Effect of the electronic structure of the radical anions of 4-substituted 1,2-and 1,3-dinitrobenzenes on the regioselectivity of reduction of the nitro groups

Article abstract of DOI:10.1134/S1070363206010154

Theoretical and experimental regularities of the regioselectivity of the reduction of one of the two nitro groups in unsymmetrical dinitrobenzenes were studied. It was found that the regioselectivity of the formation of isomeric nitroanilines depends on the structure of the substrate and the nature of the reducing agent. The reduction regioselectivity model was verified, according to which radical anion protonation is the major reaction direction. Pleiades Publishing, Inc. 2006.

Full text of DOI:10.1134/S1070363206010154

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 1, pp. 76 81.
Pleiades Publishing, Inc., 2006.
Original Russian Text
pp. 81 86.
V.Yu. Orlov, R.S. Begunov, N.Yu. Demidova, A.I. Rusakov, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 1,
Effect of the Electronic Structure of the Radical Anions
of 4-Substituted 1,2- and 1,3-Dinitrobenzenes
on the Regioselectivity of Reduction of the Nitro Groups
V. Yu. Orlov, R. S. Begunov, N. Yu. Demidova, and A. I. Rusakov
Demidov Yaroslavl State University, ul. Sovetskaya 14, Yaroslavl, 150000 Russia
e-mail: begunov@bio.uniyar.ac.ru
Received March 24, 2004
Abstract Theoretical and experimental regularities of the regioselectivity of the reduction of one of the
two nitro groups in unsymmetrical dinitrobenzenes were studied. It was found that the regioselectivity of the
formation of isomeric nitroanilines depends on the structure of the substrate and the nature of the reducing
agent. The reduction regioselectivity model was verified, according to which radical anion protonation is the
major reaction direction.
DOI: 10.1134/S1070363206010154
To direct a reaction to one of several potential re-
action centers is an urgent problem of synthetic or-
ganic chemistry. Hence selective reduction of one of
several nitro groups in polynitroaromatic compounds
forms one of the basic synthetic approaches to nitro-
arylamines. Depending on conditions, the reaction can
lead to one or another isomeric product. In the present
paper we discuss the problem of selective monoreduc-
tion of 4-substituted 1,2- and 1,3-dinitrobenzenes.
This reaction gives rise to a mixture of isomeric nitro-
anilines (Scheme 1).
Scheme 1.
H
H
H
H
O
O
N
N
N
O
O
O
2e, 2H+
O
O
O
O
2e, 2H+
+
2e, 2H+
+
+
X
N
X
N
X
N
O
O
+
N
ortho(meta) isomer
O
O
O
O
O
X
N
O
O
+
N
+
N
+
N
H
O
H
O
H
H
2e, 2H+
2e, 2H+
2e, 2H+
X
N
X
N
X
N
para isomer
In certain specific conditions, one or the other nitro
group is predominantly reduced. We previously found
that the direction of the monosubstitution of 4-sub-
stituted 1,2- and 1,3-dinitrobenzenes with compounds
of varied oxidation state elements depends on the
structure of the substrate and the nature of the reduc-
ing agent and the solvent [1, 2].
4-Substituted 1,2- and 1,3-dinitrobenzenes were
reduced to the corresponding nitroanilines with tita-
nium(III) and tin(II) chlorides (Table 1). The reactions
were performed in conditions ensuring nearly quan-
titative yields of the target products and no diamine
formation. This allows the monoreduction regioselec-
tivity to be measured by the ratio of nitroanilines
76

EFFECT OF THE ELECTRONIC STRUCTURE OF THE RADICAL ANIONS
77
formed, since neither starting dinitro compounds nor
reaction products are consumed in side processes.
To study the effect of substrate structure of the
regioselectivity of monoreduction of unsymmetrical
dinitrobenzenes, we made use of a model [3, 4], ac-
cording to which the reaction direction is controlled
by protonation of the redical anion species formed in
the first stage (Scheme 2).
Our present data, like those reported in the litera-
ture, provide evidence to show that the monosubstitu-
tion regioselectivity is strongly dependent on the
structure of the substrate and the nature of the reduc-
ing agent.
Scheme 2.
X
O
O
+
N
H+
H
+
N
X
X
O
O
O
O
+
N
+
N
e
O
O
O
X
+
N
+
N
O
O
+
N
H+
O
O
O
O
+
N
HO
Some authors believed that the reduction direction
is controlled by the steric effect of the substituent in
the starting structure [5, 6]. Bil’kis and co-workers
[7 10] stated, considering radical anions, that the
substituent effect is complex in nature and is defined
by such parameters as electronic effects, effective
volume, and capacity for hydrogen bonding with the
o-nitro group. However, such interpretation of ex-
perimental data is no more than qualitative.
and o-nitro groups [qp(O)/qo(O), qp(N)/qo(N)], as well
as on the nitro groups themselves (qp/qo); and ratio of
quantities that relate to the contributions of the
oxygen and nitrogen atoms of the o- and p-nitro
groups into the highest occupied molecular orbital
(HOMO) of the radical anion [ratio of the squared pz
atomic contributions of the reaction centers into the
molecular orbital (C2pz)]. The resulting values are
listed in Table 2.
As seen from Table 2, the charge factor has almost
no effect on the isomer ratio. Certain correlation is
only observed with iodo-2,4-dinitrobenzene, where the
preferential formation of the para isomer can be cor-
related with the charge ratio on the oxygen atoms of
the nitro groups.
In the present work we made use of quantum-
chemical characteristics of corresponding radical
anions to assess the effect of the structure of a com-
pound on the direction of the monosubstitution of
4-substituted 1,2- and 1,3-dinitrobenzenes with tita-
nium(III) chloride. The calculation method chosen
was AM1. According to published data (including
those in [11]), this method and its modifications fairly
correctly reproduce the structure of aromatic radical
anions. Obviously, monoreduction direction is dif-
ficult to correlate with any specific parameter of
substituent X. Therefore, we took into consideration
the substituent effects on various quantum-chemical
characteristics of both reaction centers of radical
anions. According to the proposed reaction model
(protonation of substrate radical anion), we chose the
following quantum-chemical parameters: ratio of the
charges on the nitrogen and oxygen atoms of the p-
The orbital factor has a stronger effect (see figure).
The resulting isomer ratio (3-nitro-4-X-aniline:2-X-5-
nitroaniline) and the ratio of the C2pz contributions
of the oxygen atoms of the o- and p-nitro groups into
the HOMOs of 1-X-2,4-dinitrobenzene radical anions.
The values for 2,4-dinitrobenzonitrile and 2,4-dinitro-
benzamide do not fit into this correlation. These com-
pounds contain substituents whose atoms contribute
much into the HOMOs of the corresponding radical
anions and thus are potential protonation centers. Thus,
the contribution of the C2pz orbital of the cyano nitro-
gen (0.05584) into the HOMO of the radical anion of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 1 2006

78
ORLOV et al.
Table 1. Effect of substrate structure on product isomer ratio in reduction of compounds Ia Ih and III with TiCl3 and
SnCl2 (molar ratios: [Ia Ih, II]: [TiCl3] = 1:3 and [Ia Ih, II]: [SnCl2] = 1: 1.5, methanol water, conversion 50%, csubstr
0.2 M)
NO2
NO2
O2N
X
Cl
NO2
Ia Ih
Content, %
II
Isomer yield, %
ortho
Comp. no.
X
p/o (m)
substrate and
anilinea
substrate
para
(meta)
Reducing agent TiCl3
Ia
Ib
Ic
Id
Ie
If
Ig
Ih
II
F
92.7
99.8
98.0
93.3
91.8
92.0
96.8
90.1
97.5
41.07
52.00
54.00
43.86
54.17
60.43
51.23
43.42
25.75
36.30
37.64
25.97
11.70
8.36
4.27 1.54
21.01
11.22
33.27
7.52
0.99
3.10
Cl
Br
I
H3C
H3CO
N C
4.50
42.36 0.71
18.89
10 50b
0.90
20.34
12.30
39.16
15.90
1.80
0.37
5.20
0.83
H2NC(O)
65.00
19.10
Reducing agent SnCl2
c
Ib
Ie
II
Cl
H3C
99.0
97.0
98.0
51.00
57.40
50.45d
49.00
8.50
11.03
34.10
23.66
0.25
0.47
a
b
In the reaction mixture. The yield of the ortho isomer is extremely low, and its slight variations only slightly affect the nitro-
c
d
aniline isomer ratio.
The ortho isomer only.
Diamine, 12.20%, and unidentified compound, 2.66%, were also found.
Table 2. Ratios of the charges (q) and C2pz contributions of the oxygen and nitrogen atoms of the p- and o-nitro groups in
the HOMOs of 1-X-2,4-dinitrobenzene radical anions
Comp. no.
para/ortho
qp/qo (N)
qp/qo (O)
C2pzp/C2pzo(N)
C2pzp/C2pzo(O)
Ia
Ib
Ic
Id
Ie
If
Ig
Ih
II
0.99
3.10
0.99
0.99
0.99
0.99
1.01
0.99
1.01
1.02
0.99
1.03
1.05
1.04
1.20
1.01
1.04
1.07
0.98
1.03
1.19
1.39
2.20
48.96
1.20
1.16
1.35
2.50
58.64
1.17
4.50
10 50a
0.90
1.80
0.37
5.20
0.83
1.44
1.44
1.56 (0.68)a
0.71 (3.78)b
76.00
1.25 (0.63)a
0.76 (3.34)b
5.49
a
2
Parenthesized are the ratios of the C p contributions of the nitrogen and oxygen atoms of the p-nitro group and the nitrogen atom
z
b
2
of the cyano group. Parenthesized are the ratios of the C p contributions of the nitrogen and oxygen atoms of the p-nitro group
z
and the carbon atom of the amido group.
2,4- dinitrobenzonitrile is higher of the respective
contributions of the p-NO2 [C2pz 0.03779 (N) and
0.03506 (O)] and o-NO2 groups [C2pz 0.02415 (N)
and 0.02257 (O)]. Thus, the radical anion should be
preferentially protonated by the cyano nitrogen.
However, as follows from the energetic characteristics
of protonated 2,4-dinitrobenzonitrile radical anions,
protonation by the o-nitro group is preferred ( H
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 1 2006

EFFECT OF THE ELECTRONIC STRUCTURE OF THE RADICAL ANIONS
79
ing isomer ratio correlates with the orbital character-
istics of the 1-X-2,4-dinitrobenzene radical anions
(R2 0.9204).
6
4
II
Chloro-3,4-dinitrobenzene falls out of the above
correlation (see figure). The fraction of the para
isomer is much lower and that the meta isomer is
much higher than expected by the orbital character-
istics of the radical anion. A possible reason for this
fact is that the activation barrier for proton transfer
between the two nitro groups in these structures is
only slightly (by 5%) is higher than the respective
parameter for the protonation of the radical anion with
a foreign donor.
Ih
Ic
2
0
If
Ie
Ib
Ig
Ia
2
4
6
As mentioned above (see [3, 4], as well as the
correlation dependence between the electronic para-
meters of radical anions and the isomer ratio of nitro-
anilines formed), a stage that predetermines the direc-
tion of selective reduction of one of several nitro
groups is protonation of the radical anion of the sub-
strate. In terms of this concept, the isomer ratio of
monoreduction products is defined by competition of
the nitro groups for protonation. The structural
characteristics of the corresponding transition states
can arbitrarily be divided into factors associated with
systems to be protonated (radical anions) and factors
associated with protonation products (protonated
radical anions). To gain a comprehensive understand-
ing of the pattern, we performed AM1 quantum-
chemical calculations of polynitrobenzene radical
species protonated by different functional groups.
Plot of the ratio of the para and ortho isomers ( ) vs.
2
ratio of the C p contributions of the oxygen atoms of
z
the p- and o-nitro groups ( ) in the HOMO of 1-X-2,4-
dinitrobenzene radical anions.
1
267 kJ mol ) over protonation by the cyano group
1
( H 303.8 kJ mol ). This fact suggests that, directing
protonation primarily toward the cyano nitrogen, the
structure of intermediate species favors protonation by
the o-nitro group. This is associated either with the
deformation of the HOMO of the species protonated
by the cyano group [C2pz: o-NO2 0.01737 (O) and
p-NO2 0.01158 (O)] and the preferential orientation of
further protonation to the o-nitro group or with proton
transfer from the substituent. In the latter case, an
important characteristic associated with reduction
orientation is the ratio of the C2pz values for the nitro-
gen (or oxygen) atom of the o-nitro group and the
nitrogen atom of the cyano group (given in paren-
theses in Table 2). The same pattern is observed with
such a protonation-susceptible substituent as the
amido group.
As models for calculating the protonated radical
anions we chose derivatives of 1-substituted 2,4-di-
nitrobenzenes: 2,4-dinitrochlorobenzene and 2,4-di-
nitritoluene. Structures protonated by nitro groups
were only taken into account (structures A D). This
is explained by the fact that atoms of the functional
groups contribute much less into the unpaired electron
orbital than nitro oxygen atoms; the principal param-
eters of these species are listed in Table 3.
Taking into account the characteristics of the pos-
sible protonation centers, we can state that the result-
O
O
O
Cl
O
N
Cl
Cl
Cl
+
+
N+
N
N
O
OH
OH
O
OH
+N
+
N
+N
+
N
OH
O
O
O
O
O
OH
O
O
O
A
B
D
O
O
O
N+
CH3
O
N
CH3
CH3
CH3
+
+
N
N
O
O
OH
+N
+
N
+N
+
N
OH
O
O
O
OH
O
C
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 1 2006

80
ORLOV et al.
Table 3. Quantum-chemical characteristics of protonated forms A D of 1-chloro-2,4-dinitrobenzene and 2,4-dinitro-
toluene radical anions (AM1 method)a
o-NO3
C2pz
p-NO3
C2pz
Atom
lN O
lN O
q
q
(lO H
,
(lO H
,
Structure A
N
O
O
H
0.3042
0.3408
0.2705
0.2490
0.00083
0.00098
0.05061
0.00090
0.5709
0.3486
0.3486
0.00000
0.00000
0.00000
1.33840
1.20720
1.20095
1.20095
Structure B
N
O
O
H
0.5697
0.3342
0.3339
0.00004
0.00007
0.00008
0.3083
0.3548
0.2717
0.2498
0.08346
0.10745
0.09598
0.00176
1.19900
1.19900
1.33938
1.20795
(0.97954)
Structure C
N
O
O
H
0.2968
0.3485
0.2758
0.2460
0.00121
0.00158
0.05189
0.00123
0.5713
0.3526
0.3526
0.00000
0.00000
0.00000
1.33895
1.20737
(0.97980)
1.20150
1.20150
Structure D
N
O
O
H
0.5700
0.3556
0.3558
0.00000
0.00000
0.00000
1.12020
1.12020
1.12020
0.2963
0.3484
0.2743
0.2464
0.00214
0.00211
0.05406
0.00126
1.33878
1.20764
(0.97944)
a
E , kJ: 96.5254 (A), 112.2170 (B), 85.9436 (C), 86.7563 (D); EV
/E
:
45.036/ 22.9480 (A), 44.8799/ 23.4862 (B),
f
HDOMO HOMO
44.6121/ 22.3563 (C), 44.1978/ 22.2893 (D).
As follows from these data, the contribution of the
suggests absence of a strong donor acceptor interac-
tion between the titanium(III) ion and dinitro com-
pound. Therefore, the resulting isomer ratio is deter-
mined by electronic characteristics of the 1-X-2,4-di=
nitrobenzene anion radical undistorted by interaction
with the reducing agent. This is confirmed by the elec-
trochemical reduction data in [14].
nitro group protonated by an oxygen atom to the
HOMO of these species much increases at the expense
of the contributions of the other functional groups.
As a result, it is this group that takes part in further
reduction. Thus we obtained evidence for our model
(previously based on general regularities for such
processes), according to which the direction of selec-
tive reduction is determined by the site of protonation
of the radical anion.
With SnCl2, the reaction with 1-chloro-2,4-dinitro-
benzene results in preferential formation of 2-chloro-
5-nitroaniline (by contrast to 4-chloro-3-nitroaniline
with TiCl3) (Table 1). In this case, a strong donor
acceptor interaction of the metal ion with the substrate
chlorine atom is possible, as evidenced by the fact that
the o-nitro group is appreciably faster reduced in the
presence of a number of substituents (including halo-
gen atoms) [15]. As a result, the electronic structure
of the radical anion is distorted and the monoreduc-
tion direction changes.
The data listed in Table 1 and reported in [12] are
also indicative of a considerable effect of the nature
of the reducing agent. Thus, when tin(II) chloride is
used instead of titanium(III) chloride, the fraction of
the reduction product by the o-nitro group appreciably
increases both with 1-chloro-2,4-dinitrobenzene and
2,4-dinitrotoluene. This result can be explained in
terms of the degree of radical ion counterion inter-
action. It is known that titanium(III) ions are mostly
reduced by an outer-sphere mechanism. This also
applies to reduction of nitro compounds [13]. The
absence of changes in the inner coordination sphere
Thus, it was shown that the monoreduction of
1-substituted dinitrobenzenes is controlled by the
electronic configuration of the radical anion, along
with the structure of the substrate and reducing agent.
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EFFECT OF THE ELECTRONIC STRUCTURE OF THE RADICAL ANIONS
81
EXPERIMENTAL
6. Miesel, J.L., O’Doherty, G.O.P., and Owen, J.M.,
Catalysis in Organic Synthesis, New York: Academic,
1976.
Dinitro compounds were reduced with tin(II) and
titanium(III) chlorides by the procedure in [1]. The
mixtures of reduction products were studied by GLC.
7. Bil’kis, I.I., Uskov, S.I., Galdilov, V.S., and Shtein-
garts, V.D., Zh. Org. Khim., 1986, vol. 22, no. 6,
p. 1247.
Quantum-chemical calculations were performed by
the AM1 method.
8. Bil’kis, I.I., Uskov, S.I., and Shteingarts, V.D., Izv.
Akad. Nauk SSSR, Ser. Khim., 1987, no. 3, p. 111.
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