Synthesis and biological study of some new chalcones and oxopyrimidines containing imidazo[1,2-a]pyridine nucleus

Article abstract of DOI:10.1002/jhet.787

Heterosubstituted chalcones and oxopyrimidines were synthesized by the reaction of 2-(4-Chlorophenyl) imidazo[1,2-a]pyridine-3-carbaldehyde 1 and different aryl acetophenone in the presence of catalytic amount of 40% alkali to give (2E)-3-(2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-1-arylprop-2-en-1- ones 2a-l. Compounds 2a-l on reaction with urea in the presence of basic catalyst such as KOH to give 6-(2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4- aryl pyrimidin-2(1H)-ones 3a-l. Their IR, ¹H-NMR, MASS spectral data, and elemental analysis were in accord with assigned structure. All the newly synthesized compounds were screened for their antimicrobial activity..

Full text of DOI:10.1002/jhet.787

130
Synthesis and Biological Study of Some New Chalcones and
Oxopyrimidines Containing Imidazo[1,2-a]Pyridine Nucleus
Vol 49
M. J. Joshi, P. B. Vekariya, B. L. Dodiya, R. M. Ghetiya, and H. S. Joshi*
Chemical Research Laboratory, Department of Chemistry, Saurashtra University,
Rajkot-360005, India
*E-mail: drhsjoshi49@gmail.com
Received August 23, 2010
DOI 10.1002/jhet.787
Published online 15 October 2011 in Wiley Online Library (wileyonlinelibrary.com).
Heterosubstituted chalcones and oxopyrimidines were synthesized by the reaction of 2-(4-Chlorophe-
nyl)imidazo[1,2-a]pyridine-3-carbaldehyde 1 and different aryl acetophenone in the presence of catalytic
amount of 40% alkali to give (2E)-3-(2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-1-arylprop-2-en-1-
ones 2a–l. Compounds 2a–l on reaction with urea in the presence of basic catalyst such as KOH to
give 6-(2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4-aryl pyrimidin-2(1H)-ones 3a–l. Their IR,
1H-NMR, MASS spectral data, and elemental analysis were in accord with assigned structure. All the
newly synthesized compounds were screened for their antimicrobial activity.
J. Heterocyclic Chem., 49, 130 (2012).
INTRODUCTION
RESULTS AND DISCUSSION
Chalcones and oxopyrimidines are potential bioactive
agents due to their wide spectrum of pharmacological
activities such as anti-inflammatory [1], antimicrobial
[2,3], calcium channel blockers [4], antihypertensive [5],
analgesic [6], antitumor [7], antiviral [8], antibacterial
[9], anti-HIV [10], anticancer [11], antimalarial [12],
and antitubercular [13].
The synthesis of chalcones 2a–l and oxopyrimidines
3a–l were performed from the following steps shown in
reaction (Scheme 1). The required compound 1 [17] has
been prepared by the literature methods. The compounds
2a–l were synthesized by reacting compound 1 with dif-
ferent aryl ketones in the presence of catalytic amount
of 40% alkali in ethanol. Compounds 2a–l on reaction
with urea in the presence of basic catalyst such as KOH
give compounds 3a–l. The purity of all the newly syn-
thesized compounds was checked on TLC. The struc-
tures of the synthesized compounds were assigned on
Our works are paying attention on introduction of
chemical multiplicity in the molecular frame work, to
synthesizing active molecules of widely different com-
position such as combination of two heterocyclic frame
works to achieve good biological profile of the newly
synthesized derivatives. So, we planned to synthesize
some new chalcones and oxopyrimidines derivatives
containing imidazo[1,2-a]pyridine moiety with hope that
they may possess antimicrobial activities.
1
the basis of spectral data such as IR, H-NMR, MASS
spectral analysis, and elemental analysis. All the newly
synthesized compounds were in full agreement with the
proposed structures.
Antimicrobial activity. The antimicrobial activity
was assayed by using the cup-plate agar diffusion
method [18] by measuring the zone of inhibition in mm.
Newly synthesized compounds were screened in vitro
for their antimicrobial activity against varieties of bacte-
rial strains such Bacillus megaterium ATCC 14518,
Staphylococcus aureus ATCC 25923, Escherichia coli
Imidazo[1,2-a]pyridine moieties represent important
building blocks in both natural and synthetic bioactive
compounds, which have been shown to possess diverse
therapeutic activities [14,15]. The nature and the posi-
tion of the substituent on the pyridinic moiety influence
these activities [16].
C
V
2011 HeteroCorporation

January 2012
Synthesis and Biological Study of Some New Chalcones and Oxopyrimidines
Containing Imidazo[1,2-a]pyridine Nucleus
131
Scheme 1. Synthesis of chalcones and oxypyrimidines.
present in 4-position in both cases, that is, chalcone and
oxopyrimidines, show potent activities against all bacte-
ria. Also compound 3j containing F group at the 3-posi-
tion exhibited very good antimicrobial activities against
B. megaterium, S. aureus, E. coli, and P. aeruginosa
and antifungal activity against A. niger.
EXPERIMENTAL
Melting points were determined on electrothermal apparatus
using open capillaries and are uncorrected. Thin layer chroma-
tography was accomplished on 0.2-mm precoated plates of
silica gel G60 F254 (Merck, St. Louis, MO). Visualization was
made with UV light (254 and 365 nm) or with an iodine
vapor. IR spectra were recorded on a FTIR-8400 spectropho-
1
tometer (Shimadzu, Kyoto, Japan), using DRS prob. H-NMR
spectra were recorded on a Bruker AVANCE II (400 MHz)
spectrometer (Bruker, Rheinstetten, Germany), in CDCl3.
Chemical shifts are expressed in d ppm downfield from TMS
as an internal standard. Mass spectra were determined using
direct inlet probe on a GCMS-QP 2010 mass spectrometer
(Shimadzu, Kyoto, Japan). Elemental analysis was performed
on a Carlo-Erba EA 1108 elemental analyzer (Waltham, MA).
Solvents were evaporated with a Laborota 4000 efficient rotary
evaporator (Heidolph, Germany). All reagents were purchased
from Fluka (New Delhi, India), Sigma Aldrich (New Delhi,
India), Merck (St. Louis, MO), and Rankem (New Delhi,
India) and used without further purification.
Procedure for synthesis of 2-(4-chlorophenyl)imidazo[1,2-a]
pyridin-3-carbaldehyde (1). To the solution of 2-(4-chlorophe-
nyl)imidazo[1,2-a]pyridine (2.28 g, 0.01 mol) in DMF (25 mL)
phosphorus oxychloride (3.06 g, 0.02 mol) was added at room
temperature under stirring. The mixture was heated to 80ꢀC
for 5.0 h. The resulting solution was evaporated to dryness in
vacuo, and the residue was treated with cold water, filtered,
and crystallized from methanol to give pure product. Yield
64%, mp 196ꢀC.
General procedure for synthesis of (2E)-3-[2-(4-chlorophe-
nyl)imidazo[1,2-a]pyridin-3-yl]-1-arylprop-2-en-1-one (2a–l). The
mixture of 2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-carbal-
dehyde (2.56 g, 0.01 mol) and aryl acetophenone (0.01 mol) in
ethanol (25 mL) was stirred at room temperature for 24 h in
the presence of catalytical amount of 40% KOH. The resulting
solution was poured on to crushed ice, and thus the solid sepa-
rated was filtered and crystallized from ethanol to give analyti-
cally pure product (2a–l).
ATCC 25922, Pseudomonas aeruginosa ATCC 27853,
and fungi Aspergillus niger ATCC 9029 at 40 lg/mL
concentration. Standard drugs such as Amoxicillin, Ben-
zyl penicillin, Ciprofloxacin, Erythromycin, and Greseo-
fulvin were used for the comparison purpose. The
results are given in Table 1.
From the result of antimicrobial data, compounds 2g,
2h, 2i, 2j, 3g, 3h, 3i, and 3j were active and compounds
2a, 2d, 2k, 3a, 3e, 3f, and 3l were moderately active
against B. megaterium. Same as compounds 2i, 2j, 3g,
3i, and 3k were active, whereas compounds 2g, 2k, 2i,
3a, 3c, 3h, and 3l were moderately active against S. aur-
eus. Further compounds 2g, 2i, 2l, 3e, 3h, 3i, 3j, and 3k
were active and compounds 2b, 2c, 2k, 3b, 3d, 3g, and
3l show moderate activity against E. coli. In case of P.
aeruginosa compounds 2i, 3d, 3i, and 3j were active
and compounds 2e, 2j, 2h, 3f, 3h, and 3k were moder-
ately active. Against A. niger compounds 2h, 2i, 2j, 3e,
3i, and 3j were active, whereas compounds 2g, 2f, 2k,
3a, 3d, 3h, and 3k were moderately active. Remaining
compounds did not show any promising activity against
tested bacteria and fungi.
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
phenyl-prop-2-en-1-one (2a). Yield 62%; m.p. 156–158ꢀC; IR
(KBr): 3015 ,1655, 1591, 1509, 1170, 785 cmꢁ1 1H-NMR
;
(400 MHz CDCl3): d, 7.33 (d, 2H, Ar-Ha,a0), 7.42 (d, 2H, Ar-
Hb,b0), 7.51 (d, 1H, ACHc), 7.63 (m, 4H, imidazo[1,2-a]pyri-
dine-H), 7.71 (d, 1H, ACHd), 7.81 (m, 5H, Ar-H); MS: m/z:
359[Mþ]; Anal. Calcd. for C22H15ClN2O: C, 73.64; H, 4.21;
N, 7.81% Found: C, 73.62; H, 4.17; N, 7.83%.
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(4-methylphenyl)prop-2-en-1-one (2b). Yield 58%; m.p. 146–
148ꢀC; IR (KBr): 3021 ,1645, 1583, 1480, 1153, 788 cmꢁ1
;
1H NMR (400 MHz CDCl3): d 2.70 (s, 3H, ACH3), 7.08 (d,
2H, Ar-Ha,a0), 7.28 (d, 2H, Ar-Hb,b0), 7.33 (d, 1H, ACHc),
7.51 (m, 4H, imidazo[1,2-a]pyridine-H), 7.62 (d,1H, ACHd),
The structure–activity relationship studies revealed
that compounds 2i and 3i containing SO2CH3 group
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

132
M. J. Joshi, P. B. Vekariya, B. L. Dodiya, R. M. Ghetiya, and H. S. Joshi
Vol 49
Table 1
Antimicrobial screening results of compounds 2a–l and 3a–l.
Zones of inhibition in mm
Antibacterial activity
Antifungal activity
Compound
R
B. megaterium
S. aureus
E. coli
P. aeruginosa
A. niger
2a
C6Hꢁ5
4-CH3AC6Hꢁ4
2-CH3AC6Hꢁ4
2,4-(CH3)2AC6Hꢁ
4-OCH3AC6Hꢁ4 3
2,4-(Cl)2AC6Hꢁ3
4-ClAC6Hꢁ4
3-ClAC6Hꢁ4
4-SO2CH3AC6Hꢁ4
3-FAC6Hꢁ4
3-NO2AC6Hꢁ4
4-NO2AC6Hꢁ4
C6Hꢁ5
4-CH3AC6Hꢁ4
2-CH3AC6Hꢁ4
2,4-(CH3)2AC6Hꢁ
4-OCH3AC6Hꢁ4 3
2,4-(Cl)2AC6Hꢁ3
4-ClAC6Hꢁ4
3-ClAC6Hꢁ4
4-SO2CH3AC6Hꢁ4
3-FAC6Hꢁ4
3-NO2AC6Hꢁ4
4-NO2AC6Hꢁ4
–
16
10
10
14
13
12
20
21
20
18
14
12
16
13
12
12
17
15
18
22
22
19
13
17
25
18
20
22
00
10
11
13
12
10
10
17
13
18
19
14
17
16
12
14
11
11
10
20
15
19
17
21
15
25
19
15
21
00
11
16
14
11
13
12
20
12
18
12
16
19
10
17
10
16
20
11
16
18
18
19
20
17
20
21
22
19
00
10
13
10
11
14
13
12
14
18
16
15
10
10
13
12
19
11
15
13
15
21
20
17
13
22
21
16
23
00
11
13
12
11
12
15
16
20
21
19
13
11
17
11
12
14
18
11
12
15
20
21
17
13
00
00
00
00
26
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
Amoxicillin
Benzyl penicillin
Ciprofloxacin
Erythromycin
Greseofulvin
–
–
–
–
7.75 (m, 4H, Ar-H); MS: m/z: 373[Mþ]; Anal. Calcd. for
C23H17ClN2O: C, 74.09; H, 4.60; N, 7.51% Found: C, 74.05;
H, 4.56; N, 7.48%.
AOCH3), 6.62 (d, 2H, Ar-Ha,a0), 6.75 (d, 2H, Ar-Hb,b0), 6.90
(d, 1H, ACHc), 7.22 (m, 4H, imidazo[1,2-a]pyridine-H), 7.56
(d, 1H, ACHd), 7.71 (m, 4H, Ar-H); MS: m/z: 389[Mþ]; Anal.
Calcd. for C23H17ClN2O2: C, 71.04; H, 4.41; N, 7.20% Found:
C, 71.03; H, 4.38; N, 7.17%.
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(2,4-dichlorophenyl)prop-2-en-1-one (2f). Yield 58%; m.p.
198–200ꢀC; IR (KBr): 3019, 1658, 1591, 1481, 1083, 785
cmꢁ1 1H-NMR (400 MHz CDCl3): d 6.62 (d, 2H, Ar-Ha,a0),
;
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(2-methylphenyl)prop-2-en-1-one (2c). Yield 65%; m.p. 187–
189ꢀC; IR (KBr): 3010, 1659, 1595, 1474, 1090, 781 cmꢁ1
;
1H-NMR (400 MHz CDCl3): d 2.93 (s, 3H, ACH3), 7.17 (d,
2H, Ar-Ha,a0), 7.24 (d, 2H, Ar-Hb,b0), 7.41 (d, 1H, ACHc),
7.59 (m, 4H, imidazo[1,2-a]pyridine-H), 7.73 (d, 1H, ACHd),
7.87 (m, 4H, Ar-H); MS: m/z: 386[Mþ]; Anal. Calcd. for
C23H17ClN2O: C, 74.09; H, 4.60; N, 7.51% Found: C, 74.08;
H, 4.56; N, 7.48%.
6.72 (d, 2H, Ar-Hb,b0), 6.92 (d, 1H, ACHc), 7.21 (m, 4H,
imidazo[1,2-a]pyridine-H), 7.55 (d, 1H, ACHd), 7.73 (m, 3H,
Ar-H); MS: m/z: 428[Mþ]; Anal. Calcd. for C22H13Cl3N2O: C,
61.78; H, 3.06; N, 6.55% Found: C, 61.75; H, 3.05; N, 6.49%.
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(4-chlorophenyl)prop-2-en-1-one (2g). Yield 55%; m.p. 180–
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(2,4-dimethylphenyl)prop-2-en-1-one (2d). Yield 62%; m.p.
152–154ꢀC; IR (KBr): 3023, 1649, 1605, 1487, 1124, 798
182ꢀC; IR (KBr): 3027, 1663, 1580, 1460, 1097, 773 cmꢁ1
;
cmꢁ1 1H-NMR (400 MHz CDCl3): d 3.04 (s, 6H, ACH3),
;
1H-NMR (400 MHz CDCl3): d 6.69 (d, 2H, Ar-Ha,a0), 6.78 (d,
2H, Ar-Hb,b0), 6.94 (d, 1H, ACHc), 7.27 (m, 4H, imidazo[1,2-
a]pyridine-H), 7.58 (d, 1H, ACHd), 7.78 (m, 4H, Ar-H); MS:
m/z: 393[Mþ]; Anal. Calcd. for C22H14Cl2N2O: C, 67.19; H,
3.59; N, 7.12% Found: C, 67.16; H, 3.58; N, 7.15%.
6.79 (d, 2H, Ar-Ha,a0), 7.23 (d, 2H, Ar-Hb,b0), 7.48 (d, 1H,
ACHc), 7.73 (m, 4H, imidazo[1,2-a]pyridine-H), 7.82 (d, 1H,
ACHd), 7.93 (m, 3H, Ar-H); MS: m/z: 387[Mþ]; Anal. Calcd.
for C24H19ClN2O: C, 74.51; H, 4.95; N, 7.24% Found: C,
74.47; H, 4.92; N, 7.23%.
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(3-chlorophenyl)prop-2-en-1-one (2h). Yield 65%; m.p. 149–
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(4-methoxyphenyl)prop-2-en-1-one (2e). Yield 67%; m.p.
214–216ꢀC; IR (KBr): 3016, 1645, 1593, 1503, 1221, 1107,
;
781 cmꢁ1 1H-NMR (400 MHz CDCl3): d 3.84 (s, 3H,
151ꢀC; IR (KBr): 3012, 1652, 1601, 1478, 1118, 797 cmꢁ1
;
1H-NMR (400 MHz CDCl3): d 6.59 (d, 2H, Ar-Ha,a0), 6.82 (d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2012
Synthesis and Biological Study of Some New Chalcones and Oxopyrimidines
Containing Imidazo[1,2-a]pyridine Nucleus
133
2H, Ar-Hb,b0), 6.99 (d, 1H, ACHc), 7.34 (m, 4H, imidazo[1,2-
a]pyridine-H), 7.61 (d, 1H, ACHd), 7.71 (m, 4H, Ar-H); MS:
m/z: 393[Mþ]; Anal. Calcd. for C22H14Cl2N2O: C, 67.19; H,
3.59; N, 7.12% Found: C, 67.18; H, 3.62; N, 7.10%.
Ar-H), 7.93 (s, 1H ANH); MS: m/z: 413[Mþ]; Anal. Calcd.
for C24H17ClN4O: C, 69.82; H, 4.15; N, 13.57 % Found: C,
69.76; H, 4.19; N, 13.48%.
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(2-meth-
ylphenyl)pyrimidin-2(1H)-one (3c). Yield 61%; m.p. 175–
177ꢀC; IR (KBr): 3317, 3024, 1652, 1589, 1451, 1136, 779
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(4-methylsulfonylphenyl)prop-2-en-1-one (2i). Yield 62%;
m.p. 177–179ꢀC; IR (KBr): 3056, 1645, 1588, 1491, 1084,
cmꢁ1 1H-NMR (400 MHz CDCl3): d 3.27 (s, 3H, ACH3),
;
773 cmꢁ1
;
1H-NMR (400 MHz CDCl3): d 2.97 (s, 3H,
5.37 (s, 1H, AHh), 7.16 (q, 2H, Ar-Ha,a0) 7.31 (d, 2H, Ar-
Hb,b0), 7.51 (m, 4H, imidazo[1,2-a]pyridine-H), 7.67 (m, 4H,
Ar-H), 7.90 (s, 1H ANH); MS: m/z: 413[Mþ]; Anal. Calcd.
for C24H17ClN4O: C, 69.82; H, 4.15; N, 13.57 % Found: C,
69.81; H, 4.12; N, 13.55%.
ASO2CH3), 6.61 (d, 2H, Ar-Ha,a0), 6.76 (d, 2H, Ar-Hb,b0),
7.03 (d, 1H, ACHc), 7.24 (m, 4H, imidazo[1,2-a]pyridine-H),
7.51 (d, 1H, ACHd), 7.88 (m, 4H, Ar-H); MS: m/z: 437[Mþ];
Anal. Calcd. for C23H17ClN2O3S: C, 68.22; H, 4.23; N, 6.92%
Found: C, 68.21; H, 4.22; N, 6.91%.
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(2,4-
dimethylphenyl) pyrimidin-2(1H)-one (3d). Yield 58%; m.p.
152–154ꢀC; IR (KBr): 3329, 3024, 2990, 1658, 1581, 1375,
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(3-fluorophenyl)prop-2-en-1-one (2j). Yield 64%, m.p. 211–
213ꢀC; IR (KBr): 3010, 1643, 1610, 1510, 1163, 790 cmꢁ1
;
1130, 784 cmꢁ1 1H-NMR (400 MHz CDCl3): d 3.37 (s, 6H,
;
1H-NMR (400 MHz CDCl3): d 6.64 (d, 2H, Ar-Ha,a0), 6.76 (d,
2H, Ar-Hb,b0), 6.97 (d, 1H, ACHc), 7.31 (m, 4H, imidazo[1,2-
a]pyridine-H), 7.59 (d, 1H, ACHd), 7.78 (m, 4H, Ar-H); MS:
m/z: 377[Mþ]; Anal. Calcd. for C22H14ClFN2O: C, 70.12; H,
3.74; N, 7.43% Found: C, 70.09; H, 3.73; N, 7.40%.
ACH3), 5.49 (s, 1H, AHh), 7.21 (q, 2H, Ar-Ha,a0) 7.38 (d,
2H, Ar-Hb,b0), 7.61 (m, 4H, imidazo[1,2-a]pyridine-H), 7.74
(m, 3H, Ar-H), 8.01 (s, 1H ANH); MS: m/z: 427[Mþ]; Anal.
Calcd. for C25H19ClN4O: C, 70.34; H, 4.49; N, 13.12% Found:
C, 70.38; H, 4.37; N, 13.09%.
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(3-nitrophenyl)prop-2-en-1-one (2k). Yield 57%; m.p. 172–
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(4-
methoxyphenyl)pyrimidin-2(1H)-one (3e). Yield 72%; m.p.
183–185ꢀC; IR (KBr): 3227, 3029, 2954, 1649, 1570, 1367,
174ꢀC; IR (KBr): 3005, 1649, 1581, 1497, 1149, 795 cmꢁ1
;
1H-NMR (400 MHz CDCl3): d 7.03 (d, Ar-Ha,a0), 7.19 (d, 2H,
Ar-Hb,b0), 7.41 (d, 1H, ACHc), 7.58 (m, 4H, imidazo[1,2-
a]pyridine-H), 7.71 (d, 1H, ACHd), 7.93 (m, 4H, Ar-H); MS:
m/z: 404[Mþ]; Anal. Calcd. for C22H14ClN3O3: C, 65.43; H,
3.49; N,10.41% Found: C, 65.45; H, 3.47; N,10.39%.
1104, 786 cmꢁ1 1H-NMR (400 MHz CDCl3): d 3.73 (s, 3H,
;
AOCH3), 5.47 (s, 1H, AHh), 7.09 (q, 2H, Ar-Ha,a0) 7.21 (d,
2H, Ar-Hb,b0), 7.57 (m, 4H, imidazo[1,2-a]pyridine-H), 7.65
(m, 4H, Ar-H), 7.80 (s, 1H ANH); MS: m/z: 429[Mþ]; Anal.
Calcd. for C24H17ClN4O2: C, 67.21; H, 4.00; N, 13.06 %
Found: C, 67.17; H, 4.07; N, 13.11%.
(2E)-3-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-1-
(4-nitrophenyl)prop-2-en-1-one (2l). Yield 59%; m.p. 167–
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(2,4-
dichlorophenyl)pyrimidin-2(1H)-one (3f). Yield 67%; m.p.
212–215ꢀC; IR (KBr): 3262, 3018, 1659, 1590, 1453, 1133,
1
169ꢀC; IR (KBr): 3005, 1649, 1581, 795 cmꢁ1. H-NMR (400
MHz CDCl3) d 7.07 (d, 2H, Ar-Ha,a0), 7.23 (d, 2H, Ar-Hb,b0),
7.49 (d, 1H, ACHc), 7.64 (m, 4H, imidazo[1,2-a]pyridine-H),
7.69 (d, 1H, ACHd), 8.03 (m, 4H, Ar-H); MS: m/z: 404[Mþ];
Anal. Calcd. for C22H14ClN3O3: C, 65.43; H, 3.49; N,10.48%
Found: C, 65.41; H, 3.46; N,10.47%.
1
791 cmꢁ1; H-NMR (400 MHz CDCl3): d 6.22 (s, 1H, AHh),
7.12 (q, 2H, Ar-Ha,a0) 7.38 (d, , 2H, Ar-Hb,b0), 7.46 (m, 4H,
imidazo[1,2-a]pyridine-H), 7.61 (m, 3H, Ar-H), 7.87 (s, 1H,
ANH); MS: m/z: 468[Mþ]; Anal. Calcd. for C23H13Cl3N4O: C,
59.06; H, 2.80; N, 11.98% Found: C, 59.13; H, 2.76; N, 11.93
%.
General procedure for synthesis of 6-[2-(4-Chlorophenyl)
imidazo [1, 2-a] pyridin-3-yl]-4-aryl pyrimidin-2(1H)-one
(3a–l). The mixture of (2E)-3-(2-(2,4-dichlorophenyl)imi-
dazo[1,2-a]pyridin-3-yl)-1-4-aryl-prop-2-en-1-one (0.01 mol)
and urea (0.77 g, 0.01 mol) in ethanol (20 mL) was refluxed
in the presence of alcoholic KOH for 8 h. The excess solvent
was distilled off under reduced pressure in vacuo, and the resi-
due was neutralized with dilute HCl, and thus, the separated
solid was filtered out and crystallized from ethanol to give
pure product (3a–l).
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(4-chlor-
ophenyl)pyrimidin-2(1H)-one (3g). Yield 34%; m.p. 195–
197ꢀC; IR (KBr): 3319, 3029, 1665, 1587, 1093, 796 cmꢁ1
;
1H-NMR (400 MHz CDCl3): d 5.53 (s, 1H, AHh), 7.11 (q,
2H, Ar-Ha,a0) 7.25 (d, 2H, Ar-Hb,b0), 7.49 (m, 4H, imi-
dazo[1,2-a]pyridine-H), 7.67 (m, 4H, Ar-H), 7.92 (s, 1H
ANH); MS: m/z: 433[Mþ]; Anal. Calcd. for C23H14Cl2N4O: C,
63.76; H, 3.26; N, 12.93% Found: C, 63.71; H, 3.30; N,
12.88%.
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-ꢀphenyl-
pyrimidin-2(1H)-one (3a). Yield 63%; m.p. 168–170 C; IR
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(3-chlor-
ophenyl)pyrimidin-2(1H)-one (3h). Yield 46%; m.p. 221–
(KBr): 3351, 3015, 1658, 1591, 1433, 1107, 785 cmꢁ1 1H-
;
NMR (400 MHz CDCl3): d 5.31 (s, 1H, AHh), 7.04 (q, 2H,
Ar-Ha,a0) 7.26 (d, 2H, Ar-Hb,b0), 7.41 (m, 4H, imidazo[1,2-
a]pyridine-H), 7.57 (m, 5H Ar-H), 7.81 (s, 1H ANH); MS: m/
z: 399[Mþ]; Anal. Calcd. for C23H15ClN4O: C, 69.26; H, 3.79;
N, 14.05% Found: C, 69.21; H, 3.83; N, 14.04%.
222ꢀC; IR (KBr): 3312, 3019, 1672, 1588, 1128, 781 cmꢁ1
;
1H-NMR (400 MHz CDCl3): d 5.45 (s, 1H, AHh), 7.19 (q,
2H, Ar-Ha,a0), 7.30 (d, 2H, Ar-Hb,b0), 7.54 (m, 4H, imi-
dazo[1,2-a]pyridine-H), 7.70 (m, 4H, Ar-H), 7.95 (s, 1H
ANH); MS: m/z: 433[Mþ]; Anal. Calcd. for C23H14Cl2N4O: C,
63.76; H, 3.26; N, 12.93% Found: C, 63.73; H, 3.21; N,
12.90%.
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(4-meth-
ylphenyl)pyrimidin-2(1H)-one (3b). Yield 54%; m.p. 192–
194ꢀC; IR (KBr): 3293, 3019, 1650, 1587, 1463, 1129, 780
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-[4(meth-
ylsulfonyl)phenyl]pyrimidin-2(1H)-one (3i). Yield 43%; m.p.
186–188ꢀC; IR (KBr): 3315, 3034, 1666, 1589, 1139, 785
cmꢁ1 1H-NMR (400 MHz CDCl3): d 3.23 (s, 3H, ACH3),
;
5.42 (s, 1H, AHh), 7.13 (q, 2H, Ar-Ha,a0) 7.34 (d, 2H, Ar-
1
Hb,b0), 7.46 (m, 4H, imidazo[1,2-a]pyridine-H), 7.63 (m, 4H,
cmꢁ1; H-NMR (400 MHz CDCl3): d 5.35 (s, 1H, AHh), 7.06
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

134
M. J. Joshi, P. B. Vekariya, B. L. Dodiya, R. M. Ghetiya, and H. S. Joshi
Vol 49
(q, 2H, Ar-Ha,a0), 7.37 (d, 2H, Ar-Hb,b0), 7.47 (m, 4H, imi-
dazo[1,2-a]pyridine-H), 7.53 (m, 4H, Ar-H), 7.87 (s, 1H
ANH); MS: m/z: 476[Mþ]; Anal. Calcd. for C24H17ClN4O3S:
C, 65.65; H, 3.75; N, 13.03% Found: C, 65.64; H, 3.73; N,
13.02%.
increases biological activity with imidazo[1,2-a]pyridine
nucleus while chalcone is moderate active.
Acknowledgments. Authors are thankful to Department of
Chemistry for providing laboratory facilities. The authors are
also thankful for facilities and grants given under UGC-SAP for
Department Research Support (DRS) and Department of Science
& Technology (DST), New Delhi for Fund for Improvement of
Science & Technology (FIST). Authors are also thankful to RSIC
Chandigarh for providing 1H-NMR spectral analysis of the
compounds.
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(3-flu-
orophenyl)pyrimidin-2(1H)-one (3j). Yield 68%; m.p. 216–
218ꢀC; IR (KBr): 3296, 3025, 1658, 1566, 1146, 781 cmꢁ1
;
1H-NMR (400 MHz CDCl3): d 5.40 (s, 1H, AHh), 7.15 (q,
2H, Ar-Ha,a0), 7.33 (d, 2H, Ar-Hb,b0), 7.53 (m, 4H, imi-
dazo[1,2-a]pyridine-H), 7.69 (m, 4H, Ar-H), 7.91 (s, 1H
ANH); MS: m/z: 417[Mþ]; Anal. Calcd. for C23H14ClFN4O:
C, 66.27; H, 3.39; N, 13.44% Found: C, 66.24; H, 3.36; N,
13.44%.
REFERENCES AND NOTES
6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(3-nitro-
phenyl)pyrimidin-2(1H)-one (3k). Yield 55%; m.p. 169–171ꢀC;
[1] Bahekar, S. S.; Shinde, D. B. Acta Pharm 2003, 53, 223.
[2] Ladani, M. J.; Tala, S. D.; Akbari, J. D.; Dhaduk, M. F.;
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1
IR (KBr): 3252, 3015, 1648, 1561, 1124, 786 cmꢁ1; H-NMR
(400 MHz CDCl3): d 5.61 (s, 1H, AHh), 7.17 (q, 2H, Ar-
Ha,a0), 7.21 (d, 2H, Ar-Hb,b0), 7.46 (m, 4H, imidazo[1,2-a]pyr-
idine-H), 7.62 (m, 4H, Ar-H), 7.97 (s, 1H ANH); MS: m/z:
444[Mþ]; Anal. Calcd. for C23H14ClFN5O3: C, 62.24; H, 3.18;
N, 15.78% Found: C, 62.25; H, 3.14; N, 15.78%.
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6-(2-(4-Chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-4-(4-nitro-
phenyl)pyrimidin-2(1H)-one (3l). Yield 40%; m.p. 185–187ꢀC;
1
IR (KBr): 3335, 3062, 1663, 1556, 1453, 1124, 789 cmꢁ1; H-
[7] Huang, Y. L.; Lin, C. F.; Lee, Y. J.; Li, W. W.; Chao, T.
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NMR (400 MHz CDCl3): d 5.65 (s, 1H, AHh), 7.20 (q, 2H,
Ar-Ha,a0), 7.39 (d, 2H, Ar-Hb,b0), 7.51 (m, 4H, imidazo[1,2-
a]pyridine-H), 7.67 (m, 4H, Ar-H), 8.05 (s, 1H ANH); MS: m/
z: 444[Mþ]; Anal. Calcd. for C23H14ClFN5O3: C, 62.24; H,
3.18; N, 15.78% Found: C, 62.21; H, 3.14; N, 15.76%.
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CONCLUSIONS
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In conclusion, we have described efficient synthesis
of imidazo[1,2-a]pyridine systems containing chalcones
and oxopyrimidines. Imidazo[1,2-a]pyridine is the key
intermediate in the formation of these heterocyclic com-
pounds. Although there are not many imidazo[1,2-a]pyr-
idine fused to chalcones or oxopyrimidines, a number of
them are incorporated into a wide variety of therapeuti-
cally important compounds possessing a broad spectrum
of biological activities. In this connection, we have syn-
thesized chalcones and oxopyrimidines.
[13] Popat, K. H.; Purohit, D. H.; Chovatia, P. T.; Joshi, H. S. J
Indian Chem Soc 2005, 82, 940.
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Biological activity data indicate imidazo[1,2-a]pyri-
dine systems containing oxopyrimidines ring show potent
activity, Finally, we concluded that oxopyrimidine ring
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet