Effect of Acyl Substituents on the Reaction Mechanism for Aminolyses of 4-Nitrophenyl X-Substituted Benzoates

Article abstract of DOI:10.1021/jo000482x

Second-order rate constants (k_N) have been measured spectrophotometrically for the reaction of 4-nitrophenyl X-substituted benzoates with a series of alicyclic secondary amines in H₂O containing 20 mol % dimethyl sulfoxide at 25.0°C.

Full text of DOI:10.1021/jo000482x

J . Org. Chem. 2000, 65, 5659-5663
5659
Effect of Acyl Su bstitu en ts on th e Rea ction Mech a n ism for
Am in olyses of 4-Nitr op h en yl X-Su bstitu ted Ben zoa tes
Ik-Hwan Um,* J i-Sook Min, J ung-Ae Ahn, and Hyun-J oo Hahn
Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea
ihum@mm.ewha.ac.kr
Received March 29, 2000
Second-order rate constants (k
4
2
N
) have been measured spectrophotometrically for the reaction of
-nitrophenyl X-substituted benzoates with a series of alicyclic secondary amines in H O containing
0 mol % dimethyl sulfoxide at 25.0 °C. The magnitude of the k values increases with increasing
2
N
the basicity of amines and with increasing the electron-withdrawing ability of the acyl substituent
X. The Hammett plots obtained are not linear but show a break or curvature as the acyl substituent
X becomes electron withdrawing for all the amines studied, while the Brønsted-type plots are linear
with large ânuc values for all the substrates investigated. The nonlinear Hammett plots suggest a
change in the rate-determining step upon changing the acyl substituent X, whereas the linear
Brønsted-type plots indicate that the rate-determining step does not change upon changing amine
basicity. The Yukawa-Tsuno plots obtained are also linear with positive F and large r values,
X
suggesting that the nonlinear Hammett plots are not due to a change in the rate-determining step
upon changing the acyl substituent X, but due to resonance demand of the π-electron donor
substituent on the acyl moiety. The magnitude of the F
the basicity of amines and with increasing the electron-withdrawing ability of the acyl substituent
X, respectively, while that of the r values decreases with increasing F values and amine basicity.
X
and ânuc values increases with increasing
X
In tr od u ction
sted-type plots have been obtained that are linear for
reactions of carboxylic esters with a series of structurally
Reactions of nucleophiles with carbonyl compounds
have been intensively studied due to the interest in
chemistry and in biochemistry. The reaction of carboxylic
acid derivatives with amines has been suggested to
proceed through a stepwise mechanism with an addition
intermediate or through a concerted mechanism without
an intermediate.1 The common and probably the most
popular probes for the determination of reaction mech-
anism are linear free energy relationships of various
kinds, e.g., Hammett and Brønsted correlation.6-8 Brøn-
similar amines when the nucleofugality of the leaving
7-9
group is relatively poor.
However, aminolyses of car-
boxylic esters with a good leaving group have often shown
a break or a curvature in Brønsted-type plots from a large
slope (ânuc ) 0.8 ( 0.2) to a small one (ânuc ) 0.2 ( 0.1)
7-9
as the basicity of amines increases.
Such a break or a
-5
curvature in Brønsted-type plots has been attributed to
a change in the rate-determining step (RDS) of a multi-
7-9
step reaction.
The pK
a
value at the center of the curvature in the
0
10
Brønsted-type plot has been defined pK
whose pK value is pK
a a
a
.
An amine
*
To whom correspondence should be addressed. Tel 822 3277-2349;
Fax 822 3277-2844.
1) (a) J encks, W. P. Prog. Phys. Org. Chem. 1964, 2, 63. (b) J encks,
0
has the same leaving group
(
ability from the addition intermediate as the leaving
W. P. Chem. Soc. Rev. 1981, 10, 345. (c) J encks, W. P. J . Phys. Org.
Chem. 1996, 9, 337.
group of the substrate, i.e., a change in the RDS of a
0
stepwise reaction occurs at pK
a
. It has been well-known
(
2) (a) Williams, A. Acc. Chem. Res. 1989, 22, 387. (b) Williams, A.
Adv. Phys. Org. Chem. 1992, 27, 2. (c) Williams, A. Chem. Soc. Rev.
994, 23, 93.
3) (a) J ohnson, C. D. Chem. Rev. 1975, 75, 755. (b) Kirby, A. J . In
0
a
that the position of the RDS change (pK ) is strongly
1
dependent on the basicity of the leaving group and the
attacking amine, i.e., the RDS changes from the rate-
determining breakdown of the addition intermediate to
the rate-determining formation of the intermediate when
the attacking amine becomes more basic than the leaving
(
Organic Reaction Mechanism; Knipe, A. C., Watt, W. E., Eds.; Wiley
and Sons: New York, 1980; p 29. (c) McClelland, R. A.; Santry, L. J .
Acc. Chem. Res. 1983, 16, 394. (d) Capon, B.; Dosunmu, M. I.; de Matos
Sanchez, M. N. Adv. Phys. Org. Chem. 1985, 21, 38. (e) Bowden, K.
Chem. Soc. Rev. 1995, 24, 431.
group by 4-5 pK
a
units.11 However, the effect of the acyl
(4) (a) Oh, H. K.; Woo, S. Y.; Shin, C. H.; Park, Y. S.; Lee, I. J . Org.
Chem. 1997, 62, 5780. (b) Koh, H. J .; Lee, J . W.; Lee, H. W.; Lee, I.
New J . Chem. 1997, 21, 447. (c) Koh, H. J .; Kim, S. I.; Lee, B. C.; Lee,
I. J . Chem. Soc., Perkin Trans. 2 1996, 1353. (d) Oh, H. K.; Shin, C.
H.; Lee, I. J . Chem. Soc., Perkin Trans. 2 1995, 1169.
(8) (a) Bruice, T. C.; Hegarty, A. F.; Felton, S. M.; Donzel, A.; Kundu,
N. G. J . Am. Chem. Soc. 1970, 92, 1370. (b) Kovach, I. M.; Belz, M.;
Larson, M.; Rousy, S.; Schowen, R. L. J . Am. Chem. Soc. 1985, 107,
7360. (c) Fishbein, J . C.; Baum, H.; Cox, M. M.; J encks, W. P. J . Am.
Chem. Soc. 1987, 109, 5790. (d) Neuvonen, H. J . Chem. Soc., Perkin
Trans. 2 1987, 159.
(9) (a) Um, I. H.; Min, J . S.; Lee, H. W. Can. J . Chem. 1999, 77,
659. (b) Um, I. H.; Chung, E. K.; Lee, S. M. Can. J . Chem. 1998, 78,
729. (c) Um, I. H.; Hong, E. J .; Kwon, D. S. Tetrahedron 1997, 53, 5073.
(d) Um, I. H.; Chung, E. K.; Kwon, D. S. Tetrahedron Lett. 1997, 38,
4787. (e) Um, I. H.; Kim, M. J .; Min, J . S. Bull. Korean Chem. Soc.
1997, 18, 523.
(
5) (a) Castro, E. A.; Pizzaro, M. I.; Santos, J . G. J . Org. Chem. 1996,
6
1, 5982. (b) Castro, E. A.; Ibanez, F.; Santos, J . G.; Ureta, C. J . Org.
Chem. 1993, 58, 4908. (c) Castro, E. A.; Cubillos, M.; Santos, J . G. J .
Org. Chem. 1996, 61, 3501. (d) Castro, E. A.; Araneda, C. A. J . Org
Chem. 1997, 62, 126. (e) Castro, E. A.; Araneda, C. A. J . Org. Chem.
1
997, 62, 126.
6) Chapman, N. B.; Shorter, J . In Advances in Linear Free Energy
Relationships; Plenum: London, 1972.
7) (a) Koh, H. J .; Han, K. L.; Lee, I. J . Org. Chem. 1999, 64, 4783.
b) Lee, I. Adv. Phys. Org. Chem. 1992, 27, 57. (c) Lee, I. Chem. Soc.
Rev. 1994, 23, 223. (d) Koh, H. J .; Han, K. L.; Lee, I. J . Org. Chem.
998, 63, 9834.
(
(
(
(10) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963,
6970.
1
1
0.1021/jo000482x CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/12/2000

5
660 J . Org. Chem., Vol. 65, No. 18, 2000
Um et al.
Sch em e 1
Ta ble 1. Su m m a r y of Ap p a r en t Secon d -or d er Ra te
group (the nonleaving group of the substrate) on pK 0
controversial. Castro et al. have reported that the pK
values are 7.3 and 7.8 for pyridinolyses of 2,4-dinitro-
phenyl acetate and 2,4-dinitrophenyl methyl carbonate,
respectively.12 Besides, in the pyridinolyses of 2,4-dini-
is
a
a
-
1 -1
Con sta n t kN (M
s
) for Rea ction s of 4-Nitr op h en yl
0
X-Su bstitu ted Ben zoa tes (X-C6H4CO-OC6H4-4-NO2) w ith a
Ser ies of Alicyclic Secon d a r y Am in es, Z(CH CH ) NH, in
2
2 2
a
H2O Con ta in in g 20 Mol % DMSO a t 25.0 °C
kN(M-1s-1
)
trophenyl X-substituted benzoates (X ) 4-NO
2
, 4-Cl, and
and
-Cl but curved when X ) H. Therefore, Castro et al.
have concluded that an electron-withdrawing substituent
Z
NCHO
7.98
O
NCH2CH2OH
NH
CH2
H), the Brønsted-type plot is linear when X ) 4-NO
2
1
3
pKa
8.65
9.38
0.0776
0.147
0.172
0.195
0.267
0.396
0.462
0.487
9.85
11.02
1.95
3.68
4.56
5.94
8.14
12.8
18.7
21.0
4
X ) 4-MeO 0.00404 0.0365
0.344
0.629
0.79
0.851
1.14
1.67
2.06
2.30
X ) 4-Me
X ) 3-Me
X ) H
X ) 4-Cl
X ) 3-Cl
X ) 4-CN
X ) 4-NO2
0.00707 0.0659
0
in the acyl moiety causes an increase in the pK
a
0.0082
0.0100
0.0126
0.0165
0.0196
0.0204
0.081
0.0876
0.111
0.15
0.179
0.201
value.1 A similar conclusion has been drawn by J encks
2,13
et al. from the reaction of 2,4-dinitrophenyl aryl carbon-
1
0
ates with quinuclidines. However, we have recently
0
suggested that the pK
a
value is not influenced by the
electronic nature of the acyl substituent for the reaction
of 2,4-dinitrophenyl X-substituted benzoates with amines.9
In this study, we expand our work on the reaction of
a
a
pKa values taken from ref 11c.
respectively. Under pseudo-first-order conditions, eq 1
can be simplified into eqs 2 and 3. It is estimated from
replicate runs that the uncertainty in any particular
measured rate constant is less than (3%. The second-
order rate constants (k ) obtained in this way are
N
summarized in Table 1 and illustrated graphically in
4
-nitrophenyl X-substituted benzoates with a series of
alicyclic amines as shown in Scheme 1. We report the
effect of acyl substituents on the reaction mechanism
using linear free energy relationships including the
Yukawa-Tsuno equation, which has never been em-
ployed in aminolyses of carboxylic esters.
Figures 1-3.
Resu lts
rate ) k k [S] [>NH]/(k + k2)
(1)
1
2
-1
The kinetic study was performed spectrophotometri-
cally, and all the reactions in the present study obeyed
pseudo-first-order kinetics. Pseudo-first-order rate con-
stants (kobs) were obtained from the well-known equation:
rate ) kobs[S], where kobs ) k k [>NH]/(k + k2)
1
2
-1
(2)
ln(A
∞
- A ) ) -kobst + c. The correlation coefficients of
t
k ) k k /(k + k2)
(3)
N
1
2
-1
the linear regressions were always higher than 0.9995.
Generally, five different concentrations of amine solutions
were used to calculate second-order rate constants (k ).
N
The plots of kobs vs amine concentration are linear and
pass through the origin, indicating that there is no
Discu ssion
Effect of Acyl Su bstitu en ts on Ra te. As shown in
Table 1, second-order rate constants (k ) increase with
N
general base catalysis by a second amine molecule, and
increasing amine basicity and with increasing electron-
withdrawing ability of the acyl substituent X. The effect
of substituent X on the reaction rate is graphically
demonstrated in Figure 1, which shows nonlinear Ham-
mett plots for all the amines studied. Since such a
nonlinear Hammett plot has been understood to indicate
a change in the RDS of a multistep reaction, one can
suggest that the RDS of the present aminolysis reactions
changes upon changing the acyl substituent X.
-
the contribution by H
2
O or HO ion from the solvolysis
of amine to kobs is negligible. Therefore, a rate equation
can be derived, as eq 1, where [S] and [>NH] represent
the concentration of the substrate and the amine used,
(
11) (a) J encks, W. P.; Gilchrist, M. J . Am. Chem. Soc. 1968, 90,
2
5
1
622. (b) Castro, E. A.; Salas, M.; Santos, J . G. J . Org. Chem. 1991,
6, 4919. (c) Um, I. H.; Kwon, H. J .; Kwon, D. S. J . Chem. Res. 1995,
801(M), 301(S).
(
12) (a) Castro, E. A.; Freudenberg, M. J . Org. Chem. 1980, 45, 906.
b) Castro, E. A.; Gil, F. J . J . Am. Chem. Soc. 1977, 99, 7611.
13) (a) Castro, E. A.; Steinfort, G. B. J . Chem. Soc., Perkin Trans.
X
It has generally been suggested that a large F value
is obtained for ester aminolyses whose RDS is the
nucleophilic attack by an amine to form an addition
(
(
2
5
1983, 453. (b) Castro, E. A.; Santander, C. L. J . Org. Chem. 1985,
0, 3595. (c) Castro, E. A.; Valdivia, J . L. J . Org. Chem. 1986, 51, 1668.
1
intermediate (the k step in Scheme 1), since the nucleo-

Aminolyses of 4-Nitrophenyl X-Substituted Benzoates
J . Org. Chem., Vol. 65, No. 18, 2000 5661
F igu r e 1. Hammett plots for reactions of 4-nitrophenyl
X-substituted benzoates with a series of alicyclic secondary
F igu r e 3. Yukawa-Tsuno plots for reaction of 4-nitrophenyl
amines, Z(CH
at 25.0 °C. Z ) CH
NCHO ([).
2
CH
2
)
2
NH, in H
2
O containing 20 mol % DMSO
CH OH (9), O (]),
X-substituted benzoates with a series of alicyclic secondary
(b), NH (O), NCH
2
2
amines, Z(CH
at 25.0 °C. Z ) CH
2
CH
2
)
2
NH, in H
2
O containing 20 mol % DMSO
CH OH (9), O (]),
2
2
(b), NH (O), NCH
2
2
NCHO ([).
i.e., an electron-withdrawing substituent X would ac-
celerate nucleophilic attack but retard leaving group
departure from the addition intermediate, while an
electron-donating substituent X would delay nucleophilic
9
,14,15
attack but enhance leaving group departure.
As shown in Figure 1, the magnitude of the slopes of
the curved Hammett plots is larger for the electron-
donating substituents than for the electron-withdrawing
ones for all the amines investigated. Therefore, one may
consider that the RDS in the present aminolysis reactions
shifts from the k
1 2
step to the k step as the acyl
substituent X varies from electron-donating to electron-
withdrawing group.
The effect of the acyl substituent on pK 0
has been
studied by several investigators. J encks et al. have found
that the magnitude of the k-1 and k values is dependent
a
2
on the electronic nature of the substituent X of the aryl
moiety in the reaction of aryl 3,4-dinitrophenyl carbon-
0
ates with quinuclidines, i.e., a plot of pK
a
against the
basicity of the aryl moiety gives a straight line with a
slope ca. -0.4.10 A similar result has been reported by
Castro et al. in the pyridinolyses of 2,4-dinitrophenyl
F igu r e 2. Brønsted-type plots for reactions of 4-nitrophenyl
X-substituted benzoates with a series of alicyclic secondary
1
2
acetate and 2,4-dinitrophenyl methyl carbonate. They
amines in H
2
O containing 20 mol % DMSO at 25.0 °C.
0
found a larger pK
latter reactions, and attributed the increase in the pK
value to the larger electron-withdrawing inductive effect
of CH O (σ group (σ
-0.05) in the tetrahedral intermediate.
a
value (7.8 compared with 7.3) for the
0
a
philic attack would be accelerated by an electron-
withdrawing substituent but retarded by an electron-
3
I
) 0.25) compared with that of CH
3
I
donating one.9
,14,15
However, on the contrary, the magni-
12,16
)
The effect
tude of F
aminolyses whose RDS is the breakdown of the addition
intermediate to products (the k step in Scheme 1) due
to the opposite substituent effect on the reaction rate,
X
values has been suggested to be small for ester
0
of the acyl substituent on pK
a
has also been investigated
in pyridinolyses of 2,4-dinitrophenyl X-substituted ben-
zoates (X ) 4-NO , 4-Cl, and H) in aqueous ethanol.
2
2
Castro et al. obtained linear Brønsted-type plots when
the acyl substituent X was electron withdrawing, such
(
14) (a) Kirsch, J . F.; Kline, A. J . Am. Chem. Soc. 1969, 91, 1841.
b) Kirsch, J . F.; Clewell, W.; Simon, A. J . Org. Chem. 1968, 33, 127.
15) (a) Menger, F. M.; Smith, J . H. J . Am. Chem. Soc. 1972, 94,
824. (b) Caplow, M.; J encks, W. P. Biochemistry 1962, 1, 883. (c)
2
as 4-NO or 4-Cl, but a curved one when the substituent
(
(
X was H.13 Accordingly, it has been concluded that an
electron-withdrawing substituent of the acyl moiety
3
Correia, V. R.; Cuccovia, I. M.; Chaimovich, H. J . Phys. Org. Chem.
991, 4, 13. (d) Colthurst, M. J .; Williams, A. J . Chem. Soc., Perkin
Trans. 2 1997, 1493.
1
(16) Charton, M. J . Org. Chem. 1964, 29, 1222.

5
662 J . Org. Chem., Vol. 65, No. 18, 2000
Um et al.
Sch em e 2
-
+
Ta ble 2. Su m m a r y of ân u c Va lu es for Rea ction s of
Ta ble 3. Su m m a r y of GX a n d r Va lu es for Rea ction s of
4-Nitr op h en yl X-Su bstitu ted Ben zoa tes
4
-Nitr op h en yl X-Su bstitu ted Ben zoa tes
(
X-C6H4CO-OC6H4-4-NO2) w ith a Ser ies of Alicyclic
Secon d a r y Am in es in H2O Con ta in in g 20 Mol % DMSO a t
(X-C6H4CO-OC6H4-4-NO2) w ith a Ser ies of Alicyclic
Secon d a r y Am in es, Z(CH2CH2)2NH, in H2O Con ta in in g 20
a
Mol % DMSO a t 25.0 °Ca
2
5.0 °C
X
4-MeO 4-Me 3-Me
-0.27 -0.17 -0.07
0.78 0.79
σX values taken from ref 21.
H
4-Cl 3-Cl 4-CN 4-NO2
Z
CH2
NH
NCH2CH2OH
O
NCHO
σX
ânuc
0
0.23 0.37 0.66
0.78
0.88
pKa
FX
r
11.02
0.75
0.75
9.85
0.54
1.05
9.38
0.51
1.20
8.65
0.44
1.29
7.98
0.42
1.38
0.80 0.81 0.82 0.85 0.87
a
a
pKa data taken from ref 11c.
increases the pK 0
value.10,12,13 In the present study, the
a
3 3
Figure 1 reveals that two points (X ) 4-CH O and 4-CH )
deviate negatively from linearity. Since through-conjuga-
tion is possible for these substituents, another parameter
Hammett plots in Figure 1 are linear if one exclude the
points for the electron-donating substituents (e.g., 4-CH
and 4-CH O). Therefore, the nonlinear Hammett plots
3
3
is necessary as in the Yukawa-Tsuno eq 4. The term
in Figure 1 seem to be consistent with the conclusion
drawn by J encks and Castro that the electronic nature
+
(
σ -σ) is the resonance substituent constant measuring
0
the capability for π-delocalization of the π-electron donor
substituent, while the r value is a parameter character-
istic for the given reaction, measuring the extent of
resonance demand.
of the acyl substituent influences the pK
a
value in
aminolysis reactions.1
0,12,13
Effect of Am in e Ba sicity on Ra te. Figure 2 il-
lustrates the effect of amine basicity on reaction rate. The
Brønsted-type plots are linear, indicating that the ami-
nolyses of these substrates proceed through the same
mechanism regardless of the electronic nature of the acyl
substituent X. It is also shown in Figure 2 and Table 2
that the slope of the straight line (ânuc) increases as the
acyl substituent X changes from an electron-donating to
an electron-withdrawing group: 0.78 for X ) 4-MeO to
+
log k/k ) F[σ + r(σ -σ)]
(4)
0
In Figure 3, the Yukawa-Tsuno plots for the present
aminolysis reactions are illustrated. Good linearity is
seen for all the amines studied. The r values in Figure 3
have been calculated to be in the range of 0.75-1.38.
When r ) 0, eq 4 becomes the Hammett equation, and
when r ) 1, it becomes the Brown-Okamoto equation.
Since the r value in the present system is neither 0 nor
1, the Yukawa-Tsuno equation results in better correla-
tion than the Hammett or Brown-Okamoto equation, in
0
2
.81 and 0.88 for X ) H and 4-NO , respectively. The
magnitude of the ânuc value has been frequently used as
a measure to determine the RDS in various aminolysis
reactions. Large ânuc values (0.8 ( 0.2) have been gener-
ally obtained for aminolysis reactions whose RDS is the
breakdown of the tetrahedral addition intermediate to
products, while small ânuc values (0.2 ( 0.1) have been
+
which σ or σ constants are used alone. This accounts
clearly for the nonlinear Hammett plots in Figure 1.
Equation 4 has been applied to mostly benzylic sol-
volyses, in which a positive charge, which can be delo-
obtained for the aminolysis reactions whose RDS is the
formation of the addition intermediate.7
-12
Since the
1
7
magnitude of ânuc values is obtained to be 0.78-0.88, the
RDS in the present aminolysis reactions is considered
to be the k step in Scheme 1. If a change in the RDS
2
occurred as the acyl substituent X changes from electron-
withdrawing to electron-donating groups as discussed in
the preceding section, the magnitude of ânuc values should
have been reduced to ca. 0.2 ( 0.1. As shown in Table 2,
the magnitude of ânuc values decreases with decreasing
calized by the π-system of the ring, is generated.
Therefore, negative F values have usually been obtained
for the reactions in which the Yukawa-Tsuno equation
was applied.17 Interestingly, as shown in Figure 3, the
FX values are positive. Such a positive FX value in
Yukawa-Tsuno plots is quite unusual and suggests that
the ground-state stabilization by resonance as shown in
Scheme 2 is significant for the present system.
σ
+
X
constants of the acyl substituent X, i.e., ânuc ) 0.096σ
0.81. However, to get a ânuc value of 0.2, the σ value
X
In Table 3, the F and r values are summarized. The
X
X
FX values increase but the r values decrease as the amine
should be -6.4, which is practically impossible. There-
fore, the electronic nature of the acyl substituents in the
basicity increases. The magnitude of the F values has
X
been suggested to represent relative charge transfer from
0
present system would not influence the pK
argument is consistent with our recent report that the
magnitude of the k-1/k values is nearly constant upon
changing the acyl substituent X from a strong electron-
donating group to a strong electron-withdrawing one for
aminolyses of 2,4-dinitrophenyl X-substituted benzoates.
Clearly, there is inconsistency between the conclusion
drawn from the nonlinear Hammett plots in Figure 1 and
the conclusion based on the linear Brønsted-type plots
with large ânuc values in Figure 2. Possible reasons for
the inconsistencies are discussed below.
a
value. This
the nucleophile to the acyl moiety or the degree of
rehybridization of the acyl moiety in the transition state.
2
Therefore, the increasing F value with increasing amine
X
basicity indicates that the degree of charge transfer or
rehybridization of the acyl moiety becomes more signifi-
cant for the more basic amine. This is reasonable since
the electron-donating ability of a base is proportional to
its basicity: the degree of charge transfer or rehybrid-
9
a
(17) (a) Tsuno, Y.; Fujio, M. Adv. Phys. Org. Chem. 1999, 32, 267-
85. (b) Tsuno, Y.; Fujio, M. Chem. Soc. Rev. 1996, 25, 129. (c) Shorter,
3
J . In Correlation Analysis in Chemistry; Chapman, N. B., Shorter, J .,
Eds.; Plenum Press: New York, 1978; ch. 4. (d) J ohnson, C. D. J . Org.
Chem. 1978, 43, 1814.
Or igin of th e Non lin ea r Ha m m ett P lots: Un u su a l
Gr ou n d -sta te Sta biliza tion . A careful examination of

Aminolyses of 4-Nitrophenyl X-Substituted Benzoates
J . Org. Chem., Vol. 65, No. 18, 2000 5663
significant. (4) The nonlinear Hammett plots are not due
to a change in the RDS but arise from large resonance
demand of the π-electron donor substituents on the acyl
moiety. (5) The magnitude of the F
X
and ânuc values
increases with increasing amine basicity and with in-
creasing electron-withdrawing ability of the acyl sub-
stituent X, respectively. (6) The magnitude of the r value
X
decreases with increasing F values and with increasing
the basicity of amines used in the present study.
Exp er im en ta l Section
Ma ter ia ls. 4-Nitrophenyl X-substituted benzoates were
easily prepared from the reaction of X-substituted benzoyl
chloride with 4-nitrophenol in the presence of triethylamine
in methylene chloride.19 Their purity was checked by means
1
of melting points and spectral data such as IR and H NMR
characteristics. Other chemicals used, including secondary
alicyclic amines, were of the highest quality available. The
reaction medium was H O containing 20 mol % dimethyl
2
sulfoxide (DMSO) in order to eliminate solubility problems.
DMSO was distilled over calcium hydride at a reduced
pressure (bp 64-66 °C at 6-7 mmHg) and stored under
nitrogen. Doubly glass distilled water was further boiled and
cooled under nitrogen just before use.
Kin etics. The kinetic study was performed with a Hitachi
U-2000 model UV-vis spectrophotometer for slow reactions
(t1/2 g 10 s) or with an Applied photophysics SX-17 MV
F igu r e 4. Plot showing dependence of the r value on the F
X
value for reaction of 4-nitrophenyl X-substituted benzoates
with a series of alicyclic secondary amines in H
0 mol % DMSO at 25.0 °C.
2
O containing
2
stopped-flow spectrophotometer for fast reactions (t1/2 < 10 s)
equipped with a Neslab RTE-110 constant temperature cir-
culating bath to keep the reaction mixture at 25.0 ( 0.1 °C.
The amine stock solution of ca. 0.2 M was prepared in a 25.0
mL volumetric flask under nitrogen by adding 2 equiv of amine
to 1 equiv of standardized HCl solution in order to obtain a
self-buffered solution. All the solutions were transferred by
Hamilton gastight syringes. The reactions were followed by
monitoring the appearance of the leaving 4-nitrophenoxide ion
at 410 nm. All the reactions were carried out under pseudo-
first-order conditions in which the amine concentrations were
at least 20 times greater than the substrate concentration.
Typically, reaction was initiated by adding 5 µL of a 0.02 M
solution of 4-nitrophenyl-substituted benzoate in acetonitrile
by syringe to a 10-mm quartz UV cell containing 2.50 mL of
the thermostated reaction mixture made up of solvent and
aliquot of the amine stock solution. Generally, the amine
ization of the acyl moiety should be more significant for
the more basic amine.
It has been generally known that there is no correlation
and r values.1
7,18
between the magnitude of F
X
However,
interestingly, the magnitude of the r values in the present
system increases linearly with decreasing F values as
shown in Table 3 and Figure 4. The slope of the linear
plot of r vs F has been calculated to be -1.85 with a
X
X
relatively good correlation coefficient (0.984). Since the
r value in eq 1 represents the extent of resonance
demand, it may be suggested that resonance demand
increases linearly with decreasing the F value in the
X
present system.
Based on the above argument, the nonlinear Hammett
plots in Figure 1 clearly are not due to a change in the
RDS upon changing the acyl substituent X. Instead, large
resonance demand in the ground state is considered to
be responsible for the nonlinearity in Figure 1. Therefore,
one can conclude that the Yukawa-Tsuno equation is
more suitable than the Hammett or Brown-Okamoto
equations to investigate the effect of acyl substituents
on the reaction mechanism in the present system.
-3
concentration was varied over the range (2-50) × 10 M,
-
5
while the substrate concentration was 4 × 10 M. Pseudo-
first-order rate constant(kobs) were calculated from the well-
known equation, ln(A
∞
- A
t
) ) - kobst + C. The plots of ln(A
∞
-
A
t
) vs time were linear over ca. 90% reaction. Usually, five
different amine concentrations were employed and replicate
values of kobs were determined to obtain the second-order rate
constants (k ) from the slope of linear plots of kobs versus amine
N
concentrations.
P r od u ct An a lysis. One of the reaction products (4-benzoyl-
1
-piperazinecarboxaldehyde, 83-84 °C)20 was anaylzed by
Con clu sion s
HPLC using a Waters 600 liquid chromatograph equipped with
a Waters 996 Photodiode Array detector, an Rheodyne 7725i
manual injector and a column of Nova-Pak C18 60 Å (4 µm)
The present study has allowed us to conclude the
following. (1) The nonlinear Hammett plots obtained for
all the amines studied suggest a change in the reaction
mechanism or the RDS. (2) However, the linear Brønsted-
type plots obtained for all the substrates with ânuc values
of 0.8 ( 0.1 indicate that the present aminolyses proceed
through the same mechanism, and the RDS is the
breakdown of the addition intermediate to the products.
(
3.9 × 150 mm length). The flow rate was 1 mL/min, and the
eluent was 50% MeCN in MeOH (v/v). Quantitative analysis
was performed by comparison of the HPLC peak area of the
reaction mixture with that of the authentic sample at 230 nm.
Ack n ow led gm en t. The authors are grateful for the
financial support from KOSEF of Korea (1999-2-123-
0
03-5).
(
3) The Yukawa-Tsuno plots are linear with positive F
X
and large r values, implying that ground-state stabiliza-
tion by through-conjugation of the π-electron donor
substituents on the acyl moiety of the substrate is
J O000482X
(
(
19) Hubbard, C. D.; Kirsch, J . F. Biochemistry 1972, 11, 2483.
20) Dhawn, B.; Southwick, P. L. Org. Prep. Proced. Int. 1975, 7,
8
5-88.
(21) J ones, R. A. Y. In Physical and Mechanistic Organic Chemistry;
Cambridge: London, 1984; p 65.
(
18) Ruff, F.; Csizmadia, I. C. In Organic Reactions Equilibria,
Kinetics and Mechanism; Elsevier: London, 1994; p 179.