Synthesis, characterization and anti-bacterial activity of 5-(alkenyl)-2-amino-and 2-(alkenyl)-5-phenyl-1,3,4-oxadiazoles

Article abstract of DOI:10.1007/s12039-010-0019-6

Fatty acid hydrazides of undec-10-enoic, (Z)-octadec-9-enoic, (Z)-12-hydroxyoctadec-9-enoic and (Z)-9-hydroxyoctadec-12-enoic acids are used as cheap starting materials in the synthesis of important biologically active 5-(alkenyl)-2-amino-1,3,4-oxadiazole

Full text of DOI:10.1007/s12039-010-0019-6

J. Chem. Sci., Vol. 122, No. 2, March 2010, pp. 177–182. © Indian Academy of Sciences.
Synthesis, characterization and anti-bacterial activity of 5-(alkenyl)-2-
amino- and 2-(alkenyl)-5-phenyl-1,3,4-oxadiazoles
MUDASIR R BANDAYa, RAYEES H MATTOOb and ABDUL RAUFa,*
aDepartment of Chemistry, bDepartment of Biochemistry, Aligarh Muslim University, Aligarh 202 002
e-mail: abduloafchem@gmail.com
MS received 24 January 2008; revised 11 February 2009; accepted 21 July 2009
Abstract. Fatty acid hydrazides of undec-10-enoic, (Z)-octadec-9-enoic, (Z)-12-hydroxyoctadec-9-enoic
and (Z)-9-hydroxyoctadec-12-enoic acids are used as cheap starting materials in the synthesis of impor-
tant biologically active 5-(alkenyl)-2-amino-1,3,4-oxadiazole and 2-(alkenyl)-5-phenyl-1,3,4-oxadiazole
using cyanogen bromide and benzoyl chloride or benzoic acid as reagents, respectively. The structure of
these compounds was confirmed by IR, 1H NMR, 13C NMR and Mass spectra. All the newly synthesized
compounds were screened for their antibacterial activity. Compounds 2c, 2d, 3a, 3c and 3d showed good
antimicrobial activity against E. coli where as compounds 2a and 2d were found active against all the
bacteria.
Keywords. 1,3,4-Oxadiazoles; antibacterial activity; MIC; IR; NMR; mass spectra.
1. Introduction
1,3,4-oxadiazole derivatives act as analgesic, anti-
inflammatory, anticonvulsive, diuretic11 and 2-
hydroxyphenyl-1,3,4 oxadiazole possess hypnotic
and sedative12 activities. Some material applications
of 1,3,4-oxadiazole derivatives lie in the field of liq-
uid crystals13 and photosensitizer.14
Many seed oils, fatty acids and their derivatives
are known for their pesticidal,15 antimicrobial16,17
and antifungal activities.18 Thus fatty acids on deri-
vatization to these heterocyclic compounds can be
used as valuable oleo-chemicals. These observations
and our interest in the chemistry of heterocycles pro-
mpted us to synthesize different 1,3,4-oxadiazoles
with different substituents at 2- and 5-positions.
These compounds have been also screened for their
in vitro antibacterial activity.
The emergence of multi-drug resistant strains of
bacteria is a problem of ever increasing significance.
Consequently, the development of new antimicrobial
agents will remain an important challenging task for
medicinal chemists. There are two basic approaches
to develop a new drug: (a) synthesis of analogues,
modifications or derivatives of existing compounds
for shortening and improving treatment and (b)
searching for novel structures, that the bacteria has
never been presented before. To pursue this goal,
our research efforts are directed to synthesize new
pharmacophores. Substituted 1,3,4-oxadiazoles are
of considerable pharmaceutical importance, which is
documented by several number of publications and
patents. A large number of drugs used clinically
have oxadiazole ring as a structural building block.
Literature survey reveals that 1,3,4-oxadiazoles have
wide range of biological activities ranging from an-
tibacterial,1–5 antifungal6,7 to anti-inflammatory.8
Derivatives of 1,3,4-oxadiazole with suitable substi-
tution at 2,5-position have been reported to possess
considerable pharmacological activities. 2-Amino-
1,3,4-oxadiazole acts as muscle relaxant9 and also
shows antimitotic activity.10 5-Aryl-2-hydroxymethyl-
2. Experimental
2.1 Materials and methods
Undec-10-enioc (purity 98%) and (Z)-octadec-9-
enoic (97%) acids were purchased from Fluka Chemi-
cals (Bucks, Switzerland). (Z)-12-hydroxyoctadec-9-
enoic acid (ricinolic acid, 98%) and (Z)-9-hydroxy-
octadec-12-enoic acid (isoricinolic acid, 98%) were
isolated from Ricinus communis and Wrightia tinc-
toria seed oils respectively following Gunstone’s
*For correspondence
177

178
Mudasir R. Banday et al
partition procedure.19 Benzoic acid and benzoyl
A mixture of the corresponding fatty acid
chloride were purchased from Merk, Mumbai, India. hydrazide (0⋅001 mol) and cyanogen bromide
Phosphorus oxychloride and hydrazine hydrate (0⋅0012 mol) in dry methanol were refluxed at 60°C
(80%) were purchased from Sd fine-chem (Mumbai, on oil bath. The resulting solution was cooled and
India). Thin layer chromatography was done on filtered. The filtrate was neutralized with sodium bi-
glass plates (20 × 5 cm) with a layer of silca gel G carbonate solution. The solid mass separated was
(Merk, Mumbai, India, 0⋅5 mm thickness). Mixture filtered, washed with excess water, dried and recrys-
of petroleum ether-diethyl ether-acetic acid (80 : tallized in chloroform-methanol. Yields, melting
20 : 1, v/v) were used as developing solvents. Col- points and reaction time are given in table 1.
umn chromatography was carried out on silca gel
(Merk, Mumbai, India, 60–120 mesh). 1H NMR was 2.2a 5-(Dec-9′-enoyl)-2-amino-1,3,4-oxadiazoles
recorded with Bruker DRX 300 spectrometer at (2a): IR (KBr) νmax: 3112, 2858-2922, 1585,
1
300 MHz and 13C NMR was recorded at 75 MHz in 1187 cm–1; H NMR (CDCl3): 1⋅26 (10H, br, s,
CDCl3. Chemical shifts (δ) are quoted in ppm. The (CH2)5), 1⋅69 (2H, m, CH2 β to ring), 2⋅03 (2H, m,
FAB mass spectra were recorded on a JEOL-SX CH2=CH-CH2), 2⋅68 (2H, t, J = 7⋅2 Hz, CH2 α to
102/DA-600 mass spectrometer employing electron ring), 4⋅90 (2H, br, s, NH2), 5⋅01 and 4⋅95 (2H, m,
impact technique at 70 eV. Melting points were CH2=CH), 5⋅81 (1H, m, CH2=CH-CH2); 13C NMR
taken in on open capillary and are uncorrected.
(CDCl3): δ 167⋅1, 164⋅7, 139⋅0, 114⋅1, 31⋅9, 29⋅7
Undec-10-enoic hydrazide 1a, (Z)-octadec-9-enoic ‘one signal hidden’, 29⋅4 ‘one signal hidden’, 29⋅1
hydrazide 1b, (Z)-12-hydroxyoctadec-9-enoic hydra- ‘two signals hidden’; MS: m/z 224 (M+, 100), 205
zide 1c and (Z)-9-hydroxyoctadec-12-enoic hydra- (45), 167 (32), 139 (20), 112 (42), 97 (55).
zide 1d were prepared from undec-10-enoate, (Z)-
octadec-9-enoate, (Z)-12-hydroxyoctadec-9-enoate
and (Z)-9-hydroxyoctadec-12-enoate respectively
following the procedure reported earlier.20
2.2b (Z)-5-(Heptadec-8'-enoyl)-2-amino-1,3,4-oxa-
diazoles (2b): IR (KBr) νmax: 3118, 2850–2921,
1
1584, 1174 cm–1; H NMR (CDCl3): 0⋅88 (3H, dist.
t, terminus CH3), 1⋅25 (20H, br, s, (CH2)10), 1⋅69 (2H,
m, CH2 β to ring), 2⋅03 (4H, m, CH2–CH=CH–CH2),
2⋅69 (2H, t, J = 7⋅5 Hz, CH2 α to ring), 4⋅86 (2H, br,
s, NH2), 5⋅41 (2H, m, CH2–CH=CH–CH2); 13C NMR
2.2 General method for synthesis of 5-(alkenyl)-
2-amino-1,3,4-oxadiazoles (2a–d)
Caution! Considering the toxic nature of CNBr the (CDCl3): δ 167⋅0, 164⋅3, 131⋅2, 125⋅5, 31⋅9 ‘one
experiment was carried in fume hood. Safety meth- signal hidden’, 31⋅7, 29⋅7 ‘one signal hidden’, 29⋅6,
ods mentioned in safety data sheet of N.I.H. were 29⋅5, 29⋅4 ‘three signals hidden’, 29⋅2, 29⋅1, 22⋅7,
adapted while handling cyanogen bromide (http:// 14⋅4; MS: m/z 322 (M+, 15), 304 (20), 237(15), 224
dohs.ors.od.nih.gov/pdf/cyanogens%20bromide.pdf).
(100), 182 (35), 167 (22), 154 (45), 112 (30), 99 (35).
Table1. Appearance, yield and reaction time of various reactions by varying the reactant.
Reaction
m.p. (°C) Yield (%) time (h)
Molecular
formula
Compound Appearance
Reactant
2a
2b
2c
2d
3a
White powder
White crystals
White powder
White flakes
Offwhite
powder
Offwhite
crystals
Oily
CNBr
CNBr
CNBr
CNBr
PhCOCl
PhCOOH
PhCOCl
PhCOOH
PhCOCl
PhCOOH
PhCOCl
PhCOOH
120–122
133–135
137–139
131–133
107–109
107–109
195–197
195–197
–
73
77
65
60
76
69
73
60
69
55
65
58
3–4
3–4
3–4
3–4
4–5
6–7
4–5
6–7
5–6
6–7
5–6
6–7
C12H21N3O
C19H35N3O
C19H35N3O2
C19H35N3O2
C18H24N2O
C18H24N2O
C25H38N2O
C25H38N2O
C25H38N2O2
C25H38N2O2
C25H38N2O2
C25H38N2O2
3b
3c
3d
–
–
–
Oily

Activity of 5-(alkenyl)-2-amino- and 2-(alkenyl)-5-phenyl-1,3,4-oxadiazoles
179
2.2c (Z)-5-(11′-Hydroxy-octadec-8′-enoyl)- 2-amino- 2.3a 2-(Dec-9′-enoyl)-5-phenyl-1,3,4-oxadiazole
1,3,4-oxadiazoles (2c): IR (KBr) νmax: 3281, 3112, (3a): IR (KBr) νmax: 2850–2926, 1579, 1154 cm–1;
2843–2924, 1581, 1187 cm–1; H NMR (CDCl3): 1H NMR (CDCl3): 1⋅24 (10H, br, s, (CH2)5), 1⋅76
1
0⋅88 (3H, dist. t, terminus CH3), 1⋅27 (18H, br, s, (2H, m, CH2 β to ring), 2⋅07 (2H, m, CH2=CH-CH2),
(CH2)9), 1⋅66 (2H, m, CH2 β to ring), 2⋅07 (4H, m, 2.77 (2H, t, J = 7⋅2 Hz, CH2 α to ring), 5⋅03 and
CH2–CH=CH–CH2), 2⋅17 (1H, br, s, CH-OH), 2⋅89 4⋅99 (2H, m, CH2=CH), 5⋅76 (1H, m, CH2=CH–
13
(2H, t, J = 7⋅2 Hz, CH2 α to ring), 3⋅66 (1H, m, CH– CH2), 7⋅50–8⋅04 (5H, m, Ph-H); C NMR (CDCl3):
OH), 4⋅90 (2H, br, s, NH2), 5⋅47 (2H, m, CH2– δ 168⋅2, 153⋅0, 133⋅4, 133⋅2, 130⋅0, 129⋅8, 127⋅9,
CH=CH–CH2); 13C NMR (CDCl3): δ 166⋅8, 163⋅5, 114⋅2, 33⋅7, 29⋅3, 29⋅1, 28⋅9 ‘one signal hidden’,
131⋅2, 125⋅5, 77⋅1, 31⋅9, 31⋅8, 29⋅7 ‘one signal hid- 28.4 ‘two signals hidden’; MS: m/z: 284 (M+, 24),
den’, 29⋅6, 29⋅2, ‘three signals hidden’, 25⋅5 ‘two 257 (20), 242 (15), 215 (10), 207 (100), 139 (25),
signals hidden’, 22⋅6, 14⋅2; MS: m/z 337 (M
+
, 25), 112 (16), 97 (20).
322 (100), 304 (22), 254 (25), 252 (32), 222 (40),
196 (34), 182 (25), 168 (22), 155 (24), 112 (25), 99
(10).
2.3b (Z)-2-(Heptatadec-8′-enoyl)-5-phenyl-1,3,4-
oxadiazole (3b): IR (KBr) νmax: 2842–2918, 1571,
1
1182 cm–1; H NMR (CDCl3): 0⋅87 (3H, dist. t, ter-
minus CH3), 1⋅24 (20H, br, s, (CH2)10), 1⋅66 (2H, m,
CH2 β to ring), 1⋅99 (4H, m, CH2-CH=CH–CH2),
2⋅79 (2H, t, J = 7⋅5 Hz, CH2 α to ring), 5⋅48 (2H, m,
CH2–CH=CH–CH2), 7⋅49–8⋅02 (5H, m, Ph–H); 13C
NMR (CDCl3): δ 168⋅4, 152⋅2, 133⋅5, 130⋅4, 129⋅3,
125⋅6, 123⋅2, ‘one signal hidden’, 38⋅6, 38⋅4, 31⋅8,
31⋅4, 29⋅2, 28⋅9, 28⋅7, 28⋅4, 28⋅2, ‘three signals hid-
den’, 27⋅9, 22⋅6, 14⋅0; MS: m/z 383 (M+, 100), 367
(25), 353 (35), 311 (10), 269(20), 229(15), 215 (15),
187 (23), 173 (20), 145 (15), 113 (35), 99 (15).
2.2d (Z)-5-(8′-Hydroxy-octadec-11′-enoyl)-2-amino-
1,3,4-oxadiazoles (2d): IR (KBr) νmax: 3281, 3122,
1
2841–2925, 1584, 1184 cm–1; H NMR (CDCl3):
0.88 (3H, dist. t, terminus CH3), 1⋅25 (18H, br, s,
(CH2)9), 1.72 (2H, m, CH2 β to ring), 2⋅04 (4H, m,
CH2–CH=CH–CH2), 2⋅15 (1H, br, s, CH-OH), 2⋅71
(2H, t, J = 7⋅2 Hz, CH2 α to ring), 3⋅66 (1H, m, CH–
OH), 4⋅91 (2H, br, s, NH2), 5⋅45 (2H, m, CH2–
CH=CH–CH2); 13C NMR (CDCl3): δ 167⋅1, 164⋅7,
133⋅4, 127⋅3, 77⋅4, 31⋅9, 31⋅7, 29⋅7 ‘one signal hid-
den’, 29⋅6, 29⋅4, ‘two signals hidden’, 29⋅2, 25⋅5,
‘two signals hidden’, 22⋅7, 14⋅3; MS: m/z 337 (M+,
22), 322 (100), 320 (23), 254 (30), 224 (35), 196
(34), 168 (15), 155 (20), 137 (32), 126 (20), 112
(44), 97 (25).
2.3c (Z)-2-(11′-Hydroxy-octadec-8′-enoyl)-5-phenyl-
1,3,4-oxadiazole (3c): IR (KBr) νmax: 3281, 2856–
2930, 1550, 1174 cm–1; 1H NMR (CDCl3): 0⋅86 (3H,
dist. t, terminus CH3), 1⋅25 (18H, br, s, (CH2)9), 1⋅67
(2H, m, CH2 β to ring), 2⋅02 (4H, m, CH2–CH=CH–
CH2), 2⋅26 (1H, br, s, CH-OH), 2⋅84 (2H, t,
J = 7⋅2 Hz, CH2 α to ring), 3⋅60 (1H, m, CH-OH),
5⋅37 (2H, m, CH2–CH=CH–CH2), 7⋅43–8⋅08 (5H, m,
Ph–H); 13C NMR (CDCl3): δ 167⋅2, 153⋅0, 139⋅8,
139⋅0, 133⋅5, 130⋅0, 129⋅8, 127⋅9, 77⋅1, 38⋅6, 38⋅4,
33⋅5, 31⋅7, 30⋅2, 29⋅9 ‘one signal hidden’, 29⋅3, 28⋅7
‘two signals hidden’, 28⋅3, 22⋅4, 14⋅4; MS: m/z: 398
(M+, 90), 383 (100), 357 (23), 339 (25), 327 (10),
257 (30), 254 (25), 243 (49), 229 (36), 215 (30), 173
(25), 160 (22), 137 (24), 112 (40), 97 (30).
2.3 General method for synthesis of 2-(alkenyl)-5-
phenyl-1,3,4-oxadiazole (3a–d)
A mixture of fatty acid hydrazide (0⋅001 mol), ben-
zoyl chloride or benzoic acid (0⋅001 mol) and phos-
phorus oxychloride (5 ml) in 1,2-dichloroethane
were refluxed at 65°C under inert atmospheric
conditions. Excess solvent and POCl3 were removed
under reduced pressure. The resulting solution
was cooled to room temperature, poured into ice
cold water and left over night. The solid mass sepa-
rated was filtered, dried and recrystalized from
methanol where as the oily compounds were dis-
solved in ether and washed with excess cold water,
dried and chromatographed over silca gel using pe-
troleum ether-diethyl ether (96 : 4, v/v) as eluent.
Yields, melting points and reaction time are given in
table 1.
2.3d (Z)-2-(8′-Hydroxy-octadec-11′-enoyl)-5-phenyl-
1,3,4-oxadiazole (3d): IR (KBr) νmax: 3219, 2841–
2925, 1594, 1180 cm–1; 1H NMR (CDCl3): 0⋅80 (3H,
dist. t, terminus CH3), 1⋅13 (18H, br, s, (CH2)9), 1⋅76
(2H, m, CH2 β to ring), 2⋅09 (4H, m, CH2–CH=CH–
CH2), 2⋅26 (1H, br, s, CH–OH), 2⋅84 (2H, t,
J = 7⋅2 Hz, CH2 α to ring), 3⋅79 (1H, m, CH–OH),
5⋅35 (2H, m, CH2–CH=CH–CH2), 7⋅43–7⋅95 (5H, m,
Ph–H); 13C NMR (CDCl3): δ 165⋅7, 151⋅4, 139⋅1,

180
Mudasir R. Banday et al
Table 2. Antibacterial activity of the newly synthesized compounds in vitro (culture).
Zone of inhibition (mm)
Gram-negative bacteria
S. typhimurium
Gram-positive bacteria
S. aureus
(MSSA 22)
B. subtilis
(ATCC 6501)
E. coli (K 12)
(MTCC 98)
Compound
50 (µg/ml) 100 (µg/ml) 50 (µg/ml) 100 (µg/ml) 50 (µg/ml) 100 (µg/ml) 50 (µg/ml) 100 (µg/ml)
2a
2b
2c
2d
3a
3b
3c
3d
++
+
++
+++
++
+
++
++
+++
–
++
++
+++
+++
+++
++
+++
+++
++++
–
+
NT
+
++
+
NT
+
NT
+++
–
++
–
++
++
++
–
++
–
++++
–
+
+
NT
+
NT
NT
+
+
+++
–
++
++
–
++
–
+
NT
+
++
NT
NT
NT
+
++
–
++
++
–
–
–
–
++
++
++++
–
++
++++
–
Chlormycetin
DMF
+++
–
Inhibition zone diameter in mm (+) 1–6; (++) 7–12; (+++) 13–18; (++++) 19–24; (–) no activity. NT = not tested
Table 3. Minimum inhibition concentration (MIC) of newly synthesized compounds.
MIC (µg/ml)
Gram-negative bacteria
Gram-positive bacteria
Compound
E. coli (K 12) S. typhimurium (MTCC 98) S. aureus (MSSA 22) B. subtilis (ATCC 6501)
2a
2b
2c
2d
3a
3b
3c
3d
12⋅5
25
12⋅5
6⋅25
12⋅5
25
12⋅5
12⋅5
3⋅125
25
NT
25
12⋅5
25
NT
25
NT
6⋅25
25
25
NT
25
NT
NT
25
25
6⋅25
25
NT
25
12⋅5
NT
NT
NT
25
Chlormycetin
6⋅25
The MIC values were evaluated at concentration range 1⋅56–50 µg/ml. NT = not tested
139⋅0, 133⋅0, 130⋅7, 129⋅4, 127⋅6, 77⋅3, 38⋅6, 36⋅4, 100 μg/ml of DMF in the nutrient agar media. Stan-
30⋅4, 31⋅8, 29⋅8, 29⋅6, 29⋅4 ‘two signals hidden’, dard antibiotic chloromycetin was screened under
28⋅9 ‘one signal hidden’, 25⋅9, 22⋅2, 14⋅3; MS: m/z similar conditions. 100 μl of these solutions were
397 (M+, 20), 381 (100), 369 (22), 357 (20), 341 added to each well. One of the wells was used as
(35), 327 (15), 321 (25), 271 (30), 257 (45), 243 control by adding 100 μl of DMF. The zone of inhi-
(15), 229 (15), 215 (30), 201 (10), 187 (25), 165 bition, if any, produced by diffusion of the com-
(15), 152 (25), 145 (15), 138 (28), 98 (15).
pounds from the cup into the surrounding medium,
was measured after incubation at 37°C for 24 h
(table 2).
2.4 Antibacterial activity
Minimum inhibitory concentrations (MICs) were
determined by broth dilution technique. The nutrient
broth, which contained logarithmic serially two-fold
diluted amount of test compound and controls were
inoculated with approximately 5 × 105 c.f.u. of actively
dividing bacteria cells. The cultures were incubated
for 24 h at 37°C and the growth was monitored visu-
ally and spectrophotometrically. The lowest concen-
The representative compounds 2a–d and 3a–d were
tested for their antibacterial activity against Gram
negative bacteria [Escherchia coli (K 12), Salmonella
typhimurium (MTCC 98)] and Gram positive bacte-
ria [Staphylococcus aureus (MSSA 22), Bacillus
subtilis (ATCC 6501)] employing the cup-plate
method21 at the concentrations of 50 μg/ml and

Activity of 5-(alkenyl)-2-amino- and 2-(alkenyl)-5-phenyl-1,3,4-oxadiazoles
181
Scheme 1.
tration (highest dilution) required to arrest the protons α to oxadiazole ring. In 13C NMR peak at
growth of bacteria was regarded as minimum inhibi- 167⋅1 and 164⋅7 were observed for ring carbons.
tory concentration (MIC). The minimum inhibitory Mass spectra also supported the structure. Molecular
concentrations are given in table 3. All the experi- ion peak M+ at m/z 224 was observed which corre-
ments were carried out in triplicate and repeated if spond to the molecular formula C12H21N3O. Similar
the results differed.
types of spectral data were observed for 2b–d.
2-(Alkenyl)-5-phenyl-1,3,4-oxadiazole 3a–d was
prepared by dehydrative cyclization of diacylhy-
drazide by dehydrating agent, phosphorus oxychlo-
ride. Reaction time and the yields were observed by
varying the reagents. It is worthy to mention that
benzoyl chloride was a better reactant than benzoic
acid under inert atmospheric conditions, which is
evident from better yields and less reaction time.
The build up of 3a–d is evident from their spectral
data. Compound 3a showed IR absorption bands at
1579 cm–1 and 1154 cm–1 due to stretching vibra-
3. Results and discussion
The reaction sequence leading to formation of title
compounds is outlined in scheme 1. The synthesis of
2,5-disubstituted 1,3,4-oxadiazoles was performed
in several steps. In the first step fatty acid hydrazides
1a–d were prepared according to literature method.20
5-(Alkenyl)-2-amino-1,3,4-oxadiazoles 2a–d were
obtained in moderate yields by reacting fatty acid
hydrazides with cyanogen bromide in dry methanol
at 60–65°C. Formation of 2a was confirmed from its
spectral data. IR spectra of the compound 2a showed
absorption bands at 3112 cm–1, 1585 and 1187 cm–1
due to NH2, C=N and C–O–C stretching vibrations.
1
tions of C=N and C–O–C functions. The H NMR
was more informative in assigning the structure.
Multiplet at δ 7⋅50–8⋅04 was observed for aromatic
protons. Also triplet at δ 2⋅77 was observed for CH2
protons α to oxadiazole ring. In 13C NMR peaks at
168⋅2 and 153⋅0 were observed for ring carbon. The
mass spectra showed molecular ion peak M+ at m/z 284
1
The H NMR showed broad singlet at δ 4⋅90 corre-
sponding to NH2 protons at 2-position of oxadiazole
ring. Also triplet at δ 2⋅68 was observed for CH2

182
Mudasir R. Banday et al
corresponding to the molecular formula C18H24N2O. Acknowledgments
Similar types of spectral data were observed for 3b–d.
The authors are thankful to the Chairman, Depart-
ment of Chemistry, Aligarh Muslim University, Ali-
garh, for providing facilities to carry out research
work. Authors are also thankful to the Director, So-
phisticated Analytical Instrumentation Facility
(SAIF) Panjab University, Chandigarh, for provid-
ing spectral analysis. One of the authors (M R Ban-
day) thanks the University Grants Commission
(UGC), New Delhi, for the award of Research Fel-
lowship.
3.1 Biological activity
The investigation of the antimicrobial screening of
compounds 2a–d and 3a–d revealed that all the syn-
thesized compounds showed moderate to good anti-
bacterial activity against E. coli. Compound 2d was
active against all the bacteria where as 2c was active
against E. coli, S. typhimurium and B. subtilis (table
2). This can be attributed to presence of pharmaco-
logically active –NH2 group attached to oxadiazole
ring and –OH group of fatty acid chain. Compound
2a was moderately active against all the bacteria,
where as 3a was moderately active against gram
negative bacteria which were in accordance with our
previous observations.17 It may be noted that com-
pounds 2c, 2d, 3a, 3c and 3d showed promising
results against E. coli. Comparing these results with
our previous studies22, we found that 1,3,4-oxadiazoles
substituted with two fatty acid chains at 2 and 5 po-
sition of the oxadiazole ring were better antibacterial
agents than 1,3,4-oxadiazoles having only one fatty
acid chain at 2 or 5 position of the oxadiazole ring.
The results thus obtained reveal that nature of
substituent at 2 and 5 position of oxadiazole ring
may have a considerable impact particularly the free
–NH2 group and the –OH group on fatty acid chain
to enhance antibacterial activity. The results indicate
that compounds 2a, 2c, 2d, 3a, 3c and 3d may be
used as control measures against different bacteria.
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This study reports the successful synthesis and anti-
bacterial activity of new 2,5-disubstituted-1,3,4-
oxadiazoles. The divergence in the antibacterial ac-
tivity of these compounds validates the significance
of this study. The antibacterial activity study
revealed that the most of the compounds tested
showed moderate to good antibacterial activity.
Structure and biological activity relationship of the
title compounds showed that the presence of free
NH2 group at position 2 of oxadiazole ring and bio-
logically active group like OH group attached to
fatty acid chain are responsible for increased antim-
icrobial activity in the newly synthesized title com-
pounds. However, the effect of compounds on the
host cell and their mode of action remain to be studied.