Ketene-forming elimination reactions from aryl thienylacetates promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq). Effect of the β-aryl group

Article abstract of DOI:10.1021/jo0612978

(Chemical Equation Presented) Ketene-forming eliminations from ArCH ₂CO₂C₆H₃-2-X-4-NO₂ (Ar = thienyl, 1) promoted by R₂NH/ R₂NH₂⁺ in 70 mol % MeCN(aq) have

Full text of DOI:10.1021/jo0612978

Ketene-Forming Elimination Reactions from Aryl Thienylacetates
+
Promoted by R2NH/R2NH2 in 70 mol % MeCN(aq). Effect of the
â-Aryl Group
Bong Rae Cho† and Sang Yong Pyun*,‡
Department of Chemistry, Korea UniVersity, 1-Anamdong, Seoul, 136-701, Korea,
and Department of Chemistry, Pukyong National UniVersity, Pusan 608-737, Korea
sypyun@pknu.ac.kr
ReceiVed June 23, 2006
Ketene-forming eliminations from ArCH2CO2C6H3-2-X-4-NO2 (Ar ) thienyl, 1) promoted by R2NH/
+
R2NH2 in 70 mol % MeCN(aq) have been studied kinetically. When X ) CF3 and NO2, the reactions
exhibit second-order kinetics as well as â ) 0.30-0.64 and |âlg| ) 0.31-0.52 that decrease with a better
leaving group. Hence, an E2 mechanism is evident. As the leaving group is made poorer (X ) H, OCH3,
and Cl), E2 transition state becomes more skewed toward the proton transfer, as revealed by the increase
in Bro¨nsted â to 0.5-0.64, and the E1cb mechanism competes. The changes in the k1 and k-1/k2 values
with the reactant structure variation provide additional support for the competing E1cb mechanism. By
comparing with existing data for 4-YC6H4CH2CO2C6H3-2-X-4-NO2, the effect of â-aryl group on ketene-
forming elimination is assessed.
Extensive studies of ketene-forming elimination reactions
have revealed mechanistic diversity in the E2 and E1cb
borderline.1-6 The mechanism changed from E2 to E1cb via
the competing E2 and E1cb mechanisms as the good leaving
group was made poorer and as the electron-withdrawing ability
of the â-aryl substituent increased.
reactions.7-10 However, the rates and the E2 transition states
were insensitive to the change of the â-aryl group from Ph to
thienyl to furyl. The only significant difference was the smaller
steric effect observed for the imine-forming elimination from
ArCH2N(X)R when Ar ) thienyl.9,10 We thought that the effect
of â-aryl group might be more pronounced in the ketene- than
in the nitrile- and imine-forming eliminations for the following
reasons: (1) the partial double bond character in the ketene-
forming transition state may be better stabilized by the â-aryl
group because the π orbitals are composed of the p-orbitals of
carbon atoms rather than those of carbon and nitrogen atoms
and (2) the heterocyclic groups may facilitate the mechanism
change from E2 to E1cb by stabilizing the negative charge at
the â-carbon. To assess the relative importance of these factors,
Earlier, we investigated the effects of heterocyclic aromatic
compounds on the nitrile- and imine-forming elimination
* To whom correspondence should be addressed. Tel: 82-51-620-6383; fax:
82-51-628-8147.
† Korea University.
‡ Pukyong National University.
(1) Pyun, S. Y.; Cho, B. R. Bull. Korean Chem. Soc. 2005, 26, 1017-
1024.
(2) Cho, B. R.; Kim, Y. K.; Maing Yoon, C. O. J. Am. Chem. Soc. 1997,
119, 691-697.
(3) Cho, B. R.; Kim, Y. K.; Seong, Y. J.; Pyun, S. Y. J. Org. Chem.
2000, 65, 1239-1241.
(7) Cho, B. R.; Cho, N. S.; Song, S. H.; Lee, S. K. J. Org. Chem. 1998,
63, 8304-8309.
(4) Cho, B. R.; Kim, N. S; Kim, Y. K.; Son, K. H. J. Chem. Soc., Perkin
Trans. 2 2000, 1419-1423.
(8) Cho, B. R.; Cho, N. S.; Chung, H. S. J. Org. Chem. 1998, 63, 4685-
4690.
(5) Cho, B. R.; Jeong, H. C.; Seong, Y. J.; Pyun, S. Y. J. Org. Chem.
2002, 67, 5232-5238.
(9) Bartsch, R. A.; Cho, B. R. J. Am. Chem. Soc. 1989, 111, 2252-
2257.
(6) Pyun, S. Y.; Lee, D. C.; Kim, J. C.; Cho, B. R. Org. Biomol. Chem.
2003, 1, 2734-2738.
(10) Pyun, S. Y.; Lee, D. C.; Cho, B. R. J. Org. Chem. 2005, 70, 5327-
5330.
10.1021/jo0612978 CCC: $37.00 © 2007 American Chemical Society
Published on Web 01/20/2007
1098
J. Org. Chem. 2007, 72, 1098-1103

Elimination, E2 and E1cb, â-Aryl Group Effect
a,b
+
TABLE 1. Rate Constant for Ketene-Forming Elimination from ArCH2CO2C6H3-2-X-4-NO2 Promoted by R2NH/R2NH2 in 70 mol %
MeCN(aq)c,d at 25.0 °C
102 k2E, M-1 s-1g,h
f
R2NHe
pKa
X ) H (1a)i
X ) OMe (1b)i
X ) Cl (1c)i
X ) CF3 (1d)
X ) NO2 (1e)
Bz(i-Pr)NH
i-Bu2NH
i-Pr2NH
16.8
18.2
18.5
18.9
0.235
1.27j
4.48
4.40
0.202
1.28
2.22
3.85
46.0
85.8
282
446
186
488
587
1040
478
1020
1260
2490
2,6-DMPk
a Ar ) thienyl. b [Substrate] ) 3.0 × 10-5 M. c [R2NH]/[R2NH2+] ) 1.0 except as otherwise noted. d µ ) 0.1 (Bu4N+Br-). e [R2NH] ) 8.0 × 10-4 to
E
5.0 × 10-2 M. f Reference 14. g Average of three or more rate constants. h Estimated uncertainty, (5%. i Calculated from the kobs by using eq 2. j k2
0.0180 M-1 s-1 when [R2NH]/[R2NH2+] ) 2.0. k cis-2,6-Dimethylpiperidine.
)
we have investigated the reactions of aryl thienylacetates (1a-
e) promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq) (eq 1).
It is well-established that the reactions of 4-YC6H4CH2CO2C6H3-
2-X-4-NO2 [Y ) H (2), NO2 (3)] with R2NH in MeCN and
R2NH/R2NH2+ in 70 mol % MeCN(aq) proceed by the ketene-
forming elimination followed by the addition.2,3 Compared to
the aminolysis of p-nitrophenyl- and 2,4-dinitrohphenyl acetates
in water,11 the aminolysis of 1a and 1e with R2NH/R2NH2+ in
70 mol % MeCN(aq) would be retarded because the zwitterionic
tetrahedral intermediate would be destabilized by the less protic
solvents and the elimination reaction would be facilitated by
the increased acidity of the Câ-H bond and the increased
basicity of the amine bases. Hence, the reactions of 1a-e with
R2NH/R2NH2+ in 70 mol % MeCN(aq) should proceed by the
elimination reaction pathway. Comparison with the existing data
for 2 and 3 reveals the influence of the â-aryl group on the
ketene-forming eliminations.2,5
FIGURE 1. Plots of kobs versus base concentration for eliminations
from 2-trifluoromethyl-4-nitrophenyl thienylacetate (1d, 9) and 2,4-
+
dinitrophenyl thienylacetate (1e, b) promoted by i-Bu2NH/i-Bu2NH2
in 70 mol % MeCN(aq) at 25.0 °C. [i-Bu2NH]/[i-Bu2NH2+] ) 1.0,
µ ) 0.10 M (Bu4N+Br-).
are expected to be similar,13 the aminolysis of 1a and 1e should
proceed at comparable rates to those of the former.3 This would
predict that the ketene-forming elimination should be the
predominant reaction pathway under the condition employed
in this study. In addition, all compounds were stable for at least
3 days in 70 mol % MeCN(aq), indicating that the solvolytic
elimination is negligible.
Results
Aryl thienylacetates 1a-e were synthesized by the reaction
between 2-thiopheneacetic acid, substituted phenols, 2-chloro-
1-methyl pyridinium, and Et3N in CH2Cl2 as reported.2,12 The
spectral and analytical data for the compounds were consistent
with the proposed structures.
The rates of elimination reactions were followed by monitor-
ing the increase in the absorption at the λmax for the aryloxides
in the range of 400-426 nm. In all cases, clean isosbestic points
were noted in the range of 290-352 nm. Excellent pseudo-
first-order kinetic plots which covered at least three half-lives
were obtained. The rate constants are summarized in Tables
S1-S4 in the Supporting Information.
+
The products of between 1a and i-Bu2NH/i-BuNH2 in 70
mol % MeCN(aq) were identified by thin-layer chromatography
(TLC) and gas chromatography (GC) as before.2 The products
were N,N-di(isobutyl)thenylamide and 4-nitrophenoxide. The
yield of N,N-di(isobutyl)thenylamide determined by GC was
86%. For all reactions, the yields of aryloxides determined by
comparing the infinity absorption of the samples from the kinetic
studies with those of the authentic aryloxides were in the range
of 96-99%.
+
For the reactions of 1d and 1e with R2NH/R2NH2 in 70
mol % MeCN(aq), the plots of kobs versus base concentration
were straight lines passing through the origin, indicating that
the reactions are second-order, first-order to the substrate and
first-order to the base (Figure 1 and Figures S1-S3). The slopes
The possibility of competition by the aminolysis reaction has
been ruled out as before.2,3 The k2 values for the reactions of
E
1a and 1e with 2,6-DMP/2,6-DMPH+ in 70 mol % MeCN(aq)
are 0.0440 and 24.9 M-1 s-1, respectively (Table 1). The values
are much larger (g100-fold) than k2 ) 0 and 0.250 M-1 s-1
reported for the aminolysis of 4-nitro- and 2,4-dinitrophenyl
butyrates.3 Because steric effects of the thenyl and butyl groups
E
of the plots are the overall second-order rate constants k2 .
Values of k2E for eliminations from 1d and 1e are summarized
in Table 1. The rate increases as the leaving group ability and
the pKa value of the promoting base are increased. On the other
hand, the corresponding plots for 1a-c were curves at low base
concentration and became straight lines at higher base concen-
tration (Figures 2 and S4-S15). The data were analyzed by
(11) Satterthwait, A. C.; Jencks, W. J. J. Am. Chem. Soc. 1974, 96, 7018-
7031.
(12) Saigo, K.; Usui, M.; Kikuchi, K.; Shimada, E.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 1977, 50, 1863-1866.
(13) Charton, M. J. Am. Chem. Soc. 1975, 97, 1552-1556.
J. Org. Chem, Vol. 72, No. 4, 2007 1099

Cho and Pyun
FIGURE 2. Plots of kobs versus base concentration for eliminations
from p-nitrophenyl thienylacetate (1a) promoted by Bz(i-Pr)NH/Bz(i-
FIGURE 3. Bro¨nsted plots for the k2E pathways for eliminations from
+
ArCH2CO2C6H3-2-X-4-NO2 (Ar ) thienyl) promoted by R2NH/R2NH2
+
Pr)NH2 in 70 mol % MeCN(aq) at 25.0 °C, Bz(i-Pr)NH/Bz(i-Pr)-
in 70 mol % MeCN(aq) at 25.0 °C, [R2NH]/[R2NH2+] ) 1.0, µ )
0.1(Bu4N+Br-). X ) H (1a, 9), OMe (1b, b), Cl (1c, 2), CF3 (1d,
1), NO2 (1e, 0).
NH2 ) 1.0, µ ) 0.1 M (Bu4N+Br-). The closed circles are the
+
experimental data and the solid line shows the fitted curve by using eq
2 (see text). The curve is dissected into the E2 and E1cb reaction
components (dashed lines).
values for the reaction of 1a have been measured at [R2NH]/
[R2NH2+] ) 2.0. At a given base concentration, the kobs is
always larger at a higher buffer ratio, as expected from eq 2
(Table S2). In addition, the rate data showed excellent correla-
TABLE 2. The k1 and k-1/k2 Values for Elimination from
a,b
+
ArCH2CO2C6H3-2-X-4-NO2 Promoted by R2NH/R2NH2 in 70 mol
% MeCN(aq)c,d at 25.0 °C
k1, M-1 s-1 e,f
10-3k-1/k2, M-1 e
E
tions with eq 2 (Figure S7). Moreover, the values of k2 , k1,
and k-1/k2 are nearly the same regardless of the buffer ratio
(Tables 1 and 2).
R2NH
1a
1b
1c
1a
1b
1c
Bz(i-Pr)NH
i-Bu2NH
i-Pr2NH
0.528
1.14g
1.58
0.183
0.627
0.936
1.45
0.770
2.35
2.73
3.47
2.11
1.21
1.26
0.289
0.480
0.0606
0.0266
0.119
1.11g
0.250
0.369
Bro¨nsted plots for the k2 pathways of 1a-e are depicted in
Figure 3. For all compounds, the plots are linear with good
correlations. The â values are in the range of 0.30-0.64 and
increase as the leaving group ability of the aryloxide decreases
(Table 3). The k1 increases and the k-1/k2 ratio decreases with
a stronger base (Table 2). When the leaving group is changed
to a better one, the k1 scatters and the k-1/k2 ratio decreases
gradually. The plots of log k1 versus pKa values of base are
straight lines (Figures S16). The slopes of the plots for 1a-c
are 0.30 ( 0.04, 0.42 ( 0.02, and 0.32 ( 0.02, respectively
(Table 2).
2,6-DMPh
2.36
0.0719
a-d See Table 1 for footnotes. e Calculated from kobs by using eq 2. f The
slopes of the plots of log k1 versus pKa of the bases for 1a-c are 0.30 (
0.04, 0.42 ( 0.02, and 0.32 ( 0.02, respectively. g k1 ) 1.18 M-1 s-1 and
k-1/k2 ) 1.22 × 103 M-1, respectively, when [R2NH]/[R2NH2+] ) 2.0.
h cis-2,6-Dimethylpiperidine.
assuming that the reaction proceeds by concurrent E2 and E1cb
mechanisms (eq 2).2,5
The plots were dissected into the E2 and E1cb reaction
E
The plots of k2 values for 1a-e against the pKlg values of
E
components, and k2 , k1, and k-1/k2 values that best fit with eq
the leaving group are depicted in Figure 4. The rate data show
good correlations with the straight lines, if the data for 1a and
b are excluded. Therefore, the âlg values were calculated from
the straight lines without the data for 1a and b. The |âlg| values
are in the range of 0.31-0.52 and show a decreasing trend with
a stronger base (Table 4).
2 were calculated. In all cases, the correlations between the
calculated and the experimental data were excellent. Calculated
values of k2 , k1, and k-1/k2 for 1a-c are summarized in Tables
1 and 2.
E
To provide additional evidence for a competing E1cb
mechanism, an H-D exchange experiment was carried out by
+
mixing 1a-c with i-Bu2NH/i-Bu2NH2 in 70 mol % MeCN-
30% D2O at 25.0 °C in an nuclear magnetic resonance (NMR)
tube. The NMR spectrum taken immediately after mixing
indicated complete H-D exchange at the â-carbon.
Discussion
The possibility of the buffer association as the cause of the
curvature was ruled out by the straight lines observed in the
plots of kobs versus [base] for the reactions of 1d and 1e (Figures
1 and S1-S3). Also, the possibility that the salt effect may have
caused the steady increase in the kobs at higher base concentration
is negated because the ionic strength is maintained to be 0.10
M with Bu4N+Br-. To assess the effect of buffer ratio, the kobs
Mechanism of Eliminations from 1. Results of kinetic
investigations and product studies reveal that the reactions of
1d and 1e with R2NH-R2NH2+ in 70 mol % MeCN(aq) proceed
by the E2 mechanism. The reactions produce elimination
products and exhibit second-order kinetics, negating all but
bimolecular pathways. In addition, an E1cb mechanism is ruled
1100 J. Org. Chem., Vol. 72, No. 4, 2007

Elimination, E2 and E1cb, â-Aryl Group Effect
E
a
+
TABLE 3. Bro1nsted â Values for the k2 Pathways for Eliminations from ArCH2CO2C6H3-2-X-4-NO2 Promoted by R2NH/R2NH2 in 70 mol
% MeCN(aq)b,c at 25.0 °C
X ) H (1a)
X ) OMe (1b)
X ) Cl (1c)
X ) CF3 (1d)
X ) NO2 (1e)
d
pKlg
20.7
20.6
18.1
17.0
16.0
b
0.64 ( 0.09e
0.60 ( 0.02e
0.5 ( 0.1e
0.33 ( 0.05
0.30 ( 0.07
a Ar ) thienyl. b [R2NH]/[R2NH2+] ) 1.0. c µ ) 0.1 (Bu4N+Br-). d Reference 15. e k2 values calculated from the kobs by using eq 2 have been used.
E
E
TABLE 4. âlg Values for the k2 Pathways for Eliminations from
a
+
ArCH2COOC6H3-2-X-4-NO2 Promoted by R2NH/R2NH2 in 70 mol
% MeCN(aq)b,c at 25.0 °C
R2NH
Bz(i-Pr)NH
i-Bu2NH
18.2
i-Pr2NH
18.5
2,6-DMPd
18.9
pKa
16.8
âlg
-0.49 ( 0.04 -0.52 ( 0.11 -0.31 ( 0.01 -0.36 ( 0.01
a Ar ) thienyl. b [R2NH]/[R2NH2+] ) 1.0. c µ ) 0.1 (Bu4N+Br-). d cis-
2,6-Dimethylpiperidine.
with [R2NH]/[R2NH2+] increases upon change of the buffer ratio
from 1.0 to 2.0, as expected from eq 2 (Table S2). Furthermore,
the calculated rate constants for the E2 and E1cb pathways
provide additional evidence for this mechanistic duality. (1) The
k2E values for 1a-c nicely fit in the trend observed for 1d and
E
1e, that is, the k2 of 1a-e increases with a stronger base and
a better leaving group (Table 1). The only exception to this
trend is the faster rate of 1a than 1b, which can be attributed to
the smaller leaving group steric effect. (2) The increase in the
k1 value with a stronger base is consistent with what would be
expected for the deprotonation step (Table 2). For a given base,
the k1 values of 1a-1c are scattered as they should be
independent for the leaving group variation. In addition, the
slopes of the plots of log k1 versus pKa of the bases for 1a-c
are in the range of 0.30-0.42, which is again consistent because
the transition state for this step should be reactant-like (see
footnote in Table 2). (3) For i-Bu2NH-promoted elimination
from 1a, the small decrease in k2E and k1 values with the increase
in the buffer ratio from 1 to 2 can be attributed to the modest
decrease in the basicity because of the enhanced hydrogen
bonding between the base and the excess conjugate acid (Tables
1 and 2). The decrease in the k-1/k2 value by the same variation
E
FIGURE 4. Plots log k2 versus pKlg values of the leaving group for
the k2E pathways for eliminations from ArCH2CO2C6H3-2-X-4-NO2 (Ar
) thienyl) promoted by R2NH/R2NH2+ in 70 mol % MeCN(aq) at 25.0
°C, [R2NH[/[R2NH2+] ) 1.0, µ ) 0.1(Bu4N+Br-). R2NH ) Bz(i-Pr)-
NH(9), i-Bu2NH(b), i-Pr2NH(2), 2,6-DMP(1).
out by the substantial values of â and |âlg|.16,17 Moreover, the
E
â values of the k2 processes for 1a-e increase with a poorer
leaving group (Table 3). This effect corresponds to a positive
xy interaction coefficient, pxy ) ∂â/∂pKlg, which describes the
p
interaction between the base catalyst and the leaving group.16,17
Furthermore, the observed increase in the |âlg| values with a
weaker base is another manifestation of this effect, that is, pxy
) ∂âlg/∂pKBH > 0 (Table 4). The positive interaction coef-
ficients, that is, pxy ) ∂â/∂pKlg ) ∂âlg/∂pKBH > 0, provide
additional evidence for the E2 mechanism (vide infra).16,17
+
of the buffer ratio is reasonable because i-Bu2NH2 would
stabilize the carbanion intermediate to decrease k-1 more than
k2 because the second step involves a higher energy barrier. (4)
The decrease in the k-1/k2 values in the order 1a ≈ 1b > 1c is
also consistent (Table 2). The k-1 should be relatively insensitive
to the leaving group variation, whereas k2 should increase in
the order 1a ≈ 1b < 1c. A combination of these factors would
be to decrease the k-1/k2 values. (5) The increase in the k-1/k2
ratio with a weaker base can also be explained similarly. The
k-1 value should increase with the acidity of R2NH2+, although
k2 should be independent of the base strength. This predicts an
increase in the k-1/k2 ratio with the weaker base. The smaller
On the other hand, the plots of kobs versus the base
concentration for the reactions of 1a-c with R2NH-R2NH2
+
in 70 mol % MeCN(aq) were curves at low buffer concentration
and became straight lines at [buffer] > 0.008-0.05 M (Figures
2 and S4-S15). Similar results were observed for eliminations
from 3 under the same condition and were ascribed to the
concurrent E2 and E1cb mechanisms.5,6 There is convincing
evidence in support of this mechanistic duality. First, all rate
E
data show excellent correlations with eq 2, that is, kobs ) k2
[B] + k1k2[B]/(k-1[BH+] + k2) (Figures 2 and S4-S15). The
shapes of the dissected lines are typical for the E2 and E1cb
mechanisms. In addition, the kobs value for the reaction of 1a
+
value of k-1/k2 for i-Pr2NH/i-Pr2NH2 than expected from the
pKa value can be attributed to the base steric effect. Because
+
i-Pr2NH2 is sterically more hindered than others, it should
decrease k-1 without changing k2 to decrease k-1/k2. Also, the
scattered values of k-1/k2 for 1c may be due to the experimental
errors caused by the small contribution of the E1cb pathway
(Figures S12-S15).
(14) Cho, B. R.; Lee, S. J.; Kim, Y. K. J. Org. Chem. 1995, 60, 2072-
2076.
(15) Coetzee, J. F. Prog. Phys. Org. Chem. 1965, 4, 45-92.
(16) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic
Chemistry; Harper and Row: New York, 1987; pp 214-218, 591-560,
and 640-644.
(17) Gandler, J. R. The Chemistry of Double Bonded Functional Groups;
Patai, S., Ed.; John Wiley and Sons: Chichester, United Kingdom, 1989;
Vol. 2, part 1, pp 734-797.
Finally, the NMR spectra taken immediately after mixing
+
1a-c with i-Bu2NH/i-Bu2NH2 in 70 mol %-30% D2O at
25.0 °C indicated complete absence of the protons on the
J. Org. Chem, Vol. 72, No. 4, 2007 1101

Cho and Pyun
TABLE 5. Effect of â-Aryl Group on the Ketene-Forming
nitrophenyl group. This result underlines the carbanion stabiliz-
ing ability of the thienyl group.
Eliminations from ArCH2CO2C6H4-4-NO2 Promoted by R2NH/
+
R2NH2 Buffers in 70 mol % MeCN(aq) at 25.0 °C
Ar ) thienyl
(1a)
Ar ) phenyl
(2)a
Ar ) p-nitrophenyl
(3)b
Experimental Section
E
c
rel. rate (k2
b
âlg
k1
)
1
0.7
70
Materials. Aryl thienylacetates 1 were synthesized by reacting
2-thiophenacetic acid, substituted phenols, 2-chloro-1-methylpyri-
dinium iodide, and triethylamine in CH2Cl2 under nitrogen.2,12 The
0.64 ( 0.09
0.77 ( 0.03c,d
0.47 ( 0.01
-0.21 ( 0.01
11.7
-0.49 ( 0.01 -0.43e
0.528
2105
1
yield (%), IR (KBr, CdO, cm-1), H NMR (400 MHz, CDCl3,
k-1/k2
560
J values are in Hz), 13C NMR (100 MHz), and mass spectral data
a Reference 2. b Reference 5. c R2NHdBz(i-Pr)NH. d Determined in the
for the new compounds are as follows.
absence of Bu4N+Br-. e Solvent was MeCN.
1
p-Nitrophenyl Thienylacetate (1a). Yield 62%; IR 1762; H
NMR δ 4.13 (s, 2H), 7.02 (dd, J ) 3.50, 5.12, 1H), 7.05 (d, J )
3.50, 1H), 7.29 (m, 3H), 8.27 (d, J ) 9.12, 2H); 13C NMR δ 35.5,
122.3, 125.2, 25.7, 127.1, 127.5, 133.4, 145.5, 155.3, 167.9; HRMS-
(EI); m/z calcd for C12H9NO4S 263.0252, found 263.0255.
â-carbon. All of these results provide strong evidence that
elimination from 1a-c promoted by R2NH/R2NH2+ in 70 mol
% MeCN(aq) proceeds by the concurrent E2 and E1cb mech-
anisms.
2-Methoxy-4-nitrophenyl thienylacetate (1b). Yield 70%; IR
1
1772; H NMR δ 3.89 (s, 3H), 4.14 (s, 2H), 7.01 (dd, J ) 3.48,
Interestingly, the k2E values for 1a and b show large negative
deviations in Figure 4. This could be because the extents of
CR-OAr bond cleavages are smaller than those of 1c-e. The
transition state would then be destabilized because of the
difficulty of the charge transfer from the â- to the R-carbon, to
decrease the degree of double bond character and the rate. In
addition, the Bro¨nsted â values increase by 2-fold from 0.30-
0.33 to 0.60-0.64 by the same variation of the reactant structure,
indicating a sharp increase in the proton transfer (Table 3).
Hence, an abrupt change of the E2 transition state is indicated
by the change from 1c-e to 1a and b. A similar result was
observed for 2 under the same condition.5 At present, the origin
of this abrupt change is not clear. Nevertheless, this result
indicates unusual sensitivity of the E2 transition state to the
reactant structure in the borderline between the E2 and E1cb.
5.12, 1H), 7.21 (d, J ) 8.60, 1H), 7.28 (dd, J ) 5.12, 1.34, 1H),
7.82 (d, J ) 2.42, 1H), 7.87 (dd, J ) 2.42, 8.60, 1H); 13C NMR δ
35.0, 56.4, 107.7, 116.4, 123.1, 125.5, 127.0, 127.4, 133.7. 144.9,
146.4, 151.6, 167.6; HRMS (EI); m/z calcd for C13H11NO5S
293.0358, found 293.0359.
2-Chloro-4-nitrophenyl thienylacetate (1c). Yield 61%; IR
1782; 1H NMR δ 4.18 (s, 2H), 7.02 (t, J ) 3.42, 1H), 7.08 (d, J )
3.42, 1H), 7.29 (dd, J ) 1.32, 5.12, 1H), 7.34 (d, J ) 8.88, 1H),
8.17 (dd, J ) 2.72, 8.88, 1H), 8.35 (d, J ) 2.72, 1H); 13C NMR δ
35.0, 123.1, 124.2, 125.7, 126.0, 127.0, 127.7, 128.3, 133.0, 145.8,
151.9, 167.1; HRMS(EI); m/z calcd for C12H8ClNO4S 296.9863,
found 296.9861.
2-Trifluoromethyl-4-nitrophenyl Thienylacetate (1d). Yield
1
65%; IR 1782; H NMR δ 4.17 (s, 2H), 7.02 (dd, J ) 3.24, 4.84,
1H), 7.05 (d, J ) 3.76, 1H), 7.29 (dd, J ) 1.08, 4.84, 1H), 7.49 (d,
J ) 9.12, 1H), 8.45 (dd, J ) 2.68, 8.60, 1H), 8.57 (d, J ) 2.68,
1H); 13C NMR δ 35.0, 120.2, 123.0, 125.5, 125.8, 127.2, 127.8,
128.2, 132.6, 145.0, 152.7, 167.4; LRMS (EI) m/z 331(20)[M]+,
124(4), 97(100); HRMS (EI); m/z calcd for C13H8F3NO4S 331.0126,
found 331.0131.
Effect of the â-Aryl Group on the Ketene-Forming
Transition State. Table 5 shows that the rates, â and |âlg|
values, for the E2 reactions of 1a and 2 are similar, indicating
similar transition-state structures. The most important finding
in this study is that 1a reacts by competing E2 and E1cb
mechanisms, whereas 2 reacts by the E2 mechanism. Because
the negative charge density at the â-carbon can be delocalized
by the thienyl group, the E1cb intermediate seems to be
stabilized and the E1cb mechanism competes. This indicates
the stronger anion stabilizing ability of the thienyl group in
comparison to the phenyl group. However, the electron-
withdrawing ability of the thienyl group is much weaker than
that of the p-nitrophenyl group. Hence, k1 of 1a is smaller than
that of 3 by 70-fold, indicating the weaker acidity of the Câ-H
bond in the former. In addition, the k-1/k2 of 1a is larger than
that of 3 by a factor of 4. Because the deprotonation from 1a
(k1) proceeds at a slower rate than that from 3, the k-1 step
should be more exothermic and faster. On the other hand, the
k2 value should be independent of the energy of the intermediate
because it involves a higher energy barrier (vide supra). This
would predict a larger k-1/k2 value for 1a.
2,4-Dinitrophenyl Thienylacetate (1e). Yield 45%; IR 1788;
1H NMR δ 4.23 (s, 2H), 7.02 (dd, J ) 3.42, 5.14, 1H), 7.08 (d,
J ) 3.42, 1H), 7.29 (dd, J ) 1.04, 5.14, 1H), 7.48 (d, J ) 8.88,
1H), 8.51 (dd, J ) 2.74, 8.88, 1H), 8.97 (d, J ) 2.74, 1H); 13C
NMR δ 35.0, 120.2, 123.0, 125.5, 125.8, 127.2, 127.8, 128.2, 132.6,
145.0, 152.7, 167.4; HRMS(EI); m/z calcd for C12H8N2O6S
308.0126, found 308.0123.
Acetonitrile was purified as described before. The solutions of
R2NH/R2NH2+ in 70 mol % MeCN(aq) were prepared by dissolving
equivalent amount of R2NH and R2NH2+ in 70 mol % MeCN(aq).
In all cases, the ionic strength was maintained to 0.1 M with
Bu4N+Br-.
+
Kinetic Studies. Reactions of 1 with R2NH/R2NH2 in 70 mol
% MeCN(aq) were followed by monitoring the increase in the
absorbance of the aryloxides at 400-426 nm with a UV-vis
spectrophotometer as described.2-6
E
Calculation of k2 , k1, and k-1/k2 Values. Utilizing the kobs
E
values and the base concentration, k2 , k1, and k-1/k2 values that
best fit with eq 2 have been calculated as before.2,5
Product Studies. The products of the reactions between 1a and
+
i-Bu2NH/i-Bu2NH2 in 70 mol % MeCN(aq) were identified as
In conclusion, we have investigated the ketene-forming
eliminations from 1a-e promoted by R2NH/R2NH2+ in 70 mol
% MeCN(aq). The rates and the transition-state structures for
the E2 pathways are similar to those for the corresponding
eliminations from 2. However, eliminations from 1a-c proceed
by the competing E2 and E1cb mechanisms, which were
reported for 3 having a strongly electron-withdrawing p-
described.2 From this reaction, N,N-diisobutylthenamide was ob-
tained in 86% yield. For all reactions, the yields of aryloxides as
determined by comparing the absorbance of the infinity absorbance
of the samples from the kinetic studies with those of the authentic
aryloxides were in the range of 96-99%.
H-D Exchange Experiment. To determine whether 1a-c may
undergo H-D exchange during the reaction, the reaction was
1102 J. Org. Chem., Vol. 72, No. 4, 2007

Elimination, E2 and E1cb, â-Aryl Group Effect
performed in an NMR tube. The reactants (0.04 mmol) were added
to a solution containing i-Bu2NH/i-Bu2NH2 (0.05 M, 0.6 mL) in
Acknowledgment. This work was supported by Pukyong
National University Research Fund in 2005(0012000200504500).
+
70 mol % MeCN-30% D2O at 25.0 °C. The NMR spectrum taken
immediately after mixing indicated complete H-D exchange at the
â-carbon.
Supporting Information Available: Synthesis, rate constants
for eliminations from 1a-e promoted by R2NH/R2NH2+ in 70 mol
% MeCN(aq), and plots of kobs versus base concentration. This
information is available free of charge via the Internet at
http://pubs.acs.org.
Control Experiments. The stabilities of 1a-e were determined
as reported.2-4 Solutions of aryl thienylacetates 1a-d were stable
for at least 1 week in 70 mol % MeCN(aq) solution at room
temperature. However, the solution of 1e was stable for only 3 days.
JO0612978
J. Org. Chem, Vol. 72, No. 4, 2007 1103