Synthesis, characterization, and antimicrobial activity of benzimidazole-derived chalcones containing 1,3,4-oxadiazole moiety

Article abstract of DOI:10.1007/s10593-015-1653-1

A series of novel benzimidazole-derived chalcones containing the 1,3,4-oxadiazole moiety were synthesized and characterized by IR, ¹H, ¹³C NMR, and mass spectra and elemental analysis. The synthesized compounds were evaluated for their efficiency as antibacterial agents against two Gram-positive and Gram-negative strains of bacteria along with antifungal activity against three fungal species. Antibacterial activity revealed that tested compounds exhibited potent activity whereas some compounds exhibited moderate antifungal activity as compared to the standards.

Full text of DOI:10.1007/s10593-015-1653-1

DOI 10.1007/s10593-015-1653-1
Chemistry of Heterocyclic Compounds 2015, 51(1), 44–50
Synthesis, characterization, and antimicrobial activity
of benzimidazole-derived chalcones
containing 1,3,4-oxadiazole moiety
Gangadhar A. Meshram1*, Vipul A. Vala1
1 Department of Chemistry, University of Mumbai,
Vidyanagari, Kalina, Santacruz (East),
Mumbai-400098, India; e-mail: meshramga@chem.mu.ac.in
Published in Khimiya Geterotsiklicheskikh Soedinenii,
Submitted November 7, 2014
2015, 51(1), 44–50
Accepted after revision December 10, 2014
O
N
N
O
N
N
N
K2CO3, DMF
rt, 20–30 min
R
+
O
Ph
N
N
H
Cl
R
O
N
Ph
A series of novel benzimidazole-derived chalcones containing the 1,3,4-oxadiazole moiety were synthesized and characterized by IR, 1H,
13C NMR, and mass spectra and elemental analysis. The synthesized compounds were evaluated for their efficiency as antibacterial
agents against two Gram-positive and Gram-negative strains of bacteria along with antifungal activity against three fungal species. Anti-
bacterial activity revealed that tested compounds exhibited potent activity whereas some compounds exhibited moderate antifungal activ-
ity as compared to the standards.
Keywords: benzimidazole, chalcone, 1,3,4-oxadiazole, antibacterial activity, antifungal activity.
Heterocyclic compounds play an important role in
designing new structural entities of medicinal importance.
In particular, benzimidazole scaffold is an important
pharmacophore in medicinal chemistry and modern drug
discovery. Specifically, the 2-substituted benzimidazoles
are known to be potent biologically active compounds.1,2
The biological activity exhibited by compounds containing
the benzimidazole moiety has prompted chemists to
synthesize an increasing number of benzimidazole
derivative libraries and screen them for potential
activities.3,4 1,3,4-Oxadiazole ring system is an important
heterocyclic group for medicinal chemistry. 1,3,4-Oxadi-
azoles have been extensively reported in literature as anti-
microbial,5 antitubercular,5 anti-inflammatory,6,7 analgesic,7
antitumor,8 and anticonvulsant agents.9 This gives a great
impetus to the search for potential pharmacologically
active drugs carrying 1,3,4-oxadiazole substituent. Chal-
cones are biosynthetic products of the shikimate pathway,
considered as the precursors of flavonoids and isoflavo-
noids. Chalcones possess a diverse array of pharmacolo-
gical activities as well.10,11 Natural and synthetic chalcone
derivatives have been object of intense study owing to their
broad spectrum of biological activities such as anti-
inflammatory,12 antituberculosis,13 antimalarial,14 antioxidant,15
and anti-HIV.16
units, namely, benzimidazole, chalcone, and 1,3,4-oxa-
diazole, in order to synthesize a novel series of benz-
imidazole-derived chalcones that would incorporate 1,3,4-oxa-
diazole and to test their antimicrobial activity.
The synthetic sequence towards the target compounds
involved a convergent protocol of coupling benzimidazole
and 1,3,4-oxadiazole heterocycles constructed from acyclic
reactants in parallel (Scheme 1). Using readily available
starting materials, o-phenylene diamine (1) and lactic acid (2),
intermediates 3 and 4 were prepared following a previously
described procedure.17 The corresponding benzimidazole-
derived chalcone derivatives 5a–m were obtained by direct
Claisen–Schimdt condensation between substituted aromatic
aldehydes and 2-acetylbenzimidazole at room temperature
in absolute ethanol, using 10% ethanolic NaOH as base.
The 1,3,4-oxadiazole ring was constructed by refluxing
benzohydrazide (6) and chloroacetyl chloride (7) on water
bath for 2 h, then POCl3 was added dropwise, and refluxing
continued for 3 h. Interaction of benzimidazoles 5a–m and
1,3,4-oxadiazole intermediate 8 in the presence of K2CO3
for 30 min led to the title compounds 9a–m. All the synthetic
compounds gave satisfactory analytical and spectroscopic
data that were in full agreement with their proposed structures.
The structures of intermediates 5a–m and 8 and those of
1
products 9a–m were determined by IR, H and 13C NMR
In present study, we have designed new hybrid mole-
cules through the combination of three active structure
spectroscopy, elemental analysis, and mass spectrometry.
In the IR spectra, all compounds 5a–m showed an
0009-3122/15/5101-0044©2015 Springer Science+Business Media New York
44

Chemistry of Heterocyclic Compounds 2015, 51(1), 44–50
Scheme 1
RCHO
NaOH
O
N
NH2
OH
Me
O
N
N
OH
Me
K2Cr2O7, H2SO4
rt, 3h
4N HCl
+
HO2C
N
H
N
H
3
N
H
4
Me
EtOH
rt, 12 h
, 6 h
NH2
R
1
2
5a–m
O
N
N
O
N
N
R
O
5a–m
1. 1,4-Dioxane, , 2 h
2. POCl3, , 3 h
N
NH2
O
+
N
Cl
O
H
K2CO3, DMF
rt, 20–30 min
Cl
N
Cl
8
6
7
a R = Ph, b R = 3-FC6H4, c R = 4-ClC6H4, d R = 4-BrC6H4, e R = p-Tol, f R = 4-F3CC6H4,
g R = 2-furyl, h R = 2-thienyl, i R = 5-bromothiophen-2-yl, j R = 3-MeOC6H4, k R = 4-MeOC6H4,
l R = 3,4-(MeO)2C6H3, m R = 3,4,5-(MeO)3C6H2
9a–m
absorption band at 3235–3267 cm–1 assigned to N–H bond,
which was absent in the spectra of compounds 9a–m due to
the alkylation of benzimidazole nitrogen atom. The
IR spectra of compounds 9a–m also displayed absorption
bands of α,β-unsaturated carbonyl system at 1645–1669 cm–1,
C–O–C stretching of the oxadiazole ring around 1054–
1069 cm–1, and C=N bonds at 1574–1611 cm–1. In the
1H NMR spectra of compounds 5a–m the signal of NH
proton was observed at 13.56–14.42 ppm. In the spectra of
compounds 9a–m such signal was not observed. The CH2
protons of compounds 9a–m were represented as a singlet
at 6.32–6.36 ppm. The two doublets at 7.76–8.05 and 8.13–
8.39 ppm were attributed to the protons of α,β-unsaturated
system with coupling constant of 15–16 Hz characteristic
of the trans isomer, although in some cases it was difficult
to measure the coupling constant because the signals
overlapped with those of the aromatic ring protons. Other
protons appeared in the expected region. The 13C NMR
spectrum of compounds 9a–m featured signals of carbonyl
carbon atoms of the chalcone fragment at ~182–183 ppm
while the signal at ~40 ppm was assigned to CH2 group in
the products 9a–m. Additionally, the presence of CH2
protons was also confirmed by DEPT-135 method. The
mass spectra of compounds were also found to be in full
agreement with the proposed molecular formula.
Antimicrobial activity of the synthesized compounds 5a–m
and 9a–m were determined by broth microdilution
method.18 The results are summarized in Table 1. Com-
pounds 5a–m were found to be less active against Gram-
negative strains while compounds 5a–d,g,l,m were more
active against Gram-positive strains, especially S. aureus,
in comparison with standard drug ampicillin. The anti-
bacterial study of compounds 9a–m revealed that
compounds 9c,f,h,k,m showed similar level of activity
while compound 9e showed higher activity than the stan-
dard drug ampicillin against Escherichia coli. Compounds
9a–d,f–j,l,m showed higher activity than ampicillin against
Staphylococcus aureus. Compounds 9i,j displayed equal
inhibitory activity, whereas compounds 9b,c,m exhibited
higher activity than ampicillin against Streptococcus
pyogenes. All the compounds were found to be more active
towards Gram-positive strains, especially S. aureus, than
against Gram-negative strains. 3,4,5-Trimethoxy-substi-
tuted compound 9m was found to be more active than
mono- and disubstituted compounds 9j,k against the Gram-
negative bacterial strains. In contrast, monomethoxy
derivatives 9j,k were equipotent or more potent than its di-
or trisubstituted analogs 9l,m against Gram-negative bac-
teria. It was noteworthy that p-tolyl (9e), furyl (9g), 4-bromo-
phenyl (9d), and 4-chlorophenyl (9c) derivatives exhibited
potent inhibitory activity (MIC= 150, 150, 100, and 125 µM,
respectively) against E. coli, P. aeruginosa, S. aureus, and
S. pyogenes, respectively, compared to both standard drugs
chloramphenicol and ampicillin (MIC 150 and 250 µM,
respectively). Compounds 9c,d,g,e showed promising
activity compared to chloramphenicol which may be explained
by the presence of halogen, furan ring, and methyl group in
the structure, respectively. Presence of an electron-donating
group like methyl, chloro, bromo at position 4 of aromatic
ring and furan ring seem to be important for antibacterial
activity due to resonance effect.
The antifungal activity test indicated that compounds 5a–m
are less active against all fungal strains in comparison with
standard drugs. Compounds 9b,d,g,l,m showed higher activity
than the standard drug griseofulvin against Candida albicans.
3,4-Dimethoxy- (9l) and 3,4,5-trimethoxy-substituted (9m)
compounds were more active than all other tested compounds
against Candida albicans. Compound 9m possessing three
methoxy groups exhibited moderate antifungal activity
(MIC = 400 µM) in comparison to nystatin and griseofulvin
(MIC 125 and 1500 µM) against Candida albicans.
However, the rest of the tested compounds showed poor to
moderate antifungal activity against all fungal strains.
In conclusion, 13 new compounds based on the
molecular hybridisation of benzimidazole derived chalcone
with 1,3,4-oxadiazole were synthesized and evaluated for
their antimicrobial activity. From the antimicrobial screen-
ing results, it can be concluded that addition of 1,3,4-oxa-
diazole ring to benzimidazole derivatives containing chalcone
fragment has enhanced their antimicrobial activity as compared
to the parent compounds. All the tested compounds were
significantly more active towards bacteria than against fungi.
45

Chemistry of Heterocyclic Compounds 2015, 51(1), 44–50
Table 1. Antimicrobial activity of compounds 5a–m and 9a–m (MIC, µM)
Gram-negative bacteria
Gram-positive bacteria
Fungi
Compound
Pseudomonas
aeruginosa
Staphylococcus Streptococcus
Aspergillus
clavatus
Escherichia coli
Candida albicans Aspergillus niger
aureus
pyogenes
1000
1000
500
2000
500
250
1000
5000
1000
500
500
1000
500
500
500
250
1000
150
250
500
250
500
300
250
500
250
250
150
–
500
500
500
>2000
500
500
300
1000
1000
500
500
1000
1000
500
500
500
1000
300
200
150
500
500
250
250
550
500
-
500
500
500
300
>2000
1000
500
1000
1000
1000
1000
500
500
250
250
250
100
1000
500
250
300
500
500
1000
250
200
750
150
–
500
300
300
500
1000
1000
1000
>2000
1000
1000
500
1000
500
300
200
125
350
500
500
500
1000
500
500
250
500
250
250
150
–
>2000
1500
>2000
1500
>2000
>2000
1500
>2000
>2000
>2000
>2000
1000
1000
2000
1000
2000
1000
2000
2000
1000
2000
2000
2000
2000
500
>2000
>2000
1000
2000
1500
1000
1500
1000
1500
500
>2000
>2000
1000
2000
1500
1000
1500
>2000
1500
1500
>2000
1500
>2000
2000
2000
1000
2000
1000
500
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
2000
1000
>2000
2000
2000
500
5k
5l
5m
9a
9b
9c
9d
9e
9f
2000
1000
500
1000
1000
1000
500
1000
2000
1000
1000
2000
1000
2000
–
9g
9h
9i
9j
2000
1000
2000
–
9k
9l
400
9m
Ampicilin
–
Chloramphenicol
Griseovulfin
Nystatin
150
–
–
–
–
1500
125
300
300
–
–
–
–
125
125
Hence, they are promising scaffolds for further modifica-
tions to obtain more efficacious antibacterial compounds.
Synthesis of 3-aryl(heteroaryl)-1-(1H-benzimidazol-
2-yl)-2-propen-1-ones 5a–m (General Method). A 10%
solution of NaOH (5 ml) in EtOH was added to a solution
of 2-acetylbenzimidazole (4) (1.6 g, 0.01 mol) in absolute
EtOH (20 ml) at 0°C with stirring. Then the solution of an
aromatic aldehyde (0.01 mol) in absolute EtOH (10 ml)
was added dropwise. The reaction mixture was stirred for
12 h at room temperature. After completion of reaction
(monitored by TLC), the reaction mixture was poured onto
crushed ice. The separated solid was filtered off, washed
with water, and dried. The residue was purified by column
chromatography (silica gel, eluent 10% ethyl acetate in
petroleum ether) to afford pure benzimidazole-derived
chalcone 5a–m.
Experimental
The IR spectra of compounds 5a–m and 8 were obtained
on a Perkin–Elmer FT-IR Spectrum 2000 spectrophoto-meter
using KBr pellets while the IR spectra of compounds 9a–m
were obtained on a Perkin–Elmer Frontier 91579 FT-IR
spectrophotometer using an ATR attachment. 1H and 13C NMR
spectra were recorded on a Bruker Avance spectrometer
(300 and 75 MHz, respectively) with 1% TMS as internal
standard. Mass spectra were obtained on a Thermo Finnigan
Discovery GC-MS instrument. Elemental analysis was
performed on a EURO EA 3000 elemental analyzer. Melting
points were determined in an open capillary tube using Buchi
M-560 melting point instrument. Completion of the reactions
was monitored by TLC using glass plates coated with silica
gel. All the reagents and solvents of analytical grade (AR) and
used without further purification.
1-(1H-Benzimidazol-2-yl)-3-phenyl-2-propen-1-one (5a).
Yield 1.92 g (77%). Pale-yellow crystals. Mp 195–196°C
(mp 194–196°C19). IR spectrum, ν, cm–1: 3242 (N–H),
3062 (С–Н Ar), 2974 (С–Н Alk), 1659 (C=O), 1593
1
(C=N). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
46

Chemistry of Heterocyclic Compounds 2015, 51(1), 44–50
1
13.51 (1H, s, NH); 8.13 (1H, d, J = 15.6, CH=); 7.98 (1H,
(C=N). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
13.45 (1H, s, NH); 7.95–7.79 (4H, m, H Ar); 7.58 (1H, d,
J = 8.1, H Ar); 7.38–7.30 (2H, m, H Ar); 7.16 (1H, d,
J = 3.6, H Fur); 6.71 (1H, dd, J= 3.3, J = 1.8, H Fur). Mass
spectrum, m/z (Irel, %): 238 [M]+ (82), 208 (46), 183 (94),
155 (100), 118 (22).
d, J = 15.9, CH=); 7.87–7.58 (4H, m, H Ar); 7.49–7.30
(5H, m, H Ar). Mass spectrum, m/z (Irel, %): 248 [M]+ (22),
219 (100), 165 (4), 118 (8), 91 (5).
1-(1H-Benzimidazol-2-yl)-3-(3-fluorophenyl)-2-propen-
1-one (5b). Yield 2.01 g (76%). Yellow crystals. Mp 190–
191°C. IR spectrum, ν, cm–1: 3248 (N–H), 3060 (С–Н Ar),
2971 (С–Н Alk), 1659 (C=O), 1579 (C=N), 1086 (C–F).
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 13.53 (1H,
s, NH); 8.17 (1H, d, J = 16.2, CH=); 7.98 (1H, d, J = 15.9,
CH=); 7.84–7.71 (3H, m, H Ar); 7.61–7.48 (2H, m, H Ar);
7.41–7.29 (3H, m, H Ar). Mass spectrum, m/z (Irel, %): 266
[M]+ (46), 237 (100), 144 (4), 101 (12), 74 (12). Found, %:
C 72.35; H 4.31; N 10.74. C16H11FN2O. Calculated, %:
C 72.17; H 4.16; N 10.52.
1-(1H-Benzimidazol-2-yl)-3-(4-chlorophenyl)-2-propen-
1-one (5c) Yield 2.28 g (80%). Yellow crystals. Mp 200–
201°C (mp 202–204°C19). IR spectrum, ν, cm–1: 3267 (N–H),
3065 (С–Н Ar), 2975 (С–Н Alk), 1662 (C=O), 1591
(C=N), 819 (C–Cl). 1H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 13.49 (1H, s, NH); 8.10 (1H, d, J = 16.2, CH=);
7.92 (1H, d, J = 16.2, CH=); 7.86–7.83 (3H, m, H Ar);
7.61–7.36 (5H, m, H Ar). Mass spectrum, m/z (Irel, %): 282
[M]+ (44), 253 (100), 218 (16), 144 (14), 118 (32).
1-(1H-Benzimidazol-2-yl)-3-(4-bromophenyl)-2-propen-
1-one (5d). Yield 2.48 g (76%). Yellow crystals. Mp 220–
221°C (mp 224–226°C19). IR spectrum, ν, cm–1: 3251 (N–H),
3062 (С–Н Ar), 2978 (С–Н Alk), 1659 (C=O), 1598
(C=N), 549 (C–Br). 1H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 13.51 (1H, s, NH); 8.16 (1H, d, J = 16.2, CH=);
7.95 (1H, d, J = 16.2, CH=); 7.88–7.80 (3H, m, H Ar);
7.66–7.58 (3H, m, H Ar); 7.43–7.33 (2H, m, H Ar). Mass
spectrum, m/z (Irel, %): 328 [M(81Br)]+ (30), 326 [M(79Br)]+
(29), 299 (72), 218 (30), 144 (20), 102 (100).
1-(1H-Benzimidazol-2-yl)-3-(2-thienyl)-2-propen-1-one
(5h). Yield 1.91 g (75%). Yellow crystals. Mp 201–202°C
(mp 201°C21). IR spectrum, ν, cm–1: 3253 (N–H), 3063 (С–Н
1
Ar), 2970 (С–Н Alk), 1649 (C=O), 1574 (C=N). H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 13.47 (1H, s, NH);
8.16 (1H, d, J = 15.9, CH=); 7.85 (1H, d, J = 4.8,
H thiophene); 7.81 (1H, d, J = 15.9, CH=); 7.72 (1H, d,
J = 3.0, H thiophene); 7.36–7.34 (4H, m, H Ar); 7.32 (1H,
dd, J= 3.6, J = 1.2, H thiophene). Mass spectrum, m/z (Irel, %):
254 [M]+ (46), 225 (100), 193 (10), 118 (30), 65 (28).
1-(1H-Benzimidazol-2-yl)-3-(5-bromothiophen-2-yl)-
2-propen-1-one (5i). Yield 2.50 g (75%). Yellow crystals.
Mp 237–238°C. IR spectrum, ν, cm–1: 3241 (N–H), 3063
(С–Н Ar), 2970 (С–Н Alk), 1654 (C=O), 1576 (C=N), 546
1
(C–Br). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
13.47 (1H, s, NH); 8.09 (1H, d, J = 15.9, CH=); 7.74–7.69
(3H, m, H Ar); 7.57 (1H, d, J = 4.2, H thiophene); 7.74–7.34
(3H, m, H Ar). Mass spectrum, m/z (Irel, %): 334 [M(81Br)]+
(12), 332 [M(81Br)]+ (11), 253 (100), 221 (22), 193 (12),
107 (8). Found, %: C 50.68; H 2.93; N 8.59; S 9.85.
C14H9BrN2OS. Calculated, %: C 50.46; H 2.72; N 8.41;
S 9.62.
1-(1H-Benzimidazol-2-yl)-3-(3-methoxyphenyl)-2-propen-1-
one (5j). Yield 2.19 g (79%). Yellow crystals. Mp 175–
176°C. IR spectrum, ν, cm–1: 3259 (N–H), 3062 (С–Н Ar),
2932 (С–Н Alk), 1658 (C=O), 1593 (C=N), 1252 and 1157
1
(C–O–C). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
13.42 (1H, s, NH); 8.15 (1H, d, J = 15.9, CH=); 7.97 (1H,
d, J = 15.9, CH=); 7.75–7.72 (2H, m, H Ar); 7.44–7.35
(5H, m, H Ar); 7.08–7.05 (1H, m, H Ar); 3.84 (3H, s,
OCH3). Mass spectrum, m/z (%): 278 [M]+ (52), 249
(100), 234 (18), 118 (8), 62 (12). Found, %: C 73.50;
H 5.07; N 10.33. C17H14N2O2. Calculated, %: C 73.37;
H 5.29; N 10.07.
1-(1H-Benzimidazol-2-yl)-3-(p-tolyl)-2-propen-1-one
(5e). Yield 2.05 g (78%). Pale-yellow crystals. Mp 209–
210°C (mp 210–212°C20). IR spectrum, ν, cm–1: 3243 (N–H),
3067 (С–Н Ar), 2980 (С–Н Alk), 1658 (C=O), 1590
1
(C=N). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
13.49 (1H, s, NH); 8.09 (1H, d, J = 16.2, CH=); 7.95 (1H,
d, J = 16.2, CH=); 7.76–7.74 (3H, m, H Ar); 7.35–7.28
(5H, m, H Ar); 2.35 (3H, s, CH3). Mass spectrum, m/z (Irel,
%): 262 [M]+ (34), 233 (100), 118 (52), 115 (64), 91 (34).
1-(1H-Benzimidazol-2-yl)-3-(4-trifluoromethylphenyl)-
2-propen-1-one (5f). Yield 2.27 g (72%). Yellow crystals.
Mp 203–204°C. IR spectrum, ν, cm–1: 3262 (N–H), 3065
(С–Н Ar), 2976 (С–Н Alk), 1664 (C=O), 1606 (C=N),
1085 (C–F); 1H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 13.55 (1H, s, NH); 8.25 (1H, d, J = 16.2, CH=);
8.10 (1H, d, J = 8.4, H Ar); 8.04 (1H, d, J = 16.2, CH=);
7.99–7.80 (4H, m, H Ar); 7.61 (1H, d, J= 7.8, H Ar); 7.42–
7.34 (2H, m, H Ar). Mass spectrum, m/z (Irel, %): 316 [M]+
(52), 287 (100), 218 (6), 151 (24), 118 (14). Found, %:
C 64.77; H 3.69; N 9.08. C17H11F3N2O. Calculated, %:
C 64.56; H 3.51; N 8.86.
1-(1H-Benzimidazol-2-yl)-3-(4-methoxyphenyl)-
2-propen-1-one (5k). Yield 2.30 g (83%). Yellow crystals.
Mp 185–187°C (mp 184–188°C19). IR spectrum, ν, cm–1:
3257 (N–H), 3064 (С–Н Ar), 2979 (С–Н Alk), 1651 (C=O),
1
1573 (C=N), 1266 and 1165 (C–O–C); H NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 13.48 (1H, s, NH); 8.03 (1H,
d, J = 15.9, CH=); 7.96 (1H, d, J = 15.9, CH=); 7.85–7.67
(4H, m, H Ar); 7.37–7.36 (2H, m, H Ar); 7.06–7.03 (2H,
m, H Ar); 3.83 (3H, s, OCH3). Mass spectrum, m/z (Irel, %):
278 [M]+ (42), 249 (100), 206 (30), 118 (38), 89 (30).
1-(1H-Benzimidazol-2-yl)-3-(3,4-dimethoxyphenyl)-
2-propen-1-one (5l). Yield 2.33 g (76%). Yellow crystals.
Mp 195–196°C (mp 196–198°C19). IR spectrum, ν, cm–1:
3235 (N–H), 3059 (С–Н Ar), 2968 (С–Н Alk), 1651
1
(C=O), 1572 (C=N), 1265 and 1163 (C–O–C); H NMR
1-(1H-Benzimidazol-2-yl)-3-(2-furyl)-2-propen-1-one
(5g). Yield 1.87 g (79%). Yellow crystals. Mp 214–215°C
(mp 215–216°C21). IR spectrum, ν, cm–1: 3248 (N–H),
3062 (С–Н Ar), 2979 (С–Н Alk), 1649 (C=O), 1575
spectrum (DMSO-d6), δ, ppm (J, Hz): 13.44 (1H, s, NH);
8.02 (1H, d, J = 15.9, CH=); 7.94 (1H, d, J = 16.2, CH=);
7.84–7.56 (2H, m, H Ar); 7.46–7.31 (4H, m, H Ar); 7.06
(1H, d, J = 8.4, H Ar); 3.86 (3H, s, OCH3), 3.81 (3H, s,
47

Chemistry of Heterocyclic Compounds 2015, 51(1), 44–50
OCH3). Mass spectrum, m/z (Irel, %): 308 [M]+ (62), 279
(100), 263 (20), 207 (14), 118 (8).
spectrum, m/z (Irel, %): 406 [M]+ (48), 405 (100), 272 (26),
247 (82). Found, %: C 74.12; H 4.73; N 13.89. C25H18N4O2.
Calculated, %: C 73.88; H 4.46; N 13.78.
1-(1H-Benzimidazol-2-yl)-3-(3,4,5-trimethoxyphenyl)-2-
propen-1-one (5m). Yield 2.37 g (70%). Yellow crystals.
Mp 215–216°C (mp 217°C22). IR spectrum, ν, cm–1: 3250
(N–H), 3065 (С–Н Ar), 2980 (С–Н Alk), 1658 (C=O), 1596
(C=N), 1271 and 1127 (C–O–C); 1H NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 13.47 (1H, s, NH); 8.09 (1H, d,
J = 16.2, CH=); 7.97 (1H, d, J = 16.2, CH=); 7.74 (2H, m,
H Ar); 7.38–7.36 (2H, m, H Ar); 7.21–7.15 (2H, m, H Ar);
3.88 (6H, s, 2OCH3); 3.73 (3H, s, OCH3). Mass spectrum, m/z
(Irel, %): 338 [M]+ (97), 309 (100), 295 (22), 263 (20), 179 (14).
2-Chloromethyl-5-phenyl-1,3,4-oxadiazole (8). Benzo-
hydrazide (6) (1.36 g, 0.01 mol) was dissolved in dry
1,4-dioxane (20 ml), and chloroacetyl chloride (7) (0.8 ml,
0.01 mol) was added dropwise. The reaction mixture was
refluxed on water bath for about 2 h, until evolution of HCl
gas ceased. POCl3 (5 ml) was added to the reaction mix-
ture, and the reaction was continued on water bath for 3 h
till evolution of HCl gas ceased. The reaction mixture was
brought to room temperature, poured carefully into ice-cold
water (100 ml), and neutralized with Na2CO3 to obtain a
precipitate. The solid was filtered off, washed with water,
and dried. The crude product was recrystallized from
MeOH. Yield 1.37 g (70%). Off-white crystals. Mp 117–
118°C (mp 118°C23). IR spectrum, ν, cm–1: 3027 (С–Н Ar),
2970 (С–Н Alk), 1604 (C=N), 1057 (C–O–C oxadiazole),
742 (C–Cl). 1H NMR spectrum (CDCl3), δ, ppm: 8.09–8.05
(2H, m, H Ar); 7.59–7.48; (3H, m, H Ar); 4.78 (2H, s,
CH2). 13C NMR spectrum (CDCl3), δ, ppm: 161.7 (C-2 oxa-
diazole); 165.5 (C-5 oxadiazole); 131.8; 128.9; 127.0;
123.4; 32.8 (CH2). Mass spectrum, m/z (Irel, %): 195 [M]+
(35), 160 (28), 146 (17), 104 (100), 77 (48). Found, %:
C 55.70; H 3.74; N 14.45. C9H7ClN2O. Calculated, %:
C 55.54; H 3.63; N 14.39.
3-(3-Fluorophenyl)-1-{1-[(5-phenyl-1,3,4-oxadiazol-2-
yl)methyl]-1H-benzimidazol-2-yl}-2-propen-1-one (9b).
Yield 0.66 g (78%). Pale-yellow crystals. Mp 190–191°C.
IR spectrum, ν, cm–1: 3063 (С–Н Ar), 2970 (С–Н Alk),
1666 (C=O), 1607 (C=N), 1161 (C–F), 1057 (C–O–C
1
oxadiazole). H NMR spectrum (CDCl3), δ, ppm (J, Hz):
8.31 (1H, d, J = 15.9, CH=); 7.98–7.88 (4H, m, H Ar);
7.66–7.64 (1H, m, H Ar); 7.53–7.37 (8H, m, H Ar); 7.17–
7.11 (1H, m, H Ar); 6.32 (2H, s, NCH2). 13C NMR spectrum
(CDCl3), δ, ppm: 182.5 (C=O); 165.7; 164.7; 161.4; 145.8;
143.8; 141.7; 136.8; 136.2; 132.0; 130.5; 128.9 (2C); 127.1
(2C); 126.9; 125.0; 124.6; 123.7; 123.2; 122.2; 118.0;
115.2; 110.7; 40.0 (CH2). Mass spectrum, m/z (Irel, %): 424
[M]+ (28), 416 (10), 290 (22), 277 (41), 264 (98); Found, %:
C 70.58; H 4.17; N 13.38. C25H17FN4O2. Calculated, %:
C 70.75; H 4.04; N 13.20.
3-(4-Chlorophenyl)-1-{1-[(5-phenyl-1,3,4-oxadiazol-2-yl)-
methyl]-1H-benzimidazol-2-yl}-2-propen-1-one (9c).
Yield 0.70 g (81%). Pale-yellow crystals. Mp 203–204°C.
IR spectrum, ν, cm–1: 3027 (С–Н Ar), 2966 (С–Н Alk),
1666 (C=O), 1607 (C=N), 1054 (C–O–C oxadiazole), 822
1
(C–Cl); H NMR spectrum (CDCl3), δ, ppm (J, Hz): 8.30
(1H, d, J = 15.6, CH=); 7.97–7.88 (4H, m, H Ar); 7.70–
7.63 (3H, m, H Ar); 7.52–7.39 (7H, m, H Ar); 6.33 (2H, s,
NCH2). 13C NMR spectrum (CDCl3), δ, ppm: 182.7 (C=O);
165.8; 161.4; 145.9; 143.9; 141.7; 137.0; 136.2; 136.0;
132.0; 130.2 (2C); 129.3 (2C); 129.0 (2C); 127.1 (2C);
127.0; 124.6; 123.2; 122.9; 122.2; 110.7; 39.9 (CH2). Mass
spectrum, m/z (Irel, %): 440 [M]+ (2), 328 (5), 306 (26), 295
(38), 280 (100), 252 (64). Found, %: C 68.24; H 4.04;
N 12.57. C25H17ClN4O2. Calculated, %: C 68.11; H 3.89;
N 12.71.
Synthesis of 3-aryl(heteroaryl)-1-{1-[(5-phenyl-1,3,4-
oxadiazol-2-yl)methyl]-1H-benzimidazol-2-yl}-2-propen-
1-one 9a–m (General Method). K2CO3 (0.29 g, 2 mmol)
was added to a mixture of the appropriate benzimidazole-
derived chalcone 5a–m (2 mmol) and 2-chloromethyl-
5-phenyl-1,3,4-oxadiazole (8) (0.39 g, 2 mmol) in DMF
(5 ml). The reaction mixture was stirred at room tempe-
rature for 20–30 min. After completion of reaction, the
reaction mixture was poured onto crushed ice. The solid
that separated was filtered off, washed with water, and
dried. The residue was purified by column chromatography
(silica gel, eluent 10% ethyl acetate in petroleum ether).
3-Phenyl-1-{1-[(5-phenyl-1,3,4-oxadiazol-2-yl)methyl]-
1H-benzimidazol-2-yl}-2-propen-1-one (9a). Yield 0.71 g
(82%). Pale-yellow crystals. Mp 178–179°C. IR spectrum,
ν, cm–1: 3027 (С–Н Ar), 2963 (С–Н Alk), 1657 (C=O),
1603 (C=N), 1069 (C–O–C oxadiazole). 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 8.30 (1H, d, J = 16.2, CH=);
8.01–7.91 (3H, m, H Ar); 7.77–7.73 (3H, m, H Ar); 7.66–
7.63 (1H, m, H Ar); 7.48–7.25 (8H, m, H Ar); 6.34 (2H, s,
NCH2). 13C NMR spectrum (CDCl3), δ, ppm: 182.9 (C=O);
165.7; 161.5; 146.2; 145.4; 141.8; 136.2; 134.5; 131.9;
131.0; 129.1 (2C); 129.0 (2C); 128.9 (2C); 127.0 (2C);
124.5; 123.2; 122.6; 122.3; 120.9; 110.7; 40.0 (CH2). Mass
3-(4-Bromophenyl)-1-{1-[(5-phenyl-1,3,4-oxadiazol-2-yl)-
methyl]-1H-benzimidazol-2-yl}-2-propen-1-one (9d).
Yield 0.70 g (82%). Yellow crystals. Mp 196–197°C.
IR spectrum, ν, cm–1: 3025 (С–Н Ar), 2967 (С–Н Alk),
1666 (C=O), 1605 (C=N), 1055 (C–O–C oxadiazole), 598
1
(C–Br). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 8.31
(1H, d, J = 15.9, CH=); 7.97–7.91 (3H, m, H Ar); 7.89 (1H,
d, J = 15.9, CH=); 7.66–7.55 (5H, m, H Ar); 7.50–7.42 (5H,
m, H Ar); 6.32 (2H, s, NCH2). 13C NMR spectrum (CDCl3),
δ, ppm: 182.7 (C=O); 165.9; 161.4; 146.0; 144.0; 141.8;
136.1; 133.4; 132.2; 132.0 (2C); 130.4 (2C); 128.9 (2C);
127.1 (2C); 126.9; 125.5; 124.7; 123.2; 123.0; 122.1; 110.7;
39.9 (CH2). Mass spectrum, m/z (Irel, %): 486 [M(81Br)]+
(20), 484 [M(79Br)]+ (17), 483 (42), 351 (29), 339 (49);
Found, %: C 61.99; H 3.39; N 11.61. C25H17BrN4O2.
Calculated, %: C 61.87; H 3.53; N 11.54.
1-{1-[(5-Phenyl-1,3,4-oxadiazol-2-yl)methyl]-1H-
benzimidazol-2-yl}-3-(p-tolyl)-2-propen-1-one (9e). Yield
0.76 g (85). Pale-yellow crystals. Mp 190–191°C.
IR spectrum, ν, cm–1: 3021 (С–Н Ar), 2968 (С–Н Alk), 1656
1
(C=O), 1595 (C=N), 1055 (C–O–C oxadiazole). H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 8.28 (1H, d, J = 15.9,
CH=); 8.00–7.90 (4H, m, H Ar); 7.68–7.63 (3H, m, H Ar);
7.51–7.38 (5H, m, H Ar); 7.29 (2H, d, J = 6.9, H Ar); 6.34
48

Chemistry of Heterocyclic Compounds 2015, 51(1), 44–50
(2H, s, NCH2); 2.40 (3H, s, CH3). 13C NMR spectrum
(9i). Yield 0.84 g (85%). Yellow crystals. Mp 199–200°C.
IR spectrum, ν, cm–1: 3053 (С–Н Ar), 2945 (С–Н Alk),
1645 (C=O), 1574 (C=N), 1069 (C–O–C oxadiazole), 707
(CDCl3), δ, ppm: 182.9 (C=O); 165.8; 161.5; 146.3; 145.6;
141.9; 141.8; 136.2; 131.9; 131.8; 129.7 (2C); 129.1 (2C);
128.9 (2C); 127.0 (2C); 126.8; 124.4; 123.3; 122.1; 121.5;
110.6; 39.9 (CH2); 21.6 (CH3). Mass spectrum, m/z (Irel, %):
420 [M]+ (17), 419 (36), 390 (10), 286 (18), 260 (100).
Found, %: C 74.38; H 4.93; N 13.65. C26H20N4O2.
Calculated, %: C 74.27; H 4.79; N 13.33.
1
(C–S), 556 (C–Br). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 7.96–7.90 (5H, m, H Ar, CH=); 7.65 (1H, d, J = 8.1,
H Ar); 7.52–7.40 (5H, m, H Ar); 7.21 (1H, d, J = 3.9,
H thiophene); 7.09 (1H, d, J = 3.9, H thiophene); 6.32 (2H,
s, NCH2). 13C NMR spectrum (CDCl3), δ, ppm: 182.2
(C=O); 165.8; 161.6; 146.0; 141.8; 140.1; 136.6; 136.4;
133.0; 131.9; 131.4; 128.9 (2C); 127.0 (2C); 126.0; 124.5;
123.3; 122.2; 121.7; 117.9; 110.6; 39.9 (CH2). Mass
spectrum, m/z (Irel, %): 492 [M(81Br)]+ (5), 490 [M(79Br)]+
(3), 411 (100), 331 (22), 252 (50). Found, %: C 56.51; H 2.81;
N 11.19; S 6.74. C23H15BrN4O2S. Calculated, %: C 56.22;
H 3.08; N 11.40; S 6.53.
1-{1-[(5-Phenyl-1,3,4-oxadiazol-2-yl)methyl]-1H-benz-
imidazol-2-yl}-3-(4-trifluoromethylphenyl)-2-propen-1-one
(9f). Yield 0.78 g (81%). Pale-yellow crystals. Mp 202–
203°C. IR spectrum, ν, cm–1: 3032 (С–Н Ar), 2981(С–Н
Alk), 1669 (C=O), 1611 (C=N), 1125 (C–F), 1057 (C–O–C
1
oxadiazole). H NMR spectrum (CDCl3), δ, ppm (J, Hz):
8.39 (1H, d, J = 16.2, CH=); 7.99–7.84 (6H, m, H Ar);
7.70–7.51 (3H, m, H Ar); 7.49–7.39 (5H, m, H Ar); 6.33
(2H, s, NCH2). 13C NMR spectrum (CDCl3), δ, ppm: 182.4
(C=O); 165.7; 161.4; 145.8; 143.2; 141.7; 137.9; 136.2;
132.5; 132.1; 132.0; 129.1 (2C); 129.0 (2C); 127.2; 127.0
(2C); 126.0; 125.9 (2C); 124.7; 123.2; 122.3; 110.7; 40.0
(CH2). Mass spectrum, m/z (Irel, %): 474 [M]+ (15), 463
(30), 456 (25), 315 (100). Found, %: C 66.01; H 3.34;
N 12.01. C26H17F3N4O2. Calculated, %: C 65.82; H 3.61;
N 11.81.
3-(3-Methoxyphenyl)-1-{1-[(5-phenyl-1,3,4-oxadi-
azol-2-yl)methyl]-1H-benzimidazol-2-yl}-2-propen-1-one
(9j). Yield 0.72 g (83%). Pale-yellow crystals. Mp 204–
205°C. IR spectrum, ν, cm–1: 3060 (С–Н Ar), 2966 (С–Н
Alk), 1662 (C=O), 1600 (C=N), 1252 and 1161 (C–O–C),
1
1059 (C–O–C oxadiazole). H NMR spectrum (CDCl3), δ,
ppm (J, Hz): 8.30 (1H, d, J = 15.9, CH=); 7.99–7.91 (4H,
m, H Ar); 7.67 (1H, d, J = 8.4, H Ar); 7.53–7.29 (8H, m,
H Ar); 7.02–6.99 (1H, m, H Ar); 6.35 (2H, s, NCH2); 3.89
(3H, s, OCH3). 13C NMR spectrum (CDCl3), δ, ppm: 182.8
(C=O); 165.9; 161.4; 160.0; 146.1; 145.5; 141.8; 136.2;
135.9; 131.9; 129.9; 128.9 (2C); 127.0 (2C); 126.9; 124.5;
123.2; 122.7; 122.2; 122.0; 117.3; 113.5; 110.6; 55.4
(CH3); 39.9 (CH2). Mass spectrum, m/z (Irel, %): 436 [M]+
(9), 435 (35), 406 (4), 302 (20), 276 (100). Found, %: C 71.69;
H 4.81; N 12.95. C26H20N4O3. Calculated, %: C 71.55; H 4.62;
N 12.84.
3-(Furan-2-yl)-1-{1-[(5-phenyl-1,3,4-oxadiazol-2-yl)-
methyl]-1H-benzimidazol-2-yl}-2-propen-1-one (9g).
Yield 0.70 g (89%). Yellow crystals. Mp 176–177°C.
IR spectrum, ν, cm–1: 3026 (С–Н Ar), 2984 (С–Н Alk),
1661 (C=O), 1599 (C=N), 1059 (C–O–C oxadiazole). 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 8.14 (1H, d, J = 15.3,
CH=); 7.96–7.90 (3H, m, H Ar); 7.76 (1H, d, J = 15.9,
CH=); 7.64–7.49 (2H, m, H Ar); 7.47–7.38 (5H, m, H Ar);
6.84 (1H, d, J = 3.3, H Fur); 6.54 (1H, dd, J= 3.5, J = 1.8,
H Fur); 6.32 (2H, s, NCH2). 13C NMR spectrum (CDCl3),
δ, ppm: 182.5 (C=O); 165.7; 161.5; 151.7; 146.1; 145.7;
141.8; 136.1; 131.9; 131.1; 128.9 (2C); 127.0 (2C); 126.8;
124.5; 123.3; 122.2; 120.4; 117.2; 112.9; 110.6; 39.9
(CH2). Mass spectrum, m/z (Irel, %): 396 [M]+ (27), 395 (55),
366 (41), 341 (100). Found, %: C 70.05; H 4.32; N 14.37.
C23H16N4O3. Calculated, %: C 69.69; H 4.07; N 14.13.
1-{1-[(5-Phenyl-1,3,4-oxadiazol-2-yl)methyl]-1H-
benzimidazol-2-yl}-3-(thiophen-2-yl)-2-propen-1-one
(9h). Yield 0.69 g (83%). Pale yellow crystals. Mp 187–
188°C. IR spectrum, ν, cm–1: 3054 (С–Н Ar), 2981 (С–Н
Alk), 1651 (C=O), 1579 (C=N), 1065 (C–O–C oxadiazole),
3-(4-Methoxyphenyl)-1-{1-[(5-phenyl-1,3,4-oxadi-
azol-2-yl)methyl]-1H-benzimidazol-2-yl}-2-propen-1-one
(9k). Yield 0.75 g (86%). Pale-yellow crystals. Mp 164–
165°C. IR spectrum, ν, cm–1: 3030 (С–Н Ar), 2964 (С–Н
Alk), 1659 (C=O), 1695 (C=N), 1258 and 1164 (C–O–C),
1
1062 (C–O–C oxadiazole). H NMR spectrum (CDCl3), δ,
ppm (J, Hz): 8.19 (1H, d, J = 15.9, CH=); 7.98–7.90 (4H,
m, H Ar); 7.74–7.71 (2H, m, H Ar); 7.65–7.63 (1H, m, H
Ar); 7.48–7.41 (5H, m, H Ar); 6.97–6.94 (2H, m, H Ar);
6.34 (2H, s, NCH2); 3.86 (3H, s, OCH3). 13C NMR
spectrum (CDCl3), δ, ppm: 182.6 (C=O); 165.7; 162.2;
161.5; 146.3; 145.5; 141.6; 136.1; 135.9; 131.9; 131.0
(2C); 128.9 (2C); 127.4; 127.0 (2C); 126.7; 124.5; 123.2;
122.0; 120.1; 114.4; 110.6; 55.4 (CH3); 39.9 (CH2). Mass
spectrum, m/z (Irel, %): 436 [M]+ (10), 435 (15), 406 (11),
302 (42), 276 (100). Found, %: C 71.75; H 4.84; N 13.01.
C26H20N4O3. Calculated, %: C 71.55; H 4.62; N 12.84.
3-(3,4-Dimethoxyphenyl)-1-{1-[(5-phenyl-1,3,4-oxadi-
azol-2-yl)methyl]-1H-benzimidazol-2-yl}-2-propen-1-one
(9l). Yield 0.76 g (81%). Yellow crystals. Mp 196–197°C.
IR spectrum, ν, cm–1: 3061 (С–Н Ar), 2960 (С–Н Alk),
1658 (C=O), 1574 (C=N), 1262 and 1159 (C–O–C), 1058
1
706 (C–S). H NMR spectrum (CDCl3), δ, ppm (J, Hz):
8.13 (1H, d, J = 15.6, CH=); 8.05 (1H, d, J = 15.9, CH=);
7.97–7.89 (3H, m, H Ar); 7.64–7.61 (1H, m, H Ar); 7.50–
7.38 (7H, m, H Ar); 7.12 (1H, dd, J = 3.6, J = 1.2, H
thiophene); 6.32 (2H, s, NCH2). 13C NMR spectrum
(CDCl3), δ, ppm: 182.4 (C=O); 165.6; 161.5; 146.1; 141.8;
140.2; 137.7; 136.2; 132.8; 131.9; 130.1; 128.9 (2C); 128.4;
126.9 (2C); 126.8; 124.4; 123.2; 122.1; 121.3; 110.6; 39.9
(CH2). Mass spectrum, m/z (Irel, %): 412 [M]+ (7), 409 (89),
330 (33), 251 (100). Found, %: C 67.16; H 4.09; N 13.74; S
7.98. C23H16N4O2S. Calculated, %: C 66.97; H 3.91; N 13.58;
S 7.77.
1
(C–O–C oxadiazole). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 8.18 (1H, d, J = 15.6, CH=); 7.98–7.91 (4H, m,
H Ar); 7.66 (1H, d, J = 7.8, H Ar); 7.51–7.30 (7H, m,
H Ar); 6.93 (1H, d, J = 8.7, H Ar); 6.35 (2H, s, NCH2);
3.99 (3H, s, OCH3); 3.94 (3H, s, OCH3). 13C NMR
3-(5-Bromothiophen-2-yl)-1-{1-[(5-phenyl-1,3,4-oxa-
diazol-2-yl)methyl]-1H-benzimidazol-2-yl}-2-propen-1-one
49

Chemistry of Heterocyclic Compounds 2015, 51(1), 44–50
3. Breslin, H. J.; Miskowski, T. A.; Kukla, M. J.; De Winter, H. L.;
spectrum (CDCl3), δ, ppm: 182.5 (C=O); 165.6; 161.5;
152.1; 149.3; 146.3; 145.9; 141.6; 136.1; 131.9; 128.9
(2C); 127.6; 127.0 (2C); 126.8; 124.7; 124.6; 123.2;
121.9; 120.1; 111.0; 110.7; 110.2; 56.1 (CH3); 56.0
(CH3); 40.0 (CH2). Mass spectrum, m/z (Irel, %): 466 [M]+
(12), 417 (20) 309 (100). Found, %: C 69.70; H 4.93;
N 12.29. C27H22N4O4. Calculated, %: C 69.52; H 4.75;
N 12.01.
Somers, M. V. F.; Roevens, P. W. M.; Kavash, R. W. Bioorg.
Med. Chem. Lett. 2003, 13, 4467.
4. Spasov, A. A.; Yozhitsa, L. N.; Bugaeva, L. I.; Anisimova, V. A.
Pharm. Chem. J. 1999, 33, 232. [Khim.-Farm. Zh. 1999, 33
(5), 6.]
5. Suresh Kumar, G. V.; Rajendraprasad, Y.; Mallikarjuna, B. P.;
Chandrashekar, S. M.; Kistayya, C. Eur. J. Med. Chem. 2010,
45, 2063.
3-(3,4,5-Trimethoxyphenyl)-1-{1-[(5-phenyl-1,3,4-oxa-
diazol-2-yl)methyl]-1H-benzimidazol-2-yl}-2-propen-
1-one (9m). Yield 0.79 g (80%). Yellow crystals. Mp 200–
201°C. IR spectrum, ν, cm–1: 3059 (С–Н Ar), 2939 (С–Н
Alk), 1660 (C=O), 1595 (C=N), 1277 and 1115 (C–O–C),
6. Manjunatha, K.; Poojary, B.; Lobo, P. L.; Fernandes, J.;
Kumari, N. S. Eur. J. Med. Chem. 2010, 45, 5225.
7. Husain, A.; Ahmad, A.; Alam, M. M.; Ajmal, M.; Ahuja, P.
Eur. J. Med. Chem. 2009, 44, 3798.
8. Lee, L.; Robb, L. M.; Lee, M.; Davis, R.; Mackay, H.;
Chavda, S.; Babu, B.; O’Brien, E. L.; Risinger, A. L.;
Mooberry, S. L.; Lee, M. J. Med. Chem., 2010, 53, 325.
9. Zarghi, A.; Tabatabai, S. A.; Faizi, M.; Ahadian, A.; Navabi, P.;
Zanganeh, V.; Shafiee, A. Bioorg. Chem. Lett. 2005, 15,
1863.
10. Star, A. E.; Mabry, T. J. Phytochemistry 1971, 10, 2817.
11. Stevens, J. F.; Taylor, A. W.; Nickerson, G. B.; Ivancic, M.;
Henning, J.; Haunold, A.; Deinzer, M. L. Phytochemistry
2000, 53, 759.
12. Nowakowska, Z. Eur. J. Med. Chem. 2007, 42, 125.
13. Lin, Y.-M.; Zhou, Y.; Flavin, M. T.; Zhou, L.-M.; Nie, W.;
Chen, F.-C. Bioorg. Med. Chem. 2002, 10, 2795.
14. Liu, M.; Wilairat, P.; Go, M.-L. J. Med. Chem. 2001, 44,
4443.
1
1060 (C–O–C oxadiazole). H NMR spectrum (CDCl3),
δ, ppm (J, Hz): 8.20 (1H, d, J = 15.9, CH=); 7.98–7.89
(4H, m, H Ar); 7.67–7.64 (1H, m, H Ar); 7.50–7.40 (5H, m,
H Ar); 7.00–6.98 (2H, m, H Ar); 6.36 (2H, s, NCH2); 3.94
(3H, s, OCH3); 3.93 (3H, s, OCH3); 3.92 (3H, s, OCH3).
13C NMR spectrum (CDCl3), δ, ppm: 182.6 (C=O); 165.7;
161.5; 153.4 (2C); 146.2; 145.8; 141.0; 136.3; 132.0; 130.1;
128.9 (2C); 127.0 (2C); 126.9; 124.5; 123.2; 122.0; 121.5;
119.9; 110.6; 106.4 (2C); 61.0 (CH3); 56.3 (CH3); 56.3 (CH3);
40.0 (CH2). Mass spectrum, m/z (Irel, %): 496 [M]+ (8), 453
(10), 337 (100). Found, %: C 67.94; H 5.06; N 11.51.
C28H24N4O5.Calculated, %: C 67.73; H 4.87; N 11.28.
15. Gacche, R. N.; Dhole, N. A.; Kamble, S. G.; Bandgar, B. P. J.
Enz. Inh. Med. Chem. 2008, 23, 28.
16. Wu, J.-H.; Wang, X.-H.; Yi, Y.-H.; Lee, K.-H. Bioorg. Med.
Chem. Lett. 2003, 13, 1813.
1
Supporting material to this article containing H and 13
C
NMR spectra compounds 9a–m are available for the
authorized users.
17. Reddy, V. M.; Reddy, K. R. Chem. Pharm. Bull. 2010, 58,
953.
18. Stalons, D. R.; Thornsberry, C. Antimicrob. Agents
Chemother. 1975, 7, 15.
19. Shaharyar, M.; Abdullah, M. M.; Bakht, M. A.; Majeed, J.
Eur. J. Med. Chem. 2010, 45, 114.
20. Sawhney, S. N.; Vir, D.; Asha, G. Indian J. Chem., Sect. B:
Org. Chem. Incl. Med. Chem. 1990, 29B, 1107.
21. Nagarajan, K.; Hendi, S. B.; Goud, A. N.; Deb, B. N. Indian
J. Pharm. Sci. 1986, 48, 85.
Authors are thankful to the Head, Department of
Chemistry, University of Mumbai for providing research
facilities. Authors are also grateful to UGC, New Delhi for
providing the Research Fellowship in Sciences for
Meritorious Students. We also express our sincere thanks
to Dr. Dhanji P. Rajani, Microcare Laboratory, Surat, for
availing the antimicrobial screening facilities for the
compounds reported herein.
References
22. Nyati, M.; Rao, N. S.; Srivastava, Y. K.; Verma, B. L. Asian
J. Chem. 2006, 18, 757.
1. Preston, P. N. Chem. Rev. 1974, 74, 279.
23. Balsells, J.; DiMichele, L.; Liu, J.; Kubryk, M.; Hansen, K.;
Armstrong, III, J. D. Org. Lett. 2005, 7, 1039.
2. Kazimierczuk, Z.; Andrzejewska, M.; Kaustova, J.;
Klimešova V. Eur. J. Med. Chem. 2005, 40, 203.
50