Structure-reactivity correlations in the reaction of 2,4-dinitrophenyl X-substituted benzoates with alicyclic secondary amines

Article abstract of DOI:10.1139/v99-046

Apparent second-order rate constants (k_app) have been measured spectrophotometrically for the reaction of 2,4-dinitrophenyl X-substituted benzoates with a series of alicyclic secondary amines in H₂O containing 20 mol% DMSO at 25°C. The microconstants involved in the reaction (k_-1/k₂, K₁, and k₁k₂/k_-1) have also been calculated. The magnitude of k_app, k₁, and k₁k₂/k_-1 values increases with increasing amine basicity and with increasing acid strengthening ability of the acyl substituent X. The k_-1/k₂ value decreases from ca. 6.5 to 0.3 with increasing the amine basicity, but remains almost constant upon changing the acyl substituent X for a given amine, indicating that the ratedetermining step is governed by the basicity of amine but not by the electronic nature of the acyl substituent X. The Bronsted-type plots for k_app show a break at pK_a = 9.1, supporting the assumption that a change in the rate-determining step occurs from rate-limiting breakdown to formation of the addition intermediate as amine basicity increases. The corresponding Bronsted-type plots for k_-1/k₂, k₁, and k₁k₂/k_-1 are linear but their β values are different. σ⁺ constants show better correlation with log k_app, log k_l and log k₁k₂/k_-1 for the reaction with low basic amines (pK_a < 9.1), while σ constants exhibit better correlation for the reaction with highly basic amines (pK_a > 9.1). The magnitude of ρ₁ is identical to that of ρ_app and ρ_eq for a given amine.

Full text of DOI:10.1139/v99-046

659
Structure–reactivity correlations in the reaction
of 2,4-dinitrophenyl X-substituted benzoates
with alicyclic secondary amines
Ik-Hwan Um, Ji-Sook Min, and Hye-Won Lee
Abstract: Apparent second-order rate constants (kapp) have been measured spectrophotometrically for the reaction of
2,4-dinitrophenyl X-substituted benzoates with a series of alicyclic secondary amines in H2O containing 20 mol%
DMSO at 25°C. The microconstants involved in the reaction (k–1/k2, k1, and k1k2/k–1) have also been calculated. The
magnitude of kapp, k1, and k1k2/k–1 values increases with increasing amine basicity and with increasing acid
strengthening ability of the acyl substituent X. The k–1/k2 value decreases from ca. 6.5 to 0.3 with increasing the amine
basicity, but remains almost constant upon changing the acyl substituent X for a given amine, indicating that the rate-
determining step is governed by the basicity of amine but not by the electronic nature of the acyl substituent X. The
Brønsted-type plots for kapp show a break at pKa = 9.1, supporting the assumption that a change in the rate-determining
step occurs from rate-limiting breakdown to formation of the addition intermediate as amine basicity increases. The
corresponding Brønsted-type plots for k–1/k2, k1, and k1k2/k–1 are linear but their β values are different. σ+ constants
show better correlation with log kapp, log k1 and log k1k2/k–1 for the reaction with low basic amines (pKa < 9.1), while
σ constants exhibit better correlation for the reaction with highly basic amines (pKa > 9.1). The magnitude of ρ1 is
identical to that of ρapp and ρeq for a given amine.
Key words: aminolysis, Brønsted-type plot, structure–reactivity correlations, rate-determining step.
Résumé : Faisant appel à la spectrophotométrie et opérant à 25°C dans H2O contenant 20 mol% de DMSO, on a
mesuré les constantes de vitesse apparentes du deuxième ordre de benzoates (portant un substituant X) de 2,4-
dinitrophényle avec une série d’amines alicycliques secondaires. On a calculé les microconstantes impliquées dans la
réaction (k–1/k2, k1 et k1k2/k–1). L’amplitude des valeurs de kapp, k1, k1k2/k–1 augmente avec une augmentation de la
basicité de l’amine et avec une augmentation de l’habilité du substituant acyle X à augmenter l’acidité. Les valeurs de
k–1/k2 diminuent d’environ 6,5 à 0,3 avec une augmentation de la basicité de l’amine, mais elles demeurent
pratiquement constantes pour un changement de substituant acyle X pour une amine donnée; ceci indique que l’étape
cinétiquement déterminante est fixée par la basicité de l’amine, mais pas par la nature électronique du substituant acyle
X. Les courbes de type Brønsted pour kapp présentent un bris à un pKa = 9,1; ce résultat supporte l’hypothèse selon
laquelle il se produit un changement dans l’étape cinétiquement limitante à cause d’un bris cinétiquement limitant dans
la formation de l’intermédiaire lorsque la basicité de l’amine augmente. Les courbes de type Brønsted correspondantes
pour k–1k/2, k1 et k1k2/k–1 sont linéaires, mais leurs valeurs β sont différentes. Pour les amines de faible basicité (pKa <
9,1), les constantes σ+ donnent une meilleure corrélation avec log kapp, log k1 et log k1k2/k–1 alors que les constantes σ
conduisent à une meilleure corrélation pour la réaction avec les amines plus fortement basiques (pKa > 9,1). Pour une
amine donnée, l’amplitude de ρ1 est identique à celle de ρapp et de ρeq.
Mots clés : aminolyse, courbe de type Brønsted, corrélations structure-activité, étape cinétiquement déterminante.
[Traduit par la Rédaction] Um et al. 666
Introduction
in biology as well as in chemistry (1–6). The reactions of
carboxylic acid derivatives with amines have been suggested
to proceed through a stepwise mechanism with an addition
intermediate or through a concerted mechanism without an
intermediate (1–6). Linear free energy relationships such as
Hammett and Brønsted-type correlations have been most
frequently used to investigate the reaction mechanism (7).
Aminolyses of carboxylic esters with a good leaving group
have often shown a break or a curvature in Brønsted-type
plots from a large slope (βnuc = 0.8 ± 0.1) to a small one (βnuc
= 0.2 ± 0.1) as the basicity of the attacking amine increases
(3, 4). Such a break or a curvature in Brønsted-type plots
has been attributed to a change in rate determining step
(RDS) of a stepwise reaction. Generally, the RDS of amin-
olysis of carboxylic esters has been suggested to be depend-
The aminolysis reaction of carbonyl compounds is one of
the most intensively investigated reactions due to the interest
Received November 9, 1998.
This paper is dedicated to Professor A.J. Kresge in
recognition of his numerous contributions to physical organic
chemistry.
I.-H. Um,1 J.-S. Min, and H.-W. Lee. Department of
Chemistry, Ewha Womans University, Seoul 120–750, Korea.
1Author to whom correspondence may be addressed.
Telephone: 822) 3277-2349. Fax: 822) 3277-2844.
e-mail: ihum@mm.ewha.ac.kr
Can. J. Chem. 77: 659–666 (1999)
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660
Can. J. Chem. Vol. 77, 1999
Scheme 1.
NO2
NO2
-
O
C
O
C
k1
X
O
NO2
X
O
NO2 +
HN
k-1
+
NH
k2
NO2
O
C
X
HO
NO2
+
N
X = MeO, Me, H, Cl, NO2
+
=
HN
NH
Z ; Z = CH2, NH, O, N-CHO, NH2
Table 1. Summary of apparent second-order rate constants (kapp) for the aminolysis reaction of 2,4-dinitrophenyl X-substituted
benzoates with secondary alicyclic amines in H2O containing 20 mol% DMSO at 25°C.
kapp (M–1 s–1)
Amine (Z)
pKaa
X = 4-NO2
4-Cl
H
4-Me
4-MeO
Piperidine (CH2)
Piperazine (NH)
Morpholine (O)
1-Formyl piperazine (NCHO)
11.02
9.85
8.65
7.98
5.95
2880
974
138
28.2
1.83
371
157
32.7
7.58
0.675
174
100
49.8
11.2
2.94
0.306
56.2
27.4
5.77
1.49
0.162
82.1
19.6
5.43
0.467
+
Piperazinium ion (NH2 )
apKa of the conjugate acid of amine taken from ref. 20.
ent on the basicity of the leaving group and the attacking
amine, i.e., the RDS changes from the rate-determining break-
down of the addition intermediate to the rate-determining
formation of the intermediate as the basicity of amines in-
creases (3, 4).
of kobs vs. [ >NH]. The kapp values obtained in this way are
summarized in Table 1. It is estimated from replicate runs
that the error in any particular measured rate constants is
less than ± 3%. Under pseudo-first-order conditions, eq. [1]
can be simplified into eqs. [2] and [3].
However, until recently, most studies were directed to in-
vestigate the reaction mechanism by changing the basicity of
the leaving or attacking groups. The effect of the acyl group
on reaction rates as well as on reaction mechanisms has been
rarely investigated (8–10). We have carried out a systematic
study as shown in Scheme 1, and evaluated all the micro-
constants involved in the aminolysis reactions to obtain fur-
ther information about the reaction mechanism.
k1k2
[1]
[2]
[3]
Rate =
[S][>NH]
k−1 + k2
k1k2
Rate = kobs[S],
where kobs
=
[>NH]
k−1 + k2
k1k2
kapp
=
k−1 + k2
Results and discussion
Reaction mechanism
All the reactions in the present study obeyed pseudo-first-
order kinetics up to over 90% of the total reaction. Pseudo-
first-order rate constants (kobs) were obtained from the equa-
tion, ln (A∞ – At) = –kobst + c. The correlation coefficients of
the linear regressions were always higher than 0.9995. The
plots of kobs vs. [ >NH] were linear, indicating that general
base catalysis by a second amine molecule is absent. There-
fore, one can derive a rate equation, as eq. [1], where [S]
and [ >NH] represent the concentration of the substrate and
the amines used, respectively. Apparent second-order rate
constants (kapp) were determined from the slope of the plots
As shown in Table 1, the kapp value increases with in-
creasing the basicity of amines and with increasing acid
strengthening ability of the acyl substituent X. In Fig. 1 is
demonstrated the effect of amine basicity on reactivity,
which was statistically corrected by using p and q, i.e., p = 2
(except p = 4 for piperazinium ion) and q = 1 (except q = 2
for piperazine) (11). The Brønsted-type plots in Fig. 1 are
nonlinear for all the acyl substituents. Such a nonlinear
Brønsted-type plot has often been observed in aminolyses of
esters with a good leaving group, and used as evidence of a
change in the rate determining step, i.e., the RDS changes
© 1999 NRC Canada

Um et al.
661
Fig. 1. Plots of logarithm of kapp versus pKa of the conjugate
acid of amines for the reaction of 2,4-dinitrophenyl X-substituted
benzoates with secondary alicyclic amines (Z) in H2O containing
20 mol% DMSO at 25°C.
Fig. 2. Plots of logarithm of kapp versus σX (or σX+) constants for
the reaction of 2,4-dinitrophenyl X-substituted benzoates with
secondary alicyclic amines (Z) in H2O containing 20 mol%
DMSO at 25°C.
from breakdown of the addition intermediate to formation of
the intermediate as the attacking amine becomes more basic
than the leaving group by 4-5 pKa units (12). Figure 1
shows that the position of the break is about 9.1, which is 5
pKa units higher than the pKa of the conjugate acid of the
leaving group (pKa of 2,4-dinitrophenol = 4.1). Therefore,
one can suggest that the RDS in the present aminolysis
changes from the k2 step to the k1 step in Scheme 1 as the
amine becomes more basic than morpholine (pKa > 9.1).
It is noted that the position of the break in Fig. 1 is nearly
unchanged although the electronic nature of the acyl
substituent X varies significantly, suggesting that the RDS
change is governed by the basicity of amines but not by the
acyl moiety. The βapp2 (the slope in Fig. 1 for the low basic
amines, pKa < 9.1) has been calculated to be 0.63, 0.66, and
0.76 for the acyl substituent X = MeO, H, and NO2, respec-
tively. The βapp1 value (the slope in Fig. 1 for the highly ba-
sic amines, pKa > 9.1) is 0.42, 0.40, and 0.55 for X = MeO,
H, NO2, respectively. Therefore, the electronic nature of the
acyl substituents X affects the magnitude of the slopes in the
Brønsted-type plots (both βapp1 and βapp2).
positive charge is developed at the reaction centre which can
resonate with an electron-donating group (EDG) (13). Ac-
cordingly, negative ρ values have generally been obtained
when σ+ constants were used. However, as shown in Fig. 2,
the slope of the Hammett plots (ρapp) is positive. Therefore,
the present result is quite unusual and suggests that the
ground-state stabilization by resonance or hyperconjugation
is significant for the reactions with the low basic amines as
shown in Scheme 2.
The ρapp values of the Hammett plots in Fig. 2 are much
larger for the reactions with the highly basic amines (ρapp
=
1.42-1.59) than for the ones with the low basic amines (ρapp
= 0.68-0.90). Since the attack of amines to the carbonyl car-
bon to form an addition intermediate would be accelerated
by an electron withdrawing group (EWG) but retarded by an
EDG in the acyl moiety, one would expect a large ρ value
for the reactions where the RDS is the first step (k1) in
Scheme 1. On the contrary, the departure of the leaving
group from the addition intermediate would be disfavoured
by an EWG but favoured by an EDG in the acyl moiety. Ac-
cordingly, the ρ value has been suggested to be small when
the RDS is the k2 step due to the opposite substituent effect,
and the magnitude of ρ values has often been used to deter-
mine the RDS for two step reactions (8–10). Based on the
magnitude of the ρapp values in the present system, one can
suggest that the RDS is the k2 step for the reactions with the
low basic amines (small ρapp) and the k1 step for the ones
with the highly basic amines (large ρapp).
Figure 2 demonstrates the effect of acyl substituent on re-
activity. Good linear Hammett plots are observed for all the
amines studied. However, interestingly, log kapp shows good
linear correlation with σ constants for the reactions with
highly basic amines (pKa > 9.1) but with σ+ constants for the
ones with low basic amines (pKa < 9.1). σ+ constants were
derived from the solvolysis of ArCMe2Cl in 90% acetone–
water mixture at 25°C, and used for reactions in which a
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662
Can. J. Chem. Vol. 77, 1999
Scheme 2.
-
-
NO2
NO2
O
O
C
+
CH3O
CH3O
C O
NO2
O
NO2
NO2
NO2
+
O
O
H
H
H
C
H
C O
NO2
C O
NO2
H
C
H
Table 2. Summary of k–1/k2 values for the aminolysis reaction of 2,4-dinitrophenyl X-substituted benzoates with secondary alicyclic
amines in H2O containing 20 mol% DMSO at 25°C.
k–1/k2
Amine (Z)
X = 4-NO2
4-Cl
H
4-Me
4-MeO
Piperidine (CH2)
Piperazine (NH)
Morpholine (O)
0.397
0.694
1.24
0.364
0.671
1.27
0.316
0.637
1.31
0.364
0.671
1.27
0.397
0.694
1.24
1-Formyl piperazine (NCHO)
Piperazinium ion (NH2 )
1.72
4.61
1.81
5.29
1.96
6.58
1.81
5.29
1.72
4.61
+
Recently, we reported a ρ value of 2.4 for the reaction of
4-nitrophenyl X-substituted benzoates with phenoxide ion
under the same reaction conditions in which the nucleophilic
attack by phenoxide ion was proposed to be the RDS (14).
The ρapp value for the present aminolysis with the highly ba-
sic amines is 1.5 ± 0.1, which is much smaller than the one
for the reaction with the anionic nucleophile. However, the
difference in the ρ value between the two systems is consid-
ered not to be due to any difference in the reaction mecha-
nism, but due to the difference in the type of nucleophiles
(phenoxide anion vs. neutral amine). Since phenoxide anion
would donate electrons more significantly to the acyl moiety
in the transition state (TS) than the neutral amines, it would
be natural to observe a larger ρ value for the former system
than the latter one.
[7]
βapp2 = d(log k1k2/k–1)/d(pKa)
= βapp1 + d(log k2/k–1)/d(pKa)
Equation [7] can be rearranged as eq. [8]. Integral of
eq. [8] from pK0 to pKa results in eq. [9], where pK0 repre-
sents the position of the break in Fig. 1.
[8]
[9]
βapp2 – βapp1 = d(log k2/k–1)/d(pKa)
(log k2/k–1)pKa – (log k2/k–1)pK0
= (βapp2 – βapp1)(pKa – pK0)
The values of βapp1 and βapp2 for the reaction of 2,4-
dinitrophenyl benzoate (X = H) were calculated to be 0.66
and 0.40, respectively, and pK0 is 9.1. Since k2 = k–1 at pK0,
the term log (k2/k–1)pK0 is zero. Therefore, one can simplify
eq. [9] as eq. [10], which allows one to calculate the k2/k–1
values for all the amines studied in the present system.
Evaluation of microconstants
To get insight into the reaction mechanism, it is necessary
to determine all the microconstants involved in the present
aminolysis reactions. The method used to calculate the
microconstants is based on Castro’s procedure (12c) as fol-
lows.
As suggested in the preceding section, the RDS is consid-
ered to change from the k2 to k1 step as the amine becomes
more basic than morpholine (or pKa > 9.1). Therefore,
eq. [3] can be simplified into eqs. [4] and [5].
[10] log (k2/k–1)pKa = 0.26(pKa – 9.1)
In a similar manner, the k2/k–1 values for the other systems
(X = NO2, Cl, Me, MeO) have been calculated and summa-
rized in Table 2.
The k2 value has been suggested to be constant upon
changing the basicity of amines for aminolysis reactions of a
given substrate (15, 16). However, the k–1 value would be
inversely proportional to the basicity of amines. Therefore,
one can expect that the k–1/k2 values become larger with de-
creasing amine basicity. In fact, as shown in Table 2, k–1/k2
values increase from ca. 0.3–6.5 as amine basicity decreases.
The magnitude of k–1/k2 values is larger than 1 for the low
basic amines (pKa < 9.1) and smaller than 1 for the highly
basic amines (pKa > 9.1), indicating that the RDS changes
from the k2 to k1 step as the amine becomes more basic than
morpholine (or pKa > 9.1). This is consistent with the
preceding suggestion based on the nonlinear Brønsted-type
[4]
[5]
kapp = k1k2/k–1 = Kk2,
when k2 << k–1
kapp = k1, when k2 >> k–1
Let βapp2 and βapp1 represent the slope for the Brønsted
plots in Fig. 1 for the reactions with the low and the highly
basic amines, respectively. Then, one can express βapp1 and
βapp2 as eqs. [6] and [7], respectively.
[6]
βapp1 = d(log k1)/d(pKa)
© 1999 NRC Canada

Um et al.
663
Table 3. Summary of k1 values for the aminolysis reaction of 2,4-dinitrophenyl X-substituted benzoates with secondary alicyclic
amines in H2O containing 20 mol% DMSO at 25°C.
k1 (M–1 s–1)
Amine (Z)
X = 4-NO2
4-Cl
H
4-Me
4-MeO
Piperidine (CH2)
Piperazine (NH)
Morpholine (O)
1-Formyl piperazine (NCHO)
4020
1650
310
76.7
10.2
506
263
74.2
21.3
4.25
229
134
45.3
16.1
3.55
136
83.3
25.4
8.26
1.93
78.5
46.5
12.9
4.05
0.907
+
Piperazinium ion (NH2 )
Fig. 3. Plots of logarithm of k–1/k2 versus pKa of the conjugate
acid of amines for the reaction of 2,4-dinitrophenyl X-substituted
benzoates with secondary alicyclic amines (Z) in H2O containing
20 mol% DMSO at 25°C.
shown in Table 2, the magnitude of k–1/k2 values appears to
be nearly constant although the acyl substituent changes
from a strong EDG to a strong EWG for a given amine,
clearly supporting the preceding argument that the position
of the RDS change (pK0) would not be influenced by the
electronic nature of the acyl substituents but governed by the
basicity of the leaving group and the attacking amines. How-
ever, it has been recently suggested that pK0 and the k–1/k2
ratio increase with increasing electron-withdrawing ability
of the acyl moiety in aminolyses of aryl carbonates and
thionocarbonates, which is inconsistent with our present re-
sult (15, 16).
[11] k1 = kapp (k–1/k2 + 1)
Equation [3] can be rewritten as eq. [11], which allows
the calculation of the k1 values using the known values of
kapp and k–1/k2 from Tables 1 and 2. The k1 values calculated
in this way are summarized in Table 3. One can see that the
magnitude of k1 decreases with decreasing the basicity of
amines and with decreasing acid strengthening ability of the
acyl substituent X. The data in Tables 1 and 3 reveal that k1
is always larger than the corresponding kapp. However, the
difference in the magnitude of k1 and kapp becomes small as
amine basicity increases for a given acyl substituent X, be-
cause the k–1/k2 values decrease with increasing amine basic-
ity.
Figure 4 shows the effect of amine basicity on the magni-
tude of k1 value. One can notice that log k1 is linearly corre-
lated with the basicity of amines for all the acyl substituent
X. The magnitude of the slopes in Fig. 4 (β1) was calculated
to be 0.55, 0.38, and 0.41 for X = NO2, H, and MeO, respec-
tively. The β1 value is about twice the value of β–1, indicating
that the k1 step is about twice more sensitive than the k–1
step toward the basicity of amines for a given acyl
substituent X.
Figure 5 demonstrates linear Hammett plots for all the
amines studied. One can see that log k1 is better correlated
with σ constants for the reactions with the highly basic
amines (pKa > 9.1) and with σ+ constants for the low basic
amines (pKa < 9.1). Besides, the magnitude of the slopes in
Fig. 5 (ρ1) is much larger for the reactions with the highly
basic amines than for the ones with the low basic amines.
One can notice that the magnitude of ρ1 and ρapp values is
same. However, this is not so surprising if one analyses
eq. [11]. Since the k–1/k2 value has been shown to be almost
constant upon changing the acyl substituent X for a given
amine, log kapp = log k1 + constant. Consequently, the slopes
in the plots of log k1 vs. σ (or σ+) and log kapp vs. σ (or σ+)
should be identical each other for a given amine.
plots shown in Fig. 1 and the difference in the magnitude of
the ρ values shown in Fig. 2.
Figure 3 demonstrates the effect of amine basicity on the
k–1/k2 values. Linear Brønsted-type plots are observed for all
the acyl substituents X. Since the k2 value has been sug-
gested to be constant upon changing the basicity of amines
(15, 16), the magnitude of the slope in Fig. 3 (β–1) would be
governed mainly by k–1. The β–1 value was calculated to be
about 0.25, indicating that log k–1 is little sensitive toward
the basicity of the amines used. Such a small β–1 value ob-
tained in the present system is consistent with the recent
suggestion by Colthurst and Williams (9b), that k–1 would
not be sensitive to the basicity of nucleophiles.
Both the k–1 and k2 steps would be accelerated by an EDG
but retarded by an EWG in the acyl moiety for a given
amine. Accordingly, k–1/k2 values would be expected to be
constant upon changing the acyl substituent X. In fact, as
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Can. J. Chem. Vol. 77, 1999
Table 4. Summary of Kk2 (= k1k2/k–1) values for the aminolysis reaction of 2,4-dinitrophenyl X-substituted benzoates with secondary
alicyclic amines in H2O containing 20 mol% DMSO at 25°C.
Kk2 (M–1 s–1)
Amine (Z)
X = 4-NO2
4-Cl
H
4-Me
4-MeO
Piperidine (CH2)
Piperazine (NH)
Morpholine (O)
1-Formyl piperazine (NCHO)
10100
2370
249
44.7
2.22
1390
390
58.5
11.8
0.801
723
211
34.5
8.22
0.537
375
124
20.0
4.56
0.363
198
66.6
10.4
2.36
0.197
+
Piperazinium ion (NH2 )
Fig. 5. Plots of logarithm of k1 versus σX (or σX+) constants for
the reaction of 2,4-dinitrophenyl X-substituted benzoates with
secondary alicyclic amines (Z) in H2O containing 20 mol%
DMSO at 25°C.
Fig. 4. Plots of logarithm of k1 versus pKa of the conjugate acid
of amines for the reaction of 2,4-dinitrophenyl X-substituted
benzoates with secondary alicyclic amines (Z) in H2O containing
20 mol% DMSO at 25°C.
The Kk2 (= k1k2/k–1) values have been calculated from the
known values of k1 and k–1/k2, and summarized in Table 4.
The Kk2 value decreases with decreasing amine basicity and
with increasing acid weakening ability of the acyl
substituent X, as expected. Comparison of the data in Ta-
bles 3 and 4 reveals that the magnitude of Kk2 is larger than
the corresponding k1 for the highly basic amines but smaller
than k1 for the low basic amines. However, this is not so sur-
prising either, since k2/k–1 > 1 for the reactions with the
highly basic amines (pKa > 9.1) and k2/k–1 < 1 for the low
basic amines (pKa < 9.1), as shown in Table 2.
Figure 6 exhibits the effect of amine basicity on Kk2. One
can see linear Brønsted-type plots. The magnitude of the
slopes in Fig. 6 (βeq) has been calculated to be 0.78, 0.66,
and 0.64 for X = NO2, H, and MeO, respectively. Since the
magnitude of k2 values has been suggested to be constant
upon changing the basicity of amines (16, 17), the slope in
the plots of log Kk2 vs. pKa (e.g., βeq) and log k1/k–1 vs. pKa
(e.g., β1 – β–1) should be same. In fact, it has been calculated
that βeq = β1 – β–1 for all the acyl substituents.
Figure 7 demonstrates the effect of acyl substituent X on
Kk2. Good linear Hammett plots are obtained for all the
amines used. Interestingly, as observed in Figs. 2 and 5, log
Kk2 shows good linear correlation with σ constants for the
reactions with the highly basic amines but with σ+ constants
for the low basic amines. Besides, the slopes in Fig. 7 (ρeq)
are much larger for the highly basic amines than for the low
basic ones, as observed in Figs. 2 and 5.
Since the magnitude of k–1/k2 values are almost constant
upon changing the acyl substituent X for a given amine, the
slopes of the plots of log Kk2 vs. σ (or σ+) and log k1 vs. σ
(or σ+) should be same for a given amine. In fact, one can
notice that the magnitude of ρeq and ρ1 is identical for a
© 1999 NRC Canada

Um et al.
665
Fig. 6. Plots of logarithm of Kk2 versus pKa of the conjugate
acid of amines for the reaction of 2,4-dinitrophenyl X-substituted
benzoates with secondary alicyclic amines (Z) in H2O containing
20 mol% DMSO at 25°C.
Fig. 7. Plots of logarithm of Kk2 versus σX (or σX+) constants for
the reaction of 2,4-dinitrophenyl X-substituted benzoates with
secondary alicyclic amines (Z) in H2O containing 20 mol%
DMSO at 25°C.
given amine. The present study clearly shows that the ρapp
and ρeq values are identical to the ρ1 value for a given amine,
and the magnitude of ρ1 dominates that of ρapp and ρeq (see
Figs. 2, 5, and 7).
and other chemicals used were of the highest quality avail-
able. To eliminate a solubility problem, 20 mol% dimethyl
sulfoxide (DMSO) – H2O mixture was used as the reaction
medium. DMSO was distilled over calcium chloride at a re-
duced pressure (bp 64-66°C at 6-7 mmHg) (1 mmHg =
133.3 Pa) and stored under nitrogen. Doubly glass distilled
water was further boiled and cooled under a nitrogen atmo-
sphere just before use.
As mentioned in the preceding section, the magnitude of
ρapp and ρeq has been generally suggested to be small for the
reactions in which the leaving group departure occurs in the
RDS (9, 10), since the effect of acyl substituents on the k1
and k2 steps would be opposite. In fact, the magnitude of
ρapp, ρeq, and ρ1 has been shown to be much smaller for the
reactions with the low basic amines (pKa < 9.1) in which the
leaving group departure is the RDS than for the ones with
the highly basic amines (pKa > 9.1) in which the leaving
group departure occurs after the RDS. However, the present
result clearly suggests that the small ρapp and ρeq values for
the low basic amines are not due to the opposite substituent
effect on the k1 and k2 steps, but due to small ρ1 value for the
low basic amines.
Kinetics
The kinetic studies were performed with a Hitachi U-2000
model UV-vis spectrophotometer for slow reactions (t1/2
=
10 s) or with an Applied Photophysics SX-17MV 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 reactions were followed by monitoring the appearance
of the leaving 2,4-dinitrophenoxide at 410 nm. All the reac-
tions were carried out under pseudo-first-order conditions in
which the amine concentrations were at least 20 times
greater than the substrate concentration. The amine stock so-
lution of ca. 0.2 M was prepared in a 25.0 mL volumetric
flask under nitrogen atmosphere 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 gas-tight syringes. Other details of kinetic methods
were reported previously (19).
Experimental
Materials
2,4–Dinitrophenyl X-substituted benzoates (X-C6H5CO2C6H3-
(NO2)2-2,4) were easily prepared from the reactions of X-
substituted benzoyl chlorides with 2,4-dinitrophenol in the
presence of triethylamine in methylene chloride (18). Their
purity was checked by means of melting points and spectral
1
data such as IR and H NMR characteristics. The amines
© 1999 NRC Canada

666
Can. J. Chem. Vol. 77, 1999
(d) E.A. Castro and C.A. Araneda. J. Org. Chem. 62, 126
Conclusions
(1997).
5. (a) A. Williams. Chem. Soc. Rev. 23, 93 (1994); (b) S. Ba-
The present study has allowed us to conclude the follow-
ing. (i) The RDS of the present aminolysis reactions changes
from the k2 step to the k1 step as the amine becomes more
basic than the leaving group by ca. 5 pKa units. (ii) σ+ con-
stants give better correlation with log kapp, log k1, and log
Kk2 when the k2 step is the RDS (e.g., the reactions with the
low basic amine, pKa < 9.1). However, σ constants show
better correlation when the k1 step is the RDS (e.g., the reac-
tions with highly basic amines, pKa > 9.1). (iii) The magni-
tude of k–1/k2 is nearly constant upon changing the acyl
substituent for a given amine, indicating that the RDS is not
governed by the electronic nature of the acyl substituent X.
(iv) The magnitude of ρ1 is identical to that of ρapp and ρeq
for a given amine. (v) The magnitude of ρapp, ρ1, and ρeq is
much smaller for the reactions with the low basic amines
(pKa < 9.1) than for the ones with the highly basic amines
(pKa > 9.1). (vi) The small values of ρapp and ρeq for the re-
actions in which the RDS is the k2 step is not because the ef-
fect of the acyl substituents on the k1 and k2 step is opposite,
but because the corresponding ρ1 value is small.
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Acknowledgements
The authors are grateful for the financial support from the
Korean Science and Engineering Foundation (KOSEF-981-
0303-017-2) and the MOST through the Women’s Univer-
sity Research Fund (97-N6-01-01-A-14).
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© 1999 NRC Canada