Synthesis and Antimicrobial Screening of 2-Aryl-5-((2-arylthiazol-4-yl)methyl)-1,3,4-oxadiazole Derivatives

Article abstract of DOI:10.1002/jhet.2747

A new series of 2-aryl-5-((2-arylthiazol-4-yl)methyl)-1,3,4-oxadiazole derivatives was synthesized by condensation of 2-(2-substituted thiazol-4-yl)acetohydrazide with aryl aldehydes followed by oxidative cyclocondensation using iodobenzene diacetate. The

Full text of DOI:10.1002/jhet.2747

Month 2016
Synthesis and Antimicrobial Screening of 2-Aryl-5-((2-arylthiazol-4-yl)
methyl)-1,3,4-oxadiazole Derivatives
a
b
c
b
*
Pravin C. Mhaske, Shivaji H. Shelke, Manish Bhoye, and Vivek D. Bobade
aPost Graduate Department of Chemistry, S. P. Mandali’s Sir Parashurambhau College, Savitribai Phule Pune University,
Tilak Road, 411 030 Pune, India
bPost Graduate Department of Chemistry, H. P. T. Arts and R. Y. K. Science College, Savitribai Phule Pune University,
College Road, 422 005 Nashik, India
cPost Graduate and Research Department of Chemistry, S. N. Arts, D. J. M. Commerce, and B. N. S. Science College,
Savitribai Phule Pune University, Sangamner, District Ahmednagar 422 005, India
*
E-mail: mhaskepc18@gmail.com
Additional Supporting Information may be found in the online version of this article.
Received April 8, 2016
DOI 10.1002/jhet.2747
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A new series of 2-aryl-5-((2-arylthiazol-4-yl)methyl)-1,3,4-oxadiazole derivatives was synthesized by
condensation of 2-(2-substituted thiazol-4-yl)acetohydrazide with aryl aldehydes followed by oxidative
cyclocondensation using iodobenzene diacetate. The structure of synthesized compounds was characterized
by IR, NMR, and mass analysis. All the newly synthesized compounds were evaluated for their in vitro an-
timicrobial activity. Some of the compounds showed moderate antimicrobial activity.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
antifungal activities. These results prompted us to design
new thiazolyl-1,3,4-oxadiazole derivatives and screen for
antifungal activity. In the present article, we report the
synthesis and antimicrobial activity of new 2-aryl-
5-((2-arylthiazol-4-yl)methyl)-1,3,4-oxadiazole derivatives.
Thiazole is an important pharmacophore, and its cou-
pling with other rings could furnish new biologically active
compounds [1–4]. Thiazole compounds have exhibited a
broad range of biological activities such as antitumor [5],
anticancer [6], antibiotic [7,8], anti-inflammatory [9–12],
antibacterial and antifungal [13–15], antitubercular [16–
18], antiviral [19], antidepressant activity [20], Peroxisome
proliferator-activated receptor (PPAR) α/γ/δ pan agonists
[21,22], and antihelmintic [23] activities. The heterocyclic
compounds containing 1,3,4-oxadiazole nuclei showed
anti-inflammatory [24], hypoglycemic [25], anti-HIV
[26], antitumor [27], antibacterial [28], antifungal [29], an-
tihypertensive [30], antituberculosis [31], analgesic [32],
anticonvulsant [33], and herbicidal [34] activities.
Literature revealed that clubbed 1,2,4-triazolyl-1,3,4-
oxadiazole and 1,3,4-triazolyl-thiazoles are new classes of
azole antimycobacterials, which are proven to be highly ac-
tive both in vitro and in vivo [35–40]. Many researchers
have synthesized 1,3,4-oxadiazole derivatives and
screened, for biological activity [41–45], 2-(4-
RESULTS AND DISCUSSION
In the present article, we wish to report the synthesis of
2-aryl-5-((2-arylthiazol-4-yl)methyl)-1,3,4-oxadiazole by
oxidative cyclization of N′-benzylidene-2-(2-arylthiazol-
4-yl)acetohydrazide (Scheme 1).
Ethyl 2-(2-substituted thiazol-4-yl) acetate 1a–c was
prepared by cyclocondensation of substituted thioamides
with ethyl 4-chloro-3-oxobutanoate in dry ethanol. Ester
1a–c on nucleophilic substitution reaction with hydrazine
hydrate gave 2-(2-substituted thiazol-4-yl)acetohydrazide
2a–c. Acetohydrazide 2a–c on condensation with aryl
aldehydes 3a–f gave Schiff’s base N′-arylidene-2-(2-
arylthiazol-4-yl)acetohydrazide 4a–r, which on oxidative
cyclocondensation using iodobenzene diacetate furnished
2-aryl-5-((2-arylthiazol-4-yl)methyl)-1,3,4-oxadiazole 5a–r.
All the newly synthesized compounds were character-
isopropylthiazol-2-yl)-5-aryl-1,3,4-oxadiazoles
[46,47],
2,3-dihydrothiazoline-substituted 1,3,4-oxadiazole [48],
1,2,4-triazolo[1,5-a]pyrimidine-substituted 1,3,4-oxadiazoles
[49], and 5-dithiazolyl-2-R-1,3,4-Δ4-oxadiazoline [50]
derivatives, which showed antimicrobial, antitumor, and
1
ized by spectral (IR, H NMR, 13C NMR, and elemental
analysis) methods. The structure of Schiff’s base 4a–r
revealed in each case absorption bands in the region:
© 2016 Wiley Periodicals, Inc.

P. C. Mhaske, S. H. Shelke, M. Bhoye, and V. D. Bobade
Vol 000
Scheme 1.
3258–3072 cm–1, 1685–1660cm–1, and 1628–1492 cm–1
corresponding to N–H, C=O, and C=N/C=C, respectively.
The H NMR spectrum of 4k showed singlet at δ 4.15
(National Collection of Industrial Microorganisms (NCIM)
545). Known antibiotics ciprofloxacin and nystatin were
used as positive controls, whereas DMSO was used as neg-
ative control. To evaluate the activity of the synthesized
compounds, the zone of inhibition was determined. The
in vitro antimicrobial screening results of tested com-
pounds are listed in Table 1.
The investigation revealed that most of the synthesized
compounds were moderately active against the Gram-positive
strain of bacteria B. subtilis and Gram-negative strain of S.
typhi. It is also observed that the acetohydrazide derivatives
4b, 4l, 4m, 4p, 4q, and 4r as well as the oxadiazole derivatives
5c, 5h, 5i, 5j, 5k, 5l, 5n, 5q, and 5r showed moderate activity
against both tested species.
The results of the in vitro antifungal activity of the syn-
thesized compounds were analyzed; some of the com-
pounds showed moderate antifungal activity against A.
niger. The acetohydrazide derivatives 4d, 4e, 4f, 4g, 4h,
4n, 4p, and 4r and oxadiazole derivatives 5c, 5c, 5l, and
5r showed moderate antifungal activity. It was also ob-
served that the antifungal activity of only acetohydrazide
4r was found to be retained in oxadiazole 5r. The results
revealed moderate to good activity for compounds 4p, 4r,
5c, 5l, and 5r against all tested species.
1
that corresponds to –CH2 protons α to carbonyl, the eight
aromatic protons, and one thiazole proton resonated as
multiplets between δ 7.01 and δ 7.82. The N=CH and
O=C–NH=N protons resonated at δ 8.02 and 10.27, re-
spectively. The two peaks of methylene, NH and CH pro-
tons, were observed because of two geometrical isomers.
The 13C NMR of 4k displayed signals at 36.6 and 173.3
that correspond to methylene and carbonyl group, respec-
tively. Oxidative cyclization of 4k gave oxadiazole 5k;
1
the H NMR spectrum of 5k revealed the deshielding of
methylene protons at δ 4.53. The aromatic and thiazole
protons resonated at δ 7.18 to 8.05. The disappearance of
the signal 10.27 further confirmed the oxidative cycliza-
tion. The 13C NMR spectrum of 5k showed shielding of
the aliphatic carbon peak at δ 28.2 and disappearance of
carbonyl signal that confirmed the oxadiazole formation.
The structure was further confirmed by liquid chromatog-
raphy-mass spectrometry (LCMS) spectrum, which
showed peak at 372.03 (M + H)+. The physical properties
of compounds 4a–r and 5a–r are given in Table 1.
ANTIMICROBIAL ACTIVITY
EXPERIMENTAL
The in vitro antibacterial activity was performed against
Gram-positive bacteria Bacillus subtilis and Gram-negative
bacteria Salmonella typhi and fungi Aspergillus niger
Melting points were determined in an open capillary on
Veego melting point apparatus (Veego Instruments
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Synthesis and Antimicrobial Screening of 2-Aryl-5-((2-arylthiazol-4-yl)methyl)-
1,3,4-oxadiazole Derivatives
Table 1
Physical properties and antimicrobial activity of compounds 4a–r and 5a–r.
Zone of inhibition
Compound
R
R1
Mp °C
Yield %
Bacillus subtilis
Salmonella typhi
Aspergillus niger
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
H
H
H
H
H
H
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
H
H
4-Cl
2-F
3-F
4-F
4-NMe2
H
4-Cl
2-F
3-F
4-F
4-NMe2
H
4-Cl
2-F
3-F
4-F
4-NMe2
H
4-Cl
2-F
3-F
4-F
4-NMe2
H
4-Cl
2-F
3-F
4-F
4-NMe2
H
4-Cl
2-F
3-F
4-F
146–148
164–166
164–166
152–153
156–158
168–170
158–160
178–180
168–170
176–177
158–160
188–189
168–170
184–185
162–164
182–184
212–214
208–210
117–118
142–144
78–80
80
78
80
84
88
74
75
80
72
74
78
68
80
84
74
77
80
72
48
52
45
48
55
40
44
50
43
48
48
40
52
50
44
48
47
45
9.44
10.60
—
—
—
—
9.64
—
—
—
—
9.68
—
—
—
11.80
12.20
11.65
9.00
11.75
—
—
—
—
—
11.20
—
9.20
—
11.30
—
10.20
11.35
—
—
—
—
—
12.50
11.90
12.10
10.80
—
10.64
12.30
11.80
9.30
12.10
9.60
9.78
10.30
11.20
12.80
10.56
—
—
12.64
12.88
—
—
11.80
9.88
11.44
—
H
H
H
H
—
—
11.88
12.36
12.80
11.40
—
9.10
11.30
12.20
12.10
11.75
—
12.10
—
—
11.20
10.18
26.05
NA
12.00
10.20
12.60
—
78–80
108–110
182–184
110–112
120–122
106–108
108–110
92–94
108–110
115–116
132–134
110–112
138–140
94–96
H
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
3-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
—
12.20
10.50
12.30
12.80
9.00
—
—
—
10.78
—
—
—
—
—
9.48
13.20
12.30
9.50
11.80
12.30
28.10
NA
5o
5p
5q
5r
4-NMe2
78–80
11.00
NA
22.10
Ciprofloxacin
Nystatin
Ciprofloxacin (10 μg/disk) and nystatin (100 U/disk) used as reference; synthesized compounds (100 μg/disk).
NA, not applicable; —, inactive.
Corporation, Mumbai, India) and are uncorrected. The
purity of the compounds was checked on silica gel-G
plates. Compounds 5a–r was purified on silica gel
(100–200) column chromatography using ethyl acetate :
hexane as eluent. Infrared spectra (cm–1) were recorded
in KBr on a Shimadzu Model FTIR-435 spectrophotometer
(Singapore). 1H NMR and 13C NMR spectra were recorded
in CDCl3 or DMSO-d6 solution on a Varian Mercury YH-
300 spectrometer (Switzerland) operating at 300MHz for
1H and 75MHz for 13C. Chemical shifts are expressed rel-
ative to tetramethylsilane and were reported as δ (ppm).
The elemental analysis was performed on FLASH EA
1112 analyzer (Thermo Electron S.p.A., Milan, Italy).
LCMS spectra were measured on a Shimadzu LCMS-
QP8000. The isotopic peak at M+ 2 was observed in the
mass spectrum of all the compounds because of S, Br,
and/or Cl.
General procedure for synthesis of compounds 4a–r.
The solution of substituted benzaldehyde, 3a–f
(0.001 mol), and 2-(2-phenylthiazol-4-yl)acetohydrazide,
2a–c (0.001 mol), was refluxed in methanol (15 mL) for
3 h. After completion of the reaction thin layer
chromatography (TLC), the reaction mixture was cooled
at room temperature. The product was filtered and
washed with cold methanol to furnish N′-substituted
benzylidene-2-(2-phenylthiazol-4-yl)acetohydrazide, 4a–r.
N′-Benzylidene-2-(2-phenylthiazol-4-yl)acetohydrazide, 4a.
IR: 3261, 3112, 2910, 2824, 1665, 1600, 1558, 1528,
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P. C. Mhaske, S. H. Shelke, M. Bhoye, and V. D. Bobade
Vol 000
1
1441, 1355, 1240, 1180, 1006cm–1; H NMR (400MHz,
DMSO-d6): δ 4.01 (s, 2H), 7.19–7.58 (m, 7H), 7.68–7.78
(m, 2H), 7.59 (s, 1H), 7.90–7.94 (m, 2H), 8.16 (s, 1H),
11.65 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ 36.8,
116.2, 128.0, 128.5, 129.0, 129.5, 130.1, 130.8, 131.3,
134.3, 143.4, 150.4, 168.5, 171.8; Anal. Calcd for:
C18H15N3OS, C, 67.27; H, 4.70; N, 13.07, found: C,
67.20; H, 4.72; N, 12.98; LCMS: 322.1 (M+ H)+.
1602, 1556, 1525, 1437, 1367, 1230, 1186, 1068, 1006,
819, 767 cm–1; 1H NMR (300MHz, CDCl3): δ 2.97(s,
6H), 4.14 (s, 2H), 6.62 (d, J= 8.8 Hz, 2H), 7.20 (s, 1H),
7.38–7.55 (m, 4H), 7.59 (s, 1H), 7.90–7.94 (m, 4H),
10.22 (s, 1H); 13C NMR (75 MHz, CDCl3): δ 35.7, 40.2,
114.6, 116.1, 126.5, 128.5, 129.0, 129.6, 130.3, 133.6,
145.0, 150.9, 151.4, 167.4, 172.1; Anal. Calcd for:
C20H20N4OS C, 65.91; H, 5.53; N, 15.37, found: C,
65.85; H, 5.47; N, 15.28; LCMS: 365.15 (M + H)+.
N′-Benzylidene-2-(2-(3-chlorophenyl)thiazol-4-yl)acetohyd-
razide, 4g. IR: 3252, 3110, 2899, 2817, 1662, 1600, 1560,
1520, 1439, 1361, 1239, 1180, 1069, 1004, 880, 811,
770 cm–1; 1H NMR (400MHz, DMSO-d6): δ 4.13 (s, 2H),
7.43–7.76 (m, 7H), 7.85–7.93 (m, 2H), 8.11 (s, 1H);
11.72 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ 36.6,
116.4, 127.0, 127.8, 129.1, 129.5, 130.6, 130.8, 131.5,
131.9, 132.3, 134.9 141.9, 150.5, 167.9; 172.6; Anal. Calcd
for: C18H14ClN3OS C, 60.76; H, 3.97; N, 11.81, found: C,
60.65; H, 3.96; N, 11.77; LCMS: 356.06 (M + H)+.
N′-(4-Chlorobenzylidene)-2-(2-phenylthiazol-4-yl)acetohydra-
zide, 4b. IR: 3258, 3110, 2899, 2817, 1662, 1600, 1560,
1520, 1439, 1361, 1239, 1180, 1069, 1004, 811, 770cm–
1; H NMR (400 MHz, DMSO-d6): δ 4.02 (s, 2H), 7.21–
1
7.60 (m, 6H), 7.68–7.78 (m, 2H), 7.59 (s, 1H), 7.90–7.94
(m, 2H), 8.16 (s, 1H), 11.65 (s, 1H); 13C NMR (75 MHz,
CDCl3): δ 36.8, 116.2, 128.0, 128.8, 129.2, 129.6, 130.5,
131.8, 133.6, 137.5, 143.4, 150.9, 168.7, 172.0; Anal.
Calcd for: C18H14ClN3OS C, 60.76; H, 3.97; N, 11.81,
found: C, 60.68; H, 4.00; N, 11.72; LCMS: 356.06 (M
+ H)+.
N′-(2-Fluorobenzylidene)-2-(2-phenylthiazol-4-yl)acetohyd-
razide, 4c. IR: 3238,3120, 3080, 2960, 2889, 2822, 1680,
1601, 1565, 1441, 1402, 1349, 1261, 1137, 1097, 1005,
N′-(4-Chlorobenzylidene)-2-(2-(3-chlorophenyl)thiazol-4-yl)
acetohydrazide, 4h. IR: 3290, 3157, 2922, 1668, 1628,
1587, 1543, 1454, 1396, 1317, 1192, 1116, 1049, 993,
912, 879cm–1; 1H NMR (400MHz, DMSO-d6): δ 4.13 (s,
2H), 7.43–7.60 (m, 5H), 7.68–7.76 (m, 2H), 7.85–7.93
(m, 2H), 8.11 (s, 1H); 11.72 (s, 1H); 13C NMR (100MHz,
DMSO-d6): δ 36.7, 116.5, 126.4, 127.9, 129.1, 129.2,
130.6, 130.8, 132.3, 134.8, 134.9, 137.2, 141.9, 150.5,
167.9; 172.6; Anal. Calcd for: C18H13Cl2N3OS C, 55.39;
H, 3.36; N, 10.77, found: C, 55.33; H, 3.38; N, 10.80;
LCMS: 390.03 (M + H)+.
1
949, 790, 731 cm–1; H NMR (400 MHz, DMSO-d6): δ
4.00 (s, 2H), 7.23–7.30 (m, 2H), 7.47–7.55 (m, 5H),
7.86–7.95 (m, 3H), 8.25 (s, 1H), 11.68 (s, 1H); 13C NMR
(100 MHz, DMSO-d6): δ 36.5, 116.4, 116.9, 118.0, 125.9,
127.7, 128.9, 130.4, 131.4, 133.1, 134.0, 141.8, 152.1,
162.8, 168.9, 173.3; Anal. Calcd for: C18H14FN3OS C,
63.70; H, 4.16; N, 12.38, found: C, 63.61; H, 4.12; N,
12.30; LCMS: 340.1 (M + H)+.
N′-(3-Fluorobenzylidene)-2-(2-phenylthiazol-4-yl)acetohyd-
razide, 4d. IR: 3178, 3080, 2974, 2899, 1666, 1604, 1577,
1492, 1427, 1386, 1352, 1327, 1275, 1139, 1001, 941, 893,
N′-(2-Fluorobenzylidene)-2-(2-(3-chlorophenyl)thiazol-4-yl)
acetohydrazide, 4i.
IR: 3182, 3078, 2968, 2890, 1682,
1600, 1562, 1457, 1358, 1293, 1259, 1133, 1080, 1006,
956, 877, 760 cm–1; 1H NMR (400MHz, DMSO-d6) δ
4.15 (s, 2H), 7.22–7.27 (m, 2H), 7.32–7.43 (m, 4H),
7.83–7.96 (m, 3H), 8.33 (s, 1H); 11.71 (s, 1H); 13C NMR
(100 MHz, DMSO-d6): δ 37.0, 116.1, 116.5, 118.8, 124.9,
126.9, 127.8, 129.1, 130.5, 130.9, 132.9, 134.6, 134.9,
142.2, 150.5, 164.0, 166.9, 172.9; Anal. Calcd for:
C18H13ClFN3OS C, 57.83; H, 3.51; N, 11.24, found: C,
57.77; H, 3.48; N, 11.27; LCMS: 374.06 (M + H)+.
1
786, 761, 684 cm–1; H NMR (400 MHz, DMSO-d6): δ
4.01 (s, 2H), 7.21–7.28 (m, 1H), 7.43–7.54 (m, 7H),
7.90–7.93 (m, 2H), 8.16 (s, 1H), 11.65 (s, 1H); 13C NMR
(100 MHz, DMSO-d6): δ 36.2, 114.6, 116.4, 116.9, 124.7,
128.0, 129.1, 129.6, 130.8, 133.1, 133.9, 142.5, 151.2,
165.3 166.1, 172.2; Anal. Calcd for: C18H14FN3OS C,
63.70; H, 4.16; N, 12.38, found: C, 63.64; H, 4.10; N,
12.31; LCMS: 340.1 (M + H)+.
N′-(4-Fluorobenzylidene)-2-(2-phenylthiazol-4-yl)acetohyd-
razide, 4e. IR: 3182, 3117, 3080, 2966, 2895, 1672, 1606,
1500, 1421, 1388, 1350, 1321, 1232, 1143, 1001, 923, 868,
N′-(3-Fluorobenzylidene)-2-(2-(3-chlorophenyl)thiazol-4-yl)
acetohydrazide, 4j.
IR: 3190, 3099, 2980, 2902, 1685,
1602, 1575, 1516, 1462, 1410, 1307, 1257, 1207, 1138,
1008, 943, 871, 779, 684cm–1; 1H NMR (300MHz,
CDCl3): δ 4.16 (s, 2H), 7.08–7.12 (m, 1H), 7.28–7.50 (m,
6H), 7.79–7.84 (m, 2H), 7.97 (s, 1H), 10.11 (s, 1H);13C
NMR (75 MHz, CDCl3): δ 36.9, 114.3, 116.5, 118.0,
125.1, 127.2, 127.7, 129.3, 130.9, 133.8, 134.1, 137.7,
142.0, 152.3, 162.9, 168.5, 173.2; Anal. Calcd for:
C18H13ClFN3OS C, 57.83; H, 3.51; N, 11.24, found: C,
57.75; H, 3.49; N, 11.23; LCMS: 374.06 (M + H)+.
1
802, 769, 688 cm–1; H NMR (400 MHz, DMSO-d6): δ
3.98 (s, 2H), 7.23–7.31 (m, 2H), 7.41–7.53 (m, 4H),
7.74–7.77 (m, 2H), 7.90–7.93 (m, 2H), 8.15 (s, 1H),
11.56 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ 36.9,
115.9, 116.4, 128.8, 129.2, 129.6, 130.5, 130.9, 131.8,
142.4, 150.4, 164.2, 168.1, 171.9; Anal. Calcd for:
C18H14FN3OS C, 63.70; H, 4.16; N, 12.38, found: C,
63.62; H, 4.12; N, 12.32; LCMS: 340.1 (M+ H)+.
N′-(4-(Dimethylamino)benzylidene)-2-(2-phenylthiazol-4-yl)
N′-(4-Fluorobenzylidene)-2-(2-(3-chlorophenyl)thiazol-4-yl)
acetohydrazide, 4k. IR: 3182, 3089, 2978, 2899, 1682,
acetohydrazide, 4f.
IR: 3242, 3080, 2893, 2808, 1666,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Synthesis and Antimicrobial Screening of 2-Aryl-5-((2-arylthiazol-4-yl)methyl)-
1,3,4-oxadiazole Derivatives
1602, 1561, 1467, 1414, 1307, 1261, 1199, 1139, 1006,
N′-(3-Fluorobenzylidene)-2-(2-(4-chlorophenyl)thiazol-4-yl)
acetohydrazide, 4p. IR: 3188, 3074, 2962, 2902, 2860,
1676, 1604, 1577, 1255, 1448, 1402, 1352, 1259, 1141,
1097, 1004, 949, 790, 731cm–1; 1H NMR (400MHz,
DMSO-d6): δ 4.00 (s, 2H), 7.20–7.27 (m, 1H), 7.22–7.58
(m, 6H), 7.90 (d, J= 8.2 Hz, 2H), 8.12 (s, 1H); 11.64 (s,
1H); 13C NMR (100MHz, DMSO-d6): δ 36.9, 115.5,
116.5, 118.1, 125.2, 129.1, 129.6, 130.8, 132.2, 134.5,
136.5, 142.6, 149.9, 163.8, 168.2, 172.5; Anal. Calcd for:
C18H13ClFN3OS C, 57.83; H, 3.51; N, 11.24, found: C,
57.84; H, 3.45; N, 11.20; LCMS: 374.06 (M + H)+.
N′-(4-Fluorobenzylidene)-2-(2-(4-chlorophenyl)thiazol-4-yl)
acetohydrazide, 4q. IR: 3185, 3120, 3078, 2960, 2851,
1682, 1603, 1552, 1438, 1358, 1318, 1227, 1139, 1004,
923, 863, 793, 761, 668cm–1; 1H NMR (300MHz, CDCl3):
δ 4.15 (s, 2H), 7.08 (dd, J =17.2 and 8.4 Hz, 2H), 7.39 (d,
J = 8.4 Hz, 2H), 7.7.66 (dd, J = 8.5 and 5.5 Hz, 2H), 7.73
(s, 1H), 7.88 (d, J = 8.4 Hz, 2H), 8.07 (s, 1H), 10.35 (s,
1H); 13C NMR (75 MHz, CDCl3): δ 36.8, 115.9, 116.4,
128.9, 129.4, 129.7, 130.8, 131.7, 133.9, 142.6, 149.2,
164.2, 167.8, 171.8; Anal. Calcd for: C18H13ClFN3OS C,
57.83; H, 3.51; N, 11.24, found: C, 57.75; H, 3.48; N,
11.20; LCMS: 374.06 (M +H)+.
1
956, 877, 777, 685cm–1; H NMR (300 MHz, CDCl3): δ
4.15 (s, 2H), 7.01–7.09 (m, 2H), 7.27–7.43 (m, 2H),
7.61–7.70 (m, 2H), 7.72–7.82 (m, 2H), 8.02 (s, 1H),
10.27 (s, 1H); 13C NMR (75 MHz, CDCl3): δ 36.6, 116.5,
116.8, 127.5, 127.9, 128.5, 129.8, 130.8, 131.0, 133.2,
134.4, 141.8, 152.1, 164.2, 168.9, 173.3; Anal. Calcd for:
C18H13ClFN3OS C, 57.83; H, 3.51; N, 11.24, found: C,
57.80; H, 3.48; N, 11.24; LCMS: 374.06 (M + H)+.
N′-(4-(Dimethylamino)benzylidene)-2-(2-(3-chlorophenyl)thi-
azol-4-yl)acetohydrazide, 4l. IR: 3248, 3155, 2919, 1660,
1622, 1581, 1549, 1450, 1391, 1317, 1190, 1109, 1045,
1
989, 910, 876 cm–1; H NMR (400 MHz, DMSO-d6): δ
2.96 (s, 6H), 3.98 (s, 2H), 6.70 (d, J= 8.4 Hz, 2H), 7.42–
7.60 (m, 5H), 7.82 (d, J = 8.4 Hz, 2H), 7.98 (s, 1H); 11.30
(s, 1H); 13C NMR (100 MHz, DMSO-d6): δ 36.2, 40.2,
115.2, 116.5, 124.2, 126.3, 127.8, 129.1, 130.3, 130.7,
134.5, 134.8, 142.2, 150.0, 151.7, 168.0 172.5; Anal. Calcd
for: C20H19ClN4OS C, 60.22; H, 4.80; N, 14.05, found: C,
60.15; H, 4.76; N, 14.08; LCMS: 399.11 (M + H)+.
N′-Benzylidene-2-(2-(4-chlorophenyl)thiazol-4-yl)acetohyd-
razide, 4m.
IR: 3239, 3109, 2908, 2821, 1668, 1602,
1565, 1517, 1441, 1360, 1240, 1171, 1058, 1004, 819,
770, 722 cm–1; 1H NMR (400 MHz, DMSO-d6): δ 4.00 (s,
2H), 7.28 (d, J = 8.4 Hz, 2H), 7.32–7.62 (m, 6H), 7.78 (d,
J =8.4 Hz, 2H), 8.16 (s, 1H), 11.58 (s, 1H); 13C NMR
(100 MHz, DMSO-d6): δ 36.9, 116.4, 128.8, 129.2, 129.6,
129.9, 130.5, 131.8, 131.8, 132.0, 135.4, 142.5, 150.4,
168.5, 172.1; Anal. Calcd for: C18H14ClN3OS C, 60.76;
H, 3.97; N, 11.81, found: C, 60.68; H, 4.00; N, 11.72;
LCMS: 356.06 (M +H)+.
N′-(4-(Dimethylamino)benzylidene)-2-(2-(4-chlorophenyl)thi-
azol-4-yl)acetohydrazide, 4r. IR: 3196, 3072, 3053, 2887,
1661, 1608, 1558, 1521, 1491, 1446, 1400, 1356, 1220,
1
1180, 1082, 1008, 949, 827cm–1; H NMR (400MHz,
DMSO-d6): δ 2.96 (s, 6H), 3.93 (s, 2H), 6.74 (d,
J = 8.6 Hz, 2H), 7.42–7.60 (m, 5H), 7.92 (d, J =8.6Hz,
2H), 7.96 (s, 1H); 11.30 (s, 1H); 13C NMR (100MHz,
DMSO-d6): δ 36.5, 40.2, 115.2, 116.4, 124.2, 129.1,
129.7, 130.2, 131.9, 134.7, 141.9, 149.9, 151.7, 167.9,
172.7; Anal. Calcd for: C20H19ClN4OS C, 60.22; H, 4.80;
N, 14.05, found: C, 60.16; H, 4.84; N, 13.98; LCMS:
399.11 (M + H)+.
N′-(4-Chlorobenzylidene)-2-(2-(4-chlorophenyl)thiazol-4-yl)
acetohydrazide, 4n. IR: 3239, 3109, 2908, 2821, 1668,
1602, 1565, 1517, 1441, 1360, 1239, 1176, 1065, 1002,
1
819, 770, 722 cm–1; H NMR (400 MHz, DMSO-d6): δ
3.99 (s, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.38 (d, J= 8.4 Hz,
2H), 7.50 (s, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.78 (d,
J =8.4 Hz, 2H), 8.16 (s, 1H), 11.58 (s, 1H); 13C NMR
(100 MHz, DMSO-d6): δ 36.9, 116.4, 128.8, 129.2, 129.6,
129.9, 130.5, 131.8, 132.0, 134.4, 137.0, 142.8, 150.5,
168.6, 172.2; Anal. Calcd for: C18H13Cl2N3OS C, 55.39;
H, 3.36; N, 10.77, found: C, 55.33; H, 3.38; N, 10.80;
LCMS: 390.03 (M +H)+.
General procedure for synthesis of compounds 5a–i.
Iodobenzene diacetate (0.0066mol) and N′-substituted
benzylidene-2-(2-phenylthiazol-4-yl)acetohydrazide 4a–r
(0.006 mol) was mixed in mortar and pestle and
transferred in round bottom flask. The reaction mixture
was heated on water bath for 2–3min to initiate the
reaction. After completion of the reaction, cold water was
added, and the product was extracted with ethyl acetate.
The organic layer was washed with sodium bicarbonate
and water and dried over anhydrous sodium sulfate. The
solvent was removed under reduced pressure, and the
product was purified by column chromatography using
ethyl acetate :hexane (2:8) as eluent to furnish the target
compound 2-(substituted phenyl)-5-((2-phenylthiazol-4-
yl)methyl)-1,3,4-oxadiazole, 5a–i.
N′-(2-Fluorobenzylidene)-2-(2-(4-chlorophenyl)thiazol-4-yl)
acetohydrazide, 4o. IR: 3189, 3079, 2970, 2889, 1684,
1602, 1560, 1455, 1365, 1286, 1261, 1128, 1086, 1004,
1
959, 869, 765 cm–1; H NMR (300 MHz, CDCl3): δ 4.15
(s, 2H), 7.02–7.47 (m, 6H), 7.87 (d, J= 8.1 Hz, 2H), 8.40
(s, 1H); 10.11 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ
36.9, 116.1, 116.5, 118.5, 124.8, 129.0, 129.6, 131.1,
131.9, 132.6, 134.5, 142.0, 150.3, 160.9, 168.5, 172.5;
Anal. Calcd for: C18H13ClFN3OS C, 57.83; H, 3.51; N,
11.24, found: C, 57.80; H, 3.50; N, 11.26; LCMS: 374.06
(M + H)+.
2-Phenyl-5-((2-phenylthiazol-4-yl)methyl)-1,3,4-oxadiazole,
5a. IR: 2930 2819, 1609, 1510, 1449, 1440, 1363, 1234,
1174, 1004, 827, cm–1; 1H NMR (300 MHz, CDCl3): δ 4.54
(s, 2H), 7.23 (s, 1H), 7.41–7.55 (m, 6H), 7.90–8.00 (m,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

P. C. Mhaske, S. H. Shelke, M. Bhoye, and V. D. Bobade
Vol 000
4H); 13C NMR (75 MHz, CDCl3): δ 28.3, 116.3, 127.8,
128.2, 128.9, 129.2, 129.8, 130.2, 130.8, 133.0, 149.8,
163.3, 166.4, 168.9; Anal. Calcd for: C18H13N3OS C,
67.69; H, 4.10; N, 13.16, found: C, 67.62; H, 4.12; N,
13.10; LCMS: 320.08 (M + H)+.
C20H18N4OS C, 66.28; H, 5.01; N, 15.46, found: C,
66.20; H, 4.96; N, 15.50; LCMS: 363.13 (M + H)+.
2-((2-(3-Chlorophenyl)thiazol-4-yl)methyl)-5-phenyl-1,3,4-ox-
adiazole, 5g. IR: 3008, 2940, 1560, 1493, 1466, 1359,
1
1303, 1249, 1178, 1004, 976, 878, 768cm–1; H NMR
2-(4-Chlorophenyl)-5-((2-phenylthiazol-4-yl)methyl)-1,3,4-
oxadiazole, 5b. IR: 2926, 2812, 1612, 1512, 1456, 1440,
(300 MHz, CDCl3): δ 4.54 (s, 2H), 7.29 (s, 1H), 7.34–
7.43 (m, 3H), 7.48 (d, J = 8.6 Hz, 2H), 7.52–7.55 (m, 1H),
7.70–7.80 (m, 1H), 7.99 (d, J = 8.6 Hz, 2H); 13C NMR
(75 MHz, CDCl3): δ 28.2, 116.5, 125.7, 126.3, 127.9,
128.7, 129.4, 129.7, 130.5, 130.8, 133.8, 134.8, 149.6,
164.2, 166.7, 168.0; Anal. Calcd for: C18H12ClN3OS C,
61.10; H, 3.42; N, 11.88, found: C, 61.00; H, 3.44; N,
11.88; LCMS: 354.03 (M +H)+.
1
1363, 1234, 1178, 1001, 950, 827, 765cm–1; H NMR
(300 MHz, CDCl3): δ 4.54(s, 2H), 7.23 (s, 1H), 7.41-7.55
(m, 5H), 7.90–8.00 (m, 4H); 13C NMR (75 MHz, CDCl3):
δ 28.2, 116.4, 127.5, 128.1, 128.9, 129.3, 129.8, 130.2,
133.0, 134.5, 149.8, 163.3, 166.4, 168.9; Anal. Calcd for:
C18H12ClN3OS C, 61.10; H, 3.42; N, 11.88, found: C,
61.02; H, 3.45; N, 11.90; LCMS: 354.03 (M + H)+.
2-(4-Chlorophenyl)-5-((2-(3-chlorophenyl)thiazol-4-yl)met-
2-(2-Fluorophenyl)-5-((2-phenylthiazol-4-yl)methyl)-1,3,4-
oxadiazole, 5c. IR: 3090, 3028, 2920, 1601, 1575, 1521,
1492, 1430, 1408, 1265, 1209, 1169, 1086, 1004, 984,
hyl)-1,3,4-oxadiazole, 5h.
IR: 2992, 2910, 1564, 1480,
1457, 1360, 1312, 1260, 1189, 1004, 976, 877, 767cm–1;
1H NMR (300MHz, CDCl3): δ 4.54 (s, 2H), 7.29 (s, 1H),
7.34–7.43 (m, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.52–7.55 (m,
1H), 7.70–7.80 (m, 1H), 7.99 (d, J = 8.6 Hz, 2H); 13C
NMR (75 MHz, CDCl3): δ 28.2, 116.5, 125.7, 126.3,
127.9, 128.7, 129.4, 129.7, 130.8, 133.8, 134.4, 134.8,
149.6, 164.2, 166.7, 168.0; Anal. Calcd for:
C18H11Cl2N3OS C, 55.68; H, 2.86; N, 10.82, found: C,
55.60; H, 2.82; N, 10.86; LCMS: 388.01 (M + H)+.
1
940, 874cm–1; H NMR (300 MHz, CDCl3): δ 4.53 (s,
2H), 7.12–7.36 (m, 5H), 7.48 (s, 1H), 7.76–7.98 (m, 4H),
13C NMR (75 MHz, CDCl3): δ 28.0, 116.5, 116.8, 125.3,
126.0, 127.6, 129.0, 129.2, 129.6, 130.8, 133.7, 149.5,
161.8, 164.1, 165.3, 168.1; Anal. Calcd for: C18H12FN3OS
C, 64.08; H, 3.59; N, 12.46, found: C, 64.02; H, 3.62; N,
12.40; LCMS: 338.06 (M + H)+.
2-(3-Fluorophenyl)-5-((2-phenylthiazol-4-yl)methyl)-1,3,4-
2-((2-(3-Chlorophenyl)thiazol-4-yl)methyl)-5-(2-fluorophenyl)-
1,3,4-oxadiazole, 5i. IR: 3080, 2929, 1564, 1489, 1458,
1363, 1310, 1269, 1196, 1080, 1004, 987, 871, 765cm–1;
1H NMR (300MHz, CDCl3): δ 4.56 (s, 2H), 7.21–7.41
(m, 3H), 7.49–7.56 (m, 2H), 7.69–7.73 (m, 1H), 7.79 (d,
J = 6.4 Hz, 1H), 7.96 (s, 1H), 8.05 (m, 1H); 13C NMR
(75 MHz, CDCl3): δ 28.2, 116.8, 117.1, 124.6, 126.4,
128.7, 129.7, 130.1, 130.2, 130.8, 133.4, 133.6, 134.8,
149.5, 161.6, 164.2, 166.8, 167.7; Anal. Calcd for:
C18H11ClFN3OS C, 58.15; H, 2.98; N, 11.30, found: C,
58.10; H, 3.00; N, 11.24; LCMS: 372.03 (M + H)+.
oxadiazole, 5d. IR: 3082, 2924, 1564, 1487, 1460, 1367,
1
1305, 1261, 1193, 1070, 1006, 976, 877, 767cm–1; H
NMR (300 MHz, CDCl3): δ 4.54(s, 2H), 7.19–7.24 (m,
2H), 7.43–7.48 (m, 5H), 7.75 (d, J= 9 Hz, 1H), 7.84 (d,
J =7.5 Hz, 1H), 7.93–7.95 (m, 2H); 13C NMR (75 MHz,
CDCl3): δ 28.3, 114.1, 116.2, 118.7, 122.7, 126.5, 128.4,
129.0, 130.3, 130.9, 133.2, 149.2, 164.1, 164.3, 165.8,
168.7; Anal. Calcd for: C18H12FN3OS C, 64.08; H, 3.59;
N, 12.46, found: C, 64.05; H, 3.55; N, 12.42; LCMS:
338.04 (M + H)+.
2-(4-Fluorophenyl)-5-((2-phenylthiazol-4-yl)methyl)-1,3,4-
oxadiazole, 5e. IR: 3119, 3063, 2899, 1606, 1581, 1518,
1498, 1413, 1332, 1294, 1230, 1182, 1159, 1091, 1006,
2-((2-(3-Chlorophenyl)thiazol-4-yl)methyl)-5-(3-fluorophenyl)-
1,3,4-oxadiazole, 5j. IR: 3070, 2922, 2854, 1595, 1566,
1527, 1456, 1413, 1301, 1273, 1228, 1197, 1082, 1008,
1
1
970, 935, 846, 775, 767, 691cm–1; H NMR (300MHz,
981, 869, 802, 767, 732, 680cm–1; H NMR (300MHz,
CDCl3): δ 4.53 (s, 2H), 7.14 (t, J = 8.2 Hz, 2H), 7.23 (s,
1H), 7.42–7.44 (m, 3H), 7.92-8.04 (m, 4H); 13C NMR
(75 MHz, CDCl3): δ 28.2, 116.2, 116.4, 120.1, 126.5,
128.9, 129.1, 130.2, 133.2, 149.3, 164.0, 164.4, 164.7,
168.6; Anal. Calcd for: C18H12FN3OS C, 64.08; H, 3.59;
N, 12.46, found: C, 64.00; H, 3.56; N, 12.50; LCMS:
338.04 (M + H)+.
CDCl3): δ 4.52 (s, 2H), 7.10–7.86 (m, 9H); 13C NMR
(75 MHz, CDCl3): δ 28.3, 116.2, 116.5, 116.8, 123.4,
126.6, 127.8, 128.3, 128.9, 130.9, 131.2, 134.8, 134.9,
149.8, 163.9, 164.5, 166.4, 166.9; Anal. Calcd for:
C18H11ClFN3OS C, 58.15; H, 2.98; N, 11.30, found: C,
58.10; H, 3.02; N, 11.27; LCMS: 372.03 (M + H)+.
2-((2-(3-Chlorophenyl)thiazol-4-yl)methyl)-5-(4-fluorophenyl)-
N,N-Dimethyl-4-(5-((2-phenylthiazol-4-yl)methyl)-1,3,4-oxadi-
azol-2-yl)benzene-amine, 5f. IR: 2926, 2812, 1612, 1512,
1456, 1440, 1363, 1234, 1178, 1001, 950, 827, 765cm–1;
1H NMR (300 MHz, CDCl3): δ 3.05 (s, 6H), 4.51 (s, 2H),
6.80 (d, J = 8.4Hz, 2H), 7.21 (s, 1H), 7.42–7.46 (m, 4H),
7.90–7.96 (m, 2H); 13C NMR (75 MHz, CDCl3): δ 28.3,
40.2, 116.1, 116.5, 118.3, 127.6, 128.9, 129.1, 129.8,
133.5, 149.0, 150.5, 164.4, 166.4, 168.6; Anal. Calcd for:
1,3,4-oxadiazole, 5k.
IR: 078, 2930, 1560, 1492, 1465,
1419, 1365, 1301, 12551, 1187, 1080, 1004, 965, 920,
1
870, 765cm–1; H NMR (300MHz, CDCl3): δ 4.53 (s,
2H), 7.18 (t, J = 8.6 Hz, 2H), 7.28 (s, 1H), 7.32–7.40 (m,
2H), 7.78 (d, J= 6.7 Hz, 1H), 7.95 (s, 1H), 8.05 (m, 2H);
13C NMR (75 MHz, CDCl3): δ 28.2, 116.4, 116.5, 124.6,
126.4, 129.1, 129.2, 130.1, 130.2, 134.8, 149.5, 163.9,
164.4, 166.4, 164.7, 166.9; Anal. Calcd for:
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Synthesis and Antimicrobial Screening of 2-Aryl-5-((2-arylthiazol-4-yl)methyl)-
1,3,4-oxadiazole Derivatives
C18H11ClFN3OS C, 58.15; H, 2.98; N, 11.30, found: C,
58.12; H, 3.00; N, 11.24; LCMS: 372.03 (M + H)+.
126.9, 128.2, 130.4, 130.9, 135.3, 148.5, 163.4, 164.2,
167.9; Anal. Calcd for: C18H11ClFN3OS C, 58.15; H,
2.98; N, 11.30, found: C, 58.11; H, 2.94; N, 11.28; LCMS:
371.03 (M + H)+.
4-(5-((2-(3-Chlorophenyl)thiazol-4-yl)methyl)-1,3,4-oxadiazol-
2-yl)-N,N-dimethyl-benzenamine, 5l. IR: 2930, 2812, 1612,
1512, 1456, 1440, 1367, 1234, 1180, 1130, 1001, 950,
2-((2-(4-Chlorophenyl)thiazol-4-yl)methyl)-5-(4-fluorophenyl)-
1,3,4-oxadiazole, 5q. IR: 3066, 2924, 1578, 1490, 1465,
1419, 1365, 1301, 12551, 1187, 1080, 1004, 965, 920,
1
827, 765, 692 cm–1; H NMR (300 MHz, CDCl3): δ 3.04
(s, 6H), 4.50 (s, 2H), 6.72 (d, J = 9Hz, 2H), 7.12 (dd, J= 8
and 2 Hz, 2H, 1H), 7.37 (s, 1H), 7.79–7.81 (m, 1H), 7.89
(d, J= 9 Hz, 2H), 7.96 (s, 1H); 13C NMR (75 MHz, CDCl3):
δ 28.3, 40.2, 116.0, 116.5, 117.4, 126.2, 127.6, 128.5,
129.0, 130.8, 133.7, 134.9, 149.1, 150.3, 164.4, 166.5,
168.7; Anal. Calcd for: C20H17ClN4OS C, 60.52; H, 4.32;
N, 14.12, found: C, 60.47; H, 4.25; N, 14.11; LCMS:
397.07 (M + H)+.
1
870, 765cm–1; H NMR (300MHz, CDCl3): δ 4.52 (s,
2H), 7.18 (t, J= 8.6 Hz, 2H), 7.26 (s, 1H), 7.40 (d,
J = 8.6 Hz, 2H), 7.86 (d, J = 8.6 Hz, 2H), 8.04 (dd, J= 8.6
and 2 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 28.1,
116.2, 116.5, 127.7, 129.0, 129.1, 129.2, 131.6, 136.2,
149.4, 163.2, 163.9, 164.4, 167.3; Anal. Calcd for:
C18H11ClFN3OS C, 58.15; H, 2.98; N, 11.30, found: C,
58.08; H, 2.95; N, 11.32; LCMS: 371.03 (M + H)+.
2-((2-(4-Chlorophenyl)thiazol-4-yl)methyl)-5-phenyl-1,3,4-ox-
adiazole, 5m. IR: 2930, 1561, 1492, 1456, 1359, 1301,
4-(5-((2-(4-Chlorophenyl)thiazol-4-yl)methyl)-1,3,4-oxadiazol-
2-yl)-N,N-dimethyl-benzenamine, 5r. IR: 3080, 2920, 1571,
1480, 1435, 1356, 1306, 1258, 1187, 1066, 1001, 976,
1
1256, 1189, 1067, 1004, 976, 877, 767cm–1; H NMR
(300 MHz, CDCl3): δ 4.52 (s, 2H), 7.25 (s, 1H), 7.39 (d,
J =8.6 Hz, 2H), 7.46–7.86 (m, 5H), 7.97 (d, J= 8.6 Hz,
2H), 13C NMR (75 MHz, CDCl3): δ 28.0, 116.4, 127.6,
127.9, 129.0, 129.2, 130.7, 130.9, 131.5, 136.1, 149.3,
163.9, 164.3, 167.6; Anal. Calcd for: C18H12ClN3OS C,
61.10; H, 3.42; N, 11.88, found: C, 61.00; H, 3.44; N,
11.90; LCMS: 354.06 (M + H)+.
1
873, 760cm–1; H NMR (300MHz, CDCl3): δ 3.04 (s,
6H), 4.49 (s, 2H), 6.72 (d, J = 9Hz, 2H), 7.22 (s, 2H, 1H),
7.40 (d, J = 8.1 Hz, 2H), 7.46–7.90 (m, 4H); 13C NMR
(75 MHz, CDCl3): δ 28.3, 40.2, 116.1, 116.5, 117.4,
128.6, 129.0, 129.7, 131.8, 134.5, 149.1, 150.2, 164.4,
166.5, 168.6; Anal. Calcd for: C20H17ClN4OS C, 60.52;
H, 4.32; N, 14.12, found: C, 60.45; H, 4.28; N, 14.15;
LCMS: 397.09 (M + H)+.
2-(4-Chlorophenyl)-5-((2-(4-chlorophenyl)thiazol-4-yl)met-
hyl)-1,3,4-oxadiazole, 5n.
IR: 2922, 1587, 1547, 1454,
1395, 1314, 1256, 1192, 1116, 1049, 993, 921, 879,
Antimicrobial activity. All the synthesized compounds
4a–r and 5a–r were screened for their in vitro
antimicrobial activity against B. subtilis and Salmonella
typhi bacterial strains by the disk diffusion method [51–
53]. Disks measuring 6 mm in diameter were punched
from Whatman no. 1 filter paper (HiMedia Laboratories
Pvt. Ltd., Mumbai, Maharashtra, India). Batches of 100
disks were dispensed to each screw-caped bottle and
sterilized by dry heat at 145°C for an hour. The test
compounds were prepared with 100-μg/mL concentration
in DMSO. Disks of each concentration were placed in
nutrient agar medium inoculated with fresh bacteria
strains separately. The incubation is carried out at 37°C
for 48h. Ciprofloxacin was used as standard drugs at a
concentration of 10 μg/mL. Solvent and growth controls
were kept, and zones of inhibition were noted.
The newly synthesized compounds were screened for their
antifungal activity A. niger (All India Institute of Medical Sci-
ences (AIIMS)) in DMSO by disk diffusion method under
standard conditions using Mueiier-Hinton agar medium as
described by National Committee for Clinical Laboratory
Standards (NCCLS) [54]. Sterile filter paper disks (6mm in
diameter) containing specific amount of antifungal agent
(100μg for the synthesized compounds) were placed on the
surface of an agar plate inoculated with the standardized sus-
pension of microorganisms tested. The plates were incubated
at 37°C for 7days for evaluating antifungal activity. The di-
ameters of inhibition zones (mm) were measured.
1
773cm–1; H NMR (300 MHz, CDCl3): δ 4.52 (s, 2H),
7.25 (s, 1H), 7.39 (d, J = 8.6 Hz, 2H), 7.46 (d, J= 8.6 Hz,
2H), 7.86 (d, J= 8.6 Hz, 2H), 7.97 (d, J = 8.6 Hz, 2H), 13C
NMR (75 MHz, CDCl3): δ 28.0, 116.4, 127.6, 127.9,
129.0, 129.2, 130.7, 131.5, 136.1, 137.8, 149.3, 163.9,
164.3, 167.6; Anal. Calcd for: C18H11Cl2N3OS C, 55.68;
H, 2.86; N, 10.82, found: C, 55.62; H, 2.80; N, 10.84;
LCMS: 387.01 (M +H)+.
2-((2-(4-Chlorophenyl)thiazol-4-yl)methyl)-5-(2-fluorophenyl)-
1,3,4-oxadiazole, 5o. IR: 3042, 2924, 2850, 1580, 1540,
1492, 1458, 1408, 1271, 1209, 1176, 1089, 1008, 979,
937, 875, 852, 786, 729cm–1; 1H NMR (300 MHz, CDCl3):
δ 4.53 (s, 2H), 7.15–7.26 (m, 3H), 7.34 (d, J = 8.6 Hz, 2H),
7.43–7.51 (m, 1H), 7.81 (d, J = 8.6 Hz, 1H), 7.97–8.02 (m,
1H); 13C NMR (75 MHz, CDCl3): δ 28.0, 116.5, 116.8,
118.0, 124.5, 127.6, 129.6, 131.5, 131.6, 136.0, 149.3,
149.5, 160.0, 161.8, 164.1, 167.1; Anal. Calcd for:
C18H11ClFN3OS C, 58.15; H, 2.98; N, 11.30, found: C,
58.08; H, 3.02; N, 11.20; LCMS: 371.03 (M + H)+.
2-((2-(4-Chlorophenyl)thiazol-4-yl)methyl)-5-(3-fluorophenyl)-
1,3,4-oxadiazole, 5p. IR: 3138, 3061, 2924, 2854, 1575,
1557, 1492, 1458, 1408, 1271, 1209, 1176, 1089, 1008,
1
979, 937, 875 cm–1; H NMR (300 MHz, CDCl3): δ 4.53
(s, 2H), 7.30 (m, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.50 (s,
1H), 7.51–7.62 (m, 1H), 7.71–7.84 (m, 1H), 7.83 (d,
J =8.6 Hz, 1H), 7.89 (d, J =8.4 Hz, 2H); 13C NMR
(75 MHz, CDCl3): δ 26.7, 116.6, 117.9, 118.1, 121.8,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

P. C. Mhaske, S. H. Shelke, M. Bhoye, and V. D. Bobade
Vol 000
[21] Rudolph, J.; Chen, L.; Majumdar, D.; Bullock, W. H.; Burns, M.;
Claus, T.; Dela Cruz, F. E.; Daly, M.; Ehrgott, F. J.; Johnson, J. S.;
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Ma, X. J Med Chem 2007, 50, 984.
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Brewster, A. G.; Donche, F.; Forest, M.; Fouchet, M.; Gellibert, F. J.;
Grillot, D. A.; Lambert, M. H.; Laroze, A.; Grumelec, C. L.; Linget, J. M.;
Montana, V. G.; Nguyen, V.; Nicodeme, E.; Patel, V.; Penfornis, X. A.;
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CONCLUSIONS
In conclusion, a series of new 2-aryl-5-((2-arylthiazol-4-
yl)methyl)-1,3,4-oxadiazole derivatives 4a–r and 5a–r
was synthesized. The pharmacological studies were under-
taken to evaluate the effects of substituent on the antimi-
crobial activities. Most of the synthesized compounds
exhibited moderate activity toward Gram-positive and
Gram-negative bacteria. Some of these compounds showed
moderate antifungal activity.
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Delhi, and University Grant Commission (UGC), New Delhi,
India, for financial support. The Department of Chemistry, Pune
University, is also acknowledged for spectral analysis.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet