Reductive cyclization of N-(2,4-dinitrophenyl)pyridinium chloride by tin(II) chloride

Full text of DOI:10.1023/B:COHC.0000048302.21953.6a

Chemistry of Heterocyclic Compounds, Vol. 40, No. 9, 2004
REDUCTIVE CYCLIZATION OF
N-(2,4-DINITROPHENYL)PYRIDINIUM
CHLORIDE BY TIN(II) CHLORIDE
R. S. Begunov and G. A. Ryzvanovich
Keywords: 7-aminopyrido[1,2-a][1,3]benzimidazole, 1,2-dipyrido[1,2-a][1,3]benzimidazol-7-yldiazene
oxide, 7-nitropyrido[1,2-a][1,3]benzimidazole, N-(2,4-dinitrophenyl)pyridinium chloride, reductive
cyclization.
Reactions of N-(2,4-dinitrophenyl)pyridinium chloride with various nucleophilic agents are widely used
in organic synthesis [1, 2].
We propose to use the reductive cyclization of N-(2,4-dinitrophenyl)pyridinium chloride (1) by
treatment with SnCl for synthesis of pyrido[1,2-a][1,3]benzimidazoles, which are potential biologically active
2
drugs [3, 4]. The reaction was conducted at a temperature of 20°C. Different end products are formed depending
on the process conditions, which is explained by the higher reactivity of the ortho nitro group compared with the
para nitro group in compound 1.
_
Cl
O
+
+
N
N
_
O
_
O
+
N
O
1
SnCl2
O
N
N
N
N +
N
NH2
_
N
N
N
O
N
3
N
2
N
O
4
When the reaction is conducted in a homogeneous medium with mole ratio 1:SnCl
2
1:3, reduction of
only the ortho nitro group and formation of 7-nitropyrido[1,2-a][1,3]benzimidazole (2) occur. Reduction of the
para nitro group was also observed when the amount of SnCl was doubled. As a result, we obtained
2
7
-aminopyrido[1,2-a][1,3]benzimidazole (3). Carrying out the cyclization in a heterogeneous medium with a
_
_________________________________________________________________________________________
P. G. Demidov Yaroslavl State University, Yaroslav 150000, Russia; e-mail: begunov@bio.uniyar.ac.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1407-1408, September, 2004. Original
article submitted February 6, 2004.
1
224
0009-3122/04/4009-1224©2004 Springer Science+Business Media, Inc.

ratio 1:SnCl
2
of 1:6 leads to accumulation in the reaction mass of products of incomplete reduction of the para
nitro group (nitroso- and hydroxylamino derivatives) and condensation of the latter to form 1,2-dipyrido[1,2-a]-
[
1,3]benzimidazol-7-yldiazene oxide (4).
Thus, by changing the reaction conditions for reaction of N-(2,4-dinitrophenyl)pyridinium chloride with
SnCl , we can obtain different pyrido[1,2-a][1,3]benzimidazoles.
2
7
-Nitropyrido[1,2-a][1,3]benzimidazole (2). Solutions of N-(2,4-dinitrophenyl)pyridinium chloride
(
5 g, 0.0178 mol) in ethyl alcohol (20 ml) and SnCl ·2H O (12 g, 0.0533 mol) in 3% hydrochloric acid (20 ml)
2
2
were added simultaneously to a three-necked flask with rapid stirring. After 10 min, the reaction mixture was
alkalinized with 25% aqueous solution of ammonia to pH 7-8 and extracted with several portions of chloroform
(
Σ = 200 ml). After distilling off chloroform, we obtained 3.44 g (91% yield) of 7-nitropyrido-
1
[1,2-a][1,3]benzimidazole; mp 290-292°C. H NMR spectrum (DMSO-d , 500 MHz), δ, ppm (J, Hz): 9.13 (1H,
6
d, J = 7, H-1); 8.64 (1H, d, J = 1.5, H-6); 8.50 (1H, d, J = 8.5, H-9); 8.20 (1H, dd, J = 8.5, J = 2, H-8); 7.78 (1H,
+
d, J = 9, H-4); 7.67 (1H, t, J = 7.5, H-3); 7.11 (1H, t, J = 7, H-2). Mass spectrum, m/z (I , %): 213 [M] (100),
rel
1
83 (4), 167 (91), 155 (14), 140 (28), 78 (12). Found, %: C 61.6; H 3.1; N 20.0. C H N O . Calculated, %:
11 7 3 2
C 62.0; H 3.3; N 19.7.
7
-Aminopyrido[1,2-a[[1,3]benzimidazole (3). Solution of N-(2,4-dinitrophenyl)pyridinium chloride
(
5 g, 0.0178 mol) in ethyl alcohol (20 ml) was added to solution of SnCl ·2H O (24 g, 0.107 mol) in 3%
2
2
hydrochloric acid (20 ml). After 10 min, the reaction mixture was alkalinized with 25% aqueous solution of
ammonia to pH 7-8 and extracted with several portions of chloroform (Σ = 200 ml). After distilling off
chloroform, we obtained 3.16 g (97% yield) of 7-aminopyrido[1,2-a][1,3]benzimidazole; mp 180-182°C.
1
H NMR spectrum (DMSO-d
6
, 500 MHz), δ, ppm (J, Hz): 8.82 (1H, d, J = 7, H-1); 7.9 (1H, d, J = 9.5, H-9);
7
.47 (1H, d, J = 10, H-4); 7.38 (1H, t, J = 7.5, H-3); 6.85 (1H, t, J = 7, H-2); 6.82 (1H, d, J = 1.5, H-6); 6.7 (1H,
+
dd, J = 10, J = 2, H-8); 5.1 (2H, s, NH ). Mass spectrum, m/z (I , %): 183 [M] (100), 166 (4), 155 (15), 78 (12).
2
rel
Found, %: C 71.9; H 4.5; N 23.3. C H N . Calculated, %: C 72.1; H 4.9; N 23.0.
1
1
9
3
1
,2-Dipyrido[1,2-a][1,3]benzimidazol-7-yldiazene Oxide (4). Solution of SnCl ·2H O (24 g,
2 2
0
.107 mol) in 3% hydrochloric acid (20 ml) was added to emulsion of N-(2,4-dinitrophenyl)pyridinium chloride
(
5 g, 0.0178 mol) in ethyl alcohol (10 ml). After 10 min, the reaction mixture was alkalinized with 25% aqueous
solution of ammonia to pH 7-8 and was extracted with several portions of chloroform (Σ = 200 ml). After
distilling off chloroform, we obtained 2.32 g (69% yield) of 1,2-dipyrido[1,2-a][1,3]-benzimidazol-7-yldiazene
1
oxide; mp >300°C. H NMR spectrum (DMSO-d , 500 MHz), δ, ppm (J, Hz): 9.13 (1H, d, J = 6.8, H-1); 9.05
6
(
1H, d, J = 6.8, H-1'); 8.88 (1H, d, J = 1.5, H-6); 8.73 (1H, d, J = 1.5, H-6'); 8.49 (1H, dd, J = 8.8, J = 1.5, H-8);
.42 (1H, dd, J = 8.8, J = 1.5, H-8'); 8.36 (1H, d, J = 8.8, H-9); 8.05 (1H, d, J = 8.8, H-9'); 7.75 (1H, d, J = 9.3,
H-4); 7.70 (1H, d, J = 9.5, H-4'); 7.65 (1H, t, J = 8, H-3); 7.56 (1H, t, J = 8.3, H-3'); 7.08 (1H, t, J = 7.5, H-2);
8
+
7
.04 (1H, t, J = 7.8, H-2'). Mass spectrum, m/z (I , %): 378 [M] (30), 197 (5), 181 (87), 167 (100), 155 (38), 78
rel
(
39), 44 (57). Found, %: C 70.6; H 3.6; N 22.7. C H N O. Calculated, %: C 69.84; H 3.7; N 22.2.
22 14 6
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