Synthesis and antimicrobial activity of some new 4-triazolylmethoxy-2H- chromen-2-one derivatives

Article abstract of DOI:10.1007/s00044-011-9881-0

4-(5-Aryl-4H-[1,2,4]triazol-3-ylmethoxy)-2Hchromen-2-ones have been synthesized by the one pot cyclocondensation reaction of 2-(2-oxo-2H-chromen-4- yloxy)acetohydrazide with aromatic/heterocyclic aldehydes in the presence of ammonium acetate in acetic aci

Full text of DOI:10.1007/s00044-011-9881-0

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:3750–3756
DOI 10.1007/s00044-011-9881-0
ORIGINAL RESEARCH
Synthesis and antimicrobial activity of some new
4-triazolylmethoxy-2H-chromen-2-one derivatives
•
•
•
Siva S. Panda Ritu Malik Mahesh Chand
Subhash C. Jain
Received: 10 August 2011 / Accepted: 4 November 2011 / Published online: 6 December 2011
Ó Springer Science+Business Media, LLC 2011
Abstract 4-(5-Aryl-4H-[1,2,4]triazol-3-ylmethoxy)-2H-
chromen-2-ones have been synthesized by the one pot
cyclocondensation reaction of 2-(2-oxo-2H-chromen-4-
yloxy)acetohydrazide with aromatic/heterocyclic alde-
hydes in the presence of ammonium acetate in acetic acid.
The structures of all the new compounds have been
established on the basis of their analytical and spectral
data. These compounds were also evaluated for their
antibacterial and antifungal activity against various strains
of bacteria and fungi and some are found to possess sig-
nificant antimicrobial activity when compared with cipro-
floxacin and miconazole.
by the emergence of resistance. Chromen-2-ones have been
known to possess various biological activities (Kaswala
et al., 2009; Jung et al., 2004; Rehman et al., 2005) such as
anticancer, anti-HIV, anticoagulant, antiproliferative, anti-
convulsant, and antimicrobial. On the other hand, triazole
moiety has also exhibited importance (Ram et al., 1990;
Upadhyay et al., 1990; Ergenc et al., 1992; El-Khawass
and Habib 1989; Bennur et al., 1976; Zhang et al., 1989)
by its presence in a large number of pharmaceuticals.
Examples of some antifungal drugs containing 1,2,4-tria-
zole moiety are fluconazole (Tsukuda et al., 1998;
Narayanan et al., 1993), itraconazole (Krakovsky and Ry-
bak 1990), ravuconazole (Roberts et al., 2000), and posa-
conazole (Pfaller et al., 1997). So triazole moiety can be
chosen as a possible scaffold as its presence will impact the
resulting molecule better activity than the two individual
moieties. Keeping this in mind, we have synthesized
4-triazolylmethoxychromen-2-ones and evaluated them for
their antibacterial and antifungal activities against three
Gram-positive bacteria, two Gram-negative bacteria and
four fungi, to find new antimicrobials which are at least as
effective as the existing ones. This article reports in detail
the synthesis and antimicrobial activity of some new
triazolylmethoxy-2H-chromen-2-ones.
Keywords 4-Triazolylmethoxy-2H-chromen-2-ones ꢀ
Cyclocondensation ꢀ Antimicrobial activity ꢀ
Minimum bactericidal concentration ꢀ
Minimum fungicidal concentration
Introduction
The exploration of heterocycles as privileged structures in
drug discovery is, beyond doubt, one of the major areas in
medicinal chemistry. These privileged structures represent
a class of molecules that act as ligands for various bio-
logical receptors with a high degree of binding affinity.
These days bacterial infections are becoming more chal-
lenging to treat because of the emergence of multi-drug
resistant pathogenic bacteria. Therefore, the demand for the
discovery of new antimicrobial drug is continually fuelled
Results and discussion
Chemistry
The reaction of 4-hyroxychromen-2-one and ethylbro-
moacetate in the presence of anhydrous K2CO3 in dry
acetone gave ethyl 2-(2-oxo-2H-chromen-4-yloxy)acetate
(2), which on further treatment with hydrazine hydrate
S. S. Panda ꢀ R. Malik ꢀ M. Chand ꢀ S. C. Jain (&)
Department of Chemistry, University of Delhi,
Delhi 110 007, India
e-mail: jainsc48@hotmail.com
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Med Chem Res (2012) 21:3750–3756
3751
gave 2-(2-oxo-2H-chromen-4-yloxy)acetohydrazide (3) by
following the literature procedure (Chimichi et al., 2002;
Abd Elhafez et al., 2003). 3 was cyclocondensed with
benzaldehyde in the presence of ammonium acetate in
acetic acid to obtain 4-(5-phenyl-4H-[1,2,4]triazol-3-yl-
methoxy)-2H-chromen-2-one (4a) (Scheme 1). Its TOF
ES ? MS showed the M??1 peak at m/z 320.445, corre-
sponding to the molecular formula C18H13N3O3. Its IR
spectrum did not show any absorption band corresponding
to NHNH2, as was present in 3 but in addition showed
characteristic absorption bands at 1,627 cm-1, thus indi-
cated that cycloaddition has occurred. This was fully sup-
ported by its 1H NMR spectrum, which displayed a
characteristic singlet at d 11.77 integrating for one D2O
exchangeable proton and also a singlet at d 5.41 (2H)
corresponding to –OCH2–. The protons of the phenyl group
and aromatic protons of chromen-2-one moiety were
observed as singlet and multiplets at d 7.90 (m, 1H), 7.69
(m, 2H), 7.62 (m, 1H), 7.39 (m, 3H), 7.33 (m, 2H), 5.88
(s, 1H). The 13C NMR spectrum showed all the expected
characteristic peaks.
Similar set of above reactions were repeated with
substituted aryl/hetero aldehyde to obtain in all 12 corre-
sponding desired compounds.
Biological activity
All the newly synthesized compounds were screened
for their in vitro antibacterial and antifungal activity.
For antibacterial studies microorganisms employed were
Staphylococcus aureus (MTCC 096), Bacillus subtilis
(MTCC 441), Staphylococcus epidermis (MTCC 435),
Escherichia coli (MTCC 443), Pseudomonas aeruginosa
(MTCC 424), Salmonella typhi (MTCC 733), and Klebsi-
ella pneumoniae (MTCC 432). For antifungal screening,
Aspergillus niger (MTCC 282), Aspergillus fumigatus
(MTCC 343), Aspergillus flavus (MTCC 277), and
Candida albicans (MTCC 227) strains were used. Both
microbial studies were assessed by Minimum Inhibitory
Concentration (MIC) by serial dilution method (Mackie
and McCartney 1989) and by measuring zone of inhibition
adopting cup-plate method (Chuickshank et al., 1975).
OCH2COOC2H5
OH
O
a
O
O
O
2
1
b
R3
OCH2CONHNH2
N
N
R2
O
O
CH2
c
N
H
R1
O
O
3
O
4a R1 = R2 = R3 = H
4b R1 =R3= H, R2 = F
c
4c R1 =R3= H, R2 = Cl
4d R1 =R3= H, R2 = Br
4e R1 =R3= H, R2 = OH
4f R1 =R3= H, R2 = CH3
4g R1 =R3= H, R2 = OCH3
4h R1 = H, R2 = R3 = OCH3
4i R1 = R2 = R3 = OCH3
4j R1 = OCH3, R2 = OH, R3 = H
N
N
O
O
CH2
N
X
H
O
4k X = O
4l X = S
a: BrCH2COOC2H5, K2CO3, acetone, reflux, 4h; b: NH2NH2.H2O, C2H5OH, rt, 6h; c: aldehyde, CH3COONH4, CH3COOH, rt, 6-8h
Scheme 1 Synthesis and antimicrobial activity of some new 4-triazolylmethoxy-2H-chromen-2-ones
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Med Chem Res (2012) 21:3750–3756
Various concentrations (6.25, 12.5, 25, 50, and 100 lg/ml)
of each compound were prepared by serially diluted DMSO
from the stock solution. For MIC, a standard drop of the
microbial culture, prepared for the assay, was added to the
different dilution of compounds in Muller Hilton (MH)
broth for bacteria and Sabouraud Dextrose (SD) broth for
fungi. Test solutions were then incubated for 16–18 h for
bacteria and 28–30 h for fungi at 37°C. MIC is the mini-
mum concentration of the compound, which inhibits the
visible growth of bacteria or fungi. To determine zone of
inhibition, inoculated MH agar for bacteria and SD agar for
fungi were separately poured into the sterilized petri dishes.
The poured material was allowed to set and thereafter the
‘‘CUPS’’ (08 mm diameter) were made by punching into
the agar surface with a sterile cork borer and scooping out
the punched part of the agar. The test compound solution
was added into these cups with the help of a sterile syringe.
The plates were incubated at 37°C for 16–18 h for bacteria
and 28–30 h for fungi. Clinically antimicrobial drugs
Ciprofloxacin and Miconazole were used as the positive
control and DMSO was used for blank. The experiments
were repeated three times, and the average values are
presented in Tables 1 and 2.
Table 2 Antifungal activity data of compounds 4a–l
Compound MIC in lg/ml and zone of inhibitiona (in mm)
A. niger A. fumigatus A. flavus C. albicans
4a
4b
4c
4d
4e
4f
12.5 (13–16) 12.5 (11–13) 12.5 (12–15) 6.25 (14–17)
12.5 (13–15) 12.5 (12–14) 12.5 (11–14) 6.25 (14–16)
12.5 (12–14) 25 (\10) 12.5 (12–14) 6.25 (14–16)
12.5 (11–14) 25 (\10) 12.5 (12–14) 6.25 (12–15)
12.5 (12–15) 12.5 (12–14) 25 (\10)
6.25 (13–15) 25 (11–12) 25 (\10)
6.25 (15–20)
6.26 (15–20)
6.25 (14–16)
6.25 (15–20)
12.5 (12–14)
6.25 (14–16)
4g
4h
4i
6.25 (12–15) 25 (\10)
6.25 (13–16) 25 (\10)
25 (\10)
25 (\10)
6.25 (14–17) 25 (11–13) 25 (\10)
12.5 (12–14) 12.5 (13–15) 25 (\10)
4j
4k
4l
6.25 (14–16) 25 (\10) 12.5 (12–14) 6.25 (13–15)
6.25 (15–20) 12.5 (12–15) 12.5 (13–15) 6.25 (15–18)
Miconazole 6.25 (17–22) 12.5 (14–17) 6.25 (17–20) 6.25 (15–20)
a
Values shown within the parentheses represent zone of inhibition
the broth alone served as a negative control. The tubes
which showed no visible growth after 30 h incubation were
subcultured on extract-free MHA and SDA plates and
incubated at 37°C for 28–30 h. The MBC and MFC were
regarded as the minimum concentration of the compound
under test, which prevented the growth of any bacterial and
fungal colony on the solid medium.
Some selected compounds 4b, 4h–l were further used
for the determination of Minimum Bactericidal Concen-
tration (MBC) and Minimum Fungicidal Concentration
(MFC) (Espinel-Ingroff et. al., 2002). The MBC and MFC
were determined by incorporating various concentrations
of compounds (6.25–100 lg/ml) in MH and SD broth in
tubes. One millilitre adjusted spore suspension was added
to each tube and incubated at 37°C for 3 days. The MH and
SD broths without incorporation of compound and 1 ml of
adjusted spore suspension served as a positive control and
The obtained results, depicted in Tables 1 and 2, revealed
that triazolylmethoxy-2H-chromen-2-ones 4a–l could
effectively, to some extent, inhibit the growth of all tested
strains in vitro. In antibacterial studies, all the compounds
tested were less active towards B. subtilis, S. epidermis, and
P. aeruginosa as compared to other four strains of bacteria,
Table 1 Antibacterial activity data of compounds 4a–l
Compound
MIC in lg/ml and zone of inhibitiona (in mm)
S. aureus
B. subtilis
S. epidermis
E. coli
P. aeruginosa
S. typhi
K. pneumonia
4a
12.5 (11–14)
6.25 (13–15)
12.5 (12–14)
12.5 (11–14)
12.5 (11–12)
12.5 (11–13)
6.25 (13–15)
6.25 (14–16)
6.25 (14-18)
6.25 (15–19)
6.25 (15–18)
6.25 (14–18)
6.25 (17–22)
12.5 (11–14)
50 (\10)
12.5 (12–14)
50 (\10)
12.5 (12–14)
12.5 (11–12)
6.25 (13–16)
6.25 (15–18)
6.25 (14–17)
12.5 (11–13)
12.5 (11–14)
25 (\10)
12.5 (11–13)
25 (\10)
25 (\10)
12.5 (11–14)
12.5 (12–14)
12.5 (11–15)
25 (10)
12.5 (11–14)
6.25 (13–15)
12.5 (12–15)
6.25 (13–17)
6.25 (14–16)
12.5 (13–15)
6.25 (14–17)
12.5 (11–14)
12.5 (11–13)
6.25 (15–20)
6.25 (14–18)
6.25 (15–20)
6.25 (17–20)
4b
4c
12.5 (11–13)
12.5 (12–14)
50 (\10)
50 (\10)
12.5 (12–15)
25 (\10)
4d
50 (\10)
4e
12.5 (11–12)
50 (\10)
50 (\10)
4f
12.5 (11–13)
12.5 (11–13)
25 (\10)
12.5 (11–13)
50 (\10)
12.5 (12–14)
25 (\10)
4g
25 (\10)
4h
25 (\10)
25 (\10)
6.25 (13–17)
6.25 (14–18)
6.25 (14–19)
25 (\10)
4i
6.25 (14–17)
12.5 (11–13)
50 (\10)
12.5 (12–14)
50 (\10)
12.5 (12–14)
6.25 (13–18)
6.25 (15–20)
6.25 (14–18)
6.25 (20–24)
25 (\10)
4j
25 (\10)
4k
25 (\10)
12.5 (11–14)
12.5 (12–15)
6.25 (16–20)
4l
12.5 (11–14)
6.25 (18–21)
12.5 (11–13)
6.25 (15–18)
25 (\10)
6.25 (19–21)
Ciprofloxacin
a
Values shown within the parentheses represent zone of inhibition
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3753
spectra were determined on a Perkin Elmer-2000 Spec-
trophotometer instrument. Elemental analyses were per-
formed on a Perkin Elmer series 11, CHNS/O analyzer
2400.
Table 3 Minimum Bactericidal Concentration (MBC) and Minimum
Fungicidal Concentration (MFC) of selected compounds
Compound MBC in lg/ml
MFC in lg/ml
S. aureus E. coli K. pneumonia A. niger C. albicans
4b
4h
4i
12.5
12.5
25
25
25
25
12.5
25
Ethyl 2-(2-oxo-2H-chromen-4-yloxy)acetate (2)
25
25
25
25
25
25
25
4-Hydroxy-2H-chromen-2-one (1) (5.0 g, 30.86 mmol)
was dissolved in 50 ml of dry acetone in a 100 ml round
bottom flask. To the mixture, bromoethylacetate (5.15 g,
30.86 mmol) was added along with anhydrous K2CO3
(8.0 g). The reaction mixture was refluxed for 6–8 h.
After completion of the reaction, the K2CO3 was filtered
and the filtrate was evaporated under reduced pressure
and the residue obtained was subjected to column
chromatography. Elutions with 5% ethylacetate:petroleum
ether gave 2 as a white solid. Yield 6.9 g (95%); mp
98°C (Lit (Chimichi et al., 2002) mp 97°C); IR mmax
1728, 1716, 1678, 1596, 1475, 1411, 1378, 1274, 1214,
4j
12.5
12.5
12.5
12.5
12.5
12.5
25
12.5
12.5
12.5
12.5
25
4k
4l
6.25
25
12.5
where as all the compounds showed moderate to comparable
activity against S. aureus, E. coli, and K. pneumonia. Out of
four strains of fungi, these triazoles have showed significant
activity against A. niger and C. albicans, where as moderate
to mild activity against A. fumigatus and A. flavus. Com-
pounds 4b, 4h–l were selected for MBC and MFC studies
against S. aureus, E. coli, K. pneumonia, A. niger, and
C. albicans. The MIC and MBC/MFC of the compounds
were not similar, as shown in Table 3. It was observed that
the MBC/MFC of the compounds were higher than that of
MIC.
1149, 1014, 995, 779, 660 cm-1
;
1H NMR (CDCl3,
400 MHz) d 8.02 (d, J = 8.0 Hz, 1H), 7.64 (d,
J = 7.8 Hz, 1H), 7.35 (m, 2H), 5.84 (s, 1H), 4.78 (s,
2H), 4.21 (q, 2H, –COOCH2CH3), 1.24 (t, J = 4.8 Hz,
3H, –COOCH2CH3).
Conclusions
2-(2-Oxo-2H-chromen-4-yloxy)acetohydrazide (3)
Twelve triazolylmethoxy-2H-chromen-2-ones were suc-
cessfully synthesized from 4-hydroxycoumarin in 81–96%
yields. The structures of all the compounds were confirmed
by their spectral data. All the newly synthesized com-
pounds were screened for their MIC and zone of inhibition
against seven strains of bacteria and four strains of fungi.
Amongst the compounds screened, some have shown sig-
nificant antibacterial and antifungal properties, which were
further used to determine MBC and MFC against some
selected strains of bacteria and fungi. Compounds con-
taining furan and thiophene moiety showed better activity
as compared to those containing substituted phenyl group.
It is also suggested that triazolylmethoxy-2H-chromen-2-
ones are worthy for further investigations as potential
antimicrobial agent.
A mixture of compound 2 (2.0 g, 8.54 mmol) and hydra-
zine hydrate (0.51 g, 10.24 mmol) in ethanol was stirred at
room temperature for 4 h. The solid that separated out on
cooling was filtered and recrystallized from aqueous etha-
nol to give 3 as white crystalline solid. Yield 1.7 g (90%);
mp 192°C; IR mmax 3302, 1720, 1686, 1623, 1521, 1413,
1356, 1276, 1207, 1113, 1033, 999, 946, 882, 849, 758,
1
582 cm-1; H NMR (DMSO-d6, 400 MHz) d 9.56 (s, 1H,
D2O exchangeable), 8.03 (d, J = 8.0 Hz, 1H), 7.62 (d,
J = 7.8 Hz, 1H), 7.34 (m, 2H), 5.82 (s, 1H), 4.76 (s, 2H),
4.38 (brs, 2H, D2O exchangeable); TOF ES ? MS m/z:
235.449.
General procedure
Synthesis of 4-(5-aryl-4H-[1,2,4]triazol-3-ylmethoxy)-2H-
chromen-2-one
Experimental section
Melting points were determined on an electronic apparatus
1
2-(2-Oxo-2H-chromen-4-yloxy)acetohydrazide (3) (0.20 g,
0.85 mmol) and benzaldehyde (0.091 g, 0.85 mmol) was
dissolved in 10 ml of glacial acetic acid in a 50-ml round
bottom flask. To the mixture, ammonium acetate was
added and then stirred for 6 h at room temperature. The
progress of the reaction was monitored by TLC. After the
and are uncorrected. H NMR spectra were recorded on a
Bruker Avance (400 MHz) and 13C NMR spectra were
recorded on Bruker Avance (100 MHz) using tetrameth-
ylsilane (TMS) as an internal standard and CDCl3/DMSO-
d6 as solvent. TOF ES ? Mass spectra (m/z) were recorded
on Micromass Autospec LCTKC455. Infrared (FTIR)
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Med Chem Res (2012) 21:3750–3756
4-(5-(4-Bromophenyl)-4H-[1,2,4]triazol-3-ylmethoxy)-2H-
chromen-2-one (4d)
completion of the reaction, the reaction mixture was
poured into ice cold water and neutralize with ammonia.
The precipitated product was filtered, washed with water,
and crystallized from chloroform/methanol to give the
desired product.
Yield 91%; mp 249°C; IR mmax 3212, 2926, 1686, 1611,
1581, 1457, 1375, 1254, 1160, 1141, 1112, 951, 818,
751 cm-1; 1H NMR (DMSO-d6, 400 MHz) d 11.71 (s, 1H,
[NH, D2O exchangeable), 7.94 (m, 1H), 7.54 (m, 1H),
7.46 (d, J = 7.6 Hz, 2H), 7.24 (m, 2H), 6.82 (d,
J = 7.6 Hz, 2H), 5.75 (s, 1H), 5.26 (s, 2H, –OCH2–); 13C
NMR (DMSO-d6, 100 MHz) d 167.4, 162.4, 153.2, 149.0,
144.1, 136.5, 127.0, 124.7, 121.8, 116.4, 110.1, 109.3,
91.4, 66.4 (–OCH2–). TOF ES ? MS m/z 399.398; Anal.
Calcd. for C18H12BrN3O3, Calculated: C 54.29%, H 3.04%,
N 10.55%, Found: C 54.33%, H 3.01%, N 10.67%.
4-(5-Phenyl-4H-[1,2,4]triazol-3-ylmethoxy)-2H-chromen-
2-one (4a)
Yield 90%; mp 226°C; IR mmax 3448, 2924, 1721, 1690,
1627, 1451, 1399, 1274, 1224, 1191, 1160, 1142, 1117,
1
941, 887, 825, 754, 690, 567 cm-1; H NMR (DMSO-d6,
400 MHz) d 11.77 (s, 1H, [NH, D2O exchangeable), 7.90
(m, 1H), 7.69 (m, 2H), 7.62 (m, 1H), 7.39 (m, 3H), 7.33 (m,
2H), 5.88 (s, 1H), 5.41 (s, 2H, –OCH2–); 13C NMR
(DMSO-d6, 100 MHz) d 167.4, 161.9, 153.2, 144.7, 134.2,
130.3, 129.0, 127.4, 124.5, 116.7, 115.7, 91.6, 66.4
(–OCH2–); TOF ES ? MS m/z 320.445; Anal. Calcd. for
C18H13N3O3, Calculated: C 67.71%, H 4.10%, N 13.16%,
Found: C 67.33%, H 4.11%, N 13.21%.
4-(5-(4-Hydroxyphenyl)-4H-[1,2,4]triazol-3-ylmethoxy)-
2H-chromen-2-one (4e)
Yield 94%; mp 219°C; IR mmax 3198, 2929, 1689, 1670,
1609, 1438, 1405, 1361, 1253, 1192, 1164, 1114, 954, 828,
765 cm-1; 1H NMR (DMSO-d6, 400 MHz) d 11.45 (s, 1H,
[NH, D2O exchangeable), 9.74 (brs, 1H, –OH, D2O
exchangeable), 7.92 (m, 1H), 7.51 (m, 1H), 7.42 (d,
J = 7.8 Hz, 2H), 7.23 (m, 2H), 6.75 (d, J = 7.8 Hz, 2H),
5.58 (s, 1H), 5.24 (s, 2H, –OCH2–); 13C NMR (DMSO-d6,
100 MHz) d 166.1, 164.7, 153.0, 146.5, 144.3, 132.9,
131.7, 126.1, 124.4, 123.0, 114.6, 110.7, 108.4, 92.6, 67.1
(-OCH2-); TOF ES ? MS m/z 336.561; Anal. Calcd. for
C18H13N3O4, Calculated: C 64.48%, H 3.91%, N 12.53%,
Found: C 64.50%, H 3.86%, N 12.61%.
4-(5-(4-Fluorophenyl)-4H-[1,2,4]triazol-3-ylmethoxy)-2H-
chromen-2-one (4b)
Yield 94%; mp 244°C; IR mmax 3448, 2970, 1715, 1683,
1628, 1500, 1433, 1402, 1310, 1276, 1256, 1231, 1159,
;
1118, 949, 867, 831, 762, 672, 521 cm-1 1H NMR
(DMSO-d6, 400 MHz) d 11.75 (s, 1H, [ NH, D2O
exchangeable), 7.91 (m, 1H), 7.87 (d, J = 7.6 Hz, 2H),
7.72 (m, 1H), 7.51 (m, 1H), 7.32 (d, J = 7.6 Hz, 2H),
7.24 (m, 1H), 5.76 (s, 1H), 5.28 (s, 2H, –OCH2–); 13C
NMR (DMSO-d6, 100 MHz) d 166.8, 164.8, 153.1, 149.2,
144.3, 133.9, 131.7, 125.2, 124.4, 122.5, 116.7, 110.4,
108.6, 92.4, 67.3 (–OCH2–); TOF ES ? MS m/z 338.449;
Anal. Calcd. for C18H12FN3O3, Calculated: C 64.09%, H
3.59%, N 12.46%, Found: C 64.01%, H 3.44%, N
12.53%.
4-(5-(4-Methylphenyl)-4H-[1,2,4]triazol-3-ylmethoxy)-2H-
chromen-2-one (4f)
Yield 90%, mp 144°C; IR mmax 3213, 2924, 1686, 1609,
1457, 1399, 1254, 1160, 1144, 1115, 944, 818, 752 cm-1
;
1H NMR (DMSO-d6, 400 MHz) d 11.87 (s, 1H,[NH, D2O
exchangeable), 7.99 (m, 1H), 7.88 (m, 1H), 7.61 (m, 2H),
7.37 (d, J = 7.8 Hz, 2H), 7.23 (d, J = 7.8 Hz, 2H), 5.86 (s,
1H), 5.44 (s, 2H, –OCH2–), 2.33 (s, 3H, -CH3); 13C NMR
(DMSO-d6, 100 MHz) d 169.5, 155.3, 148.1, 142.3, 136.4,
132.9, 130.6, 128.5, 126.6, 125.7, 124.3, 117.4, 94.7, 92.5,
68.5 (–OCH2–), 22.6 (–CH3); TOF ES ? MS m/z 334.554;
Anal. Calcd. for C19H15N3O3, Calculated: C 68.46%, H
4.54%, N 12.61%, Found: C 68.39%, H 4.66%, N 12.70%.
4-(5-(4-Chlorophenyl)-4H-[1,2,4]triazol-3-ylmethoxy)-2H-
chromen-2-one (4c)
Yield 92%; mp 205°C; IR mmax 3448, 2965, 1723, 1697,
1626, 1569, 1493, 1441, 1311, 1273, 1253, 1195, 1141,
1067, 938, 859, 815, 765, 710 cm-1; 1H NMR (DMSO-d6,
400 MHz) d 11.74 (s, 1H, [ NH, D2O exchangeable), 7.91
(m, 1H), 7.88 (d, J = 7.8 Hz, 2H), 7.70 (m, 1H), 7.55 (m,
1H), 7.32 (d, J = 7.8 Hz, 2H), 7.24 (m, 1H), 5.71 (s, 1H),
5.26 (s, 2H, –OCH2–); 13C NMR (DMSO-d6, 100 MHz) d
167.4, 164.1, 153.3, 148.9, 146.4, 135.9, 131.7, 125.2,
123.0, 122.5, 115.4, 110.4, 109.5, 92.6, 67.6 (–OCH2–);
TOF ES ? MS m/z 354.886; Anal. Calcd. for
C18H12ClN3O3, Calculated: C 61.11%, H 3.42%, N
11.88%, Found: C 61.23%, H 3.51%, N 11.79%.
4-(5-(4-Methoxyphenyl)-4H-[1,2,4]triazol-3-ylmethoxy)-
2H-chromen-2-one (4g)
Yield 96%; mp 180°C; IR mmax 3422, 2967, 1719, 1681,
1625, 1399, 1308, 1252, 1232, 1117, 946, 832, 754 cm-1
;
1H NMR (DMSO-d6, 400 MHz) d 11.64 (s, 1H,[NH, D2O
exchangeable), 7.97 (m, 1H), 7.71 (m, 1H), 7.67 (m, 2H),
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Med Chem Res (2012) 21:3750–3756
3755
7.38 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 5.88 (s,
1H), 5.44 (s, 2H, –OCH2–), 3.80 (s, 3H, –OCH3); 13C NMR
(DMSO-d6, 100 MHz) d 169.4, 167.2, 151.7, 149.6, 147.7,
142.6, 134.3, 130.1, 128.9, 126.6, 125.7, 124.4, 115.7,
94.8, 92.6, 68.5 (–OCH2–), 56.8 (-OCH3); TOF ES ? MS
m/z 350.672; Anal. Calcd. for C19H15N3O4, Calculated: C
65.32%, H 4.33%, N 12.03%, Found: C 65.41%, H 4.29%,
N 12.11%.
TOF ES ? MS m/z 366.498; Anal. Calcd. for C19H15N3O5,
Calculated: C 62.46%, H 4.14%, N 11.50%, Found: C
62.49%, H 4.09%, N 11.67%.
4-(5-(Furan-2-yl)-4H-[1,2,4]triazol-3-ylmethoxy)-2H-
chromen-2-one (4k)
Yield 83%; mp 190°C; IR mmax 3432, 2924, 1727, 1686,
1629, 1570, 1411, 1398, 1300, 1225, 1184, 1116, 930, 830,
747 cm-1; 1H NMR (DMSO-d6, 400 MHz) d 11.75 (s, 1H,
[NH, D2O exchangeable), 7.91 (m, 2H), 7.70 (m, 1H),
7.63 (m, 1H), 7.35 (m, 1H), 6.83 (m, 1H), 6.55 (m, 1H),
5.73 (s, 1H), 5.34 (s, 2H, –OCH2–); 13C NMR (DMSO-d6,
100 MHz) d 166.9, 164.7, 152.8, 149.0, 138.0, 134.5,
124.2, 123.0, 116.4, 113.9, 112.2, 91.2, 65.9 (–OCH2–).
TOF ES ? MS m/z 310.430; Anal. Calcd. for C16H11N3O4,
Calculated: C 62.14%, H 3.58%, N 13.59%, Found: C
61.91%, H 3.41%, N 13.44%.
4-(5-(3,4-Dimethoxyphenyl)-4H-[1,2,4]triazol-3-
ylmethoxy)-2H-chromen-2-one (4h)
Yield 95%; mp 196°C; IR mmax 3436, 2928, 1718, 1684,
1627, 1508, 1420, 1306, 1268, 1188, 1140, 1114, 932,
758 cm-1; 1H NMR (DMSO-d6, 400 MHz) d 11.63 (s, 1H,
[NH, D2O exchangeable), 7.93 (m, 1H), 7.66 (m, 1H),
7.36 (m, 2H), 7.31 (s, 1H), 7.19 (d, J = 7.6 Hz, 1H), 6.99
(d, J = 7.6 Hz, 1H), 5.83 (s, 1H), 5.45 (s, 2H, –OCH2–),
3.81 (s, 6H, 2 x –OCH3); 13C NMR (DMSO-d6, 100 MHz)
d 167.4, 165.2, 153.2, 144.8, 133.3, 127.1, 124.7, 121.9,
116.9, 111.9, 108.9, 91.6, 66.5 (–OCH2–), 55.9 (–OCH3);
TOF ES ? MS m/z 380.447; Anal. Calcd. for C20H17N3O5,
Calculated: C 63.32%, H 4.52%, N 11.08%, Found: C
63.41%, H 4.60%, N 11.04%.
4-(5-(Thiophen-2-yl)-4H-[1,2,4]triazol-3-ylmethoxy)-2H-
chromen-2-one (4l)
Yield 81%; mp 201°C; IR mmax 3431, 2929, 1727, 1684,
1620, 1585, 1475, 1394, 1316, 1275, 1184, 1112, 951, 836,
751 cm-1; 1H NMR (DMSO-d6, 400 MHz) d 11.78 (s, 1H,
[NH, D2O exchangeable), 7.92 (m, 2H), 7.70 (m, 1H),
7.65 (m, 1H), 7.35 (m, 1H), 6.88 (m, 1H), 6.57 (m, 1H),
5.71 (s, 1H), 5.33 (s, 2H, –OCH2–); 13C NMR (DMSO-d6,
100 MHz) d 166.9, 164.7, 152.8, 149.0, 138.0, 134.5,
132.8, 124.2, 116.4, 113.9, 112.2, 91.2, 65.9 (-OCH2-);
TOF ES ? MS m/z 326.603; Anal. Calcd. for
C16H11N3O3S, Calculated: C 59.07%, H 3.41%, N 12.92%,
Found: C 59.19%, H 3.24%, N 13.08%.
4-(5-(3,4,5-Trimethoxyphenyl)-4H-[1,2,4]triazol-3-
ylmethoxy)-2H-chromen-2-one (4i)
Yield 96%; mp 192°C; IR mmax 3420, 2941, 1718, 1684,
1621, 1505, 1417, 1329, 1248, 1196, 1128, 951, 829,
769 cm-1; 1H NMR (DMSO-d6, 400 MHz) d 11.74 (s, 1H,
[NH, D2O exchangeable), 7.92 (m, 1H), 7.86 (s, 2H), 7.54
(m, 1H), 7.28 (m, 2H), 5.64 (s, 1H), 5.34 (s, 2H, –OCH2–),
3.80 (s, 6H, 2 x -OCH3), 3.71 (s, 3H, –OCH3); 13C NMR
(DMSO-d6, 100 MHz) d 167.1, 162.1, 153.2, 145.0, 139.5,
129.5, 124.2, 116.5, 104.7, 91.3, 66.2(–OCH2–), 60.6
(–OCH3–), 56.1 (–OCH3), 55.8 (–OCH3); TOF ES ? MS
m/z 410.671; Anal. Calcd. for C21H19N3O6, Calculated: C
61.61%, H 4.68%, N 10.26%, Found: C 61.50%, H 4.65%,
N 10.18%.
Acknowledgments Siva S. Panda and Mahesh Chand are thankful
to UGC (New Delhi) for financial assistance.
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