Vicarious nucleophilic C-amination of nitrobenzene and 5- and 6-nitro-1-methylbenzimidazoles

Article abstract of DOI:10.1007/s11178-005-0339-z

Vicarious nucleophilic C-amination of nitrobenzene, 1-methyl-5- nitrobenzimidazole, and 1-methyl-6-nitrobenzimidazole in superbasic medium (potassium tert-butoxide-dimethyl sulfoxide) gave the corresponding amino-substituted derivatives. The yield of the

Full text of DOI:10.1007/s11178-005-0339-z

Russian Journal of Organic Chemistry, Vol. 41, No. 9, 2005, pp. 1306–1315. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 9, 2005,
pp. 1331–1340.
Original Russian Text Copyright © 2005 by Titova, Vakul’skaya, Larina, Mizandrontsev, Volkov, Dolgushin, Lopyrev.
Dedicated to Full Member of the Russian Academy of Sciences
N.S. Zefirov on His 70th Anniversary
Vicarious Nucleophilic C-Amination of Nitrobenzene
and 5- and 6-Nitro-1-methylbenzimidazoles
I. A. Titova, T. I. Vakul’skaya, L. I. Larina, M. I. Mizandrontsev, V. A. Volkov,
G. V. Dolgushin, and V. A. Lopyrev
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: vti@irioch.irk.ru
Received May 30, 2005
Abstract—Vicarious nucleophilic C-amination of nitrobenzene, 1-methyl-5-nitrobenzimidazole, and 1-methyl-
6-nitrobenzimidazole in superbasic medium (potassium tert-butoxide–dimethyl sulfoxide) gave the corre-
sponding amino-substituted derivatives. The yield of the amination product of 1-methyl-5-nitrobenzimidazole
considerably increased in the presence of CuCl. ESR monitoring of these reactions revealed formation of
primary radical anions from the substrates. Possible reaction mechanisms are discussed.
Vicarious nucleophilic substitution of hydrogen is
a relatively new approach to the synthesis of substitut-
ed nitroaromatic compounds. This approach provides
a convenient and often the only possible way of
introducing functional groups into aromatic [1–3] and
heteroaromatic rings [4–6]. The synthetic aspects of
such reactions in the aromatic series were examined in
detail in [7–10] and reviewed in [1, 4–6, 11, 12]. Anal-
ogous reactions in the series of heterocyclic com-
pounds have been studied to a lesser extent [13–18].
recent years via vicarious nucleophilic substitution of
hydrogen [13]. A wide series of reagents is used to
effect direct amination of nitroarenes and nitro-sub-
stituted heteroaromatic compounds under mild condi-
tions. These include 1,1,1-trimethylhydrazinium iodide
[25, 28, 29], 4-amino-1,2,4-triazole [24, 23], 4-alkyl-
amino-1,2,4-triazoles [3], sulfenamides [26, 30], and
O-alkylhydroxylamines [7].
In the preliminary communications [31, 32] we
showed that 1-methyl-4-nitroimidazole reacts with
1,1,1-trimethylhydrazinium iodide in the presence of
dry sodium methoxide or potassium tert-butoxide in
DMSO to afford 5-amino-1-methyl-4-nitroimidazole
as the major product (yield 56%) [31]. With the
goal of elucidating general relations holding in vicar-
ious nucleophilic C-amination of nitroaromatic and
nitroheteroaromatic systems and extending the scope
of application of vicarious nucleophilic substitution
of hydrogen, in the present work we examined these
reactions using nitrobenzene, 1-methyl-5-nitrobenz-
imidazole, and 1-methyl-6-nitrobenzimidazole as
substrates.
Successful vicarious nucleophilic substitution of
hydrogen is determined by a number of factors, the
main of which is the presence of a readily departing
group at the nucleophilic center. Just that group leaves
intermediate σH complex as H adduct instead of hy-
dride ion [1, 19]. Vicarious nucleophilic substitution of
hydrogen was used to effect alkylation [20, 21], hy-
droxylation [22, 23], and amination [3, 24–26]. Among
these reactions, amination seems to be the most im-
portant, for it ensures direct introduction of an amino
group into an aromatic ring, by-passing the stage of
nitroarene reduction. One of the first examples of
vicarious amination may be the reaction of 1,3-di-
nitrobenzene with hydroxylamine in the presence of
a strong base, which yields 2,4-dinitrobenzene-1,3-di-
amine [27]. A large number of azoles containing nitro
and amino groups in a single molecule, which were
difficult to obtain previously, were synthesized in the
We previously showed by NMR spectroscopy that
nitrobenzene (I) reacts with 1,1,1-trimethylhydra-
zinium halides II–IV in anhydrous DMSO in the pres-
ence of t-BuOK to give the corresponding amination
product, p-nitroaniline (V), and bis(p-nitrophenyl)-
amine (VI) [33] (Scheme 1) instead of the expected
1070-4280/05/4109-1306 © 2005 Pleiades Publishing, Inc.

VICARIOUS NUCLEOPHILIC C-AMINATION OF NITROBENZENE
1307
Scheme 1.
H2N
NO2
+
Me3N·HX
+
Me3N–NH2 X–
t-BuOK, DMSO
V
NO2
H
N
O2N
NO2
+
Me3N·HX
I
II–IV
VI
II, X = Cl; III, X = Br; IV, X = I.
mixture of o- and p-nitroanilines, as reported in [25].
Here, the nature of halide ion in the reagent (Cl, Br, I)
did not affect the yield of the target products to an ap-
preciable extent.
In fact, when the reaction of nitrobenzene with
1,1,1-trimethylhydrazinium iodide (IV) in t-BuOK–
DMSO was performed in an inert atmosphere in
a special ampule placed into the probe of ESR spec-
trometer, we detected an ideally resolved signal be-
longing to nitrobenzene radical anion VII (Fig. 1).
Bis(p-nitrophenyl)amine (VI) was also obtained by
13
15
independent synthesis [33], and its C and N NMR
spectra were recorded. The 15N NMR spectrum of
compound VI characteristically contained signals from
nitrogen atoms in the two equivalent nitro groups
(δN –10.7 ppm) and from the amino nitrogen atom
NO2
·
–
1
VII
(δN –271.8 ppm) [34]. In the H NMR spectrum of
VI we observed a singlet from the NH proton at
δ 9.92 ppm and two doublets from two pairs of equiv-
alent aromatic protons at δ 7.35 and 8.20 ppm with
a coupling constant 3J of 9.5 Hz.
This means that vicarious nucleophilic substitution
of hydrogen in nitrobenzene (which is a classical nitro-
arene), as well as in 1-methyl-4-nitroimidazole [31],
involves formation of primary radical anions from
the substrate. Taking into account that the reagent in
superbasic medium (t-BuOK–DMSO) is activated (it
exists as anion), its nucleophilicity increases while
the ionization potential decreases. Therefore, electron
transfer from the reagent anion to electrophilic sub-
strate to produce radical anion of the latter should be
facilitated (Scheme 2). Here, the formation of nitro-
benzene radical anions implies simultaneous formation
of radical species from the reagent. However, we
detected no other radical species than nitrobenzene
radical anions in the reaction mixture obtained from
nitrobenzene and an equimolar amount of 1,1,1-tri-
methylhydrazinium iodide in t-BuOK–DMSO.
When the reaction was carried out under purified
argon, the mixture initially turned blue–violet for
a short time, and the color quickly deepened up to
black. These findings prompted us to examine the
process by ESR spectroscopy. Despite numerous pre-
vious attempts to study the mechanism of vicarious
nucleophilic substitution of hydrogen [35–37], the
problem concerning elementary steps of this process
remains unclear. There is a concept according to which
the reaction follows a polar mechanism involving
intermediate formation of σH complex [1, 4, 6, 8, 11,
12]. In fact, this concept implies simultaneous transfer
of a couple of electrons, which is thermodynamically
less favorable than two-step one-electron transfer.
DeBoos and Milner [38] were the only to report on the
formation of nitrobenzene radical anion in the reaction
with methyl dichloroacetate, though it has long been
known that irreversible electron transfer between un-
saturated compounds and their dihydro derivatives to
give radical anions occurs in strongly basic medium
such as t-BuOK–DMSO [39]. Therefore, it is more
reasonable to presume that electron transfer from the
reagent anion to the substrate precedes formation of
σH complex in vicarious nucleophilic C-amination.
We also studied amination of nitrobenzene with
4-amino-1,2,4-triazole (VIII) in the superbasic system
t-BuOK–DMSO. According to the NMR data, the re-
action leads to formation of several products: p-nitro-
aniline (V) (amination product) and bis(p-nitrophenyl)-
amine (VI), 4-nitrophenyl(1,2,4-triazol-4-yl)amine
(IX), and bis(4-nitrophenyl)(1,2,4-triazol-4-yl)amine
(X) (condensation products; Scheme 3). The structure
of the products was proved by two-dimensional NMR
spectroscopy (see Experimental). The product ratio
depended on the reaction conditions.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

TITOVA et al.
1308
Scheme 2.
Exit from cage
NO2
t-BuOK, DMSO
I, t-BuOK, DMSO
·
Me3N NH2 I–
Me3N NH
Me3N NH
·
–
–HI
O
O
N
NH
N
O
O
H
H
–HNMe3
·
·
O2N
HN NMe3
HN NMe3
σ
H Complex
NH2
H+
O2N
V
(a)
ESR monitoring of the reaction involving 4-amino-
1,2,4-triazole (VIII) as aminating agent showed
a more complicated pattern. The ESR lines belonging
to nitrobenzene radical anion were strongly broadened.
When the aminating agent (compound VIII) was taken
in excess, the ESR spectrum of the reaction mixture
(according to computer simulation) was a superposi-
tion of two signals, one of which belongs to nitroben-
zene radical anion. The other signal is characterized
by interaction of unpaired electron with four nitrogen
nuclei and three protons; therefore, it was assigned to
neutral hydrazyl radical XI with the following hyper-
fine coupling constants (HCC), mT: 2(1H) 1.020,
3(1Nβ) 0.780, 3(1Nα) 0.390, 5(2N) 0.040, 3(2H) 0.330.
These data are consistent with the known HCC ratio
aNα/aNβ = 0.5 for analogous hydrazyl radicals [40].
0.5 mT
(b)
N
N
·
α N NH
β
XI
To verify our conclusions, we performed ab initio
calculations* of spin density distribution in radical XI.
The results of calculations were consistent with the
experimental parameters characterizing hyperfine
coupling between the unpaired elecron and paramag-
netic atoms. However, the experimental HCC values
indicate that radical XI in DMSO becomes even more
planar; this follows from similarity in the hyperfine
coupling constants for the N1 and N2 atoms in the
0.5 mT
Fig. 1. (a) High-resolution ESR spectrum of the reaction
mixture in the amination of nitrobenzene with 1,1,1-tri-
methylhydrazinium iodide in the system t-BuOK–DMSO
and (b) simulated ESR spectrum with the following hyper-
fine coupling constants, mT: 3[1N(NO2)] 1.100, 2(1Hp)
0.377, 3(2Ho) 0.335, 3(2Hm) 0.111.
* The complete set of calculation results is available from the
authors.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

VICARIOUS NUCLEOPHILIC C-AMINATION OF NITROBENZENE
1309
Scheme 3.
NH2
O2N
V
H
N
NO2
O2N
NO2
t-BuOK, DMSO
N
N
VI
+
N
NH2
H
N
3'
N
I
N
N
5'
O2N
O2N
IX
3
6
NO2
2
4
5
1
N
N
5'
3'
N
N
X
heteroring and hydrogen atoms on C3 and C5, as well
as from the relative stability of the radical anion.
substrate with formation of intermediate radical ion
pairs A and B, respectively. Presumably, unexpected
products VI, IX, and X were formed via reaction of
radicals XI which left solvent cage and anions V with
the substrate.
We can conclude that vicarious nucleophilic sub-
stitution of hydrogen in nitrobenzene in superbasic
medium with the use of both 1,1,1-trimethylhydra-
zinium iodide and 4-amino-1,2,4-triazole as aminating
agent follows a common mechanism which may be
illustrated by Schemes 2 and 4. These schemes include
electron transfer from the deprotonated reagent to the
Benzimidazole, 1-methylbenzimidazole, and 5(6)-
nitrobenzimidazole cannot be involved in vicarious
nucleophilic substitution of hydrogen because of
a weak electrophilicity of the benzimidazole ring [10].
Scheme 4.
Exit from cage
NO2
N
N
N
N
N
N
t-BuOK, DMSO
I, t-BuOK, DMSO
·
·
–
N
NH2
N
NH
HN
N
–H+
B
O
N
O
NH
N
O
O
N
N
H
H
·
O2N
N
N
N
N
·
–
HN
N
HN
H Complex
NH2
N
N
H
σ
H+
O2N
V
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

TITOVA et al.
1310
Scheme 5.
NH2
O2N
O2N
N
N
N
N
Me3NNH2 ·I–, t-BuOK, DMSO
Me
Me
XII
XIII
Introduction of a strong electron-withdrawing sub-
stituent, e.g., trifluoromethyl group, into position 2 of
the benzimidazole ring favors this process. N-Substi-
tuted 5- and 6-nitrobenzimidazoles react with carb-
anions derived from aryl chloromethyl sulfones to give
hydrogen replacement products, and the new substit-
uent enters the ortho position with respect to the nitro
group [10].
and 6.88 ppm with a coupling constant J of 9.3 Hz.
1
The latter value is typical of H–1H coupling through
three bonds in structurally related compounds [34].
These data indicate that the amino group occupies the
4-position and that the two doublet signals belong to
1
6-H and 7-H. In the H–1H NOESY spectrum we ob-
served a cross peak between protons of the N-methyl
group (δ 3.82 ppm) and proton with a chemical shift
δ of 6.88 ppm; i.e., this signal corresponds to 7-H.
Carbon signals were assigned using 2D CH-CORR and
HMBC-GP 1H–13C techniques. The latter allowed us to
identify signals from the quaternary C4, C5, C8, and C9
atoms. Likewise, 15N signals were assigned using the
two-dimensional HMBC-GP 1H–15N technique.
The reaction of 1-methyl-5-nitrobenzimidazole
(XII) with 1,1,1-trimethylhydrazinium iodide (IV) in
t-BuOK–DMSO at room temperature (reaction time
10 h) afforded the corresponding amination product
at the 4-position, 4-amino-1-methyl-5-nitrobenzimida-
zole (XIII), in 39% yield (Scheme 5). Compound XIII
was not reported previously. Its structure was proved
by NMR (1H, 13C, 15N) spectroscopy, including two-
In the reaction performed in thoroughly purified
solvent under argon, the mixture turned intense blue
for a short time, and the color then changed to dark
red. The amination of XII with an equimolar amount
of the aminating agent in superbasic medium in an
inert atmosphere was monitored by ESR spectroscopy.
After a few minutes, the ESR spectrum of the mixture
contained a signal with hyperfine structure, whose
intensity gradually increased up to a certain stationary
1
dimensional (2D) NMR techniques. Signals in the H,
13C, and 15N NMR spectra of XIII were unambigu-
ously assigned on the basis of the 2D NOESY, CH-
1
1
CORR, and HMBC-GP H–13C data. The H NMR
spectrum of XIII contained a downfield singlet at
δ 8.18 ppm, a broadened signal from protons in the
amino group at δ 7.66 ppm, and two doublets at δ 7.91
Scheme 6.
·
–
O2N
N
O2N
N
N
t-BuOK, DMSO
·
+
Me3NNH2 ·I–
Me3NNH
–H+
N
Me
Me
XII
II
D
·
–
O2N
N
N
Exit from cage
Me
XIV
H
NH2
O
H
N
NMe3
N
O2N
N
N
N
O
–HNMe3
N
Me
Me
XIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

VICARIOUS NUCLEOPHILIC C-AMINATION OF NITROBENZENE
1311
(a)
value. According to the computer simulation data, the
observed ESR signal may be assigned to radical anion
XIV. Its parameters almost coincided with those of
1-methyl-5-nitrobenzimidazole radical anion (XIV)
(Scheme 6) generated by electrochemical reduction of
compound XII [HCC, mT: 3(NNO2) 1.260, 2(1H4)
0.420, 2(1H6) 0.210, 2(1H7) 0.068, 2(1H2) 0.080,
3(1N1) 0.032, 3(1N3) 0.040, 4(3H, CH3) 0.029;
Fig. 2a]. The hyperfine coupling constants were as-
signed on the basis of ab initio calculations of spin
density distribution in the radical anion. Thus our
results suggest that vicarious nucleophilic amination of
1-methyl-5-nitrobenzimidazole follows Scheme 6.
0.5 mT
Vicarious nucleophilic substitution of hydrogen in
1-methyl-6-nitrobenzimidazole (XV) with 1,1,1-tri-
methylhydrazinium iodide (IV) in superbasic medium
afforded two amination products at positions 7 and 2,
compounds XVI and XVII, respectively (Scheme 7).
Their structure was determined by NMR spectroscopy.
(b)
0.5 mT
ESR monitoring of the reaction of 1-methyl-6-
nitrobenzimidazole (XV) with an equimolar amount of
1,1,1-trimethylhydrazinium iodide (IV) in an inert
atmosphere revealed a signal with the following hyper-
fine coupling constants, mT: 3(NNO2) 1.135, 2(1H7)
0.460, 2(1H5) 0.240, 2(1H4) 0.126, 2(1H2) 0.044,
3(1N1) 0.030, 3(1N3) 0.240, 4(3H, CH3) 0.020
(Fig. 2b). These data coincided with those correspond-
ing to 1-methyl-6-nitrobenzimidazole radical anion
(XVIII) generated by electrochemical reduction. The
hyperfine coupling constants were assigned on the
basis of computer simulation of the ESR spectrum and
ab initio quantum-chemical calculations of spin dens-
ity distribution. The reaction mechanism is shown in
Scheme 8.
Fig. 2. ESR spectra of the reaction mixtures in the amination
of (a) 1-methyl-5-nitrobenzimidazole and (b) 1-methyl-6-
nitrobenzimidazole with 1,1,1-trimethylhydrazinium iodide
in the system t-BuOK–DMSO.
nucleophile at the site with maximal positive spin
density in radical anions derived from the substrate
[41], in keeping with the calculation data.
–0.69
·
–
·
–
0.81
O2N
N
N
N
N
0.69
0.37
–0.35
0.74
O2N
0.77
–0.70
Me
Me
XIV
XVIII
It should be emphasized that we were the first to
consider the mechanism of vicarious nucleophilic sub-
stitution of hydrogen from the viewpoint of possible
electron transfer. The observed similarity in the ESR
patterns for vicarious C-amination of 1-methyl-4-nitro-
imidazole [31], nitrobenzene, and 5- and 6-nitro-1-
methylbenzimidazoles suggests the existence of single-
electron transfer channel in these processes. The pro-
posed concept allows us to rationalize orientation of
Detection of components of radical pairs A, B, D,
and E by ESR spectroscopy indicates their fairly high
stability and high rate of electron transfer. On the other
hand, recombination of a radical pair within a solvent
cage (formation of σH complex) should be slow, which
should increase the probability for radical species to
leave the cage and go into the bulk solution. Radical
anions that left solvent cage are detected by ESR spec-
Scheme 7.
N
N
N
N
N
N
Me3NNH2 ·I–, AlkOM, DMSO
NH2
+
O2N
O2N
O2N
Me
Me
Me
NH2
NH2
XVII
XV
XVI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

TITOVA et al.
1312
Scheme 8.
·
–
N
N
N
N
t-BuOK, DMSO
·
+
Me3NNH2·I–
Me3NNH
–H+
O2N
O2N
Me
Me
XV
II
E
·
–
N
Exit from cage
N
O2N
Me
XVIII
N
N
N
O
N
N
O
O2N
–HNMe3
H
NH
Me
Me
NH2
NMe3
XVI
N
N
N
N
H
NH2
NMe3
O
N
H
N
O
O2N
–HNMe3
Me
Me
XVII
troscopy. Transfer of radical anions from solvent cage
to bulk solution is favored by the solvating power of
dimethyl sulfoxide. However, it remains unclear
whether the out-of-cage radicals participate in the
formation of amination products or not.
imidazole (XIII) increased by 42%. The ESR spectrum
of the reaction mixture displayed a strong signal of
Cu2+ (g|| = 2.112; g┴ = 2.010; aCu = 7.3 mT; in the g┴
region we observed a hyperfine structure consisting of
7 lines with a coupling constant of about 0.9 mT,
presumably due to two nonequivalent nitrogen atoms
in the benzimidazole ring).
Electron transfer from the highest occupied mo-
lecular orbital of a donor molecule to the lowest
unoccupied molecular orbital of an acceptor molecule
may be facilitated or hindered by various factors, e.g.,
redox properties of the reacting species, properties of
the medium, and some extra effects such as irradiation,
temperature, catalysis, etc. In the recent years, much
effort is given to the development of so-called catalysis
in electron-transfer reactions [42]. Insofar as electron
transfer is an elementary step of a reaction, increase in
the rate of electron transfer by the action of a catalyst
(promoter) should involve change of its driving force
via binding of promoter with the electron-transfer
product.
EXPERIMENTAL
The IR spectra were recorded on a Specord 75IR
spectrometer from samples prepared as KBr pellets.
1
The H, 13C, and 15N NMR spectra were obtained on
Bruker DPX-400 and Bruker AV-400 spectrometers at
400.13, 100.62, and 40.56 MHz, respectively. The
1H and 13C chemical shifts were measured relative
to tetramethylsilane with an accuracy of ±0.01 and
15
±0.02 ppm, respectively. The N chemical shifts were
15
measured relative to CH3 NO2 (external) with an ac-
curacy of ±0.1 ppm. All NMR spectra were recorded
We made an attempt to increase the efficiency of
vicarious nucleophilic substitution of hydrogen with
the use of copper(I) chloride. In the amination of
1-methyl-5-nitrobenzimidazole with 1,1,1-trimethyl-
hydrazinium iodide in the presence of copper(I)
chloride, the yield of 4-amino-1-methyl-5-nitrobenz-
from solutions in DMSO-d6 at 27°C. Signals were
1
13
15
assigned using two-dimensional (2D) H, C, and N
NMR techniques: 2D 1H–1H NOESY and inverse two-
1
1
dimensional H–13C and H–15N spectra with account
taken of long-range coupling constants using gradient
probe (HMBC-GP 13C and HMBC-GP 15N).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

VICARIOUS NUCLEOPHILIC C-AMINATION OF NITROBENZENE
1313
The mass spectra were run on a Shimadzu
GC-17/Gcms-QP5050 1 system. The ESR spectra were
recorded on a Radiopan SE/X-2547 spectrometer
(Poland) at 20°C. ESR monitoring was performed
using special cells which ensured the reactions to
proceed in an inert atmosphere; ESR signals were re-
corded continuously during several hours. All reagents
(both individual and as mixtures of two or three com-
ponents) were preliminarily checked for the absence of
paramagnetic properties. Computer simulation of the
ESR spectra was performed using WINEPR SimFonia
1.25 program (Bruker, 1996).
lution of 1.8 g (1 mmol) of 1-methyl-5-nitrobenz-
imidazole (XII) in 30 ml of anhydrous DMSO. The
mixture was stirred until it became homogeneous, and
3.36 g (3 mmol) of potassium tert-butoxide was added.
The mixture quickly turned dark red. It was stirred
for 10 h at room temperature, poured onto ice, and
acidified with 10% hydrochloric acid to pH ≈ 3. The
precipitate was filtered off, the filtrate was extracted
with three portions of ethyl acetate, and the extracts
were combined, washed with distilled water, dried over
anhydrous magnesium sulfate, and evaporated. The
residue was combined with the previously separated
product and recrystallized first from dimethylform-
amide and then from water. Yield 0.76 g (39%),
mp 280–280.5°C. When potassium hydroxide was
used instead of potassium tert-butoxide, the yield was
53%. IR spectrum, ν, cm–1: 3410 NH2, 1620–1595
Quantum-chemical calculations of spin density dis-
tribution in radical anions derived from 5- and 6-nitro-
1-methylbenzimidazoles were performed by the
UHF/6-31G* method using Gaussian 98 software
package [43].
1
(δNH2), 1500 (NO2), 1230 (δCHring). H NMR spec-
General procedure for the amination of nitroben-
zene was described in [24, 25, 33].
trum, δ, ppm: 3.82 s (3H, Me), 6.88 d (1H, 7-H, J =
9.3 Hz), 7.66 br.s (2H, NH2), 7.90 d (1H, 6-H, J =
9.3 Hz), 8.18 s (1H, 2-H). 13C NMR spectrum, δC,
ppm: 31.05 (CH3), 99.92 (C7), 120.38 (C6), 124.90
(C5), 131.67 (C9), 137.44 (C8), 140.46 (C4), 143.77
(C2). 15N NMR spectrum, δN, ppm: –3.3 (NO2), –131.8
(N3), –222.9 (N1), –307.6 (NH2). Mass spectrum, m/z
(Irel, %): 192 (100) [M]+, 162 (27), 146 (21), 134 (12),
119 (24), 105 (12), 92 (15), 76 (16), 65 (18), 42 (36).
Found, %: C 50.00; H 4.23; N 29.10. C8H8N4O2.
Calculated, %: C 50.00; H 4.20; N 29.15.
1
p-Nitroaniline (V). H NMR spectrum, δ, ppm:
6.61 d (2H, 2-H, 6-H, J = 8.3 Hz), 6.70 br.s (2H, NH2),
8.05 d (2H, 3-H, 5-H, J = 8.3 Hz). 13C NMR spectrum,
δC, ppm: 111.45 (C2, C6), 126.44 (C3, C5), 135.00 (C4),
156.00 (C1).
Bis(p-nitrophenyl)amine (VI). 1H NMR spectrum,
δ, ppm: 7.35 d (2H, 2-H, 6-H, J = 9.5 Hz), 8.20 d (2H,
13
3-H, 5-H, J = 9.5 Hz), 9.92 br.s (1H, NH). C NMR
spectrum, δC, ppm: 117.04 (C2, C6), 125.77 (C3, C5),
140.05 (C4), 147.60 (C1). 15N NMR spectrum, δN, ppm:
–10.7 (NO2), –271.8 (NH).
b. In the presence of CuCl. 1-Methyl-5-nitrobenz-
imidazole (XII), 0.89 g (0.5 mmol), was dissolved in
15 ml of anhydrous DMSO, and 0.05 g (0.05 mmol) of
CuCl and 1.51 g (0.75 mmol) of 1,1,1-trimethylhydra-
zinium iodide were added. When the latter dissolved
completely, 1.68 g (1.5 mmol) of potassium tert-but-
oxide was added. The mixture quickly turned dark red.
It was stirred for 10 h at room temperature, poured
onto ice, and acidified with 10% hydrochloric acid to
pH ≈ 3. The precipitate was filtered off, the filtrate was
extracted with three portions of ethyl acetate, and the
extracts were combined, washed with water, dried over
anhydrous magnesium sulfate, and evaporated. The
residue was combined with the previously separated
product and recrystallized first from dimethylform-
amide and then from water. Yield 0.78 g (81%),
mp 280–280.5°C.
4-Nitrophenyl(1,2,4-triazol-4-yl)amine (IX).
1H NMR spectrum, δ, ppm: 6.59 d (2H, 2-H, 6-H, J =
9 Hz), 8.16 d (2H, 3-H, 5-H, J = 9 Hz), 8.87 s (2H,
13
3'-H, 5'-H), 10.52 br.s (1H, NH). C NMR spectrum,
δ, ppm: 111.70 (C2, C6), 126.13 (C3, C5), 140.05 (C4),
144.08 (C3', C5'), 156.00 (C1).
Bis(4-nitrophenyl)(1,2,4-triazol-4-yl)amine (X).
1H NMR spectrum, δ, ppm: 6.79 d (2H, 3-H, 5-H,
J = 9 Hz), 7.44 d (2H, 2-H, 6-H, J = 9 Hz), 8.61 s (2H,
3'-H, 5'-H).
1-Methyl-5-nitrobenzimidazole (XII) and
1-methyl-6-nitrobenzimidazole (XV) were prepared
by the procedures described in [44, 45]. Compound
XII: mp 211–212°C; published data [44]: mp 212°C.
Compound XV: mp 182–183°C; published data [44]:
mp 182°C.
7-Amino-1-methyl-6-nitrobenzimidazole (XVI).
1,1,1-Trimethylhydrazinium iodide (IV), 1.52 g
(0.75 mmol), was slowly added under stirring to a so-
lution of 0.9 g (0.5 mmol) of 1-methyl-6-nitrobenz-
imidazole (XIV) in 15 ml of anhydrous DMSO. The
4-Amino-1-methyl-5-nitrobenzimidazole (XIII).
a. 1,1,1-Trimethylhydrazinium iodide (IV), 3.03 g
(1.5 mmol), was slowly added under stirring to a so-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 9 2005

TITOVA et al.
1314
4. Makosza, M., Izv. Akad. Nauk SSSR, Ser. Khim., 1996,
mixture was stirred until it became homogeneous, and
1.68 g (1.5 mmol) of potassium tert-butoxide was
added. The mixture quickly turned dark red. It was
stirred for 10 h at room temperature and poured onto
ice, and the precipitate was filtered off and recrys-
tallized from methanol. The product, 0.44 g (45%),
mp 242–248°C, was a mixture of 2-amino-1-methyl-
6-nitrobenzimidazole (XVII) and 7-amino-1-methyl-
6-nitrobenzimidazole (XVI). Recrystallization from
pyridine gave 7-amino-1-methyl-6-nitrobenzimidazole
(XVI), mp 270–273°C. IR spectrum, ν, cm–1: 3420
(NH2), 1610–1580 (δ NH2), 1495 (NO2), 1380
(δCHring). 1H NMR spectrum, δ, ppm: 4.17 s (3H, Me),
6.92 d (1H, 4-H, J = 9.3 Hz), 7.46 br.s (2H, NH2), 7.84 d
(1H, 5-H, J = 9.3 Hz), 8.21 s (1H, 2-H). 13C NMR
spectrum, δC, ppm: 34.24 (CH3), 109.37 (C4), 119.98
(C5), 122.56 (C8), 126.57 (C6), 137.10 (C7), 148.44
(C2), 148.76 (C9). 15N NMR spectrum, δN, ppm: –3.2
(NO2), –129.0 (N3), –222.5 (N1), –305.6 (NH2). Mass
spectrum, m/z (Irel, %): 192 (72) [M]+, 162 (20), 146
(20), 134 (7), 119 (11), 105 (11), 92 (13), 78 (23), 66
(28), 52 (43), 42 (31). Found, %: C 49.92; H 4.24;
N 29.12. C8H8N4O2. Calculated, %: C 50.00; H 4.20;
N 29.15.
p. 531.
5. Knyazev, V.N. and Drozd, V.N., Russ. J. Org. Chem.,
1995, vol. 31, p. 1.
6. Makosza, M. and Winiarski, J., Acc. Chem. Res., 1987,
vol. 20, p. 282.
7. Seko, S. and Miyake, K., J. Synth. Org. Chem. Jpn.,
2003, vol. 61, p. 192.
8. Makosza, M. and Wojciechowski, K., Justus Liebigs
Ann. Chem., 1997, p. 1805.
9. Katritzky, A.R. and Xie, L., Tetrahedron Lett., 1996,
vol. 37, p. 347.
10. Makosza, M., Chem. Unsere Zeit, 1996, vol. 30, p. 134.
11. Makosza, M., Current Trends in Organic Synthesis
(Proc. Fourth Int. Conf. on Organic Synthesis, Tokyo,
Japan, August 22–27, 1982), Nozaki, H., Ed., Oxford:
Pergamon, 1983. Translated under the title Sovremennye
napravleniya v organicheskom sinteze, Moscow: Mir,
1986, p. 518.
12. Makosza, M., Polish J. Chem., 1992, vol. 66, p. 3.
13. Donskaya, O.V., Dolgushin, G.V., and Lopyrev, V.A.,
Khim. Geterotsikl. Soedin., 2002, p. 435.
14. Makosza, M., Synthesis, 1991, p. 103.
15. Makosza, M. and Wojciechowski, K., Heterocycles,
2001, vol. 54, p. 445.
The pyridine mother liquor was diluted with diethyl
ether, and the mixture was left to stand for several
days. After prolonged storage, 2-amino-1-methyl-6-
nitrobenzimidazole (XVII) separated from the solu-
tion. Its properties coincided with published data
16. Makosza, M. and Kwast, E., Tetrahedron, 1995, vol. 51,
p. 8339.
17. Chupakhin, O.N. and Beresnev, D.G., Usp. Khim., 2002,
vol. 71, p. 803.
18. Chupakhin, O.N., Charushin, V.N., and Rusinov, V.L.,
Panorama sovremennoi khimii Rossii. Sovremennyi
organicheskii sintez (Panorama of Modern Chemistry in
Russia. Modern Organic Synthesis), Moscow: Khimiya,
2003, p. 99.
1
(mp 272°C [46]). H NMR spectrum, δ, ppm: 3.58 s
(3H, Me), 7.18 d (1H, 4-H, J = 9.1 Hz), 7.21 br.s (2H,
NH2), 7.93 d.d (1H, 5-H, J = 9.1, 2.4 Hz), 8.06 d (1H,
13
7-H, J = 2.4 Hz). C NMR spectrum, δC, ppm: 28.84
(CH3), 103.64 (C9), 113.48 (C4), 117.91 (C5), 134.67
(C8), 138.89 (C6), 149.74 (C7), 159.71 (C2). Mass spec-
trum, m/z (Irel, %): 192 (100) [M]+, 162 (76), 146 (23),
134 (20), 119 (12), 105 (26), 92 (12), 63 (17), 52 (7),
43 (7). When potassium hydroxide was used instead of
potassium tert-butoxide, we isolated only 7-amino-1-
methyl-6-nitrobenzimidazole (XVI) in 35% yield.
19. Golinski, J. and Makosza, M., Tetrahedron Lett., 1978,
p. 3495.
20. Drew, M.D., Jackson, D.A., Lawrence, N.J., Liddle, J.,
and Pritchard, R.G., Chem. Commun., 1997, p. 189.
21. Lawrence, N.J., Liddle, J., Bushell, S.M., and Jack-
son, D.A., J. Org. Chem., 2002, vol. 67, p. 457.
22. Makosza, M. and Sienkeiwicz, M., J. Org. Chem., 1990,
vol. 55, p. 4979.
This study was performed under financial support
by the Russian Academy of Sciences (Division of
Chemistry and Material Sciences, project no. 4.1.7).
23. Makosza, M. and Podraza, R., Eur. J. Org. Chem., 2000,
p. 193.
24. Katrizky, A.R., Laurenzo, K.S., and Schmidt, R.D.,
J. Org. Chem., 1986, vol. 51, p. 5039.
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