Reaction of reductive intermolecular heterocyclization of n-(2-nitroaryl)pyridinium chlorides with salts of variable valence metals

Full text of DOI:10.1134/S1070428014080296

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 8, pp. 1220–1222. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © R.S. Begunov, А.А. Sokolov, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 8, pp. 1234–1236.
SHORT
COMMUNICATIONS
Reaction of Reductive Intermolecular Heterocyclization
of N-(2-Nitroaryl)pyridinium Chlorides with Salts of Variable
Valence Metals
R. S. Begunov and А. А. Sokolov
Demidov Yaroslavl State University, Sovetskaya ul. 14, Yaroslavl, 150000 Russia
e-mail: begunov@bio.uniyar.ac.ru
Received April 9, 2014
DOI: 10.1134/S1070428014080296
Depending on the nature of the electron donor the
chemical reduction of N-(2-nitro-4-R-phenyl)
pyridinium salts affords either primary amines like N-
(2-amino-4-R-phenyl)pyridinium chlorides or products
of intermolecular cyclization, derivatives of pyrido
[1,2-а]benzimidazole [1]. The yield and purity of the
specific azaheterocycles depend on the nature of the
reducing agent. The application of TiCl3 led to the
formation of multicomponent mixture of compounds;
from the mixture 1-(2-amino-4-R-phenyl)pyridinium
chloride was isolated in a small yield. During the
reduction with SnCl2 intramolecular amination took
place. Yield of 7-R-pyrido[1,2-а]benzimidazole was
86–98%. The use of FeCl2 also allowed obtaining a
fused tricycle system, but in significantly lower yield.
The complication in the analysis of this reaction
may be due to two simultaneous chemical
transformations: the reduction and the intramolecular
cyclization. It is known that the reduction of NO2
proceeds in several steps of consequential addition of
three electron pairs (Scheme 1) forming the compounds
of different nature: ArNO, ArNHOH, ArNH2.
Considering the electron-deficient character of
pyridinium ring, the cyclization should take place as a
result of an attack of nucleophilic species on the α-
carbon atom of the heterocycle. That is why the course
of the reaction involving a nitroso group looks unlikely
(path а, Scheme 1). Most likely, the reductive amination
takes place as a result of the addition of more than one
electron pair to the initial substrate (b and c, Scheme 1).
To understand the influence of the reducer nature
on the direction of the reduction of N-(2-nitroaryl)
pyridinium salts and also the possibility of this reac-
tion application to obtain various condensed polycyclic
nitrogen heterocycles studies were performed on the
nature of the key species formed during the synthesis
taking part in cyclization.
To get experimental evidence of the nitro group
conversion stage at reduction when the cyclization
occurs we applied an approach of electrons
calculation: The number of electrons required to obtain
condensed azaheterocycles was calculated. To make it
possible, the influence of the ratio substrate SnCl2 on
Scheme 1.
_
Cl
_
Cl
_
_
Cl
+ 2 e
+ 2 e
+ 2 H+
+ 2 e
+ 2 H+
Cl
+ 2 H+
N+
N+
R
N+
R
N+
R
R
d
NH
NH2
NO2
NO
HO
a
b
c
N
R
N
1220

REACTION OF REDUCTIVE INTERMOLECULAR HETEROCYCLIZATION
1221
Scheme 2.
_
Cl
N
N
O2N
N+
H2N
O2N
N
N
NO2
I
II
III
the yield of the reaction products has been
investigated. N-(2,4-dinitrophenyl)pyridinium chloride
(I) was used as a model compound, since at the
application of mononitroderivative it was impossible to
consider the excess of the reducing agent in the
reaction mass and consequently also the number of the
electrons required for generation of the attacking
particle. As it has been previously established, in
compound I the reduction first occurs at the оrtho-nitro
group [1]. That is why the generation of amine III
(Scheme 2) will be observed after introducing into
reaction mass a larger amount of the reducer than it is
necessary for conversion of the substrate into
cyclization product II.
reductive cyclization, 6 in the conver-sion of nitro
groups into amino groups. The obtained data evidence
that the structure of the intermediate taking part in the
cyclization corresponds to 1-[2-(hydroxylamino)-4-
nitrophenyl]pyridinium chloride, and the generation of
compound II occurs along the path b (Scheme 1).
Basing on this data the influence of the nature of the
reducing agent may be understood in the following
way.
It is known, that the titanium(III) chloride is a
stronger reducing agent (redox potential TiIV + e– →
TiIII = –0.092 V) than the tin chloride(II) and iron
chloride(II) (Sn4+ + 2e– → Sn2+ = +0.14 V, Fe3+ + e– →
Fe2+ = +0.771 V) [2]. Therefore the reduction with
these two last chlorides of N-(2-nitroaryl)pyridinium
will go slower, and at the stage b Ar-hydroxylamine
will undergo cyclization. When TiCl3 is used, this
intermediate turns into amine (Scheme 1, stage d).
A series of experiments has been performed where
the ratio (I)–SnCl2 has varied from 1 : 1.5 to 1 : 6 with
a step of 0.5 with the purpose of establishing the
reagents ratio giving the maximal yield of compound
II at no admixtures of the initial compound I and
amine III, and also of determining the minimal amount
of SnCl2 necessary for full transformation of both nitro
groups and for generation of compound III.
Nonaqueous 98% tin(II) chloride [7772-99-8] of Acros
Organics was used in the investigation.
Hence, to synthesize condensed nitrogen
heterocyclic systems in conditions of chemical
reduction of N-[2-nitro(heth)aryl]pyridinium salts a
reducing agent is necessary, whose application in
certain amounts transforms the nitro group into
hydroxylamino group.
To exclude the influence of the air oxygen on the
experimental results the solutions of dinitroderivative I
in 90% aqueous alcohol and the reducing agent in 3%
HCl were preliminary flushed with nitrogen for 5 min.
The reductive cyclization was also carried out in
nitrogen atmosphere.
The influence of the reagents ratio on the yield of the
reaction products of reduction with tin(II) chloride of N-
(2,4-dinitrophenyl)pyridinium chloride (I) [сI 0.036,
с(SnCl2 ) 0.074–0.202 mol/L, 20ºС, 5 min].
Yield, %
Ratio
(I)–SnCl2
Overall yield,
%
The results of the investigation are given in the
table.
II
III
1 : 1.5
1 : 2.0
1 : 2.5
72.8
95.1
81.2
0
0
13.4
72.8
95.1
94.6
As it follows from the table, after introducing SnCl2
in the amount necessary to reduce one nitro group to
hydroxylamine, 7-nitropyrido-[1,2-a]benzimidazol (II)
was isolated from the reaction mass in 95% yield. With
increasing ratio of tin chloride(II)–compound I to > 2.0
the generation of pyrido[1,2-a]benzimidazol-7-amine
(III) is observed beside the compound II. Pure
heterocyclic amine III was obtained, as it was
expected, as a result of addition of 10 electrons to the
substrate, 4 of them took part in the reaction of the
1 : 3.0
1 : 3.5
1 : 4.0
1 : 4.5
1 : 5.0
1 : 5.5
1 : 6.0
57.9
50.7
34.0
17.2
0
31.6
42.4
60.7
77.1
96.7
97.1
96.9
89.5
93.1
94.7
94.3
96.7
97.1
96.9
0
0
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 8 2014

BEGUNOV, SOKOLOV
1222
To confirm this suggestion we carried out the
20.01. С11H7N3О2 Calculated, %: C 61.97; H 3.29; N
19.71. М 213.20.
reduction of the N-[2-nitro-4-(trifluormethylphenyl)]-
pyridinium chloride (IV) with zinc powder by the
method used for the synthesis of aromatic
hydroxylamines [3]. As a result 7-(trifluormethyl)-
pyrido[1,2-a]benzimidazole (V) was obtained in 85%
yield that evidences the validity of the suggested path
in the course of the reaction of the reductive
intramolecular heterocyclization of the N-(2-nitroaryl)-
pyridinium salts.
Pyrido[1,2-а]benzimidazol-7-amine (III). mp
1
180–182°C. Н NMR spectrum (DMSO-d6), δ, ppm:
5.1 s (2H, NH2), 6.7 d.d (1H, H8, J 10, 2.0 Hz), 6.82 d
(1H, H6, J 1.5 Hz), 6.85 t (1H, H2, J 7.0 Hz), 7.38 t
(1H, H3, J 7.5 Hz), 7.47 d (1H, H4, J 10.0 Hz), 7.9 d
(1H, H9, J 9.5 Hz), 8.82 d (1H, H1, J 7.0 Hz). Mass-
spectrum, m/z (Irel., %): 183 (100) [M]+, 166 (4), 155
(15), 78 (12). Found, %: С 71.98; H 4.63; N 23.15.
С11H9N3. Calculated, %: C 72.13; H 4.92; N 22.95. М
183.21.
General method of reduction with SnCl2. To a
solution of 0.51 g (1.8 mmol) of N-(2,4-dinitrophenyl)-
pyridinium chloride (I) in 25 mL of 90% isopropyl
alcohol in nitrogen flow at 20°С was introduced a
solution of 0.70–1.91 g (3.7–10.1 mmol) of 98% SnCl2
in 25 mL of 3% HCl. After 5 min the reaction mixture
was treated with NH4OH to pH 8, reaction products
were extracted with several portions of hot chloroform.
The dry precipitate obtained after distillation of
chloroform was treated with small portions of cold
95% ethyl alcohol. Insoluble part of the organic
fraction was 7-nitropyrido[1,2-а]benzimidazol (II), the
compound isolated after evaporation of the alcohol
was pyrido[1,2-а]benzimidazol-7-amine (III).
7-(Trifluomethyl)pyrido[1,2-а]benzimidazol (V).
1
mp 233–235°C. Н NMR spectrum (DMSO-d6), δ,
ppm: 7.09 t (1H, H2, J 7.0 Hz), 7.66 t (1H, H3, J 8.0 Hz),
7.68 d (1H, H9, J 8.0 Hz), 7.75 d (1H, H4, J 9.0 Hz),
8.16 d (1H, H6, J 1.5 Hz), 8.53 d.d (1H, H8, J 2, 8 Hz),
9.15 d (1H, H1, J 7.5 Hz). Mass-spectrum, m/z (Irel.,
%): 236 (100) [M]+, 217 (20), 186 (12), 167 (4), 118
(5), 69 (5), 63 (11), 51 (17), 39 (20). Found, %: С
60.79; H 2.96; N 12.01. С12H7F3N2 Calculated, %: C
61.02; H 2.99; N 11.86. М 236.12.
1Н NMR spectra were recorded on a Bruker
DRX500 SF-500 МHz instrument, solvent DMSO-d6–
CCl4, internal reference TMS. Mass spectra were
recorded on a FINNIGAN MAT. INCOS 50,
instrument, ionizing electrons energy 70eV. Elemental
composition was determined on elemental analyzer
CHN-1.
General method of reduction with Zn. To a
solution of 1.50 g (4.9 mmol) of N-(2-dinitro-4-
trifluormethylphenyl)pyridinium chloride (IV) and
0.332 g (6.2 mmol) of NH4Cl in 50 mL of 50%
isopropyl alcohol at 60°С was introduced by small
portions 1.60 g (24.5 mmol) of zinc powder. After 3 h
the reaction products were extracted with some
portions of hot chloroform. After distillation of
chloroform 0.98 g (85%) of 7-trifluormethylpyrido-
[1,2-α]benzimidazol (V) was obtained.
This study was carried out with the financial
support of the Ministry of Education and Science of
the Russian Federation (project no. 178) in context of
the basic part of the governmental contract for
Yaroslavl State University.
7-Nitropyrido[1,2-a]benzimidazole (II). mp 290–
REFERENCES
1
292°C. Н NMR spectrum (DMSO-d6), δ, ppm: 7.11 t
(1H, H2, J 7 Hz), 7.67 t (1H, H3, J 7.5 Hz), 7.78 d (1H,
H4, J 9 Hz), 8.20 d.d (1H, H8, J 2.0, 8.5 Hz), 8.50 d
(1H, H9, J 8,5 Hz), 8.64 d (1H, H6, J 1.5 Hz), 9.13 d
(1H, H1, J 7 Hz). Mass-spectrum, m/z (Irel., %): 213
(100), [M]+, 183 (4), 167 (91), 155 (14), 140 (28), 78
(12), 63 (11), 51 (9). Found, %: С 61.88; H 3.14; N
1. Begunov, R.S., Sokolov, A.A., and Shebunina, T.V.,
Russ. J. Org. Chem., 2013, vol. 49, p. 773.
2. Bard, A.J., Parsons, R., and Jordan, J., Standard
Potentials in Aqueous Solution, New York, 1985.
3. Preparativnaya Organicheskaya Khimiya, Vulfson, N.S.,
Ed., Moscow: Gos. Nauch.-Tekh. Izd. Khim. Lit., 1959.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 8 2014