Role of hydrogen-bonded nucleophiles in aromatic nucleophilic substitutions in aprotic solvents. Reactions of halonitrobenzenes with ethylenediamine, 3-dimethylamino-1-propylamine and histamine in toluene

Article abstract of DOI:10.1002/poc.957

The kinetics of the reactions between 1-halogeno-2,4-dinitrobenzene (halogen = F, C1) and the amines ethylenediamine (EDA) and 3-dimethylamino-1- propylamine (DMPA) were studied in toluene at 25° ±0.2C under pseudo-first-order conditions using varying amounts of amine. Even with C1 as the nucleofugue (where usually the first step is rate-determining), a third-order-in-amine kinetic law was observed: these results can be interpreted within the 'dimer nucleophile' mechanism where the amine homo-aggregates are better nucleophiles than the amine monomers. To confirm this interpretation, the reaction of 2,4-dinitrofluorobenzene with histamine was studied in the same solvent. Because of the rigid geometry, an intramolecular hydrogen bond is easily established, which prevents the formation of self-aggregates. Consequently, the plot of k_A vs. [histamine] is a straight line, as expected for a classical mechanism of base-catalysed decomposition of the zwitterionic intermediate. All these results are well explained in the frame of the 'dimer nucleophile' mechanism. Copyright

Full text of DOI:10.1002/poc.957

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2005; 18: 880–885
Published online 6 June 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.957
Role of hydrogen-bonded nucleophiles in aromatic
nucleophilic substitutions in aprotic solvents.
Reactions of halonitrobenzenes with ethylenediamine,
3
-dimethylamino-1-propylamine and histamine
y
in toluene
1
2
Cecilia E. Silvana Alvaro and Norma Sbarbati Nudelman *
1
Departamento de Qu ı´ mica, Facultad de Ingenier ı´ a, Universidad Nacional del Comahue, Buenos Aires 1400, 8300 Neuqu e´ n, Argentina
2
Departamento de Qu ı´ mica Org a´ nica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pab. II, P 3 Ciudad Universitaria
(1428), Buenos Aires, Argentina
Received 20 January 2005; revised 23 March 2005; accepted 5 April 2005
ABSTRACT: The kinetics of the reactions between 1-halogeno-2,4-dinitrobenzene (halogen ¼ F, Cl) and the amines
ꢀ
ethylenediamine (EDA) and 3-dimethylamino-1-propylamine (DMPA) were studied in toluene at 25 ꢁ 0.2C under
pseudo-first-order conditions using varying amounts of amine. Even with Cl as the nucleofugue (where usually the
first step is rate-determining), a third-order-in-amine kinetic law was observed: these results can be interpreted within
the ‘dimer nucleophile’ mechanism where the amine homo-aggregates are better nucleophiles than the amine
monomers. To confirm this interpretation, the reaction of 2,4-dinitrofluorobenzene with histamine was studied in the
same solvent. Because of the rigid geometry, an intramolecular hydrogen bond is easily established, which prevents
the formation of self-aggregates. Consequently, the plot of k vs. [histamine] is a straight line, as expected for a
A
classical mechanism of base-catalysed decomposition of the zwitterionic intermediate. All these results are well
explained in the frame of the ‘dimer nucleophile’ mechanism. Copyright # 2005 John Wiley & Sons, Ltd.
KEYWORDS: hydrogen bond; aromatic nucleophilic substitution; aprotic solvents; hydrogen-bonded nucleophiles; mixed
aggregates; dimer nucleophile mechanism
5
INTRODUCTION
polarity have been proposed and reviewed recently. The
most successful solvent scales are those that involve
several parameters, each one related to a specific solvent
The role that inter- or intramolecular hydrogen bonding
plays in defining the physical properties and reactivity of
a large variety of structures is now widely recognized in
6–8
property. Regarding the particular interaction of hy-
drogen bonding, the ꢀ and ꢁ parameters have been
defined to be good descriptors of the ability of a solvent
1
to be a hydrogen-bond donor or acceptor, respectively.
Nevertheless, for the case of aprotic non-polar sol-
vents, solute–solvent hydrogen bonding almost does not
occur and properties measured in the gas phase or solid
state can afford useful information. Fine measures of
amine basicities in the gas phase have been reported
1,2
chemical and biological systems. On the other hand,
other types of weak non-covalent interactions in deter-
mining chemical reactivity are also current subjects of
,9
3
,4
increasing interest. When the reactions are carried out
in solution, intermolecular forces of different types are
established that can be involved in the general concept of
‘
solvent effects’, of which hydrogen bonding could be
10
one of the more important specific microscopic interac-
tions. Several scales of quantitative measures of solvent
recently, as well as theoretical calculations, mainly
performed by Zou and co-workers, at the HF/6–31G*
11,12
level for different data sets of solvents.
The authors
established linear correlations between empirical para-
*
Correspondence to: N. S. Nudelman, Departamento de Qu ´ı mica
13
meters and theoretical descriptors, and Katritzky and
Org a´ nica, Facultad de Ciencias Exactas y Naturales, Universidad de
Buenos Aires, Pab. II, P 3 Ciudad Universitaria (1428), Buenos Aires,
Argentina.
E-mail: nudelman@qo.fcen.uba.ar
Contract/grant sponsor: University of Buenos Aires; Contract/grant
number: EX213-UBA.
14
co-workers reported an extensive attempt to relate
solvent scales to the theoretical descriptors. On the other
15
hand, Spange and co-workers estimated the empirical
donor–acceptor and polarity parameters of several solids
and they concluded that empirical polarity parameters are
recommended as useful characteristics for describing the
surface properties of several solids.
Contract/grant sponsor: Universidad Nacional del Comahue; Con-
tract/grant number: I094-UNCo.
y
Otto Exner on the occasion of his 80th birthday.
Selected paper presented for a special issue dedicated to Professor
Copyright # 2005 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2005; 18: 880–885

H-BONDED DIAMINES IN S
N
Ar
881
Aromatic nucleophilic substitution (S Ar) by amines has
N
The reactions proceed in a straightforward manner to
give the expected N-substituted-2,4-dinitroaniline, and a
quantitative yield of the substitution product was obtained
in all reactions under study. The determinations were
carried out under pseudo-first-order conditions; the rate
dependence on the amine concentration was studied and
good kinetic behaviour was observed throughout the work.
been recognized to be extremely affected by the sol-
16,17
vent.
Such study is currently receiving increased inter-
est because S Ar by amines is a suitable model to
N
contribute to the understanding of the microscopic proper-
ties of solvent in reactions due to the complex interactions
between the amine, the substrate and/or the intermediate
1
8–20
that occur involving the solvent molecules.
The me-
chanisms of reactions in protic solvents are well established
Reactions of DNFB and DNClB with
EDA and DMPA in toluene
but S Ar in aprotic solvents exhibits peculiar features for
N
17
studying specific and non-specific solvent effects. Evi-
21
dence for nucleophile aggregation, substrate–nucleophile
The kinetics of the reactions of DNFB and DNClB, both
with DMPA and EDA, in toluene were studied at
22
electron-donor acceptor (EDA) complexes and other
23,24
types of complexes
ꢀ
has been reported by different
authors when reactions were carried out in aprotic solvents.
25 ꢁ 0.2 C in the presence of variable amounts of the
nucleophile. Table 1 shows the observed results for the
reactions with DNFB: the bimolecular rate coefficient kA
In the present work, we describe the study of S Ar
N
using diamines that were purposefully selected for their
special structures, because potentially they would be able
to form intra- or intermolecular hydrogen bonds in
aprotic solvents. The substrates are 2,4-dinitrochloroben-
and the ratio k /[B] are given. Table 2 shows the corre-
A
sponding values for the reactions of EDA and DMPAwith
DNClB in toluene. It can be observed that the second-
order rate coefficient k increases rapidly with amine
A
zene and 2,4-dinitrofluorobenzene: S Ar of chlorine by
N
concentration [B] and the plot of k vs. [B] (see Fig. 1),
A
amines is known to occur in the first rate-determining
step but S Ar of fluorine by amines is susceptible to base
catalysis because the decomposition of the zwitterionic
shows a quadratic dependence. On the other hand, the plot
of k /[B] vs. [B] (Fig. 2) shows a straight line; this result is
N
A
consistent with a third-order-in-amine term in the kinetic
law. This kinetic behaviour has been observed previously
16,17
intermediate is very often rate-determining.
1
7,28
in other systems,
mechanism shown in Eqns (1)–(3), where the dimer
B:B) of the nucleophile attacks the substrate S to form
and can be interpreted by the
RESULTS AND DISCUSSION
(
Self-association of amines to form mainly dimers by
hydrogen-bonding interactions is a long-known phenom-
the intermediate SB ; then a third molecule of amine
2
assists in the decomposition step. The intermediate in Eqn
(2) is zwitterionic; the extra amine molecule is needed to
stabilize the developing charge in this solvent of very low
permitivity. The kinetic law is given by Eqn (3), where
25
enon and it has been shown that the dimers are respon-
sible for the ‘dimer nucleophile’ mechanism when amines
are used as nucleophilic reagents in S Ar carried out in
N
21
2
aprotic solvents. Intermolecular hydrogen bonding in-
creases the nucleophilicity of the dimer compared with
K ¼ [B:B]/[B] is the amine self-association constant.
17
K
the monomer, as confirmed by semi-empirical and ab
2
BÐB:B
ð1Þ
ð2Þ
26
initio calculations. On the other hand, when two amino
groups are in a rigid appropriate geometry, strong intra-
molecular hydrogen bonding is easily established and
k1
S þ B:B Ð ½SB ꢃ
Products
2
27
such compounds exhibit unusually high basicity.
To examine the importance of hydrogen-bonding inter-
kꢂ1
actions in S Ar with amines carried out in aprotic solvents,
N
2
k k K½Bꢃ þ k k K½Bꢃ
1
2
1 3
the reactions of 2,4-dinitrofluorobenzene (DNFB) and 2,4-
dinitrochlorobenzene (DNClB) with diamines in toluene
were studied. The selected amines were ethylenediamine
kA ¼
ð3Þ
k
þ k þ k ½Bꢃ
ꢂ1
2
3
The magnitudes of the rates with both amines are
similar but it can be observed in Fig. 2 that the straight
line for the reaction with EDA has a no-null intercept.
This indicates that both the monomer and the dimer
(EDA), 3-dimethylamino-1-propylamine (DMPA) and his-
tamine, specially chosen for their potential ability to form
inter- and/or intramolecular hydrogen bonding.
H
H
H
H
H
C
NCH3
N
H
H
H
H
H
C
C
H
N
N
N
CH2
CH2
H
N
H C
3
C
H
C
H
H
H
N
H
H
H
EDA
DMPA
Histamine
Copyright # 2005 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2005; 18: 880–885

8
82
C. E. SILVANA ALVARO AND N. S. NUDELMAN
ꢂ4
Table 1. Reaction of 2,4-dinitrofluorobenzene (DNFB, 5 ꢄ 10 M) with 3-dimethylamino-1-propylamine (DMPA) and ethyle-
ꢀ
nediamine (EDA) (B) in toluene at 25.0 ꢁ 0.2 C (second- and third-order rate coefficients are k and k /[B], respectively)
A
A
DMPA
EDA
3
0 [B] (M)
ꢂ1 Mꢂ1
ꢂ2
ꢂ1 Mꢂ2
3
10 [B] (M)
ꢂ1 Mꢂ1
ꢂ2
ꢂ1 Mꢂ2
1
kA (s
)
10 kA/[B] (s
)
kA (s
)
10 kA/[B] (s )
4
6
6
8
8
.97
.01
.97
.00
.97
1.19
1.54
2.12
2.78
3.64
2.39
2.56
3.04
3.48
4.06
4.94
6.00
7.00
7.94
8.99
0.72
0.96
1.21
1.43
1.75
2.09
1.46
1.60
1.72
1.80
1.95
2.09
1
0.0
ꢂ4
Table 2. Reaction of 2,4-dinitrochlororobenzene (DNClB, 5 ꢄ 10 M) with 3-dimethylamino-1-propylamine (DMPA) and
ꢀ
ethylenediamine (EDA) (B) in toluene at 25.0 ꢁ 0.2 C (second- and third-order rate coefficients are k and k /[B], respectively)
A
A
DMPA
EDA
3
ꢂ1 Mꢂ1
3
ꢂ1 Mꢂ2
3
ꢂ1 Mꢂ1
3
ꢂ1 Mꢂ2
)
[B](M)
k ꢄ 10 (s
)
k /[B] ꢄ 10 (s
)
[B] (M)
k ꢄ 10 (s
)
k /[B] ꢄ 10 (s
A
A
A
A
0
0
0
0
0
1
1
1
2
.497
.601
.697
.800
.897
.00
.20
.50
.01
0.485
0.976
0.494
0.60
0.704
0.794
0.899
1.00
1.69
3.42
3.75
4.03
5.18
5.03
6.21
6.99
8.98
0.72
0.99
1.26
1.55
1.98
2.59
3.93
5.92
1.20
1.42
1.57
1.73
1.98
2.16
2.62
2.94
2.25
2.84
4.11
4.52
6.21
8.39
13.50
1.20
1.50
nucleophile mechanisms are operating in the reaction
with this amine, whereas the reaction with DMPA pro-
ceeds entirely through the dimer nucleophile and is
slightly faster than with EDA.
Although, as expected for a less-activated substrate, the
reactions of DNClB are slower than those of DNFB,
the kinetic behaviour is very similar. The second-order
rate coefficient k was found to increase rapidly with
A
Table 2 shows the k and k /[B] values for the reactions
A
of DNClB with DMPA and EDA in toluene at 25 C in the
presence of variable amounts of the nucleophile.
amine concentration [B]; the plot of k vs. [B] (Fig. 3)
A
shows a quadratic dependence whereas the plot of k /[B]
A
vs. [B] is a straight line as shown in Fig. 4. These results
A
ꢀ
5
4
3
2
1
0
5
4
3
2
1
0
0
2
4
6
8
10
12
0
3
6
9
12
3
3
1
0 [Amine]/M
10 [Amine]/M
Figure 1. Second-order rate coefficients, k , for the
Figure 2. Third-order rate coefficients, k /[B], for the reac-
A
A
reactions of 2,4-dinitrofluorobenzene (DNFB) with (*) 3-
tions of 2,4-dinitrofluorobenzene (DNFB) with (*)
dimethylamino-1-propylamine (DMPA) and (&) ethylenedia-
3-dimethylamino-1-propylamine (DMPA) and (&) ethylene-
ꢀ
ꢀ
mine (EDA) in toluene at 25.0 ꢁ 0.2 C as a function of
diamine (EDA) in toluene at 25.0 ꢁ 0.2 C as a function of
amine concentration
amine concentration
Copyright # 2005 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2005; 18: 880–885

H-BONDED DIAMINES IN S
N
Ar
883
1
1
5
2
9
6
3
0
10
8
6
4
2
0
0
0,5
1
1,5
2
2,5
0
0,5
1
1,5
2
2,5
[
Amine]/M
[
Amine]/M
Figure 4. Third-order rate coefficients, k /[B], for the
reactions of 2,4-dinitrochlorobenzene (DNClB) with (*) 3-
dimethylamino-1-propylamine (DMPA) and (&) ethylenedia-
mine (EDA) in toluene at 25.0 ꢁ 0.2 C as a function of
A
Figure 3. Second-order rate coefficients, k , for the reac-
tions of 2,4-dinitrochlorobenzene (DNClB) with (*) 3-di-
methylamino-1-propylamine
A
(DMPA)
and
(&)
ꢀ
ꢀ
ethylenediamine (EDA) in toluene at 25.0 ꢁ 0.2 C as a
amine concentration
function of amine concentration
are consistent with a third-order-in-amine term in the
kinetic law, similar to what was observed with DNFB,
confirming the presence of dimers of DMPA and EDA
acting as nucleophiles following the mechanism shown
by Eqns (1)–(3). For both amines the intercept in Fig. 4 is
null, indicating that the reactions proceed fully by the
second-order rate coefficient increases steadily with [B];
the plot of k vs. [B] is a straight line with a null intercept
A
2
and a correlation coefficient of R ¼ 0.991 (Fig. 5). For
histamine the intramolecular hydrogen bonding prevents
the formation of intermolecular dimers and the classical
mechanism of base-catalysed decomposition of the zwit-
16
‘
dimer nucleophile’ mechanism. It can be observed that
terionic intermediate SB is obeyed. The null intercept
indicates that the spontaneous decomposition of SB is
negligible, as expected from the poor nucleofugacity of
fluorine in an aprotic solvent.
in this case the reaction with EDA is faster than with
DMPA, reflecting the steric effects of the more hindered
amine in attacking the substrate S and forming the
intermediate SB , where the nucleofugue is now a rather
2
The present results show that for S Ar reactions of
N
bulky atom. Molecular structures of the open-chain
dimers of EDA and DMPA are shown below.
nitro-activated substrates and amines in non-polar aprotic
solvents auto-association of amines is very important
H
H
H
H
H
N
CH3
N
H
N
C
H
H
H
N
C
H
C
H
3
C
C
C
H
N
H
H
N
H
C
H
H
H
H
H H
H H
H
H
C
N
H
H
C
C
C
CH3
H
H
H
H
H
H
N
3
H C
EDA
DMPA
Table 3. Reaction of 2,4-dinitrofluorobenzene (DNFB,
ꢂ4
ꢀ
1
ꢄ 10 M) with histamine in toluene at 40.0 ꢁ 0.2 C (k
A
Reactions of DNFB with histamine in toluene
is second-order rate coefficient)
3
0 [Histamine] (M)
3
ꢂ1 Mꢂ1
)
1
k ꢄ 10 (s
A
To confirm the overall interpretation that the intermole-
cular hydrogen bondings in EDA and DMPA are respon-
sible for the observed results, the reactions of a
nucleophile able to form intramolecular hydrogen bond-
5
.00
5.30
5.99
7.00
.98
8.98
0.1
6.26
7.75
8.79
9.69
7
ing were studied. Table 3 shows the k values for the
A
ꢀ
reaction of histamine with DNFB in toluene at 40 C in
the presence of variable amounts of the nucleophile. The
1
10.5
Copyright # 2005 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2005; 18: 880–885

8
84
C. E. SILVANA ALVARO AND N. S. NUDELMAN
1
2
0
8
6
4
2
0
spectra were recorded on a Bruker ARX-300 spectro-
meter. The J values are given in hertz. The NMR spectra
were determined in CDCl as solvent and thin-layer
3
chromatography was performed on Merck Kiesegel 60
F254. Melting points were determined in a Kofler hot
stage and are uncorrected.
1
Reagents and solvents
All solvents and reagents were analytical reagent grade.
Toluene was kept over sodium wire for several days and
0
3
6
9
12
3
1
3
distilled twice over sodium as described previously.
Solvent was stored in a special vessel protected from light
that allows delivery without air contamination.
1
0 [Histamine]/M
Figure 5. Second-order rate coefficients, k , for the reac-
A
tions of 2,4-dinitrofluorobenzene (DNFB) with histamine
Ethylenediamine (EDA, Fluka) was kept overnight
over potassium hydroxide, distilled over zinc powder
and then over sodium; both distillations were carried
out at normal pressure and retrieve the fraction b.p.
ꢀ
in toluene at 40.0 ꢁ 0.2 C as a function of histamine
concentration
because of the low permittivity of the media and the
importance of hydrogen-bonding interactions. Because of
the higher electron density on the hydrogen-bond donor
nitrogen, hydrogen-bonded amines are better nucleo-
philes than those in which no hydrogen-bonding interac-
tions are possible. So, the reactions with inter- or
intramolecular homo-aggregate, as well as mixed (het-
ero-) aggregates with other hydrogen-bond acceptors
present in the reaction media, are faster than with the
non-hydrogen-bonded nucleophile. The intervention of
the amine on the leaving group departure from the
zwitterionic intermediate is the more usual explanation
of the autocatalytic behaviour.
ꢀ
ꢀ
32
116–118 C (lit. 116.5 C). It was kept in a desiccator
0
protected from light. 4(5)-2 -Aminoethylimidazole (his-
tamine base) (Fluka) was used without any purification
and was kept in a desiccator protected from light.
2,4-Dinitrochlorobenzene (DNClB, Sigma) was crys-
ꢀ
tallized twice from absolute ethanol (m.p. 52–53 C,
ꢀ
18a
lit.
52–53 C). 2,4-Dinitrofluorobenzene (DNFB,
Merck) was distilled at reduced pressure under nitrogen
(b.p. 122–123 C at 5 mmHg, lit. 119 C at 2 mmHg)
and was kept in a desiccator protected from light under a
nitrogen atmosphere.
ꢀ
ꢀ
30
0
2-Amino-1-(N-2,4-dinitrophenyl)ethylamine, 4(5)-2 -
Some other proposals have been given for the third-
order-in-amine kinetic law observed in some special
(N-2,4-dinitrophenyl)aminoethyl imidazole and 3-di-
methylamino-1-(N-2,4-dinitrophenyl)propylamine were
prepared from DNClB and the corresponding amine
following the procedure reported for N-(2,4-dinitrophe-
23,24,29
systems.
In particular, the formation of the homo-
þ
(
or hetero-) conjugated acid BH B by proton transfer
29
33
from the intermediate, proposed by Hirst, and the
electrophilically catalysed departure of the nucleofugue
due to this aggregate are common to the ‘dimer nucleo-
phile’ mechanism and both can be formulated as essen-
tially the same and as reflecting parts of a spectrum of
methods for the formation of the second intermediate.
Nevertheless, only the ‘dimer nucleophile’ mechanism
explains other experimental findings such as the ‘inver-
sion’ plots and the conformational effects observed in
reactions with cis- and trans- 1,2-diaminocyclohexane.
As observed in the present case with histamine, the
intramolecular hydrogen-bonding interaction in the cis-
isomer makes this amine more nucleophilic in spite of the
nyl)-2-methoxyaniline. In all cases, the compounds
were obtained in almost quantitative yields as yellow
crystals. [2-Amino-1-(N-2,4-dinitrophenyl)ethylamine
ꢀ
1
(m.p. 108–110 C); H NMR (CDCl ): ꢂ 2.30 (s, 1H),
3
8.93 (d, 1H), 6.87 (d, 1H), 8.12 (m, 1H), 3.28 (t, 2H), 3.00
13
(t, 2H), 1,40 (s, 2H); C NMR (CDCl ): ꢂ 40.90, 48.31,
3
121.51, 121.87, 132.55, 148.10, 148.50, 149.90. 4(5)-2’-
(N-2,4-Dinitrophenyl)aminoethylimidazole (m.p. 158–
ꢀ
1
160 C), H NMR (CDCl ): ꢂ 2.22 (s, 1H), 9.03 (d,
3
1H), 7.10 (d, 1H), 8.25 (m, 1H), 3.24 (t, 2H), 3.05 (t,
13
2H), 7.59 (s, 1H), 8.08 (s, 1H), 12.60 (s, 1H); C NMR
(CDCl ): ꢂ 23.19, 38.79, 118.85, 120.56, 123.12, 130.01,
3
141.88, 147.80, 148.50, 149.00. 3-Dimethylamino-1-(N-
1
30
ꢀ
stronger steric effects.
2,4-dinitrophenyl)propylamine (m.p. 100–102 C);
NMR (CDCl ): ꢂ 2.10 (s, 1H), 9.30 (d, 1H), 7.40 (d,
H
3
1
H), 8.48 (m, 1H), 3.70 (t, 2H), 2.01(t, 2H), 2.65 (t, 2H),
13
EXPERIMENTAL
2.31 (s, 6H); C NMR (CDCl ): ꢂ 27.65, 44.48, 45.40,
3
58.01, 119.34, 122.35, 128.87, 147.80, 148.48, 149.90.]
General procedures
3-Dimethylamino-1-propylamine (DMPA) was pre-
pared from dimethylamine and acrylonitrile following a
34
The UV–Vis spectra were recorded in a Shimadzu UV-
1 13
VIS 240 spectrophotometer and the H and C NMR
known technique. After 2 days, the excess of dimethy-
ꢀ
lamine was distilled under reduce pressure at 75–77 C/
Copyright # 2005 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2005; 18: 880–885

H-BONDED DIAMINES IN S
N
Ar
885
1
1 mmHg). The N,N-dimethylpropanenitrile obtained
del Comahue (grant no. I094-UNCo) is gratefully ac-
knowledged.
was reduced with Na/EtOH. Distillation of the resulting
product gave DMPA as a liquid, which was stored under a
ꢀ
1
nitrogen atmosphere at 5 C. [ H NMR (CDCl ): ꢂ 1.30
3
REFERENCES
(
s, 2H, -NH ), 1.71 (m, 2H, -CH -), 2.32 (s, 6H, CH ),
2 2 3
2
.41 (t, 2H, -CH -), 2.84 (t, 2H, -CH -).]
2 2
1
2
3
4
5
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tion coefficients of the products were determined at ꢃmax
and at ꢃ ¼ 400 and 450 nm; at these wavelengths the
reagents are transparent under these conditions. All the
solutions were found to obey Beer’s law.
2
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1
1
1
[
2-Amino-1-N-(2,4-dinitrophenyl)ethylamine: ꢃ
¼
max
4
ꢂ1 ꢂ1
M
1
1
1
1
3
48 nm, "348 ¼ 1.08 10 cm
; 4(5)-2’-(N-2,4-dini-
imidazole:
ꢃmax ¼ 349 nm,
ꢂ1 Mꢂ1
; 3-dimethylamino-1-N-(2,4-di-
trophenyl)aminoethyl
"349
3
¼ 9.55 10 cm
nitrophenyl)propylamine: ꢃ ¼ 351 nm, " ¼ 1.66 ꢄ
max
349
4
ꢂ1 ꢂ1
3
ꢂ1 ꢂ1
M .]
1
0 cm
M
, "450 ¼ 1.60 ꢄ 10 cm
Kinetic procedures
Kinetic runs were performed by the methods reported
1
1
35
previously, following the appearance of the reaction
product at ꢃ ¼ 450 or 400 nm. The reactions of DNClB
and DNFB with DMPA and EDA were carried out at
ꢀ
2
5 ꢁ 0.2 C and the reactions of DNFB with histamine
1
ꢀ
were carried out at 40 ꢁ 0.2 C. The reactions were
followed directly in the thermostated cell of the spectro-
photometer at the indicated temperature. The absorption
spectrum of the reaction mixture at ‘infinite time’ corre-
sponded within ꢁ 2% with the ‘theoretical’ value calcu-
lated from application of Beer’s law to solutions of the
product prepared independently in the desired solvent. In
all cases pseudo-first-order kinetics were observed.
1
2
2
2
2
2
Pseudo-first-order coefficients, k , were obtained by the
ꢀ
least-square method as the slope of the correlation ln
2
7. Llamas-Saiz AL, Foces-Foces C, Elguero J. J. Mol. Struct. 1994;
3
(
A ꢂ A )/A against time, where A is the optical
1
t
1
1
28: 297.
density of the reaction mixture measured at ‘infinity’
more than ten half-lives); the second-order rate coeffi-
cients, k , were obtained by dividing kꢀ by the amine
2
8. (a) Nudelman NS, Palleros D. Acta Sud. Am. Quim. 1981; 1: 125;
(b) Nudelman NS, Palleros D. J. Org. Chem. 1983; 48: 1607.
9. Hirst J. J. Phys. Org. Chem. 1994; 7: 68.
(
2
3
A
0. Nudelman NS, Montserrat JM. J. Chem. Soc. Perkin Trans. 2
concentrations. Rate coefficients were reproducible to
ꢁ
1
990; 1073–1076.
31. Nudelman NS, Alvaro CES, Yankelevich JS. J. Chem. Soc. Perkin
Trans. 2 1997; 2125–2130.
2%. No corrections for expansion coefficients were
applied to the concentration values.
3
2. Weast RC (ed). Handbook of Chemistry and Physics (57th edn).
CRC Press, Inc: Cleveland, Ohio, USA; 1977.
3
3. Nudelman NS, Marder M, Gurevich A. J. Chem. Soc. Perkin
Trans. 2 1993; 229–233.
Acknowledgements
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3
5. Bunnet JF, Kato T, Nudelman NS. In Fundamental Organic
Chemistry Laboratory Manual, Finley KT, Wilson J (eds). Pre-
ntice-Hall: New Jersey, 1974, 112.
Financial help from the University of Buenos Aires (grant
no. EX213-UBA) and the Universidad Nacional
Copyright # 2005 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2005; 18: 880–885