Synthesis and antimicrobial evaluation of 1,3,4-oxadiazole-based chalcone derivatives

Article abstract of DOI:10.1007/s00044-013-0791-1

A series of chalcones-bearing 1,3,4-oxadiazole derivatives was synthesized as novel bio-active antimicrobial agents against multidrug-resistant bacteria and fungi. The lead compounds (Z)-2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio) -N-(4-(3-(aryl)acryloyl)phenyl)acetamides 5a-n were synthesized via acid-catalyzed aldol condensation (SOCl₂) by reacting N-(4-acetylphenyl)-2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide (4) with differently substituted aldehydes. Compound (4) was obtained by reacting 5-(3-nitrophenyl)-1,3,4-oxadiazole-2-thiol (2) with N-(4-acetylphenyl)-2- chloroacetamide (3) in the presence of K₂CO₃. The intermediates (2) and (3) were synthesized simultaneously from 3-nitrobenzohydrazide (1) and 4-aminoacetophenone, respectively. The formation of intermediates and targeted compounds were confirmed for their structure by means of various spectral-analytical techniques like IR, ¹H NMR, ¹³C NMR, elemental analysis, and mass spectra. Antimicrobial properties of all the synthesized compounds have been evaluated against broad panel of bacteria and fungi. Springer Science+Business Media 2013.

Full text of DOI:10.1007/s00044-013-0791-1

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2014) 23:1855–1864
DOI 10.1007/s00044-013-0791-1
ORIGINAL RESEARCH
Synthesis and antimicrobial evaluation of 1,3,4-oxadiazole-based
chalcone derivatives
•
Deepkumar Joshi Kalpesh Suryakant Parikh
Received: 31 March 2013 / Accepted: 11 September 2013 / Published online: 22 September 2013
Ó Springer Science+Business Media New York 2013
Abstract A series of chalcones-bearing 1,3,4-oxadiazole
derivatives was synthesized as novel bio-active antimi-
crobial agents against multidrug-resistant bacteria and
fungi. The lead compounds (Z)-2-(5-(3-nitrophenyl)-1,3,4-
oxadiazol-2-ylthio)-N-(4-(3-(aryl)acryloyl)phenyl)aceta-
mides 5a–n were synthesized via acid-catalyzed aldol
condensation (SOCl2) by reacting N-(4-acetylphenyl)-2-(5-
(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide (4) with
differently substituted aldehydes. Compound (4) was
obtained by reacting 5-(3-nitrophenyl)-1,3,4-oxadiazole-2-
thiol (2) with N-(4-acetylphenyl)-2-chloroacetamide (3) in
the presence of K2CO3. The intermediates (2) and (3) were
synthesized simultaneously from 3-nitrobenzohydrazide
(1) and 4-aminoacetophenone, respectively. The formation
of intermediates and targeted compounds were confirmed
for their structure by means of various spectral–analytical
development of novel and effective drugs against human
diseases. It is, therefore, necessary to develop therapeutic
agents with improved potential for treating broad-spectrum
microbial infections. In continuation with our earlier con-
tribution of presenting clubbed molecules (Parikh and Jo-
shi, 2013), we report here a series of hybrid heterocyclic
scaffolds by clubbing chalcone with 1,3,4-oxadiazole in the
present study.
The versatility of chalcone and its wide range of
applicability in medicinal chemistry has attracted scientists
all over the globe to concentrate their research around it.
Chalcones have always been promising antifungal (Sarma
et al., 2007; Parikh and Joshi, 2013) and antibacterial
(Parikh and Joshi, 2013) entities. They are found to be
prominent as antioxidants (Padhyee et al., 2009) and anti-
inflammatory agents (Iwalewa et al., 2008). Some of the
substituted chalcones have exhibited excellent anticancer
(De Meyer et al., 1991), antimitotic (Ducki et al., 1998),
antiplasmodial (Mei-Lin et al., 2004), and antiprotozoal
activities (Azam et al., 2011). Chalcones have also dis-
played a variety of important biological properties such as
anti-tubercular (Linn et al., 2002) and analgesics (Iwalewa
et al., 2008) and a few of them have exhibited anti-
hyperglycemic activity (Satyanarayana et al., 2004).
The small nitrogen and oxygen containing molecules
have been under investigation since long because of their
important medicinal properties. The chemistry and phar-
macology of 1,3,4-oxadiazole ring system is of a consid-
erable interest as the core structure remains the same as
that of the various bio-active drugs possessing nitrogen and
oxygen atoms. It can be clearly noticed from the literature
survey that many of the lead molecules utilized for
developing potent bio-active agents possess 1,3,4-oxadi-
azole as a nucleus. The presence of 1,3,4-oxadiazole as an
important entity in the synthesis of several therapeutic
1
techniques like IR, H NMR, 13C NMR, elemental ana-
lysis, and mass spectra. Antimicrobial properties of all the
synthesized compounds have been evaluated against broad
panel of bacteria and fungi.
Keywords Chalcones ꢀ 1,3,4-Oxadiazole ꢀ
Antifungal activity ꢀ Antibacterial activity ꢀ MIC
Introduction
The high resistance acquired by microbes against the
antimicrobial drugs existing in the market is of a great
challenge to the scientific fraternity, involved in the
D. Joshi ꢀ K. S. Parikh (&)
Chemistry Research Laboratory, Chemistry Division, Sheth M.
N. Science College, Patan 384265, India
e-mail: deepjoshi359@yahoo.co.in
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Med Chem Res (2014) 23:1855–1864
Scheme 1 Synthesis of Compounds 5a–n
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Med Chem Res (2014) 23:1855–1864
1857
Table 1 Results for
antibacterial and antifungal
screening of compounds 5a–n
–R (Derivatives)
Minimum inhibitory concentration (MIC) in lg/ml
Gram-positive bacteria Gram-negative bacteria Fungi
S. aureus E. faecalis E. coli P. aeruginosa C. albicans A. niger
-4-OH-3-OCH3
-4-NO2
62.5
62.5
62.5
62.5
125
62.5
62.5
62.5
31.25
125
31.25
62.5
125
125
125
125
62.5
62.5
125
–
31.25
31.25
62.5
62.5
62.5
31.25
62.5
31.25
62.5
62.5
62.5
62.5
62.5
31.25
–
62.5
62.5
62.5
62.5
62.5
62.5
62.5
62.5
62.5
62.5
62.5
62.5
31.25
31.25
–
250
250
250
500
250
250
250
62.5
125
125
125
62.5
62.5
62.5
125
–
250
250
250
500
250
125
125
125
125
125
125
62.5
62.5
62.5
62.5
–
-4-Br
-3,4-diOCH3
-2-NO2
-C6H5
31.25
62.5
31.25
62.5
62.5
62.5
-3,4,5-triOCH3
N,N-diCH3
-2-OH
-4-OCH3
-2,5-diOCH3
-2-Hydroxy-1-napthaldehyde 62.5
-4-Cl
62.5
125
–
MIC, minimum inhibitory
concentration; Std., standard
drug Fluconazole for antifungal
and Ciprofloxacin for
-4-OH
Fluconazole
Ciprofloxacin
62.5
125
125
125
antibacterial tests
agents is because of its several biological properties viz.
antimicrobial (Palaska et al., 2002; Ahsan et al., 2011),
antimitotic (Lokanatha Rai and Linganna, 2000), and anti-
tubercular (Joshi et al., 2008). The mechanism of action
and chemistry of various 1,3,4-oxadiazoles are of great
interest; as they possess various biological activities such
as antioxidant (Fadda et al., 2011; Kotaiah et al., 2012),
anti-inflammatory (Maddi et al., 2012), and antitumor
(Bondock et al., 2012). A variety of substituted 1,3,4-
oxadiazole derivatives are utilized as benzodiazepine
receptor agonist (Zarghi et al., 2005). Several other bio-
logical activities associated with 1,3,4-oxadiazole nucleus
include antimicrobial (Krishnamurthy et al., 2012) and
anticancer property (Maity et al., 2011).
Nitrophenyl)-1,3,4-oxadiazole-2-thiol (2) was obtained by
reacting 3-nitrobenzohydrazide with carbon disulfide and
KOH in the presence of ethanol. Another reaction was
undertaken to produce N-(4-acetylphenyl)-2-chloroacet-
amide (3) from 4-aminoacetophenone using chloroacetyl-
chloride as a reactant and triethylamine as a catalyst. Thus
obtained two intermediates: 5-(3-nitrophenyl)-1,3,4-oxadi-
azole-2-thiol (2) and N-(4-acetylphenyl)-2-chloroacetamide
(3) were reacted in the presence of K2CO3 and acetone
leading to the formation of N-(4-acetylphenyl)-2-(5-(3-
nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide (4). Vari-
ous substituted aldehydes were made to react with N-(4-
acetylphenyl)-2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)
acetamide (4) via acid-catalyzed (SOCl2) aldol condensa-
tion (Petrov et al., 2008) resulting in the syntheses of the
desired compounds 5a–n. The MIC values of the synthe-
sized molecules are presented in Table 1.
Presently, in search for clubbed heterocyclic agents with
potent antimicrobial activity and improved pharmacologi-
cal properties, our group is pursuing investigations on
designing various biologically active molecules by club-
bing chalcones with different heterocyclic scaffolds. The
research work conducted by Patil et al. supports that sev-
eral heterocyclic scaffolds like benzofuran when incorpo-
rated with chalcones have resulted in the formation of bio-
active scaffolds (Patil et al., 2010).
Characterization
IR spectra
IR spectra of the compound 5g ((Z)-2-(5-(3-nitrophenyl)-
1,3,4-oxadiazol-2-ylthio)-N-(4-(3-(3,4,5-trimethoxyphenyl)
acryloyl)phenyl)acetamide) have given a sharp absorption
peak at 3260 cm-1 pointing out the presence of the sec-
ondary amine group. The stretching vibrations for the aro-
matic –C–H were observed atafrequency of 2981 cm-1. The
carbonyl functional group present in vicinity to the chalcone
(–CH=HC–) has shown a sharp and intense absorption peak
at 1663 cm-1. Another stretching vibration at 1592 cm-1 in
Result and discussion
Chemistry
The synthetic methods adopted for the formation of the
targeted compounds (5a–n) are depicted in Scheme 1. 5-(3-
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Med Chem Res (2014) 23:1855–1864
NO2
the spectra of compound 5g confirmed the presence of
–CH=CH– (chalcone formation) near the carbonyl group.
The presence of –C=C– in the aromatic ring was proved by
the presence of an absorption peak at 1415 cm-1. The car-
bon–nitrogen (–C–N–) linkage of the secondary amine group
was further confirmed by an intensified absorption band at
1347 cm-1. The formation of oxadiazole nucleus was con-
firmed by the presence of two absorption bands at 1035 and
1243 cm-1 indicating the –C–O–C– linkage in the structure.
Thus the IR spectral data support the formation of the desired
motifs 5a–n.
O
1
2
S
O
10
HN
11
3
8
9
6
7
N
4
N
5
16
15
12
5a: 4-OH-3-OCH3
5b: 4-NO2
13
5c: 4-Br
14
5d: 3,4-diOCH3
5e: 2-NO2
19
25
5f: H
20
17
O
5g: 3,4,5triOCH3
5h: N,N-diCH3
5i: 2-OH
5j: 4-OCH3
5k: 2,5-diOCH3
5l: Napthaldehyde
5m: 4-Cl
1H NMR
24
18
R
21
Let us consider compound 5g and try to evaluate the proton
NMR spectral data. Two broad but singlet peaks examined
at d = 3.41 and d = 3.78 indicated the presence of meth-
oxy group in the final structure. Of the three methoxy
groups present, the protons of the two methoxy groups at
C-22 and C-24 exhibited a single peak whereas the third
present at C-23 (between C-22 and C-24) was observed at a
higher d (3.78) value than the other two. The singlet peak
obtained at d = 4.36 helped to confirm the presence of the
methylene group in the final structure. The presence of the
protons intact with the two carbon atoms each of the
chalcone group was confirmed by the presence of two
doublets at d = 7.71 and d = 7.89, respectively. Also, the
geometry of the compound 5g was found to be of cis
(Z) type, as the coupling constant values for the two pro-
tons were 8.8 Hz. The protons belonging to the aromatic
rings of the final molecule were found to correspond
between the d values 7.01–8.72. A singlet peak observed at
d value of 10.69 proved the presence of proton on the
secondary amine group.
23
22
synthesized bioactive molecules
5n: 4-OH
Fig. 1 Carbon numbering of the synthesized compounds 5a–n
C-2 possessing the –NO2 functional group was confirmed
by an absorption peak obtained at a more downfield value
of d = 148.4 compared to the other carbon atoms of the
phenyl ring. The carbon numbering for the general
structure is given in Fig. 1.
Antimicrobial activity
A broad panel of microbes was used for testing the anti-
bacterial and antifungal properties of the molecules syn-
thesized. The results obtained are reproduced in Table 1 as
MIC values. The antimicrobial values showed that most of
the synthesized derivatives exhibited excellent activities
against different strains of bacteria and moderate activity
against fungi. Ciprofloxacin and fluconazole were used as
the standard drugs for antimicrobial and antifungal testing,
respectively. When ciprofloxacin was used as a standard
drug for testing the MIC values against the Gram-positive
bacterial strains, it exhibited MIC value of 62.5 and
125 lg/ml against S. aureus and E. faecalis, respectively.
The MIC values were found to be 125 lg/ml against both
the Gram-negative bacteria (E. coli and P. aeruginosa)
when tested for the standard drug ciprofloxacin. The stan-
dard drug fluconazole used against fungal strains C. albi-
cans and A. niger showed MIC values of 125 and 62.5 lg/
ml, respectively.
13C NMR
The conformation regarding the formation of the final
compound 5g was executed by the 13C NMR data varying
between d = 38.8 and d = 190.5. The carbon atoms of
the two carbonyl groups present at C-10 and C-17
appeared more downfield at 168.3 and 190.5 ppm. The
carbonyl carbon atom present in between the aromatic
ring and the –CH=HC– appeared more downfield
(d = 190.5) than the other obtained at d = 168.3 (C-10).
The two carbon of the chalcone linkage corresponded to
the absorption peaks at d = 145.5 (C-19) and d = 121.3
(C-18). The methylene group present in between the
sulfur and the carbonyl (–C=O) functional group was
observed to exhibit an absorption peak at d = 38.5. The
two carbon C-7 and C-8 of the –C–O–C– linkage in
oxadiazole nucleus exhibited absorption peaks at
d = 164.7 and d = 170.8, respectively. The carbon atom
Antibacterial activity
The newly synthesized molecules 5a–n were tested by
micro dilution/broth titer method, keeping in consideration
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1859
the standard protocols put forward. All the compounds
were screened against Gram-positive bacteria S. aureus
(ATCC no. 25923) and E. faecalis (ATCC no. 29212) and
Gram-negative bacteria E. coli (ATCC no. 25922) and
P. aeruginosa (ATCC no. 27853) by preparing the serial
dilutions of the samples. Compounds 5f and 5h exhibited
excellent activity (31.25 lg/ml) against the Gram-positive
bacterial strain S. aureus. Compounds 5a, 5b, 5c, 5d, 5g,
5i, 5j, 5k, 5l, and 5m showed MIC value (62.5 lg/ml)
equivalent to that reported by the standard ciprofloxacin.
Only two derivatives 5e and 5n were found to exhibit low
activity (125 lg/ml) as compared to the standard, whereas
most of the other compounds exhibited good activity
against the Gram-positive bacteria S. aureus. When E.
faecalis was introduced as another Gram-positive strain for
conducting the antibacterial test, it was found that not a
single derivative from the series exhibited poor activity as
compared to the standard. The derivatives 5d and 5f
showed excellent activity (31.25 lg/ml) against E. faecalis.
It was also observed that the compounds 5a, 5b, 5c, 5g, 5l,
and 5m exhibited even better MIC value (62.5 lg/ml) than
the standard ciprofloxacin. MIC values equal to that of the
standard drug was shown by the remaining derivatives 5e,
5h, 5i, 5j, 5k, and 5n. The complete series of derivatives
synthesized was tested for their antibacterial property
against two different strains of Gram-negative bacteria
E. coli and P. aeruginosa. When the compounds were
exposed against Gram-negative bacteria E. coli, it was
observed that the compounds 5a, 5b, 5f, 5m, and 5n
exhibited excellent activity (31.25 lg/ml) as compared to
the standard drug. Other derivatives 5c, 5d, 5e, 5g, 5h, 5i,
5j, 5k, and 5l have also showed much better activity
(62.5 lg/ml) than the standard drug ciprofloxacin. Overall,
all the compounds 5a–n have exhibited very good activity,
even better than the standard drug against Gram-negative
strain E. coli. Even the MIC values recorded for the
derivatives against P. aeruginosa were found to be exhib-
iting much better activity than that of the standard used.
The compounds 5m and 5n showed excellent activity
(31.25 lg/ml) as compared to the standard drug cipro-
floxacin. All the remaining derivatives 5a–l showed very
good activity (62.5 lg/ml) as compared to the standard. It
was observed that very few derivatives were found to
exhibit less MIC value than the standard ciprofloxacin,
when tested against the bacterial strains. Other than that, all
the compounds have shown excellent activity against the
broad panel of Gram-positive and Gram-negative bacterial
strains.
antifungal activity (MIC). It was found that as compared to
the antibacterial activity, very few derivatives exhibited
good activity. When the molecules 5a–n were tested
against C. albicans, derivatives 5h, 5l, 5m, and 5n showed
excellent activity (62.5 lg/ml) as compared to the standard
drug fluconazole. A few molecules 5i, 5j, and 5k exhibited
MIC value (125 lg/ml) equivalent to that of the standard
drug fluconazole. Other chemical motifs 5a, 5b, 5c, 5e, 5f,
and 5g showed less activity (250 lg/ml) as compared to the
standard drug. The compound 5d showed much poor MIC
value (500 lg/ml). A. niger was also used as a fungal strain
for checking the antifungal potency of the derived bio-
active compounds. It was observed that very few com-
pounds viz. 5l, 5m, and 5n showed antifungal activity
equivalent to the standard drug fluconazole (62.5 lg/ml).
All the other derivatives were found to exhibit poor
activity. The compound 5d was found to be least active
against the fungal strains.
SAR study
Structure–activity relationship (SAR) study helped to
reveal the effect of different substituents on the microbial
strains depending upon the different electronic environ-
ments developed on the aromatic ring by substituting both
electron-withdrawing and electron-donating groups. It was
observed that compounds 5h (3,4-dimethoxy), 5i (2-OH),
5j (4-OCH3), 5k (2,5-diOCH3), 5l (2-OH-1-napthalde-
hyde), and 5n (4-OH) with electron-donating functional
groups executed good antifungal results, displaying much
lesser MIC value than the standard drug fluconazole
against C. albicans and A. niger. It was not very clear to
justify what kind of substituted derivatives were more
potent antibacterial agents, as most of them were having
good MIC results as compared to the standard drug cip-
rofloxacin. On comparing the MIC values of all the syn-
thesized bio-active molecules (5a–n) mutually, it was
found that the derivatives with electron-donating substitu-
ents like –OH and –OCH3 exhibited much promising
results; leading to a conclusion that the derivatives having
capacity of increasing the electron density (electron-
withdrawing groups) can lead to generation of more potent
bio-molecules and can be more effective toward the
broad panel of microorganism.
Experimental
Methods, materials, and physical measurements
Antifungal activity
All the chemicals and solvents required for the synthesis were
purchased from Merck ltd., sdfine chemicals, LOBA Chemie,
and HIMEDIA. Open-end capillary method was used to
The synthesized motifs were tested against C. albicans
(ATCC no. 10231) and A. niger (ATCC no. 1015) for their
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Med Chem Res (2014) 23:1855–1864
determine the melting points of the synthesized derivatives
and the results were reported uncorrected. The completion of
reaction was monitored on TLC plates purchased from Merck
(TLC Silica gel 60F254) and appropriate solvents were used as
mobile phase. Bruker FT-IR alpha-t (ATR) was used to
determine the IR spectral data for the conformation of func-
tional groups present in the synthesized derivatives. The
1H NMR and 13C NMR spectral data were obtained using
Bruker Spectrophotometer-400 and -100 MHz, respectively,
where DMSO-d6 was used as solvent and TMS was used as
reference. Schimadzu mass spectrophotometer was used for
the Mass spectral analysis. Perkin-Elmer 2400 CHN was
utilized for the elemental analysis.
(7:3). The obtained intermediate was buff in color and solid
by state. Crystallization was carried in toluene.
Compound 3: Solid light-brown crystals; Yield: 87 %;
m.p.: 154 °C; IR (ATR, cm-1): 740 (C–Cl str.), 1413 (C=C
str. aromatic ring), 1640 (C=O str.), 3017 (–C–H str. aro-
1
matic ring), 3262 (NH str.); H NMR (400 MHz, DMSO-
d6, d, ppm): 2.56 (3H, s, –CH3), 4.89 (2H, s, –CH2), 7.77
– 8.10 (4H, d, Ar–H), 9.97 (1H, s, –NH); 13C NMR
(400 MHz, DMSO-d6, d, ppm): 27.2 (C18), 43.2 (C9), 121.0
(C12), 121.0 (C16), 129.2 (C13), 129.2 (C15), 137.2 (C14),
142.2 (C11), 166.0 (C10), 198.2 (C17); (MS (m/z): 212
(M?); Anal. calcd. for C10H10ClNO2: C-56.75, H-4.76,
N-6.62 Found: C-56.79, H-4.81, N-6.68 %.
Step-3: synthesis of N-(4-acetylphenyl)-2-(5-(3-nitrophenyl)-
Synthesis and physical data
1,3,4-oxadiazol-2-ylthio)acetamide (4)
Step-1: synthesis of 5-(3-nitrophenyl)-1,3,4-oxadiazole-2-
The compounds (2) and (3) obtained above were used as
precursors for the synthesis of titled compound (4). 5-(3-
Nitrophenyl)-1,3,4-oxadiazole-2-thiol (2) (0.01 mol, 223 g/
mol, 2.23 g) was made soluble in acetone and N-(4-acetyl-
phenyl)-2-chloroacetamide (3) (0.01 mol, 211 g/mol,
2.11 g) was added to it with stirring. K2CO3 (0.02 mol,
138 g/mol, 2.76 g) was added to it and the solution was
stirred at room temperature for 4 h. The completion of
reaction was monitored by using TLC using toluene:acetone
(7:3) as mobile phase. The solution was poured in ice-cold
water and stirred for 30 min. The separated product was
filtered, dried, and recrystallized from methanol.
thiol (2)
3-Nitrobenzohydrazide (0.01 mol, 181 g/mol, 1.81 g) was
taken in a round bottom flask containing ethanol (40 ml)
and KOH (0.01 mol, 56.11 g/mol, 0.56 g in 2 ml H2O).
Carbon disulfide (0.02 mol, 76.14 g/mol, 1.2 ml) was
added to the well-stirred solution and refluxed for 12–15 h.
The ethanol was then distilled off and cooled to room
temperature. The content was poured into ice-cold water
and acidified with diluted HCl till the precipitates were
obtained. The separated solid was washed with cold water
and dried to get the desired product. The formation of titled
intermediate was confirmed by observing the TLC using
ethyl acetate:benzene (6:4) as a mobile phase.
Compound 4: Light yellow; Yield: 79 %; IR (ATR,
cm-1): 1036, 1244 (–C–O–C– str.), 1351 (–C–N– str. sec.
amine), 1417 (–C=C– str. aromatic ring), 1593 (C=C str.
conjugated to carbonyl group), 1643 (C=O str.), 2981 (C–H
Compound 2: Solid light-green crystals; Yield: 66 %;
m.p.: 155 °C; IR (ATR, cm-1): 1035, 1248 (–C–O–C–
str.), 1419 (–C=C– str. aromatic ring), 2571 (–S–H str.),
2988 (–C–H str. aromatic ring); 1H NMR (400 MHz,
DMSO-d6, d, ppm): 7.60–8.35 (4H, m, Ar–H), 11.72 (1H,
s, –SH); 13C NMR (400 MHz, DMSO-d6, d, ppm): 122.8
(C1), 123.9 (C3), 127.4 (C6), 130.4 (C4), 133.6 (C5), 148.4
(C2), 164.5 (C7), 170.8 (C8); MS (m/z): 224 (M?); Anal.
calcd. for C8H5ClN3O3 S: C-43.05, H-2.26, N-18.83,
S-14.37 Found: C-43.08, H-2.30, N-18.86, S-14.40 %.
1
str. aromatic ring), 3266 (NH str. sec. amine); H NMR
(400 MHz, DMSO-d6, d, ppm): 2.37 (3H, s, –CH3), 4.36
(2H, s, –CH2), 7.01–8.62 (8H, m, Ar–H), 10.71 (1H, s,
–NH); 13C NMR (100 MHz, DMSO-d6, d, ppm): 27.4
(C18), 38.8 (C9), 122.5 (C12), 122.5 (C16), 122.8 (C1), 123.8
(C3), 127.4 (C6), 130.3 (C4), 131.6 (C13), 131.6 (C15),
136.8 (C14), 133.7 (C5), 144.6 (C11), 148.4 (C2), 164.7
(C7), 168.3 (C10), 170.8 (C8), 196.6 (C17); LCMS (m/z):
399 (M?); Anal. calcd. for C18H14N4O5S: C, 54.27 %; H,
3.54 %; N, 14.06 %; S, 8.05 %. Found: C, 54.32 %; H,
3.59 %; N, 14.10 %; S, 8.08 %.
Step-2: synthesis of N-(4-acetylphenyl)-2-chloroacetamide
(3)
Step-4: general procedure for the synthesis of final
compounds 5a–n
The titled compound (3) was obtained by reacting 4-ami-
noacetophenone (0.01 mol, 135 g/mol, 1.35 g) with chlo-
roacetylchloride (0.015 mol, 113 g/mol, 1.19 ml) and
Triethylamine (3–4 drops) in toluene (25 ml). The reaction
mixture was refluxed for 4 h. The completion of reaction was
monitored using TLC with mobile phase toluene:acetone
The formation of final compounds was undertaken by uti-
lizing popular acid-catalyzed aldol condensation. SOCl2
was used as an acid catalyst in the reaction, where N-(4-
acetylphenyl)-2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)
acetamide 4 (398 g/mol, 0.01 mol, 3.98 g) was made
123

Med Chem Res (2014) 23:1855–1864
1861
soluble in an appropriate amount of ethanol. To this well-
stirred solution, various substituted aldehydes (0.01 mol)
were added and stirred at room temperature for 4 h. The
obtained precipitates were poured onto crushed ice and
stirred for 1 h. The products were washed with water
periodically and then dried. All the obtained derivatives
were recrystallized from alcohol and their melting points
were recorded.
(–C–O–C– str.), 1356 (–C–N– Str. sec. amine), 1427 (–C=
C– str. aromatic ring), 1591 (C=C str. conjugated to car-
bonyl group), 1672 (C=O str. a,b-unsaturation), 2984 (C–H
1
str. aromatic ring), 3263 (NH str. sec. amine); H NMR
(400 MHz, DMSO-d6, d, ppm): 4.30 (2H, s, –CH2), 7.70
(1H, d, –HC=CH–, J = 8.7 Hz) 7.85 (1H, d, –HC=CH–,
J = 8.7 Hz), 7.03–8.56 (12H, m, Ar–H), 10.63 (1H, s,
–NH); 13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9),
121.5 (C18), 122.5 (C12), 122.5 (C16), 122.5 (C23), 122.8
(C1), 123.8 (C3), 127.4 (C6), 128.9 (C21), 128.9 (C25), 130.3
(C4), 131.6 (C13), 131.6 (C15), 131.8 (C24), 131.8 (C22), 133.
4 (C14), 133.7 (C5), 134.2 (C20), 144.6 (C11), 145.5 (C19),
148.4 (C2), 164.7 (C7), 168.3 (C10), 170.8 (C8), 190.5 (C17);
LCMS (m/z): 566 (M?2); Anal. calcd. for C25H17BrN4O5S:
C, 53.11 %; H, 3.03 %; N, 9.91 %; S, 5.67 %. Found: C,
53.15 %; H, 3.07 %; N, 9.95 %; S, 5.71 %.
(Z)-N-(4-(3-(4-Hydroxy-3-methoxyphenyl)acryloyl)phenyl)
-2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide
5a Chrome yellow; Yield: 68 %; m.p.: 162 °C; IR (ATR,
cm-1): 1039, 1244 (–C–O–C– str.), 1350 (–C–N– Str. sec.
amine), 1421 (–C=C– str. aromatic ring), 1595 (C=C str.
conjugated to carbonyl group), 1668 (C=O str. a,b-unsat-
uration), 2981 (C–H str. aromatic ring), 3262 (NH str. sec.
amine); 1H NMR (400 MHz, DMSO-d6, d, ppm): 3.46 (3H,
s, –OCH3), 4.16 (2H, s, –CH2), 7.71 (1H, d, –HC=CH–,
J = 8.8 Hz) 7.79 (1H, d, –HC=CH–, J = 8.8 Hz), 7.09–8.
52 (11H, m, Ar–H), 10.68 (1H, s, –NH); 13C NMR
(100 MHz, DMSO-d6, d, ppm): 38.8 (C9), 111.7 (C21), 116.
2 (C24), 121.5 (C18), 122.5 (C12), 122.5 (C16), 122.8 (C1),
123.0 (C25), 123.8 (C3), 127.3 (C20), 127.4 (C6), 130.3
(C4), 131.6 (C13), 131.6 (C15), 133.4 (C14), 133.7 (C5), 144.
6 (C11), 145.5 (C19), 147.5 (C23), 149.7 (C22), 148.4 (C2),
164.7 (C7), 168.3 (C10), 170.8 (C8), 190.5 (C17); LCMS (m/
z): 533 (M?); Anal. calcd. for C26H20N4O7S: C, 58.64 %;
H, 3.79 %; N, 10.52 %; S, 6.02 %. Found: C, 58.68 %; H,
3.81 %; N, 10.56 %; S, 6.06 %.
(Z)-N-(4-(3-(3,4-Dimethoxyphenyl)acryloyl)phenyl)-2-(5-
(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide 5d Dark
orange; Yield: 73 %; m.p.: 160 °C; IR (ATR, cm-1): 1040,
1254 (–C–O–C– str.), 1363 (–C–N– Str. sec. amine), 1424
(–C=C– str. aromatic ring), 1598 (C=C str. conjugated to
carbonyl group), 1671 (C=O str. a,b-unsaturation), 2992
1
(C–H str. aromatic ring), 3268 (NH str. sec. amine); H
NMR (400 MHz, DMSO-d6, d, ppm): 4.18 (2H, s, –CH2),
7.71 (1H, d, –HC=CH–, J = 8.8 Hz) 7.88 (1H, d, –HC=
CH–, J = 8.8 Hz), 7.16–8.54 (11H, m, Ar–H), 10.52 (1H,
s, –NH); 13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8
(C9), 121.5 (C18), 122.5 (C12), 122.5 (C16), 122.8 (C1), 123.8
(C3), 127.4 (C6), 149.8 (C23), 122.8 (C25), 149.8 (C22), 111.
9 (C24), 130.3 (C4), 131.6 (C13), 131.6 (C15), 133.4 (C14),
133.7 (C5), 127.3 (C20), 144.6 (C11), 145.5 (C19), 111.4
(C21), 148.4 (C2), 164.7 (C7), 168.3 (C10), 170.8 (C8), 190.
5 (C17); LCMS (m/z): 547 (M?); Anal. calcd. for
C27H22N4O7S: C, 59.33 %; H, 4.06 %; N, 10.25 %; S,
5.87 %. Found: C, 59.38 %; H, 4.10 %; N, 10.28 %; S,
5.92 %.
(Z)-2-(5-(3-Nitrophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-(3-
(4-nitrophenyl)acryloyl)phenyl)acetamide 5b Dark brown;
Yield: 74 %; m.p.: 156 °C; IR (ATR, cm-1): 1038, 1240
(–C–O–C– str.), 1361 (–C–N– Str. sec. amine), 1417 (–C=
C– str. aromatic ring), 1584 (C=C str. conjugated to car-
bonyl group), 1660 (C=O str. a,b-unsaturation), 2992 (C–H
1
str. aromatic ring), 3254 (NH str. sec. amine); H NMR
(400 MHz, DMSO-d6, d, ppm): 4.22 (2H, s, –CH2), 7.76
(1H, d, –HC=CH–, J = 8.8 Hz) 7.83 (1H, d, –HC=CH–,
J = 8.8 Hz), 7.12–8.59 (12H, m, Ar–H), 10.52 (1H, s,
–NH); 13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9),
121.5 (C18), 122.5 (C12), 122.5 (C16), 122.8 (C1), 123.8 (C3),
123.8 (C24), 123.8 (C22), 129.4 (C21), 129.4 (C25), 127.4
(C6), 130.3 (C4), 131.6 (C13), 131.6 (C15), 133.4 (C14), 133.7
(C5), 141.3 (C20), 144.6 (C11), 145.5 (C19), 147.7 (C23), 148.
4 (C2), 164.7 (C7), 168.3 (C10), 170.8 (C8), 190.5 (C17);
LCMS (m/z): 532 (M?); Anal. calcd. for C25H17N5O7S: C,
56.49 %; H, 3.22 %; N, 13.18 %; S, 6.03 %. Found: C, 56.
54 %; H, 3.26 %; N, 13.22 %; S, 6.06 %.
(Z)-2-(5-(3-Nitrophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-(3-
(2-nitrophenyl)acryloyl)phenyl)acetamide 5e Brown; Yield:
71 %; m.p.: 148 °C; IR (ATR, cm-1): 1035, 1249 (–C–O–
C– str.), 1359 (–C–N– Str. sec. amine), 1414 (–C=C– str.
aromatic ring), 1587 (C=C str. conjugated to carbonyl
group), 1662 (C=O str. a,b-unsaturation), 2987 (C–H str.
aromatic ring), 3271 (NH str. sec. amine); 1H NMR
(400 MHz, DMSO-d6, d, ppm): 4.09 (2H, s, –CH2), 7.78
(1H, d, –HC=CH–, J = 8.7 Hz) 7.89 (1H, d, –HC=CH–,
J = 8.7 Hz), 7.04–8.62 (12H, m, Ar–H), 10.58(1H, s, –NH);
13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9), 121.5
(C18), 122.5 (C12), 122.5 (C16), 122.8 (C1), 123.8 (C3), 127.4
(C6), 127.9 (C23), 128.5 (C25), 128.8 (C22), 128.8 (C24),
130.3 (C4), 131.6 (C13), 131.6 (C15), 133.4 (C14), 133.7 (C5),
127.4 (C20), 144.6 (C11), 145.5 (C19), 147.8 (C21), 148.4
(Z)-N-(4-(3-(4-Bromophenyl)acryloyl)phenyl)-2-(5-(3-nitro-
phenyl)-1,3,4-oxadiazol-2-ylthio)acetamide
5c Brown;
Yield: 65 %; m.p.: 158 °C; IR (ATR, cm-1): 1041, 1242
123

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Med Chem Res (2014) 23:1855–1864
(C2), 164.7 (C7), 168.3 (C10), 170.8 (C8), 190.5 (C17); LCMS
(m/z): 532 (M?); Anal. calcd. for C25H17N5O7S: C, 56.49 %;
H, 3.22 %; N, 13.18 %; S, 6.03 %. Found: C, 56.54 %; H,
3.25 %; N, 13.22 %; S, 6.07 %.
1H NMR (400 MHz, DMSO-d6, d, ppm): 4.29 (2H, s, –CH2),
7.71 (1H, d, –HC=CH–, J = 8.8 Hz), 7.83 (1H, d, –HC=
CH–, J = 8.8 Hz) 7.10–8.48 (12H, m, Ar–H), 10.52 (1H, s,
–NH); 13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9),
111.9 (C22), 111.9 (C24), 121.3 (C18), 122.5 (C12), 122.5
(C16), 122.8 (C1), 123.9 (C3), 124.9 (C20), 127.4 (C6), 129.6
(C21), 129.6 (C25), 130.4 (C4), 131.6 (C13), 131.6 (C15),
133.4 (C14), 133.7 (C5), 144.6 (C11), 145.5 (C19), 148.4 (C2),
150.8 (C23), 164.7 (C7), 168.3 (C10), 170.8 (C8), 190.5 (C17);
LCMS (m/z): 530 (M?); Anal. calcd. for C27H23N5O5S: C,
61.24 %; H, 4.38 %; N, 13.22 %; S, 6.05 %. Found: C, 61.
29 %; H, 4.41 %; N, 13.25 %; S, 6.11 %.
(Z)-N-(4-Cinnamoylphenyl)-2-(5-(3-nitrophenyl)-1,3,4-ox-
adiazol-2-ylthio)acetamide 5f Black; Yield: 62 %; m.p.:
205 °C; IR (ATR, cm-1): 1037, 1246 (–C–O–C– str.),
1351 (–C–N– Str. sec. amine), 1419 (–C=C– str. aromatic
ring), 1599 (C=C str. conjugated to carbonyl group), 1654
(C=O str. a,b-unsaturation), 2991 (C–H str. aromatic ring),
3263 (NH str. sec. amine); 1H NMR (400 MHz, DMSO-d6,
d, ppm): 4.27 (2H, s, –CH2), 7.74 (1H, d, –HC=CH–, J =
8.7 Hz) 7.81 (1H, d, –HC=CH–, J = 8.8 Hz), 7.16–8.57
(13H, m, Ar–H), 10.73 (1H, s, –NH); 13C NMR (100 MHz,
DMSO-d6, d, ppm): 38.8 (C9), 121.5 (C18), 122.5 (C12),
122.5 (C16), 122.8 (C1), 123.8 (C3), 127.4 (C6), 127.9
(C23), 128.5 (C21), 128.5 (C25), 128.8 (C22), 128.8 (C24),
130.3 (C4), 131.6 (C13), 131.6 (C15), 133.4 (C14), 133.7
(C5), 135.2 (C20), 144.6 (C11), 145.5 (C19), 148.4 (C2), 164.
7 (C7), 168.3 (C10), 170.8 (C8), 190.5 (C17); LCMS (m/z):
487.5 (M?); Anal. calcd. for C25H18N4O5S: C, 61.72 %; H,
3.73 %; N, 11.52 %; S, 6.59 %. Found: C, 61.77 %; H,
3.76 %; N, 11.56 %; S, 6.63 %.
(Z)-N-(4-(3-(2-Hydroxyphenyl)acryloyl)phenyl)-2-(5-(3-
nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide 5i Dark
violet; Yield: 78 %; m.p.: 180 °C; IR (ATR, cm-1): 1038,
1247 (–C–O–C– str.), 1356 (–C–N– str. sec. amine), 1424
(–C=C– str. aromatic ring), 1587 (C=C str. conjugated to
carbonyl group), 1654 (C=O str. a,b-unsaturation), 2984
1
(C–H str. aromatic ring), 3271 (NH str. sec. amine); H
NMR (400 MHz, DMSO-d6, d, ppm): 4.38 (2H, s, –CH2),
7.75 (1H, d, –HC=CH–, J = 8.7 Hz), 7.88 (1H, d, –HC=
CH–, J = 8.7 Hz) 7.19–8.58 (12H, m, Ar–H), 10.34 (1H, s,
–NH);13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9),
117.8 (C22), 121.3 (C18), 121.6 (C24), 122.5 (C12), 122.5
(C16), 122.8 (C1), 122.9 (C20), 123.9 (C3), 127.4 (C6), 129.
3 (C25), 129.7 (C23), 130.4 (C4), 131.6 (C13), 131.6 (C15),
133.4 (C14), 133.7 (C5), 144.6 (C11), 145.5 (C19), 148.4
(C2), 157.6 (C21), 164.7 (C7), 168.3 (C10), 170.8 (C8),
190.5 (C17); LCMS (m/z): 503 (M?); Anal. calcd. for C25
H18N4O6S: C, 59.75 %; H, 3.61 %; N, 11.15 %; S, 6.38 %.
Found: C, 59.80 %; H, 3.66 %; N, 11.18 %; S, 6.44 %.
(Z)-2-(5-(3-Nitrophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-(3-
(3,4,5-trimethoxyphenyl)acryloyl)phenyl)acetamide 5g Light
brown; Yield: 67 %; m.p.: 142 °C; IR (ATR, cm-1): 1035,
1243 (–C–O–C– str.), 1347 (–C–N– str. sec. amine), 1415
(–C=C– str. aromatic ring), 1592 (C=C str. conjugated to
carbonyl group), 1663 (C=O str. a,b-unsaturation), 2981
1
(C–H str. aromatic ring), 3260 (NH str. sec. amine); H
NMR (400 MHz, DMSO-d6, d, ppm): 3.41 (6H, s, –OCH3),
3.78 (3H, s, –OCH3), 4.36 (2H, s, –CH2), 7.71 (1H, d,
–HC=CH–, J = 8.8 Hz), 7.89 (1H, d, –HC=CH–, J = 8.
8 Hz) 7.01–8.72 (10H, m, Ar–H), 10.69 (1H, s, –NH); 13C
NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9), 103.6
(C21), 103.6 (C25), 121.3 (C18), 122.5 (C12), 122.5 (C16),
122.8 (C1), 123.9 (C3), 126.6 (C20), 127.4 (C6), 130.4 (C4),
131.6 (C13), 131.6 (C15), 133.4 (C14), 133.7 (C5), 138.7
(C23), 144.6 (C11), 145.5 (C19), 148.4 (C2), 153.5 (C22), 153.
5 (C24), 164.7 (C7), 168.3 (C10), 170.8 (C8), 190.5 (C17);
LCMS (m/z): 577 (M?); Anal. calcd. for C28H24N4O8S: C,
58.33 %; H, 4.20 %; N, 9.72 %; S, 5.56 %. Found: C,
58.37 %; H, 4.23 %; N, 9.75 %; S, 5.60 %.
(Z)-N-(4-(3-(4-Methoxyphenyl)acryloyl)phenyl)-2-(5-(3-nitro-
phenyl)-1,3,4-oxadiazol-2-ylthio)acetamide
5j Yellow;
Yield: 72 %; m.p.: 170 °C; IR (ATR, cm-1): 1029, 1239 (–
C–O–C– str.), 1350 (–C–N– str. sec. amine), 1419 (–C=C–
str. aromatic ring), 1594 (C=C str. conjugated to carbonyl
group), 1663 (C=O str. a,b-unsaturation), 2993 (C–H str.
aromatic ring), 3269 (NH str. sec. amine); 1H NMR
(400 MHz, DMSO-d6, d, ppm): 4.27 (2H, s, –CH2), 7.72
(1H, d, –HC=CH–, J = 8.8 Hz), 7.83 (1H, d, –HC=CH–,
J = 8.8 Hz) 7.03–8.61 (12H, m, Ar–H), 10.51 (1H, s,
–NH); 13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9),
114.8 (C22), 114.8 (C24), 121.3 (C18), 122.5 (C12), 122.5
(C16), 122.8 (C1), 123.9 (C3), 127.8 (C20), 127.4 (C6), 130.
6 (C25), 130.4 (C4), 130.6 (C21), 131.6 (C13), 131.6 (C15),
133.4 (C14), 133.7 (C5), 144.6 (C11), 145.5 (C19), 148.4
(C2), 160.2 (C23), 164.7 (C7), 168.3 (C10), 170.8 (C8), 190.
5 (C17); LCMS (m/z): 517 (M?); Anal. calcd. for
C26H20N4O6S: C, 60.46 %; H, 3.90 %; N, 10.58 %; S, 6.
21 %. Found: C, 60.52 %; H, 3.95 %; N, 10.62 %; S, 6.
25 %.
(Z)-N-(4-(3-(4-(Dimethylamino)phenyl)acryloyl)phenyl)-2-
(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide 5h
Light yellow; Yield: 60 %; m.p.:170 °C; IR (ATR, cm-1):
1042, 1256 (–C–O–C– str.), 1353 (–C–N– str. sec. amine),
1427 (–C=C– str. aromatic ring), 1594 (C=C str. conju-
gated to carbonyl group), 1669 (C=O str. a,b-unsaturation),
2995 (C–H str. aromatic ring), 3267 (NH str. sec. amine);
123

Med Chem Res (2014) 23:1855–1864
1863
(Z)-N-(4-(3-(2,5-Dimethoxyphenyl)acryloyl)phenyl)-2-(5-(3-
nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide 5k Orange;
Yield: 61 %; m.p.: 160 °C; IR (ATR, cm-1): 1032, 1246
(–C–O–C– str.), 1354 (–C–N– str. sec. amine), 1417 (–C=
C– str. aromatic ring), 1597 (C=C str. conjugated to car-
bonyl group), 1657 (C=O str. a,b-unsaturation), 2979 (C–H
121.3 (C18), 122.5 (C12), 122.5 (C16), 122.8 (C1), 123.9
(C3), 127.4 (C6), 129.0 (C24), 129.0 (C22), 129.2 (C25),
129.2 (C21), 130.4 (C4), 131.6 (C13), 131.6 (C15), 133.3
(C20), 133.4 (C14), 133.7 (C5), 133.8 (C23), 141.3 (C19),
144.6 (C11), 148.4 (C2), 164.7 (C7), 168.3 (C10), 170.8
(C8), 190.5 (C17); LCMS (m/z): 522 (M?2); Anal. calcd.
for C25H17ClN4O5S: C, 57.64 %; H, 3.29 %; N, 10.75 %;
S, 6.16 %. Found: C, 57.68 %; H, 3.32 %; N, 10.78 %;
S, 6.20 %.
1
str. aromatic ring), 3274 (NH str. sec. amine); H NMR
(400 MHz, DMSO-d6, d, ppm): 4.34 (2H, s, –CH2), 7.79
(1H, d, –HC=CH–, J = 8.8 Hz), 7.87 (1H, d, –HC=CH–,
J = 8.8 Hz) 7.02–8.52 (11H, m, Ar–H), 10.73 (1H, s,
–NH); 13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9),
115.4 (C22), 152.8 (C24), 121.3 (C18), 122.5 (C12), 122.5
(C16), 122.8 (C1), 123.9 (C3), 115.8 (C20), 127.4 (C6), 111.
7 (C25), 130.4 (C4), 151.6 (C21), 131.6 (C13), 131.6 (C15),
133.4 (C14), 133.7 (C5), 144.6 (C11), 145.5 (C19), 148.4
(C2), 114.6 (C23), 164.7 (C7), 168.3 (C10), 170.8 (C8),
190.5 (C17); LCMS (m/z): 547 (M?); Anal. calcd. for
C27H22N4O7S: C, 59.33 %; H, 4.06 %; N, 10.25 %; S,
5.87 %. Found: C, 59.38 %; H, 4.10 %; N, 10.29 %; S,
5.90 %.
(Z)-N-(4-(3-(4-Hydroxyphenyl)acryloyl)phenyl)-2-(5-(3-nitro-
phenyl)-1,3,4-oxadiazol-2-ylthio)acetamide
5n Yellow;
Yield: 63 %; m.p.: 208 °C; IR (ATR, cm-1): 1041, 1248
(–C–O–C– str.), 1360 (–C–N– str. sec. amine), 1421 (–C=
C– str. aromatic ring), 1597 (C=C str. conjugated to car-
bonyl group), 1664 (C=O str. a,b-unsaturation), 2990 (C–H
1
str. aromatic ring), 3258 (NH str. sec. amine); H NMR
(400 MHz, DMSO-d6, d, ppm): 4.25 (2H, s, –CH2), 7.68
(1H, d, –HC=CH–, J = 8.7 Hz), 7.82 (1H, d, –HC=CH–,
J = 8.8 Hz) 7.03–7.64 (12H, m, Ar–H), 10.59 (1H, s,
–NH); 13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9),
116.4 (C24), 116.4 (C22), 121.3 (C18), 122.5 (C12), 122.5
(C16), 122.8 (C1), 123.9 (C3), 127.4 (C6), 127.9 (C20),
130.4 (C4), 130.8 (C25), 130.8 (C21), 131.6 (C13), 131.6
(C15), 133.4 (C14), 133.7 (C5), 141.3 (C19), 144.6 (C11),
148.4 (C2), 157.9 (C23), 164.7 (C7), 168.3 (C10), 170.8
(C8), 190.5 (C17); LCMS (m/z): 503 (M?2); Anal. calcd. for
C25H18N4O6S: C, 59.75 %; H, 3.61 %; N, 11.15 %; S,
6.38 %. Found: C, 59.81 %; H, 3.65 %; N, 11.17 %; S,
6.42 %.
(Z)-N-(4-(3-(3-Hydroxynaphthalen-2-yl)acryloyl)phenyl)-
2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide 5l
Dark brown; Yield: 58 %; m.p.: 220 °C; IR (ATR, cm-1):
1041, 1250 (–C–O–C– str.), 1352 (–C–N– str. sec. amine),
1422 (–C=C– str. aromatic ring), 1589 (C=C str. conju-
gated to carbonyl group), 1664 (C=O str. a,b-unsaturation),
2985 (C–H str. aromatic ring), 3259 (NH str. sec. amine);
1H NMR (400 MHz, DMSO-d6, d, ppm): 4.28 (2H, s,
–CH2), 7.72 (1H, d, –HC=CH–, J = 8.7 Hz), 7.82 (1H, d,
–HC=CH–, J = 8.7 Hz) 6.94–8.61 (14H, m, Ar–H), 10.49
(1H, s, –NH); 13C NMR (100 MHz, DMSO-d6, d, ppm):
38.8 (C9), 111.8 (C22), 121.3 (C18), 122.5 (C12), 122.5
(C16), 122.8 (C1), 123.9 (C3), 126.7 (C20), 127.0 (C25),
127.4 (C6), 129.3 (C24), 130.4 (C4), 131.6 (C13), 131.6
(C15), 133.4 (C14), 133.7 (C5), 137.9 (C23), 141.3 (C19),
144.6 (C11), 148.4 (C2), 154.9 (C21), 164.7 (C7), 168.3
(C10), 170.8 (C8), 190.5 (C17); LCMS (m/z): 553 (M?);
Anal. calcd. for C29H20N4O6S: C, 63.04 %; H, 3.65 %; N,
10.14 %; S, 5.80 %. Found: C, 63.08 %; H, 3.68 %; N, 10.
18 %; S, 5.84 %.
Conclusion
The synthesized 1,3,4-oxadiazoles-clubbed chalcone deriv-
atives (5a–n) have shown significant antifungal and anti-
bacterial property. More than half of the derivatives have
exhibited MIC value even better than that of the standards
used. These bio-active molecules can be further optimized as
potent lead molecules by introducing more electron-donat-
ing groups in the basic structure as stated in the SAR study.
It can be concluded that, the presence of electron-donating
groups hydroxy (–OH) and methoxy (–OCH3) in the titled
derivatives having the property of generating optimum
electron density has helped to achieve better heterocyclic
scaffolds possessing potent antibacterial and antifungal
properties. Furthermore, there is an ample scope in devel-
oping these derivatives as potent lead molecules, which can
be used as antimicrobial therapeutics.
(Z)-N-(4-(3-(4-Chlorophenyl)acryloyl)phenyl)-2-(5-(3-nitro-
phenyl)-1,3,4-oxadiazol-2-ylthio)acetamide 5m Dark brown;
Yield: 65 %; m.p.: 195 °C; IR (ATR, cm-1): 1038, 1246
(–C–O–C– str.), 1359 (–C–N– Str. sec. amine), 1428 (–C=
C– str. aromatic ring), 1592 (C=C str. conjugated to car-
bonyl group), 1661 (C=O str. a,b-unsaturation), 2982 (C–H
1
str. aromatic ring), 3273 (NH str. sec. amine); H NMR
(400 MHz, DMSO-d6, d, ppm): 4.21 (2H, s, –CH2), 7.70
(1H, d, –HC=CH–, J = 8.7 Hz), 7.79 (1H, d, –HC=CH–,
J = 8.7 Hz) 7.12–8.54 (12H, m, Ar–H), 10.53 (1H, s,
–NH); 13C NMR (100 MHz, DMSO-d6, d, ppm): 38.8 (C9),
Acknowledgments Authors KSP and DSJ are thankful to North
Gujarat Education Society, Mumbai and Sheth M. N. Science Col-
lege, Patan for the infrastructural facilities. Also, we would like to
appreciate the support provided by SAIF, Chandigarh for providing
123

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Med Chem Res (2014) 23:1855–1864
the spectral data on request. We are also indebted to Department of
Science and Technology, India for providing INSPIRE fellowship to
the author DSJ.
Linn L-M, Zhou Y, Flavin MT, Zhou LM, Nie W, Chen F-C (2002)
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antimitotic activity of alkylated 2-amino-1,3,4-oxadiazole deriv-
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00056-2
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