1496 Kushwaha et al.
Asian J. Chem.
In recent years several improved conditions have been
reported [15]. Lei et al. [16] published the results on synthesis
of imidazo[1,2-a]pyridines using silver carbonate in dioxane
at 110 °C, with moderate yields [16] and Cai et al. [17] reported
synthesis of imidazo[1,2-a]pyridines using I2/CuO in methanol.
Though these methods are useful, but use of water as solvent
for organic reactions is the most interesting and attracted step
because of its economic and environmental friendly nature.
2-(tert-Butyl)imidazo[1,2-a]pyridine (3a): m.p.: 81-82
°C (80 °C) [1]; 1H NMR (400 MHz, DMSO-d6): δ 8.51 (d, J =
6.8 Hz, 1H), 7.77 (s, 1H), 7.55 (d, J = 9.2 Hz, 1H), 7.34-7.30
(m, 1H), 6.96-6.93 (m, 1H), 1.33 (s, 9H). MS, m/z: 175.04
(M+H+).
2-(tert-Butyl)-7-methylimidazo[1,2-a]pyridine (3b):
m.p.: 94-96 °C (lit. 96-98 °C) [2]. 1H NMR (400 MHz, CDCl3):
δ 7.90 (d, J = 6.8 Hz, 1H), 7.32 (s, 1H), 7.24 (s, 1H), 6.53 (d,
J = 6.8 Hz, 1H), 2.35 (s, 3H), 1.38 (s, 9H). 13C NMR (100
MHz, CDCl3): δ 156.97, 145.46, 134.59, 124.60, 115.64,
114.16, 106.04, 32.22, 30.22, 21.32. MS, m/z: 189.13 (M+H+).
2-(tert-Butyl)-7-chloroimidazo[1,2-a]pyridine (3c):
m.p.: 136-138 °C; 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J =
7.2 Hz, 1H), 7.56 (s, 1H), 7.31 (s, 1H), 6.70 (dd, J = 6.8 Hz, J
= 1.6 Hz, 1H), 1.38 (s, 9H). 13C NMR (100 MHz, CDCl3): δ
158.36, 144.78, 130.17, 125.58, 116.12, 113.23, 106.95, 32.35,
30.11. MS, m/z: 209.0 (M+H+).
EXPERIMENTAL
Unless otherwise noted all reactions were carried out at
room temperature. Solvents and reagents were purchased at
the highest commercial quality and used without further drying
and purification respectively. Reactions were monitored by
thin-layer chromatography (TLC) analysis using TLC
aluminum sheets silica gel 60 F254.
1H NMR and 13C NMR spectra were recorded in CDCl3
and DMSO-d6 at 400 MHz. The chemical shifts are reported
in ppm downfield to TMS (δ = 0) for 1H NMR and 13C NMR.
The water was prepared from tap water after sand filter-carbon
filter-ionic exchange resin-reverse osmosis-UV-micro filter by
passing through pre-packed cartridges.
General procedure and representative analytical data
of imidazo[1,2-]pyridines:A solution of 2-aminopyridine (1
eq) and α-bromoketone (1 eq) in water was stirred at room tempe-
rature for 8 h (Scheme-II). For some insoluble 2-amino-
pyridine, it was dissolved by heating up to 60-70 °C and then
added α-bromoketones. The reactions were performed at room
temperature for 8 h (Scheme-III). After completion of the
reaction, the reaction mixture was basified (pH = 9) with 10
% NaOH aqueous solution. In many cases product was
precipitated out, so it was filtered to get pure compound. If
product was not solid, it was extracted with pentane to get
product in pure form.
1
2-Ethylimidazo[1,2-a]pyridine (3d): H NMR (400
MHz, CDCl3): δ 8.03 (d, J = 6.8 Hz, 1H), 7.52 (d, J = 9.2 Hz,
1H), 7.33 (s, 1H), 7.12-7.08 (m, 1H), 6.73-6.71 (m, 1H), 2.82
(q, J = 7.6 Hz, 2H), 1.34 (t, J = 7.6 Hz, 3H). MS, m/z: 146.99
(M+H+).
2-Ethyl-7-methylimidazo[1,2-a]pyridine (3e): 1H NMR
(400 MHz, CDCl3): δ 7.90 (d, J = 6.8 Hz, 1H), 7.25 (d, J =
8.0 Hz, 2H), 6.54 (d, J = 6.8 Hz, 1H), 2.79 (q, J = 7.6 Hz,
2H), 2.36 (s, 3H), 1.33 (t, J = 7.6 Hz, 3H). MS, m/z: 161.07
(M+H+).
7-Chloro-2-ethylimidazo[1,2-a]pyridine (3f): 1H NMR
(400 MHz, CDCl3): δ 7.95 (d, J = 7.2 Hz, 1H), 7.51 (s, 1H),
7.31 (s, 1H), 6.71 (dd, J = 7.2 Hz, J = 2.0 Hz 1H), 2.80 (q, J
= 7.6 Hz, 2H), 1.33 (t, J = 7.6 Hz, 3H). MS, m/z: 181.09
(M+H+).
1
2-Cyclohexylimidazo[1,2-a]pyridine (3g): H NMR
(400 MHz, DMSO-d6): δ =8.43 (d, J = 6.8 Hz, 1H), 7.64 (s,
1H), 7.43 (d, J = 8.8 Hz, 1H), 7.16-7.12 (m, 1H), 6.81-6.78
(m, 1H), 2.65 (bs, 1H), 2.02-1.99 (m, 2H), 1.78-1.67 (m, 3H),
1.58-1.32 (m, 4H), 1.27-1.23 (m, 1H). MS, m/z: 201.20
(M+H+).
R
H2O
rt
O
R
N
2-Cyclohexyl-7-methylimidazo[1,2-a]pyridine (3h): 1H
NMR (400 MHz, DMSO-d6): δ 8.30 (d, J = 6.8 Hz, 1H), 7.53
(s, 1H), 7.20 (s, 1H), 6.64 (d, J = 6.8 Hz, 1H), 2.61 (bs, 1H),
2.31 (s, 3H), 2.06-2.01 (m, 2H), 1.77-1.61 (m, 3H),1.45-1.31
(m, 4H), 1.08-1.00 (m, 1H). MS, m/z: 215.21 (M+H+).
7-Chloro-2-cyclohexylimidazo[1,2-a]pyridine (3i): 1H
NMR (400 MHz, CDCl3): δ 7.95 (d, J = 7.2 Hz, 1H), 7.52 (s,
1H), 7.28 (s, 1H), 6.71 (d, J = 7.2 Hz, 1H), 2.74-2.72 (m, 1H),
2.12-2.09 (m, 2H), 1.85-1.82 (m, 2H), 1.76-1.30 (m, 1H), 1.52-
1.37 (m, 4H), 1.35-1.26 (m, 1H). MS, m/z: 235.11 (M+H+).
Br
R1
R
1
N
N
NH2
1
2
3
R= H, Me, Cl
R1= Et, t-Bu, Ph,Cyclohexyl
Scheme-II
Synthesis of zolimidine: The suspension of 2-bromo-1-
(4-(methylsulfonyl)phenyl)ethanone (1 eq) and pyridin-2-
amine (3 eq) in water was stirred at room temperature for 18 h
(Scheme-IV). The heterogeneous reaction mixture was directly
filtered and washed with water, followed by diethyl ether to
get yellow solid zolimidine (91 %).
1
2-Phenylimidazo[1,2-a]pyridine (3j): H NMR (400
MHz, CDCl3): δ 8.13 (d, J = 6.8 Hz, 1H), 7.98-7.96 (m, 2H),
7.87 (s, 1H), 7.64 (d, J = 9.2 Hz, 1H), 7.46-7.42 (m, 2H),
7.35-7.31 (m, 1H), 7.19-7.15 (m, 1H), 6.80-6.77 (m, 1H). MS,
m/z: 195.00 (M+H+).
R
4
O
N
3
H2O
rt
5
R
1
Br
7-Methyl-2-phenylimidazo[1,2-a]pyridine (3k): H
N
N
NH2
NMR (400 MHz, CDCl3): δ 7.99 (d, J = 6.8 Hz, 1H), 7.93 (d,
J = 7.6 Hz, 2H), 7.78 (s, 1H), 7.44-7.30 (m, 3H), 7.26 (s, 1H),
6.6 (d, J = 6.8 Hz, 1H), 2.39 (s, 3H). MS, m/z: 209.08 (M+H+).
4
5
6
R=4-bromo,3-cyano, 3-chloro,5-chloro,5-bromo
Scheme-III: Reaction of different substituted 2 amino pyridine and 1-
1
7-Chloro-2-phenylimidazo[1,2-a]pyridine (3l): H
bromo-3,3-dimethylbutan-2-one
NMR (400 MHz, CDCl3): δ 8.05 (d, J = 7.2 Hz, 1H), 7.93 (d,