Elimination reactions of aryl phenylacetates promoted by R2NH/R2NH2+ in 70 mol % MeCn(aq). Effect of the β-phenyl group on the ketene-forming transition state

Full text of DOI:10.1021/jo991473v

J . Org. Chem. 2000, 65, 1239-1242
1239
Elim in a tion Rea ction s of Ar yl
P h en yla ceta tes P r om oted by R NH/R
The relative importance of these factors on the ketene-
forming transition state is assessed.
+
2
2
NH
2
in 70 m ol % MeCN(a q). Effect of th e
â-P h en yl Gr ou p on th e Keten e-F or m in g
Tr a n sition Sta te
Resu lts
Aryl phenylacetates 1 and 2 were synthesized by the
reaction between phenylacetic acid and diphenylacetic
acids with substituted phenols, 2-chloro-1-methylpyri-
Bong Rae Cho,*,† Yong Kwan Kim, Yoon J e Seung,
†
‡
‡
,‡
J u Chang Kim, and Sang Yong Pyun*
dinium iodide, and Et
3
N in CH
The reactions between 1 and 2 and R
buffers in 70% MeCN(aq) produced aryloxides
2
Cl
2
as described previ-
ously.1
4,15
NH/
2
Department of Chemistry, Division of Chemistry and
+
2 2
R NH
Molecular Engineering, Korea University, 1-Anamdong,
Seoul 136-701, and Department of Chemistry, Pukyong
National University, Pusan 608-737, Korea
in 92-99% yields.
To probe whether the aminolysis reaction may compete
with the ketene-forming elimination reaction, the reac-
Received September 17, 1999
tions of 4-nitro- and 2,4-dinitrophenyl butyrates with
+
R
2
NH/R
2
NH
2
buffers in 70% MeCN(aq) were briefly
It is well established that the base-catalyzed hydrolysis
of aryl p-nitrophenylacetates and other activated esters
proceed by an E1cb elimination to afford the ketene
+
2 2 2
examined. For reactions of the former with R NH/R NH
buffers, no trace of 4-nitrophenoxide could be detected
by a UV-vis spectrophotometer after 10 h. On the other
hand, the latter underwent slow aminolysis under the
reaction conditions. The second-order rate constant for
intermediate followed by the addition of water under
various conditions.1
-13
The reaction proceeded by the E2
NH in MeCN was employed as the
mechanism when R
2
the reactions of 2,4-dinitrophenyl butyrates with R
R NH
2 2
2
NH/
buffers in 70% MeCN(aq) are summarized in the
footnote in Table 1. The values are approximately 60-
000-fold smaller than the k values for the corresponding
base-solvent system.14 Concurrent E2 and E1cb mech-
+
anisms were noted for the reactions of p-nitrophenyl
+
p-nitrophenylacetate with R
2
NH/R
2
NH
2
buffer in 70%
3
2
MeCN(aq).14 These results demonstrate the mechanistic
diversity of the ketene-forming eliminations in the E2
and E1cb borderline.
ketene-forming eliminations from 1c under the same
conditions. Because the steric requirements of the propyl
16
and benzyl groups are similar, the aminolysis of 1c, if
To further expand our understanding of ketene-form-
any, is expected to proceed at a rate comparable to that
of 2,4-dinitrophenyl butyrate. Hence, it is highly unlikely
that the aminolysis reaction would compete with the
ketene-forming elimination of 1c. Furthermore, since the
steric requirement of the diphenylmethyl group is much
larger than that of the propyl group, the aminolysis of
ing eliminations, reactions of â-substituted aryl phenyl-
+
acetates 1 and 2 with R
2
NH/R
2
NH
2
buffer in 70%
MeCN(aq) have now been studied (eq 1). The phenyl
2
c should be even less important. Therefore, the pos-
sibility of competing aminolysis for the reactions of 1 and
2
is strongly negated by this result.
Rates of reactions between 1 and 2 and R NH/R NH
2 2 2
+
buffers in 70% MeCN(aq) were followed by monitoring
the increase in the absorption of the aryloxides at 400-
426 nm with a UV-vis spectrophotometer as described
previously.14 Excellent pseudo-first-order kinetic plots,
which covered at least 3 half-lives, were obtained. Divid-
ing the pseudo-first-order rate constants by the base
concentration provided the second-order rate coefficients
â
group is expected to increase the acidity of the C sH
bond, the stability of the CdC bond, and the steric effect.
†
Korea University.
Pukyong National University.
‡
(
1) Holomquist, B.; Bruice, T. C. J . Am. Chem. Soc. 1969, 91, 2993-
3
3
5
1
002.
k
2
presented in Table 1.
The k values showed excellent correlation with the pK
values of the promoting base on the Br o¨ nsted plot
Figures 1 and 2). The â value decreases as the leaving
group is made less basic (Table 2). Similarly, the k values
correlated satisfactorily with the leaving group pK
(2) Holomquist, B.; Bruice, T. C. J . Am. Chem. Soc. 1969, 91, 3003-
006.
2
a
(
3) Pratt, R. F.; Bruice, T. C. J . Am. Chem. Soc. 1970, 92, 5956-
964.
(
653.
(
4) Inoue, M.; Bruice, T. C. J . Am. Chem. Soc. 1982, 104, 1644-
2
(
(
(
(
5) Inoue, M.; Bruice, T. C. J . Org. Chem. 1982, 47, 959-963.
a
6) William, A. J . Chem. Soc., Perkin Trans. 2 1972, 808-812.
7) William, A.; Douglas, K. T. Chem. Rev. 1975, 75, 7-649.
8) Tagaki, W.; Kobayashi, S.; Kurihara, K.; Kurashima, K.; Yoshida,
values (Figures 3 and 4). The |âlg| value decreases with
a stronger base (Table 3).
Y.; Yano, J . J . Chem. Soc., Chem. Commun. 1976, 843-845.
9) Broxton, T. J .; Duddy, N. W. J . Org. Chem. 1981, 46, 1186-
191.
10) Chandrasekar, R.; Venkatasubramanian, N. J . Chem. Soc.,
Perkin Trans. 2 1982, 1625-1631.
11) Douglas, K. T.; Alborz, M.; Rullo, G. R.; Yaggi, N. F. J . Chem.
Soc., Chem. Commun. 1982, 242-246.
12) Isaac, N. S.; Najem, T. S. J . Chem. Soc., Perkin Trans. 2 1988,
57-562.
13) Chung, S. Y.; Yoh, S. D.; Choi, J . H.; Shim, K. T. J . Korean
Chem. Soc. 1992, 36, xxxx.
14) Cho, B. R.; Kim, Y. K.; Maing Yoon, C.-O. J . Am. Chem. Soc.
997, 119, 691-697.
(
1
Discu ssion
(
Mech a n ism of Elim in a tion fr om 1 a n d 2 P r o-
(
+
m oted by R
2
NH/R
2
NH
2
Bu ffer s in 70% MeCN(a q).
(
Results of kinetic investigations and product studies
5
(
(15) Saigo, K.; Usui, M.; Kikuchi, K.; Shimada, E.; Mukaiyama, T.
Bull. Chem. Soc. J pn. 1977, 50, 1863-1866.
(16) Charton, M. J . Am. Chem. Soc. 1975, 97, 1552-1556.
(
1
1
0.1021/jo991473v CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/02/2000

1
240 J . Org. Chem., Vol. 65, No. 4, 2000
Notes
Ta ble 1. Ra te Con sta n ts for Elim in a tion s fr om P h CH(R)CO2C6H4-2-X-4-NO2a P r om oted by R2NH/R2NH2+ Bu ffer s in 70%
MeCN(a q)b
k2,f-h M-1 s-1
R2NHc,d
pKae
1a
1b
1c
2a
2b
2c
morpholine
THIQ
16.6
17.1
18.9
18.9
19.6
0.0510
0.0759
1.31
0.142
13.3
1.71
3.29
11.5
28.0
45.3
97.5
0.00389
0.00888
0.104
0.000937
0.485
0.217
0.403
2.36
0.00917
7.28
9.67
i
19.3
52.5
0.188
119
piperidine
j
k
7.10k
2
,6-DMP
pyrrolidine
25.8
154
a
Substrate] ) 3.0 × 10 M. b µ ) 1.0 M (Bu4N Br ). [Base] ) 8.0 × 10 to 1.0 × 10 M. d [R2NH]/[R2NH2 ] ) 1.0. e References 24
-5
+
-
c
-4
-1
+
[
f
g
h
and 25. Average of three or more rate constants. Estimated uncertainty ( 3%. The k2 values for the aminolysis reactions of 2,4-
dinitrophenyl butyrate with R2NH/R2NH2 buffers in 70% MeCN(aq) are 0.00985, 0.0174, 0.250, and 2.55 M
THIQ, piperidine, and pyrrolidine, respectively. 1,2,3,4-Tetrahydroisoquinoline. cis-2,6-Dimethylpiperidine. Reference 14.
+
-1 -1
s
when R2NH is morpholine,
i
j
k
F igu r e 2. Br o¨ nsted plots for the ketene-forming eliminations
from aryl diphenylacetates [Ph CHCO -2-X-4-NO ] pro-
moted by R NH/R NH buffers in 70% MeCN(aq) at 25.0 °C
F igu r e 1. Br o¨ nsted plots for the ketene-forming eliminations
2
2
C
6
H
3
2
from aryl phenylacetates [PhCH
2
CO
2
C
6
H
3
-2-X-4-NO
2
] pro-
+
2
+
moted by R
2
NH/R
2
NH
2
buffers in 70% MeCN(aq) at 25.0 °C
2
2
2
[X ) H (9), Cl (b), NO (2)].
[X ) H (9), Cl (b), NO
2
(2)].
Ta ble 2. Br o1 n sted â Va lu es for Keten e-F or m in g
clearly establish that the reactions of aryl phenylacetates
Elim in a tion s fr om P h CH(R)CO2C6H4-2-X-4-NO2 P r om oted
+
+
1
and 2 with R
2
NH/R
2
NH
2
buffers in 70% MeCN(aq)
by R2NH/R2NH2 Bu ffer s in 70% MeCN(a q) a t 25.0 °C
proceed by the E2 mechanism. Because the possibility
of the competing aminolysis is ruled out and the ketene-
forming elimination reactions exhibit second-order kinet-
ics, all but bimolecular pathways can be ruled out. In
addition, an E1cb mechanism is negated by the substan-
â
X
pKaa
R ) H
R ) Ph
H
Cl
NO2
20.7
18.6
16.0
0.78 ( 0.04
0.37 ( 0.03
0.23 ( 0.02
0.67 ( 0.04
0.49 ( 0.03
0.33 ( 0.04
1
7-19
tial values of â and |âlg|.
a
Reference 24.
This conclusion is supported by the interaction coef-
ficients. Table 2 shows that the â values for 1 decrease
gradually as the leaving groups are made less basic.20
The result can be described by a positive pxy interaction
coefficient, pxy ) ∂â/∂pKlg ) ∂âlg/∂pKBH, which describes
the interaction between the base catalyst and the leaving
group.19,23 The observed decrease in the |âlg| values as
the catalyst is made more basic is another manifestation
of this effect, i.e., pxy ) ∂âlg/∂pKBH > 0 (Table 3). On the
More-O’Ferall-J encks energy diagram in Figure 5, a
change to a better leaving group will raise the energy of
the top edge of the diagram. The transition state on the
diagonal reaction coordinate will then move slightly
toward the right as depicted by a shift from A to B on
(
17) Saunders, W. H. J r.; Cockerill, A. F. Mechanism of Elimination
Reactions; Wiley: New York, 1973; pp 510-523.
18) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in
Organic Chemistry; Harper and Row: New York, 1987; pp 591-616.
19) Gandler, J . R. In The Chemistry of Double Bonded Functional
(
the energy diagram, resulting in a small decrease in â
Similarly, a stronger base will raise the
energy of the right side of the energy diagram and shift
(
9,23
(
vide supra).1
Groups; Patai, S., Ed.; J ohn Wiley & Sons: Chichester, 1989; Vol. 2,
Part 1, pp 734-797.

Notes
J . Org. Chem., Vol. 65, No. 4, 2000 1241
F igu r e 3. log k
eliminations from aryl phenylacetates [PhCH
2
vs pKlg values for the ketene-forming
CO -2-X-
buffers in 70% MeCN(aq)
NH ) morpholine (9), tetrahydroisoquinoline
b), piperidine (2), pyrrolidine (1)].
F igu r e 4. log k2 vs pKlg values for the ketene-forming
2
2
C
6
H
3
eliminations from aryl diphenylacetates [Ph CHCO C H -2-
2
2
6
3
+
+
4
-NO
2
] promoted by R
2
NH/R
2
NH
2
2 2 2 2
X-4-NO ] promoted by R NH/R NH buffers in 70% MeCN-
at 25.0 °C [R
2
(aq) at 25.0 °C [R NH ) cis-2,6-dimethylpiperidine (1), mor-
2
(
pholine (9), tetrahydroisoquinoline (b), piperidine (2), pyrroli-
dine ([)].
Ta ble 3. Br o1 n sted âlg Va lu es for Keten e-F or m in g
Elim in a tion s fr om P h CH(R)CO2C6H4-2-X-4-NO2 P r om oted
by R2NH/R2NH2 Bu ffer s in 70% MeCN(a q) a t 25.0 °C
+
âlg
R2NH
pKaa
R ) H
R ) Ph
morpholine
THIQ
piperidine
16.6
17.1
18.9
18.9
19.6
-0.58 ( 0.07
-0.58 ( 0.10
-0.40 ( 0.03
-0.72 ( 0.06
-0.71 ( 0.04
-0.57 ( 0.04
-0.49 ( 0.01
-0.51 ( 0.03
b
2
,6-DMP
-0.37
pyrrolidine
-0.23 ( 0.05
a
References 24 and 25. b Reference 14.
the transition state from A to C to decrease the extent of
-OAr bond cleavage. The positive pxy coefficients are
C
R
inconsistent with an E1cb mechanism for which pxy ) 0
is expected, but provide additional support for the
concerted E2 mechanism.1
9,23
A similar interpretation can be put forward for the
changes in â and |âlg| values with the leaving group and
base strength variations for 2. However, it should be
noted that the transition state for 2 is relatively insensi-
(
20) A reviewer argued that the 500-fold difference in rate for the
F igu r e 5. Reaction coordinate diagram for ketene-forming
eliminations. The effects of the change to a better leaving
group and a stronger base are shown by the shift of the
transition state from A to B and from A to C, respectively.
reactions of 1a -c is relatively small and would not result in such
changes in the â values. However, we have previously observed a large
change of the k
group in the imine-forming eliminations from ArCH
by Et NH in MeCN, even though the rate difference was only 30-fold.
H
/k
D
values from 7.8 to 1.6 by the change in the N-R
2
N(Cl)R promoted
2
1
2
A similar result was observed for MeONa-promoted eliminations from
tive to the variations of the leaving group and base
the same substrates.2
2
(Tables 2 and 3).
(
(
21) Cho, B. R.; Suh, Y. W. J . Org. Chem. 1989, 54, 2855-2858.
22) Cho, B. R.; Maeng, J . H.; Yoon, J . C.; Kim, T. R. J . Org. Chem.
Effect of th e â-P h en yl Gr ou p on th e Keten e-
1
987, 52, 4752-4756.
F or m in g Tr a n sition Sta te. Table 4 shows that the rate
of piperidine-promoted elimination from 2a is 12.5-fold
slower than that from 1a probably because of the steric
effect by the â-phenyl group (vide supra). The â value is
(
(
(
23) J encks, W. P. Chem. Rev. 1985, 85, 511-527.
24) Coetzee, J . F. Prog. Phys. Org. Chem. 1965, 4, 45-92.
25) Cho, B. R.; Lee, S. J .; Kim, Y. K. J . Org. Chem. 1995, 60, 2072-
076.
2

1
242 J . Org. Chem., Vol. 65, No. 4, 2000
Notes
Ta ble 4. Effect of th e â-R Gr ou p a n d Am in e Ba ses on
th e Keten e-F or m in g Elim in a tion s fr om
bond cleavage by the â-Ph group. A significant base steric
effect was noted for the reaction of 2 with 2,6-DMP buffer.
P h CH(R)CO2C6H4-2-X-4-NO2 P r om oted by R2NH/R2NH2+
Bu ffer s in 70% MeCN(a q) a t 25.0 °C
Exp er im en ta l Section
R ) H
piperidine
R ) Ph
piperidine 2,6-DMP
0.08 0.0008
Ma ter ia ls. Aryl esters of phenylacetic acid 1a -c and 4-nitro-
and 2,4-dinitrophenyl butyrates were available from a previous
study.14 Diphenylacetic acid derivatives 2a -c were synthesized
by reacting diphenylacetic acid, substituted phenols, 2-chloro-
R2NH
2,6-DMP
0.1
relative
rate
â
âlg
1
a
1
-methylpyridinium iodide, and triethylamine in CH
2
Cl
2
under
0.78 ( 0.04
0.67 ( 0.03
-0.57 ( 0.04 -0.49 ( 0.01
14,15
nitrogen as described previously.
The spectral and analytical
-0.40 ( 0.03 -0.37b
X ) H. b Reference 14.
data of the compounds were consistent with the proposed
structures. The yield (%), melting point (°C), IR (KBr, CdO,
a
-
1
cm ), NMR (CDCl
compounds are as follows.
CHCO -p-NO
760 (CdO); NMR δ 8.25 (d, 2H, J ) 9.0), 7.41-7.32 (m, 10H),
7.25 (d, 2H, J ) 9.0), 5.28 (s, 1H). Anal. Calcd for C20 NO :
C, 72.06; H, 4.54; N, 4.20. Found: C, 72.23; H, 4.68; N, 4.05.
CHCO -2-Cl-4-NO (2b): yield 77%; mp 87-88;
IR 1770 (CdO); NMR δ 8.26 (d, 1H, J ) 2.4), 8.07 (dd, 1H, J )
.9, 2.6), 7.37-7.25 (m, 10H), 7.21 (d, 1H, J ) 9.0), 5.29 (s, 1H).
Anal. Calcd for C20 14ClNO C, 65.31; H, 3.84; N, 3.81.
Found: C, 65.42; H, 4.02; N, 3.60.
(C H ) CHCO C H -2,4-(NO ) (2c): yield 42%; mp 88-89;
3
), and combustion analysis data for the new
smaller and |âlg| is larger for the latter, indicating a
(
C
6
H
5
)
2
2
C
6
H
4
2
(2a ): yield 51%; mp 88-89; IR
smaller extent of proton transfer and a larger degree of
1
C
R
-OAr bond rupture in the transition state. The transi-
tion state for 2 appears to be more symmetrical than that
for 1, with similar extents of C -H and C -OAr bond
R
H
15
4
(
C
6
H
5
)
2
2
C
6
H
3
2
â
cleavage.
8
The transition-state differences for 1 and 2 can most
reasonably be interpreted with the substrate steric effect
and the stability of the CdC bond. The bulky phenyl
substituent at the â-carbon may hinder the approach of
H
4
:
6
5
2
2
6
3
2 2
IR 1774 (CdO); NMR δ 8.88 (d, 1H, J ) 2.7), 8.41 (dd, 1H, J )
.0, 2.7), 7.33-7.25 (m, 11H), 5.33 (s, 1H). Anal. Calcd for C20
: C, 63.49; H, 3.73; N, 7.40. Found: C, 63.63; H, 3.77; N,
9
14
H -
the base to the C
â
-H bond to decrease the extent of the
2 6
N O
C
â
-H bond cleavage in the transition state. The predic-
7
.13.
Buffer solutions were prepared by dissolving equivalent
tion is borne out by the smaller â value observed for 2.
In addition, because the phenyl group can stabilize the
CdC bond, more of the electron density on the â-carbon
would be transferred between C
transition-state double bond character, to obtain a maxi-
mum stabilization. This would predict a greater extent
+
amounts of R
2
NH and R
2
NH
2
in 70% MeCN(aq). In all cases,
Br
NH
+
-
the ionic strength was maintained to be 0.1 with Bu N
4
.
+
2
and C
R
to increase the
Kin etic Stu d ies. Reactions of 1 and 2 with R
2
NH/R
2
â
in 70% MeCN(aq) were followed by monitoring the increase in
absorption of the aryloxides at 400-426 nm with the reaction
1
4
time with a UV-vis spectrophotometer as described previously.
of C
R
sOAr bond rupture and a larger |âlg| value for 2, as
P r od u ct Stu d ies. The products of the reactions between
a -c and R NH/R NH in 70% MeCN(aq) were identified with
observed. Similar results were observed for the imine-
+
2
2 2 2
N(X)R.2
1,22
Thus, the
forming eliminations from ArCH
2
a UV-vis spectrophotometer. For all reactions, the absorbance
corresponding to the reactant decreased at 240-300 nm and
those for the aryloxides increased at 300-480 nm as the reaction
proceeded. Clean isosbestic points were observed at 310, 320,
and 310 nm for 2a , 2b, and 2c, respectively. The yields of
aryloxides determined by comparing the absorbance of the
infinity samples from the kinetic studies with those of the
authentic aryloxides were in the range 92-99%.
extent of the C sH bond cleavage decreased and the
â
degree of double bond character increased as the steric
requirements of the R group and the base were increased.
It is interesting to note that the rate of the ketene-
forming transition state is significantly influenced by the
base steric effect. Thus, the rate of elimination from 1 is
decreased by approximately 10-fold when the base is
changed from piperidine to more bulky cis-2,6-dimeth-
ylpiperidine. The corresponding difference in rate is much
larger for 2, apparently because of the increased steric
requirement of the substrate. For both substrates, the
To determine whether 1 and 2 may undergo aminolysis
reaction, solutions of 4-nitro- and 2,4-dinitrophenyl butyrates
-
5
+
-2
(
3.0 × 10 M) and R
2
NH/R
2
NH
2
buffers (2.0 × 10 M, buffer
ratio 1.0) in 70 mol % MeCN(aq) were allowed to react in a
cuvette at 25.0 °C. The former did not undergo any reaction for
1
0 h. However, the latter underwent slow aminolysis under the
|
â
lg| values decrease slightly, indicating a decrease in the
reaction conditions. The rate constant for the aminolysis was
determined by monitoring the increase in the 2,4-dinitrophe-
noxide concentration with time with a UV-vis spectrophotom-
eter as described previously.14
extent of C -OAr bond cleavage, as the steric effect of
R
the promoting base increases. However, due to the lack
of data for the degree of proton transfer, it is difficult to
assess the change in the transition-state structure caused
by the base steric effect.
Con tr ol Exp er im en ts. The stability of 2a -c was determined
14
as reported earlier. They were stable for 6 months in the solid
state. However, the solutions of 2a -c decomposed after 2 days
at room temperature.
In conclusion, the ketene-forming elimination reactions
from 1 and 2 promoted by R
MeCN(aq) proceed by the E2 mechanism. The rate is
retarded and the transition-state structure becomes more
+
2
NH/R
2
NH
2
buffer in 70%
Ack n ow led gm en t. This research was supported by
CRM-KOSEF.
symmetrical with similar extents of C
â
-H and C
R
-OAr
J O991473V