886
S. D. Diwakar, R. S. Joshi, and C. H. Gill
Vol 48
using mobile phase hexane:ethyl acetate (9:1) to afford pure 7.
Compounds 7a–h synthesized by this method are listed in
Table 1. The physical, analytical, and spectral data of final
compounds are given in the following text.
7.86 (s, 1H, C2AH), 8.15 (s, 1H, Ar), 8.23–8.25 (d, 2H, J ¼
8.8 Hz, ArH); ESI (þve): 424.1; Anal. Calcd. for
C21H14ClN3O5 (423.82): C, 59.52; H, 3.33; and N, 9.91.
Found: C, 59.60; H, 3.41; and N, 10.01.
6-Methyl-3-((Z)-2-(5-methyl-1,2,4-oxadiazol-3-yl)-2-(4-nitrophe-
nyl)vinyl)-4H-chromen-4-one (7g). Yield: 35%; mp 196–198ꢀC;
1H NMR (400 MHz, CDCl3): d 2.45 (s, 3H, CH3), 2.69 (s, 3H,
oxadiazole-CH3), 7.27 (s, 1H, ArH), 7.38 (s, 1H, vinylic-CH),
7.46–7.49 (dd, 1H, J ¼ 2.0 and 8.4 Hz, ArH), 7.54 (d, 2H,
J ¼ 8.4 Hz, ArH), 7.99 (s, 1H, C2AH), 8.02 (s, 1H, ArH),
8.26–8.29 (d, 2H, J ¼ 8.4 Hz, ArH); ESI (þve): 390.2; Anal.
Calcd. for C21H15N3O5 (389.37): C, 64.78; H, 3.88; and N,
10.79. Found: C, 64.84; H, 3.94; and N, 10.82.
3-((Z)-2-(5-methyl-1,2,4-oxadiazol-3-yl)-2-(4-nitrophenyl)vinyl)-
4H-chromen-4-one (7a). Yield: 54%; mp 205–207ꢀC; IR
(KBr): 1654, 1615, 1595, 1571, 1518, 1466, 1353, 1315, 1260,
1224, 760 cmꢁ1
;
3H, oxadiazole-CH3), 7.30–7.45 (3H,
1H NMR (400 MHz, CDCl3): d 2.45 (s,
vinylic-CH and
1
2 ArH), 7.53–7.58 (d, 2H, J ¼ 8.6 Hz, ArH), 7.63–7.70
(m, 1H, ArH), 7.99 (s, 1H, C2AH), 8.20–8.25 (d, 1H, J ¼
7.6 Hz, ArH), 8.26–8.30 (d, 2H, J ¼ 8.6 Hz, ArH); ESI (þve):
376.2; Anal. Calcd. for C20H13N3O5 (375.33): C, 64.00; H,
3.49; and N, 11.20. Found: C, 64.12; H, 3.52; and N, 11.23.
6-Chloro-3-((Z)-2-(5-methyl-1,2,4-oxadiazol-3-yl)-2-(4-nitrophe-
nyl)vinyl)-4H-chromen-4-one (7b). Yield: 76%; mp 214–216ꢀC;
6,8-Dimethyl-3-((Z)-2-(5-methyl-1,2,4-oxadiazol-3-yl)-2-(4-
nitrophenyl)vinyl)-4H-chromen-4-one (7h). Yield: 30; mp
168–170ꢀC; 1H NMR (400 MHz, CDCl3): d 2.35 (s, 3H,
ArCH3), 2.41 (s, 3H, ArCH3), 2.63 (s, 3H, oxadiazole-CH3),
7.32 (s, 1H, ArH), 7.43 (s, 1H, vinylic-CH), 7.55–7.57 (d, 1H,
J ¼ 8.4 Hz, ArH), 7.86 (s, 1H, ArH), 8.00 (s, 1H, C2AH),
8.27–8.30 (d, 2H, J ¼ 8.4 Hz, ArH); ESI (þve): 404.2; Anal.
Calcd. for C22H17N3O5: (403.40): C, 65.50; H, 4.25; and N,
10.42. Found: C, 65.57; H, 4.32; and N, 10.45.
In vitro antibacterial screening procedure. All the oxadi-
zolyl chromones (7a–h) were assayed for their in vitro antibac-
terial activity by MIC determination against a panel of patho-
genic bacterial strains such as E. coli (ATCC 25922), S. aureus
(ATCC 13709 ‘‘Smith’’), S. aureus 032, E. faecalis (ATCC
29212), and S. pneumoniae (ATCC 49619). S. aureus 032 is a
methicillin resistant S. aureus (MRSA) strain and was obtained
as a clinical isolate [17], and remaining strains were obtained
from ATCC, USA. S. aureus (ATCC 13709 ‘‘Smith’’) is a wild
type methicillin sensitive strain. Reference strains used as qual-
ity control for MIC testing included S. aureus ATCC 29213.
Erythromycin, Gentamicin, Ampicillin, and Ciprofloxacin were
recovered from their commercial preparations. The purities and
potencies of the agents recovered from commercial preparations
were documented by ascertaining the purity of >98.5% by
high-pressure liquid chromatographic analysis and by showing
that the MICs of antibacterials were within acceptable limits
against quality control strains.
IR (KBr): 1650, 1590, 1563, 1518, 1469, 1351, 1306 cmꢁ1
;
1H NMR (400 MHz, CDCl3): d 2.64 (s, 3H, oxadiazole-CH3),
7.30–7.35 (d, 1H, J ¼ 8.4 Hz, ArH), 7.37–7.39 (d, 1H, J ¼
0.8 Hz, vinylic-CH), 7.50–7.56 (d, 2H, J ¼ 8.4 Hz, ArH),
7.60–7.62 (dd, 1H, J ¼ 2.0 and 7 Hz, ArH), 7.94–7.96 (d, 1H,
J ¼ 0.8 Hz, C2AH), 8.18–8.20 (d, 1H, J ¼ 2.0 Hz, ArH),
8.25–8.28 (d, 2H, J ¼ 8.4 Hz, ArH); ESI (þve): 410.3; Anal.
Calcd. for C20H12ClN3O5 (409.79): C, 58.62; H, 2.95; and N,
10.25. Found: C, 58.69; H, 2.93; and N, 10.30.
6-Bromo-3-((Z)-2-(5-methyl-1,2,4-oxadiazol-3-yl)-2-(4-nitrophe-
nyl)vinyl)-4H-chromen-4-one (7c). Yield: 72%; mp 230–232ꢀC;
IR (KBr): 1664, 1598, 1561, 1515, 1464, 1429, 1351, 1302
1
cmꢁ1; H NMR (400 MHz, CDCl3): d 2.63 (s, 3H, oxadiazole-
CH3), 7.29–7.27 (d, 1H, J ¼ 8.8 Hz, ArH), 7.38 (d, 1H, J ¼
0.8 Hz, vinylic-CH), 7.52–7.54 (dd, 2H, J ¼ 2.0 and 7.2 Hz,
ArH), 7.72–7.75 (dd, 1H, J ¼ 2.4 and 8.8 Hz, ArH), 7.94 (s,
1H, J ¼ 0.8 Hz, C2AH), 8.25–8.29 (dd, 2H, J ¼ 2.0 and 7.2
Hz, ArH), 8.34–8.35 (d, 1H, J ¼ 2.4 Hz, ArH); ESI (þve):
455.2; Anal. Calcd. for C20H12BrN3O5 (454.24): C, 52.88; H,
2.66; and N, 9.25. Found: C, 52.77; H, 2.71; and N, 9.30.
6-Fluoro-3-((Z)-2-(5-methyl-1,2,4-oxadiazol-3-yl)-2-(4-nitrophe-
nyl)vinyl)-4H-chromen-4-one (7d). Yield: 68%; mp 222–224ꢀC;
IR (KBr): 1651, 1630, 1590, 1519, 1482, 1351, 1325, 1306
1
cmꢁ1; H NMR (400 MHz, CDCl3): d 2.63 (s, 3H, oxadiazole-
MICs were determined as per CLSI (Clinical and Labora-
tory Standards Institute) recommendations on Mueller Hin-
ton Agar containing serial twofold dilutions of drugs [18].
For each strain, ꢃ104 CFU were applied per spot using a
multipoint inoculator (Applied Quality Services, UK). Incu-
bations were done at 35ꢀC, and growth was scored at 24 hr.
In MIC studies, twofold differences were confirmed by a
third repetition, and more frequent result were reported.
MICs employing S. pneumoniae were determined as per
CLSI recommendations on Mueller Hinton Agar supple-
mented with yeast extract (0.25%, Difco, US), glucose
(0.5%, Sigma, India) and sheep blood (5%). The incubation
was carried out in a CO2 incubator (5% CO2) [18]. Di-
methyl sulfoxide and potent antibacterial drugs Erythromy-
cin, Ampicillin, Gentamicin, and Ciprofloxacin, were used
as solvent control and standards, respectively.
CH3), 7.34–7.38 (m, 2H, ArH), 7.38 (d, 1H, J ¼ 1.2 Hz,
vinylic-CH), 7.52–7.55 (d, 2H, J ¼ 8.8 Hz, ArH),7.83–7.84
(m, 1H, Ar),7.95 (d, 1H, J ¼ 1.2 Hz, C2AH), 8.25–8.28 (d,
2H, J ¼ 8.8 Hz, ArH); ESI (þve): 394.2; Anal. Calcd. for
C20H12FN3O5 (393.33): C, 61.07; H, 3.08; and N, 10.68.
Found: C, 61.10; H, 3.12; and N, 10.69.
6,8-Dichloro-3-((Z)-2-(5-methyl-1,2,4-oxadiazol-3-yl)-2-(4-
nitrophenyl)vinyl)-4H-chromen-4-one (7e). Yield: 66%; mp
210–212ꢀC; IR (KBr): 1696, 1656, 1615, 1557, 1522, 1493,
1
1467, 1400, 1347, 1266 cmꢁ1; H NMR (400 MHz, CDCl3): d
2.45 (s, 3H, oxadiazole-CH3), 7.63–7.66 (dd, 2H, J ¼2.0 and 7.2
Hz, ArH), 7.76 (s, 1H, vinylic-CH), 7.83–7.84 (d, 1H, J ¼ 2.4
Hz, ArH), 8.18–8.19 (d, 1H, J ¼2.4 Hz, ArH), 8.36–8.39 (dd,
2H, J ¼2.0 and 7.2 Hz, ArH), 8.54 (s, 1H, C2AH); ESI (þve):
444.0; Anal. Calcd. for C20H11Cl2N3O5 (443.23): C, 54.08; H,
2.50; and N, 9.46. Found: C, 54.17; H, 2.56; and N, 9.50.
6-Chloro-7-methyl-3-((Z)-2-(5-methyl-1,2,4-oxadiazol-3-yl)-
2-(4-nitrophenyl)vinyl)-4H-chromen-4-one (7f). Yield: 62%;
mp 197–198ꢀC; 1H NMR (400 MHz, CDCl3): d 2.45 (s, 3H,
Ar-CH3), 2.61 (s, 3H, oxadiazole-CH3), 7.21 (s, 1H, ArH),
7.32 (s, 1H, vinylic-CH), 7.50–7.52 (d, 2H, J ¼ 8.8 Hz, ArH),
Acknowledgment. The authors are thankful to the Head of the
Department of Chemistry, Dr. Babasaheb Ambedkar Marath-
wada University, Aurangabad, for constant encouragement and
providing necessary facilities.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet