, 2006, 16(2), 119–120
Synthesis of pyrido[3',2':4,5]imidazo[1,2-a]pyridines by reductive cyclisation
of pyridinium salts
Roman S. Begunov,* Galina A. Ryzvanovich and Ol’ga I. Nozdracheva
Department of Biology and Ecology, P. G. Demidov Yaroslavl State University, 150000 Yaroslavl, Russian Federation.
Fax: +7 0852 79 7751; e-mail: begunov@bio.uniyar.ac.ru
DOI: 10.1070/MC2006v016n02ABEH002236
The reduction of N-(3-nitro-2-pyridyl)pyridinium chlorides by SnCl2 resulted in the formation of pyrido[3',2':4,5]imidazo[1,2-a]-
pyridines or N-(3-amino-2-pyridyl)-3,5-dimethylpyridinium chloride depending on the structure of the substrate.
The annealing of heterocycles with participation of the amino
Me
group formed by the reduction of nitroarenes1 is a convenient
Cl
N
Cl
1 N
N
N1'
R
procedure for the synthesis of heterocyclic compounds.
Previously,2,3 we described the preparation of substituted
benzo[4,5]imidazo[1,2-a]pyridines by the reductive cyclisation
of N-(2-nitro-4-R-phenyl)pyridinium salts. This methodology
can also be used for the synthesis of other heterocyclic systems.
In the present work we extended the intramolecular amina-
tion reaction to the synthesis of pyrido[3',2':4,5]imidazo[1,2-a]-
pyridines, biologically active compounds isolated from natu-
rally occurring raw materials.4,5 These condensed heterocyclic
arenes are synthesised from inaccessible 2-aminoimidazo[1,2-a]-
pyridine.6,7
We experimentally found that, depending on the structure of
the substrate, the interaction of N-(3-nitro-2-pyridyl)pyridinium
salts 1a–d with tin(II) chloride resulted in the formation of various
substances: pyrido[3',2':4,5]imidazo[1,2-a]pyridines 2a–c, which
are the products of reductive amination of 1a–c, respectively,
and N-(3-amino-2-pyridyl)-3,5-dimethylpyridinium chloride 3,
which is the product of the reduction of 1d.† The structures of
the prepared compounds were determined by 1H NMR spectro-
scopy, mass spectrometry and elemental analysis.‡
It was found that steric hindrances have no effect on the
reductive amination process. Thus, in the reduction of N-(3-nitro-
2-pyridyl)-3-methylpyridinium chloride, intramolecular amina-
tion occurred at the α-carbon atom in the ortho position to the
methyl group. As a result, 6-methylpyrido[3',2':4,5]imidazo-
[1,2-a]pyridine 2b was isolated from the reaction mass.
The absence of cyclisation in the case of 1d and, con-
sequently, the formation of product 3 were explained by the
presence of two strong electron-releasing substituents at the
ortho and para positions to the electrophilic reaction centre in
reduced substrate 1d. As a result of this, its reactivity towards a
nucleophile (the amino group formed in the course of reduction)
dramatically decreased.
5
6
2
6'
5'
4'
4
2'
3
R1
3'
O2N
1a–d
Me
H2N
3
1a R = R1 = H
1b R = 3-Me, R1 = H
1c R = 4-Me, R1 = H
1d R = 3-Me, R1 = 5-Me
R
N
9
6
1
N10
2
3
8
7
2a R = R1 = H
2b R = 6-Me, R1 = H
2c R = 7-Me, R1 = H
5
4
N
R1
2a–c
The 1H NMR spectra were recorded on a Bruker DRX500 spectrometer
‡
(500 MHz) in [2H6]DMSO using TMS as an internal standard. The mass
spectra were measured on an MX-1310 instrument. Elemental analysis
was performed on a CHN-1 analyser.
2a: mp 120–122 °C (lit.,6 130 °C). 1H NMR, d: 8.95 (d, 1H, H-9,
J 8.5 Hz), 8.51 (d, 1H, H-2, J 7.0 Hz), 8.24 (d, 1H, H-4, J 10.0 Hz),
7.65–7.75 (m, 2H, H-6 and H-7), 7.59 (m, 1H, H-3), 7.08 (t, 1H, H-8,
J 9.5 Hz). MS, m/z (%): 169 (100) [M]+, 142 (7), 78 (28), 51 (12). Found
(%): C, 70.8; H, 4.1; N, 25.0. Calc. for C10H7N3 (%): C, 71.0; H, 4.2;
N, 24.8.
2b: mp 111–113 °C (lit.,6 117 °C). 1H NMR, d: 8.59 (dd, 1H, H-9, J 8.0
and 1.5 Hz), 8.42 (d, 1H, H-2, J 7.0 Hz), 8.20 (d, 1H, H-4, J 10.0 Hz),
7.30–7.45 (m, 2H, H-3 and H-7), 6.83 (t, 1H, H-8, J 9.5 Hz), 2.61 (s,
3H, Me). MS, m/z (%): 183 (100) [M]+, 169 (8), 157 (26), 78 (31), 51
(10). Found (%): C, 71.7; H, 5.1; N, 23.3. Calc. for C11H9N3 (%): C,
72.1; H, 4.9; N, 23.0.
2c: mp 135–137 °C (lit.,6 148 °C). H NMR, d: 8.61 (d, 1H, H-9, J
1
7.5 Hz), 8.41 (d, 1H, H-2, J 7.0 Hz), 8.20 (d, 1H, H-4, J 9.5 Hz), 7.45
(m, 1H, H-3), 7.23 (s, 1H, H-6), 6.81 (d, 1H, H-8, J 8.0 Hz), 2.46 (s, 3H,
Me). MS, m/z (%): 184 (19) [M]+ + 1, 183 (100) [M]+, 157 (31), 78 (37),
65 (8), 51 (13). Found (%): C, 71.7; H, 5.1; N, 23.1. Calc. for C11H9N3
(%): C, 72.1; H, 4.9; N, 23.0.
†
Solutions of compounds 1a–d (0.01 mol) in 20 ml of ethanol were
1
added to a solution of 0.03 mol of SnCl2·2H2O in 15 ml of 3% hydro-
chloric acid under stirring. After 10 min, the reaction mixture was
alkalised with a 25% aqueous ammonia solution to pH 7–8 and extracted
with several portions of chloroform (150 ml). After the distillation of
chloroform, the yields of compounds were 91% for 2a, 82% for 2b, 84%
for 2c and 87% for 3.
3: mp 204–206 °C. H NMR, d: 9.05 (s, 2H, H-2 and H-6), 8.50 (s,
1H, H-4), 7.85 (d, 1H, H-6', J 6.5 Hz), 7.44–7.50 (m, 2H, H-4' and H-5'),
6.05 (s, 2H, NH2), 2.51 (s, 6H, Me). MS, m/z (%): 200 (50) [M]+, 198
(100), 184 (34), 120 (39), 108 (17), 77 (10), 36 (26). Found (%): C, 60.21;
H, 6.24; Cl, 15.39; N, 18.01. Calc. for C12H14ClN3 (%): C, 61.15; H, 5.95;
Cl, 15.07; N, 17.83.
Mendeleev Commun. 2006 119
Begunov, Roman S.
