Synthesis and anti-microbial screening of some Schiff bases of 3-amino-6,8-dibromo-2-phenylquinazolin-4(3H)-ones

Article abstract of DOI:10.1016/j.ejmech.2008.04.010

In the present study, a series of novel Schiff bases were synthesized by condensation of 3-amino-6,8-dibromo-2-phenylquinazolin-4(3H)-ones with different aromatic aldehydes via cyclized intermediate 6,8-dibromo-2-phenyl benzoxazin-4-one. The chemical stru

Full text of DOI:10.1016/j.ejmech.2008.04.010

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European Journal of Medicinal Chemistry 44 (2009) 2328e2333
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Laboratory note
Synthesis and anti-microbial screening of some Schiff bases of
3-amino-6,8-dibromo-2-phenylquinazolin-4(3H )-ones
*
Perumal Panneerselvam , Bilal Ahmad Rather, Dontireddy Ravi Sankar Reddy,
Natesh Ramesh Kumar
Department of Pharmaceutical Chemistry, C.L. Baid Metha College of Pharmacy, Jyothi Nagar, Rajiv Gandhi Salai,
Thorapakkam, Chennai 600 097, Tamil Nadu, India
Received 27 February 2008; received in revised form 20 March 2008; accepted 8 April 2008
Available online 29 April 2008
Abstract
In the present study, a series of novel Schiff bases were synthesized by condensation of 3-amino-6,8-dibromo-2-phenylquinazolin-
4(3H )-ones with different aromatic aldehydes via cyclized intermediate 6,8-dibromo-2-phenyl benzoxazin-4-one. The chemical structures
were confirmed by means of IR, 1H NMR, 13C NMR, Mass spectral and Elemental analysis. These compounds were screened for anti-
bacterial (Staphylococcus aureus ATCC-9144, Staphylococcus epidermidis ATCC-155, Micrococcus luteus ATCC-4698, Bacillus cereus
ATCC-11778, Escherichia coli ATCC-25922, Pseudomonas aeruginosa ATCC-2853, and Klebsiella pneumoniae ATCC-11298) and anti-
fungal (Aspergillus niger ATCC-9029 and Aspergillus fumigatus ATCC-46645) activities by paper disc diffusion technique. The minimum
inhibitory concentrations (MICs) of the compounds were also determined by agar streak dilution method. Among the synthesized
compounds 3-(3,4,5-trimethoxybenzylideneamino)-6,8-dibromo-2-phenylquinazolin-4(3H )-one 10 was found to be the most potent anti-
microbial activity with MICs of 18.9, 19.1, 18.8, 21.7, 18.2, 19.3, 16.7, 8.6 and 10.1 mg/ml against above mentioned respective strains.
Compounds were found to exhibit more anti-fungal than anti-bacterial activity.
Ó 2008 Elsevier Masson SAS. All rights reserved.
Keywords: Quinazolin-4(3H )-one; Schiff base; Anti-bacterial; Anti-fungal
1. Introduction
its medicinal properties. Quinazolin-4(3H )-ones with substitu-
tion at 3rd position has been reported to be associated with
anti-microbial properties [14,15]. The various substitutions
at 3rd position of the quinazolin-4(3H )-ones which were
reported are substituted phenyl ring moieties [16,17], bridged
phenyl rings [18,19], heterocyclic rings [20,21] and aliphatic
system [22,23]. In general Schiff bases and presence of
pharmacophores like eNO2, eBr, phenolic eOH, and eCl
are reported to possess anti-microbial activities [5,24,25].
These observations led to the conception that a series of novel
Schiff bases of 3-amino-6,8-dibromo-2-phenylquinazolin-
4(3H )-ones 1e12 were synthesized using different aromatic
aldehydes by condensation and their chemical structures
The search of new anti-microbial agents with reduced
toxicity and lower side effects is of continuous process. One
of the most frequently encountered heterocyclic in medicinal
chemistry is quinazolin-4(3H )-one and its derivatives were
reported to possess diverse biological applications including
anti-microbial [1e5], analgesic and anti-inflammatory [6,7],
anti-convulsant [8], anti-cancer [9], anti-tubercular [10], anti-
malarial [11], anti-viral [12] and anti-helmintic [13] activities.
The literature survey revealed that the presence of substituted
aromatic ring at position 3 as well as substituent like methyl
and phenyl groups at position 2 is necessary requirement for
1
were confirmed by IR, H NMR, 13C NMR, Mass spectral
and Elemental analysis. These compounds were screened
for their anti-bacterial activity against four Gram-positive
bacteria (Staphylococcus aureus ATCC-9144, Staphylococcus
* Corresponding author. Tel.: þ91 44 24960151/24960425, þ91
9442712951 (mobile).
E-mail address: pps2k2000@yahoo.co.in (P. Panneerselvam).
0223-5234/$ - see front matter Ó 2008 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2008.04.010

P. Panneerselvam et al. / European Journal of Medicinal Chemistry 44 (2009) 2328e2333
2329
epidermidis ATCC-155, Micrococcus luteus ATCC-4698 and
Bacillus cereus ATCC-11778), three Gram-negative bacteria
(Escherichia coli ATCC-25922, Pseudomonas aeruginosa
ATCC-2853 and Klebsiella pneumoniae ATCC-11298) and
anti-fungal (Aspergillus niger ATCC-9029 and Aspergillus
fumigatus ATCC-46645) activities by paper disc diffusion
technique. The minimum inhibitory concentrations (MICs)
of the compounds were also determined by agar streak dilution
method.
anti-microbial activity of the synthesized compounds and
standard drugs are given in Table 1.
4. Results and discussion
In this present work a novel series of quinazolin-4(3H )-ones
compounds were synthesized. Synthetic scheme illustrates the
way used for the synthesis of target compounds. As a starting
material 3,5-subsituted anthranilic acid and benzoyl chloride
were used to produce Schiff bases of substituted quinazolin-
4(3H )-one via the intermediate substituted benzoxazin-4-one
and substituted 3-amino-2-phenylquinazolin-4(3H )-one. The
structures of the compounds were characterized by IR, 1H
NMR, 13C NMR, Mass spectral data and Elemental analysis.
All the synthesized compounds were active against all tested
micro-organisms with the range of MIC values for S. aureus
(17.3e35.4 mg/ml), S. epidermidis (19.1e33.6 mg/ml), M.
luteus (17.2e34.2 mg/ml), B. cereus (19.3e36.1 mg/ml), E.
coli (18.2e33.4 mg/ml), P. aeruginosa (19.3e37.2 mg/ml), K.
pneumoniae (16.7e35.7 mg/ml), A. niger (8.6e15.2 mg/ml)
and A. fumigatus (10.1e15.9 mg/ml). 3-(3,4,5-Trimethoybenzy-
lideneamino)-6,8-dibromo-2-phenylquinazolin-4(3H )-one 10
was found to exhibit the most potent in vitro anti-microbial
activity with the MICs of 8.6, 10.1, 16.7, 18.2, 18.8, 18.9,
19.1, 19.3 and 21.7 mg/ml against A. niger, A. fumigatus, K.
pneumoniae, E. coli, M. luteus, S. aureus, S. epidermidis, P.
aeruginosa and B. cereus, respectively. Compound 7 exhibited
significant anti-microbial activity when compared to standard
drugs Ciprofloxin and Ketokonazole. Other compounds 1e6,
8e9, 11e12 showed mild to moderate anti-bacterial and anti-
fungal activity. The results revealed that most of the synthesized
compounds exhibited significant anti-fungal activity. The most
potent anti-bacterial and anti-fungal activity exhibited by
2. Chemistry
In the present study 3,5-dibromoanthranilic acid 1 was
reacted with benzoyl chloride in the presence of pyridine to
form cyclized intermediate 6,8-dibromo-2-phenyl benzoxazin-
4-one 2 which further treated with hydrazine hydrate resulted
in 3-amino-6,8-dibromo-2-phenylquinazolin-4(3H )-one 3. The
compound 3 was subjected to react with various aromatic
aldehydes in the presence of ethanol as a solvent to form a series
of novel Schiff bases 1e12.
3. Biology investigation
3.1. Anti-microbial activity
All the synthesized compounds were screened for anti-
microbial activities by paper disc diffusion technique. The
tested micro-organism strains were: S. aureus (ATCC-9144),
S. epidermidis (ATCC-155), M. luteus (ATCC-4698), B. cereus
(ATCC-11778), E. coli (ATCC-25922), P. aeruginosa (ATCC-
2853), K. pneumoniae (ATCC-11298), A. niger (ATCC-9029)
and A. fumigatus (ATCC-46645). The observed data on the
Table 1
Anti-microbial activity of the synthesized compounds
Compound
In vitro activity-zone of inhibition in mm (MIC in mg/ml)
S. aureus, S. epidermidis, M. luteus, B. cereus,
ATCC-9144 ATCC-155 ATCC-4698 ATCC-11778 ATCC-25922 ATCC-2853
E. coli,
P. aeruginosa, K. pneumoniae, A. niger,
A. fumigatus,
ATCC-9092 ATCC-46645
ATCC-11298
1
17 (35.4)
19 (32.1)
20 (21.8)
19 (27.9)
21 (22.6)
18 (31.1)
24 (17.3)
19 (28.4)
22 (22.4)
26 (18.9)
23 (21.6)
20 (23.8)
18 (33.6)
20 (22.2)
24 (21.3)
25 (19.8)
22 (21.8)
20 (22.6)
22 (20.9)
20 (25.6)
22 (21.8)
25 (19.1)
23 (24.2)
24 (21.4)
19 (31.8)
18 (34.2)
18 (28.2)
21 (26.2)
23 (30.1)
23 (25.1)
26 (17.2)
23 (33.8)
23 (27.4)
24 (18.8)
24 (28.1)
21 (22.8)
20 (29.4)
19 (31.9)
21 (19.9)
19 (30.1)
22 (23.6)
21 (21.9)
21 (19.3)
19 (36.1)
20 (32.8)
23 (21.7)
17 (35.1)
23 (21.9)
17 (33.4)
19 (29.9)
22 (20.4)
20 (29.1)
26 (19.8)
24 (19.8)
23 (21.8)
27 (20.2)
23 (30.2)
27 (18.2)
24 (31.2)
25 (20.1)
19 (28.7)
16 (36.2)
17 (37.2)
18 (32.1)
19 (36.1)
22 (21.2)
25 (22.6)
26 (22.8)
21 (34.2)
24 (19.3)
19 (33.4)
19 (25.1)
21 (27.7)
20 (33.4)
22 (24.3)
23 (22.7)
21 (34.6)
19 (29.1)
27 (19.0)
25 (21.8)
20 (35.7)
28 (16.7)
23 (28.2)
25 (19.8)
24 (9.7)
22 (11.1)
24 (12.3)
23 (13.6)
22 (15.9)
23 (11.6)
24 (14.6)
21 (10.7)
22 (12.6)
25 (10.9)
24 (10.1)
23 (15.2)
22 (14.6)
2
23 (10.1)
22 (12.2)
19 (14.7)
25 (10.7)
22 (15.2)
24 (9.1)
3
4
5
6
7
8
25 (10.2)
24 (14.4)
26 (8.6)
9
10
11
12
24 (12.7)
24 (11.8)
Ciprofloxacin
(100 mg/disc)
29 (0.2)
31 (0.39)
30 (0.1)
29 (0.3)
32 (0.2)
33 (0.25)
33 (0.1)
e
e
Ketoconazole
(100 mg/disc)
Dimethyl
e
e
e
e
e
e
e
e
e
e
e
e
e
e
30 (6.1)
29 (0.23)
e
e
formamide

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P. Panneerselvam et al. / European Journal of Medicinal Chemistry 44 (2009) 2328e2333
compound 10 might be due to the presence of electron donating
substituent three methoxy groups on the benzylideneamino
moiety of the 2-phenyl substituted quinazolin-4(3H )-one.
Similarly 3-(4-hydroxybenzylideneamino)-6,8-dibromo-2-phe-
nylquinazolin-4(3H )-one 7 also exhibited significant anti-
microbial activity due to the presence of phenolic eOH group
on the benzylideneamino group of the quinazoline-4(3H )-one
moiety. While other compounds, though they contain both
electron withdrawing groups like nitro, chloro and electron
donating group like methoxy group do not exhibit significant
in vitro anti-microbial activity (Scheme 1).
and bromine which might increase the lipophilic character of
the molecule, which facilitate the crossing through the biolog-
ical membrane of the micro-organism and thereby inhibit their
growth.
6. Experimental protocols
6.1. Chemistry
The melting points were taken in open capillary tube and
are uncorrected. The IR spectra of the compounds were
recorded on ABB Bomem FT-IR spectrometer MB 104 with
1
5. Conclusion
KBr pellets. The H NMR (300 MHz) and 13C NMR (300
MHz) spectra were recorded on a Bruker 300 NMR
spectrometer. Mass spectra were recorded on Shimadzu
GCeMS QP 5000. Microanalyses were obtained with an
The anti-microbial activity of the synthesized compounds
may be due the presence of the versatile pharmacophores
O
Br
COOH
Br
COOH
i
O
ii
NH2
C6H5
iii
N
NH2
Br
1
Br
2
iv
O
N
Br
NH2
N
C6H5
Br
3
v
vi
O
CH R
Br
N
N
N
C6H5
Br
( 1-12 )
,
R =
,
OCH3,
N(CH3)2
HO
,
,
,
,
CH3
Cl
OH
NO2
OCH3
NO2,
,
OCH3
OCH3
, -CH=CH
.
OH
OCH3
Scheme 1. Synthesis of Schiff bases of 3-amino-6,8-dibromo-2-phenylquinazolin-4(3H )-ones 1e12. Reagents: (i) Br2 in boiling glacial acetic acid; (ii) 0 ꢀC in dry
pyridine; (iii) C6H5COCl; (iv) NH2NH2$H2O; (v) C2H5OH; and (vi) R-CHO, reflux, 3 h.

P. Panneerselvam et al. / European Journal of Medicinal Chemistry 44 (2009) 2328e2333
2331
Elemental analyses system GmbH VarioEL V300 element
analyzer. The purity of the compounds was checked by TLC
on pre-coated SiO2 gel (HF254, 200 mesh) aluminium plates
(E Merk) using ethyl acetate:n-hexane (20:80) and visualized
(C-100), 125.3 (C-10), 123.9 (C-50), 118.6 (C-þ10), 121.5 (C-30),
116.0 (C-500), 43.6 (C-8); EI-MS (m/z): M 499.9 (M þ 2,
25%); Anal. Calcd. for C21H13Br2N3O2: C, 50.53; H, 2.63; N,
8.42; Found: C, 50.52; H, 2.64; N, 8.43.
1
in UV chamber. IR, H NMR, 13C NMR, Mass spectra and
Elemental analysis were consistent with the assigned
structures.
6.1.1.4. 3(4-(Dimethylamino)benzylideneamino)-6,8-dibromo-
2-phenylquinazolin-4(3H )-one 4. Yield 71%; mp 225e
227 ꢀC; IR: 1793 (C]O), 1557 (C]C), 1375 (CeN) 1603
1
6.1.1. General method of synthesis 1e12
(C]N), 1445 (CeH), 3082 (CeH, Ar), 559 (CeBr) cmꢁ1; H
The 3-amino-6,8-dibromo-2-phenylquinazolin-4(3H )-one
was prepared according to reported literatures [2,26,27].
Equimolar quantities (0.01 mol) of 3-amino-6,8-dibromo
2-phenylquinazolin-4(3H )-one and substituted aromatic alde-
hydes were dissolved in sufficient quantity of ethanol and
refluxed for 6e8 h then kept aside for 3 days, the product
which separated out was filtered, dried and recrystallised
from absolute ethanol.
NMR (CDCl3): d 8.02 (s, 1H, He5, Ar-H), 8.13 (s, eN]CHe
), 7.82 (s, 1H, He7, Ar-H), 7.23e7.64 (m, 9H, Ar-H),
2.80 (s, 6H, eN(CH3)2); 13C NMR (CDCl3): d 163.9 (C-2),
160.2 (C-4), 153.4 (C-9), 151.9 (C-40), 143.9 (eN]CHe),
139.9 (C-7), 131.4 (C-5), 130.1 (C-20 and C-60), 130.2 (C-400),
128.9 (C-300 and C-500), 126.2 (C-200 and C-600), 125.4 (C-10),
123.9 (C-6), 114.6 (C-30 and C-50), 113.6 (C-8), 40.4 (e
N(CH3)2); EI-MS (m/z): Mþ 526.2 (M þ 2, 30%); Anal. Calcd.
for C23H18Br2N4O: C, 52.50; H, 3.45; N, 10.65; Found: C,
52.51; H, 3.46; N, 10.64.
6.1.1.1. 3(Benzylideneamino)-6,8-dibromo-2-phenylquinazolin-4
(3H )-one 1. Yield 82%; mp 231e233 ꢀC; IR: 1771 (C]O),
1557 (C]C), 1607 (C]N), 1201 (CeOeC), 549 (CeBr),
6.1.1.5. 3(3-Nitrobenzylideneamino)-6,8-dibromo-2-phenylqui-
nazolin-4(3H )-one 5. Yield 64%; mp 222e224 ꢀC; IR: 1703
(C]O), 1561 (C]C), 1348 (CeN), 1667 (C]N), 1432
(CeH), 3125 (CeH, Ar), 529 (CeBr), 1561 (CeNO2)
1
3124 (CeH), 1258 (CeN) cmꢁ1; H NMR (CDCl3): d 8.09 (s,
1H, H-5, Ar-H), 8.12 (s, eN]CHe), 7.82 (s, 1H, H-7, Ar-H),
7.25e7.60 (m, 10H, Ar-H); 13C NMR (CDCl3): d 164.1 (C-2),
160.2 (C-4), 154.3 (C-9), 143.6 (eN]CHe), 139.6 (C-7),
133.7 (C-10), 131.2 (C-40), 129.3 (C-60 and C-20), 128.8 (C-30
and C-50), 128.7 (C-1000), 128.6 (C-300 and C-500), 130.4 (C-400),
126.2 (C-200 and C-600), 131.6 (C-5), 125.4 (C-10), 123.9 (C-6),
113.5 (C-8); EI-MS (m/z): Mþ 483.6 (M þ 2, 28%); Anal. Calcd.
for C21H13Br2N3O: C, 52.20; H, 2.71; N, 8.70; Found: C, 52.21;
H, 2.70; N, 8.71.
1
cmꢁ1; H NMR (CDCl3): d 8.03 (s, 1H, H-5, Ar-H), 8.12
(s, eN]CHe), 7.80 (s, 1H, H-7, Ar-H), 7.20e7.60 (m, 8H,
Ar-H); 13C NMR (CDCl3): d 163.8 (C-2), 160.1 (C-4), 154.4
(C-9), 143.2 (eN]CHe), 139.3 (C-7), 148.4 (C-30), 135.4
(C-60), 134.7 (C-10), 131.2 (C-5), 130.4 (C-400), 128.9 (C-300
and C-50), 129.7 (C-30), 125.3 (C-10), 123.9 (C-6), 123.4
(C-40), 128.7 (C-10), 126.3 (C-200 and C600), 124.2 (C-20),
113.4 (C-8); EI-MS (m/z): Mþ 528.1 (M þ 2); Anal. Calcd.
for C21H12Br2N4O3: C, 47.76; H, 2.29; N, 10.61; Found: C,
47.77; H, 2.26; N, 10.60.
6.1.1.2. 3(4-Methoxybenzylideneamino)-6,8-dibromo-2-phe-
nylquinazolin-4(3H )-one 2. Yield 68%; mp 235e237 ꢀC; IR:
1771 (C]O), 1557 (C]C), 1605 (C]N), CeN (1376), 1010
(CeOeC), 853 (CeH), 3125 (CeH, Ar), 549 (CeBr), cmꢁ1
;
8.07 (s, 1H, H-5, Ar-H),
6.1.1.6. 3(4-Methylbenzylideneamino)-6,8-dibromo-2-phenyl-
quinazolin-4(3H )-one 6. Yield 78%; mp 219e221 ꢀC; IR:
1702 (C]O), 1669 (C]C), 1398 (CeN), 1684 (C]N),
1H NMR (CDCl3):
8.12 (s, eN]CHe), 3.72 (s, 1H, H-7, eOCH3), 7.27e7.62 (m,
d
9H, Ar-H); C NMR (CDCl3): d 163.9 (C-2), 163.0 (C-40),
1448 (CeH), 3096 (CeH, Ar), 550 (CeBr) cmꢁ1; H NMR
13
1
160.3 (C-4), 153.9 (C-9), 142.9 (N]CHe), 139.6 (C-7), 132.3
(C-5), 130.4 (C-20), 130.3 (C-400), 130.2 (C-20 and C-400), 128.7
(C-100), 128.9 (C-300 and C-500), 126.1 (C-10), 126.3 (C-200 and
C-60), 125.6 (C-10), 123.8 (C-6), 114.2 (C-30 and C-50), 113.4
(C-8), 4.01 (eOCH3); EI-MS MS (m/z): Mþ 513.1 (M þ 2,
30%); Anal. Calcd. for C22H15Br2N3O2: C, 51.49; H, 2.95; N,
8.19; Found: C, 51.48; H, 2.96; N, 8.20.
(CDCl3): d 8.09 (s, 1H, H-5, Ar-H), 8.12 (s, eN]CHe),
7.82 (s, 1H, H-7, Ar-H), 7.25e7.61 (m, 9H, Ar-H), 2.30 (s,
3H, eCH3); 13C NMR (CDCl3): d 164.3 (C-2), 160.2 (C-2),
154.9 (C-9), 143.4 (eN]CHe), 139.6 (C-7), 129.6 (C-50),
140.1 (C-40), 130.9 (C-10), 131.2 (C-5), 130.2 (C-400), 129.2
(C-30 and C-50), 129.1 (C-20 and C-60), 128.7 (C-10), 128.6
(C-30 and C-50), 126.1 (C-200 and C-60), 125.3 (C-10), 123.9
(C-6), 113.4 (C-8), 24.2 (eCH3); EI-MS (m/z): Mþ 497.1
(M þ 2, 35%); Anal. Calcd. for C22H15Br2N3O: C, 53.15; H,
3.04; N, 8.45; Found: C, 53.14; H, 3.05; N, 8.44.
6.1.1.3. 3(2-Hydroxybenzylideneamino)-6,8-dibromo-2-phe-
nylquinazolin-4(3H )-one 3. Yield 65%; mp 226e228 ꢀC; IR:
1771 (C]O), 1576 (C]C), 1607 (C]N), 1377 (CeN), 1431
(CeH), 3125 (CeH, Ar), 508 (CeBr), 3565 (OeH, s), 1201
6.1.1.7. 3(4-Hydroxybenzylideneamino)-6,8-dibromo-2-phe-
nylquinazolin-4(3H )-one 7. Yield 75%; mp 238e240 ꢀC; IR:
1771 (C]O), 1665 (C]C), 1377 (CeN), 1665 (C]N), 1447
(CeH), 3132 (CeH, Ar), 550 (CeBr), 3525 (OeH, s), 1202
(OeH, b) cmꢁ1; 1H NMR (CDCl3): d 8.08 (s, 1H, ;H-5, Ar-H),
8.12 (s, eN]CHe), 5.91 (s, AreOH ), 7.31e7.62 (m, 9H,
Ar-H); 13C NMR (CDCl3): d 164.4 (C-2), 160.6 (C-4), 154.7
1
(OeH, b) cmꢁ1; H NMR (CDCl3): d 8.0 (s, 1H, H-5, Ar-H),
8.13 (s, eN]CHe), 7.83 (s, 1H, H-7, Ar-H), 7.29e7.63 (m,
8H, Ar-H), 5.29 (s, 1H, Ar-H); 13C NMR (CDCl3): d 163.9 (C-2),
160.3 (C-40), 161.2 (C-20), 153.6 (C-9), 143.7 (eN]CHe),
139.8 (C-7), 131.6 (C-5), 130.6 (C-60), 132.6 (C-40), 130.4
(C-400), 128.9 (C-300 and C-500), 126.2 (C-200 and C-600), 128.7

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P. Panneerselvam et al. / European Journal of Medicinal Chemistry 44 (2009) 2328e2333
(C-9), 160.9 (C-40), 143.3 (eN]CHe), 139.5 (C-7), 131.4(C-5),
128.7 (C-10), 126.3 (C-20 and C-60), 116.9 (C-30 and C-50), 125.3
(C-10), 123.8 (C-6), 128.7 (C-10), 128.6 (C-30þand C-50), 126.3
(C-200 and C-60), 113.6 (C-8); EI-MS (m/z): M 499.15 (M þ 2,
30%); Anal. Calcd. for C21H13Br2N3O2: C, 50.53; H, 2.63; N,
8.42; Found: C, 50.54; H, 2.62; N, 8.43.
1667 (C]N), 1447 (CeH), 3125 (CeH, Ar), 529 (CeBr),
1
1200 (CeOCH3), 3489 (OeH, s), 1301 (OeH, b) cmꢁ1; H
NMR (CDCl3): d 8.10 (s, 1H, H-5, Ar-H), 8.16 (s, eN]CHe),
7.80 (s, 1H-7, Ar-H), 7.29e7.62 (m, 7H, H-20, H-30, H-40, H-50,
H-60, H-200, H-300, Ar-H), 7.09 (s, 1H, H-60, Ar-H); 13C NMR
(CDCl3): d 164.2 (C-2), 160.2 (C-4), 154.3 (C-9), 151.6 (C-50),
143.6 (eN]CHe), 138.7 (C-40), 139.9 (C-7), 131.4 (C-5),
130.5 (C-400), 126.3 (C-200 and C-600), 128.7 (C-30 and C-50),
128.7 (C-10), 128.5 (C-10), 125.6 (C-10), 123.9 (C-6), 127.4
(C-10), 122.8 (C-20), 119.7 (C-60), 117.2 (C-30), 113.4 (C-8),
56.70 (eOCH3); EI-MS (m/z): Mþ 529.1 (M þ 2, 30%); Anal.
Calcd. for C22H15Br2N3O3: C, 49.93; H, 2.86; N, 7.94; Found:
C, 49.94; H, 2.85; N, 7.95.
6.1.1.8. 3(4-Chlorobenzylideneamino)-6,8-dibromo-2-phenyl-
quinazolin-4(3H )-one 8. Yield 70%; mp 244e246 ꢀC; IR:
1703 (C]O), 1683 (C]C), 1377 (CeN), 1670 (C]N),
1447 (CeH), 3125 (CeH, Ar), 529 (CeBr), 784 (CeCl)
1
cmꢁ1; H NMR (CDCl3): d 8.07 (s, 1H, H-5, Ar-H), 8.13 (s,
eN]CHe), 7.80 (s, H-7, Ar-H), 7.29e7.64 (m, 9H, Ar-H);
13C NMR (CDCl3): d 164.8 (C-2), 160.4 (C-4), 154.4 (C-9),
136.4 (C-40), 143.9 (eN]CHe), 139.5 (C-7), 131.6 (C-5),
131.9 (C-10), 130.6 (C-20 and C-60), 130.2 (C-40), 128.9
(C-30 and C-50), 128.7 (C-10), 125.4 (C-10), 129.2 (C-30 and
C-50), 126.7 (C-200 and C-60), 123.7 (C-6), 113.6 (C-8);
EI-MS (m/z): Mþ 517.6 (M þ 2, 32%); Anal. Calcd. for
C21H12Br2ClN3O: C, 48.72; H, 2.34; N, 8.12; Found: C,
48.71; H, 2.35; N, 8.11.
6.1.1.12. 3(3-Phenylallylideneamino)-6,8-dibromo-2-phenyl-
quinazolin-4(3H )-one 12. Yield 79%; mp 228e231 ꢀC; IR:
1704 (C]O), 1667 (C]C), 1378 (CeN), 1667 (C]N), 1401
;
(CeH), 3126 (CeH, Ar), 550 (CeBr) cmꢁ1 1H NMR
(CDCl3): d 8.10 (s, 1H, H-5, Ar-H), 7.89 (s, eN]CHe), 7.82
(s, H-7, Ar-H), 6.62e6.63 (d, 5.8H-2, eN]CHeCH]CHe),
7.31e7.65 (m, 10H, Ar-H), 5.61 (s, eN]CHCH]CH); 13C
NMR (CDCl3): d 164.9 (C-2), 160.3 (C-4), 154.6 (C-9),
139.01 (N]CHCH]CH), 135.3 (C-10), 139.6 (C-7), 131.4
(C-5), 137.6 (N]CH), 130.2 (C-400), 128.5 (C-30 and C-50),
128.9 (C-30 and C-50), 126.4 (eN]CHeCH]CHe), 125.5
(C-10), 126.5 (C-20 and C-60), 126.1 (C-200 and C-60), 123.4
(C-6), 113.6 (C-8); EI-MS (m/z): Mþ 509.58 (M þ 2, 25%);
Anal. Calcd. for C23H15Br2N3O: C, 54.25; H, 2.97; N, 8.25;
Found: C, 49.92; H, 2.87; N, 8.24.
6.1.1.9. 3(4-Nitrobenzylideneamino)-6,8-dibromo-2-phenylqui-
nazolin-4(3H )-one 9. Yield 78%; mp 228e230 ꢀC; IR: 1703
(C]O), 1667 (C]C), 1378 (CeN), 1607 (C]N), 1433
(CeH), 3115 (CeH, Ar), 529 (CeBr), 1523 (CeNO2)
1
cmꢁ1; H NMR (CDCl3): d 8.09 (s, 1H, H-5, Ar-H), 8.13 (s,
eN]CHe), 7.84 (s, H-7, Ar-H), 7.31e7.80 (m, 9H, Ar-H);
13C NMR (CDCl3): d 164.3 (C-2), 160.7 (C-4), 54.3 (C-9),
150.7 (C-40), 143.8 (eN]CHe), 139.2 (C-10), 139.5 (C-7),
131.4 (C-5), 130.3 (C-400), 130.2 (C-20 and C-60), 128.9
(C-30 and C-50), 128.7 (C-10), 125.4 (C-10), 121.3 (C-30 and
C-50), 126.2 (C-200 and C-60), 123.6 (C-6), 113.7 (C-8); EI-MS
(m/z): Mþ 528.9 (M þ 2, 30%); Anal. Calcd. for
C21H12Br2N4O3; C, 47.76; H, 2.29; N, 10.61; Found: C,
47.75; H, 2.28; N, 10.62.
6.2. Anti-microbial screening
The anti-bacterial activity of the synthesized compounds
was tested against four Gram-positive bacteria (S. aureus
ATCC-9144, S. epidermidis ATCC-155, M. luteus ATCC-
4698 and B. cereus ATCC-11778) and three Gram-negative
bacteria (E. coli ATCC-25922, P. aeruginosa ATCC-2853
and K. pneumoniae ATCC-11298) using nutrient agar medium
(Hi-Media Laboratories, India). The anti-fungal activities of
the compounds were tested against two fungi namely A. niger
ATCC-9029 and A. fumigatus ATCC-46645 using sabouraud
dextrose agar medium (Hi-Media Laboratories, India).
6.1.1.10. 3(3,4,5-Trimethoxybenzylideneamino)-6,8-dibromo-
2-phenylquinazolin-4(3H )-one 10. Yield 72%; mp 236e238
ꢀC; IR: 1703 (C]O), 1670 (C]C), 1377 (CeN), 1607
(C]N), 1449 (CeH), 3126 (CeH, Ar), 518 (CeBr), 1202
1
(CeOCH3) cmꢁ1; H NMR (CDCl3): d 8.10 (s, 1H, H-5, Ar-
H), 8.14 (s, eN
ce:glyph name="dbnd"/>CHe), 7.83 (s, H-7, Ar-H), 6.76e7.62
(m, 5H, Ar-H), 7.71 (H-7, Ar-H), 6.99 (s, H60, Ar-H), 3.70 (s,
9H, (OCH3)3); 13C NMR (CDCl3): d 164.2 (C-2), 160.3 (C-4),
154.2 (C-9), 150.9 (C-30 and C-50), 143.4 (eN]CHe), 141.6
(C-40), 139.6 (C-7), 131.3 (C-5), 130.2 (C-400), 128.7 (C-10),
128.9 (C-30 and C-50), 125.6 (C-10), 128.1 (C-10), 126.2 (C-200
and C-600), 123.7 (C-6), 113.7 (C-8), 106.7 (C-20 and C-60),
53.3 (OCH3)3; EI-MS (m/z): Mþ 570.3 (M þ 2, 40%); Anal.
Calcd. for C24H19Br2N3O4: C, 50.29; H, 3.34; N, 7.33; Found:
C, 50.28; H, 3.35; N, 7.34.
6.2.1. Paper disc diffusion technique
The sterilized [28] (autoclaved at 120 ꢀC for 30 min)
medium (40e50 ꢀC) was inoculated (1 ml/100 ml of medium)
with the suspension (105 cfu mlꢁ1) of the micro-organism
(matched to McFarland barium sulphate standard) and poured
into a petridish to give a depth of 3e4 mm. The paper impreg-
nated with the test compounds (mg mlꢁ1 in dimethyl formam-
ide) was placed on the solidified medium. The plates were
pre-incubated for 1 h at room temperature and incubated
at 37 ꢀC for 24 and 48 h for anti-bacterial and anti-fungal
activities, respectively. Ciprofloxacin (100 mg/disc) and
Ketoconazole (100 mg/disc) were used as standard for anti-
bacterial and anti-fungal activity, respectively. The observed
zone of inhibition is presented in Table 1.
6.1.1.11.
3(4-Hydroxy-3-methoxybenzylideneamino)-6,8-di-
bromo-2-phenylquinazolin-4(3H )-one 11. Yield 82%; mp
246e248 ꢀC; IR: 1704 (C]O), 1686 (C]C), 1377 (CeN),

P. Panneerselvam et al. / European Journal of Medicinal Chemistry 44 (2009) 2328e2333
2333
[7] P. Pannerselvam, R.V. Pradeepchandran, S.K. Sridhar, Indian J. Pharm.
Sci. 65 (2003) 268e273.
6.2.2. Minimum inhibitory concentration (MIC)
MIC [29] of the compound was determined by agar streak
dilution method. A stock solution of the synthesized
compound (100 mg mlꢁ1) in dimethyl formamide was prepared
and graded quantities of the test compounds were incorporated
in specified quantity of molten sterile agar (nutrient agar for
anti-bacterial activity and sabouraud dextrose agar medium
for anti-fungal activity). A specified quantity of the medium
(40e50 ꢀC) containing the compound was poured into
a petridish to give a depth of 3e4 mm and allowed to solidify.
Suspension of the micro-organism was prepared to contain
approximately 105 cfu mlꢁ1 and applied to plates with serially
diluted compounds in dimethyl formamide to be tested and
incubated at 37 ꢀC for 24 and 48 h for bacteria and fungi,
respectively. The MIC was considered to be the lowest
concentration of the test substance exhibiting no visible
growth of bacteria or fungi on the plate. The observed MIC
is presented in Table 1.
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