The effect of acyl substituents on the α-effect: Contrasting α-effect profiles for reactions of 4-nitrophenyl substituted benzoates with neutral and anionic nucleophiles

Article abstract of DOI:10.1016/S0040-4039(01)01719-1

The magnitude of the α-effect for reactions of 4-nitrophenyl substituted benzoates with a pair of anionic nucleophiles is independent of the electronic nature of the acyl substituent, while the one for the corresponding reactions with a pair of neutral nucleophiles increases as the acyl substituent changes from a strong electron withdrawing substituent to electron donating ones.

Full text of DOI:10.1016/S0040-4039(01)01719-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8051–8053
The effect of acyl substituents on the a-effect: contrasting
a-effect profiles for reactions of 4-nitrophenyl substituted
benzoates with neutral and anionic nucleophiles
Ik-Hwan Um,* Hyun-Joo Han and Eun-Kyung Chung
Department of Chemistry, Ewha Womans University, Seoul 120-750, South Korea
Received 22 August 2001; accepted 13 September 2001
Abstract—The magnitude of the a-effect for reactions of 4-nitrophenyl substituted benzoates with a pair of anionic nucleophiles
is independent of the electronic nature of the acyl substituent, while the one for the corresponding reactions with a pair of neutral
nucleophiles increases as the acyl substituent changes from a strong electron withdrawing substituent to electron donating ones.
©
2001 Elsevier Science Ltd. All rights reserved.
The term a-effect was given to the abnormally
enhanced nucleophilic reactivity shown by nucle-
ophiles having an atom with one or more nonbond-
ing electron pairs at the a-position from the
with a maximum a-effect at ca. 50 mol% DMSO has
also been observed for the corresponding reaction of
4-nitrophenyl diphenyl phosphinate and 4-nitrophenyl
6
benzenesulfonate. Similarly, the increasing a-effect
1
nucleophilic center. The magnitude of the a-effect
profile upon addition of MeCN in the medium has
been found to be common for the reactions of substi-
has been suggested to be governed by many factors
2
such as the basicity of a-effect nucleophiles, the mag-
tuted phenyl acetates in MeCN–H
2
O
mixtures,
3
nitude of Brønsted b values, the hybridization type
although the magnitude of the a-effect was demon-
nuc
4
,5
6
of electrophiles, electrophilic center atoms and sol-
strated to be significantly dependent on the electronic
nature of the substituent in the leaving group.
7
–9
9b
vents.
Recently, we have demonstrated that the magnitude
It appeared to us as highly informative to investigate
the effect of acyl substituents on the a-effect. Herein
we report the first such results for an a-effect system,
kinetic studies of the reactions of 4-nitrophenyl X-
substituted benzoates (1a–1j) with a pair of anionic
of the a-effect is strongly dependent on the medium
for the reaction of 4-nitrophenyl acetate with butane-
−
2
,3-dione monoximate (Ox ) as an a-effect nucle-
−
ophile and 4-chlorophenoxide (ClPhO ) as
a
−
−
nucleophiles, Ox and ClPhO , as shown in Eq. (1).
Surprisingly, the a-effect profile obtained from the
reactions of 1a–1j with the anionic nucleophiles con-
trasts with the one obtained previously from the reac-
tions of 1a–1j with a pair of neutral nucleophiles,
corresponding normal nucleophile in DMSO–H O
2
and in MeCN–H O mixtures of varying composi-
2
6
–9
tions.
The a-effect (k
Ox
−
/kClPhO ) increased on addi-
−
tion of DMSO in the reaction medium up to near 50
mol% DMSO, and then decreased upon further addi-
tion of DMSO, resulting in a bell-shaped dependence
hydrazine (NH NH ) as an a-effect nucleophile and
2
2
7
glycylglycine (glygly) as
a
corresponding normal
The a-effect for the reactions with the
/k , is independent of
of the a-effect on solvent composition. However, the
10a
nucleophile.
a-effect for the same reactions run in MeCN–H O
2
anionic nucleophiles, kOx
−
ClPhO
−
mixtures increased steadily as the mol% MeCN in the
8
the electronic nature of the acyl substituents, while
medium increased. The bell-shaped a-effect profile
the a-effect for the corresponding reactions with the
neutral nucleophiles, k
/k
, increases as the
NH
2
NH2 glygly
acyl substituent changes from a strong electron with-
drawing substituent to electron donating ones. Two
plausible causes of the contrasting a-effect profile are
discussed.
Keywords: a-effect; amines; kinetics; mechanism; substituent effect.
Corresponding author. Tel.: 822 3277-2349; fax: 822 3277-2844;
e-mail: ihum@mm.ewha.ac.kr
*
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01719-1

8
052
I.-H. Um et al. / Tetrahedron Letters 42 (2001) 8051–8053
O
C
O
Nu-
+
-O
O
NO2
C
Nu
+
NO2
X
X
(1)
-
-
-
-
-
Nu = MeC(O)C(Me)=NO ( Ox ) and 4-ClC H O ( ClPhO )
6
4
X = 4-MeO (1a), 4-Me (1b), 3-Me (1c), H (1d), 4-Cl (1e), 3-Cl (1f),
-CN (1g), 4-NO (1h), 4-Cl-3-NO (1i), 3,5-(NO ) (1j)
4
2
2
2 2
−
−
The kinetic study was performed spectrophotomerically
by monitoring the appearance of 4-nitrophenoxide ion
at 410 nm. All the reactions obeyed pseudo-first-order
kinetics up to over 90% of the total reaction, and the
observed pseudo-first order rate constants (kobs) were
obtained from the well known equation, ln(A −A )=−
the a-effect for reactions of 1a–1j with Ox and ClPhO
remains independent of the electronic nature of the acyl
substituents, while the one for the reaction with
NH NH and glygly increases as the acyl substituent
changes from a strong electron withdrawing substituent
(EWS) to electron donating substituents (EDS).
2
2
ꢀ
t
kobst+c. Usually, five different concentrations of nucle-
ophiles were employed and replicate values of kobs were
determined to obtain the second-order rate constants
from the slope of linear plots of kobs versus nucleophile
concentrations. The second-order rate constants
obtained in this way are summarized in Table 1.
One might attribute the contrasting a-effect profile to a
difference in the reaction mechanism between the reac-
tions with the anionic nucleophiles and with the neutral
amine nucleophiles. It has generally been understood
that aminolyses of carboxylic esters proceed through an
addition intermediate and the rate determining step
(RDS) is dependent on the basicity of the leaving group
As shown in Table 1, the second-order rate constants
are strongly dependent on the electronic nature of the
acyl substituent, i.e. the second-order rate constant for
10–12
and the amine nucleophile.
The RDS of aminolysis
reactions has been suggested to change from break-
down of the addition intermediate to products to for-
mation of the intermediate as the amine nucleophile
−
−1 −1
the reaction with Ox increases from 6.43 M
s
to
as the acyl substituent X
changes from 4-MeO to H and 3,5-(NO ) , respectively.
−
1
−1
34.2 and 15,500 M
s
becomes more basic than the leaving group by 4–5 pK
a
2
2
10–12
units.
The RDS of the reactions of 1a–1j with
A similar result is obtained for the reaction with
−
−
NH NH and glygly has been reported to be the break-
ClPhO . It is also seen that Ox is much more reactive
2 2
−
down of the addition intermediate, since these amines
are only ca. 1 pK unit more basic than the leaving
than ClPhO for all the substrates, indicating the a-
effect is significant in the present reaction system. The
a
0a
1
4
-nitrophenoxide.
On the other hand, acyl-transfer
effect of acyl substituents on the a-effect (k
−
/k
−
)
Ox
ClPhO
−
−
reactions with anionic nucleophiles have been suggested
to proceed either through a one-step concerted or
for the reaction of 1a–1j with Ox and ClPhO is
1
3
demonstrated in Fig. 1 together with the a-effect for the
14
through a stepwise mechanism. However, the RDS of
the acyl transfer reaction with anionic nucleophiles as
in the present system has been suggested to be the
nucleophilic attack process, whether the reaction pro-
ceeds concertedly or in stepwise fashion. Therefore,
the difference in the RDS between the reactions with
amines and with the anionic nucleophiles might be a
plausible cause of the contrasting a-effect profile shown
in Fig. 1.
reaction of 1a–1j with NH NH and glygly (k
/
NH2NH2
2
2
kglygly) for comparison. One can see that the magnitude
of the a-effect for the reactions of 1a–1j with the
anionic nucleophiles is much larger than that for the
corresponding reaction with the neutral amine nucle-
ophiles. More surprisingly, the a-effect profile obtained
14
−
−
from the reaction of 1a–1j with Ox and ClPhO con-
trasts with the one obtained from the corresponding
reaction with NH NH and glygly, i.e. the magnitude of
2
2
The magnitude of the a-effect has been suggested to be
governed by the ground-state (GS) and transition-state
Table 1. Summary of second-order rate constants for
7–9
−
(
TS) energies. Ox has recently been reported to be
−
reactions of 4-nitrophenyl X-substituted benzoates with
−
−
5.7 kcal/mol less solvated than ClPhO in 20 mol%
Ox and ClPhO in water containing 20 mol% DMSO at
5.090.1°C
7
b
−
DMSO. This difference in the GS energy between Ox
2
−
and ClPhO should be responsible for the a-effect
−
1
s−1
kClPhO− (M−1 s−1
−
X
kOx− (M
)
)
shown by Ox to a certain degree. However, the GS
energy difference between these nucleophiles is con-
−
−
4
4
3
-MeO
-Me
-Me
6.43
12.9
22.8
34.2
113
254
990
1470
3160
15500
0.0316
0.0754
0.110
0.185
0.604
1.30
5.92
8.01
15.4
72.7
stant, since Ox and ClPhO were used for all the
reactions of 1a–1j. Similarly, the GS energy difference
between NH NH and glygly is also constant. Accord-
2
2
H
ingly, if the GS contribution to the a-effect is more
responsible than the TS contribution, one can expect
that the magnitude of the a-effect would be constant.
As shown in Fig. 1, the a-effect for the reactions with
4
3
4
4
4
3
-Cl
-Cl
-CN
-NO2
-Cl-3-NO2
,5-(NO2)2
−
−
Ox and ClPhO is nearly constant, indicating that the
GS contribution to the a-effect is more significant than
the TS contribution. However, the a-effect for the

I.-H. Um et al. / Tetrahedron Letters 42 (2001) 8051–8053
8053
Acknowledgements
The authors are grateful for the financial support from
KOSEF of KOREA (1999-2-123-003-5).
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−
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