One-pot multicomponent synthesis of novel substituted imidazo[1,2-a]pyridine incorporated thiazolyl coumarins and their antimicrobial activity

Article abstract of DOI:10.1002/jhet.2116

A series of novel substituted imidazo[1,2-a]pyridine incorporated thiazolyl coumarin derivatives (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m, 4n, 4o, 4p, 4q, 4r, 4s, 4t) were synthesized in good yields via one-pot multicomponent condensation of su

Full text of DOI:10.1002/jhet.2116

Month 2014
One-Pot Multicomponent Synthesis of Novel Substituted Imidazo[1,2-a]
Pyridine Incorporated Thiazolyl Coumarins and their Antimicrobial Activity
Rajitha Gali, Janardhan Banothu, and Rajitha Bavantula*
Department of Chemistry, National Institute of Technology, Warangal, Andhra Pradesh, India
*
E-mail: rajitabhargavi@yahoo.com
Received May 23, 2013
DOI 10.1002/jhet.2116
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel substituted imidazo[1,2-a]pyridine incorporated thiazolyl coumarin derivatives (4a–t)
were synthesized in good yields via one-pot multicomponent condensation of substituted imidazo[1,2-a]pyr-
idine-3-carbaldehyde (3a–e), thiosemicarbazide (2), and substituted 3-(2-bromoacetyl)-2H-chromen-2-ones
(1a–d)/2-(2-bromoacetyl)-3H-benzo[f]chromen-3-one (1e) in refluxing ethanol with catalytic amount of
acetic acid. All the synthesized compounds (4a–t) have been characterized by IR, NMR, and mass spectral
studies as well as elemental analyses and evaluated for their in vitro antimicrobial activity against different
bacterial and fungal strains. All the compounds displayed moderate antibacterial activity with minimum
inhibitory concentration 150 μg/mL, but none of the compounds have shown any antifungal activity.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
our studies on several new heterocycles [24], we attempted
to design a moiety embodied imidazo[1,2-a]pyridine-3-
carbaldehyde, thiazole, and coumarins in a single frame work
and evaluated for their in vitro antimicrobial activity.
Multicomponent reactions have emerged as an efficient
and powerful tool in modern synthetic organic chemistry
in which three or more different starting materials react to
give a final product in a one-pot procedure [1]. Such reac-
tions offer a wide range of possibilities for the efficient
construction of highly complex molecules in a single step;
these reactions are the best tools because of their produc-
tivity, simple procedures, and facile execution [2].
RESULTS AND DISCUSSION
Fused imidazo[1,2-a]pyridines-3-carbaldehydes (3a–e)
and substituted 3-(2-bromoacetyl)-2H-chromen-2-ones
(1a–e) were synthesized according to the literature methods
[7,25]. The targeted compounds (4a–t) were prepared via
multicomponent condensation of substituted imidazo[1,2-a]
pyridine-3-carbaldehydes (3a–e), thiosemicarbazide (2),
and 3-(2-bromoacetyl)-2H-chromen-2-ones/2-(2-bromo-
acetyl)-3H-benzo[f]chromen-3-one (1a–e) in absolute
ethanol with catalytic amount of acetic acid under reflux
condition with good yields. The synthetic pathway was
outlined in Scheme 1.
A large number of nitrogen bridgehead-fused heterocycles
containing an imidazole ring have been reported in the liter-
ature as important pharmacophores [3–5]. The most widely
used heterocyclic system from this group is imidazo[1,2-a]
pyridine. Compounds derived from imidazo[1,2-a]pyridine
were found to possess anticancer [6], anticonvulsant [7],
anti-inflammatory [8], antimicrobial [9], antiviral [10], and
anticoccodial [11] properties. These also act as inhibitors of
hepatitis C virus replication [12], inhibitors of insulin-like
growth factor-1 receptor [13], as well as melatonin receptor
ligands [14] and DNA-directed alkylating agents [15]. These
have high affinity towards human β-amyloid plaques [16].
They are also reported as prominent drugs such as Zolpidem,
Olprinone, and Zolimidine used for the treatment of insom-
nia, heart failure, and peptic ulcer, respectively [17,3,4].
On the other hand, thiazole [5], coumarin [18], and
thiazolylcoumarin [19–23] derivatives displayed signifi-
cant biological properties such as antitumor, cytotoxic, anti-
inflammatory, anticoagulant, antioxidant, antifungal,
antitubercular, anticonvulsant, antimicrobial, antiviral,
neuroprotective and diuretic activities. In continuation of
To find out the optimal conditions, initially, a model
reaction was carried out with 3-(2-bromoacetyl)-2H-
chromen-2-one (1a), thiosemicarbazide (2), and 2-(4-
bromophenyl)imidazo[1,2-a]pyridine-3-carbaldehyde (3a) in
absolute ethanol and ethanol with catalytic amount of acetic
acid at solvent refluxing temperature. In absolute ethanol, we
obtained only 75% yield after 12 h, but we obtained 90% yield
in ethanol with catalytic amount of acetic acid within 2 h.
In the IR spectrum of the compound, the appearance of a
À1
À1
broad band at 3400 cm for NH, 1719 cm for C═O of
À1
lactone, and a medium band at 1605 cm for C═N group;
and in H NMR, the presence of a singlet at 8.58 ppm
1
©
2014 HeteroCorporation

R. Gali, J. Banothu, and R. Bavantula
Vol 000
Scheme 1. Synthesis of substituted 3-(2-{N′-[2-aryl-imidazo[1,2-a]pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one derivatives.
(
coumarin 4th proton) and 12.5 ppm (NH) indicated the
uncorrected. The progress of the reactions as well as purity of the
compounds was monitored by thin layer chromatography with
F254 silica-gel precoated sheets (Merck, Darmstadt, Germany)
using hexane/ethyl acetate 7/3 as eluent. Products were charac-
terized by spectral data (IR, NMR, and mass). IR spectra were
recorded on PerkinElmer 100S spectrophotometer (Perkin-Elmer
Ltd., United Kingdom) using KBr pellet. NMR spectra were
recorded on Bruker 400MHz spectrometer (Bruker Corporation
formation of product 4a. Molecular ion peak from the mass
spectrum further confirmed the formation of product.
After optimizing the reaction conditions, we examined the
scope and generality of this method by extending to other
substrates with different imidazo[1,2-a]pyridine-3-carbalde-
hydes (3a–e) and 3-(2-bromoacetyl)-2H-chromen-2-ones
Ltd., Germany) using DMSO-d as solvent and TMS as internal
(1a–d)/2-(2-bromoacetyl)-3H-benzo[f]chromen-3-one (1e).
6
standard. Elemental analysis was performed on a Carlo Erba modal
EA1108 (Triad Scientific Ltd., NJ), and mass spectra were recorded
on a Jeol JMSD-300 spectrometer (Jeol Ltd., Tokyo, Japan).
General procedure for the synthesis of (4a–q). A mixture
of substituted imidazo[1,2-a]pyridine-3-carbaldehyde (3a–e,
All the products were obtained in good yields (80–90%)
within 2–4 h, and the results are postulated in Table 1. All
the synthesized compounds were characterized by their
analytical and spectral studies.
1
mmol), thiosemicarbazide (1 mmol) and 3-(2-bromo-acetyl)-2H-
chromen-2-ones (1a–d, 1 mmol) were taken in 10 mL of
ethanol, to this a catalytic amount of acetic acid was added and
refluxed for 2–4 h. The progress of the reaction was monitored
by TLC. The solid separated out was filtered, washed with
ethanol, and recrystallized from acetic acid to afford the pure
product in good yields.
CONCLUSION
In conclusion, we have synthesized some new derivatives
of imidazo[1,2-a]pyridine ring incorporated thiazolylcoumarins
via multicomponet condensation of substituted imidazo[1,2-a]
pyridine-3-carbaldehyde (3a–e), thiosemicarbazide (2) and 3-
2-bromoacetyl)-2H-chromen-2-one (1a–d)/2-(2-bromoacetyl)-
H-benzo[f]chromen-3-one (1e) in ethanol with catalytic
amount of acetic acid under reflux condition for 2–4 h. All the
compounds were evaluated for their in vitro antimicrobial activ-
ity. Antimicrobial results revealed that all the compounds
displayed moderate antibacterial activity at MIC 150 μg/mL
against all the tested bacterial strains. None of the compounds
displayed antifungal activity against all the tested fungal strains.
3
-(2-{N′-[2-(4-Bromo-phenyl)-imidazo[1,2-a]pyridin-3-
(
3
ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one (4a).
Light
À1
green solid; mp: 233–235°C; IR (KBr, cm ) υmax: 3400,
1
1719, 1605, 1578, 1425, 1008, 757, 649, 510; H NMR
(
(
7
400 MHz, DMSO-d6):
d, J = 8.0 Hz, 1H), 7.63–7.68 (m, 3H), 7.8 (d, J = 8.4 Hz, 2H),
.89–7.99 (m, 4H), 8.04 (d, J = 9.2 Hz, 1H), 8.53 (s, 1H), 8.58
s, 1H), 9.54 (d, J = 6.8 Hz, 1H), 12.5 (s, 1H); MS (ESI): m/z
δ 7.41 (d, J = 8.0 Hz,1H), 7.46
(
5
2
43 (M + H); Anal. Calcd for C H BrN O S: C, 57.57; H,
26 16 5 2
.97; N, 12.91; Found: C, 57.51; H, 3.04; N, 12.81.
-(2-{N′-[2-(4-Chloro-phenyl)-imidazo[1,2-a]pyridin-3-
3
ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one (4b).
Light
À1
green solid; mp: 260–262 °C; IR (KBr, cm ) υmax: 3400, 3137,
EXPERIMENTAL
1
1
720, 1604, 1578, 1426, 1094, 757, 581; H NMR (400MHz,
DMSO-d ): δ 7.39–7.48 (m, 3H), 7.62–7.68 (m, 5H), 7.83 (d,
J=8.8Hz, 3H), 7.89 (d, J= 8.4 Hz, 2H), 8.58 (s, 1H), 9.45 (d,
Melting points were determined in open capillaries using Stuart
SMP30 apparatus (Bibby Scientific Ltd., United Kingdom) and are
6
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Imidazo[1,2-a]pyridine Incorporated Thiazolyl Coumarins
Table 1
Synthesis of substituted 3-(2-{N′-[2-aryl-imidazo[1,2-a]pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one derivatives.
a
b
a
b
Entry
Product
Time (h)
Yield (%)
Entry
Product
Time (h)
Yield (%)
4a
4b
4c
2
90
89
87
4k
3
89
90
87
2
2
4l
3
4
4m
4
4
d
e
3
2
88
89
4n
4o
4
4
86
88
4
4
f
3
3
87
85
4p
4q
4
4
84
87
g
4
4
h
3
3
84
88
4r
4s
2
2
85
83
i
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Gali, J. Banothu, and R. Bavantula
Vol 000
Table I
(Continued)
a
b
a
b
Entry
Product
Time (h)
Yield (%)
Entry
Product
Time (h)
Yield (%)
4j
4
87
4t
2
86
a
Reaction conditions: Substituted imidazo[1,2-a]pyridine-3-carbaldehydes (1 mmol), thiosemicarbazide (1 mmol), substituted 3-(2-bromoacetyl)-2H-
chromen-2-ones (1 mmol), ethanol, catalytic amount of acetic acid, reflux.
b
Isolated yields.
À1
J= 6.8 Hz, 1H), 12.25 (s, 1H); MS (ESI): m/z 498 (M + H); Anal. Calcd
solid; mp: 293–295°C; IR (KBr, cm ) υmax: 3379, 3302, 1633, 1731,
1
for C26
.30; N, 14.17.
-(2-{(N′-[2-(4-Nitro-phenyl)-imidazo[1,2-a]pyridin-3-
H
16ClN
5
O
2
S: C, 62.71; H, 3.24; N, 14.06. Found: C, 62.60; H,
1589, 1547, 1513, 1345, 1247, 1104, 753; H NMR (400MHz,
DMSO-d ): δ 7.19 (t, J=6.4Hz, 1H), 7.61 (t, J= 7.6 Hz, 2H), 7.83 (d,
J= 9.2 Hz, 1H), 7.94 (s, 1H), 8.06 (d, J=8.4Hz, 3H), 8.35 (d,
3
6
3
ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one (4c). Orange
J= 8.8 Hz, 4H), 8.75 (s, 1H), 9.6 (d, J=6.4Hz, 1H), 11.38 (s, 1H);
À1
solid; mp: 275–277 °C; IR (KBr, cm ) υmax: 3379, 3136, 1720, 1630,
6 4
MS (ESI): m/z 543 (M + H); Anal. Calcd for C26H15ClN O S: C,
1
1
600, 1567, 1519, 1347, 752, 689; H NMR (400 MHz, DMSO-d
6
): δ
57.51; H, 2.78; N, 15.48; Found: C, 57.36; H, 2.85; N, 15.40.
7
2
8
5
.28 (t, J=6.8Hz, 2H), 7.72 (t, J=7.2Hz, 1H), 7.89 (d, J=9.2Hz,
H), 7.99 (s, 1H), 8.06 (d, J= 8.8 Hz, 3H), 8.4 (d, J=8.8Hz, 4H),
.72 (s, 1H), 9.66 (d, J= 6.8 Hz, 1H), 11.43 (s, 1H); MS (ESI): m/z
09 (M + H); Anal. Calcd for C26 S: C, 61.41; H, 3.17; N,
6.53; Found: C, 61.62; H, 3.01; N, 16.78.
-(2-{N′-[2-(4-Bromo-phenyl)-7-methyl-imidazo[1,2-a]
3-(2-{N′-[2-(4-Bromo-phenyl)-imidazo[1,2-a]pyridin-3-
ylmethylene]-hydrazino}-thiazol-4-yl)-6-chloro-chromen-2-one
À1
(4h).
Dark green solid; mp: 281–283°C; IR (KBr, cm
)
H
16
N
6
O
4
υmax: 3384, 3142, 1731, 1708, 1564, 1374, 1244, 1109, 1080,
1
1
1008, 780, 647, 647, 564; H NMR (400MHz, DMSO-d ): δ
6
3
7.37–7.5 (m, 2H), 7.63–7.67 (m, 2H), 7.74–7.81 (m, 4H), 7.85–
8.05 (m, 3H), 8.52 (s, 1H), 8.59 (s, 1H), 9.42(d, J = 6.8Hz, 1H),
12.25 (s, 1H); MS (ESI): m/z 577 (M + H); Anal. Calcd for
pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-
one (4d). Dark green solid; mp: 269–271°C; IR (KBr, cm ) υmax
À1
:
1
3400, 3135, 1718, 1560, 1582, 1434, 779, 603, 514; H NMR
C
26 5 2
H15BrClN O S: C, 54.13; H, 2.62; N, 12.14; Found: 54.02; H,
(
400 MHz, DMSO-d ): δ 2.36 (s, 3H), 7.35 (s, 1H), 7.68–7.82
2.73; N, 12.30.
6
(
(
m, 7H), 8.07–8.20 (m, 3H), 8.33 (s, 1H), 8.51 (s, 1H), 9.3
d, J= 6.8 Hz, 1H), 12.5 (s, 1H); MS (ESI): m/z 557 (M + H); Anal.
Calcd for C27 18BrN S: C, 58.28; H, 3.26; N, 12.59; Found: C,
8.36; H, 3.15; N, 12.67.
-(2-{N′-[2-(4-Methoxy-phenyl)-imidazo[1,2-a]pyridin-3-
6-Chloro-3-(2-{N′-[2-(4-methoxy-phenyl)-imidazo[1,2-a]
pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one
À1
H
5
O
2
(4i).
Dark green solid; mp: 297–299°C; IR (KBr, cm1 ) υmax
:
5
3380, 3259, 1730, 1710, 1570, 1234, 1104, 1074, 753; H NMR
3
(400 MHz, DMSO-d ): δ 3.89 (s, 3H), 7.21 (d, J= 8.8 Hz, 2H),
6
ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one (4e). Dark
7.46 (d, J= 8.8 Hz, 1H), 7.61 (s, 2H), 7.73 (d, J= 8.4 Hz, 2H),
7.86–8.01 (m, 4H), 8.47 (s, 1H), 8.52 (s, 1H), 9.47 (d, J=6.8Hz,
1H), 12.39 (s, 1H); MS (ESI): m/z 528 (M + H); Anal. Calcd for
À1
green solid; mp: 236–238°C; IR (KBr, cm ) υmax: 3379, 3143,
1
1
720, 1698, 1606, 1564, 1177, 1093, 614; H NMR (400 MHz,
6
DMSO-d ): δ 3.88 (s, 3H), 7.18 (d, J = 8.0 Hz, 2H), 7.38–7.47
27 5 3
C H18ClN O S: C, 61.42; H, 3.44; N, 13.26; Found: C, 61.59;
(
4
m, 3H), 7.61–7.65 (m, 1H), 7.74 (d, J = 8.8 Hz, 3H), 7.84–7.9 (m,
H, 3.48; N, 13.17.
3-(2-{N′-[2-(4-Bromo-phenyl)-7-methyl-imidazo[1,2-a]pyridin-
3-ylmethylene]-hydrazino}-thiazol-4-yl)-6-chloro-chromen-2-one
13
H), 8.57 (s, 1H), 9.47 (d, J = 7.2Hz, 1H), 12.3 (s, 1H); C NMR
): 55.31, 110.0, 114.2, 114.7, 115.8, 116.9,
(100 MHz, DMSO- d
6
À1
1
1
19.1, 120.47, 124.6, 125.6, 127.3, 128.8, 130.3, 131.6, 134.1,
38.3, 144.22, 145.8, 148.6, 152.3, 158.7, 159.7, 167.2, 171.9;
(4j). Light green solid; mp: 272–274°C; IR (KBr, cm1 ) υmax
:
3384, 3132, 1736, 1583, 1378, 1247, 1078, 715, 596; H NMR
MS (ESI): m/z 494 (M + H); Anal. Calcd for C H N O S: C,
(400 MHz, DMSO-d ): δ 2.50 (s, 3H), 7.24 (d, J = 6.0 Hz, 1H),
2
7
19
5
3
6
6
5.71; H, 3.88; N, 14.19; Found: C, 65.52; H, 3.98; N, 14.29.
-Chloro-3-(2-{N′-[2-(4-chloro-phenyl)-imidazo[1,2-a]
7.47 (d, J = 8.8 Hz, 1H), 7.63 (s, 2H), 7.72–7.79 (m, 4H), 7.85 (s,
1H), 8.02 (s, 1H), 8.50 (s, 1H), 8.54 (s, 1H), 9.28 (d, J = 6.8 Hz,
1H), 12.19 (s, 1H); MS (ESI): m/z 591 (M+ H); Anal. Calcd for
C H BrClN O S: C, 54.88; H, 2.90; N, 11.85; Found: C,
6
pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one
À1
(
3
4f). Dark green solid; mp: 279–281°C; IR (KBr, cm1 ) υmax
:
27
17
5 2
395, 3141, 1708, 1566, 1244, 1093, 1079, 754, 564; H NMR
54.63; H, 3.02; N, 11.90.
(
(
(
400 MHz, DMSO-d ): δ 7.37 (t, J = 6.8 Hz, 1H), 7.48–7.67
m, 5H), 7.81–8.05 (m, 5H), 8.52 (s, 1H), 8.6 (s, 1H), 9.41
d, J = 6.8 Hz, 1H), 12.25 (s, 1H); MS (ESI): m/z 533 (M + H);
6
6-Bromo-3-(2-{N′-[2-(4-bromo-phenyl)-imidazo[1,2-a]
pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one
À1
(4k). Dark green solid; mp: 300–302°C; IR (KBr, cm ) υmax
:
Anal. Calcd for C H Cl N O S: C, 58.65; H, 2.84; N, 13.15.
3384, 2919, 1726, 1563, 1244, 1008, 824, 1008, 824, 756, 649,
26
15
2 5 2
1
Found: 58.80; H, 2.93; N, 13.01.
-Chloro-3-(2-{N′-[2-(4-nitro-phenyl)-imidazo[1,2-a]pyridin-
-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one (4g). Brown
584, 509; H NMR (400 MHz, DMSO-d ): δ 7.42 (d, J=7.2Hz,
6
6
3H), 7.54–7.86 (m, 7H), 8.14 (d, J= 9.6 Hz, 1H), 8.5 (s, 1H), 8.57
(s, 1H), 9.41 (d, J= 6.8 Hz, 1H), 12.28 (s, 1H); MS (ESI): m/z 622
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Imidazo[1,2-a]pyridine Incorporated Thiazolyl Coumarins
(
1
M + H); Anal. Calcd for C H Br N O S: C, 50.26; H, 2.43; N,
1.27; Found: C, 50.16; H, 2.55; N, 11.31.
1 mmol), thiosemicarbazide, (1 mmol) and 2-(2-bromoacetyl)-3H-
benzo[f]chromen-3-one (1e, 1 mmol) were taken in 10mL of
ethanol, to this catalytic amount of acetic acid was added and
refluxed for 2 h. The progress of the reaction was monitored by
TLC, the solid separated out was filtered, washed with ethanol
and recrystallized from acetic acid to afford the pure product in
good yields.
26
15
2 5 2
6
-Bromo-3-(2-{N′-[2-(4-methoxy-phenyl)-imidazo[1,2-a]
pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one
(
3
À1
4l). Dark green solid; mp. 256–258°C; IR (KBr, cm1 ) υmax
:
380, 3024, 1730, 1580, 1025, 780, 649, 589, 504; H NMR
(
400 MHz, DMSO-d ): δ 3.89 (s, 3H), 7.16–7.23 (m, 2H), 7.39
6
(
d, J = 10.4 Hz, 2H), 7.49–7.75 (m, 3H), 7.86 (s, 2H), 7.90 (t,
2-(2-{N′-[2-(4-Bromo-phenyl)-imidazo[1,2-a]pyridin-3-
J = 9.6 Hz, 1H), 8.13 (s, 1H), 8.26 (s, 1H), 8.47–9.5 (m, 2H),
2.4 (s, 1H); MS (ESI): m/z 573 (M + H); Anal. Calcd for
C H BrN O S: C, 56.65; H, 3.17; N, 12.23; Found: C, 56.42;
ylmethylene]-hydrazino}-thiazol-4-yl)-benzo[f]chromen-2-one
À1
1
(4r). Yellowish brown solid; mp: 264–266°C; IR (KBr, cm
)
υ
max: 3307, 3054, 1720, 1578, 1405, 1245, 1085, 742, 602, 506;
27
18
5 3
1
H, 3.28; N, 12.33.
-Bromo-3-(2-{N′-[2-(4-bromo-phenyl)-7-methyl-imidazo
6
H NMR (400MHz, DMSO-d ): δ 7.33–7.67 (m, 4H), 7.77–7.89
6
(m, 7H), 8.10 (d, J = 8.0 Hz, 1H), 8.22 (d, J =9.6 Hz, 1H), 8.37 (d,
J = 7.6 Hz, 1H), 8.62 (s, 1H), 9.32 (s, 1H), 9.43 (d, J = 8.0Hz,
1H), 12.37 (s, 1H); MS (ESI): m/z 517 (M+ H); Anal. Calcd for
C H BrN O S: C, 60.82; H, 3.06; N, 11.82; Found: C, 60.92;
[
1,2-a]pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-
À1
one (4m). Dark green solid; mp: 330–332°C; IR (KBr, cm
)
υ
max: 3379, 3049, 1730, 1583, 1245, 1068, 779, 649, 559, 509;
30
18
5 2
1
H NMR (400 MHz, DMSO-d
6
): δ 2.38 (s, 3H), 7.2–7.44
H, 2.96; N, 11.73.
(m, 2H), 7.63 (s, 1H), 7.73–7.8 (m, 5H), 7.86 (s, 1H), 8.18 (s,
2-(2-{N′-[2-(4-Nitro-phenyl)-imidazo[1,2-a]pyridin-3-
1
1
H), 8.51 (s, 1H), 8.56 (s, 1H), 9.28 (d, J= 7.2 Hz, 1H), 12.2 (s,
H); MS (ESI): m/z 636 (M + H); Anal. Calcd for
ylmethylene]-hydrazino}-thiazol-4-yl)-benzo[f]chromen-2-
À1
one (4s). Dark brown solid; mp: 335–337°C; IR (KBr, cm
)
1
C H Br N O S: C, 51.04; H, 2.70; N, 11.02. Found: C, 51.22;
H, 2.89; N, 11.14.
,8-Dibromo-3-(2-{N′-[2-(4-bromo-phenyl)-imidazo[1,2-a]
pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-
one (4n).
υmax: 3325, 3241, 1720, 1597, 1575, 1548, 1247, 742, 602; H NMR
(400MHz, DMSO-d ): δ 7.18–7.3 (m, 1H), 7.59–7.93 (m, 4H),
27
17
2 5 2
6
6
8.10–8.30 (m, 4H), 8.36–8.67 (m, 6H), 8.75 (s, 1H), 9.60 (s, 1H),
11.37 (s, 1H); MS (ESI): m/z 559 (M + H); Anal. Calcd for
C H N O S: C, 64.51; H, 3.25; N, 15.05; Found: C, 64.45; H,
À1
Brown solid; mp: 286–288°C; IR (KBr, cm
)
30 18 6 4
υ
6
max: 3389, 3068, 1744, 1580, 1445, 1245, 1079, 997, 758, 718,
3.29; N, 15.36.
1
47, 582, 560, 512; H NMR (400 MHz, DMSO-d
6
): δ 7.53
2-(2-{N′-[2-(4-Chloro-phenyl)-imidazo[1,2-a]pyridin-3-
ylmethylene]-hydrazino}-thiazol-4-yl)-benzo[f]chromen-2-
(s, 1H), 7.71 (d, J = 7.6 Hz, 2H), 7.83 (d, J = 8.0Hz, 3H), 7.91 (s,
1
1
H), 7.95 (d, J = 8.8 Hz, 1H), 8.14 (s, 1H), 8.21 (s, 1H), 8.50 (s,
H), 8.57 (s, 1H), 9.48 (d, J = 6.4Hz, 1H), 12.37 (s, 1H); MS
one (4t).
Yellowish brown solid; mp. 266–268°C; IR (KBr,
À1
cm ) υ : 3379, 3060, 1720, 1586, 1407, 1097, 1008, 1247,
max
1
(
4
ESI): m/z 701 (M+ H); Anal. Calcd for C26
H14Br N O
3 5 2
S: C,
4.60; H, 2.02; N, 10.00; Found: C, 44.45; H, 2.26; N, 10.17.
,8-Dibromo-3-(2-{N′-[2-(4-chloro-phenyl)-imidazo[1,2-a]
pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-
one (4o). Yellowish brown solid; mp. 290–292°C; IR
KBr, cm ) υmax: 3393, 3126, 1744, 1579, 1245, 1094, 1079,
742, 602; H NMR (400MHz, DMSO-d ): δ 7.37–7.67 (m, 6H),
6
7.83 (d, J = 8.0 Hz, 4H), 7.89 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H),
8.21 (d, J = 9.2Hz, 1H), 8.36 (d, J = 8.4 Hz, 1H), 8.61 (s, 1H), 9.3
(s, 1H), 9.43 (d, J =6.8 Hz, 1H), 12.39 (s, 1H); MS (ESI): m/z 549
(M+ H); Anal. Calcd for C H ClN O S: C, 65.75; H, 3.31; N,
6
30
18
5 2
À1
(
12.78. Found: C, 65.70; H, 3.21; N, 12.79.
1
7
6
58, 647, 560, 511; H NMR (400 MHz, DMSO-d ): δ 7.43
(
d, J = 7.6 Hz, 1H), 7.67 (d, J = 8.0Hz, 3H), 7.82–7.89 (m, 4H),
.14 (s, 1H), 8.29 (s, 1H), 8.5 (s, 1H), 8.6 (s, 1H), 9.44
d, J = 6.0 Hz, 1H), 12.30 (s, 1H); MS (ESI): m/z 656 (M + H);
Anal. Calcd for C26 ClN S: C, 47.62; H, 2.15; N, 10.68;
Found: C, 47.53; H, 2.28; N, 10.74.
,8-Dibromo-3-(2-{N′-[2-(4-nitro-phenyl)-imidazo[1,2-a]
8
(
ANTIMICROBIAL ACTIVITY
H14Br
2
5 2
O
All the newly synthesized compounds (4a–t) were
evaluated for their in vitro antibacterial activity against
three representative Gram-positive organisms viz. Bacillus
subtilis, Staphylococcus aureus, Staphylococcus epidermidis,
and three representative Gram-negative organisms viz.
Escherichia coli, Pseudomonas aeruginosa, and Klebsiella
pneumonia with respect to the standard drugs penicillin and
streptomycin. Minimum inhibitory concentration (MIC) of
the compounds as well as standards was measured in μg/mL
by micro dilution method recommended by Clinical
and Laboratory Standards Institute standard protocol [26].
All the compounds displayed moderate antibacterial activity
with MIC 150 μg/mL compared with the standard drugs
against all the tested bacterial strains.
6
pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-one
À1
(
4p). Dark brown solid; mp: 295–297°C; IR (KBr, cm ) υmax
:
3
370, 3033, 1742, 1597, 1575, 1548, 1511, 1345, 1106, 849, 755,
1
6
510; H NMR (400 MHz, DMSO-d ): δ 7.16–7.61 (m, 3H), 7.82
(
(
1
d, J=8.8Hz, 1H), 7.93 (s, 1H), 8.07 (d, J=8.8Hz, 2H), 8.36
t, J= 8.8 Hz, 4H), 8.75 (s, 1H), 9.59 (d, J= 6.0 Hz, 1H), 11.37 (s,
H); MS (ESI): m/z 667 (M + H); Anal. calcd for C H Br N O S:
26
14
2 6 4
C, 46.87; H, 2.12; N, 12.61; Found: C, 46.66; H, 2.30; N, 12.49.
,8-Dibromo-3-(2-{N′-[2-(4-bromo-phenyl)-7-methyl-imidazo
1,2-a]pyridin-3-ylmethylene]-hydrazino}-thiazol-4-yl)-chromen-2-
6
[
À1
one (4q). Brown solid; mp: 277–279°C; IR (KBr, cm1 ) υmax
380, 3120, 1744, 1581, 1245, 758, 649, 540, 528; H NMR
400 MHz, DMSO-d ): δ 2.62 (s, 3H), 7.43 (s, 1H), 7.74 (d,
J= 7.2 Hz, 3H), 7.84–8.20 (m, 5H), 8.48 (s, 1H), 8.51 (s, 1H),
.36 (s, 1H), 12.35 (s, 1H); MS (ESI): m/z 715 (M + H); Anal.
Calcd for C H Br N O S: C, 45.40; H, 2.26; N, 9.81; Found: C,
:
3
(
6
All the synthesized compounds were also screened for in
vitro antifungal activity against the five human pathogenic
fungal cultures viz. Candida albicans, Candida rugosa,
Saccharomyces cervisiae, Aspergillus flavus, and Aspergil-
lus niger by taking amphotericin B as a standard drug.
9
27
16
3 5 2
4
5.31; H, 2.29; N, 9.92.
General procedure for the synthesis of (4r–t). A mixture
of substituted imidazo[1,2-a]pyridine-3-carbaldehyde (3a–e,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Gali, J. Banothu, and R. Bavantula
Vol 000
[
11] Dennis, F.; Michael, F.; Gui-Bai, L.; Xiaoxia, Q.; Chris, B.;
Zone of inhibition was measured in millimeter by agar
well diffusion method using potato dextrose agar [27].
But none of the compound has shown antifungal activity
against all fungal strains.
Anne, G.; Penny, S. L.; Paul, A. L.; John, M.; Andrew, M.; Samantha, S.;
Tamas, T.; Dennis, M. S.; Matthew, W.; Tesfaye, B. Bioorg Med Chem Lett
2006, 16, 5978.
[12] Inge, V.; Jan, P.; Tine, D. B.; Laura, S. L.; Matthew, P.; Hung, I. S.;
Eric, M.; Nina, B.; Erik, D. C.; Hans, R.; David, O.; William, A. L.; Zhong, W.;
Steven, B.; Gerhard, P.; Johan, N. J Hepatol 2009, 50, 999.
[
13] Richard, D.; Iain, S.; Frederic, J. H.; Willem, N. J.; Peter, W.;
Acknowledgments. We would like to thank the Director, National
Institute of Technology, Warangal for providing facilities under
RSM project. We are grateful to Dr. U.S.N Murthy, Head
Department of Biology, Indian Institute of Chemical Technology,
Hyderabad for screening antimicrobial activity. One of the
authors, R. G., is thankful to UGC, and B. J. to MHRD for
research fellowships.
Martina, F.; Graeme, E. W.; Lara, T. W.; Kevin, H. Bioorg Med Chem
Lett 2011, 21, 4698.
[14] Kazzouli, S.; Griffon du Bellay, A.; Berteina-Raboin, S.;
Delagrange, P.; Daniel-Henry, C.; Guillaumet, G. Eur J Med Chem
2011, 46, 4252.
[15] Ahmed, K.; Ramakrishna, G.; Janaki, R. M.; Viswanath, A.;
Subba Rao, A. V.; Chandrakant, B.; Mukhopadyay, D.; Pushpavalli,
S. N. C. V. L.; Manika, P. B. Med Chem Commun 2013, 4, 697.
[16] Lisheng, C.; Jessica, C.; Sebastian, T.; Mary, M. H.; Claudio,
D.; David, A. W.; Robert B. I.; Victor, P. W. J Med Chem 2007, 50, 4746.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet