Synthesis and antimicrobial activity of novel 1,3,4-oxadiazolyl-quinazolin- 4(3H)ones

Article abstract of DOI:10.1002/jhet.383

A series of 1,3,4-oxadiazolyl-quinazolin-4(3H)ones have been synthesized using known methods. All the compounds have been established on basis of elemental analysis, IR and NMR spectral data. The in vitro antimicrobial screening of the synthesized compounds were carried out against two gram-positive bacteria (S. aureus, S. pyogenes), two gram-negative bacteria (E. coli, P. aeruginosa), and three fungal species (C. albicans, A. niger, A. clavatus) using the broth microdilution method. The compounds 7d, 7g, 7l, 7o, 7p, and 7r possessed pronounced antibacterial activity whereas compound 7p exhibited promising antifungal activity.

Full text of DOI:10.1002/jhet.383

July 2010
Synthesis and Antimicrobial Activity of Novel 1,3,4-Oxadiazolyl-
quinazolin-4(3H)ones
923
Navin B. Patel* and Jaymin C. Patel
Department of Chemistry, Veer Narmad South Gujarat University, Surat 395007, Gujarat, India
*E-mail: drnavin@satyam.net.in
Received September 5, 2009
DOI 10.1002/jhet.383
Published online 18 June 2010 in Wiley InterScience (www.interscience.wiley.com).
A series of 1,3,4-oxadiazolyl-quinazolin-4(3H)ones have been synthesized using known methods. All
the compounds have been established on basis of elemental analysis, IR and NMR spectral data. The in
vitro antimicrobial screening of the synthesized compounds were carried out against two gram-positive
bacteria (S. aureus, S. pyogenes), two gram-negative bacteria (E. coli, P. aeruginosa), and three fungal
species (C. albicans, A. niger, A. clavatus) using the broth microdilution method. The compounds 7d,
7g, 7l, 7o, 7p, and 7r possessed pronounced antibacterial activity whereas compound 7p exhibited
promising antifungal activity.
J. Heterocyclic Chem., 47, 923 (2010).
INTRODUCTION
RESULT AND DISCUSSION
Heterocyclic skeleton contained nitrogen atom is the
basic of many pharmaceuticals, to be an active com-
pound. 1,3,4-Oxadiazoles are five member nitrogen
atom contained heterocycles, represent broad spectrum
of biological activity in both agrochemicals and pharma-
ceuticals such as insecticidal [1], herbicidal [2], antibac-
terial [3], antifungal [4], analgesic [5], anti-inflammatory
[6], antimalarial [7], antiviral [8], anti-HBV [9], antia-
nexiety [10], anticancer [11], anti-HIV [12], antitubercu-
lar [13], and anticonvulsant [14]. Quinazolin-4(3H)one
derivatives are six member fused heterocycles, possess
potent pharmacological activities like antibacterial [15],
antifungal [16], analgesic [17], anti-inflammatory [18],
anthelminthic [19], antitumor [20], anticonvulsant [21],
antihistaminic [22], anti HIV [23], antiproliferative [24],
antitubercular [25], antiviral [26], CNS depressant [27],
cytotoxicity [28], diuretic [29], and hypolipidemic [30].
The 1,3,4-oxadiazole and quinazolin-4(3H)one containing
various heterocycle exhibited good pharmacological activ-
ities. The aim of this work was to attach 1,3,4-oxadiazole to
quinazolin-4(3H)one in order to find new biologically active
molecule. Thus, synthesis of novel 1,3,4-oxadiazolyl-quina-
zolin-4(3H)one derivatives has been achieved.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3,1-benzoxazin-
4(H)ones 3a-c were synthesized from substituted anthra-
nilic acids and acid chloride according to the reported
process (Scheme 1) [31,32]. The required 2-[(2,6-dichlo-
rophenyl)amino]phenyl acetyl chloride 2, which is mois-
ture sensitive and easily hydrolysable compound, was
synthesized by reported method [33] and used directly in
the next step. The cyclization reaction of acid chloride
and substituted anthranilic acid in highly basic medium
of pyridine at 0–5ꢀC afforded 2-[2-(2,6-dichlorophenyl)-
amino]benzyl-3,1-benzoxazin-4(H)ones 3a-c. The struc-
tural determinations of these compounds have been
Scheme 1
C
V
2010 HeteroCorporation

924
N. B. Patel and J. C. Patel
Vol 47
Scheme 2
Scheme 3
carried out using IR and NMR spectral data. IR spectra
showed strong C¼¼O and C¼¼N stretching at around 1740
and 1620 cmꢁ1 while 13C-NMR spectra showed C¼¼O
and C¼¼N signal at around d 159 ppm and d 165 ppm
respectively. 2-(4-Aminophenyl)-5-substitutedphenyl-1,3,
4-oxadiazoles 6a-f were synthesized according to reported
method (Scheme 2) [34]. All amino substituted 1,3,4-oxa-
diazole derivatives showed satisfactory IR and NMR
spectral results. Finally the condensation reaction of
4-benzoxazinones 3a-c with amino substituted 1,3,4-oxa-
diazoles 6a-f in pyridine afforded the desired compounds
7a-r (Scheme 3) [35]. IR spectra showed strong C¼¼O
and C¼¼N stretching of quinazolin-4(3H)ones at around
1680 and 1610 cmꢁ1, respectively. 13C-NMR spectra
showed C¼¼O and C¼¼N signal of quinazolin-4(3H)ones
near d 161 ppm and d 163 ppm respectively. All the syn-
thesized compounds showed satisfactory H-NMR spec-
tral results and for all compounds satisfactory elemental
analyses were obtained.
1
The in vitro antibacterial activities of the synthesized
compounds are shown in Table 1. The antibacterial
activities are expressed in terms of Minimal Bactericidal
Concentrations (MBCs lg/mL). The synthesized com-
pounds were screened against two gram positive bacteria
(S. aureus MTCC 96, S. pyogenes MTCC 443) and two
Table 1
Antibacterial activity of compounds 6a-f and 7a-r.
Minimal bactericidal concentration (MBC) (lg/mL)
Gram positive bacteria Gram negative bacteria
S. aureus
MTCC-96
S. pyogenes
MTCC-443
E. coli
MTCC-442
P. aeruginosa
MTCC-441
Compound
R1
R2
6a
6b
6c
6d
6e
6f
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7q
7r
–
–
H
250
500
250
250
500
250
500
500
500
200
250
500
200
500
500
500
500
200
500
250
250
200
150
200
250
250
500
500
250
500
250
1000
250
1000
250
250
250
250
500
500
500
500
250
500
500
250
200
250
150
100
250
500
500
250
500
500
250
150
250
250
500
200
100
150
250
250
500
100
250
100
125
150
500
100
100
200
250
500
500
1000
500
200
100
200
250
500
100
250
200
250
500
1000
250
200
150
150
250
200
250
100
2-OH
4-OH
3-NO2
4-NO2
4-OCH3
H
2-OH
4-OH
3-NO2
4-NO2
4-OCH3
H
–
–
–
–
H
H
H
H
H
H
Br
Br
Br
Br
Br
Br
I
2-OH
4-OH
3-NO2
4-NO2
4-OCH3
H
2-OH
4-OH
3-NO2
4-NO2
4-OCH3
–
I
I
I
I
I
–
Ampicillin
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July 2010
Synthesis and Antimicrobial Activity of Novel 1,3,4-Oxadiazolyl-quinazolin-4(3H)ones
925
Table 2
Antifungal activity of compounds 6a-f and 7a-r.
Minimal Fungicidal Concentration (MFC) (lg/mL)
Fungal species
C. albicans
MTCC-227
A. niger
MTCC-282
A. clavatus
MTCC-323
Compound
R1
R2
6a
6b
6c
6d
6e
6f
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
–
–
–
H
500
250
500
250
> 1000
500
>1000
>1000
>1000
>1000
>1000
>1000
500
2-OH
4-OH
3-NO2
4-NO2
4-OCH3
H
2-OH
4-OH
3-NO2
4-NO2
4-OCH3
H
1000
>1000
>1000
>1000
500
–
–
500
–
>1000
500
500
H
H
H
H
H
H
Br
Br
Br
Br
Br
Br
I
500
500
500
200
250
500
>1000
250
200
>1000
1000
>1000
500
>1000
>1000
>1000
500
1000
500
500
200
2-OH
4-OH
3-NO2
4-NO2
4-OCH3
H
500
500
500
500
500
200
250
500
200
250
>1000
>1000
>1000
500
250
500
1000
100
>1000
>1000
>1000
1000
250
I
2-OH
4-OH
3-NO2
4-NO2
4-OCH3
–
1000
500
200
250
1000
500
I
I
7p
7q
I
I
500
>1000
100
7r
Greseofulvin
–
gram negative bacteria (E. coli MTCC 442, P. aerugi-
nosa MTCC 441). Ampicillin was used as a standard
drug. The results show that some of the amino substi-
tuted 1,3,4-oxadiazoles possessed good activity against
S. aureus while moderate activity against S. pyogenes,
E. coli and P. aeruginosa compared to ampicillin but its
4-quinazolinonyl derivative displayed very good activity
in some cases. Compounds 7d, 7e, 7g, 7l, 7n, 7o, 7p,
7q, and 7r showed very good activity (150–250 lg/mL)
against S. aureus. Compounds 7b, 7d, 7e, 7f, 7g, 7l, 7o,
7p, 7q, and 7r exhibited moderate activity (150–250 lg/
mL) against S. pyogenes. Compounds 7g, 7l, 7n, 7o,
and 7r possessed good activity (100–125 lg/mL) while
7a, 7b, 7c, 7d, 7f, 7h, 7i, 7j, 7m, and 7p showed mod-
erate activity (150–250 lg/mL) against E. coli. Com-
pounds 7b and 7f exhibited good activity (100 lg/mL)
while 7a, 7c, 7d, 7g, 7h, 7i, 7l, 7m, 7n, 7o, 7p, 7q, and
7r possessed moderate activity (150–250 lg/mL) against
P. aeruginosa.
albicans, A. niger and A. clavatus. Greseofulvin was
used as a standard drug. Results show that amino substi-
tuted 1,3,4-oxadiazoles possessed good activity while its
4-quinazolinonyl derivative showed increased activity
against C. albicans. Compounds 7d, 7e, 7g, 7j, 7k, 7l,
7m, 7p, and 7q showed pronounced activity (200–250
lg/mL) against C. albicans. Amino substituted 1,3,4-
oxadiazoles possessed poor activity against A. niger and
A. clavatus while some of its 4-quinazolinonyl deriva-
tive exhibited moderate activity. Compound 7p was
found active against A. niger (MFC ¼ 250 lg/mL)
whereas compounds 7b, 7c, and 7p were found active
against A. clavatus (MFC ¼ 200–250 lg/mL) among
the whole series.
CONCLUSION
The in vitro antimicrobial screening results were found
satisfactory. Amino substituted 1,3,4-oxadiazoles pos-
sessed good antibacterial activity but its 4-quinazolinonyl
derivative showed increased activity in most of cases. All
the compounds displayed very good antifungal activity
In vitro antifungal activity results are shown in Table
2. Antifungal activities are shown in minimal fungicidal
concentrations (MFCs lg/mL). The synthesized com-
pounds were screened against three fungal species C.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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N. B. Patel and J. C. Patel
Vol 47
(CH2), 116.31 (16-C), 118.64 (10-C), 120.62 (14-C), 121.67
(6-C), 124.31 (22-C), 124.57 (8-C), 126.54 (15-C), 127.17 (12-
C), 127.43 (21- and 23-C), 129.41 (20- and 24-C), 131.12 (17-
C), 135.22 (5-C), 137.29 (19-C), 138.23 (7-C), 141.78 (13-C),
148.73 (9-C), 159.23 (4-C), 164.33 ppm (2-C). Anal. Calcd.
for C21H13BrCl2N2O2 (476.15): C, 52.97; H, 2.75; N, 5.88.
Found: C, 52.94; H, 2.74; N, 5.90.
against C. albicans while poor activity was observed
against A. niger and A. clavatus, except 7p, 7b, and 7c
(7p was found active against A. niger and A. clavatus
while 7b and 7c were found active against A. clavatus).
EXPERIMENTAL
2-[2-(2,6-Dichlorophenyl)amino]benzyl-6-iodo-3,1-benzoxa-
zin-4(H)one (3c). This compound was obtained as brown
solid, yield 58%, mp 189–193ꢀC; IR (KBr): NH 3450, CH2
2923, 2848, CO 1745, CN 1617, CO 1148, CCl 747, CI 620
All chemical were of analytical grade and used directly.
Melting points were determined in PMP-DM scientific melting
point apparatus and are uncorrected. The purity of compound
was confirmed by TLC using Merck silica gel 60 F254. Infra-
red spectra were recorded on a Perkin-Elmer RX 1 FTIR spec-
trophotometer, using potassium bromide (KBr) pellets, the fre-
quencies are expressed in cmꢁ1. The nuclear magnetic reso-
nance spectra were recorded with a Bruker Avance II 400
NMR spectrometer, using tetramethylsilane (TMS) as the inter-
nal reference, with dimethylsulphoxide (DMSO-d6) as solvent.
The chemical shifts are reported in parts per million (d ppm).
Elemental analyses were performed on a Heraeus Carlo Erba
1180 CHN analyzer.
1
cmꢁ1; H-NMR (DMSO-d6): d 3.53 (s, 2H, CH2), 6.41 (d, 1H,
14-H, J ¼ 7.92 Hz), 6.89 (t, 1H, 16-H, J ¼ 7.36 Hz), 7.04–
7.09 (m, 2H, 15- and 22-H), 7.22 (d, 1H, 17-H, J ¼ 7.54 Hz),
7.25 (d, 1H, 8-H, J ¼ 8.28 Hz), 7.42 (d, 2H, 21- and 23-H, J
¼ 8.12 Hz), 8.05 (d, 1H, 7-H, J ¼ 8.28 Hz), 8.48 (s, 1H, 5-H),
9.10 ppm (br s, 1H, NH); 13C-NMR (DMSO-d6): d 32.53
(CH2), 93.14 (6-C), 116.25 (16-C), 118.23 (10-C), 120.57 (14-
C), 123.74 (8-C), 124.19 (22-C), 126.58 (15-C), 127.05 (12-
C), 127.33 (21- and 23-C), 129.39 (20- and 24-C), 131.14 (17-
C), 137.42 (19-C), 138.87 (5-C), 141.81 (13-C), 144.27 (7-C),
148.62 (9-C), 159.53 (4-C), 164.47 ppm (2-C). Anal. Calcd.
for C21H13Cl2IN2O2 (523.15): C, 48.21; H, 2.50; N, 5.35.
Found: C, 48.25; H, 2.49; N, 5.33.
General procedure for the synthesis of 2-(4-amino-
phenyl)-5-substitutedphenyl-1,3,4-oxadiazoles (6a-f). A mix-
ture of 0.69 g (0.005 mole) of 4-amino benzoic acid and sub-
stituted benzoic acid hydrazides (0.005 mole) in 5 mL of phos-
phorus oxychloride was refluxed on water bath for 7–10 h.
The progress of the reaction was monitored by TLC using tol-
uene:ethylacetate:methanol (70:20:10) as mobile phase. After
the completion of reaction, it was cooled and poured onto
crushed ice with continuous stirring. The solid mass separated
was neutralized with sodium bicarbonate solution (10% w/v).
The resulting solid thus obtained was collected by filtration,
washed well with cold water, dried and crystallized from abso-
lute ethanol.
General procedure for the synthesis of 2-[2-(2,6-dichloro-
phenyl)amino]benzyl-3,1-benzoxazin-4(H)ones
(3a-c). The
mixture of 3.05 g (0.01 mole) of acid chloride (2) and 1.37 g
(0.01 mole) of anthranilic acid (1a) in 20 mL of dry pyridine
were stirred at 0–5 ꢀC for 1 h, further stirred for 1 h at room
temperature. Progress of reaction was check by TLC using tol-
uene:ethylacetate (80:20) as mobile phase. After completion of
reaction, a pasty mass obtained, was washed thoroughly with
sodium bicarbonate (5% w/v) to remove unreacted acid. A
solid separated was filtered, dried and recrystallized from
methanol. Other benzoxazinone derivatives 3b, c were synthe-
sized by the same method.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3,1-benzoxazin-4(H)
one (3a). This compound was obtained as reddish solid, yield
53%, mp 183–186ꢀC; IR (KBr): NH 3449, CH2 2925, 2851,
1
CO 1742, CN 1620, CN 1316, CO 1151, CCl 745 cmꢁ1; H-
NMR (DMSO-d6): d 3.52 (s, 2H, CH2), 6.39 (d, 1H, 14-H, J
¼ 7.96 Hz), 6.88 (t, 1H, 16-H, J ¼ 7.4 Hz), 7.04–7.09 (m, 2H,
15- and 22-H), 7.21 (d, 1H, 17-H, J ¼ 7.54 Hz), 7.42 (d, 2H,
21- and 23-H, J ¼ 8.08 Hz), 7.51 (d, 1H, 8-H, J ¼ 8.12 Hz),
7.84 (t, 1H, 7-H, J ¼ 7.8 Hz), 8.06 (t, 1H, 6-H, J ¼ 7.64 Hz),
8.12 (d, 1H, 5-H, J ¼ 7.72 Hz), 9.12 ppm (br s, 1H, NH); 13C-
NMR (DMSO-d6): d 32.47 (CH2), 116.27 (16-C), 116.54 (10-
C), 120.54 (14-C), 122.35 (8-C), 124.15 (22-C), 126.61 (15-
C), 127.12 (12-C), 127.32 (21- and 23-C), 127.54 (6-C),
129.34 (20- and 24-C), 131.23 (17-C), 131.52 (5-C), 135.43
(7-C), 137.23 (19-C), 141.76 (13-C), 149.53 (9-C), 159.36
(4-C), 164.51 ppm (2-C). Anal. Calcd. for C21H14Cl2N2O2
(397.25): C, 63.49; H, 3.55; N, 7.05. Found: C, 63.45; H,
3.56; N, 7.03.
2-(4-Aminophenyl)-5-phenyl-1,3,4-oxadiazole
(6a). This
compound was obtained as white solid, yield 72%, mp 196–
200ꢀC; IR (KBr): NH2 3495, 3405, CN 1655, COC 1277,
;
1035 cmꢁ1 1H-NMR (DMSO-d6): d 5.44 (s, 2H, NH2), 6.81
(d, 2H, 8- and 10-H, J ¼ 8.4 Hz), 7.30 (d, 2H, 7- and 11-H, J
¼ 8.4 Hz), 7.41 (t, 3H, 14-, 15- and 16-H, J ¼ 6.24 Hz), 7.80
ppm (dd, 2H, 13- and 17-H, J ¼ 6.48 Hz, 1.96 Hz); 13C-NMR
(DMSO-d6): d 107.47 (6-C), 114.53 (8- and 10-C), 124.34
(12-C), 124.87 (13- and 17-C), 128.53 (15-C), 128.74 (7- and
11-C), 129.82 (14- and 16-C), 148.56 (9-C), 163.15 ppm (2-
and 5-C). Anal. Calcd. for C14H11N3O (237.26): C, 70.87; H,
4.67; N, 17.71. Found: C, 70.78; H, 4.65; N, 17.77.
2-(4-Aminophenyl)-5-(2-hydroxyphenyl)-1,3,4-oxadiazole
(6b). This compound was obtained as white solid, yield 74%,
mp 167–171ꢀC; IR (KBr): NH2 3502, 3408, OH 3135, CN
2-[2-(2,6-Dichlorophenyl)amino]benzyl-6-bromo-3,1-benzoxa-
zin-4(H)one (3b). This compound was obtained as orange
solid, yield 55%, mp 194–198ꢀC; IR (KBr): NH 3446, CH2
2926, 2850, CO 1740, CN 1618, CO 1153, CCl 743, CBr 565
1
1661, COC 1265, 1058 cmꢁ1; H-NMR (DMSO-d6): d 5.46 (s,
2H, NH2), 6.78 (d, 2H, 8- and 10-H, J ¼ 8.36 Hz), 6.92 (t,
1H, 16-H, J ¼ 7.56 Hz), 6.97 (d, 1H, 14-H, J ¼ 8.12 Hz),
7.24 (t, 1H, 15-H, J ¼ 7.76 Hz), 7.29 (d, 2H, 7- and 11-H, J
¼ 8.36 Hz), 7.45 (dd, 1H, 17-H, J ¼ 7.72 Hz), 10.05 ppm (br
s, 1H, OH); 13C-NMR (DMSO-d6): d 107.52 (6-C), 109.15
(12-C), 114.48 (8- and 10-C), 116.58 (14-C), 119.57 (16-C),
125.42 (17-C), 128.82 (7- and 11-C), 131.63 (15-C), 148.65
(9-C), 155.67 (13-C), 162.74 ppm (2- and 5-C). Anal. Calcd.
1
cmꢁ1; H-NMR (DMSO-d6): d 3.53 (s, 2H, CH2), 6.40 (d, 1H,
14-H, J ¼ 8 Hz), 6.88 (t, 1H, 16-H, J ¼ 7.44 Hz), 7.03–7.08
(m, 2H, 15- and 22-H), 7.22 (d, 1H, 17-H, J ¼ 7.58 Hz), 7.41
(d, 2H, 21- and 23-H, J ¼ 8.16 Hz), 7.65 (d, 1H, 8-H, J ¼
8.32 Hz), 8.12 (d, 1H, 7-H, J ¼ 8.32 Hz), 8.16 (s, 1H, 5-H),
9.10 ppm (br s, 1H, NH); 13C-NMR (DMSO-d6): d 32.43
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Synthesis and Antimicrobial Activity of Novel 1,3,4-Oxadiazolyl-quinazolin-4(3H)ones
927
for C14H11N3O2 (253.26): C, 66.40; H, 4.38; N, 16.59. Found:
C, 66.34; H, 4.41; N, 16.64.
2-(4-Aminophenyl)-5-(4-hydroxyphenyl)-1,3,4-oxadiazole
(6c). This compound was obtained as white solid, yield 78%,
mp 190–195ꢀC; IR (KBr): NH2 3475, 3415, OH 3152, CN 1653,
COC 1285, 1023 cmꢁ1 1H-NMR (DMSO-d6): d 5.45 (s, 2H,
;
(70:20:10) was used as mobile phase. The product obtained
was filtered and washed several times with cold water, dried
and recrystallized from ethanol.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-[4-(5-phenyl-1,3,4-
oxadiazol-2-yl)phenyl] quinazolin-4(3H)one (7a). This com-
pound was obtained as white solid, yield 57%, mp 240–244ꢀC;
IR (KBr): NH 3445, CH2 2927, 2852, CO 1681, CN 1649,
NH2), 5.61 (br s, 1H, OH), 6.80 (d, 2H, 8- and 10-H, J ¼ 8.36),
6.93 (d, 2H, 14- and 16-H, J ¼ 8.46 Hz), 7.32 (d, 2H, 7- and
11-H, J ¼ 8.36 Hz), 7.69 ppm (d, 2H, 13- and 17-H, J ¼ 8.46
Hz); 13C-NMR (DMSO-d6): d 107.37 (6-C), 114.42 (8- and 10-
C), 116.63 (14- and 16-C), 118.22 (12-C), 128.34 (13- and 17-
C), 128.66 (7- and 11-C), 148.46 (9-C), 160.18 (15-C), 163.57
ppm (2- and 5-C). Anal. Calcd. for C14H11N3O2 (253.26): C,
66.40; H, 4.38; N, 16.59. Found: C, 66.43; H, 4.35; N, 16.57.
2-(4-Aminophenyl)-5-(3-nitrophenyl)-1,3,4-oxadiazole (6d). This
compound was obtained as pale yellow solid, yield 80%, mp
210–214ꢀC; ir (KBr): NH2 3489, 3407, CN 1658, NO2 1531,
1
1611, COC 1273, 1057, CCl 748 cmꢁ1; H-NMR (DMSO-d6):
d 3.52 (s, 2H, CH2), 6.39 (d, 1H, 14-H, J ¼ 7.96 Hz), 6.89 (t,
1H, 16-H, J ¼ 7.4 Hz), 7.04–7.09 (m, 2H, 15- and 22-H), 7.21
(d, 1H, 17-H, J ¼ 7.56 Hz), 7.38–7.45 (m, 7H, 21-, 23-, 26-,
30-, 38-, 39- and 40-H), 7.49–7.55 (m, 3H, 6-, 27- and 29-H),
7.59 (d, 1H, 8-H, J ¼ 8.12 Hz), 7.75 (t, 1H, 7-H, J ¼ 7.8 Hz),
7.83 (dd, 2H, 37- and 41-H, J ¼ 6.44 Hz, 1.92 Hz), 8.11 (d,
1H, 5-H, J ¼ 7.68 Hz), 9.12 ppm (br s, 1H, NH); 13C-NMR
(DMSO-d6): d 32.47 (11-C), 116.18 (16-C), 120.41 (14-C),
120.82 (10-C), 121.46 (28-C), 121.84 (26- and 30-C), 122.57
(8-C), 124.28 (22-C), 124.36 (36-C), 124.85 (37- and 41-C),
126.79 (15-C), 127.25 (12-C), 127.48 (21- and 23-C), 127.63
(6-C), 127.73 (27- and 29-C), 128.55 (39-C), 128.81 (5-C),
129.42 (20- and 24-C), 129.84 (38- and 40-C), 131.16 (17-C),
132.69 (25-C), 133.72 (7-C), 137.22 (19-C), 141.75 (13-C),
147.21 (9-C), 160.67 (4-C), 162.65 (2-C), 163.07 ppm (32-
and 35-C). Anal. Calcd. for C35H23Cl2N5O2 (616.5): C, 68.19;
H, 3.76; N, 11.36. Found: C, 68.12; H, 3.71; N, 11.41.
1
1352, COC 1280, 1024 cmꢁ1; H-NMR (DMSO-d6): d 5.47 (s,
2H, NH2), 6.78 (d, 2H, 8- and 10-H, J ¼ 8.4 Hz), 7.31 (d, 2H,
7- and 11-H, J ¼ 8.4 Hz), 7.82 (t, 1H, 16-H, J ¼ 7.84 Hz),
8.23 (d, 1H, 17-H, J ¼ 7.12 Hz), 8.34 (d, 1H, 15-H, J ¼ 7.72
Hz), 8.45 ppm (s, 1H, 13-H); 13C-NMR (DMSO-d6): d 107.59
(6-C), 114.68 (8- and 10-C), 120.17 (13-C), 124.37 (15-C),
125.68 (12-C), 128.64 (7- and 11-C), 130.74 (16-C), 133.43
(17-C), 148.42 (14-C), 148.55 (9-C), 163.95 ppm (2- and 5-C).
Anal. Calcd. for C14H10N4O3 (282.25): C, 59.57; H, 3.57; N,
19.85. Found: C, 59.51; H, 3.54; N, 19.80.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(2-hydrox-
yphenyl)-1,3,4-oxadiazol-2-yl]phenyl}quinazolin-4(3H)one
(7b). This compound was obtained as off white solid, yield
61%, mp 228–232ꢀC; IR (KBr): NH 3451, OH 3130, CH2
2924, 2850, CO 1678, CN 1661, 1610, COC 1263, 1060, CCl
2-(4-Aminophenyl)-5-(4-nitrophenyl)-1,3,4-oxadiazole (6e). This
compound was obtained as light yellow solid, yield 85%, mp
201–205ꢀC; ir (KBr): NH2 3498, 3410, CN 1655, NO2 1535,
1
1
1354, COC 1283, 1027 cmꢁ1; H-NMR (DMSO-d6): d 5.45 (s,
745 cmꢁ1; H-NMR (DMSO-d6): d 3.54 (s, 2H, CH2), 6.41 (d,
2H, NH2), 6.81 (d, 2H, 8- and 10-H, J ¼ 8.36 Hz), 7.32 (d,
2H, 7- and 11-H, J ¼ 8.36 Hz), 8.07 (d, 2H, 13- and 17-H, J
¼ 8.76 Hz), 8.32 ppm (d, 2H, 14- and 16-H, J ¼ 8.76 Hz);
13C-NMR (DMSO-d6): d 107.56 (6-C), 114.57 (8- and 10-C),
124.55 (14- and 16-C), 127.18 (13- and 17-C), 128.75 (7- and
11-C), 131.23 (12-C), 148.18 (15-C), 148.67 (9-C), 164.28
ppm (2- and 5-C). Anal. Calcd. for C14H10N4O3 (282.25): C,
59.57; H, 3.57; N, 19.85. Found: C, 59.54; H, 3.59; N, 19.83.
2-(4-Aminophenyl)-5-(4-methoxyphenyl)-1,3,4-oxadiazole
(6f). This compound was obtained as white solid, yield 75%,
mp 203–207ꢀC; ir (KBr): NH2 3505, 3415, CN 1660, COC
1H, 14-H, J ¼ 8 Hz), 6.88 (t, 1H, 16-H, J ¼ 7.44 Hz), 6.93 (t,
1H, 40-H, J ¼ 7.52 Hz), 6.98 (d, 1H, 38-H, J ¼ 8.12 Hz),
7.03–7.08 (m, 2H, 15- and 22-H), 7.21–7.26 (m, 2H, 17- and
39-H), 7.41 (d, 2H, 21- and 23-H, J ¼ 8.12 Hz), 7.45 (d, 2H,
26- and 30-H, J ¼ 8.32 Hz), 7.47–7.54 (m, 4H, 6-, 27-, -29
and 41-H), 7.58 (d, 1H, 8-H, J ¼ 8.16 Hz), 7.77 (t, 1H, 7-H, J
¼ 7.84 Hz), 8.09 (d, 1H, 5-H, J ¼ 7.72 Hz), 9.08 (br s, 1H,
NH), 10.04 ppm (br s, 1H, OH); 13C-NMR (DMSO-d6): d
32.54 (11-C), 109.22 (36-C), 116.14 (16-C), 116.61 (38-C),
119.63 (40-C), 120.51 (14-C), 120.84 (10-C), 121.48 (28-C),
121.76 (26- and 30-C), 122.53 (8-C), 124.32 (22-C), 125.42
(41-C), 126.73 (15-C), 127.28 (12-C), 127.44 (21- and 23-C),
127.62 (6-C), 127.85 (27- and 29-C), 128.75 (5-C), 129.36
(20- and 24-C), 131.11 (17-C), 131.64 (39-C), 132.52 (25-C),
133.68 (7-C), 137.23 (19-C), 141.83 (13-C), 147.25 (9-C),
155.75 (37-C), 160.58 (4-C), 162.55 (2-C), 162.68 ppm (32-
and 35-C). Anal. Calcd. for C35H23Cl2N5O3 (632.49): C,
66.46; H, 3.67; N, 11.07. Found: C, 66.53; H, 3.63; N, 11.03.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(4-hydrox-
yphenyl)-1,3,4-oxadiazol-2-yl]phenyl}quinazolin-4(3H)one
(7c). This compound was obtained as white solid, yield 65%,
mp 251–255ꢀC; IR (KBr): NH 3453, OH 3151, CH2 2928,
2855, CO 1677, CN 1650, 1607, COC 1278, 1022, CCl 741
;
1257, 1025 cmꢁ1 1H-NMR (DMSO-d6): d 3.59 (s, 3H,
OCH3), 5.43 (s, 2H, NH2), 6.77 (d, 2H, 8- and 10-H, J ¼ 8.4
Hz), 6.80 (d, 2H, 14- and 16-H, J ¼ 8.72 Hz), 7.26 (d, 2H, 7-
and 11-H, J ¼ 8.4 Hz), 7.46 ppm (d, 2H, 13- and 17-H, J ¼
8.72 Hz); 13C-NMR (DMSO-d6): d 55.19 (OCH3), 107.43 (6-
C), 114.28 (14- and 16-C), 114.45 (8- and 10-C), 116.85 (12-
C), 126.57 (13- and 17-C), 128.62 (7- and 11-C), 148.51 (9-
C), 160.61 (15-C), 163.77 ppm (2- and 5-C). Anal. Calcd. for
C15H13N3O2 (267.28): C, 67.40; H, 4.90; N, 15.72. Found: C,
67.48; H, 4.86; N, 15.75.
General procedure for the synthesis of 2-[2-(2,6-dichloro-
phenyl)amino]benzyl-3-{4-[5-(substituted phenyl)-1,3,4-oxa-
diazol-2-yl]phenyl}quinazolin-4(3H)ones (7a-r). A mixture
of 4-benzoxazinone (0.0025 mole) and 2-(4-aminophenyl)-5-
substitutedphenyl-1,3,4-oxadiazole (0.0025 mole) in 10 mL of
pyridine was refluxed on an oil bath for 6–8 h. After comple-
tion of the reaction, the oily mass was slowly poured onto
crushed ice cold water contained HCl (5 mL) with continues
stirring. For TLC monitoring toluene:ethylacetate:methanol
cmꢁ1 1H-NMR (DMSO-d6): d 3.51 (s, 2H, CH2), 5.59 (br s,
;
1H, OH), 6.40 (d, 1H, 14-H, J ¼ 7.96 Hz), 6.90–6.95 (m, 3H,
16-, 38- and 40-H), 7.04–7.10 (m, 2H, 15- and 22-H), 7.23 (d,
1H, 17-H, J ¼ 7.52 Hz), 7.39 (d, 2H, 21- and 23-H, J ¼ 8.08
Hz), 7.44 (d, 2H, 26- and 30-H, J ¼ 8.36 Hz), 7.50 (t, 1H, 6-
H, J ¼ 7.56 Hz), 7.55 (d, 2H, 27- and 29-H, J ¼ 8.36 Hz),
7.61 (d, 1H, 8-H, J ¼ 8.12 Hz), 7.70 (d, 2H, 37- and 41-H, J
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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N. B. Patel and J. C. Patel
Vol 47
¼ 8.44 Hz), 7.78 (t, 1H, 7-H, J ¼ 7.76 Hz), 8.12 (d, 1H, 5-H,
J ¼ 7.64 Hz), 9.13 ppm (br s, 1H, NH); 13C NMR (DMSO-
d6): d 32.51 (11-C), 116.12 (16-C), 116.68 (38- and 40-C),
118.31 (36-C), 120.54 (14-C), 120.78 (10-C), 121.53 (28-C),
121.87 (26- and 30-C), 122.46 (8-C), 124.32 (22-C), 126.84
(15-C), 127.31 (12-C), 127.37 (21- and 23-C), 127.64 (6-C),
127.77 (27- and 29-C), 128.29 (37- and 41-C), 128.82 (5-C),
129.44 (20- and 24-C), 131.19 (17-C), 132.63 (25-C), 133.74
(7-C), 137.22 (19-C), 141.76 (13-C), 147.23 (9-C), 160.22 (39-
C), 160.64 (4-C), 162.74 (2-C), 163.52 ppm (32- and 35-C);
Anal. Calcd. for C35H23Cl2N5O3 (632.49): C, 66.46; H, 3.67;
N, 11.07. Found: C, 66.42; H, 3.72; N, 11.01.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(4-methoxy-
phenyl)-1,3,4-oxadiazol-2-yl] phenyl}quinazolin-4(3H)one
(7f). This compound was obtained as off white, yield 67%,
mp 265-268ꢀC; ir (KBr): NH 3453, CH2 2924, 2850, CO
1672, CN 1654, 1608, COC 1257, 1023, CCl 743 cmꢁ1 1H
;
nmr (DMSO-d6): d; 3.51 (s, 2H, CH2), 3.60 (s, 3H, OCH3),
6.38 (d, 1H, 14-H, J ¼ 7.96 Hz), 6.79 (d, 2H, 38- and 40-H, J
¼ 8.68 Hz), 6.88 (t, 1H, 16-H, J ¼ 7.36 Hz), 7.03–7.08 (m,
2H, 15- and 22-H), 7.19 (d, 1H, 17-H, J ¼ 7.52 Hz), 7.39–
7.56 (m, 9H, 6-, 21-, 23-, 26-, 27-, 29-, 30-, 37- and 41-H),
7.62 (d, 1H, 8-H, J ¼ 8.16 Hz), 7.75 (t, 1H, 7-H, J ¼ 7.84
Hz), 8.12 (d, 1H, 5-H, J ¼ 7.68 Hz), 9.15 ppm (br s, 1H, NH);
13C-NMR (DMSO-d6): d 32.53 (11-C), 55.23 (OCH3), 114.32
(38- and 40-C), 116.14 (16-C), 116.79 (36-C), 120.47 (14-C),
120.74 (10-C), 121.54 (28-C), 121.83 (26- and 30-C), 122.56
(8-C), 124.27 (22-C), 126.62 (37- and 41-C), 126.74 (15-C),
127.22 (12-C), 127.42 (21- and 23-C), 127.51 (6-C), 127.75
(27- and 29-C), 128.76 (5-C), 129.43 (20- and 24-C), 131.13
(17-C), 132.70 (25-C), 133.66 (7-C), 137.23 (19-C), 141.72
(13-C), 147.16 (9-C), 160.56 (39-C), 160.73 (4-C), 162.78
(2-C), 163.75 ppm (32- and 35-C). Anal. Calcd. for
C36H25Cl2N5O3 (646.52): C, 66.88; H, 3.90; N, 10.83. Found:
C, 66.97; H, 3.88; N, 10.78.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(3-nitrophenyl)-
1,3,4-oxadiazol-2-yl] phenyl}quinazolin-4(3H)one (7d). This
compound was obtained as light orange solid, yield 58%, mp
280–285ꢀC; IR (KBr): NH 3443, CH2 2918, 2847, CO 1675,
CN 1653, 1610, NO2 1533, 1351, COC 1275, 1024, CCl 744
1
cmꢁ1; H NMR (DMSO-d6): d 3.55 (s, 2H, CH2), 6.42 (d, 1H,
14-H, J ¼ 7.96 Hz), 6.91 (t, 1H, 16-H, J ¼ 7.44 Hz), 7.03–
7.09 (m, 2H, 15- and 22-H), 7.23 (d, 1H, 17-H, J ¼ 7.6 Hz),
7.42 (d, 2H, 21- and 23-H, J ¼ 8.16 Hz), 7.47 (d, 2H, 26- and
30-H, J ¼ 8.28 Hz), 7.52 (t, 1H, 6-H, J ¼ 7.6 Hz), 7.57 (d,
2H, 27- and 29-H, J ¼ 8.28 Hz), 7.62 (d, 1H, 8-H, J ¼ 8.12
Hz), 7.74 (t, 1H, 7-H, J ¼ 7.8 Hz), 7.84 (t, 1H, 40-H, J ¼ 7.8
Hz), 8.11 (d, 1H, 5-H, J ¼ 7.68 Hz), 8.26 (d, 1H, 41-H, J ¼
7.12 Hz), 8.36 (d, 1H, 39-H, J ¼ 7.68 Hz), 8.46 (s, 1H, 37-H),
9.11 ppm (br s, 1H, NH); 13C-NMR (DMSO-d6): d 32.46 (11-
C), 116.23 (16-C), 120.22 (37-C), 120.53 (14-C), 120.64 (10-
C), 121.47 (28-C), 121.75 (26- and 30-C), 122.45 (8-C),
124.34 (22-C), 124.46 (39-C), 125.73 (36-C), 126.73 (15-C),
127.21 (12-C), 127.47 (21- and 23-C), 127.58 (6-C), 127.65
(27- and 29-C), 128.85 (5-C), 129.52 (20- and 24-C), 130.78
(40-C), 131.21 (17-C), 132.54 (25-C), 133.45 (41-C), 133.62
(7-C), 137.19 (19-C), 141.68 (13-C), 147.07 (9-C), 148.51 (38-
C), 160.53 (4-C), 162.77 (2-C), 163.89 ppm (32- and 35-C).
Anal. Calcd. for C35H22Cl2N6O4 (661.49): C, 63.55; H, 3.35;
N, 12.70. Found: C, 63.48; H, 3.39; N, 12.75.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-[4-(5-phenyl-1,
3,4-oxadiazol-2-yl)phenyl]-6-bromo-quinazolin-4(3H)one
(7g). This compound was obtained as light reddish, yield
63%, mp 261–264ꢀC; IR (KBr): NH 3452, CH2 2929, 2855,
CO 1682, CN 1651, 1614, COC 1272, 1053, CCl 742, CBr
1
574 cmꢁ1; H nmr (DMSO-d6): d 3.54 (s, 2H, CH2), 6.41 (d,
1H, 14-H, J ¼ 8 Hz), 6.89 (t, 1H, 16-H, J ¼ 7.48 Hz), 7.04–
7.09 (m, 2H, 15- and 22-H), 7.22 (d, 1H, 17-H, J ¼ 7.6 Hz),
7.39–7.44 (m, 5H, 21-, 23-, 38-, 39- and 40-H), 7.46 (d, 2H,
26- and 30-H, J ¼ 8.32 Hz), 7.55 (d, 2H, 27- and 29-H, J ¼
8.32 Hz), 7.65 (d, 1H, 8-H, J ¼ 8.36 Hz), 7.81 (dd, 2H, 37-
and 41-H, J ¼ 6.48 Hz, 1.96 Hz), 8.06 (d, 1H, 7-H, J ¼ 8.36
Hz), 8.15 (s, 1H, 5-H), 9.11 ppm (br s, 1H, NH); 13C-NMR
(DMSO-d6): d 32.55 (11-C), 116.16 (16-C), 120.57 (14-C),
121.41 (28-C), 121.54 (6-C), 121.74 (26- and 30-C), 123.18
(10-C), 124.26 (22-C), 124.35 (36-C), 124.58 (8-C), 124.84
(37- and 41-C), 126.85 (15-C), 127.24 (12-C), 127.47 (21-
and 23-C), 127.62 (27- and 29-C), 128.54 (39-C), 129.46
(20- and 24-C), 129.80 (38- and 40-C), 131.15 (17-C),
132.26 (5-C), 132.53 (25-C), 136.41 (7-C), 137.31 (19-C),
141.82 (13-C), 146.23 (9-C), 160.71 (4-C), 162.74 (2-C),
163.11 ppm (32- and 35-C). Anal. Calcd. for
C35H22BrCl2N5O2 (695.39): C, 60.45; H, 3.19; N, 10.07.
Found: C, 60.54; H, 3.12; N, 10.11.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(4-nitrophenyl)-
1,3,4-oxadiazol-2-yl] phenyl}quinazolin-4(3H)one (7e). This
compound was obtained as pale yellow solid, yield 74%, mp
245–249ꢀC; IR (KBr): NH 3448, CH2 2927, 2852, CO 1676,
CN 1652, 1612, NO2 1537, 1356, COC 1282, 1028, CCl 747
1
cmꢁ1; H-NMR (DMSO-d6): d 3.53 (s, 2H, CH2), 6.39 (d, 1H,
14-H, J ¼ 7.92 Hz), 6.89 (t, 1H, 16-H, J ¼ 7.36 Hz), 7.04–
7.10 (m, 2H, 15- and 22-H), 7.21 (d, 1H, 17-H, J ¼ 7.52 Hz),
7.39 (d, 2H, 21- and 23-H, J ¼ 8.04 Hz), 7.45 (d, 2H, 26- and
30-H, J ¼ 8.36 Hz), 7.48 (t, 1H, 6-H, J ¼ 7.64 Hz), 7.55 (d,
2H, 27- and 29-H, J ¼ 8.36 Hz), 7.61 (d, 1H, 8-H, J ¼ 8.16
Hz), 7.76 (t, 1H, 7-H, J ¼ 7.84 Hz), 8.05 (d, 2H, 37- and 41-
H, J ¼ 8.72 Hz), 8.10 (d, 1H, 5-H, J ¼ 7.72 Hz), 8.34 (d, 2H,
38- and 40-H, J ¼ 8.72 Hz), 9.13 ppm (br s, 1H, NH); 13C
NMR (DMSO-d6): d 32.61 (11-C), 116.27 (16-C), 120.63 (14-
C), 120.73 (10-C), 121.54 (28-C), 121.82 (26- and 30-C),
122.58 (8-C), 124.26 (22-C), 124.47 (38- and 40-C), 126.62
(15-C), 127.12 (37- and 41-C), 127.33 (12-C), 127.55 (21- and
23-C), 127.63 (6-C), 127.74 (27- and 29-C), 128.76 (5-C),
129.44 (20- and 24-C), 131.18 (36-C), 131.27 (17-C), 132.63
(25-C), 133.56 (7-C), 137.29 (19-C), 141.77 (13-C), 147.15 (9-
C), 148.13 (39-C), 160.65 (4-C), 162.63 (2-C), 164.25 ppm
(32- and 35-C). Anal. Calcd. for (661.49): C, 63.55; H, 3.35;
N, 12.70. Found: C, 63.46; H, 3.41; N, 12.74.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(2-hydroxy-
phenyl)-1,3,4-oxadiazol-2-yl] phenyl}-6-bromo-quinazolin-4(3H)one
(7h). This compound was obtained as white solid, yield 55%,
mp 246–250ꢀC; IR (KBr): NH 3448, OH 3128, CH2 2928,
2850, CO 1679, CN 1658, 1607, COC 1260, 1055, CCl 745,
C-Br 566 cmꢁ1 1H-NMR (DMSO-d6): d 3.53 (s, 2H, CH2),
;
6.39 (d, 1H, 14-H, J ¼ 7.96 Hz), 6.88–6.93 (m, 2H, 16- and
40-H), 6.96 (d, 1H, 38-H, J ¼ 8.12 Hz), 7.04–7.10 (m, 2H,
15- and 22-H), 7.21 (d, 1H, 17-H, J ¼ 7.56 Hz), 7.26 (t, 1H,
39-H, J ¼ 7.76 Hz), 7.40–7.46 (m, 5H, 21-, 23-, 26-, 30- and
41-H), 7.54 (d, 2H, 27- and 29-H, J ¼ 8.28 Hz), 7.67 (d, 1H,
8-H, J ¼ 8.32 Hz), 8.08 (d, 1H, 7-H, J ¼ 8.32 Hz), 8.16 (s,
1H, 5-H), 9.08 (br s, 1H, NH), 10.06 ppm (br s, 1H, OH);
13C-NMR (DMSO-d6): d 32.48 (11-C), 109.18 (36-C), 116.12
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Synthesis and Antimicrobial Activity of Novel 1,3,4-Oxadiazolyl-quinazolin-4(3H)ones
929
(16-C), 116.59 (38-C), 119.54 (40-C), 120.53 (14-C), 121.46
(6-C), 121.57 (28-C), 121.86 (26- and 30-C), 123.14 (10-C),
124.33 (22-C), 124.66 (8-C), 125.38 (41-C), 126.75 (15-C),
127.15 (12-C), 127.36 (21- and 23-C), 127.79 (27- and 29-C),
129.34 (20- and 24-C), 131.10 (17-C), 131.57 (39-C),
132.17 (5-C), 132.74 (25-C), 136.39 (7-C), 137.22 (19-C),
141.76 (13-C), 146.34 (9-C), 155.66 (37-C), 160.67 (4-C),
162.58 (2-C), 162.74 ppm (32- and 35-C). Anal. Calcd. for
C35H22BrCl2N5O3 (711.39): C, 59.09; H, 3.12; N, 9.84. Found:
C, 58.95; H, 3.17; N, 9.89.
mp 258–262ꢀC; IR (KBr): NH 3440, CH2 2918, 2844, CO
1673, CN 1647, 1605, NO2 1536, 1356, COC 1267, 1023, CCl
741, CBr 561 cmꢁ1 1H NMR (DMSO-d6): d 3.52 (s, 2H,
;
CH2), 6.43 (d, 1H, 14-H, J ¼ 7.92 Hz), 6.91 (t, 1H, 16-H, J ¼
7.36 Hz), 7.04–7.09 (m, 2H, 15- and 22-H), 7.20 (d, 1H, 17-H,
J ¼ 7.52 Hz), 7.41 (d, 2H, 21- and 23-H, J ¼ 8.08 Hz), 7.46
(d, 2H, 26- and 30-H, J ¼ 8.36 Hz), 7.57 (d, 2H, 27- and 29-
H, J ¼ 8.36 Hz), 7.65 (d, 1H, 8-H, J ¼ 8.36 Hz), 8.05 (d, 1H,
7-H, J ¼ 8.36 Hz), 8.08 (d, 2H, 37- and 41-H, J ¼ 8.68 Hz),
8.15 (s, 1H, 5-H), 8.31 (d, 2H, 38- and 40-H, J ¼ 8.68 Hz),
9.13 ppm (br s, 1H, NH); 13C NMR (DMSO-d6): d 32.55 (11-
C), 116.27 (16-C), 120.56 (14-C), 121.54 (6-C), 121.63 (28-
C), 121.85 (26- and 30-C), 123.05 (10-C), 124.36 (22-C),
124.42 (8-C), 124.64 (38- and 40-C), 126.94 (15-C), 127.15
(37- and 41-C), 127.26 (12-C), 127.54 (21- and 23-C), 127.77
(27- and 29-C), 129.43 (20- and 24-C), 131.17 (36-C), 131.24
(17-C), 132.19 (5-C), 132.59 (25-C), 136.54 (7-C), 137.20 (19-
C), 141.91 (13-C), 146.24 (9-C), 148.15 (39-C), 160.72 (4-C),
162.81 (2-C), 164.33 ppm (32- and 35-C). Anal. Calcd. for
C35H21BrCl2N6O4 (740.39): C, 56.78; H, 2.86; N, 11.35.
Found: C, 56.68; H, 2.89; N, 11.31.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(4-hydroxy-
phenyl)-1,3,4-oxadiazol-2-yl]
phenyl}-6-bromo-quinazolin-
4(3H)one (7i). This compound was obtained as off white
solid, yield 66%, mp 232–236ꢀC; IR (KBr): NH 3450, OH
3143, CH2 2924, 2849, CO 1672, CN 1656, 1610, COC 1274,
;
1022, CCl 739, CBr 571 cmꢁ1 1H-NMR (DMSO-d6): d 3.55
(s, 2H, CH2), 5.62 (br s, 1H, OH), 6.43 (d, 1H, 14-H, J ¼ 8
Hz), 6.90–6.96 (m, 3H, 16-, 38-, and 40-H), 7.04–7.09 (m, 2H,
15- and 22-H), 7.23 (d, 1H, 17-H, J ¼ 7.6 Hz), 7.41 (d, 2H,
21- and 23-H, J ¼ 8.12 Hz), 7.47 (d, 2H, 26- and 30-H, J ¼
8.32 Hz), 7.56 (d, 2H, 27- and 29-H, J ¼ 8.32 Hz), 7.64 (d,
1H, 8-H, J ¼ 8.36 Hz), 7.71 (d, 2H, 37- and 41-H, J ¼ 8.48
Hz), 8.05 (d, 1H, 7-H, J ¼ 8.36 Hz), 8.12 (s, 1H, 5-H), 9.14
ppm (br s, 1H, NH); 13C NMR (DMSO-d6): d 32.55 (11-C),
116.18 (16-C), 116.65 (38- and 40-C), 118.26 (36-C), 120.52
(14-C), 121.53 (6-C), 121.64 (28-C), 121.89 (26- and 30-C),
123.24 (10-C), 124.37 (22-C), 124.45 (8-C), 126.85 (15-C),
127.21 (12-C), 127.53 (21- and 23-C), 127.72 (27- and 29-C),
128.32 (37- and 41-C), 129.44 (20- and 24-C), 131.22 (17-C),
132.26 (5-C), 132.71 (25-C), 136.47 (7-C), 137.18 (19-C),
141.75 (13-C), 146.21 (9-C), 160.15 (39-C), 160.62 (4-C),
162.72 (2-C), 163.64 ppm (32- and 35-C); Anal. Calcd. for
C35H22BrCl2N5O3 (711.39): C, 59.09; H, 3.12; N, 9.84. Found:
C, 58.98; H, 3.08; N, 9.86.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(4-methoxy-
phenyl)-1,3,4-oxadiazol-2-yl] phenyl}-6-bromo-quinazolin-4(3H)one
(7l). This compound was obtained as orange solid, yield 70%,
mp 289–292ꢀC; ir (KBr): NH 3443, CH2 2918, 2844, CO
1683, CN 1659, 1610, COC 1255, 1023, CCl 743, CBr 565
1
cmꢁ1; H NMR (DMSO-d6): d 3.53 (s, 2H, CH2), 3.61 (s, 3H,
OCH3), 6.39 (d, 1H, 14-H, J ¼ 8 Hz), 6.77 (d, 2H, 38- and
40-H, J ¼ 8.72 Hz), 6.89 (t, 1H, 16-H, J ¼ 7.44 Hz), 7.04–
7.10 (m, 2H, 15- and 22-H), 7.21 (d, 1H, 17-H, J ¼ 7.56 Hz),
7.39 (d, 2H, 21- and 23-H, J ¼ 8.12 Hz), 7.43 (d, 2H, 26- and
30-H, J ¼ 8.32 Hz), 7.48 (d, 2H, 37- and 41-H, J ¼ 8.72 Hz),
7.55 (d, 2H, 27- and 29-H, J ¼ 8.32 Hz), 7.67 (d, 1H, 8-H, J
¼ 8.4 Hz), 8.08 (d, 1H, 7-H, J ¼ 8.4 Hz), 8.16 (s, 1H, 5-H),
9.10 ppm (br s, 1H, NH); 13C NMR (DMSO-d6): d 32.63 (11-
C), 55.15 (OCH3), 114.25 (38- and 40-C), 116.27 (16-C),
116.83 (36-C), 120.47 (14-C), 121.57 (6-C), 121.68 (28-C),
121.88 (26- and 30-C), 123.13 (10-C), 124.34 (22-C), 124.46
(8-C), 126.55 (37- and 41-C), 126.91 (15-C), 127.17 (12-C),
127.56 (21- and 23-C), 127.82 (27- and 29-C), 129.38 (20-
and 24-C), 131.25 (17-C), 132.19 (5-C), 132.73 (25-C), 136.52
(7-C), 137.23 (19-C), 141.94 (13-C), 146.12 (9-C), 160.56 (39-
C), 160.68 (4-C), 162.65 (2-C), 163.80 ppm (32- and 35-C).
Anal. Calcd. for C36H24BrCl2N5O3 (725.42): C, 59.61; H,
3.33; N, 9.65. Found: C, 59.69; H, 3.37; N, 9.58.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(3-nitrophenyl)-
1,3,4-oxadiazol-2-yl] phenyl}-6-bromo-quinazolin-4(3H)one
(7j). This compound was obtained as yellow solid, yield 62%,
mp 274–277ꢀC; ir (KBr): NH 3444, CH2 2920, 2846, CO 1682,
CN 1647, 1612, NO2 1528, 1345, COC 1280, 1025, CCl 748,
1
CBr 569 cmꢁ1; H NMR (DMSO-d6): d 3.53 (s, 2H, CH2), 6.41
(d, 1H, 14-H, J ¼ 7.96 Hz), 6.89 (t, 1H, 16-H, J ¼ 7.36 Hz),
7.03–7.08 (m, 2H, 15- and 22-H), 7.21 (d, 1H, 17-H, J ¼ 7.52
Hz), 7.39 (d, 2H, 21- and 23-H, J ¼ 8.12 Hz), 7.44 (d, 2H, 26-
and 30-H, J ¼ 8.36 Hz), 7.53 (d, 2H, 27- and 29-H, J ¼ 8.36
Hz), 7.66 (d, 1H, 8-H, J ¼ 8.4 Hz), 7.81 (t, 1H, 40-H, J ¼ 7.88
Hz), 8.06 (d, 1H, 7-H, J ¼ 8.4 Hz), 8.14 (s, 1H, 5-H), 8.25 (d,
1H, 41-H, J ¼ 7.16 Hz), 8.36 (d, 1H, 39-H, J ¼ 7.76 Hz), 8.44
(s, 1H, 37-H), 9.11 ppm (br s, 1H, NH); 13C NMR (DMSO-d6):
d 32.47 (11-C), 116.22 (16-C), 120.12 (37-C), 120.48 (14-C),
121.57 (6-C), 121.68 (28-C), 121.91 (26- and 30-C), 123.15 (10-
C), 124.26 (22-C), 124.35 (39-C), 124.49 (8-C), 125.64 (36-C),
126.82 (15-C), 127.21 (12-C), 127.42 (21- and 23-C), 127.82
(27- and 29-C), 129.52 (20- and 24-C), 130.69 (40-C), 131.17
(17-C), 132.25 (5-C), 132.65 (25-C), 133.37 (41-C), 136.46 (7-
C), 137.22 (19-C), 141.79 (13-C), 146.32 (9-C), 148.41 (38-C),
160.56 (4-C), 162.78 (2-C), 163.93 ppm (32- and 35-C). Anal.
Calcd. for C35H21BrCl2N6O4 (740.39): C, 56.78; H, 2.86; N,
11.35. Found: C, 56.87; H, 2.82; N, 11.29.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-[4-(5-phenyl-1,3,4-
oxadiazol-2-yl)phenyl]-6-iodo-quinazolin-4(3H)one (7m). This
compound was obtained as light brownish solid, yield 63%,
mp 256–258ꢀC; IR (KBr): NH 3452, CH2 2926, 2852, CO
1680, CN 1648, 1613, COC 1270, 1052, CCl 749, CI 618
1
cmꢁ1; H-NMR (DMSO-d6): d 3.52 (s, 2H, CH2), 6.42 (d, 1H,
14-H, J ¼ 8 Hz), 6.92 (t, 1H, 16-H, J ¼ 7.48 Hz), 7.03–7.09
(m, 2H, 15- and 22-H), 7.23 (d, 1H, 17-H, J ¼ 7.64 Hz), 7.29
(d, 1H, 8-H, J ¼ 8.4 Hz), 7.38–7.43 (m, 5H, 21-, 23-, 38-, 39-
and 40-H), 7.45 (d, 2H, 26- and 30-H, J ¼ 8.28 Hz), 7.56 (d,
2H, 27- and 29-H, J ¼ 8.28 Hz), 7.78 (dd, 2H, 37- and 41-H,
J ¼ 6.44 Hz, 1.92 Hz), 7.97 (d, 1H, 7-H, J ¼ 8.4 Hz), 8.30 (s,
1H, 5-H), 9.13 ppm (br s, 1H, NH); 13C NMR (DMSO-d6): d
32.46 (11-C), 93.17 (6-C), 116.22 (16-C), 120.45 (14-C),
121.53 (28-C), 121.84 (26- and 30-C), 122.43 (10-C), 124.18
(8-C), 124.25 (22-C), 124.37 (36-C), 124.86 (37- and 41-C),
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(4-nitrophenyl)-
1,3,4-oxadiazol-2-yl] phenyl}-6-bromo-quinazolin-4(3H)one
(7k). This compound was obtained as yellow solid, yield 65%,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

930
N. B. Patel and J. C. Patel
Vol 47
126.76 (15-C), 127.33 (12-C), 127.44 (21- and 23-C), 127.78
(27- and 29-C), 128.55 (39-C), 129.34 (20- and 24-C), 129.77
(38- and 40-C), 131.27 (17-C), 132.75 (25-C), 136.24 (5-C),
137.18 (19-C), 141.86 (13-C), 142.38 (7-C), 146.05 (9-C),
160.62 (4-C), 162.82 (2-C), 163.21 ppm (32- and 35-C). Anal.
Calcd. for C35H22Cl2IN5O2 (742.39): C, 56.62; H, 2.99; N,
9.43. Found: C, 56.73; H, 2.91; N, 9.36.
6.40 (d, 1H, 14-H, J ¼ 7.96 Hz), 6.91 (t, 1H, 16-H, J ¼ 7.36
Hz), 7.04–7.09 (m, 2H, 15- and 22-H), 7.21 (d, 1H, 17-H, J ¼
7.52 Hz), 7.28 (d, 1H, 8-H, J ¼ 8.44 Hz), 7.39 (d, 2H, 21- and
23-H, J ¼ 8.08 Hz), 7.44 (d, 2H, 26- and 30-H, J ¼ 8.32 Hz),
7.55 (d, 2H, 27- and 29-H, J ¼ 8.32 Hz), 7.80 (t, 1H, 40-H, J
¼ 7.84 Hz), 7.96 (d, 1H, 7-H, J ¼ 8.44 Hz), 8.22 (d, 1H, 41-
H, J ¼ 7.12 Hz), 8.29 (s, 1H, 5-H), 8.35 (d, 1H, 39-H, J ¼
7.72 Hz), 8.45 (s, 1H, 37-H), 9.10 ppm (br s, 1H, NH); 13C
NMR (DMSO-d6): d 32.61 (11-C), 93.17 (6-C), 116.22 (16-C),
120.23 (37-C), 120.52 (14-C), 121.52 (28-C), 121.83 (26- and
30-C), 122.57 (10-C), 124.10 (8-C), 124.30 (22-C), 124.35 (39-
C), 125.72 (36-C), 126.84 (15-C), 127.32 (12-C), 127.53 (21-
and 23-C), 127.74 (27- and 29-C), 129.47 (20- and 24-C), 130.76
(40-C), 131.22 (17-C), 132.64 (25-C), 133.44 (41-C), 136.46 (5-
C), 137.34 (19-C), 141.92 (13-C), 142.46 (7-C), 146.21 (9-C),
148.38 (38-C), 160.62 (4-C), 162.77 (2-C), 164.05 ppm (32- and
35-C). Anal. Calcd. for C35H21Cl2IN6O4 (787.39): C, 53.39; H,
2.69; N, 10.67. Found: C, 53.47; H, 2.63; N, 10.61.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(2-hydroxy-
phenyl)-1,3,4-oxadiazol-2-yl] phenyl}-6-iodo-quinazolin-4(3H)one
(7n). This compound was obtained as light reddish solid, yield
67%, mp 266–270ꢀC; IR (KBr): NH 3446, OH 3135, CH2
2921, 2846, CO 1673, CN 1656, 1611, COC 1255, 1048, CCl
1
743, CI 620 cmꢁ1; H NMR (DMSO-d6): d 3.53 (s, 2H, CH2),
6.40 (d, 1H, 14-H, J ¼ 7.96 Hz), 6.87–6.95 (m, 2H, 16- and
40-H), 6.98 (d, 1H, 38-H, J ¼ 8.12 Hz), 7.04–7.09 (m, 2H,
15- and 22-H), 7.21 (d, 1H, 17-H, J ¼ 7.52 Hz), 7.23–7.28 (m,
2H, 8- and 39-H), 7.40 (d, 2H, 21- and 23-H, J ¼ 8.12 Hz),
7.44–7.47 (m, 3H, 26-, 30- and 41-H), 7.57 (d, 2H, 27- and
29-H, J ¼ 8.28 Hz), 7.95 (d, 1H, 7-H, J ¼ 8.36 Hz), 8.28 (s,
1H, 5-H), 9.11 (br s, 1H, NH), 10.06 ppm (br s, 1H, OH); 13C
NMR (DMSO-d6): d 32.62 (11-C), 93.33 (6-C), 109.28 (36-C),
116.19 (16-C), 116.67 (38-C), 119.68 (40-C), 120.46 (14-C),
121.48 (28-C), 121.80 (26- and 30-C), 122.53 (10-C), 124.16
(8-C), 124.25 (22-C), 125.51 (41-C), 126.85 (15-C), 127.31
(12-C), 127.45 (21- and 23-C), 127.68 (27- and 29-C), 129.44
(20- and 24-C), 131.18 (17-C), 131.72 (39-C), 132.64 (25-C),
136.30 (5-C), 137.21 (19-C), 141.82 (13-C), 142.47 (7-C),
146.22 (9-C), 155.61 (37-C), 160.73 (4-C), 162.52 (2-C),
162.69 ppm (32- and 35-C). Anal. Calcd. for C35H22Cl2IN5O3
(758.39): C, 55.43; H, 2.92; N, 9.23. Found: C, 55.40; H,
2.95; N, 9.29.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(4-nitrophenyl)-
1,3,4-oxadiazol-2-yl] phenyl}-6-iodo-quinazolin-4(3H)one
(7q). This compound was obtained as light brownish solid,
yield 70%, mp 254–257ꢀC; IR (KBr): NH 3440, CH2 2918,
2846, CO 1684, CN 1656, 1613, NO2 1535, 1348, COC 1278,
1
1025, CCl 750, CI 618 cmꢁ1; H-NMR (DMSO-d6): d 3.54 (s,
2H, CH2), 6.42 (d, 1H, 14-H, J ¼ 8 Hz), 6.89 (t, 1H, 16-H, J
¼ 7.44 Hz), 7.04–7.10 (m, 2H, 15- and 22-H), 7.22 (d, 1H,
17-H, J ¼ 7.6 Hz), 7.29 (d, 1H, 8-H, J ¼ 8.36 Hz), 7.41 (d,
2H, 21- and 23-H, J ¼ 8.12 Hz), 7.47 (d, 2H, 26- and 30-H, J
¼ 8.36 Hz), 7.56 (d, 2H, 27- and 29-H, J ¼ 8.36 Hz), 7.95 (d,
1H, 7-H, J ¼ 8.36 Hz), 8.06 (d, 2H, 37- and 41-H, J ¼ 8.72
Hz), 8.31 (s, 1H, 5-H), 8.35 (d, 2H, 38- and 40-H, J ¼ 8.72
Hz), 9.12 ppm (br s, 1H, NH); 13C-NMR (DMSO-d6): d 32.51
(11-C), 93.25 (6-C), 116.15 (16-C), 120.47 (14-C), 121.60 (28-
C), 121.87 (26- and 30-C), 122.50 (10-C), 124.16 (8-C),
124.22 (22-C), 124.61 (38- and 40-C), 126.78 (15-C), 127.23
(37- and 41-C), 127.26 (12-C), 127.45 (21- and 23-C), 127.82
(27- and 29-C), 129.42 (20- and 24-C), 131.12 (17-C), 131.28
(36-C), 132.68 (25-C), 136.34 (5-C), 137.25 (19-C), 141.84
(13-C), 142.39 (7-C), 146.15 (9-C), 148.24 (39-C), 160.72 (4-
C), 162.85 (2-C), 164.30 ppm (32- and 35-C). Anal. Calcd. for
C35H21Cl2IN6O4 (787.39): C, 53.39; H, 2.69; N, 10.67. Found:
C, 53.52; H, 2.61; N, 10.63.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(4-hydroxy-
phenyl)-1,3,4-oxadiazol-2-yl] phenyl}-6-iodo-quinazolin-4(3H)one
(7o). This compound was obtained as off white solid, yield
65%, mp 269–273ꢀC; IR (KBr): NH 3453, OH 3145, CH2
2927, 2854, CO 1681, CN 1657, 1614, COC 1273, 1024, CCl
1
740, CI 619 cmꢁ1; H-NMR (DMSO-d6): d 3.51 (s, 2H, CH2),
5.63 (br s, 1H, OH), 6.38 (d, 1H, 14-H, J ¼ 7.96 Hz), 6.88 (t,
1H, 16-H, J ¼ 7.4 Hz), 6.94 (d, 2H, 38- and 40-H, J ¼ 8.44
Hz), 7.03–7.08 (m, 2H, 15- and 22-H), 7.19 (d, 1H, 17-H, J ¼
7.56 Hz), 7.26 (d, 1H, 8-H, J ¼ 8.4 Hz), 7.38 (d, 2H, 21- and
23-H, J ¼ 8.08 Hz), 7.43 (d, 2H, 26- and 30-H, J ¼ 8.36 Hz),
7.54 (d, 2H, 27- and 29-H, J ¼ 8.36 Hz), 7.70 (d, 2H, 37- and
41-H, J ¼ 8.44 Hz), 7.94 (d, 1H, 7-H, J ¼ 8.4 Hz), 8.27 (s,
1H, 5-H), 9.09 ppm (br s, 1H, NH); 13C NMR (DMSO-d6): d
32.45 (11-C), 93.21 (6-C), 116.13 (16-C), 116.71 (38- and 40-
C), 118.32 (36-C), 120.48 (14-C), 121.46 (28-C), 121.76 (26-
and 30-C), 122.42 (10-C), 124.16 (8-C), 124.25 (22-C), 126.76
(15-C), 127.20 (12-C), 127.49 (21- and 23-C), 127.67 (27- and
29-C), 128.39 (37- and 41-C), 129.52 (20- and 24-C), 131.11
(17-C), 132.56 (25-C), 136.35 (5-C), 137.26 (19-C), 141.81
(13-C), 142.36 (7-C), 146.14 (9-C), 160.22 (39-C), 160.74 (4-
C), 162.83 (2-C), 163.60 ppm (32- and 35-C); Anal. Calcd. for
C35H22Cl2IN5O3 (758.39): C, 55.43; H, 2.92; N, 9.23. Found:
C, 55.48; H, 2.98; N, 9.18.
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(4-methoxy-
phenyl)-1,3,4-oxadiazol-2-yl] phenyl}-6-iodo-quinazolin-4(3H)one
(7r). This compound was obtained as light orange solid, yield
68%, mp 276–278ꢀC; IR (KBr): NH 3453, CH2 2925, 2850,
CO 1676, CN 1651, 1609, COC 1258, 1074, CCl 746, CI 618
1
cmꢁ1; H NMR (DMSO-d6): d 3.52 (s, 2H, CH2), 3.58 (s, 3H,
OCH3), 6.39 (d, 1H, 14-H, J ¼ 7.96 Hz), 6.78 (d, 2H, 38- and
40-H, J ¼ 8.68 Hz), 6.88 (t, 1H, 16-H, J ¼ 7.36 Hz), 7.04–
7.09 (m, 2H, 15- and 22-H), 7.20 (d, 1H, 17-H, J ¼ 7.52 Hz),
7.26 (d, 1H, 8-H, J ¼ 8.4 Hz), 7.39 (d, 2H, 21- and 23-H, J ¼
8.08 Hz), 7.44–7.49 (m, 4H, 26-, 30-, 37- and 41-H), 7.54 (d,
2H, 27- and 29-H, J ¼ 8.36 Hz), 7.97 (d, 1H, 7-H, J ¼ 8.4
Hz), 8.28 (s, 1H, 5-H), 9.10 ppm (br s, 1H, NH); 13C-NMR
(DMSO-d6): d 32.43 (11-C), 55.22 (OCH3), 93.21 (6-C),
114.32 (38- and 40-C), 116.13 (16-C), 116.92 (36-C), 120.42
(14-C), 121.58 (28-C), 121.87 (26- and 30-C), 122.56 (10-C),
124.17 (8-C), 124.33 (22-C), 126.63 (37- and 41-C), 126.82 (15-
C), 127.21 (12-C), 127.48 (21- and 23-C), 127.69 (27- and 29-
C), 129.42 (20- and 24-C), 131.14 (17-C), 132.57 (25-C), 136.39
2-[2-(2,6-Dichlorophenyl)amino]benzyl-3-{4-[5-(3-nitrophenyl)-
1,3,4-oxadiazol-2-yl] phenyl}-6-iodo-quinazolin-4(3H)one
(7p). This compound was obtained as brown solid, yield 61%,
mp 286–290ꢀC; IR (KBr): NH 3444, CH2 2926, 2853, CO
1675, CN 1653, 1610, NO2 1530, 1346, COC 1276, 1028, CCl
1
742, CI 613 cmꢁ1; H NMR (DMSO-d6): d 3.53 (s, 2H, CH2),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2010
Synthesis and Antimicrobial Activity of Novel 1,3,4-Oxadiazolyl-quinazolin-4(3H)ones
931
[4] George, S.; Parameswaran, M. K.; Chakraborty, A. R.;
Ravi, T. K. Acta Pharm 2008, 58, 119.
(5-C), 137.28 (19-C), 141.83 (13-C), 142.44 (7-C), 146.12 (9-C),
160.54 (39-C), 160.67 (4-C), 162.74 (2-C), 163.77 ppm (32- and
35-C). Anal. Calcd. for C36H24Cl2IN5O3 (772.42): C, 55.98; H,
3.13; N, 9.07. Found: C, 55.89; H, 3.07; N, 9.14.
[5] Narayana, B.; Raj, K. K. V.; Ashalatha, B. V.; Kumari, N.
S. Arch Pharm 2005, 338, 373.
[6] Sharma, S.; Srivastava, V. K.; Kumar A. Eur J Med Chem
2002, 37, 689.
General procedure for in vitro antimicrobial screening. The
MICs of synthesized compounds were carried out by broth
microdilution method as described by Rattan [36]. Antibacterial
activity was screened against two gram-positive bacteria (S. aur-
eus MTCC 96, S. pyogenes MTCC 443) and two gram-negative
bacteria (E. coli MTCC 442, P. aeruginosa MTCC 441). Ampi-
cillin was used as a standard antibacterial agent. Antifungal ac-
tivity was screened against three fungal species C. albicans
MTCC 227, A. niger MTCC 282 and A. clavatus MTCC 1323.
Greseofulvin was used as a standard antifungal agent.
[7] Zareef, M.; Iqbal, R.; Dominguez, N. G.; Rodrigues, J.; Zaidi,
J. H.; Arfan, M.; Supuran, C. T. J Enz Inhib Med Chem 2007, 22, 301.
[8] Hashem, A. I.; Youssef, A. S. A.; Kandeel, K. A.; Abou-
Elmagd, W. S. I. Eur J Med Chem 2007, 42, 934.
[9] El-Essawy, F. A.; Khattab, A. F.; Abdel-Rahman, A. A. H.
Monatsh Chem 2007, 138, 777.
[10] Amr, A. E. E.; Mohamed, S. F.; Abdel-Hafez, N. A.;
Abdalla, M. M. Monatsh Chem 2008, 139, 1491.
[11] Wagner, E.; Al-Kadasi, K.; Zimecki, M.; Dobrowolska, W.
S. Eur J Med Chem 2008, 43, 2498.
All MTCC cultures were collected from Institute of Microbial
Technology, Chandigarh and tested against above mentioned
known drugs. Mueller Hinton broth was used as nutrient medium
to grow and dilute the drug suspension for the test. Inoculum size
for test strain was adjust to 108 CFU (Colony Forming Unit) per
milliliter by comparing the turbidity. DMSO was used as diluents
to get desired concentration of drugs to test upon standard bacterial
strains. Serial dilutions were prepared in primary and secondary
screening. The control tube containing no antibiotic was immedi-
ately sub cultured (before inoculation) by spreading a loopful
evenly over a quarter of plate of medium suitable for the growth of
the test organism and put for incubation at 37ꢀC overnight. The
tubes were then incubated overnight. The MIC of the control orga-
nism was read to check the accuracy of the drug concentrations.
The lowest concentration inhibiting growth of the organism was
recorded as the MIC. All the tubes not showing visible growth (in
the same manner as control tube described above) was sub cultured
and incubated overnight at 37ꢀC. The amount of growth from the
control tube before incubation (which represents the original inocu-
lum) was compared. Subcultures might show: similar number of
colonies indicating bacteriostatic; a reduced number of colonies
indicating a partial or slow bactericidal activity and no growth if
the whole inoculum has been killed. The test must include a second
set of the same dilutions inoculated with an organism of known
sensitivity. Each synthesized drug was diluted obtaining 2000 lg/
mL concentration, as a stock solution. In primary screening 500,
250, and 125 lg/mL concentrations of the synthesized drugs were
taken. The active synthesized drugs found in this primary screening
were further tested in a second set of dilution against all microor-
ganisms. The drugs found active in primary screening were simi-
larly diluted to obtain 100, 50, 25, 12.5, 6.250, 3.125, and 1.5625
lg/mL concentrations. The highest dilution showing at least 99 %
inhibition is taken as MIC.
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Acknowledgments. The authors are thankful to Veer Narmad
South Gujarat University for providing necessary facilities. We
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet