The reaction of 1,2-dichloro-4,5-dinitrobenzene with hydroxide ion: Roles of meisenheimer complexes and radical pairs

Article abstract of DOI:10.5935/0103-5053.20130148

The reaction of 1,2-dichloro-4,5-dinitrobenzene (DCDNB) with aqueous OH- produces (after acidification) 2-nitro-4,5-dichlorophenol with loss of NO ₂. Nevertheless, with > 2 mol L^-1 OH^-, only DCDNB was recovered due to the

Full text of DOI:10.5935/0103-5053.20130148

http://dx.doi.org/10.5935/0103-5053.20130148
J. Braz. Chem. Soc., Vol. 24, No. 7, 1146-1159, 2013.
Printed in Brazil - ©2013 Sociedade Brasileira de Química
0
103 - 5053 $6.00+0.00
Article
A
The Reaction of 1,2-Dichloro-4,5-dinitrobenzene with Hydroxide Ion:
Roles of Meisenheimer Complexes and Radical Pairs
a
a
a
a
Andrei Blaskó, Clifford A. Bunton, Nichollas D. Gillitt, Radu Bacaloglu,
,
b
,b
Santiago F. Yunes* and César Zucco*
a
Department of Chemistry and Biochemistry, University of California,
Santa Barbara, 93106 California, USA
b
Departamento de Química, Universidade Federal de Santa Catarina,
8
8090-400 Florianópolis-SC, Brazil
-
A reação de 1,2-dicloro-4,5-dinitrobenzeno (DCDNB) com OH aquoso produz (após
-
-1
acidificação) 2-nitro-4,5-diclorofenol com perda de NO . No entanto, com OH > 2 mol L ,
2
DCDNB foi recuperado devido à formação do complexo estável 3,6-di-hidroxi Meisenheimer
2-
(
M ), e que em ácido, reverteu ao reagente inicial. A formação rápida do complexo mono-hidroxi
1
-
Meisenheimer (M ) pode ser acompanhada em DMSO:H O 7:3 v/v e as constantes para sua
2
2-
interconversão com DCDNB e formação e retorno com M foram estimadas, com evidência destas
reações em DMSO:H O 1:1 v/v e H O. A troca rápida de hidrogênio em OD /D O limita o uso da
-
2
2
2
1
técnica de ressonância magnética nuclear (NMR) de H na identificação de intermediários. Sinais
1
13
de RMN de H e C para o di-hidroxi Meisenheimer foram observados em DMSO-H O-KOH.
2
Existe evidência da formação de radicais livres em DMSO:H O 4:1 v/v, e a cinética global em
2
meio mais aquoso foi tratada considerando a existência transitória de pares de radicais aniônicos.
-
The reaction of 1,2-dichloro-4,5-dinitrobenzene (DCDNB) with aqueous OH produces (after
-1
-
acidification) 2-nitro-4,5-dichlorophenol with loss of NO . Nevertheless, with > 2 mol L OH ,
2
only DCDNB was recovered due to the formation of the long-lived 3,6-dihydroxy Meisenheimer
2
-
complex (M ), and that in acid, reverted to the starting material. Fast formation of monohydroxy
1
-
Meisenheimer complex (M ) can be followed in DMSO:H O 7:3 v/v and rate constants for its
2
2
-
interconversion with DCDNB and for formation and return with M complex were estimated,
with evidence for these reactions in DMSO:H O 1:1 v/v and H O. The rapid hydrogen exchange
in OD /D O limits the use of H nuclear magnetic resonance (NMR) spectroscopy in identifying
2
2
-
1
2
1
13
2-
intermediates. H and C NMR signals of M complex were observed in DMSO-H O-KOH.
2
There is evidence for the formation of free radicals in DMSO:H O 4:1 v/v, and overall kinetics
2
in more aqueous medium were treated in terms of the transient existence of anionic radical pairs.
Keyword: aromatic nucleophilic substitution, Meisenheimer complexes
9
,10
Introduction
be on the reaction path. The formation of transient
7
,8,11
12
π-complexes has been postulated,
and demonstrated.
Aromatic nucleophilic substitutions involve a
variety of reaction paths, depending upon the reactant
Arynes are intermediates in reactions with strong bases in
1
3
apolar solvents, the S (radical-nucleophilic aromatic
RN1
1
-5
structure and the reaction medium. In polar, hydroxylic,
solvents reactions of hydroxide or alkoxide ions with
halonitroarenes can be described in terms of formation
of short lived ipso-Meisenheimer complexes, although
unproductive Meisenheimer complexes can form and
substitution) reaction with, for example, potassium
1
4
in liquid ammonia is a radical-chain process, and
there is evidence of radical reactions under other
9
,15
conditions.
Dediazonization is often described in
terms of rate-limiting loss of N , and rapid trapping of
2
1
-8
16
return to starting material, and radicaloid species may
a putative aryl cation, although there is evidence of
1
7
pre-association with a nucleophile. These reactions are
synthetically important, and the large scale decomposition
*
e-mail: c.zucco@ufsc.br, santiago.yunes@ufsc.br

Vol. 24, No. 7, 2013
Blaskó et al.
1147
of polynitroarenes in hot aqueous alkali is used in
described later, but under conditions very different from
those subsequently used in the kinetic work. The simplest
1
8
destruction of energetic materials.
-
-
The reaction of OH and other nucleophiles with
,2-dichloro-4,5-dinitrobenzene (DCDNB) shows some
unusual features. It involves the displacement of a nitro
explanation for our failure in obtaining aryloxide ion (ArO )
-
1
in reaction with moderately concentrated OH is that a
19,20
relatively long-lived 3,6-dihydroxy Meisenheimer complex
-
19
20
2-
group, by either OH (Scheme 1) or aliphatic amines,
(M ) can form and return to DCDNB on acidification or over
-
-
although these reactions generally occur with loss of Cl
assisted by electron withdrawal by a nitro group.
a long period of time. In dilute OH , an ipso-Meisenheimer
1
-
complex (M ipso) could be reversibly, or irreversibly,
formed in competition with a postulated unproductive
1-
-
monoanionic complex (M ), so that ArO should be the
thermodynamically controlled product (Scheme 2).
The deprotonated dihydroxy Meisenheimer complex
3-
(
M ) in this hypothetical scheme was included because
there is evidence for deprotonation of unproductive
1,4,6-8
Scheme 1.
Meisenheimer complexes.
These qualitative observations
indicate that the unproductive Meisenheimer complexes
have higher negative charges than the postulated ipso
complex on the reaction path, irreversibly leading to the
nitrodichlorophenoxide. This classical heterolytic reaction
path (Scheme 2) does not explain the H/D exchange observed
in the preliminary observations, and this weakness of the
conventional mechanistic treatment is discussed later.
The conversion of DCDNB into final products involves
various reactions, some competing, other consecutive, and
it is convenient to consider them as relaxations, which are
well separated in time, and may involve several reactions,
but can be simply analyzed, provided that the individual
reactions follow first-order kinetics. Relaxations did not
need to be spectrophotometrically followed at wavelengths
corresponding to lmax of the reaction species, provided that
Beer’s law is obeyed, although it is best to select wavelengths
giving significant changes in the absorbance. The rate
measurements were made by UV-Vis spectroscopy with very
The scale and conditions of the original preparation
1
9
were unspecified, but when our group attempted on
making the reaction under heterogeneous conditions in
-
1
aqueous 2.5 mol L NaOH and acidified the reaction
mixture, only the starting material was obtained, and an
experiment in homogeneous conditions in DMSO (dimethyl
sulfoxide)-H O provided a similar result. A small-scale
2
-
preparation in very dilute aqueous OH , and under reflux,
19
gave the phenolic product described in the literature.
In this qualitative exploratory work, the UV-Vis spectra
typical of a nitro phenol in the reaction of DCDNB in
21
dilute aqueous KOH and DMSO:H O were observed. The
2
1
13
solubility of DCDNB is very low in water, and H and C
nuclear magnetic resonance (NMR) spectra were examined
in DMSO:H O because there is an isotopic exchange in
2
DMSO:D O, and the technique in DMSO:H O was used
2
2
to identify compounds formed in the course of reaction as
Scheme 2.

1
148
The Reaction of 1,2-Dichloro-4,5-dinitrobenzene with Hydroxide Ion
J. Braz. Chem. Soc.
-
1
dilute DCDNB, but the products were isolated, or identified
by NMR spectroscopy, at much higher concentrations.
Some NMR measurements were made in the course of
reaction, with short accumulation times and high substrate
concentrations. The necessity of using reaction conditions
for product identification very different from those used in
the kinetic work is a major problem, but in considering the
various reaction steps, which fit first-order kinetics, it was
assumed that kinetic forms are independent of [DCDNB].
with 0.05 or 0.1 mol L substrate to avoid long accumulation
-
times in the course of reaction, and therefore [OH ] decreased
during the reaction.
Kinetics
The slower relaxations were followed on diode-
array spectrophotometers at 25.0 ± 0.1 °C, and the rapid
formation of a monohydroxy Meisenheimer complex was
followed on the stopped-flow spectrophotometer. For the
slower relaxations, DCDNB in 10 mL DMSO was added
to 2 mL of the reaction solution to give 5 × 10 mol L
DCDNB in the reaction mixture. The reciprocal relaxation
-3
Experimental
-5
-1
Materials and preparation
-1
times (t ) fitted the first-order equations for 3-5 half-lives.
1
,2-Dichloro-4,5-dinitrobenzene (Aldrich) was
In following the slowest-relaxation, the postulated
2-
3-
converted into 2-nitro-4,5-dichlorophenol (ArOH)
by heating 1.2 mg DCDNB with 100 mL of aqueous
.1 mol L NaOH, (two-fold excess), under reflux for
h, followed by acidification and separation of the crude
phenol. Details of the earlier preparation of the phenolic
product are not given in reference 19. Recrystallization
aq. EtOH) produced yellow crystals, mp 66.5 °C
return of M and M (Scheme 2), these complexes were
prepared by the reaction of KOH with DCDNB in solution
under conditions such that DCDNB had fully reacted
-
1
0
5
-
without forming ArO and it was added the appropriate
1
9
amount of this solution to the reaction mixture to give the
-
desired [OH ], [DCDNB] and solvent composition. Under
-
(
(
7
these conditions, OH was in considerable excess over the
1
9,20
1
68 °C)
in 85% yield. H NMR (DMSO-d ) d/ppm:
substrate, giving first-order kinetics in the relaxations.
6
13
.18, d, J 1.5 Hz; 7.93, d, J 1.5 Hz; C NMR (DMSO-d )
6
d/ppm: 121.4, 122.51, 127.3, 136.0, 139.2, 152.3. For
Structural optimization
-
the phenoxide ion, ArO , NMR signals (DMSO-d ) were,
6
1
3
d/ppm: 1H, 6.71, 7.80; C, 113.0, 127.9, 128.2,
The structures were optimized with the HF/6-31G(d) or
BP/6-31G(d) methods for neutral molecules and the
HF/6-31+G(d) method for anions, with Spartan 04 software
(Wavefunction, Inc.). The optimization considers species in
vacuum, i.e., not solvated in the kinetic conditions.
1
3
37.1, 139.1, 166.4, in D O and referred to sodium
-(trimethylsilyl)tetrapropionate (TSP). The reaction in
2
aqueous alkali was in heterogeneous conditions, but various
preparative experiments in homogeneous conditions in
KOH-H O-DMSO did not give the phenolic product and
2
DCDNB was recovered after acidification, as for a reaction
Results
-1
in aqueous 2.5 mol L NaOH at room temperature. The
1
H NMR signal of DCDNB in DMSO-H O 7:3 v/v is a
Formation of the alkoxide ion
2
singlet at 8.39 ppm. DMSO was distilled in vacuum through
a helix-packed column and stored under N . Solutions were
The preparative reactions of DCDNB with dilute
2
-
-
made up with redistilled, deionized, CO -free water.
OH in water produced ArO in good yield (Experimental
2
-
section and reference 19), but with higher [OH ], the
-
Instrumentation
absorbance of ArO was not observed. The reactions in
water were heterogeneous, but the results were similar
-
1
Absorption spectra were obtained on HP 8450, 8451 or
452A diode array and on Beckman DU-7 UV-Vis
to 2.5 mol L KOH in water and to DCDNB in solution
-
8
in DMSO-H O. Under these conditions of high [OH ],
2
spectrophotometers at 25.0 ± 0.1 °C, and for the short-lived
regardless of the solvent composition, there was no
indicative of formation of a phenoxide ion and only the
substrate was recovered on acidification. The course of
the reaction is not controlled by substrate solubility, but
it involves the formation of compounds that do not give
ArOH under acidification but revert to starting material, and
1-
Meisenheimer complex (M ) on a Durrum stopped-flow
o
spectrophotometer at 25.0 ± 0.1 C. The NMR spectra
were obtained on a Bruker 200F, or GN500 or Varian Unity
1
(
500 MHz for H) instrument, at 25.0 ± 0.1 °C, generally with
TSP as internal reference, although occasionally mesitoate
-
-
ion was added as a chemically inert aromatic reference
ArO is formed only in dilute OH with the reaction mixture
7,8
o
compound. The NMR spectra were generally monitored
left for many hours at 25.0 ± 0.1 C.

Vol. 24, No. 7, 2013
Blaskó et al.
1149
-
The phenolic product (ArO ) was isolated from
The low solubility of DCDNB in water meant that it
-
the reaction with dilute OH (Schemes 1 and 2 and
could not be examined by the NMR in H O. However,
2
reference 19), but for some reactions in DMSO-d -H O,
the incomplete reactions of DCDNB with KOD in
6
2
1
1
minor H NMR signals of what was probably a second
DMSO-d -D O produced no H signals of DCDNB or other
6
2
-
aryloxide ion (designated Ar’O ) were observed, as
compounds, showing that the isotopic hydrogen exchange
is rapid under alkaline condition but there was no indicative
discussed later. This product could have been formed by
-
-
-
13
the displacement of Cl by OH in the initial reaction of
DCDNB, but alternative reactions can be considered. The
of hydrogen exchange withArO . The C NMR spectra of
the Meisenheimer complexes and phenolic products were
observed in DMSO-d -D O and KOD, or the corresponding
concentration of DCDNB in H O is too low for the use of
2
6
2
NMR spectroscopy in the course of reaction. The minor
phenolic product in Schemes 1 and 2 were not shown.
acidic media, with, or without, proton decoupling.
Moreover, H NMR signals of DCDNB, aryloxide
1
ions and of what is probably a Meisenheimer complex
Reactivities and characterization of intermediates
in DMSO-d -H O and KOH, generally with suppression
6
2
1
of the H O signal, were observed. These observations
2
The absorption and NMR spectroscopies were used to
identify compounds formed by the reaction of DCDNB with
are discussed in the context of the kinetic data, but were
in experiments with [DCDNB] much higher than in the
-
-4
-1
-5
-1
OH . Aqueous 10 mol L DCDNB has l at 275 nm, and
kinetic work (ca. 5 × 10 mol L ), which complicates the
max
-1
-
1
in 3 mol L OH , this signal disappeared and a broad signal
comparison of kinetic and NMR data. The H NMR signals
-
(
lmax ca. 320 nm) appeared, plus, but only in very dilute OH ,
were also observed, probably of a second nitrophenoxide
derivative, as discussed later.
-
a very weak signal ofArO at > 400 nm. The signal at 320 nm
disappeared on acidification and that of DCDNB reappeared,
with little formation of phenolic product, in agreement with
Reactions in DMSO:H O 7:3 v/v
2
-
results in preparative experiments. However, in dilute OH
-1
(
< 0.1 mol L ), it was observed, after some time, the signal
In this solvent, there is a rapid increase in absorbance
at 520-530 nm ascribed to reversible formation of
the short-lived monohydroxy Meisenheimer complex
(Scheme 2), and no indicative of formation of a phenoxide
-
of ArO and a weak signal at 320 nm.
Monohydroxy Meisenheimer complexes derived
-
from polynitroarenes and OH absorb strongly at
–
1
-
l > 500 nm, and this absorption was observed when the
ion. The variation of t with [OH ] fits equation 1 (Table 1),
1
-
absorbance in DMSO-H O 7:3 v/v was rapidly examined
but the small value of the intercept at zero [OH ] leads to
2
in a stopped-flow spectrophotometer, but the color soon
disappeared and there was no formation ofArO . There was
uncertainty in the values of k and the related equilibrium
constant given by the ratio of k and k for concentrations
2 -2
-2
-
no indicative of formation of this complex in more aqueous
media, but it is probably on the reaction path to longer
lived Meisenheimer complexes, and mono- and dihydroxy
as in the course of reaction:
(1)
22
complexes have been identified in other systems. It was
2
-
expected a M complex, which is not aromatic, to be
transparent in the visible region due to loss of conjugation
of the nitro groups with the double bond.
The subsequent, much slower, relaxations were
followed at various wavelengths in a conventional
spectrophotometer and showed increase in the absorbance
at 320 and 420 or 480 nm, and decreasing absorbance at
The absorption spectra were repetitively scanned in
alkaline H O, and DMSO:H O 1:1 v/v, and 7:3 v/v. On
–
1
275 and 520 nm and the values of t2 are in Table 2. There
was no indicative of build-up of an ipso-Meisenheimer
complex (Scheme 2) and it was assumed that it would
2
2
the basis of these spectra, and evidence for formation
of a dihydroxy Meisenheimer complex, the absorbance
over time at various wavelengths was followed, and the
-
rapidly generate ArO , which is not evident to any
-
1
reciprocal relaxation times (t ) were estimated for the
significant extent in some of these conditions (Scheme 2).
The second minor phenolic product is not shown in
this scheme, and if it is formed directly from DCDBN,
the rate constant would include a minor contribution
from this reaction. The literature describes that similar
nucleophilic aromatic substitutions may be stepwise or
processes following first-order kinetics. It was designated
–
1
–1
2
–1
–1
t , t and t3 from the shortest to the largest, and t1 was
1
monitored only by stopped-flow spectroscopy in DMSO:H O
2
o
7
:3 v/v. All reactions were at 25.0 ± 0.1 C. The relaxations
were followed at 275 nm, in which DCDNB absorbs,
2
-
23
at 320 nm, in which M absorbs, at 420 nm, in which
concerted. The NMR evidence on phenolic products and
-
1-
ArO absorbs, and at 520-530 nm, in which M absorbs.
Meisenheimer complexes was obtained with higher

1
150
The Reaction of 1,2-Dichloro-4,5-dinitrobenzene with Hydroxide Ion
J. Braz. Chem. Soc.
a
Table 1. Initial formation of monohydroxy Meisenheimer complex
-
-1
[
OH ] / (mol L )
0.013
0.15
0.032
0.35
0.37
0.047
0.52
0.50
0.064
0.66
0.64
0.10
1.00
0.94
0.15
1.40
1.35
0.20
1.70
1.77
–1
-1
t1 / s , observed
–1
-1
t1 / s , calculated
0.22
a
o
In DMSO:H O 7:3 v/v at 25.0 ± 0.1 C, calculated values are from data in Table 5.
2
Table 2. Formation of aryloxide ion and dihydroxy Meisenheimer complex
DMSO:H O 7:3 v/v
2
-
-1
[
OH ] / (mol L )
0.025
0.048
0.093
0.190
0.270
0.320
0.370
0.400
–1
3
-1
a
c
d
c
c
d
d
c
t2 × 10 / s , observed
3.9
8.0
20.6
41.9
70.1
92.7
115
137
–
1
3
-1
e
e
e
t2 × 10 / s , calculated
4.1
8.3
17.9
44.6
72.8
93.3
116
131
DMSO:H O 1:1 v/v
2
-
-1
[
OH ] / (mol L )
0.013
0.032
0.047
0.064
0.100
0.150
–1
3
-1
a
a
c
c
d
d
t2 × 10 / s , observed
0.15
0.35
0.52
0.66
1.15
1.95
–1
3
-1
t2 × 10 / s , calculated
0.12
0.31
0.48
0.68
1.18
2.00
H O
2
-
-1
[
OH ] / (mol L )
0.14
0.22
0.30
0.38
0.50
0.60
0.72
0.92
0.99
1.00
–1
3
-1
c
c
c
c
c
c
b
b
b
b
t2 × 10 / s , observed
0.11
0.25
0.36
0.51
0.77
1.12
1.50
2.41
2.25
2.67
2.55
2.71
2.60
–1
3
-1
t2 × 10 / s , calculated
0.13
0.23
0.37
0.52
0.81
1.09
1.47
a
b
c
d
e
At 275 nm; at 320 nm; at 420 nm; at 520 nm; calculated from data in Table 5.
–
1
substrate concentrations than the one used in the kinetic
work which fitted the first-order kinetics.
The slowest relaxation, followed by the decreasing
absorbance at 320 nm, or increasing absorbance at 480 nm (or
320 and 480 nm, and values of t were in good agreement,
3
but the higher absorbance change at 320 nm made this
wavelength the most convenient, and there is a slight tail
in the absorbance spectrum of the Meisenheimer complex
-
4
20 nm), involves the return of a dihydroxy Meisenheimer
which interferes with the signal of ArO at 420 nm.
3
-
complex (and M ), which had been formed in high
-
[OH ] and is long-lived under these conditions (Scheme 2).
Reactions in DMSO:H O 1:1 v/v and in water
2
Its decomposition was induced by dilution to give the desired
solvent composition (Table 3). This relaxation (t ) is much
slower than the others, even in dilute KOH, and they are
well separated. A few experiments were monitored at both
The examination of the UV-Vis spectra in the
stopped-flow spectrophotometer gave no evidence of the
absorbance at > 500 nm, and M or an ipso-Meisenheimer
3
1-
Table 3. Return of M and M3-
2-
DMSO:H O 7:3 v/v
2
-
3
-1
[
OH ] × 10 / (mol L )
0.5
2.0
4.7
8.6
35.0
5.26
5.22
76.0
2.57
2.49
95.0
1.90
1.97
143
1.27
1.21
270
0.51
0.53
–1
5
-1
t3 × 10 / s , observed
22.8
23.2
19.1
20.3
14.6
16.8
13.7
13.4
–1
5
-1
t3 × 10 / s , calculated
DMSO:H O 1:1 v/v
2
-
3
-1
[
OH ] × 10 / (mol L )
3.39
8.83
8.84
4.23
8.66
8.69
5.08
8.45
8.50
7.62
8.24
8.14
8.47
8.04
8.04
10.2
7.86
7.84
13.6
7.60
7.43
15.2
7.38
7.26
16.9
7.06
7.08
19.1
6.89
6.87
20.1
6.75
6.78
–1
5
-1
t3 × 10 / s , observed
–1
5
-1
t3 × 10 / s , calculated
H O
2
-
4
-1
[
OH ] × 10 / (mol L )
0.169
18.4
0.170
17.3
0.394
15.9
0.402
14.4
1.31
9.23
1.47
9.16
3.20
5.50
–1
5
-1
t3 × 10 / s , observed
a
o
At 25.0 ± 0.1 C, calculated values are from data in Table 5.

Vol. 24, No. 7, 2013
Blaskó et al.
1151
–
1
complex was not detected. The values of t for
complex was dominant and it was expedient to use the
higher wavelength.
2
1-
disappearance of DCDNB (and M ) and appearance of
ArO and M , depending on the conditions, were obtained
at various wavelengths in a conventional spectrometer, for
-
2-
NMR Spectroscopy
reactions in DMSO:H O 7:3 v/v (Table 2). Data for the
2
–1
1
slowest relaxation, t , followed at 320 nm, are in Table 3.
The loss of the H NMR signals of DCDNB on
3
-
This relaxation is inhibited by OH and is so slow in water
addition to DMSO-D O and KOD is typical of reactions
2
-
that it was possible only to use very dilute OH which was
of polynitroarenes in which the hydrogen exchange is
1
,7,8,24,25
1
13
not in significant excess over DCDNB.
rapid.
It was not possible to use H or C NMR
The fastest relaxation (t ) in more aqueous solvents
spectroscopy in H O because of the low solubility of
DCDNB, and it was used short accumulation times because
the composition changes with time. Therefore, the NMR
1
2
was not observed, and it was assumed that, in our
1
-
experimental conditions, M is then present in very low
concentration and that its formation and return to DCDNB
are considerably faster than the other relaxations.
spectra were examined only in DMSO-H O, generally
2
1:1 v/v, and usually with water signal suppression. The
1
3
C NMR spectrum of the dihydroxy Meisenheimer
Competitive formation of ArO and M2-
-
complexes (M2- and M ) confirms the presence of only
3-
two equivalent hydrogens in the complex over a range of
-
-1
The initial reaction of DCDNB with very dilute OH
conditions. In one experiment after 40 min with 0.05 mol L
-
-1
generates the thermodynamicallystablearyloxideion(ArO )
DCDNB and 2.0 mol L KOH in DMSO-d :H O 1:1 v/v,
6
2
probably via a transient ipso complex, and the “dead-end”
with and without proton decoupling, the dihydroxy
Meisenheimer complex was the dominant species and
the splitting of the signal at 71.6 ppm (with proton
2-
3-
dihydroxy Meisenheimer complexes (M and M ) via the
monohydroxy Meisenheimer complex (Scheme 2). These
reactions compete, and the subsequent decomposition
of the dihydroxy complex is so slow that the relative
concentrations were spectrophotometrically estimated
1
3
coupling) and the observation of only three C signals
demonstrate the formation of a dihydroxy Meisenheimer
complex and assignments are: C-1, C-2, 119.5, s; C-3,
C-6, 71.6, JCH 149 Hz; C-4, C-5, s, 133.5 ppm. With proton
decoupling, the signal at 71.6 ppm was a singlet. These
spectra were taken within 40 min of mixing, but did not
-
from the absorbance of ArO at 480 nm, under conditions
1
-
2-
3-
such that [DCDNB] → 0, [M ] = 0, and M and M
are in equilibrium, and are transparent at 480 nm. The
comparison was generally based on the concentration
13
change overnight. In this experiment, the C NMR signals
-
-
-
of ArO estimated by using solutions of known [ArO ].
of ArO were not observed because almost no aryloxide
2
-
3-
-
-
-
-
Values of ([M ] + [M ])/[ArO ] as a function of [OH ]
are in Table 4. The residual absorption of the double
Meisenheimer complex near lmax of the aryloxide ion
at 420 nm was a complication when the Meisenheimer
ion is formed in high [OH ], however, with lower [OH ],
signals of the aryloxide ions and dihydroxy Meisenheimer
complex were observed. These observations show that the
OH groups of the dihydroxy complex on C-3 and C-6 are
a
Table 4. Competitive formation of Meisenheimer complex and aryloxide ion
DMSO:H O 7:3 v/v
2
-
-1
[
[
[
OH ] / (mol L )
0.06
0.17
0.17
0.08
0.23
0.23
0.14
0.41
0.40
0.19
0.55
0.54
0.24
0.66
0.69
0.29
0.83
0.83
-
M ]/[ArO ], observed
T
-
M ]/[ArO ], calculated
T
DMSO:H O 1:1 v/v
2
-
-1
[
[
[
OH ] / (mol L )
0.21
0.76
0.74
0.43
1.59
1.52
0.60
2.08
2.12
0.75
2.65
2.65
1.00
3.50
3.53
1.10
3.80
3.88
1.20
4.18
4.23
1.40
4.82
4.94
-
M ]/[ArO ], observed
T
-
M ]/[ArO ], calculated
T
H O
2
-
-1
[
[
OH ] / (mol L )
0.22
0.68
0.69
0.43
1.30
1.34
0.72
2.19
2.25
0.92
2.71
2.87
1.16
3.41
3.62
1.40
4.50
4.37
-
M ]/[ArO ], observed
T
-
[
M ]/[ArO ], calculated
T
a
At 25.0 ± 0.1 C, calculated values are based on data in Table 2; M denotes M + M3-.
o
2-
T

1
152
The Reaction of 1,2-Dichloro-4,5-dinitrobenzene with Hydroxide Ion
J. Braz. Chem. Soc.
in identical positions, or that there is a rapid exchange
between positions, which is improbable in view of kinetic
data considered later.
aryloxide ions, and the mesitoate ions at 6.50 ppm, were
singlets, and long-range coupling was not observed, as with
phenol (Experimental section).
In several experiments with relatively high [DCDNB],
These observations were confirmed in a subsequent
1
-
-1
weak H signals of ArO and weaker signals of a second
product, d ca. 6.7 and 8.1 ppm, were observed. The chemical
shifts varied slightly depending upon concentrations and
changes in the solvent composition. These signals, like
experiment in the same conditions with 0.1 mol L
-1
DCDNB and 0.15 mol L KOH and no substrate signal was
observed after 2 min, but it reappeared as a broad singlet at
8.39 ppm after 4 min. The sharp phenoxide signals were at
6.28, 6.55, 7.67 and 7.86. The pH was reduced to < 4 after
further 30 min by addition of HCl and signals of phenols
were then observed at 7.17, 7.27, 7.93 and 8.10 ppm. In
all these experiments, the signals at 6.28 and 7.86 ppm, or
at 7.17 and 8.10 ppm after acidification, were those of the
minor aryloxide product.
-
those ofArO , were singlets and with chemical shifts typical
of dinitrobenzene derivatives and the chemical shifts, and
ratios of major and minor products varied slightly, probably
depending on the conditions of the measurements. Our
group considers possible sources of this second signal
later. The addition of NaNO at concentration similar to
2
1
[
DCDNB] did not affect the NMR signals.
The loss and return of the H NMR signals of DCDNB
All these NMR measurements were made with high
could be ascribed to the rapid formation and subsequent
decomposition of a dihydroxy Meisenheimer complex, but
the forward reaction should be too slow to fit the results in
the dilute KOH used here, and the transient existence of free
radicals explains the reversible loss of the NMR signal. It
seems that the formation of a radicaloid species of DCDNB
markedly broadens its signals, but not those of phenoxide
or mesitoate ions. Similar results had been obtained with
reactant concentrations, relative to those used in the kinetic
-1
work. Usually with 0.1 mol L DCDNB and 5-10 fold excess
KOH in DMSO-d :H O, a sharp singlet at ca. 5.2 ppm was
6
2
observed slightly depending on the conditions. This signal
was on the side of the very broad signal of H O. With
2
1
careful suppression of the H O signal, a base line resolution
2
between the signals was obtained. The signal at 5.2 ppm
-
1
7,8
at ambient temperature with 0.1 mol L DCDNB and
other polynitroarenes in aqueous DMSO, but not in more
aqueous media. Because of the complexity of the system,
-
1
0
3
.5 mol L KOH in DMSO:H O 1:1 v/v disappeared after
2
-1
days, but was still present in 1.0 mol L KOH. This signal
kinetics in DMSO:H O 4:1 v/v was not examined, but the
2
is upfield of nitroarene signals and it was assumed that it is
probable kinetic role of radicaloid species in the reactions
in more aqueous media is discussed later, although there
was no evidence from NMR spectroscopy for the evidence
of free radicals in these more aqueous solutions.
2-
from the dihydroxy Meisenheimer complex (M ) and, as it
disappeared, signals in the nitrophenoxide region increased.
1
13
It was observed a cross peak of this H signal and the C
signal of the Meisenheimer complex at 71.6 ppm, consistent
with this assignment.
Structural predictions
1
H NMR Spectroscopy in DMSO:H O 4:1 v/v
Coplanarity of the dinitro and phenyl groups is sterically
unfavorable and a forced planar structure of DCDNB is
predicted to be disfavored by 13.5 kcal mol , relative to
2
1
-1
Some H NMR measurements were made in DMSO:H O
2
-1
-1
4
:1 v/v with 0.1 mol L DCDNB and 0.15 mol L KOH,
one with the nitro groups twisted out of plane by 40° or 38°,
from calculations with the HF/6-31G(d) or BP/6-31G(d)
methods, respectively. This lack of coplanarity is consistent
i.e., insufficient for complete reaction, and with suppression
of the H O signal, in the spectral region where the signals
of DCDNB and the phenoxide ions were observed. The
signal of DCDNB at 8.39 ppm disappeared on addition
of KOH and new sharp aryloxide ion signals at 6.57 and
1
2
2
6
with extensive evidence on nitroarenes, and the well-
established steric hindrance to resonance should affect
-
-
the relative leaving group properties of Cl and NO . The
2
7
.67 ppm (major signals) and 6.30 and 7.88 ppm (minor
predicted inter Cl distance of 3.22Å is slightly less than the
sum of the van der Waals radii, and the subtended angles
27
signals) appeared within 2 min of mixing, but with the
decreasing [OH ], a very strong broad signal of DCDNB
-
at C-1 and C-2 were predicted to increase slightly to 121°.
–
2
-
reappeared within 6 min, sharpened after 10 min and
became sharp after 15 min. Signals of the aryloxide
ions and of mesitoate ion at 6.50 ppm, added as an inert
marker, are sharp. Excess KOH (up to 0.22 mol L ) was
then added and more aryloxide ion signals appeared,
but there were no signals of DCDNB. The signals of the
The observed loss of NO by attack of OH is consistent
with a high LUMO density adjacent to the nitro groups
rather than at positions adjacent to the chloro substituents.
-1
2-
The dihydroxy Meisenheimer complex (M )
(Scheme 2) is a cyclohexene derivative, and has syn- or
anti-3,6-hydroxy groups. The geometrical optimization

Vol. 24, No. 7, 2013
Blaskó et al.
1153
with the HF/6-31+G(d) method indicates that the syn-isomer
should be more stable than the anti- by 1.8 kcal mol , but,
Table 5. Rate and equilibrium constants for reactions of DCDNB with
OH
–
a
-1
when hydration (H O) is included at the semi-empirical SM
2
Solvent
/ (L mol s )
DMSO:H O 7:3 DMSO:H O 1:1
H O
2
8
2
2
2
5
8
.4 level, the anti-isomer is predicted to be preferred by
.6 kcal mol . The estimated effect of solvation by water
-1
-1
-3
-4
-1
k
1
0.152
8.70 × 10
6.31 × 10
(0.035)
(0.1)
-1
-1
k / (L mol s )
8.33
0.104
80
(0.48)
(0.1)
may not apply to the organic kinetic solvent mixtures.
2
-1
-1
k / (L mol s )
-2
-1
-1
Discussion
K
2
/ (L mol s )
(4.8)
(0.3)
-1
-1
-3
-3
-3
k / (L mol s )
5.45 × 10
0.439
(5 × 10 )
(5 × 10 )
3
Kinetic data
2
-2 -2
-2
-3
K k / (L mol s )
3.06 × 10
1.97 × 10
2
3
-
1
-4
-4
-4
k / s
2.4 × 10
23
1 × 10
2 × 10
-3
The various relaxations are well separated and rate and
product data (Tables 1-4) can be rationalized in terms
of the reactions in Scheme 2, which are similar to those
postulated in other reactions of polynitroarenes with oxide
ions. It was not included the π-complexes in the kinetic
scheme, although they may be transient species. There is
-
1
K / (L mol )
–
–
–
3
-1
K / (mol L )
0.011
2.9
0.072
3.7
b
k K /k
1
3.1
3
2
k3/k-2
0.052
a
Values in parentheses are approximate and are estimated by comparison
with values from reactions in DMSO:H O 7:3 v/v; see text.
2
rapid hydrogen exchange in DMSO-D O and KOD, as with
2
1,7,8,29
other nitroarenes,
but no evidence for build-up of a
carbanion of DCDNB, and this exchange does not perturb
the kinetics, but requires consideration of the conventional
reaction Scheme 2.
1-
The interconversion of DCDNB and M in DMSO:H O
2
7
:3 v/v is so much faster than the other relaxations
(
Tables 1, 2 and 4) that in treating them in KOH it was
1-
assumed an equilibrium between DCDNB and M , on the
time scale of the other relaxations, with the equilibrium
constant, K = k /k in terms of the changing concentrations
2
2
-2
in the course of reaction. The inspection of a molecular
model of a hypothetical ipso complex in the formation
-
of ArO indicates that there should be hydrogen bonding
between OH and NO on the adjacent carbon. Values of
2
k and K in DMSO:H O 7:3 v/v are in Table 5, together
2
2
2
with other rate and equilibrium constants. The values of
Figure 1. Predicted fit of kinetic data (equation 5) for DMSO:H O 7:3 v/v.
2
–
1
k and K depend on the intercept of a plot of t against
-2
2
1
-
scale of this relaxation should be higher than that of M1-,
based on the disappearance of its color or its nonappearance
in more aqueous solvents.
[
OH ] and are less reliable than the value of k from the
2
slope (equation 1). The predicted fit to experimental data
in DMSO:H O 7:3 v/v is shown in Figure 1.
2
2
-
The formation of M is reversible (Scheme 2), but
-
1-
except in very dilute OH , the reversion to M and then
(2)
-
to DCDNB and ArO is slow. Therefore, the conversion
2
-
-
–1
2
-
of DCDNB into M and ArO , the second relaxation,
fits equation 2 with the assumption that the postulated
ipso-Meisenheimer complex (Scheme 2) goes rapidly to
ArO . Except in very dilute OH , the formation of ArO is
much slower than the formation of the nonproductive
Meisenheimer complexes, so that the first term in
equation 2 is relatively unimportant, but with time, there
The relationship between t and [OH ] gives values of
k and k K . For reaction in DMSO:H O 7:3 v/v , the values
1
3
2
2
of k and k (i.e., K ) allow the estimate of k (Table 5)
2
-2
2
3
-
-
-
with K in terms of concentrations in the course of reaction
2 .
This kinetic model is confirmed by the estimate of
-
[ArO ] after approximately 10 half-lives of the second
-
relaxation, in which only ArO and the dihydroxy
-
2-
3-
is return to DCDNB and irreversible formation of ArO .
Meisenheimer complexes (M + M ) are present, and the
concentrations are estimated by absorbance differences
(equation 3):
The relaxation in equation 2 is first-order with respect to
the changing concentration of DCDNB, which on the time

1
154
The Reaction of 1,2-Dichloro-4,5-dinitrobenzene with Hydroxide Ion
J. Braz. Chem. Soc.
some of the rate constants involved in the return of the
dihydroxy Meisenheimer complex.
(3)
The complete rate equation 5 includes K and some
b
Under the conditions for which equation 3 is applicable,
rate constants whose values are experimentally available
–
1
the low concentration of DCDNB can be neglected. The fits
to the model are illustrated by comparison of observed and
only in DMSO:H O 7:3 v/v and the values of t in
2
3
terms of k and K with an extrapolated value of k to
-3
b
-3
–
1
–1
-
predicted values of t and t2 in Tables 1-3 and of
zero [OH ] were fitted. The estimated values of k and
-3
1
2
-
3-
-
-4 –1
-1
(
[M ] + [M ])/[ArO ] in Table 4.
K are 2.4 × 10 s and 0.011 mol L , respectively. The
b
-4
-1
Although all the rate and equilibrium constants in
extrapolated value of k = 10 s in DMSO:H O 1:1 v/v
-3 2
equations 1-3 can be estimated for reaction in DMSO:H O
is similar to that in the less aqueous solvent, but this
extrapolation in water is uncertain, as noted earlier.
2
7
:3 v/v, it is not possible to estimate K for interconversion
2
1
-
of DCDNB and M in the other solvents, and then, only
2-
k K for formation of M can be determined. The values
3
2
(5)
of k K , like those of k , decrease with increasing water
3
2
1
content of the solvent, as it is typical of rates of reactions
30
with nucleophilic or basic anions. Both k and K should
Solvent effects upon the reactions
3
2
be solvent sensitive, but most results in the literature are for
nucleophilic reactions involving nonionic substrates. The
separation of the constants is not experimentally feasible
for the more aqueous solvents. In these cases, it was not
observed the monohydroxy Meisenheimer complex, which
can readily form the dianionic dihydroxy Meisenheimer
Kinetic solvent effects should be similar for reactions
-
-
1-
of OH and DCDNB, giving either ArO or M , on the
assumption that both involve formation of monoanionic
-
Meisenheimer complexes from OH and a nonionic
-
substrate. If k /k , which describes reactions of OH
1
2
2
-
complex (M ) under these conditions.
with DCDNB, is solvent independent it is possible to
combine its value in DMSO:H O 7:3 v/v with those of k
2
1
Return and deprotonation of the dihydroxy Meisenheimer
complex
in the three solvents (Table 5) to obtain k ca. 0.48 and
2
-
1
-1
0.035 L mol
s in DMSO:H O 1:1 v/v and water,
2
respectively. With these values and those of k k /k , i.e.,
2
3
-2
The third relaxation (t ) is relatively very slow,
of k K (Table 5), it was obtained values of k /k equal
3 2 3 -2
3
-
2-
-1
especially with high [OH ] which deprotonates M , thereby
to 0.064 and 0.056 mol L in DMSO:H O 1:1 v/v and
2
1-
1-
inhibiting the return to M and hence to DCDNB and there
water, respectively, on the assumption that M is on the
1
-
-1
is little absorbance of M at 520-530 cm and on the time
reaction path, although it was not observed its absorption
in these solvents. The directly estimated value of k /k
1-
-
scale of t , M and DCDNB should produce largelyArO .
Therefore, the extrapolation of t3 to zero [OH ] gives an
3
3
-2
–1
-
-1
is 0.052 mol L in DMSO:H O 7:3 v/v (Table 5), and
2
approximate value of k3.
the apparent similarities of these relative rate constants
1
-
In DMSO:H O 7:3 v/v, there is, after a short time,
indicate that partitioning of M between the return to
2
-
2-
no absorbance of the monohydroxy Meisenheimer
complex at 520-530 nm, i.e., both it and DCDNB behave
as low concentration intermediates. The equilibrium
DCDNB (+ OH ) and the conversion into M (Scheme 2),
is not very sensitive to solvent composition.
The apparently similar values of k /k in the three
3
-2
2
-
3-
constant (K ) for the interconversion of M and M
solvents are consistent with the forward and reverse
b
–
1
-
1-
(
equation 4) is given by the dependence of t3 upon [OH ]
reactions of M involving no change of net charge,
provided that
although they have different kinetic orders. Mole
fractions of H O in the three solvent mixtures are not very
2
different, and in the least aqueous solvent, DMSO:H O
(4)
2
7
:3 v/v, the mole fraction of H O is ca. 0.61. It is possible
2
1
-
that, except for the initial formation of M , individual rate
constants are not very sensitive to solvent composition and
it is noted that the extrapolated values of k for loss
of OH from M (Scheme 2) are not very different in
DMSO:H O 7:3 v/v and DMSO:H O 1:1 v/v (Table 5).
1-
2-
allowance is made for the return of M to M (Scheme 2).
This calculation is not feasible for reaction in water
-
3
-
-
2-
where the relaxation is very slow, even in very dilute OH
whose concentration is uncertain, because it may not be
significantly greater than initial [DCDNB] (Table 3). In
2
2
Based on this hypothesis, it appears that the addition
of OH to an anionic Meisenheimer complex (M ) and
-
1-
DMSO:H O 1:1 v/v, we have experimental values of only
2

Vol. 24, No. 7, 2013
Blaskó et al.
1155
the reverse reaction are not subject to large kinetic
solvent effects, although they are typically large for the
corresponding reactions involving nonionic substrates,
7:3 v/v k /k ca. 55 which fits the slow formation of
phenolic products (Table 5 and Scheme 2). It is generally
assumed that in these conditions, ipso-complexes are very
2
1
3
0
1
-6,22
which should include DCDNB. If this speculation is
correct, the decrease in experimentally estimated values
of k K in going to more aqueous solvents (Table 5) is
short-lived and do not return to the substrate,
or the
23
reaction is concerted.
Several factors contribute to build-up of the dihydroxy
Meisenheimer complex (M and M ) in > 0.3 mol L
OH (Tables 4 and 5 and reference 19). The return of
M is slow, especially in highly alkaline media, as shown
3
2
2
-
3-
-1
due to a decrease in K which describes the equilibrium
2
-
-
for overall addition of hydrophilic OH to nonionic
2-
DCDNB, although it is possible only to estimate its value
in DMSO:H O 7:3 v/v.
by values of k (Table 5), and in moderately concentrated
2
-3
-
-
These qualitative generalizations accord with the
Hughes-Ingold charge-type treatment of solvent effects
upon nucleophilic substitutions, although it was developed
for heterolytic reactions of nonionic and cationic
OH , the formation ofArO does not compete strongly with
-
addition of OH to DCDNB. As a result, the dihydroxy
2
-
Meisenheimer complex (M ) slowly decomposes in
-
-
dilute OH , and even more so with increasing [OH ]
(Tables 3 and 5).
3
1
1-
2-
aliphatic substrates. In M and M , the negative
charge is probably largely located on oxygens of the
nitro groups and the generalizations may not apply to
reactions of anionic substrates in which the charge is more
delocalized.
Stabilities of the dihydroxy Meisenheimer complexes
There are many examples of the formation of
unproductive monohydroxy Meisenheimer complexes
1
-8
Nucleophilic addition and substitution
derived from di- and tri-nitroarenes, and dihydroxy
complexes typically form from moderately concentrated
-
Rate and equilibrium constants for the various reactions
OH in solvents of relatively low water content. The
-5
-1
2-
-
with dilute DCDNB (5 × 10 mol L ) are given with some
estimated values in Table 5. Values in parentheses depend
on the assumptions described earlier, or on extrapolations.
Some aspects of the reaction of OH with DCDNB were
unexpected, but they are consistent with the rate and
equilibrium constants of the reactions in Scheme 2. The
substitution of a nitro group by OH , or other anionic
nucleophile, is not unusual, although many examples
involve polarizable, low charge-density, nucleophiles.
In DCDNB, the displacement of Cl should be assisted by
electron withdrawal by a nitro group, but the interference
between the nitro groups reduces this resonance effect. The
structural optimization indicates that the nitro groups are
twisted out of plane (Results section), and this unfavorable
interaction is relieved by loss of a nitro group. Steric
hindrance to resonance is a well-studied phenomenon, the
loss of a nitro group should be sterically accelerated, and
there is high LUMO density adjacent to the nitro groups
rapid formation of M , even in dilute aqueous OH
(Tables 2 and 4), was therefore unexpected, and this
-
behavior was not observed in reactions of OH with
-
8
other chlorodinitrobenzenes, although it is observed in
1
-8
reactions of 1,3,5-trinitrobenzene and its derivatives.
There is evidence for deprotonation of unproductive
-
1-2,4
Meisenheimer complexes in strongly alkaline media,
2
-
but M is apparently partially deprotonated in dilute
OH . This dihydroxy complex is an aliphatic diol, but
1
9,20,32
-
-
it is more acidic than expected from comparisons with
acidities of alcohols with strongly electron-withdrawing
substituents, e.g., the pK values in water are 1.5 and 0.45
b
-
-
34
for CF CH O and HC≡CCH O , respectively, and the
3
2
2
3-
classical pK for M is 2.0 in DMSO:H O 7:3 (Table 5).
The pK value cannot be estimated for M in water, but
the slow return of M to M in very dilute KOH (Table 3)
indicates the deprotonation of M . The negative charges in
M should be localized largely on nitro oxygens, favoring
the deprotonation. Our kinetic data on formation of M in
b
2
3-
b
3
3
2-
1-
2-
2-
1-
(Results section).
-
1-
The observed initial formation of ArO in very dilute
DMSO:H O 7:3 v/v indicate that M is not deprotonated
2
-
-
OH is consistent with values of k K /k (Tables 4 and 5),
in dilute OH and it therefore appears that the aliphatic
3
2
1
2-
1-
which indicate that partitioning of DCDNB is not very
sensitive to solvent composition. The initial formation
of unproductive Meisenheimer complexes is typical of
arenes with strongly electron-withdrawing substituents in
M is more acidic than M . The inductive effect of one
OH group in M could increase the acidity of the other,
but these groups are isolated and any effect should be
2
-
35
small. K was used in these comparisons rather than K
b
a
-
1-5,7,8
moderately concentrated OH .
because our data are in nonaqueous media and based on
-
The formation of the unproductive Meisenheimer
stoichiometric [OH ]. Comparison with literature data for
complexes is kinetically controlled, and in DMSO:H O
the alcohols is therefore qualitative.
2

1
156
The Reaction of 1,2-Dichloro-4,5-dinitrobenzene with Hydroxide Ion
J. Braz. Chem. Soc.
2
-
3-
ThepreferentialformationofunproductiveMeisenheimer
The dihydroxy Meisenheimer complex (M or M ) might
react nucleophilically in a classical aromatic nucleophilic
-
complexes overArO is kinetically controlled, but the long
lifetime of the dihydroxy Meisenheimer complex, in
-
substitution, displacing Cl rather than the congested nitro
group. On the basis of earlier work, such a first-formed
dinitroaryl ether could react with OH . It is difficult to test
this speculation because in the kinetic experiments, with
very dilute DCDNB, OH is in very large excess over any
-
other than dilute OH , is, on the time scale of the first
-
3,4
two relaxations, thermodynamically controlled. However,
-
ArO is the thermodynamically controlled product of the
-
overall reaction, but is the kinetically controlled product in
-
2-
very dilute OH (Experimental section and reference 19).
other nucleophile. Another possible route, with M and
3
-
M
in relatively high concentration, involves stepwise
Phenolic products
decomposition of the dihydroxy complex (Scheme 3)
with initial intramolecular nucleophilic addition forming
o
-
Thepreparativeworkinwateratca. 100 C(Experimental
a transient chlorohydrin, and loss of Cl and aromatization
-
section and reference 19) and UV-Vis spectroscopy give
evidence of only one phenolic product from loss of a nitro
group in this heterogeneous system. However, the NMR
giving Ar’O . A similar reaction could involve the base of
1
-
-
M , but such a reaction, or displacement of Cl from the
substrate, should not be very sensitive to the initial substrate
concentration.
data, with more concentrated DCDNB in DMSO-H O,
2
-
indicate that a second phenolic product is formed, probably
The formation of Ar’O involves initial loss of two
-
-
by loss of Cl . Such a dinitrophenoxide ion would not have
OH groups, and aromatization (Scheme 3), as does
2
-
been spectrophotometrically detected, but only in the NMR
spectra in concentrated solutions very different from the
kinetic conditions and may have been promoted by the
change of solvent composition. The direct formation of both
phenolic products with loss of NO or Cl from DCDNB
should be first-order in [DCDNB], and a minor phenolic
product would not affect the kinetic form. Conditions for
preparation of the phenolic product and examination
of the NMR spectra differ considerably in temperature,
solvent and substrate concentration from those in the
kinetic work and it is impracticable to monitor the NMR
spectra during reaction with the very dilute DCDNB used
in the kinetic work. However, the dihydroxy Meisenheimer
complex, which in the NMR experiments is in relatively high
concentration, could be the source of the minor phenoxide
product rather than the different reaction conditions,
although we know of no precedent for such a reaction.
formation of aryloxide ions, via return of M to DCDNB
in a conventional reaction (Scheme 2). These speculative
individual reactions may be stepwise or concerted, with the
possibility of reversible steps. However, other substitution
routes fit the kinetic and preparative evidence and are
consistent with earlier evidence.
-
-
2
1
9
Mechanism of substitution
Descriptions of organic reaction mechanisms often
involve the distinction between so-called “heterolytic” and
“homolytic” reactions, which is descriptively convenient,
and, for the former, nucleophilicity and leaving-group
35
ability are often related to Brønsted basicity. However,
the avoided-crossing model of nucleophilic substitution
indicates how “heterolytic” reactions can have radicaloid
3
6
character. Many aspects of aromatic nucleophilic
Scheme 3.

Vol. 24, No. 7, 2013
Blaskó et al.
1157
-
substitution by OH or alkoxide ions are characteristic of
"
results, and the overall kinetics, can be explained in terms
of reversible formation of tight anionic radical pairs, or
charge-transfer complexes, e.g., 1, on the reaction path,
leading to long-lived, but unproductive, Meisenheimer
1-6
heterolytic" reactions, especially in polar, protic, media,
but there is extensive evidence for the involvement of radical
species in some substitutions, i.e., they have “homolytic”
7
,8,36,37
-
character.
There is probably not a sharp distinction
complexes, and H/D exchange and displacement of NO or
2
-
between these limiting reaction paths, and a given reaction
may exhibit both “ionic” and “radicaloid” characteristics.
For example, the decomposition of trinitrotoluene in
Cl , written as involving transient Meisenheimer complexes
(Scheme 4). The initial pairs with the delocalized negative
charge could rapidly exchange hydrogen with D O and their
2
1
8
25,29
hot aqueous alkali generates formate and acetate ions
return would explain the rapid H/D exchange.
In less
which are not products expected in a simple nucleophilic
substitution, but could be formed by intervention of
radicaloid species and oxidation.
water content, e.g., DMSO:H O 4:1 v/v, the dissociation
2
of 2 would form transient radicals giving the observed
NMR line broadening and signal loss. In Scheme 4, which
shows reactions involving radicaloid species, intermediates
with finite lives, and products are numbered. Provided that
these radical ion pairs do not dissociate to free radicals,
the kinetic form in the higher water content media will
be as for a classical heterolytic reaction (Scheme 2), and
the rate constants in Tables 1-3 and 5 can be rewritten in
terms of rate and equilibrium constants for the individual
steps in Scheme 4. The initial rapid and reversible
formation of a resonance stabilized anionic radical pair, 1,
from DCDNB allows formation of the productive and
unproductive Meisenheimer complexes and H/D exchange
The reaction path shown in Scheme 2 follows classical
models of nucleophilic reactions with haloarenes,
allowing the estimation of rate and equilibrium constants
for individual steps, and the possible displacement of
-
Cl is not shown because of the limited evidence for
this reaction. The rapid H/D exchange in D O, or the
2
radical induced line broadening in DMSO:H O 4:1 v/v,
2
is not considered, and they could be ascribed to side
reactions unrelated to the overall nucleophilic reaction,
for example, by formation of a carbanion, although it is
-
unlikely in dilute OD and D O-DMSO. However, these
2
Scheme 4.

1
158
The Reaction of 1,2-Dichloro-4,5-dinitrobenzene with Hydroxide Ion
J. Braz. Chem. Soc.
in DCDNB, and the observed Meisenheimer complexes and
aryloxide products.
Conclusions
-
The partitioning between productive and unproductive
Meisenheimer complexes involves the anionic radical
pair, 2, rather than DCDNB, but it was assumed that 2 and
DCDNB are in rapid equilibrium on the time scale of
the overall reaction (Scheme 4). The conversion of the
The initial rapid reaction of OH with DCDNB in
DMSO:H O 7:3 v/v gives an unproductive, short-lived
2
1-
monohydroxy Meisenheimer complex (M ) and very slow
formation of aryloxide ion, largely with displacement of
a nitro group, while M forms a long-lived dihydroxy
1
-
1
-
2-
unproductive monohydroxy Meisenheimer complex (M )
Meisenheimer complex (M ) which is deprotonated in
2
-
3-
into M (Scheme 2) could also involve an anionic radical
pair, which is not shown to simplify Scheme 4, and the
deprotonation of OH groups at high pH inhibits return
of the dihydroxy Meisenheimer complex to the final
alkali giving M . The unproductive Meisenheimer complex
1
-
(M ) is not observed in reactions in more aqueous media.
The dihydroxy Meisenheimer complex has a lifetime
long enough for identification by NMR spectroscopy
phenolic products. The competitive losses of NO - or Cl-
in DMSO-H O-KOH. There is rapid exchange of arene
2
2
-
depend on the abilities of the postulated ipso complexes,
hydrogens, even in dilute OD , which is not explained
3
and 4, to lose either an anion or return to 1 and DCDNB
in terms of a classical heterolytic reaction scheme, even
though it fits the chemical kinetics. Rate and equilibrium
constants of all the individual reactions were determined
(
Scheme 4), and should be related to electron distributions
in the complexes and, as noted earlier, to intramolecular
hydrogen bonding in the postulated intermediate, 3.
In both aromatic substitution models, formations of
ipso-Meisenheimer complexes are shown as reversible but
are followed by irreversible loss of the leaving group, as in
Scheme 2. The explanation of the observed H/D exchange
in terms of a postulated radical pair, 1, follows that earlier
applied to exchange in nitroarenes, with exchange being
faster than nucleophilic substitution. However, we note
that the NMR evidence for H/D exchange was obtained
by NMR spectroscopy in nonkinetic conditions. In both
mechanistic descriptions, intermediates are negatively
charged and to those extent distinctions between
Scheme 4 and the classical description (Scheme 2) depend
on the postulated electron distributions and noncovalent
in DMSO:H O 7:3 v/v and some could be estimated in
2
more aqueous media. The preferential loss of a nitro
group and ready formation of an unproductive dihydroxy
Meisenheimer complex is probably related to intramolecular
hydrogen bonding and repulsions between the nitro groups.
2-
The dihydroxy Meisenheimer complex (M ) slowly reverts
to starting material and then to aryloxide ion, and in the
concentrations required for examination of the NMR
spectrum, weak signals of a second aryloxide ion are
2
5
-
observed, and its formation probably involves loss of Cl .
As an alternative to the classical model of nucleophilic
substitution, the overall reactions, and the kinetics, can
be described in terms of formation of tight anionic radical
pairs, or charge-transfer complexes, which allow rapid H/D
-
-
interactions, as does the relative loss of NO2 or Cl .
exchange and, in DMSO:H O 4:1 v/v, formation of free
2
Unless free radical ions are detected, as in DMSO:H O
radicals. These results are consistent with evidence on the
role of radicaloid species in other aromatic nucleophilic
substitutions by ionic nucleophiles in aqueous-organic
solutions.
2
4
:1 v/v, either model fits the rate data, but the reaction
path in Scheme 4 is consistent with the overall kinetics,
rapid H/D exchange and evidence for the formation of
free radicals with extensive NMR line broadening in
-
the less aqueous media. The loss of NO , rather than
Acknowledgements
2
-
Cl , can be explained in either mechanistic model in
terms of intramolecular hydrogen bonding involving
C. Z. thanks CNPq for a travel grant and we thank
Dr. A. Shirazi for valuable advice on NMR spectroscopy.
3
8
NO and OH and relief of steric strain. Although in the
2
mechanistic models, exchange and NMR line broadening
are not necessarily on the overall reaction path, they can
be explained in terms of reactions involving radicaloid
species. The distinction between the reactions in Schemes
References
1. Terrier, F.; Nucleophilic Aromatic Substitution. The Influence
of the Nitro Group; Wiley-VCH: New York, USA, 1991.
2. Crampton, M. R.; In Organic Reaction Mechanisms; Knipe; A.
C., ed.; John Wiley & Sons, Ltd.: NewYork, USA, 2005, p. 103.
3. Miller, J.; Aromatic Nucleophilic Substitution; Elsevier: New
York, USA, 1968.
2
and 4 reflects limitations in graphical depictions of
the organic chemical bond, for example as in single
electron transfer in gas phase S 2 reactions of quaternary
N
3
9
ammonium salts. The postulated initial formation of
the anionic radical pair, 2, is consistent with theoretical
4
0
treatments and recent experimental evidence.
4. Terrier, F.; Chem. Rev. 1982, 82, 77.

Vol. 24, No. 7, 2013
Blaskó et al.
1159
5
6
. Bunnett, J. F.; Q. Rev. Chem. Soc. 1958, 12, 1; Crampton, M. R.;
In Organic Reaction Mechanisms; Knipe;A. C., ed.; JohnWiley
Sons, Ltd.: New York, USA, 2007, p. 193.
. Crampton, M. R.; Ghiarini, M. A.; Khan, H. A.; Tetrahedron
972, 28, 1778; Gibson, B.; Crampton, M. R.; J. Chem. Soc.,
25. Bacaloglu, R.; Bunton, C. A.; Cerichelli, G.; Ortega, F.; J. Am.
Chem. Soc. 1988, 110, 3495 and cited referecences therein.
26. Willis, J. S.; Stewart, J. M.;Ammon, H. L.; Preston, S.; Ghysas,
R. E.; Harris, R. M.; Acta Crystallogr. Sect. B: Struct. Sci. 1971,
B27, 786.
&
1
Perkin Trans. 1979, 2, 648.
27. Cotton, F. A.; Wilkinson, G.; Advanced Inorganic Chemistry,
rd
7
8
9
. Bacaloglu, R.; Bunton, C. A.; Ortega, F.; J. Am. Chem. Soc.
3 ed.; Wiley-Interscience: New York, USA, 1972, ch. 4.
1
988, 110, 3503.
28. Hawkins, G. D.; Cramer, C. J.; Truhlar, D. G.; J. Phys. Chem.
1996, 100, 19824.
. Bacaloglu, R.; Blasko,A.; Bunton, C.A.; Dorwin, E.; Ortega, F.;
Zucco, C.; J Am. Chem. Soc. 1991, 113, 238.
29. Bacaloglu, R.; Blasko,A.; Bunton, C.A.; Ortega, F.; Zucco, C.;
J. Am. Chem. Soc. 1992, 114, 7708.
. Paradisi, C.; Scorrano, G. In Nucleophilicity; Harris, J. M.;
McManus, S. P., eds.;American Chemical Society:Washington,
DC, USA, 1987, ch. 24.
30. Buncel, E.; Wilson, H.; Adv. Phys. Org. Chem. 1977, 14, 133;
Blandamer, M. J.; Adv. Phys. Org. Chem. 1977, 14, 203.
31. Ingold, C. K.; Structure and Mechanism in Organic Chemistry,
1
1
1
1
0. Denney, D. B.; Denney, D. Z.; Perez,A.; Tetrahedron 1993, 49,
463.
nd
4
2 ed.; Cornell University Press: Ithaca, NY, USA, 1969, ch. 7.
1. Nudelman, N. S.; Palleros, D.; J. Org. Chem. 1983, 48, 1607;
Vergas, E. B.; de Rossi, R. H.; J. Org. Chem. 1984, 49, 3978.
2. Sepulcri, P.; Gournont, R.; Halle, J. C.; Buncel, L. E.; Terrier, F.;
Chem. Comm. 1997, 787.
32. Sammes, P. G.; Thetford, D.;Voyle, M.; Chem. Commun. 1987,
1373; Beck, J. R.; Tetrahedron 1978, 34, 2057; Marsh, J.;
rd
Advanced Organic Chemistry, 3 ed.; Wiley-Interscience: New
York, USA, 1985, ch. 15.
3. Wittig, G.; Pure Appl. Chem. 1963, 7, 173; Bunnett, J. F.;
J. Chem. Educ. 1961, 38, 278.
33. Wepster, B. M.; Rec. Trav. Chim. 1952, 71, 661; Hammett, L. P.;
nd
Physical Organic Chemistry, 2 ed.; McGraw-Hill: NewYork,
1
1
4. Bunnett, J. F.; Acc. Chem. Res. 1978, 11, 413.
USA, 1970, ch. 11.
5. Mariani, C.; Modena, G.; Pizzo, C. P.; Scorrano, G.;
Kistenberger, L. J.; Chem. Soc., Perkin Trans. 1979, 2, 1187.
6. Zollinger, H.; Azo and Diazo Chemistry, Interscience: New
York, USA, 1961.
34. Ballinger, R.; Long, F. A.; J. Am. Chem. Soc. 1960, 82, 795.
35. Jencks, W. P.; Catalysis in Chemistry and Enzymology;
McGraw-Hill: New York, USA, 1969, ch. 2; Bruice, T. C.;
Benkovic, S.; Bioorganic Mechanisms, vol. 1; Benjamin: New
York, USA, 1966, ch. 1.
1
1
7. Soldi, V.; Keiper, J.; Romsted, L. S.; Cuccovia, I. M.;
Chaimovich, H.; Langmuir 2000, 16, 59; Cuccovia, I. M.;
da Silva, M. A.; Ferraz, H. M. C.; Josefredo, J. R.; Rivieros,
J. M.; Chaimovich, H.; J. Chem. Soc., Perkin Trans. 2000, 2,
36. Pross, A.; Acc. Chem. Res. 1985, 18, 212; Shaik, S. S.; Acta
Chem. Scand. 1990, 44, 205; Shaik, S.; Joffe, A.; Reddy, A. C.;
Pross, A.; J. Am. Chem. Soc. 1994, 116, 262.
1
896.
8. Bishop, R. L.; Flesner, R. L.; Larson, S. A.; J. Energetic Mater.
000, 18, 275.
37. Ritchie, C. D.; J. Am. Chem. Soc. 1983, 105, 7313; Buncel, E.;
Shaik, S. S.; Um, I. H.; Wolfe, S.; J. Am. Chem. Soc. 1988, 110,
1275.
1
2
1
2
9. Acheson, R. M.; Taylor, N. F.; J. Chem. Soc. 1956, 4727.
0. Senskey, M. P.; Bradshaw, J. D.; Tessier, C. A.; Youngs, W. J.;
Tetrahedron Lett. 1996, 36, 6217.
38. Sanderson, R. T.; Chemical Bonds and Bond Energy;Academic
Press: New York, USA, 1971; Buckingham, A. D.; In The
Hydrogen Bond in Theoretical Treatment of Hydrogen Bonding;
Hadzi, D., ed.; Wiley: New York, USA, 1997, ch. 1.
39. Sauers, R. B.; J. Chem. Theory Comput. 2010, 6, 602.
40. Wheeler, J. E.; Houk, K. N.; J. Phys. Chem. A 2010, 114, 8658.
2
2
1. Bernasconi, C. F.; Relaxation Kinetics; Academic Press: New
York, USA, 1976.
2. Crampton, M. C.; Rotbotham, I. A.; Can. J. Chem. 1988, 76,
6
27; Chamerlin, R. A.; Crampton, M. R.; Rotbotham, I. A.;
J. Phys. Org. Chem. 1996, 9, 152.
Submitted: February 27, 2013
Published online: June 18, 2013
2
2
3. Hunter, A.; Renfrew, M.; Rettura, D.; Taylor, J. A.; Whitmore,
J. M. J.; Williams, A.; J. Am. Chem. Soc. 1996, 117, 5484.
4. Streitwieser,A.; Hammons, J. H.; Prog. Phys. Org. Chem. 1965,
3
, 41; Gold, V.; McAdam, M. E.; Acc. Chem. Res. 1978, 11,
1
136.