Synthesis and biological activity of 5-substituted-2-amino-1,3,4-oxadiazole derivatives

Article abstract of DOI:10.3906/kim-0908-177

Electrical energy offers numerous benefits for performing synthesis, including increased reaction rates, enhanced yields, and cleaner chemistries. 5-Substituted-2-amino-1,3,4-oxadiazoles were synthesized directly from the semicarbazone at a platinum elect

Full text of DOI:10.3906/kim-0908-177

Turk J Chem
35 (2011) , 99 – 108.
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˙
c
ꢀ TUBITAK
doi:10.3906/kim-0908-177
Synthesis and biological activity of
5-substituted-2-amino-1,3,4-oxadiazole derivatives
Sanjeev KUMAR
Department of Chemistry, Iswar Saran Degree College University of Allahabad,
Allahabad-211004, INDIA
e-mail: sanjeevks78@gmail.com
Received 12.08.2009
Electrical energy offers numerous benefits for performing synthesis, including increased reaction rates,
enhanced yields, and cleaner chemistries. 5-Substituted-2-amino-1,3,4-oxadiazoles were synthesized directly
from the semicarbazone at a platinum electrode under controlled potential electrolysis in an undivided cell
assembly in acetonitrile. The compounds were screened for antibacterial and antifungal activity against
Staphylococcus aureus, Klebsiella pneumoniae, Pellicularia salmonicolor, and Macrophomina phaseolina.
Key Words: Antibacterial, antifungal, controlled potential, electrolysis, platinum electrode
Introduction
Recent trends and advances in the technology for the development of ecofriendly synthetic methods in chemical
research have great importance and are urgently needed for society. At present, organic synthesis involving elec-
trochemical techniques under suitable solvents and electrolytes are basic requirements, as multistep conventional
synthesis produces a considerably large amount of environmentally unfavorable wastes, mainly due to a series of
complex isolation procedures involving expensive and toxic solvents after each step. Electrochemical oxidation
has various merits. These reactions do not require oxidizing reagents and can be performed at room tempera-
ture. Application of electricity as a nonconventional energy source for activation of reactants in suitable solvents
has now gained popularity over the usual homogeneous and heterogeneous reactions. It provides chemical pro-
cesses with special attributes, such as enhanced reaction rate, higher yield of pure products, better selectivity,
and several ecofriendly advantages. Electroorganic synthesis of 5-substituted-2-amino-1,3,4-oxadiazole is an
important step in this direction.
Various 1,3,4-oxadiazoles have been reported to have a broad spectrum of biological activity, includ-
ing antimicrobial,1−3 antifungal,4,5 antiinflammatory,6 and hypotensive activity.7 During hit-to-lead efforts
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Synthesis and biological activity of ..., S. KUMAR
following a recent high-throughput screening campaign, we initiated a program that required the synthesis
of a series of 5-substituted-2-amino-1,3,4-oxadiazoles 4. Literature syntheses of these oxadiazoles8−14 include
bromine oxidation of a semicarbazide derivative and the cyclodesulfurization of acylthiosemicarbazide deriva-
tives in a solution using I2 /NaOH or 1,3-dicyclohexylcarbodimide (DCC),15−20 as well as mercury(II) acetate
(Hg(OAc)2) or yellow mercury(II) oxide HgO,21−23 and they produce undesirable mercury byproducts that
must be removed and properly disposed of after the reaction is completed. These aforementioned solution
phase methods, while successful, were deemed not readily amenable to high-throughput synthesis, and thus did
not meet our needs. A solution-phase dehydrative synthesis from 1,2-diacylhydrazines and several solid-phase
methods were also considered.24,25 Evans26 synthesized a similar cyclized product with one-pot preparation
using resin-bound reagents.
Experimental
General procedure
Melting points were recorded from an open capillary and were uncorrected. The IR spectra, in KBr, were
recorded on a Shimadzu 8201 PC IR spectrophotometer. 1 H-NMR (300, 300 MHz) and 13 C-NMR (75, 300
MHz) spectra were measured at room temperature on Bruker DRX 300 FT spectrometer instruments with
TMS and CDCl3 or C6 D6 as internal standards. Carbon multiplities were assigned by DEPT techniques.
Microanalyses were carried out in an Elementar Vario EL III. The purity of the compounds was confirmed by
TLC on silica gel-coated glass plates.
Synthesis of semicarbazone 3
Semicarbazide hydrochloride (9.0 mmol) 2 and sodium acetate (12.2 mmol) were dissolved in water (10 mL),
and then aldehyde (4.16 mmol) 1 was added with continuous stirring. The mixture was left overnight, which
gave semicarbazone 3.
Preparative-scale controlled potential electrolysis
Thoroughly mixed semicarbazone (18.0 mmol) 3 and lithium perchlorate (3.0 mmol) in acetonitrile acid (200
mL) were taken in a 250 mL 3-electrode cell assembly with a platinum plate (1.0 cm × 1.0 cm) as working,
as well as a counter electrode and saturated calomel electrode (SCE) as a reference electrode. Preparative-
scale controlled potential electrolysis27−32 was performed (25 ◦ C) at the corresponding oxidation potential and
completed in 3-5 h. The current potential data were recorded with a potentiostat (Table 1). A magnetic stirrer
was used for the diffusion of the product from the electrode and the proper mixing of the reaction mixture. The
products were extracted from the acetic acid solution with chloroform by the simple solvent extraction, and the
extracted chloroform layer was left overnight to evaporate the extract. Purification by silica gel chromatography
afforded 4 in excellent yield. Analytical and spectral data were obtained from all compounds.
100

Synthesis and biological activity of ..., S. KUMAR
Table 1. Synthesis of 5-substituted-2-amino-1,3,4-oxadiazole derivatives.
Entry
R
Time (h) Product
Applied
Potential (V)
1.85
Current (A) Yield (%)
1
2
2-Cl,5-(NO2)C6H3
2,3-Cl2C6H3
3
5
4
3
4
5
5
5
3
4
3
5
5
4a
4b
4c
4d
4e
4f
0.16
0.18
0.15
0.14
0.16
0.19
0.17
0.16
0.15
0.18
0.11
0.16
0.17
78
82
91
86
89
75
74
90
89
78
83
75
78
1.90
3
2-CH3C6H4
1.60
4
9-Anthryl
1.65
5
3-OEt,4-(OH)C6H3
2-F, 6-ClC6H3CH2
C6H4CH=CBr
3,5-(OMe)2, 4-(OH)C6H2
4-Et2NC6H4
1.65
6
1.85
7
4g
4h
4i
1.95
8
1.70
9
1.60
10
11
12
13
2-(HOOC)C6H4
3,5-Cl2, 2-OHC6H2
2,5-F2C6H3
4j
1.85
4k
4l
2.00
2.10
3,5-F2C6H3
4m
2.20
2-amino-5-(2-chloro-5-nitrophenyl)-1,3,4-oxadiazole (4a)
◦
Dark yellow needles; mp 80-82 C; IR υmax /cm−1 750, 815, 1032 (C-O-C), 1560, 1618 (C=N-N=C), 1660, 3035,
3341; 1 H-NMR (300 MHz, CDCl3) δ 7.25-7.69 (dd, J = 2.6, 5.6 Hz, 3H, Ph), 7.75 (s, 2H, NH2); 13 C-NMR
(75 MHz, CDCl3) δ 113.3, 122.2, 123.1, 138.2, 139.8, 148.3, 149.6, 156.7, 171.5. MS (ESI) m/z 241.60 (M+H),
found: 241.22. Analysis Calc. for C8 H5 N4 O3 Cl (241.60): C, 42.47; H, 2.21; N, 24.77; Cl, 15.70%, found: C,
42.21; H, 2.09; N, 24.48; Cl, 15.40%.
2-amino-5-(2,3-dichlorophenyl)-1,3,4-oxadiazole (4b)
Brownish needles; mp 85-86 ◦ C; IR υmax /cm−1 600, 655, 775, 1020 (C-O-C), 1603 (C=N-N=C), 3045, 3360;
1 H-NMR (300 MHz, CDCl3) δ 6.94-7.14 (dd, J = 2.6, 5.6 Hz, 4H, Ph), 7.75 (s, 2H, NH2); 13 C-NMR (75
MHz, CDCl3) δ 128.5, 128.7, 131.7, 133.5, 135.0, 143.0, 157, 163.2, 171.4. MS (ESI) m/z 231.048 (M+H),
found: 230.542. Analysis Calc. for C8 H5 N3 OCl2 (231.048): C, 41.73; H, 2.17; N, 18.26; Cl, 30.86%, found:
C, 41.15; H, 2.08; N, 18.17; Cl, 30.54%.
2-amino-5-(2-methylphenyl)-1,3,4-oxadiazole (4c)
Brownish needles; mp 71-72 ◦ C; IR υmax /cm−1 765, 1060 (C-O-C), 1609 (C=N-N=C), 2927, 2965, 3444;
1 H-NMR (300 MHz, CDCl3) δ 0.9 (s, 3H, CH3), 6.52-7.14 (dd, J =2.6, 5.6 Hz, 4H, Ph), 7.75(s, 2H, NH2);
13 C-NMR (75 MHz, CDCl3) δ 126.5, 126.6, 126.8, 129.1, 136.6, 138.6, 141.3, 149.9, 171.6. MS (ESI) m/z
175.191 (M+H), found: 174.324. Analysis Calc. for C9 H9 N3 O (175.191): C, 61.71; H, 5.14; N, 24.00%, found:
C, 61.56; H, 5.06; N, 23.89%.
101

Synthesis and biological activity of ..., S. KUMAR
2-amino-5-(9-anthryl)-1,3,4-oxadiazole (4d)
Light brown needles; mp 84-86 ◦ C; IR υmax /cm−1 775, 1055 (C-O-C), 1612 (C=N-N=C), 3045, 3330; 1 H-NMR
(300 MHz, CDCl3) δ 7.25-7.69 (dd, J = 2.6, 5.6 Hz, 9H, Ar), 7.75 (s, 2H, NH2); 13 C-NMR (75 MHz, CDCl3)
δ 125.3, 128.3, 131.5, 139.2, 139.5, 149.5, 171.5. MS (ESI) m/z 262.284 (M+H), found: 2671.746. Analysis
Calc. for C16 H11 N3 O (262.284): C, 73.56; H, 4.21; N, 16.09%, found: C, 73.23; H, 4.05; N, 15.89%.
2-amino-5-(3-ethoxy-4-hydroxyphenyl)-1,3,4-oxadiazole (4e)
Pale yellow needles; mp 78-80 ◦ C; IR υmax /cm−1 750, 790, 1055 (C-O-C), 1200-1275, 1611 (C=N-N=C),
2810, 2865, 2927, 3330, 3444; 1 H-NMR (300 MHz, CDCl3) δ 1.4 (t, J = 5 Hz, 3H, CH3), 3.2 (q, J =7.2
Hz, 2H,CH2), 5.68 (s, 1H, OH), 6.52-7.14 (dd, J = 2.6, 5.6 Hz, 3H, Ph), 7.75 (s, 2H, NH2); 13 C-NMR (75
MHz, CDCl3) δ 17.1, 67.4, 115.5, 120.0, 134.9, 138.5, 139.6, 145.4, 147.1, 149.5, 171.7. MS (ESI) m/z 222.217
(M+H), found: 221.116. Analysis Calc. for C10 H11 N3 O3 (222.217): C, 58.53; H, 5.36; N, 20.48%, found: C,
58.32; H, 5.15; N, 20.22%.
2-amino-5-(6-chloro-2-fluorophenyl)-1,3,4-oxadiazole (4f)
Yellow needles; mp 81-83 ◦ C; IR υmax /cm−1 745, 810, 1035 (C-O-C), 1220, 1618 (C=N-N=C), 3050, 3360;
1 H-NMR (200 MHz; CDCl3 /TMS) δ 6.94-7.04 (dd, J =2.6, 5.6 Hz, 4H, Ph), 7.75 (s, 2H, NH2); 13 C-NMR
(300 MHz; CDCl3 /TMS) δ 113.4, 124.1, 126.5, 128.8, 134.0, 138.6, 149.8, 162.5, 172.0. MS (ESI) m/z 228.628
(M+H), found: 227.068. Analysis Calc. for C9 H7 N3 OFCl (228.628): C, 47.57; H, 3.08; N, 18.50; F, 8.27; Cl,
15.63%, found: C, 47.32; H, 2.95; N, 18.19; F, 8.11; Cl, 15.52%.
2-amino-5-(α-bromocinnamyl)-1,3,4-oxadiazole (4g)
Dark yellow crystal; mp 82-84 ◦ C; IR υmax /cm−1 580, 695, 1025 (C-O-C), 1609 (C=N-N=C), 1670, 2855, 3030,
3033, 3336; 1 H-NMR (300 MHz, CDCl3) δ 6.52 (d, J = 16.8 Hz, 1H, PhCH =CBr), 6.94-7.14 (dd, J =2.6,
5.6 Hz, 5H, Ph), 7.75 (s, 2H, NH2); 13 C-NMR (75 MHz, CDCl3) δ 126.5, 126.6, 128.2, 128.7, 137.6, 138.6,
149.0, 171.5. MS (ESI) m/z 254.175 (M+H), found: 253.425. Analysis Calc. for C10 H7 N3 OBr (254.175): C,
45.11; H, 3.01; N, 15.48; Br, 29.66%, found: C, 44.89; H, 2.98; N, 15.27; Br, 29.43%.
2-amino-5-(3,5-dimethoxy-4-hydroxyphenyl)-1,3,4-oxadiazole (4h)
Dark brownish crystal; mp 83-85 ◦ C; IR υmax /cm−1 752, 810, 1028 (C-O-C), 1602 (C=N-N=C), 2856, 2870,
2927, 3335, 3444; 1 H-NMR (300 MHz, CDCl3) δ 3.10-3.73 (s, 6H, OCH3), 6.09 (s, 1H, OH), 6.52-7.14 (dd,
J =2.6, 5.6 Hz, 2H, Ph), 7.75 (s, 2H, NH2); 13 C-NMR (75MHz, CDCl3) δ 46.7, 54.1, 108.0, 120.8, 126.8, 135.6,
138.3, 148.2, 149.6, 173.4. MS (ESI) m/z 238.224 (M+H), found: 237.232. Analysis Calc. for C10 H11 N3 O4
(238.224): C, 50.42; H, 5.04; N, 17.64%, found: C, 50.12; H, 4.73; N, 17.35%.
102

Synthesis and biological activity of ..., S. KUMAR
2-amino-5-(4-N,N-diethylaminophenyl)-1,3,4-oxadiazole (4i)
Black needles; mp 79-81 ◦ C; IR υmax /cm−1 850, 1032 (C-O-C), 1610 (C=N-N=C), 2870, 3030, 3334; 1 H-NMR
(300 MHz, CDCl3) δ 1.38 (t, J = 7.2 Hz, 6H, CH3), 3.12 (q, J =7.2 Hz, 4H, CH2), 6.94-7.14 (dd, J = 2.6,
5.6 Hz, 4H, Ph), 7.75 (s, 2H, NH2); 13 C-NMR (75 MHz, CDCl3) δ 13.7, 14.2, 116.2, 116.3, 128.5, 128.9, 131.1,
138.6, 146.5, 149.5, 172.5. MS (ESI) m/z 233.285 (M+H), found: 232.557. Analysis Calc. for C12 H16 N4 O
(233.285): C, 62.06; H, 6.89; N, 24.13%, found: C, 61.80; H, 6.70; N, 24.00%.
2-amino-5-(2-carboxyphenyl)-1,3,4-oxadiazole (4j)
Pale yellow needles; mp 81-83 ◦ C; IR υmax /cm−1 690, 750, 810, 890, 1021 (C-O-C), 1654 (C=N-N=C), 1715,
2750, 3035, 3341; 1 H-NMR (300 MHz, CDCl3) δ 7.25-7.69 (dd, J = 2.6, 5.6 Hz, 4H, Ph), 7.75 (s, 2H, NH2);
13 C-NMR (75 MHz, CDCl3) δ 127.1, 129.6, 129.8, 132.5, 133.2, 142.8, 167.0, 171.9, 172.6. MS (ESI) m/z
206.173 (M+H), found: 205.221. Analysis Calc. for C9 H7 N3 O3 (206.173): C, 47.05; H, 2.91; N, 20.38%,
found: C, 46.80; H, 2.70; N, 20.03%.
2-amino-5-(3,5-dichloro-2-hydroxyphenyl)-1,3,4-oxadiazole (4k)
Brown needles; mp 83-85 ◦ C; IR υmax /cm−1 600, 655, 775, 1026 (C-O-C), 1070, 1633 (C=N-N=C), 3045,
3360, 3640; 1 H-NMR (300 MHz, CDCl3) δ 4.70 (s, 1H, OH), 6.8-7.30 (dd, J = 2.6, 5.6 Hz, 2H, Ph), 7.72 (s,
2H, NH2); 13 C-NMR (75 MHz, CDCl3) δ 117.8, 123.2, 126.5, 128.6, 128.9, 153.3, 167.2, 171.6. MS (ESI) m/z
247.046 (M+H), found: 246.372. Analysis Calc. for C8 H5 N3 O2 Cl2 (247.046): C, 39.06; H, 2.04; N, 17.08; Cl,
28.82%, found: C, 38.62; H, 1.94; N, 16.75; Cl, 28.56%.
2-amino-5-(2,5-difluorophenyl)-1,3,4-oxadiazole (4l)
Yellow needles; mp 77-79 ◦ C; IR υmax /cm−1 815, 830, 850, 1035 (C-O-C), 1260, 1665 (C=N-N=C), 3050,
3360; 1 H-NMR (300 MHz, CDCl3) δ 6.94-7.04 (dd, J = 2.6, 5.6 Hz, 3H, Ph), 7.75 (s, 2H, NH2); 13 C-NMR
(75 MHz CDCl3) δ 113.3, 113.5, 123.1, 127.2, 138.5, 147.6, 149.2, 149.5, 171.8. MS (ESI) m/z 198.148 (M+H),
found: 197.235. Analysis Calc. for C8 H7 N3 OF2 (198.148): C, 48.24; H, 3.51; N, 21.10; F, 19.09%, found: C,
48.07; H, 3.38; N, 21.00; F, 18.90%.
2-amino-5-(3,5-difluorophenyl)-1,3,4-oxadiazole (4m)
Yellow needles; mp 77-79 ◦ C; IR υmax /cm−1 815, 830, 850, 1022 (C-O-C), 1260, 1652 (C=N-N=C), 3050,
3360; 1 H-NMR (300 MHz, CDCl3) δ 6.94-7.04 (dd, J = 2.6, 5.6 Hz, 3H, Ph), 7.75 (s, 2H, NH2); 13 C-NMR
(75 MHz, CDCl3) δ 113.3, 113.5, 123.3, 127.5, 138.5, 147.6, 149.2, 149.5, 171.6. MS (ESI) m/z 198.164 (M+H),
found: 197.352. Analysis Calc. for C8 H7 N3 OF2 (198.164): C, 48.24; H, 3.51; N, 21.10; F, 19.09%, found: C,
48.07; H, 3.38; N, 21.00; F, 18.90%.
103

Synthesis and biological activity of ..., S. KUMAR
Results and discussion
Our objective was to find a new environmentally benign general synthetic method for the preparation of
1,3,4-oxadiazoles, in which the use of the aforementioned reagents could be minimized in both amount and
number. Keeping that objective in mind, we synthesized some 5-substituted-2-amino-1,3,4-oxadiazoles 4 by
electrooxidative cyclization of semicarbazone 3 at the platinum electrode. This electrochemical cyclization gave
the oxadiazoles (Scheme 1) without the requirement of any hazardous reagents. We used acetonitrile as a
solvent and lithium perchlorate (LiClO4) as an electrolyte, which can be handled very easily, without major
precautions.
Compounds 4b, 4c, and 4j are not new and have been previously reported.33−35 Compounds 4a, 4f,
4l, and 4m are commercially available. The present study proposes a new methodology for obtaining these
compounds.
O
O
AcONa
+ H2N NH C NH2
R
CHO
R
CH N NH C NH2
2
1
N
N
N
N
CH3CN, Pt Electrode
LiClO4
NH2
R
R
NH2
H HO
O
4
3
Scheme 1. Synthesis of 5-substituted-2-1,3,4-oxadiazols 4.
N
N
N
H
N
N
H
N
-H
e
C
C
C
C
C
C
NH2
C
O
R
H O
R
R
O
NH2
NH2
H
3b
3a
3
N
C
N
N
H
N
N
N
C
O
- H
+e
C
C
C
R
O
R
NH2
O
R
NH2
NH2
H
4
3c
3d
Scheme 2. Mechanistic proposal.
2-Amino-5-substituted-1,3,4-oxadiazoles were synthesized in excellent yields using the synthetic route
outlined in Scheme 1. IR, 1 H-NMR, 13 C-NMR, and mass spectral data are in agreement with the proposed
structures of all synthesized compounds. Lack of 1 H NMR resonances observed with NH and NH2 functions
in the 1 H-NMR spectrum of 4a-m proved that ring closure starting from 3 resulted in the formation of a
104

Synthesis and biological activity of ..., S. KUMAR
2-amino-1,3,4-oxadiazole ring. This was further substantiated by the 13 C-NMR data of 4, which showed peaks
at δ 170-173 and 145-150 due to the C2 and C5 of oxadiazole, respectively. The IR spectrum showed 1600-1620
cm−1 for (C=N-N=C) and 1063-1073 cm−1 for (C-O-C) in compounds 4a-m, which confirmed the synthesis
of 1,3,4-oxadiazoles.
Compounds 4a-m were screened for their antibacterial activity against Staphylococcus aureus and Kleb-
siella pneumoniae by comparing them with standard streptomycin, and antifungal activity against Pellicularia
salmonicolor and Macrophomina phaseolina was compared with the standard fungicide griseofulvin. It is inter-
esting to observe that the maximum compounds had excellent antifungal and antibacterial activity.
The antimicrobial activity of the compounds varied upon the type and position of the substituents at
5-substituted-2-amino-1,3,4-oxadiazole moiety. It can be concluded from the antimicrobial screening results
that when 5-substituted-2-amino-1,3,4-oxadiazoles were substituted with aryl halide, the antimicrobial activity
was altered to an appreciable extent.
Biological activity
All of the synthesized compounds were tested for antimicrobial activity with the experimental method of
Benson.36,37 Whatman No. 1 filter paper disks, 6 mm in diameter, were placed in a petri dish and autoclaved.
The test compounds, in measured quantities (1.0 and 0.5 mg), were dissolved in 5 mL of dimethylformamide
to produce 200 ppm and 100 ppm solutions, respectively. The filter paper disks were allowed to dry, and the
amount of substance per disk was taken as 500 and 250 μg. The bacterial (24 h) and fungal (48 h) cultures from
the slants were diluted with sterile water and mixed thoroughly to prepare a clear homogeneous suspension.
These suspensions were uniformly spread on solidified agar (nutrient and potato dextrose agar) medium. The
filter paper disks prepared from the dimethylformamide medium were carefully placed over the spread cultures
and incubated at 37 ◦ C for 24 h for bacteria and at 28-30 ◦ C for 48 h for fungi. Paper disks treated with
dimethylformamide alone served as the control. After the incubation period, the plates were examined for
inhibition zones. The diameters of the inhibition zones (including the diameter of the disk) were measured.
All determinations were made in triplicate for each of the compounds and the average value was taken. The
compounds were assayed for antimicrobial activity against registered bacterial isolates.
Compounds 4a-m (Table 2) were screened for their antifungal activity against Pellicularia salmonicolor
and Macrophomina phaseolina along with the standard fungicide griseofulvin. The disk diffusion method36,37
was followed for screening the compounds at 3 concentrations (25, 50, and 100 μg disk−1). Their antibacterial
activity (Table 3) was also evaluated according to the disk diffusion method at 3 different concentrations against
Staphylococcus aureus and Klebsiella pneumoniae by comparing them with the standard streptomycin.
It is obvious from Table 2 that compound 4g had a higher antifungal activity than the standard
griseofulvin for both Pellicularia salmonicolor and Macrophomina phaseolina. Compounds 4a, b, f, and k
were slightly less active than the standard, while 4c, e, g, h, i, l, and m had moderate activity. Compounds
4d and 4j were much less active or had negligible activity. It is evident from Table 3 that compound 4g
had higher antibacterial activity than the standard streptomycin for both Staphylococcus aureus and Klebsiella
pneumoniae. Compounds 4a, b, f, k, and l were slightly less active than the standard, while 4d, e, i, and j
had moderate activity.
It is interesting to observe that all 4a-m compounds with antifungal activity were also antibacterial.
105

Synthesis and biological activity of ..., S. KUMAR
Table 2. Antifungal activity of compounds 4a-m.
Diameter of zone of growth inhibition (mm)
Pellicularia salmonicolor Macrophomina phaseolina
(μg disk−1
)
(μg disk−1
)
Compound
25
2
4
1
-
50
5
6
4
-
100
8
25
2
3
2
-
50
4
6
4
-
100
9
4a
4b
10
6
9
4c
7
4d
2
2
4e
2
2
3
2
3
-
4
5
7
5
6
2
4
3
4
6
7
2
3
4
1
1
-
3
5
8
3
4
2
6
4
3
7
6
4f
9
10
11
5
4g
11
7
4h
4i
7
6
4j
4
4
4k
4l
2
1
2
-
8
3
2
1
3
9
6
6
4m
7
6
Griseofulvin
10
11
Table 3. Antibacterial activity of compounds 4a-m.
Diameter of zone of growth inhibition (mm)
Pellicularia salmonicolor Macrophomina phaseolina
(μg disk−1
)
(μg disk−1
)
Compound
25
4
3
3
-
50
7
6
5
-
100
11
10
8
25
3
2
1
-
50
6
6
4
-
100
10
8
4a
4b
4c
6
4d
4
3
4e
1
3
5
2
1
-
3
6
8
4
3
2
6
5
4
7
6
3
4
5
2
2
-
5
7
9
5
4
2
7
6
4
7
7
4f
9
9
4g
12
7
13
8
4h
4i
5
7
4j
6
5
4k
2
3
1
2
9
3
3
2
2
10
9
4l
4m
8
7
8
Streptomycin
11
10
106

Synthesis and biological activity of ..., S. KUMAR
Conclusion
It is evident from the electrochemical method that the electroorganic synthesis of 1,3,4-oxadiazole derivatives is
an example of electrochemical cyclization by electrooxidation of semicarbazone. It provides a good method for
the synthesis of oxadiazoles with antimicrobial activity in excellent yields. In the present electrolytic method,
electrolysis was carried out at ordinary temperatures and no hazardous chemicals were used. Therefore, the
method is environmentally benign and a great contribution to the field of green chemistry.
Acknowledgements
The author thanks the University Grant Commission, New Delhi, for the financial assistance, and SAIF (Sophis-
ticated Analytical Instrumentation Facility), a division of CDRI Lucknow, India, for providing microanalyses
and spectra.
References
1. Holla, B. S.; Gonaslaves, R.; Shenoy, S. Eur. J. Med. Chem. 2000, 35, 267-271.
2. Cesur, N.; Birteksoz, S.; Otuk, G. Acta Pharm. Turc. 2002, 44, 23-41.
3. Laddi, U. V.; Desai, S. R.; Bennur, R. S.; Bennur, S. C. Indian J. Heterocyclic Chem. 2002, 11, 319-322.
4. Zou, X.; Zhang, Z.; Jin, G. J. Chem. Res. (S) 2002, 228-230.
5. Zou, X. J.; Lai, L. H.; Jin, G. Y.; Zhang, Z. X. J. Agric. Food Chem. 2002, 50, 3757-3760.
6. Palaska, E.; Sohin, G.; Kalicen, P.; Darlu, N. T.; Altinok, G. Farmaco 2002, 57, 101-107.
7. Tyagi, M.; Kumar, A. Orient. J. Chem. 2002, 18, 125-130.
8. Hetzheim, A.; Moeckel, K. Adv. Heterocyclic Chem. 1966, 7, 183-224.
9. Hill, J. In Comprehensive Heterocyclic Chemistry; Potts, K. T., Ed.; Pergamon Press, Oxford, 1984.
10. Chiba, T.; Okimoto, M. J. Org. Chem. 1992, 57, 1375-1379.
11. Butler, R. N.; Scott, F. L.; O’Mahony, T. A. F. Chem. Rev. 1973, 73, 93-102.
12. Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J.
S.; Storer, I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815-4195.
13. Adams, G. L.; Graybill, T. L.; Sanchez, R. M.; Magard, V. W.; Burton, G.; Rivero, R. A. Tetrahedron Lett. 2003,
44, 5041-5045.
14. Tori, S. Electroorganic Syntheses, Kodansha, Tokyo, 1985.
15. Aboulwafa, O. M.; Omar, O. M. M. E. Sulfur Lett. 1992, 14, 181-188.
16. Omar, F. A.; Mahfouz, N. M.; Rahman, M. A. Eur. J. Med. Chem. 1996, 31, 819-825.
17. Golovlyova, S. M.; Moskvichev, Y. A.; Alov, E. M.; Kobylinskey, D. B.; Ermolaeva, V. V. Chem. Heterocycl.
Compd. 2001, 37, 1102-1106.
18. Liu, F. M.; Wang, B. L.; Zhang, Z. F. Youji Huaxue 2001, 21, 1126-1131.
107

Synthesis and biological activity of ..., S. KUMAR
19. Gani, R. S.; Pujar, R. S.; Gadaginamath, G. S. Indian J. Heterocycl. Chem. 2002, 12, 25-28.
20. Wang, X.; Li, Z.; Yang, J. Synth. Commun. 2002, 32, 1097-1103.
21. Brain, C. T.; Brunton, S. A. Synlett 2001, 382-384.
22. Brain, C. T.; Paul, J. M.; Loong, Y.; Oakley, P. J. Tetrahedron Lett. 1999, 40, 3275-3278.
23. Faidallah, H. M.; Sharshira, E. M.; Basaif, S. A.; A-Ba-Oum, A. E. Phosphorus Sulfur Silicon 2002, 177, 67.
24. Kilburn, J. P.; Lau, J.; Jones, R. C. F. Tetrahedron Lett. 2001, 42, 2583-2586.
25. Brown, B. J.; Clemens, I. R.; Neesom, J. K. Synlett 2000, 131-133.
26. Cappo, F. T.; Evans, K. A.; Graybill, T. L.; Burton, G. Tetrahedron Lett. 2004, 45, 3257-3260.
27. Shono, T. Electroorganic Synthesis, Academic Press, London, 1991.
28. Mann, C. K.; Barnes, K. K. Electrochemical Reactions in Nonaqueous Systems, Marcel Dekker, New York, 1970.
29. Fry, A. J. Synthetic Organic Electrochemistry, 2nd ed., Wiley-Interscience, New York, 1989.
30. Singh, S.; Kumar, S.; Sharma, L. K.; Singh, R. K. P. J. Indian Chem. Soc. 2009, 86, 734-738.
31. Sharma, L. K.; Kumar, S.; Yadav, P.; Singh, R. K. P. Indian J. Chem., Sec. B 2008, 47, 1277-1280.
32. Sharma, L. K.; Kumar, S.; Singh, S.; Singh, R. K. P. Russian J. Electrochem. 2010, 46, 34-40.
33. Murthy, G. R.; Rao, A. B.; Reddy, V. M.; Sisodia, P. Indian Drugs 1986, 23, 354-357.
34. Yale, H. L.; Losee, K. J. Med. Chem. 1966, 9, 478-483.
35. Hejsek, M.; Wiedermannova, I. Acta Universitatis Palackianae Olomucensis, Facultas Rerum Naturalium, Chemica
2001, 40, 15-24.
36. Benson, H. J. Microbiological Applications, 5th ed., W. C. Brown Publications, Boston, 1990.
37. Vincent, J. C.; Vincent, H. W. Proc. Soc. Expt. Biol. Medi. 1944, 55, 162-164.
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