by R2NH in MeCN (Eq. (1)). By comparing with
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ISSN (Print) 0253-2964 | (Online) 1229-5949
KOREAN CHEMICAL SOCIETY
the existing data for elimination reactions from 1–3 pro-
1.4
0.7
moted by R2NH/R2NH2 in 70 mol % MeCN(aq)4–6 and
+
from 2 and 3 promoted by R2NH in MeCN,4a,7,8 the effects
of base solvent and β-aryl groups are assessed.
O
O
O
0.0
CH2CO
NO2 +
R2NH
C
H
C
O
(1)
MeCN
1
X
+
O
NO2
-0.7
-1.4
-2.1
X = H (a), OCH3 (b), Cl (c), NO2(d)
R2NH = Bz(i-Pr)NH, i-Bu2NH, i-Pr2NH, 2,6-DMP
X
Results
16.5
17.0
17.5
18.0
18.5
19.0
Aryl furylacetates 1a–1d were available in our laboratory.6
The products of the reaction of 1a–1d with R2NH in MeCN
were characterized as before.4–8 The yields of aryloxides
for the reactions of 1a–1d with R2NH in MeCN were deter-
mined as reported.4–8 The yields were in the range of
95–98%. These results established that the reactions pro-
duce elimination products only.
The kinetic experiments were performed under pseudo-
first-order condition.4–8 The kinetic plots showed straight
lines with excellent correlations up to three half-lives. The
pKa
Figure 1. Brönsted plots for the elimination from C4H3(O)CH2C
(O)OC6H3-2-X-4-NO2 promoted by R2NH in MeCN at 25.0 ꢀC
[X = H (1a, ●), OMe (1b, ▪), Cl (1c, ▲), NO2 (1d, ▼].
Table 2. Brönsted β values for elimination from C4H3(O)CH2C
(O)OC6H3-2-X-4-NO2 promoted by R2NH in MeCN at 25.0 ꢀC.
X = p-OMe
X = H
20.7
0.67 ꢁ 0.09 0.67 ꢁ 0.11 0.68 ꢁ 0.14 0.51 ꢁ 0.05
Ref. 11.
X = Cl
X = NO2
a
pKlg 21.6
18.1
16.0
observed rate constants (kobs
)
are summarized in
β
a
Tables S1–S4, Supporting Information. The plots of kobs
vs. base concentration were straight lines passing through
the origin. This outcome indicates that the reactions pro-
ceed by the second-order kinetics, first order to the sub-
strate and first order to the base (Figures S1–S4). The
second-order rate constants (k2) were calculated from the
slopes of these plots. The only exception is the reaction
between 1d with 2,6-DMP, for which the rate was mea-
sured at a single base concentration because the rate was
too fast to follow at a higher base concentration. The k2
value for this reaction was calculated by dividing the kobs
by the base concentration. The k2 values are summarized in
Table 1.
range of 0.51−0.68 and almost the same within experimental
error (Table 2). Similarly, the log k2 values showed reason-
able correlation with the pKlg values of the leaving groups
(Figure 2). The |βlg| values are in the range of 0.47−0.53.
Here again, the values are very similar (Table 3).
Rates of the reactions of ArCH2C(O)OC6H4-4-NO2 (1a, 2,
3) with Bz(i-Pr)NH in MeCN and those of 1a with Bz(i-Pr)
1.4
0.7
The Brönsted plots for the reactions of 1a–1d were linear
with excellent correlations (Figure 1). The β values are in the
Table 1. Rate constants for ketene-forming elimination from
C4H3(O)CH2C(O)OC6H3-2-X-4-NO2a promoted by R2NH in
MeCN at 25.0 ꢀC.
0.0
k2, M−1 s-1d,e
-0.7
-1.4
-2.1
R2NHb
pKa
X = H X = OMe X = Cl X = NO2
c
Bz(i-Pr)NH 16.8 0.0176
0.00798
0.0405
0.123
0.258
1.03
3.46
8.12
2.67
10.6
21.4
31.6
i-Bu2NH
i-Pr2NH
2,6-DMPf
a
18.2 0.045
18.5 0.139
18.9 0.279
0.207
16
17
18
19
20
21
[Substrate] = 5.0 × 10−5 M.
[R2NH] = 2.0 × 10−3 to 5.0 × 10−2 M.
Ref. 10.
Average of three or more rate constants.
Estimated uncertainty, ꢁ3%.
cis-2,6-Dimethylpiperidine.
b
c
d
e
f
pKlg
Figure 2. Plots log k2 vs. pKlg values of the leaving group for the
elimination from C4H3(O)CH2C(O)OC6H3-2-X-4-NO2 (1a–1d)
promoted by R2NH in MeCN at 25.0 ꢀC [R2NH = Bz(i-Pr)NH
(■), i-Bu2NH (▲), i-Pr2NH (●), 2,6-DMP (▼)].
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Elimination Reactions of Aryl Furylacetates
KOREAN CHEMICAL SOCIETY
Table 3. Brönsted βlg values for elimination from C4H3(O)CH2C
faster as the base solvent system was changed from R2NH/
(O)OC6H3-2-X-4-NO2 promoted by R2NH in MeCN at 25.0 ꢀC.
+
R2NH2 −70 mol% MeCN(aq) to R2NH–MeCN (Table 4).
¼
¼
2,6-DMPa
However, the β, |βlg|, ΔH , and ΔS values remained
nearly the same by the same change in the base solvent,
indicating that the ketene-forming transition state is insensi-
tive to the base solvent variation. Similar results were
reported for the ketene-forming eliminations from 2 and
3.4a,7,8 The combined results indicate that the ketene-
forming transition states are relatively insensitive to the
base solvent variation regardless of the β-aryl group. This
outcome could be explained, if the developing negative
charge at the β-carbon is more stabilized by the combined
effects of β-aryl group, carbonyl group, and leaving group
than by the solvation.
R2NH Bz(i-Pr)NH
i-Bu2NH
18.2
i-Pr2NH
18.5
b
pKa 16.8
18.9
βlg
−0.53 ꢁ 0.03 −0.52 ꢁ 0.02 −0.49 ꢁ 0.03 −0.47 ꢁ 0.06
a
cis-2,6-Dimethylpiperidine.
b
Ref. 10.
+
NH/Bz(i-Pr)NH2 in 70 mol% MeCN(aq) were measured at
ꢀ
25.0, 35.0, and 45.0 C, respectively (Table S5). Arrhenius
plots were linear with excellent correlations (Figure S5). The
enthalpies and entropies of activation were calculated from
the Arrhenius plots. The values are summarized in Table 4.
For eliminations from ArCH2C(O)OC6H3-2-X-4-NO2
[Ar = furyl (1a), thienyl (2), Ph (3)] promoted by R2NH
in MeCN, the rate was similar for 1a and 2 and slightly
Discussion
¼
¼
Mechanism of Eliminations from 1. The reactions of 1a–
1d with R2NH in MeCN produced only elimination prod-
ucts. Neither aminolysis nor SNAr product was obtained
presumably because of the high acidity of the Cβ H bond
and the steric hindrance of the secondary amines, which
would have facilitated the elimination reaction while retard-
ing the aminolysis and SNAr reactions. All of the reactions
exhibited second-order kinetics, indicating that the reactions
proceed either by the E2 or E1cb mechanism.2 The E1cb
mechanism is negated by the substantial values of Brönsted
β and |βlg|, for which either Brönsted β values near unity or
negligible |βlg| values are expected.2,12 Hence, the most rea-
sonable mechanism for these reactions is E2. This conclu-
sion is supported by the interaction coefficients. The
decrease in the Brönsted βlg value decreases with a stronger
base corresponds to a positive pxy interaction coefficient,
pxy = ∂βlg/∂pKBH (Table 3). The positive pxy interaction
coefficient is in agreement with the concerted E2 mecha-
nism, but not with an E1cb mechanism for which pxy = 0 is
expected.12
slower for 3. Moreover, the β, |βlg|, ΔH , and ΔS
values are similar for 1a and 2, indicating similar
transition-state structures. This outcome indicates that the
change of the β-aryl group from furyl to thienyl does not
appreciably influence the ketene-forming transition state.
The smaller resonance energy of the furan than that of
thiophene9 is not reflected in the transition-state structure.
The only noticeable difference is the increase in the β
value from 0.62−0.67 to 0.82 and the decrease in the |βlg|
value from 0.50 to 0.43 by the change in the β-aryl sub-
stituent from furyl and thienyl to phenyl. This indicates a
skewed transition state toward more Cβ H bond cleavage
and less Cα OAr bond rupture by the change in the
β-aryl group. This result is in good agreement with the
greater double bond stabilizing ability of the heterocycles
compared with that of the phenyl group. Since the devel-
oping double bond character can be more stabilized by
resonance with the former, a greater amount of the nega-
tive charge would be shifted from the β-carbon to the
Cβ Cα bond, thereby increasing the partial double bond
character and the extent of the Cα OAr bond rupture.
This would predict a larger |βlg| value for 1a and 2, as
observed.
Effects of Base Solvent and β-Aryl Group on the
Ketene-forming Transition State. The rate of elimination
from 1a promoted by Bz(i-Pr)NH increased by eightfold
Table 4. Transition-state parameters for nitrile-forming eliminations from ArCH2C(O)OC6H4-4-NO2 promoted by R2NH in MeCN at
25.0 ꢀC.
Ar = furyl (1a)a,b
Ar = furyl (1a)c
Ar = thienyl (2)d
Ar = phenyl (3)e
Rel. ratec
1
8
10
1
β
βlg
0.54 ꢁ 0.12
−0.45
10.6 ꢁ 0.4
−32.8 ꢁ 0.7
0.67 ꢁ 0.11
−0.53 ꢁ 0.06
10.1 ꢁ 0.2
−30.7 ꢁ 0.5
0.62 ꢁ 0.05
−0.53 ꢁ 0.03
9.60 ꢁ 0.4
−33.1 ꢁ 0.9
0.82 ꢁ 0.01
−0.43 ꢁ 0.01
11.1 ꢁ 0.6
−31.1 ꢁ 1.2
f
ΔH¼c kcal/mol
ΔS , euc
¼
a
Ref. 6.
Base solvent = R2NH/R2NH2+−70 mol % MeCN(aq).
b
c
d
e
f
This study.
Ref. 8.
Ref. 4a.
R2NH = Bz(i-Pr)NH.
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BULLETIN OF THE
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Elimination Reactions of Aryl Furylacetates
KOREAN CHEMICAL SOCIETY
In conclusion, we have studied the R2NH-promoted
Support Information. Observed rate constants for elimi-
nation from 1a–1d promoted by R2NH in MeCN, plots of
kobs vs. base concentration, and Arrhenius plots are avail-
able in the online version of this article.
eliminations from aryl furylacetates in MeCN. The reaction
proceeded through the E2 mechanism via an E2-central
transition state. The change of the base solvent from R2NH/
+
R2NH2 −70 mol% MeCN(aq) to R2NH–MeCN increased
the reaction rate by eightfold without appreciable change in
the transition-state structure. For eliminations from
ArCH2C(O)OC6H3-2-X-4-NO2 promoted by R2NH in
MeCN, the transition-state structures for 1a and 2 were
similar and more symmetrical than that for 3. This outcome
has been attributed to the greater double bond stabilizing
ability of the former than that of the latter. Noteworthy was
the relative insensitivity of the ketene-forming transition
state to the variation of the β-aryl group from thienyl to
furyl.
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Acknowledgment.
This work was supported by a
Research Grant of Pukyong National University (2017).
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