Synthesis, Antimicrobial Evaluation, and Structure Activity Relationship Studies of New Biphenyl-2-Carbonitrile Clubbed 1,3,4-Oxadiazole Derivatives

Article abstract of DOI:10.1007/s11094-015-1320-y

Aseries of biphenyl-2-carbonitile clubbed 1,3,4-oxadiazole derivatives have been synthesized by the condensation of biphenyl-2-carbonitrile with various substituted 2-mercapto-5-aryl-1,3,4-oxadiazoles. Structures of the newly synthesized compounds IVa IVh were characterized using FTIR, ¹H NMR, ¹³C NMR, mass spectroscopy, and elemental analysis. All the compounds were screened for their antimicrobial properties against a broad spectrum of bacteria and fungi. It was very clearly noted from SAR study that the derivatives bearing electron-withdrawing functional groups (-NO₂, -Cl) were more promising than the derivatives with electron-donating group (-CH₃) as antimicrobial agents.

Full text of DOI:10.1007/s11094-015-1320-y

DOI 10.1007/s11094-015-1320-y
Pharmaceutical Chemistry Journal, Vol. 49, No. 8, November, 2015 (Russian Original Vol. 49, No. 8, August, 2015)
SYNTHESIS, ANTIMICROBIAL EVALUATION,
AND STRUCTURE ACTIVITY RELATIONSHIP STUDIES
OF NEW BIPHENYL-2-CARBONITRILE
CLUBBED 1,3,4-OXADIAZOLE DERIVATIVES
Kalpesh Parikh,1 Abhishek Joshi,1 Rahulsingh Kshatriya,2
and Deepkumar Joshi1,*
Original article submitted May 3, 2015.
A series of biphenyl-2-carbonitile clubbed 1,3,4-oxadiazole derivatives have been synthesized by the conden-
sation of biphenyl-2-carbonitrile with various substituted 2-mercapto-5-aryl-1,3,4-oxadiazoles. Structures of
the newly synthesized compounds IVa – IVh were characterized using FTIR, 1H NMR, 13C NMR, mass spec-
troscopy, and elemental analysis. All the compounds were screened for their antimicrobial properties against a
broad spectrum of bacteria and fungi. It was very clearly noted from SAR study that the derivatives bearing
electron-withdrawing functional groups (-NO2, -Cl) were more promising than the derivatives with elec-
tron-donating group (-CH3) as antimicrobial agents.
Keywords: 1,3,4-oxadiazole; carbonitrile; antimicrobial activity; Minimum Inhibitory Concentration (MIC);
Structure Activity Relationship (SAR).
INTRODUCTION
rile (-CN) substituent is found to be an excellent pharmaco-
phore perceiving the property of accepting H atom (H-bond
acceptor) on the basis of 2D-QSAR undertaken by Rajani-
kant and Teli [13]. Several research papers devoted to vari-
ous biological activities, e.g., antifungal [14] and antimyco-
bacterial [15], reported on compounds possessing carbonit-
rile functional groups clubbed with heterocyclic moieties.
Taking into consideration the above findings and in context
of our earlier work [16], here we present a series of
1,3,4-oxadiazole-clubbed carbonitrile derivatives IVa – IVh
with the pharmacophore structure shown in Fig. 2.
In recent years, several complications associated with the
human body were found to be caused by bacterial and fungal
infections. There is urgent task of discovering entities capa-
ble of acting as potent antibacterial and antifungal agents.
Literature survey reveals extensive use of nitrogen and oxy-
gen containing compounds in medicines for treating various
microbial diseases viz. antimicrobial [1], anticancer [2] and
anti-inflammatory [3]. Several derivatives of five-membered
ring compound, 1,3,4-oxadiazole, are found to possess a
wide variety of biological properties [4]. Other properties as-
sociated with 1,3,4-oxadiazole derivatives include anti-HIV
[5], antitubercular [6, 7], antimalarial [8], anticonvulsant [9]
and antitumoractivity [10].
RESULTS AND DISCUSSION
1,3,4-oxadiazoles are considered as an excellent class of
heterocyclic compounds possessing biological activities such
as antiulcer [11] and analgesic [12]. 1,3,4-Oxazdiazole skele-
ton is present in several drugs available on market, in partic-
ular, furamizole, zibotentan, and nesapadil (Fig. 1). Carbonit-
Chemistry
The title compounds IVa – IVh were synthesized in two
steps initiated with the synthesis of various derivatives of
5-aryl-1,3,4-oxadiazole-2-thiol (IIa – IIh) from benzoic acid
hydrazide derivatives Ia – Ih in the presence of carbondisul-
fide and potassiumhydroxide, using ethanol as solvent. The
intermediates IIa – IIh were mixed with 4¢-(bromomethyl)bi-
phenyl-2-carbonitrile(III) in acetone and stirred for 6h at
1
Chemistry Research Laboratory, Chemistry Division, Sheth M. N. Science
College, Patan, Gujarat, 384265 India.
2
Department of Chemistry, Hemchandracharya North Gujarat University,
Patan, Gujarat, 384265 India.
*
e-mail: deepjoshi359@yahoo.co.in.
523
0091-150X/15/4908-0523 © 2015 Springer Science+Business Media New York

524
Kalpesh Parikh et al.
Scheme 1. Synthesis of biphenyl-2-carbonitrile clubbed 1,3,4-oxadiazole derivatives
room temperature in the presence of potassiumcarbonate, re-
sulting in the formation of title derivatives IVa – IVh.
termined. The d values corresponded to the methylene group
and to protons of the aromatic ring. For compound IVc, the
signal at d = 4.68 ppm as a singlet clearly proved the pres-
ence of two hydrogen atoms of the methylene group. A
multiplet observed at 7.57 – 7.99 ppm confirmed the pres-
ence of aromatic protons.
Characterization
IR spectroscopy. The IR spectral data obtained for the
final derivatives IVa – IVh were useful to a great extent in
confirming their structure. Let us consider the spectral details
of compound IVc and correlate the vibrational frequencies
with functional groups present in the structure. The absorp-
tion peaks at 1065 and 1269 cm-1 helped to confirm the pres-
ence of -C-O-C- in the oxadiazole nucleus. The absorption
band at 1474 cm-1 proved the presence of -C=C- in the aro-
matic ring. The presence of the CN functional group
(carbonitrile) was also confirmed by a sharp peak at
2220cm-1. A sharp absorption band at 2844 cm-1 helped to
13C NMR spectroscopy. The d values in the 13C NMR
spectrum were found between 38.4 and 164.5. The carbon in
contact with the -CN functional group was found to exhibit a
peak at d = 104.7 ppm. A sharp peak at d = 117.4 ppm corre-
sponded to the carbon atom of -CN functional group. The
lowest d value at 38.4 ppm in the spectrum of compound IVc
proved the presence of methylene group (-CH ). A sharp
2
peak at d = 164.5 ppm indicated the presence of carbon atom
(C-15) in contact with the phenyl ring with various func-
tional groups. The d values for C-17, C-18 and C-19 were
found to vary with for different substituents. In particular,
assign the presence of –CH (methylene group) in compound
2
thepresence of -NO functional group in position C-18 and
IVc. The stretching frequency for aromatic -C-H was in com-
pound IVc noticed at 3054 cm-1.
2
C-19 in compounds IVa and IVb corresponded to d = 148.7
and 148.2 ppm, respectively. The presence of –Cl in com-
pounds IVc, IVg and IVh was confirmed by d = 134.6
1H NMRspectroscopy.The 1H NMR study was con-
ducted for each of the derivatives and the d values were de-

Synthesis, Antimicrobial Evaluation, and Structure Activity
525
Fig. 1. Drugs with 1,3,4-oxadiazole nucleus available on market.
Fig. 2. Pharmacophore site for derivatives IVa – IVh.
(C-19), 132.5 (C-17) and 135.1 ppm (C-18), respectively.
Ciprofloxacin and fluconazole purchased from HIMEIDA
(solid powder) were used as standard drugs for antibacterial
and antifungal testing, respectively. MIC values reported for
the standard drug ciprofloxacin are. 62.5 mg/mL against
S. aureus, 125 mg/mL against E. faecalis, 125 mg/mL against
E. coli and 125 mg/mL against P. aeruginosa. Fluconazole
drug as a standard exhibits MIC values of 125 and
62.5 mg/mL against C. albicans and A. niger, respectively.
Antibacterial and antifungal activity. Antibacterial po-
tential of the synthesized compounds IVa – IVh was tested
against gram-positive bacteria S. aureus (ATCC no. 25923)
and E. faecalis (ATCC no. 27853) and gram-negative bacte-
ria E. coli (ATCC no. 25922) and P. aeruginosa (ATCC no.
Methyl group (-CH ) in C-18 was manifested by a sharp
3
peak at d = 136.6 ppm for IVe and at d = 132.0 (C-19) for
IVf. Also it was found that, in the absence of any substituent,
the d values for 13C NMR at C-17, C-18 and C-19 were
within 127.8 – 129.5 ppm (compound IVd). The numbering
of carbon atoms is shown in Fig. 3.
Antimicrobial Activity
Various bacterial and fungal strains were employed for
the antimicrobial testing of the title derivatives IVa – IVh.
The potential of these compounds against the test microor-
ganisms is characterized by the minimum inhibitory concen-
tration (MIC)values in Table1. The synthesized compounds
IVa – IVh were tested using microdilution method, by dilut-
ing the solutions and preparing sets from 1000 to 7.8 mg/mL.
27853). Compounds IVb (p-NO ), IVc (p-Cl), IVg (o-Cl)
2
and IVh (m-Cl) were found to exhibit excellent or equivalent
activity as compared to the standard drug ciprofloxacin.
Other compounds, namely IVa (m-NO ), IVd (H), IVe
2

526
Kalpesh Parikh et al.
Fig. 3. Carbon numbering in biphenyl-2-carbonitrile clubbed 1,3,4-oxadiazole derivatives (by data of 13C NMR spectroscopy).
(m-CH ) and IVf (p-CH ) were found to possess lower activ-
dard drug. The only derivative possessing poor activity as
3
3
ity as compared to the standard drug and were even less ac-
tive than the aforementioned derivatives. When the same set
of derivatives IVa – IVh was tested against another gram-po-
sitive bacterial strain E. faecalis, all the compoundsexcept
compared to the standard drug was compound IVe (m-CH )
3
against the gram-negative bacterial strain P. aeruginosa.
The antifungal tests were performed against two differ-
ent fungal strains, A. niger and C. albicans, with fluconazole
used as a standard drug. The antifungal activity of the syn-
thesized derivatives IVa – IVh was found to be more pro-
nounced with respect to A. nigerthat to C. albicans. On test-
ing the synthesized compounds against C. albicans, deriva-
tive IVg (o-Cl) was found to show excellent activity as
compared to the standard drug fluconazole. Few other deriv-
IVd (H) and IVf (p-CH ) showed equivalent or excellent ac-
3
tivity. Compounds IVa – IVh were exposed to gram-negative
bacteria E. coli, and IVh showed excellent activity with
MIC = 15.62 mg/mL. Compounds IVc (p-Cl) and IVg (o-Cl)
exhibited MIC = 31.25 mg/mL, indicating better antibacterial
potential than the standard drug ciprofloxacin. Derivatives
IVa (m-NO ), IVb (p-NO ), IVd (H) and IVe (m-CH ) also
atives IVa (m-NO ), IVc (p-Cl) and IVh (m-Cl) exhibited ac-
2
2
2
3
tivity equivalent to that of the standard drug, while others
were found to be poor in activity. Same derivatives tested for
their antifungal property against the fungal strain A. niger
showed much better results in comparison to the tests on C.
albicans. Compounds IVc and IVg possessing -Cl as a sub-
stituent exhibited excellent activity (31.25 and 62.5 mg/mL),
which was even better than that of the standard drug flucona-
showed better activity than the standard drug. When the syn-
thesized derivatives IVa – h were tested against gram-nega-
tive bacteria P. aeurginosa, it was found that compound IVg
(o-Cl) and IVh (p-Cl) exhibited excellent activity
(31.25 mg/mL). Along with other derivatives IVa (m-NO ),
2
IVc (p-Cl), IVd (H) and IVf (p-CH ) exhibiting equivalent
3
activity (125 mg/mL) to that of the standard, derivative IVb,
zole. Also, the derivatives possessing -NO were found to
(p-NO ) showed higher activity (62.5 mg/mL) than the stan-
2
2
TABLE 1. Antimicrobial Test Results for Compounds IVa – IVh
Minimum Inhibitory Concentration (MIC) in mg/mL
Gram-negative bacteria
E. coli P. aeruginosa
Derivatives (-R)
Gram-positive bacteria
S. aureus E. faecalis
Fungi
C. albicans
125
A. niger
62.5
62.5
31.25
125
IVa (m-NO2)
IVb (p-NO2)
IVc (p-Cl)
125
62.5
62.5
250
250
125
31.25
62.5
–
125
125
62.5
250
125
250
62.5
62.5
–
125
62.5
31.25
125
125
62.5
125
125
250
125
31.25
31.25
–
250
125
IVd (H)
250
IVe (m-CH3)
IVf (p-CH3)
IVg (o-Cl)
125
250
125
250
500
250
31.25
15.62
–
62.5
125
31.25
62.5
62.5
–
IVh (m-Cl)
Fluconazole (Std)
Ciprofloxacin (Std)
125
62.5
125
125
125
–
Standard (Std) drugs : fluconazole for antifungal and ciprofloxacin for antibacterial tests.

Synthesis, Antimicrobial Evaluation, and Structure Activity
527
off and the residual mixture was cooled to room temperature.
The content was poured into water and acidified with diluted
HCl until asolid precipitate wasformed. The precipitated
solid was filtered, washed with cold water, and dried to ob-
tain the desired product. The completion of reaction was
monitored by TLC using ethyl acetate – benzene (6:4) mix-
ture as the mobile phase. All derivatives (IIa – IIh) were ob-
tained using the above procedure.
possess equivalent activity (62.5 mg/mL) comparable to that
of fluconazole. Derivatives possessing –CH as a functional
3
group showed poor activity (125 and 250 mg/mL) as com-
pared to that of the standard drug and other test compounds.
Structure Activity Relationship (SAR) Study
A larger difference in the biological activity was ob-
served between the compounds bearing electron-withdraw-
ing and electron-donating functional group as substituent
(-R). From the MIC data in Table 1, it is clear that the deriva-
Synthesis of title derivatives (IVa – IVh). 4¢-(Bromo-
methyl)biphenyl-2-carbonitrile (III) (0.01 mol, 272 g/mol,
2.72 g) was charged in a round bottom flask and acetone was
added to make the content soluble. To this solution, various
5-aryl-1,3,4-oxadiazole-2-thiol derivatives (IIa – IIh) were
added with constant stirring until solution became clear.
Then, K CO (0.02 mol, 138 g/mol, 2.76 g) was added and
tives bearing electron-withdrawing substituent (-Cl, NO )
2
exhibited higher antimicrobial potential as compared to that
of compounds with electron-donating substituent (-CH ). On
3
comparing MIC values between the derivatives possessing
electron-withdrawing functional groups (IVa – IVc, IVg, and
IVh) and derivative IVd (H) for most of the bacterial and
fungal strains, it is clearthat compound IVd with H atom as
substituent exhibits poor activity as compared to that of the
derivatives with electron-withdrawing groups. MIC data for
compounds IVe and IVf show their poor activity in compari-
2
3
the mixture was stirred for 6h at room temperature. The com-
pletion of reaction was checked by TLC using ethylace-
tate – n-hexane (6:4) mobile phase. Upon the completion of
reaction, the contents was poured into cold water and stirred
for 30 min. The resulting precipitates were washed with cold
water and crystallized from alcohol.
son to derivatives with -Cl and -NO substituent. Thus the
4¢-((5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)methyl)-
biphenyl-2-carbonitrile (IVa). Brownsolid; yield, 55%; mp
148 – 150°C; IR (ATR; n, cm-1): 1059, 1264 (-C-O-C- str.),
2
SAR study indicates that the presence of electron-withdraw-
ing functional groups can help enhancing the antibacterial
and antifungal properties.
1481 (-C=C str. aromatic ring), 2215 (-CN str.), 2841 (-CH
2
1
str. methylene group), 3060 (-C-H str. aromatic ring); H
EXPERIMENTAL
NMR (400 MHz, DMSO-d ; d, ppm): 4.59 (s, 2H, -CH ),
6
2
7.50 – 7.96 (m, 12H, Ar-H); 13C NMR (100 MHz,
Methods, Materials and Physical Techniques
DMSO-d ; d, ppm): 38.4 (C ), 104.7 (C ), 117.4 (CN),
6
13
1
All chemicals required for the synthesis were purchased
from Merck Ltd., HIMEDIA, and SD Fine Chemicals Ltd.
Open-end capillary method was used for the determination
of melting points (m.p.) of intermediates and the title deriva-
tives and reported uncorrected. The completion of reaction
was checked using TLC plates purchased from Merck (TLC
123.1 (C ), 124.2 (C ), 127.3 (C ), 128.2 (C , C ), 128.5
17
19
16
8
12
(C , C11), 128.6 (C ), 128.9 (C ), 130.4 (C ), 133 (C ),
9
3
5
20
2
133.8 (C ), 133.9 (C ), 136.2 (C ), 136.3 (C ), 142.5 (C ),
4
21
7
10
6
148.7 (C ), 164.5 (C ); mass spectrum (m/z): 415; elemen-
18
15
tal analysis: C H N O S. C, 63.76; H, 3.40; N, 13.52%.
22 14
4
3
Found: C, 63.81; H, 3.43; N, 13.55%.
Silica gel 60 F ). Bruker Alpha-TFTIR spectrometer was
254
4¢-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)methyl
)biphenyl-2-carbonitrile (IVb). Yellowsolid; yield, 57%;
mp 165°C; IR (ATR; n, cm-1): 1061, 1266 (-C-O-C- str.),
used to record the vibrational frequencies of functional
groups in the derivatives synthesized. The title compounds
were studied using Bruker spectrometers operating at 400
and 100 MHz to determine 1H NMR and 13C NMR data, re-
spectively. Schimadzu mass spectrometer was used to con-
duct mass-spectral analysis and Perkin-Elmer 2400 CHN an-
alyzer was used to carry out elemental analyses. Results of
elemental analysis corresponded to the calculated values.
1479 (-C=C str. aromatic ring), 2211 (-CN str.), 2856 (-CH
2
1
str. methylene group), 3057 (-C-H str. aromatic ring); H
NMR (400 MHz, DMSO-d ; d, ppm): 4.61 (s, 2H, -CH ),
6
2
7.54 – 8.03 (m, 12H, Ar-H); 13C NMR (100 MHz,
DMSO-d ; (, ppm): 38.4 (C ), 104.7 (C ), 117.4 (CN), 131.2
6
13
1
(C ), 148.2 (C ), 132.5 (C ), 128.2 (C , C ), 128.5 (C ,
17
19
16
8
12
9
C11), 128.6 (C ), 128.9 (C ), 129.1 (C ), 133 (C ), 133.8
3
5
20
2
Synthesis and Physicochemical Data
(C ), 131.2 (C ), 136.2 (C ), 136.3 (C ), 142.5 (C ), 129.2
4
21
7
10
6
(C ), 164.5 (C ); mass spectrum (m/z): 415; elemental anal-
Synthesis of 5-Aryl-1,3,4-oxadiazole-2-thiols (IIa – IIh).
18
15
ysis: C H N O S. C, 63.76; H, 3.40; N, 13.52%. Found: C,
Round bottom flasks containing ethanol (40 mL) and potas-
22 14
4
3
63.80; H, 3.43; N, 13.54%.
sium hydroxide (0.01 mol, 56.11 g/mol, 0.56 g in 2 mL H O)
2
4¢-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)meth
yl)biphenyl-2-carbonitrile (IVc). White solid; yield, 59%;
mp 140°C; IR (ATR; n, cm-1): 1065, 1269 (-C-O-C- str.),
were taken, various aryl substituted benzoic acid hydrazides
(0.01 mol) were added, and the mixtures were stirred well to
obtain clear solutions. To this solution, carbon disulfide
(0.02 mol, 76.14 gm/mol, 1.2 mL) was added and the mix-
ture was refluxed for 12 – 15 h. Then, ethanol was distilled
1474 (-C=C str. aromatic ring), 2220 (-CN str.), 2844 (-CH
2
1
str. methylene group), 3056 (-C-H str. aromatic ring); H

528
Kalpesh Parikh et al.
(-CH str. methylene group), 3048 (-C-H str. aromatic ring);
NMR (400 MHz, DMSO-d ; d, ppm): 4.68 (s, 2H, -CH ),
2
6
2
7.57 – 7.99 (m,12H, Ar-H); 13C NMR (100 MHz, DMSO-d ;
1H NMR (400 MHz, DMSO-d ; d, ppm): 4.51 (s, 2H, -CH ),
6
6
2
7.43 – 7.92 (m,12H, Ar-H); 13C NMR (100 MHz, DMSO-d ;
d, ppm): 38.4 (C ), 104.7 (C ), 117.4 (CN), 129.2 (C ),
6
13
1
17
134.6 (C ), 124.5 (C ), 128.2 (C , C ), 128.5 (C , C11),
d, ppm): 38.4 (C ), 104.7 (C ), 117.4 (CN), 132.5 (C ),
19
16
8
12
9
13
1
17
128.6 (C ), 128.9 (C ), 129.6 (C ), 133 (C ), 133.8 (C ),
130.4 (C ), 137.2 (C ), 128.2 (C , C ), 128.5 (C , C11),
3
5
20
2
4
19
16
8
12
9
129.2 (C ), 136.2 (C ), 136.3 (C ), 142.5 (C ), 129.6 (C ),
128.6 (C ), 128.9 (C ), 127.6 (C ), 133 (C ), 133.8 (C ),
21
7
10
6
18
3
5
20
2
4
164.5 (C ); mass spectrum (m/z): 404; elemental analysis:
129.2 (C ), 136.2 (C ), 136.3 (C ), 142.5 (C ), 129.6 (C ),
15
21
7
10
6
18
C H ClN OS. C, 65.42; H, 3.49; N, 10.40%. Found: C,
164.5 (C ); mass spectrum (m/z): 404; elemental analy-
22 14
3
15
65.45; H, 3.51; N, 10.44%.
sis:C H ClN OS. C, 65.42; H, 3.49; N, 10.40%. Found: C,
22 14
3
4¢-((5-phenyl-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-
2-carbonitrile (IVd). Buff solid; yield, 59%; mp 130°C; IR
(ATR; n, cm-1): 1049, 1253 (-C-O-C- str.), 1471 (-C=C str.
65.46; H, 3.53; N, 10.43%.
4¢-((5-(3-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)meth
yl)biphenyl-2-carbonitrile (IVh). Llight-yellowsolid; yield,
59%; mp 140°C; IR (ATR; n, cm-1): 1061, 1248 (-C-O-C-
str.), 1486 (-C=C str. aromatic ring), 2217 (-CN str.), 2847
aromatic ring), 2223 (-CN str.), 2851 (-CH str. methylene
2
1
group), 3051 (-C-H str. aromatic ring); H NMR (400 MHz,
DMSO-d ; d, ppm): 4.53 (s, 2H, -CH ), 7.58 – 7.91 (m,12H,
(-CH str. methylene group), 3080 (-C-H str. aromatic ring);
6
2
2
Ar-H); 13C NMR (100 MHz, DMSO-d ; d, ppm): 38.4 (C ),
1H NMR (400 MHz, DMSO-d ; d, ppm): 4.49 (s, 2H, -CH ),
6
13
6
2
7.49 – 7.89 (m,12H, Ar-H); 13C NMR (100 MHz, DMSO-d ;
104.7 (C ), 117.4 (CN), 127.8 (C ), 129.0 (C ), 126.4 (C ),
1
17
19
16
6
128.2 (C , C ), 128.5 (C , C11), 128.6 (C ), 128.9 (C ),
d, ppm): 38.4 (C ), 104.7 (C ), 117.4 (CN), 127.7 (C ),
8
12
9
3
5
13
1
17
129.5 (C ), 133 (C ), 133.8 (C ), 127.8 (C ), 136.2 (C ),
129.1 (C ), 127.8 (C ), 128.2 (C , C ), 128.5 (C , C11),
20
2
4
21
7
19
16
8
12
9
136.3 (C ), 142.5 (C ), 129.5 (C ), 164.5 (C ); mass spec-
10
6
18
15
128.6 (C ), 128.9 (C ), 129.8 (C ), 133 (C ), 133.8 (C ),
3 5 20 2 4
trum (m/z): 370; elemental analysis: C H N OS. C, 71.52;
22 15
3
125.9 (C ), 136.2 (C ), 136.3 (C ), 142.5 (C ), 135.1 (C ),
21 7 10 6 18
H, 4.09; N, 11.37%. Found: C, 71.55; H, 4.11; N, 11.40%.
4¢-((5-m-tolyl-1,3,4-oxadiazol-2-ylthio)methyl)biphe-
nyl-2-carbonitrile (IVe). White solid; yield, 54%; mp
110°C; IR (ATR; n, cm-1): 1044, 1256 (-C-O-C- str.), 1463
164.5 (C ); mass spectrum (m/z): 404; elemental analysis:
15
C H ClN OS. C, 65.42; H, 3.49; N, 10.40%. Found: C,
22 14
3
65.45; H, 3.53; N, 10.44%.
(-C=C str. aromatic ring), 2229 (-CN str.), 2859 (-CH str.
1
methylene group), 3071 (-C-H str. aromatic ring); H NMR
2
CONCLUSION
(400 MHz, DMSO-d ; d, ppm): 4.54 (s, 2H, -CH ),
6
2
The title compounds containing electron-withdrawing
substituents were found to exhibit excellent antibacterial and
antifungal properties. Several derivatives showed better re-
sults than the standard drug ciprofloxacin. In particular, MIC
valuesof compound IVg (o-Cl) were better than those of the
standard drug against all bacterial and fungal strains
(31.25 – 62.5 mg/mL), and compound IVh (m-Cl) exhibited
excellent activity against gram-negative bacteria E. coli and
P. aeruginosa. Thus, compounds with excellent biological
properties can be further optimized by introducing electron
withdrawing functional groups in order to develop new po-
tent leads.
7.29 – 7.94 (m,12H, Ar-H); 13C NMR (100 MHz, DMSO-d ;
6
d, ppm): 21.6 (-CH ),38.4 (C ), 104.7 (C ), 117.4 (CN),
3
13
1
130.7 (C ), 129.3 (C ), 126.3 (C ), 128.2 (C , C ), 128.5
17
19
16
8
12
(C , C11), 128.6 (C ), 128.9 (C ), 129.4 (C ), 133 (C ),
9
3
5
20
2
133.8 (C ), 124.8 (C ), 136.2 (C ), 136.3 (C ), 142.5 (C ),
4
21
7
10
6
139.2 (C ), 164.5 (C ); mass spectrum (m/z): 384.5; ele-
18
15
mental analysis: C H N OS. C, 72.04; H, 4.47; N, 10.96%.
23 17
3
Found: C, 72.09; H, 4.51; N, 10.99%.
4¢-((5-p-tolyl-1,3,4-oxadiazol-2-ylthio)methyl)biphe-
nyl-2-carbonitrile (IVf). White solid; yield, 54%; mp
142°C; IR (ATR; n, cm-1): 1053, 1266 (-C-O-C- str.), 1470
(-C=C str. aromatic ring), 2216 (-CN str.), 2850 (-CH str.
2
1
methylene group), 3049 (-C-H str. aromatic ring); H NMR
ACKNOWLEDGMENTS
(400 MHz, DMSO-d ; d, ppm): 4.62 (s, 2H, -CH ),
6
2
7.60 – 8.05 (m,12H, Ar-H); 13C NMR (100 MHz, DMSO-d ;
6
The authors are thankful to Sheth M. N. Science College
(Patan) and North Gujarat Education Society (Mumbai) for
providing laboratory and library facility. We extend our sin-
cere thanks to Vraj Pansuriya for his valuable help in procur-
ing spectral data.
d, ppm): 21.6 (-CH ), 38.4 (C ), 104.7 (C ), 117.4 (CN),
3
13
1
127.7 (C ), 132.0 (C ), 123.4 (C ), 128.2 (C , C ), 128.5
17
19
16
8
12
(C , C11), 128.6 (C ), 128.9 (C ), 126.6 (C ), 133 (C ),
9
3
5
20
2
133.8 (C ), 127.7 (C ), 136.2 (C ), 136.3 (C ), 142.5 (C ),
4
21
7
10
6
126.6 (C ), 164.5 (C ); mass spectrum (m/z): 384.5; ele-
18
15
mental analysis: C H N OS. C, 72.04; H, 4.47; N, 10.96%.
23 17
3
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Found: C, 72.09; H, 4.51; N, 11.00%.
4¢-((5-(2-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)me-
thyl)biphenyl-2-carbonitrile (IVg). White solid; yield,
62%; mp 125°C; IR (ATR; n, cm-1): 1039, 1245 (-C-O-C-
str.), 1469 (-C=C str. aromatic ring), 2213 (-CN str.), 2856
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