The "dimer nucleophile mechanism" for reactions with rate-determining first step: Derivation of the whole kinetic law and further treatment of kinetic results

Article abstract of DOI:10.1002/kin.20523

Overwhelming evidence has been previously reported for the existence of the so-called "dimer nucleophile mechanism" in aromatic nucleophilic substitutions by amines in aprotic solvents, for which the most prominent feature is the fourth-order kinetics (third order in amine) that has been observed with many different substrate-nucleophile systems, especially those in which departure of the nucleofuge is the rate-determining step. The mechanism has been confirmed by several other features, although other alternative mechanisms were suggested to explain the fourth-order kinetics, no one has been able to explain the other above-mentioned features. The present paper affords additional experimental evidence and derivation of the kinetic expressions for reactions with good nucleofugues, where the first step is rate determining. The work involves studies of the reactions of 2,4-dinitrofluorobenzene and 2,4-dinitrochlorobenzene with aniline and with alkyldiamines in toluene. The novelty of this work lies in the selection of substrate-nucleophile systems exhibiting kinetic behavior that allows estimations of the different k's involved. The satisfactory agreement between the quotients of k's calculated from sets of data obtained under different reaction conditions hereby reported indicates that the assumptions made are correct and that the whole treatment applied to the kinetic data is justified. All together, the results fit well with the reaction scheme involving the dimer nucleophile mechanism, adding new evidence to this mechanism that it is well established in the current literature.

Full text of DOI:10.1002/kin.20523

The “Dimer Nucleophile
Mechanism” for Reactions
with Rate-Determining First
Step: Derivation of the
Whole Kinetic Law and
Further Treatment of
Kinetic Results
CECILIA E. SILVANA ALVARO,1 NORMA SBARBATI NUDELMAN2
1Departamento de Qu´ımica, Facultad de Ingenier´ıa, Universidad Nacional del Comahue, Buenos Aires 1400,
(8300) Neuque´n, Argentina
2Departamento de Qu´ımica Orga´nica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires,
Pab. II, P 3 Ciudad Universitaria (1428), Buenos Aires, Argentina
Received 3 March 2010; revised 6 May 2010, 22 July 2010; accepted 27 July 2010
DOI 10.1002/kin.20523
Published online 1 October 2010 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: Overwhelming evidence has been previously reported for the existence of the
so-called “dimer nucleophile mechanism” in aromatic nucleophilic substitutions by amines
in aprotic solvents, for which the most prominent feature is the fourth-order kinetics (third
order in amine) that has been observed with many different substrate–nucleophile systems,
especially those in which departure of the nucleofuge is the rate-determining step. The mech-
anism has been confirmed by several other features, although other alternative mechanisms
were suggested to explain the fourth-order kinetics, no one has been able to explain the other
above-mentioned features. The present paper affords additional experimental evidence and
Correspondence to: Norma Sbarbati Nudelman; e-mail:
nudelman@qo.fcen.uba.ar.
Contract grant sponsor: Universidad Nacional del Comahue.
Contract grant number: I149-UNCo.
Contract grant sponsor: National Research Council (CONICET)
from Argentina.
Contract grant number: PIP 6019.
2010 Wiley Periodicals, Inc.
c
ꢀ

736
ALVARO AND NUDELMAN
derivation of the kinetic expressions for reactions with good nucleofugues, where the first step
is rate determining. The work involves studies of the reactions of 2,4-dinitrofluorobenzene
and 2,4-dinitrochlorobenzene with aniline and with alkyldiamines in toluene. The novelty of
this work lies in the selection of substrate–nucleophile systems exhibiting kinetic behavior
that allows estimations of the different kꢀs involved. The satisfactory agreement between the
quotients of kꢀs calculated from sets of data obtained under different reaction conditions
hereby reported indicates that the assumptions made are correct and that the whole treatment
applied to the kinetic data is justified. All together, the results fit well with the reaction scheme
involving the dimer nucleophile mechanism, adding new evidence to this mechanism that it
is well established in the current literature. ꢁ 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42:
C
735–742, 2010
hydrogen bonding are one of the principal types of
weak noncovalent interactions that plays a role in defin-
ing the physical properties and reactivity of a large va-
riety of structures in chemical and biological systems
[19].
INTRODUCTION
Active research is currently carried out on several new
mechanistic features of some aromatic nucleophilic
substitutions (ANS) [1]. The renewed interest stems
from the fact that they can proceed in a great variety
of ways, and the mechanistic elucidation of the sev-
eral pathways could allow the ANS to be led to the
desired products [2,3]. For example, the selective syn-
thesis of the highly functionalized xanthone core of the
antibiotic FD-594a has been recently achieved by the
solvent-controlled inversion of leaving group ability
in an ANS [4]. Several mechanistic pathways have re-
cently been proposed to explain some “anomalous” ob-
served kinetics, in the reactions of substituted haloni-
troaromatic compounds, specially in dipolar aprotic
solvents [5–7]. Extensive research is recently carried
out trying to elucidate several leaving groups’ effects in
the reactions of substituted nitrophenylethers with ani-
lines [8a–c] and also with aliphatic amines [8d,e]. Ther-
modynamic studies of σ-complexes in ANS have re-
cently been carried out by electrochemically generated
radicals [9]. The sensitivity of the ANS with amines
to the solvent effects is very well recognized, although
not fully understood yet [3,10]. It has been recently
reported that in reactions with a sulfur nucleophile, the
mechanism is also distinctively different in nonpolar
solvents compared with polar solvents [11]. The study
of solvent effects in ANS contributes to the understand-
ing of the microscopic properties of solvent due the
complex interactions between the amine, the substrate,
and/or the intermediate that occur involving the solvent
molecules [12–14]. Intense research on the differential
effects of mixed solvents is also being carried out at
present [3,15,16], and it has been reported that prop-
erly selected and trained neural network could fairly
represent the dependence of the reaction rate constant
on solvatochromic parameters [17]. On the other hand,
self-association of amines by hydrogen bonding inter-
actions in nonpolar aprotic solvents is a long known
phenomenon [18]. The inter- and intramolecular
In several previous papers, we reported overwhelm-
ing evidence for the existence of the so-called “dimer
nucleophile mechanism” in ANS by amines in apro-
tic solvents [3], and recently, we published atypical
findings in ANS carried out using di- and polyamines
that were purposefully designed because their special
structures would allow forming intra- or intermolecular
hydrogen bond in aprotic solvents [1,20]. The results
obtained are well explained in the frame of the “dimer
nucleophile” mechanism. In this paper, we afford new
kinetic evidence of the involvement of the dimer mech-
anism, even in reactions with 2,4-dinitrochlorobenzene
(DNClB) where the first step is known to be rate de-
termining. Special substrate–nucleophile systems were
designed that allow kinetic determinations in toluene
at relatively low and high [B]; these are third-order re-
actions in amine and they exhibit appropriate kinetic
behavior to apply refined treatments for the estimation
of the different kꢀs involved.
EXPERIMENTAL
Experimental details on the materials and equipments,
on the techniques applied in each case for the purifi-
cation of solvents and amines, for the synthesis and
characterization of the reaction products, and for the
kinetic determinations can be found in the references
of previous publications.
RESULTS AND DISCUSSION
The most prominent feature of the “dimer nucle-
ophile” mechanism is the fourth-order kinetics (third
order in amine) that has been observed with many
different substrate–nucleophile systems, especially
International Journal of Chemical Kinetics DOI 10.1002/kin

“DIMER NUCLEOPHILE MECHANISM” FOR REACTIONS WITH RATE-DETERMINING STEP
737
R
NH
2
H
X
+
NHR
X
NO
NO
2
2
k
k
1
k
3
[B]
H
RH N
2
NHR
+
+
-1
k
2
B:B
NO
X
NO
2
SB
2
2
K
B
2
B
K
1
NHR
+
X
NH R
2
NO
2
NO
2
NO
2
k
k
k
5
4
RNH
B
2
+
X
-4
NO
2
NO
2
NO
2
SB
P
Scheme 1
those in which departure of the nucleofuge is the
rate-determining step. The mechanism was confirmed
by other features such as observation of a negative
energy of activation, catalysis by hydrogen bond
acceptor (HBA) agents, preferential solvation in
mixed solvents, conformational unusual effects in
cycloalkyldiamines, linear kinetic behavior in “inverse
plots,” and nuclear magnetic resonance spectroscopic
evidence of the homo- and mixed aggregates. Although
other alternative mechanisms have been suggested
to explain the fourth-order kinetics, no one has been
able to explain the other above-mentioned features. In
the “dimer nucleophile” mechanism with poor nucle-
ofugues, the inter- or intramolecular hydrogen-bonded
homodimer as well as mixed dimers of the amine with
other HBAs intervene as the true nucleophile forming
the intermediate complex, and a third molecule of
amine assists the decomposition step, as shown in
Scheme 1. The intermediate SB2 is highly zwitterionic
and the extra amine molecule should help to stabilize
the developing charges in nonpolar aprotic solvents.
The proposed mechanism does not preclude attack by
the monomer, as shown in the two-step mechanism
depicted in Scheme 1. Nevertheless, due to the higher
electron density on the hydrogen-bonded nitrogen, the
H-bonded amines (forming inter- or intramolecular ho-
moaggregates) are better nucleophiles than monomeric
amines. Recently, Raczynska and co-workers reported
intramolecular hydrogen bonding in gas phase of
polyfunctional compounds such as cyclic and acyclic
substituted diamines, vinamidines guanidines [21],
substituted formamidines, and amidinazines [22].
The whole kinetic expression for the second-order
coefficient, kA, when the second step is rate deter-
mining, as well as the simplification that can be ap-
plied to limiting situations, were fully discussed in
[3a]. The expression for kA considering only the
attack by the dimer can be reduced to Eqs. (1)–
(3), where K is the equilibrium constant for the
monomer:dimer equilibrium shown by Eq. (1):
K
2B ꢀ B:B
(1)
k [B]
3
k
k
1
S B
Products
2
S
+
B:B
_
1
k
2
(2)
(3)
k1k2K[B] + k1k3K[B]2
kA =
k
−1 + k2 + k3[B]
For poor nucleofugues, decomposition of the inter-
mediate is the rate-determining step, the inequality
k
ꢂ (k2 + k3 [B]) holds, and Eq. (3) can be fur-
−1
ther simplified to Eq. (4), which predicts a linear de-
pendence of kA/[B] vs. [B], as has been observed in
several systems where amine homoaggregates plays a
role.
kA
k1k2K k1k3K[B]
=
+
(4)
[B]
k
k
−1
−1
Initially, most of the systems in which third order in
amine kinetic law was observed were performed using
poor nucleofuge substrates [3]; in recent years, we re-
ported evidence for this atypical kinetic behavior, using
a good nucleofuge also [12,20].
In order to afford additional assessment to the scope
of “dimer nucleophile” mechanism, further treatment
International Journal of Chemical Kinetics DOI 10.1002/kin

738
ALVARO AND NUDELMAN
of the different kinetic equations is reported in this pa-
per, as well as the deduction of kA and kA/[B] expres-
sions for reactions where the first step is rate determin-
ing. The reactions of 2,4-dinitrofluorobenzene (DNFB)
and DNClB with aniline, ethylenediamine (ETDA),
3-dimethylamino-1-propylamine (DMPA), and 1-(2-
aminoethyl)piperidine (2-AEPip) in toluene are third-
order reactions in amine, and they exhibit appropriate
kinetic behavior to apply refined treatments for the es-
timation of the different kꢀs involved.
intercepts, the values k3k4 and k1K1k5 are negli-
∼
gible ( 0), which implies that k and k are also
=
4
5
negligible. Therefore, the mechanism involving
the monomer if it exists should be negligible,
and the mathematical expression for kA can be
simplified to Eq. (7):
(k3k4 + k1k5K1K2) [B] + k1k3K1 [B]2
kA =
K2 (k−4 + k5)
(7)
The third-order rate coefficient is given by
Eq. (8):
Reactions Where the First Step
is Rate Limiting
kA
k3k4 + k1k5K1K2
K2 (k−4 + k5)
k1k3K1 [B]
=
+
It is very well accepted that in ANS reactions of amines
with good nucleofuges substrates such as DNClB, the
first step is the rate limiting. To analyze this situa-
tion, involving attack by the dimer and the monomer,
it should be considered that: (a) the first step is slower
than the second one and (b) that the dimer is bet-
ter nucleophile than the monomer [3]. Application of
the steady-state treatment to the whole mechanism for
the dimer and monomer leads to Eq. (5) that involves
the specific rate constants for each step, the association
equilibrium for the nucleophile, K1, and the constant
for the equilibrium between the intermediates SB and
SB2, K2.
[B]
K2 (k−4 + k5)
(8)
d If it is assumed that amine aggregation is not
relevant (K1 is negligible), the third-order rate
coefficient would be independent of [B] and the
slope of plot of kA/[B] vs. [B] should be null, ac-
cording to Eq. (9), which has not been observed.
kA
k3k4
=
(9)
[B]
K2 (k−4 + k5)
Even when the first step is rate determining, our re-
sults show a linear dependence of kA/[B] vs. [B],
what affords a further empirical support to “dimer nu-
cleophile” mechanism, as shown by the fulfillment
of Eq. (8) observed for the reactions with DNClB
[1,12,20].
ꢀ
ꢁ
k3
K2
k3
K2
k4k5 +
k4 + k1k5K1 [B] + k1 K1 [B]2
ꢀ
ꢁ
kA =
k
k3
K2
−1
K2
k
−4 + k5 +
+
[B]
(5)
the kinetic expression for the third-order rate coeffi-
cient is given by Eq. (6):
Reactions of DNFB (Second Step Rate
Determining): Inversion Plots
ꢀ
ꢁ
K2
k3
K2
k3
K2
k4 + k1k5K1 + k1 K1 [B]
kA
ꢀ
ꢁ
=
(6)
In a simplified form, attack only by the dimer nucle-
ophile can be considered, as shown by Eq. (2), and
the derived expression for kA for reactions where the
second step is rate determining is Eq. (3). Inversion
of Eq. (3) gives expression (10), which allows some
estimation of the different k’s involved:
k
k3
K2
−1
[B]
k
−4 + k5 +
+
[B]
Taking into account that in the reactions carried out
with DNClB [1,12,20]:
a. In the plots of kA vs. [B] the intercept = 0, which
indicates that at least one of these two factors,
k4k5, are worthless.
b. The plots of kA/[B] vs. [B] are linear in the
whole range of [B] studied, what implies that
[B]
kA
1
k1 K
k
−1
=
+
(10)
k1 k2 K + k1 k3 K [B]
Taking into account that the uncatalyzed decompo-
sition of zwitterionic intermediate is slower than the
base-catalyzed one, Eq. (10) can be simplified to
Eq. (11):
k
−4 + k5 ꢂ (k−1 + k3)[B]/K2. This inequality is
clear at low concentrations of [B] because the in-
termediate from the monomer, SB, is more acidic
than the dimer one, SB2, and it should revert
quickly to reagents (k ꢂ k
)
[B]
kA
1
k1 K
k
−4
−1.
−1
=
+
k1 k3 K [B]
(11)
c. As the plots of kA/[B] vs. [B] are linear with null
International Journal of Chemical Kinetics DOI 10.1002/kin

“DIMER NUCLEOPHILE MECHANISM” FOR REACTIONS WITH RATE-DETERMINING STEP
739
an estimation of the magnitude of the quotient:
8
7
6
5
4
3
2
1
0
Slope
k1k3K1
=
Intercept
k3k4 + k1k5K1K2
k5 should be smaller than k3 because the reaction with
the dimer is faster, k1 should be smaller than k3 as the
first step is rate limiting, and K1 and K2 are small values
(K1 0.1 M−1) (see [3]). Therefore, considering the
∼
=
limiting situation k3 k4 ꢂ (k1k5)K1K2, the ratio can be
simplified to the equation
Slope
0
0.05
0.1
0.15
0.2
0.25
= k1K1/k4
Intercept
10−3[Amine]−1 (M−1
)
Figure 1 Reactions of 2,4-dinitrofluorobenzene with
ꢁ
which allows an estimation of the incidence of both
mechanisms in the global reaction.
Inversion of Eq. (8) gives the expression given by
Eq. (12):
ethylenediamine, 3-dimethylamino-1-propylamine, and ꢂ
•
1-(2-aminoethyl)piperidine in toluene at 25 0.2◦C. Inver-
sion plots.
[B]
kA
K2 (k−4 + k5) + (k−1 + k3) [B]
(k3k4 + k1k5K1K2) + k1k3K1 [B]
A plot of the [B]/kA vs. [B]−1 should be linear, ex-
cept where the conditions that allow the simplification
to Eq. (10) are not fulfilled. The data for [B]−1 and
[B]/kA for the reactions of DNFB with aniline [3b],
ETDA [20], DMPA [20], and 2-AEPip [1] in toluene
are gathered in Table I. The plots of [B]/kA vs. [B]−1
(“inversion plots”) for the reactions of DNFB with the
diamines are shown in Fig. 1. (Data for aniline are not
included in the plot because they have a different or-
der of magnitude.) As can be observed, the three plots
are linear, and they allow evaluation of the different
k’s. These reactions exhibit useful kinetic behavior in
a range of [B] for the evaluation of the similar expres-
sions from the plot of kA/[B] vs. [B]. Table II sum-
marizes the values for the intercepts and the slopes
obtained by application of Eqs. (4) and (11). The in-
tercepts allow an estimation of the order of magnitude
of k1k2K/k−1; the slope gives k1k3K/k−1; from both
quotients the ratio k3 /k2 can be reckoned. The good
agreement between both sets of values, built from in-
dependent measurements, is a further evidence that
Eqs. (4) and (11) hold and the simplifications are jus-
tified; when the intercept is zero, the quotient cannot
be calculated, but Table II shows that in the case of the
reactions with ETDA, the base catalyzed decomposi-
tion of SB2 is two orders of magnitude more important
than the uncatalyzed step.
=
(12)
Taking into account that reaction with the dimer is
faster than with the monomer and that the equi-
librium constants are small values, the inequality
(k3k4 + k1k5K1K2) ꢃ k1k3K1[B] holds and Eq. (13)
can be derived.
[B]
kA
K2 (k−4 + k5) (k−1 + k3)
=
+
(13)
k1k3K1 [B]
k1k3K1
Reactions of DNClB (First Step Rate
Determining): Inversion Plots
The data of [B]−1 and quotients [B]/kA for the reac-
tions of DNClB with aniline [12d], ETDA [20], DMPA
[20], and 2-AEPip [1] in toluene are gathered in Ta-
ble III, and the “inversion plot” for the reactions with
the diamines is shown in Fig. 2. Table IV summa-
rizes the results obtained for the slopes and intercepts
obtained from Eqs. (8) and (13) for the reactions where
third order in amine was observed. The intercepts of
Eq. (8) considering the condition k3 k4 ꢂ (k1 k5)K1
K2 allow an estimation of the order of magnitude of
k3k4/K2(k−4 + k5); the slope allows estimation of the
value k1k3K1/K2(k−4 + k5). From the quotient of the
slope and the intercept, the relationship k1K1/k4 can be
reckoned. The results in Table IV show that the values
obtained from the slopes of both groups of data are
of the same order of magnitude for the reactions with
the four amines, even when the slope of Eq. (8) and
the inverse slope of Eq. (13) were obtained from inde-
pendent set of data; this gives a further confidence to
Kinetic Treatment for ANS with Good
Nucleofuge Substrates Considering the
Monomer and the Dimer Mechanisms
The slope/intercept ratio of Eq. (7), derived for the
reactions where the first step is rate determining, allows
International Journal of Chemical Kinetics DOI 10.1002/kin

740
ALVARO AND NUDELMAN
Table I Reactions of DNFB with Aniline, ETDA, DMPA, and 2-AEPip in Toluene
Aniline DMPA ETDA
10−31/[B]
(M−1
2-AEPiP
10−31/[B] 103 [B]/kA
1/[B]
(M−1
10−4[B]/
10−31/
[B] (M−1
103 [B]/kA
103 [B]kA
)
kA (M−2
)
)
(s−1M−2
)
)
(s−1M−2
)
(M−1 (s−1M−2
)
)
10.0
5.00
3.33
2.50
1.99
1.43
7.57
5.83
5.07
4.87
4.55
4.37
0.201
0.166
0.143
0.125
0.111
4.18
3.90
3.29
2.88
2.46
0.202
0.167
0.143
0.126
0.111
0.100
6.86
6.25
5.79
5.55
5.14
4.78
0.199
0.168
0.144
0.125
0.112
0.102
3.16
2.55
2.21
1.90
1.63
1.51
2-AEPip, 1-(2-aminoethyl)piperidine; DMPA, 3-dimethylamino-1-propylamine; DNFB, 2,4-dinitrofluorobenzene; ETDA,
ethylenediamine.
Values of [B]−1 and quotients [B]/kA.
Table II Rate Coefficient Relationships for Aromatic Nucleophilic Substitutions Reactions of
2,4-Dinitrofluorobenzene in Toluene
Amine
Temp. (◦C) k k Ka/k−1(s−1M−2
)
k k Kb/k−1(s−1M−3
)
k k Kc/k−1(s−1M−3
)
kd/k (M−1
)
ke/k (M−1
)
1
2
1
3
1
3
2
2
3
3
Aniline
DMPA
ETDA
30 0.2
25 0.2
25 0.2
25 0.2
13.7 × 10−6
15.2 × 10 −6
42.4 × 103
12.1 × 103
64.9 × 103
26.7 × 10−6
51.6 × 103
33.8 × 103
62.5 × 103
1.11
1.95
∞
0
86.2
0
∞
1.41 × 102 3.90 × 102
2-AEPip
∞
∞
aIntercept and bslope from Eq. (4).
cInverted slope from Eq. (11).
d From the quotient between the slope and the intercept of Eq. (4).
eFrom the quotient between the inverted slope from Eq. (11) and the intercept from Eq. (4).
the dimer mechanism, even when the first step is rate
determining.
Taking into account the value of the quotient
slope/intercept in the reactions with aniline, it can be
concluded that the contribution of both mechanisms
to the global reaction is similar; the dimer mechanism
contributes significantly at relatively high aniline con-
centrations, whereas the contribution is smaller when
[aniline] is close to zero (Table IV).
In the reaction with DMPA and ETDA, the intercept
of kA/[B] vs. [B] plot is close to zero, and the “infinite”
values of the quotient indicate that these reactions pro-
ceed only by the dimer mechanism. In the reactions
with 2-AEPip, the quotient slope/intercept obtained
from the third-order plot indicates that the contribution
of the dimer nucleophile to the global reaction is almost
twice as that of the monomer, whereas this quotient
calculated from the reciprocal double plot, when [2-
AEPip] is close to zero, is 3.06 M−1. Both results indi-
cate that the dimer mechanism contributes significantly
to the rate of the global reaction, also with this diamine.
One of the reviewers of this paper pointed out that in
the simpler case when the nucleofugue is good leaving
group, the expression for kA should lead to Eqs. (14)
and (15)
1.2
1.0
0.8
0.6
0.4
0.2
0.0
0.0
0.5
1.0
1.5
2.0
2.5
[Amine] (M
)
k1k2K[B] + k1k3K[B]2
Figure 2 Reactions of 2,4-dinitrochlorobenzene with
ꢁ
kA =
(14)
(15)
ethylenediamine, 3-dimethylamino-1-propylamine, and ꢂ
•
k2 + k3[B]
1-(2-aminoethyl)piperidine in toluene at 25 0.2 ◦C. Inver-
sion plots.
kA = k1K[B]
International Journal of Chemical Kinetics DOI 10.1002/kin

“DIMER NUCLEOPHILE MECHANISM” FOR REACTIONS WITH RATE-DETERMINING STEP
741
Table III Reactions of 2,4-Dinitrochlorobenzene with Aniline, ETDA, DMPA, and 2-AEPip in Toluene
Aniline
DMPA
ETDA
2-AEPiP
1/[B]
(M−1
10−6 [B]/
kA s M2
1/[B]
10−3 [B]/kA
1/[B]
10−3 [B]/kA
1/[B]
10−3 [B]/kA
(s−1 M−2
)
)
(M−1
)
(s−1 M−2
)
(M−1
)
(s−1 M−2
)
(M−1
)
1.98
2.08
1.70
1.32
1.23
1.14
0.990
2.01
1.66
1.43
1.25
1.11
1.00
0.830
0.670
0.500
1.02
2.02
1.67
1.42
1.26
1.11
1.00
0.833
0.667
0.292
0.267
0.248
0.193
0.199
0.161
0.143
0.111
2.02
1.67
1.26
1.00
0.833
0.662
0.578
0.498
0.433
0.394
0.258
0.241
0.254
0.205
0.201
0.173
0.159
0.131
0.101
0.096
0.990
0.667
0.498
0.405
0.332
0.835
0.704
0.635
0.579
0.505
0.463
0.382
0.340
2-AEPip, 1-(2-aminoethyl)piperidine; DMPA, 3-dimethylamino-1-propylamine; DNFB, 2,4-dinitrofluorobenzene; ETDA,
ethylenediamine.
Values of [B]−1 and quotients [B]/kA.
Table IV Rate Coefficient Relationships for Aromatic Nucleophilic Substitutions Reactions of
2,4-Dinitrochlorobenzene in Toluene
k ka/K (k + k5)
k k Kb/K (k + k5)
k k Kc/K (k + k5)
k Kd/k
k Ke/k
1 4
1
3
2
−4
1
3
2
−4
1
3
2
−4
1
4
4
1
1
1
Amine
Temp. (◦C)
(s−1M−1
)
(s−1M−2
)
(s−1M−2
)
(M−1
)
(M−1
)
Aniline
DMPA
ETDA
40 0.2
25 0.2
25 0.2
25 0.2
3.29 × 10−7
2.8 × 10−7
1.73 × 10−3
6.00 × 10−3
3.21 × 10−3
1.67 × 10−7
2.20 × 10−3
7.24 × 10−3
5.03 × 10−3
0.85
∞
0.51
∞
0
0
∞
∞
2-AEPip
1.64 × 10−3
1.96
3.06
aIntercepts and bslopes from Eq. (8).
cInverted slope from Eq. (13).
d From quotient between the slope and the intercept of Eq. (8).
eFrom quotient between the inverted slope from Eq. (11) and the intercept from Eq. (8).
This follows the well acceptable equation used in ANS.
The concentrations of the amine at which the kinetic
measurements were made are high enough to promote
amine aggregation, but Eq. (15) is a simpler and valid
equation for the treatment of the kinetic data, and it
has been previously used in similar cases (see, e.g.,
[12c,d]).
pressions for reactions where the first step is rate de-
termining. The work involves kinetic studies of the
reactions of DNFB and DNClB with aniline and alkyl-
diamines in toluene. Besides the fourth-order kinetics,
the special substrate–nucleophile systems designed ex-
hibit such differential behavior in an attainable range of
[B] that allows a refined treatment of the kinetic results
and calculations of the different k’s involved, consider-
ing a reaction scheme including the monomer and the
dimer nucleophile mechanisms for reactions in aprotic
solvents. Calculations were carried out with different
set of data determined at low and high [B]. The satisfac-
tory agreement between the quotients of k’s calculated
from both sets of data obtained under different reaction
conditions here reported indicates that the assumptions
made are correct and that the whole treatment applied
to the kinetic data is justified. These results allow us
to conclude that the dimer nucleophile mechanism is
well established.
CONCLUSIONS
In several previous papers, we reported overwhelm-
ing evidence for the existence of the so-called “dimer
nucleophile mechanism” in ANS by amines in apro-
tic solvents, derivation of the different kinetic expres-
sions were described, especially for reactions in which
departure of the nucleofuge from the zwitterionic in-
termediate is the rate-determining step. The present pa-
per affords additional kinetic evidences for the dimer
mechanism, and derivation of the different kinetic ex-
International Journal of Chemical Kinetics DOI 10.1002/kin

742
ALVARO AND NUDELMAN
Verlag GmcH & Co. KgaA: Weinheim, Germany,
2003.
BIBLIOGRAPHY
11. Jacobsson, M.; Oxgaard, J.; Abrahamsson, C.; Norrby,
P.; Goddard, W. A.; Ellervik, U. Molecules 2008, 13,
1282–1302.
1. Alvaro, C. E. S.; Ayala, A. D.; Nudelman, N. S. J Phys
Org Chem 2010, 23.
2. Buncel, E.; Dust, J. M.; Terrier, F. Chem Rev 1995, 95,
2261.
12. (a) Alvaro, C. E. S.; Nudelman, N. S. ARKIVOC 2003,
X, 95–106; (b) Nudelman, N. S.; Alvaro, C. E. S.; Savini,
M.; Nicotra, V.; Yankelevich, J. S. Collect Czech Chem
Commun 1999, 64, 1583–1593; (c) Nudelman, N. S.;
Savini, M.; Alvaro, C. E. S.; Nicotra, V.; Yankelevich,
J. S. J Chem Soc, Perkin Trans 2 1999, 1627–1630;
(d) Nudelman, N. S.; Alvaro, C. E. S.; Yankelevich,
J. S. J Chem Soc, Perkin Trans 2 1997, 2125–2130.
13. (a) Mancini, P. M. E.; Perez, A. del C.; Vottero, L. R.
J Solution Chem 2001, 30, 695–707; (b) Mancini,
P. M. E.; Fortunato, G.; Adam, C.; Vottero, L. R.;
Terenzani, A. J Phys Org Chem 2002, 15, 258–269;
(c) Mancini, P. M. E.; Adam, C.; Perez, A. del C.;
Vottero, L. R. J Phys Org Chem 2000, 13, 221–231.
14. (a) Boga, C.; Forlani, L. J Chem Soc Perkin Trans 2
2001, 1408–1413, and references cited therein; (b) For-
lani, L.; Boga, C.; Forconi, M. J Chem Soc Perkin Trans
2 1999, 1455–1458.
15. Bhuvaneshwari, D. S.; Kalaimani, N.; Rathinam, S.
Indian J Chem 2008, 47A, 1348–1354.
16. Habibi-Yangjieh, A.; Jafari-Tarzanag, Y.; Banaei, A. R.
Int J Chem Kinet 2009, 41, 153–159.
17. Khodadadi-Moghaddam, M.; Habibi-Yangjeh, A.;
Gholami, M. R. Monatsh Chem 2009, 140, 329–334.
18. Rao, C. N.; Pradeep, T. Chem Soc Rev 1991, 20,477.
19. (a) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond
in Structural Chemistry and Biology; Oxford University
Press: New York, 1999; (b) Scheiner, S. Hydrogen Bond-
ing: A Theorical Perspective; Oxford University Press:
New York, 1997.
3. (a) Nudelman, N. S. In The Chemistry of Amino, Ni-
troso, Nitro and Related Groups; Patai, S. (Ed.); Wiley
J & Sons Ltd.: London, 1996; Ch. 29, pp. 1215–1300,
and references therein; (b) Nudelman N.S.; Montserrat
J.M. J Chem Soc, Perkin Trans 2 1990, 1073–1076.
4. Hintermann, L.; Masuo, R.; Suzuki, K. Org Lett 2008,
10, 4859–4862.
5. (a) Meenakshisundaram, S.; Selvaraju, M.; Made
Gowda, N. M.; Rangappa, K. S. Int J Chem Kinet 2005,
37, 649–657; (b) Karunakaran, C.; Kamalam, R. J Org
Chem 2002, 67, 1118; (c) Karunakaran, C.; Palanisamy,
P. N. Int J Chem Kinet 1999, 31, 571.
6. (a) Banjoko, O.; Babatunde, I. Tetrahedron 2004, 60,
4645–4654; (b) Banjoko, O.; Babatunde, I. Tetrahedron
2005, 61, 8035–8040; (c) Emokpae, T. A.; Isanbor, C.
Int J Chem Kinet 2004, 36, 188–196; (d) Emokpae, T.
A.; Atasie, N. V. Int J Chem Kinet 2005, 37, 744–750.
7. (a) Bhuvaneshwari, D. S.; Elango, K. P. Int J Chem Kinet
2006, 38, 166–175; (b) Bhuvaneshwari, D. S.; Elango,
K. P. Z Phys Chem 2006, 220, 697–721.
8. (a) Crampton, M. R.; Emokpae, T. A.; Howard,
J. A. K.; Isanbor, C.; Mondal, R. J Phys Org Chem 2004,
17, 65–70; (b) Isanbor, C.; Emokpae, T. A.; Crampton,
M. R. J Chem Soc, Perkin Trans 2 2002, 2019–2024;
(c) Crampton, M. R.; Emokpae, T. A.; Isanbor, C. J
Phys Org Chem 2006, 19, 75–80; (d) Crampton, M. R.;
Emokpae, T. A.; Isanbor, C.; Batsanov, A. S.; Howard,
J. A. K.; Mondal, R. Eur J Org Chem 2006, 5, 1222–
1230; (e) Crampton, M. R.; Emokpae, T. A.; Isanbor,
C. Eur J Org Chem 2007, 8, 1378–1383.
20. Alvaro, C. E. S.; Nudelman, N. S. J Phys Org Chem
2005, 18, 880–885, and references therein.
21. Raczynska, E. D.; Maria, P. C.; Gal, J. F.; Decouzon, M.
J Phys Org Chem 1994, 7, 725–733.
22. Raczynska, E. D.; Decouzon, M.; Gal, J. F.; Maria, P. C.;
Taft, R. W.; Anvia, F. J Org Chem 2000, 65, 4635–4640.
9. (a) Gallardo, I.; Guirado, G. Eur J Org Chem 2008, 14,
2463–2472; (b) Al-Kaysi, R. O.; Gallardo, I.; Guirado,
G. Int J Chem Kinet 2008, 40, 125–135.
10. Reichardt, C. In Solvent and Solvents Effects
in Organic Chemistry, 3rd ed.; Wiley-VCH,
International Journal of Chemical Kinetics DOI 10.1002/kin