Synthesis and antimicrobial assessment of novel coumarins featuring 1,2,4-oxadiazole

Article abstract of DOI:10.1007/s00044-015-1399-4

Oxadiazoles are heterocyclic compounds with a variety of application in many pharmaceuticals and agrochemical products. We report herein the convenient synthesis of 4-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-coumarins (4a-f), 6-[(3-aryl-1,2,4-oxadiazol-5-yl

Full text of DOI:10.1007/s00044-015-1399-4

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2015) 24:3743–3751
DOI 10.1007/s00044-015-1399-4
ORIGINAL RESEARCH
Synthesis and antimicrobial assessment of novel coumarins
featuring 1,2,4-oxadiazole
1
2
1
•
Challa Krishna
G. L. David Krupadanam
•
M. Vijaya Bhargavi
1
•
Ch. Prasad Rao
Received: 12 June 2014 / Accepted: 29 June 2015 / Published online: 26 July 2015
Ó Springer Science+Business Media New York 2015
Abstract Oxadiazoles are heterocyclic compounds with a
variety of application in many pharmaceuticals and agro-
chemical products. We report herein the convenient
synthesis of 4-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-cou-
marins (4a–f), 6-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-4-
methylcoumarins (7a–f) and 7-[(3-aryl-1,2,4-oxadiazol-5-
yl)methoxy]-4-phenylcoumarins (10a–f) in high yields by
one-pot condensation reaction of esters with amidoximes.
The structures of the synthesized compounds were estab-
lished on the basis of IR, NMR and mass spectrometry. The
antibacterial and antifungal activities of synthesized com-
pounds were evaluated.
Introduction
Coumarins and their analogs have attracted considerable
attention in organic and medicinal chemistry (Murray
et al., 1982). They have wide applications in food, phar-
maceutical and optical chemistry (Murray, 1989; Zabrad-
nik, 1992; Keating and Kennedy, 1997). Natural coumarins
and their synthetic structural analogs show broad biological
activities (Negwer, 1987), such as antimicrobial (Maxwell,
1993), antitumor (Dexeus et al., 1990) and antiviral
activities (Zembower et al., 1997). Meanwhile, some
coumarin derivatives could affect human immunodefi-
ciency virus integrase inhibitors (Yu et al., 2003). Some
Graphical Abstract
coumarins have inhibitory activity against some serine
proteases and matrix metalloproteases (MMPs) (Kempen
et al., 2003) and also act as a selective antiproliferative
agents (Finn et al., 2003, 2004; Kontogiorgis and Hadji-
pavlou-Litina, 2003; Morita et al., 2004).
Keywords Amidoximes Á Esters Á 1,2,4-oxadiazoles Á
Coumarins Á Antibacterial activity Á Antifungal activity
&
G. L. David Krupadanam
gldkrupa@gmail.com
Recently, the compounds containing 1,2,4-oxadiazole
scaffold have received considerable attention because of
their unique chemical structure and broad spectrum of
biological properties including antimycobacterial (Raju
et al., 2011), histamine H3 antagonism (Clitherow et al.,
1
2
Department of Chemistry, Osmania University,
Hyderabad 500007, India
Department of Pharmacy, Faculty of Technology, Osmania
University, Hyderabad 500007, India
1996), muscarinic agonism (Orlek et al., 1991), tyrosine
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Med Chem Res (2015) 24:3743–3751
kinase inhibition (Vu et al., 1999), antitumor (Zhang et al.,
005), antiinflammation activity (Nicolaides et al., 1998)
pot. The preparation of 1,2,4-oxadiazoles from esters and
amidoximes in the presence of K CO is known (Pushpak
2
2
3
and monoamine oxidase inhibition (Chimirri et al., 1996).
and Bekington, 2006). The process has been applied here
for the synthesis of coumarin–oxadiazoles (4a–f, 7a–f and
10a–f) to evaluate their antibacterial and antifungal activ-
ities at various concentrations.
In addition, anticancer activity of some 3,5-disubstituted-
1
,2,4-oxadiazoles has recently been reported (Kumar et al.,
009, Peng et al., 2012). The 1,2,4-oxadiazoles are also
2
widely used as heterocyclic amide or ester bioisosters
Luthman et al., 1999) and in the design of dipep-
(
tidomimetics as peptide building blocks (Borg et al., 1999).
Generally, five synthetic methods are used for the
preparation of 1,2,4-oxadiazole scaffold: (1) cyclization of
O-acylamidoxime which is formed from the reaction of
amidoxime with a carboxylic acid or its activated deriva-
tive (Evans et al., 2003; Katritzky et al., 2005; De Freitas
et al., 2007; Kaboudin and Malekzadeh, 2011; Barahman
and Farzaneh, 2014); (2) condensation of N-acylami-
doximes (Korbonits et al., 1989); (3) 1,3-dipolar cycload-
dition of nitriles to nitrile oxides (Jochims, 1996); (4)
oxidation of 4,5-dihydro-1,2,4-oxadiazoles (Swinbourne
et al., 1979); and (5) electrocyclic ring closure of nitre-
noides (Tsuge et al., 1980). Thus, we considered activated
ester method to get the target molecules in a single step as
there is no intermediate is involved.
Results and discussion
Chemistry
In the present study, we have synthesized the novel
series of 4-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-
coumarins (4a–f), 6-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]
-4-methylcoumarins (7a–f) and 7-[(3-aryl-1,2,4-oxadiazol-
5-yl)methoxy]-4-phenylcoumarins (10a–f) via condensation
of esters (2, 6 and 9) with amidoximes (3a–f) under reflux
conditions shown in schemes 1, 2 and 3.
4-Hydroxy coumarin (1) was synthesized bythe reactionof
o-hydroxyacetophenone, diethyl carbonate in the presence of
NaH(Peietal., 2010),6-Hydroxy-4-methyl-coumarin(5)was
obtained by the reaction of hydroquinone, ethyl acetoacetate,
CHCl in the presence of conc. H SO at 0 °C to RT (Maria
We are interested to synthesize the combination of two
chromophoric groups containing coumarin–oxadiazole as
biologically active compounds since coumarin system is
known in various naturally occurring bioactive compounds
3
2
4
et al., 2008), and 7-Hydroxy-4-phenyl-coumarin (8) was
synthesized via Pechmann condensation of resorcinol, ethyl
benzoylacetate in the presence of conc. H SO (Gareau et al.,
2
4
(
Borges et al., 2005) and oxadiazole possessing compounds
2004), followed by alkylation of hydroxy coumarins (1, 5, 8)
with ethyl bromoacetate to give esters 2,6 and 9 (Chimichi
et al., 2002). Amidoximes 3a–f were prepared as per literature
(Mathivananetal., 2012). Finally, 4-[(3-aryl-1,2,4-oxadiazol-
5-yl)methoxy]-coumarins (4a–f), 6-[(3-aryl-1,2,4-oxadiazol-
5-yl)methoxy]-4-methylcoumarins (7a–f) and 7-[(3-aryl-
reported to exhibit various biological activities. The bio-
logical importance of coumarin derivatives and 1,2,4-oxa-
diazoles encouraged us to investigate the synthesis of novel
coumarin–oxadiazoles (4a–f, 7a–f and 10a–f) in high
yields via condensation of esters with amidoximes in one
NH2
1
OH
O
8 8a
2
O
Ar
N
O
7
6
O
O
Br
O
O
O
OEt
K CO / DMF
3 a-f
3
4a
4
5
2
3
K CO / Toulene
2
3
O
OH
O
O
5'
1
'
O
N
1
4
'
N
2
'
3'
Ar
2
4
a-f
a) Ar = Benzyl
b) Ar = Phenyl
O
O
Ar =
Ar =
e)
c) Ar = o-Methoxy phenyl
d) Ar = o-Benzyloxy phenyl
f)
N
Scheme 1 Synthesis of 4-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-coumarins (4a–f)
1
23

Med Chem Res (2015) 24:3743–3751
3745
NH2
1
O
OH
8
8
a
O
O
O 2 O
Ar
N
O
O
Br
7
4
'
OEt
K CO / DMF
O
3 a-f
5'
3
4
N
O
O
6
4a
HO
Ar
5
2
3
O
K CO / Toulene
3'
O
N
2'
2
3
CH3
1
'
5
6
7
a-f
a) Ar = Benzyl
b) Ar = Phenyl
O
e) Ar =
c) Ar = o-Methoxy phenyl
O
d) Ar = o-Benzyloxy phenyl
f) Ar =
N
Scheme 2 Synthesis of 6-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-4-methyl-coumarins (7a–f)
O
2
'
NH2
1'
N
O
O
3
'
1
HO
O
O
O
OH
8
5
Ar
N
Ar
8a
2
O
O
O
O
O
7
6
O
Br
N
4
'
5'
OEt
K CO / DMF
3 a-f
3
4a
4
K CO / Toulene
2
3
2
3
1"'
6
"'
2
"'
5"'
3"'
8
9
4"'
1
0 a-f
a) Ar = Benzyl
O
O
e) Ar =
b) Ar = Phenyl
c) Ar = o-Methoxy phenyl
f) Ar =
d) Ar = o-Benzyloxy phenyl
N
Scheme 3 Synthesis of 7-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-4-phenyl-coumarins (10a–f)
1
3
1
,2,4-oxadiazol-5-yl)methoxy]-4-phenylcoumarins
(10a–
7.85 (dd, J = 1.6 Hz, J = 1.6 Hz, H-5). The C NMR of
4a supports the assigned oxadiazole ring structure by
f) were prepared in high yields by one-pot condensation
reaction of esters (2, 6 and 9) with amidoximes (3a–f) under
reflux temperature for 24–36 h.
0
0
observing peaks at 164.3 (C-5 ) and 170.1 (C-3 ). Mass
spectrum was consistent with assigned structure showing
1
M ? Na) peak at 357.6. In the H-NMR spectra of 7a,
(
Spectral analysis
–OCH , –CH protons appeared at d 5.29 (s), 4.11 (s) and
2
2
the other protons appeared at d 6.33 (s, H-3), 7.13 (dd,
J = 3.2 Hz, J = 2.8 Hz, H-7 and H-8), 7.27 (s, H-5),
The structural assignment of the title compounds (4a–f,
7
NMR and mass spectrometry which were in full agreement
1 13
a–f, 10a–f) has been made on the basis of H-NMR, C-
00
00
7.31–7.38 (m, H-2 to H-6 ). Mass spectrum was consis-
tent with assigned structure showing (M ? 1) peak at
1
349.3. In the similar way, the H-NMR spectra of 10a,
1
with the proposed structures. In the H-NMR spectra 4a,
the characteristic –OCH appeared at d 5.38 as singlet,
–OCH , –CH protons appeared at d 5.33 (s), 4.11 (s) and
2
2
2
–
CH protons appeared at d 4.14 as singlet, and the other
the other protons appeared at 6.26 (s, H-3), 6.85 (dd,
2
protons appeared at 5.77 (s, H-3), 7.29–7.33 (m, H-6 and
00
J = 1.4 Hz, J = 0.4 Hz, H-8), 6.96 (d, J = 8.6 Hz, H-6),
00
00
00
H-8), 7.33–7.35 (m, H-2 to H-6 ), 7.57–7.61 (m, H-7),
7.31 (m, H-1 to H-6 ), 7.41 (m, H-1¢¢¢ to H-6¢¢¢), 7.51 (d,
123

3
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Med Chem Res (2015) 24:3743–3751
J = 2 Hz, H-5). Mass spectrum was consistent with
assigned structure showing (M ? 1) peak at 411.5.
H-8), 7.58–7.62 (m, H-7), 7.9 (dd, J = 1.2 Hz,
13
0
0
00
J = 1.6 Hz, H-2 and H-6 ), 8.09–8.12 (m, H-5);
C
NMR (CDCl , 100.6 MHz) d (ppm): 61.2 (4-OCH ), 91.6
3
2
(
C-3), 116.7 (C-8), 114.9 (C-4a), 116.8 (C-5), 123.1 (C-6),
00 00 00
Experimental
Chemistry
124.2 (C-4 ), 125.8 (C-7), 127.4 (C-5 ), 127.5 (C-3 ),
00 00 00
29.0 (C-6 ), 131.7 (C-2 ), 133.0 (C-1 ), 153.3 (C-8a),
1
0
0
162.0 (2-C=O), 164.3 (C-5 ), 168.8 (C-3 ), 172.3 (C-4);
ESI–MS: m/z 343 (M ? Na); CHN analysis; calculated for
All melting points were obtained on a Polmon instrument,
India (model MP96), and are uncorrected. IR spectra were
recorded on a Fourier transform infrared spectroscopy (FT-
C
18
H
12
N
2
O
4
: C, 67.5; H, 3.78; N, 8.75. Found: C, 67.5; H,
3.75; N, 8.75.
4
-[(3-(2-Methoxyphenyl)-1,2,4-oxadiazol-5-yl)methoxy]-
1
13
IR), USA (Perkin-Elmer model 337), instrument. H and
C
coumarin (4c) Yield: 75 %; white solid; mp
NMR spectra were recorded on Bruker 400 MHz, Switzer-
land, using TMS as an internal standard (chemical shift in d,
ppm). J values are given in Hz. Mass spectral data were
obtained with Agilent 6310 ion trap mass spectrometer, USA.
-
1
1
1
4
7
7
58–159 °C; IR (KBr) cm : 1110 (C–O–C), 1629 (C=N),
719 (–C=O) cm ; H NMR (CDCl , 400 MHz) d (ppm):
-1 1
3
0
0
.01 (s, 2 -OCH ), 5.51 (s, 4-OCH ), 5.87 (s, H-3),
3
2
0
0
00
00
.07–7.1 (m, H-3 and H-8), 7.3–7.34 (m, H-5 and H-4 ),
0
0
.5–7.54 (m, H-7 & H-6), 7.89–8.01 (m, H-6 and H-5);
00
Synthesis
1
3
C NMR (CDCl , 100.6 MHz) d (ppm): 56.1 (2 -OCH ),
3
3
0
0
00
6
1
1
1
1
1.2 (4-OCH ), 91.7 (C-3), 111.7 (C-2 ), 114.8 (C-3 ),
2
General procedure for the synthesis of 1,2,4-oxadiazoles
0
00
14.9 (C-4a), 116.8 (C-6 ), 120.7 (C-5 ), 123.2 (C-5),
0
(
4a-f), (7a–f) and (10a–f).
To a stirred solution of ester (1.2 mmol) in toluene
30 mL), K CO (3.62 mmol) and amidoxime (1.8 mmol)
0
00
00
24.2 (C-6 ), 131.3 (C-7 ), 132.9 (C-4 ), 132.9 (C-6 ),
0
0
0
53.3 (C-8a), 158.2 (C-2 ), 162.0 (2-C=O), 164.4 (C-5 ),
0
(
2
3
67.3 (C-3 ), 171.1 (C-4); ESI–MS: m/z 373 (M ? Na);
were added and refluxed for 24–36 h. After completion of
the reaction monitored by TLC, K CO was filtered. Water
CHN analysis; calculated for C H N O : C, 65.14; H,
19 14 2 5
2
3
4.03; N, 8.00. Found: C, 65.13; H, 4.01; N, 8.01.
(
30 mL) was added to the filtrate and extracted with ethyl
acetate (50 mL). The separated organic layer was dried
over Na SO , filtered and concentrated, and the residue
4-[(3-(2-(Benzyloxy)phenyl)-1,2,4-oxadiazol-5-yl)methoxy]-
coumarin (4d) Yield: 65 %; white solid; mp 185–186 °C;
IR (KBr) cm : 1184 (C–O–C), 1626 (C=N), 1715 (–C=O)
2
4
-
1
was purified by column chromatography using (silica gel
0–120 mesh) pet ether:ethyl acetate (7:3) as eluent to get
the pure titled compound as white solid.
-
1
1
00
6
cm ; H NMR (CDCl
3
, 400 MHz) d (ppm): 5.3 (s, 2 -
OCH ), 5.52 (s, 4-OCH ), 5.78 (s, H-3), 7.09–7.28 (m,
2
2
0
00
H-4¢¢¢, H-3 and H-3¢¢¢, H-5¢¢¢), 7.34–7.44 (m, H-5 , H-8 and
4
-[(3-Benzyl-1,2,4-oxadiazol-5-yl)methoxy]-coumarin (4a)
-
00
H-2¢¢¢, H-6¢¢¢), 7.59–7.68 (m, H-4 & H-7), 7.72–7.88 (m,
H-6 & H-6 ), 7.95–8.1 (d, J = 6 Hz, H-5); C NMR
1
:
Yield: 80 %; white solid; mp 147–148 °C; IR (KBr) cm
1
00
13
-
113 (C–O–C), 1632 (C=N), 1730 (–C=O) cm ; H NMR
1 1
00
(
CDCl , 100.6 MHz) d (ppm): 56.0 (4-OCH ), 61.2 (2 -
3
2
00
0
(
CDCl , 400 MHz) d (ppm): 4.14 (s, 3 -CH ), 5.53 (s,
00
3
2
OCH ), 91.7 (C-3), 111.7 (C-2 ), 114.8 (C-3 ), 114.9 (C-
2
4
-OCH ), 5.77 (s, H-3), 7.29–7.33 (m, H-6 and H-8),
2
0
00
0
4a), 116.8 (C-6 ), 120.7 (C-5 ), 123.2 (C-5), 124.2 (C-6 ),
0
0
00
7
.33–7.35 (m, H-2 to H-6 ), 7.57–7.61 (m, H-7), 7.85 (dd,
3
1
27.1 (C-2¢¢¢ and C-6¢¢¢), 127.6 (C-4¢¢¢), 128.9 (C-3¢¢¢ and
C-5¢¢¢), 131.3 (C-7 ), 132.9 (C-4 ), 132.9 (C-6 ), 136.7 (C-
1¢¢¢), 153.3 (C-8a), 158.2 (C-2 ), 162.0 (2-C=O), 164.4 (C-
), 167.3 (C-3 ), 171.1(C-4); ESI–MS: m/z 449 (M ? Na);
1
J = 1.6 Hz, J = 1.6 Hz, H-5);
0
C
NMR (CDCl3,
0
00
00
1
00.6 MHz) d (ppm): 32.2 (3 -CH ), 61.2 (4-OCH ), 91.6
00
2
2
(
C-3), 116.7 (C-8), 116.8 (C-4a), 123.2 (C-5), 124.2 (C-6),
0
0
5
00 00 00
1
1
1
27.4 (C-4 ), 128.7 (C-7), 128.8 (C-5 ), 128.9 (C-3 ),
CHN analysis; calculated for C H N O : C, 70.42; H,
25 18 2 5
0
0
00
00
29.0 (C-6 ), 132.9 (C-2 ), 134.8 (C-1 ), 153.2 (C-8a),
0
4
.25; N, 6.57. Found: C, 70.41; H, 4.24; N, 6.56.
0
62.0 (2-C=O), 164.3 (C-5 ), 170.0 (C-3 ), 172.4 (C-4);
4
2
-[(3-(4,5-Dimethoxy-1,2-dihydrocyclobutabenzen-1-yl)-1,
4-oxadiazol-5-yl)methoxy]-coumarin (4e) Yield: 60 %;
ESI–MS: m/z 357.6 (M ? Na); CHN analysis; calculated
for C H N O :C, 68.26; H, 4.22; N, 8.38. Found: C,
19 14 2 4
-
1
white solid; mp 162–163 °C; IR (KBr) cm : 1181 (C–O–
6
8.28; H, 4.22; N, 8.37.
-
1 1
C), 1626 (C=N), 1730 (–C=O) cm ; H NMR (CDCl ,
3
4
-[(3-Phenyl-1,2,4-oxadiazol-5-yl)methoxy]-coumarin (4b)
-
400 MHz) d (ppm): 3.41 (dd, J = 15.6 Hz, J = 5.4 Hz,
H-6 ), 3.64 (dd, J = 15.6 Hz, J = 8.0 Hz, H-6 ), 3.73 (s,
00 00
3 -OCH ), 3.73 (s, 4 -OCH ), 4.77 (dd, J = 8.0 Hz,
3 3
00
J = 5.4 Hz, H-1 ), 5.29 (s, 4-OCH ), 5.78 (s, H-3), 6.77 (s,
2
1
:
0
0
0
0
Yield: 75 %; white solid; mp 138–139 °C; IR (KBr) cm
-
1
1
1
113 (C–O–C), 1633 (C=N), 1735 (–C=O) cm ; H NMR
CDCl , 400 MHz) d (ppm): 5.5 (s, 4-OCH ), 5.87 (s, H-3),
(
3
2
0
0
00
00
00 00
7
.3–7.36 (m, H-3 and H-4 ), 7.49–7.55 (m, H-5 , H-6 and
H-5 & H-2 ), 7.29 (dd, J = 8 Hz, J = 8.4 Hz, H-8 and
1
23

Med Chem Res (2015) 24:3743–3751
3747
1
H-7), 7.57–7.66 (m, H-6), 7.86–7.92(m, H-5); C NMR
3
0
0
153.8 (C-6), 160.6 (2-C=O), 168.6 (C-5 ), 174.2 (C-3 );
ESI–MS: m/z 335 (M ? 1); CHN analysis; calculated for
C H N O : C, 68.26; H, 4.22; N, 8.38. Found: C, 68.16;
00 00
(
CDCl , 100.6 MHz) d (ppm): 35.2 (C-6 ), 37.3 (C-1 ),
3
5
2
1
1
1
4
5.2 (29 –OCH ’s), 61.3 (4-OCH ), 91.6 (C-3), 106.6 (C-
3 2
19 14 2 4
0
0
00
), 107.2 (C-5 ), 114.8 (C-8), 116.8 (C-4a), 123.1 (C-5),
00
H, 4.12; N, 8.34.
00
24.2 (C-6), 132.9 (C-7), 133.9 (C-1a ), 134.7 (C-5a ),
0
6
4
1
1
2
-[(3-(2-Methoxyphenyl)-1,2,4-oxadiazol-5-yl)methoxy)]-
-methyl-coumarin (7c) Yield: 65 %; white solid; mp
0
00
0
50.0 (C-4 ), 150.8 (C-3 ), 153.3 (C-8a), 162.0 (C-3 ),
0
64.3 (2-C=O), 171.7 (C-5 ), 172.4 (C-4); ESI–MS: m/z
-
1
35–136 °C; IR (KBr) cm : 1172 (C-O-C), 1605 (C=N),
704 (–C=O) cm ; H NMR (CDCl , 400 MHz) d (ppm):
29 (M ? Na); CHN analysis; calculated for C H N O :
2
2
18
2
6
-1 1
3
C, 65.02; H, 4.46; N, 6.89. Found: C, 65.01; H, 4.46; N,
0
0
.42 (s, 4-CH ), 3.98 (s, 2 -OCH ), 5.42 (s, 6-OCH ), 6.32
3
3
2
6
.88.
(
s, H-3), 7.05 (dd, J = 4 Hz, J = 3.2 Hz, H-7 & H-8),
00 00 00
4-[(3-(Pyridine-4-yl)-1,2,4-oxadiazol-5-yl)methoxy]-coumarin
7.23–7.23 (m, H-3 , H-5 and H-5), 7.27–7.31 (m, H-4 ),
13
0
0
(
4f) Yield: 65 %; white solid; mp 122–124 °C; IR (KBr)
8.01 (d, J = 7.6 Hz, H-6 );
C
NMR (CDCl3,
-
1
-1 1
cm : 1118 (C–O–C), 1631 (C=N), 1739 (–C=O) cm ; H
00
100.6 MHz): d 18.7 (4-CH ), 56.0 (2 -OCH ), 61.7 (6-
3
3
NMR (CDCl , 400 MHz) d (ppm): 5.22 (s, 4-OCH ), 5.81
OCH ), 109.8 (C-5), 111.7 (C-3), 113.9 (C-7), 115.8 (C-
2
3
2
00 00 00
(
s, H-3), 7.42–7.44 (m, H-6 & H-8), 7.65 (m, H-7),
3 ), 118.2 (C-1 ), 119.4 (C-4a), 120.6 (C-5 ), 120.7 (C-8),
0
0
7
.84–7.87 (m, H-5), 7.99 (dd, J = 1.2 Hz, J = 1.6 Hz,
131.3 (C-4¢¢¢), 132.7 (C-6 ), 148.7 (C-8a), 151.7 (C-4),
153.8 (C-2 ), 158.1 (C-6), 160.6 (2-C=O), 167.1 (C-5 ),
0
0
00
00
00
13
H-3 and H-5 ), 8.75 (m, H-2 and H-6 ); C NMR
00
0
0
(
CDCl , 100.6 MHz) d (ppm): 61.2 (4-OCH ), 91.6 (C-3),
173.1 (C-3 ); ESI–MS: m/z 365 (M ? 1); CHN analysis;
3
2
1
16.7 (C-8), 114.9 (C-4a), 116.8 (C-5), 123.1 (C-6), 125.8
00
calculated for C H N O : C, 65.93; H, 4.43; N, 7.69.
20 16 2 5
0
0
00
00
(
(
(
C-7), 127.4 (C-5 & C-3 ), 131.7 (C-6 and C-2 ), 133.0
0
Found: C, 65.89; H, 4.42; N, 7.64.
0
0
C-1 ), 153.3 (C-8a), 162.0 (2-C=O), 164.3 (C-5 ), 168.8
0
6
4
1
1
-[(3-(2-Benzyloxyphenyl)-1,2,4-oxadiazol-5-yl)methoxy)]-
-methyl-coumarin (7d) Yield: 60 %; white solid; mp
C-3 ), 172.3 (C-4); ESI–MS: m/z 322 (M ? 1); CHN
analysis; calculated for C H N O : C, 63.55; H, 3.45; N,
3
1
7
11
4
-1
72–173 °C; IR (KBr) cm : 1170 (C–O–C), 1603 (C=N),
1
3.08. Found: C, 63.54; H, 3.45; N, 13.06.
-
1 1
709 (–C=O) cm ; H NMR (CDCl , 400 MHz) d (ppm):
3
00
2.4 (s, 4-CH ), 5.28 (s, 2 -OCH ), 5.42 (s, 6-OCH ), 6.31
3 2 2
6
-[(3-Benzyl-1,2,4-oxadiazol-5-yl)methoxy]-4-methyl-cou-
marin (7a) Yield: 75 %; white solid; mp 115–116 °C; IR
(s, H-3), 6.97 (dd, J = 8.3 Hz, J = 2.3 Hz, H-7), 7.21 (dd,
J = 8.3 Hz, J = 4.2 Hz, H-8), 7.24–7.29 (m, J = 7.5 Hz,
-
KBr) cm : 1126 (C–O–C), 1626 (C=N), 1750 (–C=O)
1
(
-
1
1
00
cm
;
H NMR (CDCl , 400 MHz) d (ppm): 2.33 (s,
J = 1.1 Hz, H-4¢¢¢), 7.27–7.34 (m, H-3¢¢¢, H-5¢¢¢ and H-3
3
0
00
00
4
-CH ), 4.11 (s, 3 -CH ), 5.29 (s, 6-OCH ), 6.31 (s, H-3),
3
and H-5 ), 7.44–7.58 (m, H-2¢¢¢ and H-6¢¢¢, H-5 and H-4 ),
2
2
0
0
13
7
.13 (dd, J = 3.2 Hz, J = 2.8 Hz, H-7 & H-8), 7.27 (s,
7.95 (d, J = 7.6 Hz, H-6 );
C
NMR (CDCl3,
00
00
00
13
H-5), 7.31–7.38 (m, H-2 to H-6 ); C NMR (CDCl3,
100.6 MHz) d (ppm): 18.6 (4-CH ), 61.8 (2 -OCH ), 70.9
3
2
0
1
00.6 MHz) d (ppm): 18.6 (4-CH ), 32.2 (3 -CH ), 61.7 (6-
(6-OCH ), 109.8 (C-5), 113.4 (C-3), 115.8 (C-7), 118.8 (C-
2
3
2
00
00
00
00
OCH ), 109.7 (C-5), 115.8 (C-3), 118.0 (C-5 ), 118.2 (C-
2
2 ), 119.3 (C-1 ), 120.6 (C-4a), 121.0 (C-5 ), 126.7 (C-8),
0
0
00
7
1
1
1
), 118.8 (C-3 ), 119.3 (C-4a), 120.6 (C-8), 127.3 (C-4 ),
00
127.7 (C-2¢¢¢ and C-6¢¢¢), 128.7 (C-4¢¢¢), 131.3 (C-3¢¢¢ and
0
0
00
00
00
28.8 (C-6 ), 128.9 (C-2 ), 135.0 (C-1 ), 148.8 (C-8a),
0
C-5¢¢¢), 132.6 (C-4 ), 136.5 (C-6 ), 148.7 (C-1¢¢¢), 151.7 (C-
8a), 153.8 (C-4), 157.1 (C-6 and C-2 ), 160.6 (2-C=O),
00
51.7 (C-4), 153.7 (C-6), 160.6 (2-C=O), 169.7 (C-5 ),
0
0
0
74.3 (C-3 ); ESI–MS: m/z 349.3 (M ? 1); CHN analysis;
167.1 (C-5 ), 173.0 (C-3 ); ESI–MS: m/z 441 (M ? 1);
calculated for C H N O : C, 68.96; H, 4.63; N, 8.04.
4
CHN analysis; calculated for C H N O : C, 70.90; H,
26 20 2 5
2
0
16
2
Found: C, 68.95; H, 4.62; N, 8.03.
-[(3-Phenyl-1,2,4-oxadiazol-5-yl)methoxy]-4-methyl-cou-
4.58; N, 6.36. Found: C, 70.81; H, 4.47; N, 6.32.
6
6-[(3-(4,5-Dimethoxy-1,2-dihydrocyclobutabenzen-1-yl)-
marin (7b) Yield: 70 %; white solid; mp 118–119 °C; IR
1,2,4-oxadiazol-5-yl)methoxy)]-4-methyl-coumarin (7e)
-1
-
KBr) cm : 1176 (C–O–C), 1574 (C=N), 1723 (–C=O)
1
(
Yield: 55 %; white solid; mp 142–143 °C; IR (KBr) cm
1171 (C–O–C), 1606 (C=N), 1715 (–C=O) cm ; H NMR
:
-
1
1
-1 1
cm
;
H NMR (CDCl , 400 MHz) d (ppm): 2.43 (s,
3
4
-CH ), 5.42 (s, 6-OCH ), 6.33 (s, H-3), 7.24 (dd,
3
(CDCl , 400 MHz) d (ppm): 2.37 (s, 4-CH ), 3.38 (dd,
J = 2 Hz, J = 2.4 Hz, H-6 ), 3.62 (dd, J = 5.2 Hz,
00 00 00
J = 5.2 Hz, H-6 ), 3.86 (s, 3 -OCH ), 3.87 (s, 4 -OCH ),
3 3
00
4.74 (t, H-1 ), 5.32 (s, 6-OCH ), 6.31 (s, H-3), 6.74 (s,
2
2
3
3
00
J = 1.6 Hz, J = 2.4 Hz, H-5 and H-7), 7.31–7.37 (m,
00
0
0
00
H-4 ), 7.5–7.51 (m, H-3 , H-5 and H-8), 8.08 (dd,
13
00
00
J = 1.6 Hz, J = 1.6 Hz, H-2 and H-6 ); C NMR
CDCl , 100.6 MHz) d (ppm): 18.7 (4-CH ), 61.7 (6-
0
0
00
(
H-5 ), 6.76 (s, H-2 ), 7.17 (d, J = 2.8 Hz, H-7), 7.19 (d,
J = 3.2 Hz, H-8), 7.28 (dd, J = 0.4 Hz, J = 0.8 Hz, H-5);
13
3
3
0
OCH ), 109.8 (C-5), 115.8 (C-3), 118.8 (C-7 ), 119.3 (C-
2
0
00
0
00
00
4
a), 120.6 (C-8), 126.1 (C-1 ), 127.4 (C-2 & C-6 ), 128.
0
C NMR (CDCl , 100.6 MHz) d (ppm): 18.6 (4-CH ),
00 00
35.2 (C-6 ), 37.3 (C-1 ), 56.2 (29 -OCH ’s), 61.7 (6-
3
3
3
0
00
(
C-3 & C-5 ), 131.6 (C-4 ), 148.8 (C-8a), 151.7 (C-4),
123

3
748
Med Chem Res (2015) 24:3743–3751
0
0
00
00
1 ), 160.2 (C-8a), 160.7 (C-4), 160.9 (C-7), 167.9 (C=O),
OCH ), 106.6 (C-2 ), 107.2 (C-5), 109.7 (C-5 ), 113.7 (C-
2
0
00
0
0
0
?
169.8 (C-5 ), 173.8 (C-3 ); ESI–MS: m/z 396.5 (M ); CHN
7
1
1
1
), 115.8 (C-3), 118.3 (C-4a), 119.2 (C-8), 120.6 (C-1a ),
00
0
0
34.7 (C-5a ), 148.8 (C-8a), 150.0 (C-4 ), 150.8 (C-3 ),
0
analysis; calculated for C H N O : C, 72.72; H, 4.07; N,
24 16 2 4
0
51.7 (C-4), 153.7 (C-6 ), 160.6 (C-5 ), 171.4 (2-C=O),
0
7.07; Found: C, 72.62; H, 4.02; N, 7.02.
74.3 (C-3 ); ESI–MS: m/z 421 (M ? 1); CHN analysis;
7
4
1
-[(3-(2-Methoxyphenyl)-1,2,4-oxadiazol-5-yl)methoxy)]-
-phenyl-coumarin (10c) Yield: 55 %; white solid; mp
calculated for C H N O : C, 65.71; H, 4.79; N, 6.66.
23 20 2 6
Found: C, 65.62; H, 4.67; N, 6.62.
-Methyl-6-[(3-pyridin-4-yl)-1,2,4-oxadiazol-5-yl-methoxy)]-
coumarin (7f) Yield: 65 %; white solid; mp 127–128 °C;
-
1
28–129 °C; IR (KBr) cm : 1176 (C–O–C), 1604 (C=N),
-
1 1
4
1711 (–C=O) cm ; H NMR (CDCl , 400 MHz) d (ppm):
3.98 (s, 2 –OCH ), 5.44 (s, 7-OCH ), 6.26 (s, H-3), 6.91
3
3
0
0
2
-
1
IR (KBr) cm : 1126 (C–O–C), 1610 (C=N), 1726 (–C=O)
(dd, J = 2.4 Hz, J = 2.8 Hz, H-6), 7.05–7.12 (m, H-8 and
00
-
1
1
00
00
cm
;
H NMR (CDCl , 400 MHz) d (ppm): 2.43 (s,
-CH ), 5.44 (s, 6-OCH ), 6.33 (s, H-3), 6.97–7.21 (m, H-7
3
H-3 , H-5 ), 7.31–7.32 (m, H-2¢¢¢ to H-6¢¢¢ and H-4 ),
7.48–7.49 (m, H-5), 8.01 (dd, J = 1.6 Hz, J = 2 Hz,
3
4
2
0
0
00 13
00
and H-8), 7.5 (dd, J = 4.2 Hz, J = 2.3 Hz, H-6 ),
00
H-6 ); C NMR (CDCl , 100.6 MHz) d (ppm): 56.0 (2 -
3
00
7
.84–7.89 (m, H-5 and H-2 ), 8.66–8.69 (m, H-5 and
13
OCH ), 61.1 (7-OCH ), 102.4 (C-8), 111.7 (C-6), 112.4 (C-
3
2
0
0
00
00
H-3 ); C NMR (CDCl , 100.6 MHz) d (ppm): 18.7 (4–
4a), 112.7 (C-3), 113.8 (C-3 ), 115.1 (C-1 ), 120.7 (C-4¢¢¢),
127.8 (C-5), 128.8 (C-3¢¢¢ and C-5¢¢¢), 129.7 (C-2¢¢¢ and
3
CH ), 61.7 (6-OCH ), 109.8 (C-5), 115.9 (C-3), 118.4 (C-
2
3
00
00
0
00
00
00
7
), 119.1 (C-4a), 120.7 (C-2 and C-6 ), 121.2 (C-8 ),
0
C-6¢¢¢), 131.4 (C-4 and C-5 ), 132.7 (C-6 ), 135.3 (C-1¢¢¢),
155.5 (C-4), 155.7 (C-8a), 158.1 (C-2 ), 160.3 (C-7), 160.8
0
00
00
00
1
33.59 (C-1 ), 148.9 (C-8a), 150.7 (C-3 and C-5 ), 151.6
0
0
0
(
C-4), 153.6 (C-6), 160.5 (2-C=O), 167.1 (C-5 ), 175.1 (C-
0
(2-C=O), 167.1 (C-5 ), 172.5 (C-3 ); ESI–MS: m/z 426.5
?
(M ); CHN analysis; calculated for C H N O : C, 70.42;
3
); ESI–MS: m/z 336 (M ? 1); CHN analysis; calculated
2
5 18 2 5
for C H N O : C, 64.47; H, 3.91; N, 12.53; Found: C,
18 13 3 4
H, 4.25; N, 6.57; Found: C, 70.62; H, 4.22; N, 6.52.
-[(3-(2-Benzyloxyphenyl)-1,2,4-oxadiazol-5-yl)methoxy)]-
4-phenyl-coumarin (10d) Yield: 50 %; white solid; mp
6
4.62; H, 3.87; N, 12.62.
7
7
-[(3-Benzyl-1,2,4-oxadiazol-5-yl)methoxy]-4-phenyl-cou-
-
1
marin (10a) Yield: 65 %; white solid; mp 107–108 °C;
IR (KBr) cm : 1118 (C–O–C), 1610 (C=N), 1721 (–C=O)
155–156 °C; IR (KBr) cm : 1158 (C–O–C), 1607 (C=N),
-
1
-1 1
1722 (–C=O) cm ; H NMR (CDCl , 400 MHz) d (ppm):
3
-
1
1
0
cm ; H NMR (CDCl , 400 MHz) d (ppm): 4.11 (s, 3 -
5.28 (s, 1¢¢¢-OCH ), 5.42 (s, 7-OCH ), 6.31 (s, H-3), 6.91
3
2
2
CH ), 5.31 (s, 7-OCH ), 6.26 (s, H-3), 6.85 (dd,
2
(dd, J = 2.4 Hz, J = 2.8 Hz, H-6), 7.05–7.12 (m, H-8 and
0000
2
0
0
00
0000
J = 1.4 Hz, J = 0.4 Hz, H-8), 6.96 (d, J = 8.6 Hz, H-6),
0
H-3 , H-5 ), 7.15–7.22 (m, H-2 to H-6 ), 7.31–7.38 (m,
00
0
00
7
.31 (m, H-1 to H-6 ), 7.41 (m, H-1¢¢¢ to H-6¢¢¢), 7.51 (d,
H-2¢¢¢ to H-6¢¢¢ and H-4 ), 7.48–7.52 (m, H-5), 8.01 (dd,
J = 1.6 Hz, J = 2 Hz, H-6 );
1
3
00
13
J = 2 Hz, H-5); C NMR (CDCl , 100.6 MHz) d (ppm):
2.2 (3 -CH ), 61.1 (7-OCH ), 101.9 (C-8a), 102.3 (C-6),
2
C
NMR (CDCl3,
3
0
00
3
100.6 MHz) d (ppm): 61.2 (2 -OCH ), 70.5 (7-OCH ),
2
2
2
0
0
1
12.4 (C-4a), 112.5 (C-3), 112.8 (C-4 ), 113.8 (C-5), 127.3
00
102.5 (C-8), 112.5 (C-7), 112.7 (C-4a), 111.3 (C-6), 113.4
00 00 00
00
(
C-4¢¢¢), 128.4 (C-5 ), 128.8 (C-3 ), 128.8 (C-6¢¢¢), 128.9
C-5¢¢¢), 129.0 (C-3¢¢¢), 129.7 (C-2¢¢¢), 134.9 (C-6 ), 135.2
C-2 ), 155.5 (C-1¢¢¢), 155.7 (C-1 ), 160.2 (C-8a), 160.7 (C-
), 160.9 (C-7), 167.9 (2-C=O), 169.8 (C-5 ), 173.8 (C-3 );
(C-3), 113.8 (C-3 ), 115.8 (C-1 ), 121.0 (C-5 ), 126.8 (C-
0000 0000 0000
1 ), 127.74 (C-5), 128.3 (C-6 ), 128.4 (C-2 ), 128.5
00
(
0
0
00
00
0000
0000
0000
(
(C-4 ), 128.8 (C-6 ), 129.7 (C-2¢¢¢), 131.4 (C-3 and
0
0
00
4
C-5 ), 132.5 (C-3¢¢¢ and C-5¢¢¢), 135.3 (C-1 ), 136.6 (C-
0
0
0000
ESI–MS: m/z 411.5 (M ? 1); CHN analysis; calculated for
6 ), 155.5 (C-1¢¢¢), 155.7 (C-1 ), 157.1 (C-4), 157.3 (C-
2 ), 160.4 (C-8a), 160.8 (2-C=O), 167.2 (C-5 ), 172.5 (C-
0
0
0
C H N O : C, 73.16; H, 4.42; N, 6.83; Found: C, 73.62;
25 18 2 4
0
?
3 ); ESI–MS: m/z 502.6 (M ); CHN analysis; calculated
H, 4.32; N, 6.62.
-[(3-Phenyl-1,2,4-oxadiazol-5-yl)methoxy]-4-phenyl-cou-
marin (10b) Yield: 60 %; white solid; mp 117–118 °C;
for C H N O : C, 74.09; H, 4.41; N, 5.57; Found: C,
31 22 2 5
7
74.62; H, 4.22; N, 5.52.
-
1
IR (KBr) cm : 1156 (C–O–C), 1610 (C=N), 1721 (–C=O)
7-[(3-(4,5-Dimethoxy-1,2dihydrocyclobutabenze-1-yl)-1,2,
-
1
1
cm
;
H NMR (CDCl , 400 MHz) d (ppm): 5.43 (s,
4-oxadiazol-5-yl)methoxy)]-4-phenyl-coumarin
(10e)
-
3
1
7
-OCH ), 6.27 (s, H-3), 6.92 (dd, J = 2.4 Hz, J = 2.8 Hz,
2
Yield: 50 %; white solid; mp 142–143 °C; IR (KBr) cm
1116 (C–O–C), 1614 (C=N), 1719 (–C=O) cm ; H NMR
:
-
1 1
H-8), 7.05 (d, J = 2.4 Hz, 1H, H-6), 7.31 (m, H-1¢¢¢ to
0
0
00
H-6¢¢¢), 7.41 (m, H-1 to H-6 ), 7.51 (d, J = 2 Hz, H-5);
(CDCl3, 400 MHz)
00
d
(ppm): 3.38 (dd, J = 2 Hz,
1
3
C NMR (CDCl , 100.6 MHz) d (ppm): 61.1 (7-OCH ),
J = 2.4 Hz, H-6 ), 3.62 (dd, J = 5.2 Hz, J = 5.2 Hz,
3
2
00 00 00
H-6 ), 3.86 (s, 3 -OCH ), 3.87 (s, 4 -OCH ), 4.74 (dd,
3 3
00
J = 2.4 Hz, J = 2.4 Hz, H-1 ), 5.32 (s, 7-OCH ), 6.48 (s,
2
1
01.9 (C-8a), 102.3 (C-6), 112.4 (C-4a), 112.5 (C-3), 112.8
0
0
00
(
C-4 ), 113.8 (C-5), 127.3 (C-4¢¢¢), 128.4 (C-5 ), 128.8 (C-
0
0
00
00
3
2
), 128.8 (C-6¢¢¢), 128.9 (C-5¢¢¢), 129.0 (C-3¢¢¢), 129.7 (C-
H-3), 6.57 (s, H-5 ), 6.62 (d, J = 3.7 Hz, H-2 ), 6.69 (dd,
J = 1.9 Hz, J = 0.4 Hz, H-8), 7.2 (dd, J = 8.4 Hz,
0
0
00
¢¢¢), 134.9 (C-6 ), 135.2 (C-2 ), 155.5 (C-1¢¢¢), 155.7 (C-
1
23

Med Chem Res (2015) 24:3743–3751
3749
Table 1 Antimicrobial activity of compounds (4a–f), (7a–f) and (10a–f)
Compd. no.
Conc. (lg/ mL)
Antibacterial activity
Antifungal activity
a
a
a
a
S. aureus
E. coli
A. terreus
R. solani
4
4
4
4
4
4
7
7
7
7
7
7
1
1
1
1
1
1
a
200
15
11
19
13
18
8
31
23
26
17
28
20
30
22
30
24
27
18
24
19
32
23
21
13
28
21
32
24
28
22
28
17
24
16
21
32
24
31
22
28
27
24
20
NA
25
18
32
23
27
19
30
21
33
26
26
18
21
11
28
19
39
27
26
15
34
25
28
19
26
20
13
16
26
15
34
25
28
19
26
20
NA
21
25
18
32
23
21
17
30
21
31
24
29
11
16
10
28
19
39
27
26
15
24
26
25
19
29
20
17
16
15
34
25
28
19
26
21
23
NA
22
1
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
200
00
b
1
c
1
d
18
12
22
12
16
10
27
13
21
10
13
7
1
e
1
f
1
a
1
b
1
c
1
d
19
12
28
19
31
12
29
11
31
10
19
12
28
19
18
12
28
11
18
NA
1
e
1
f
1
0a
0b
0c
0d
0e
0f
1
1
1
1
1
1
Ampicillin
20 lg/mL
20 lg/mL
Clotrimazole
S. aureus, Staphylococcus aureus; E.coli Escherichia coli; A.terreus, Aspergillus terreus and R.solani, Rhizoctonia solani
a
Zone of inhibition
J = 1.9 Hz, H-6), 7.41–7.47 (m, H-4¢¢¢), 7.43–7.49 (m,
H-2¢¢¢ and H-6¢¢¢, H-3¢¢¢ and H-5¢¢¢), 7.7 (d, J = 8.4 Hz,
113.8 (C-5¢¢¢), 115.4 (C-4), 127.8 (C-5), 127.9 (C-1¢¢¢),
0
0
128.3 (C-3¢¢¢), 128.9 (C-6¢¢¢), 134.1 (C-2¢¢¢), 134.7 (C-1a ),
1
3
00
00
00
00
H-5); C NMR (CDCl , 100.6 MHz) d (ppm): 35.2 (C-6 ),
135.2 (C-5a ), 135.4 (C-1¢¢¢), 150.1 (C-4 ), 150.8 (C-3 ),
155.5 (C-8a), 155.7 (C-4 ), 160.2 (C-3 ), 160.7 (C-7), 171.5
3
0
0
0
0
3
7.4 (C-1 ), 56.2 (29 –OCH ’s), 61.2 (7-OCH ), 106.7 (C-
2
3
0
0
0
?
(C=O), 173.3 (C-5 ); ESI–MS: m/z 482.6 (M ); CHN
8
), 107.2 (C-2 ), 111.5 (C-4a), 112.4 (C-6), 112.7 (C-3),
123

3
750
Med Chem Res (2015) 24:3743–3751
analysis; calculated for C H N O : C, 69.70; H, 4.60; N,
28 22 2 6
of the compounds showed good antibacterial activity (4c,
4e, 7a, 7e, 7f, 10a, 10b and 10f) and antifungal activity (4c,
5
.81; Found: C, 69.62; H, 4.52; N, 5.82.
4e, 4f, 7e, 7f, 10a and 10f) in higher concentrations com-
4-Phenyl-7-[(3-(pyridine-4-yl)-1,2,4-oxadiazol-5-yl)methoxy]-
parable with that of standard drugs tested. Although with
respect to standard drugs, all the tested compounds were
found to be moderate to poor in their activity. So, the result
of all preliminary study indicated that the 4-[(3-aryl-1,2,4-
oxadiazol-5-yl)methoxy]coumarins (4a–f), 6-[(3-aryl-1,2,4-
oxadiazol-5-yl)methoxy]-4-methylcoumarins (7a–f) and
coumarin (10f) Yield: 60 %; white solid; mp 112–113 °C;
IR (KBr) cm : 1158 (C–O–C), 1614 (C=N), 1716 (–C=O)
-
1
-
1
1
cm
; H NMR (CDCl , 400 MHz) d (ppm): 5.46 (s,
3
7
-OCH ), 6.28 (s, H-3), 6.92 (dd, J = 2.4 Hz, J = 2.8 Hz,
2
H-8), 7.05 (d, J = 2.4 Hz, H-6), 7.31–7.37 (m, H-1¢¢¢ to
0
0
H-6¢¢¢), 7.41 (dd, J = 8.4 Hz, H-5), 7.96–7.98 (m, H-2 and
7-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-4-phenylcoumarins
0
0
00
00 13
H-6 , H-3 and H-5 ); C NMR (CDCl , 100.6 MHz) d
3
(10a–f) moiety represent a new class of pharmacophore for
broad spectrum of antibacterial and antifungal activity.
(
ppm): 61.1 (7-OCH ), 102.3 (C-8), 112.3 (C-6), 112.9 (C-
2
00
00
0
4
1
a), 113.9 (C-3), 121.2 (C-2 and C-6 ), 128.3 (C-5 ),
28.0 (C-4¢¢¢), 128.9 (C-3¢¢¢ and C-5¢¢¢), 129.7 (C-2¢¢¢ and
0
0
00
00
C-6¢¢¢), 133.5 (C-1 ), 135.2 (C-1¢¢¢), 150.7 (C-3 and C-5 ),
1
Conclusion
55.4 (C-8a), 155.7 (C-4), 160.1 (C-7), 160.7 (2-C=O),
0
0
?
67.2 (C-5 ), 174.6 (C-3 ); ESI–MS: m/z 397.5 (M ); CHN
1
Herewith, we report the simple and efficient method for
synthesis of novel mixed heterocyclic compounds, 4-[(3-
aryl-1,2,4-oxadiazol-5-yl)methoxy]-coumarins (4a–f), 6-
analysis; calculated for C H N O : C, 69.52; H, 3.80; N,
23 15 3 4
1
0.57; Found: C, 69.62; H, 3.72; N, 10.62.
[
(
(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-4-methyl-coumarins
Antimicrobial activity
7a–f) and 7-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-4-phe-
nyl-coumarins (10a–f). Some of these compounds have
shown good antimicrobial activity.
The in vitro antimicrobial activity (Ayer and Nozawa 1990;
Pfefferle et al., 1990; Atwal et al., 1993) of all the syn-
thesized compounds was carried out using paper disk
method. These compounds were screened against Staphy-
lococcus aureus (Gram-positive) and Escherichia coli
Acknowledgments Authors thank Head—Department of Chemistry,
and Director—CFRD, Osmania University, for providing facilities.
(
Gram-negative) for antibacterial activity, whereas Asper-
gillus terreus and Rhizoctonia solani for antifungal activ-
ity. The strains used for the activity procured from the
Institute of Microbial Technology (IMT), Chandigarh.
Cultures of test organisms were maintained on nutrient
agar (bacterial) and potato dextrose agar (fungal) media
and subcultured in petri dishes prior to testing. The com-
pounds were tested at the concentrations of 200 and
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