Microwave assisted synthesis and in vitro antimicrobial assessment of quinolone based s-triazines

Article abstract of DOI:10.1515/HC.2011.006

A series of 1,3,5-triazine derivatives that contain aniline, 4-hydroxy-N-methylquinolone and different piperazine and piperidine moieties as substituents on the carbon atoms of the triazine ring has been synthesized by a simple and efficient synthetic pro

Full text of DOI:10.1515/HC.2011.006

Heterocycl. Commun., Vol. 17(1-2), pp. 33–41, 2011 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/HC.2011.006
Microwave assisted synthesis and in vitro antimicrobial
assessment of quinolone based s-triazines
Divyesh Patel1, Rahul Patel1, Premlata Kumari1,*
bacterial and fungal strains in order to reduce drug resistance
to the pathogenic strains and in order to maintain a pool of
new bioactive candidates at all times.
and Navin Patel2
1Applied Chemistry Department, S.V. National Institute of
Technology, Surat-395007, India
Various 1,3,5-triazines show powerful antimicrobial
(Srinivas et al., 2006; Zhou et al., 2008), antiprotozoal (Ales-
2 Department of Chemistry, V.N. South Gujarat University,
sandro et al., 2005), anticancer (Rita et al., 2004), antima-
Surat-395007, India
larial (Sergio et al., 2008) and antiviral (Yuan-Zhen et al.,
2008) activities. On the other hand, quinolones such as cip-
rofloxacin, ofloxacin, lomefloxacin, and enoxacin are estab-
lished synthetic antibacterial agents (Boehm et al., 2000).
They are widely prescribed for the treatment of infections
in humans. They corrupt the activities of prokaryotic type
II topoisomerases, DNA gyrase and topoisomerase IV, and
induce them to kill cells by generating high levels of double-
stranded DNA breaks. Type II topoisomerases modulate the
topological state of the genetic material by passing an intact
DNA helix through a transient double stranded break that
they generate in a separate DNA segment (Zhang et al., 1991;
Drlica and Zhao, 1999). Like bacterial cells, eukaryotic spe-
cies require a type II topoisomerase, known as topoisomerase
II, for viability (Burden and Osheroff, 1998). Thus, in addi-
tion to the antibacterial quinolones, specific members of this
drug family display high activity against eukaryotic type II
topoisomerases, as well as cultured mammalian cells and in
vivo tumor models (Clement et al., 1995). Quinolone deriva-
tives are used as anticancer (Karl and Xilin, 1997), anti-HIV
(Enrica et al., 2001), antitumor (Sun et al., 2006), antioxidant,
anti-inflammatory (Anastasia et al., 2007) and antithyroid
agents (Ukrainets et al., 1997). Quinolones are also used as
components of organic-laser active media, luminophores, and
fluorescent labels (Vasil’eva et al., 2002). Compounds syn-
thesized as part of this work are structural combinations of
1,3,5-triazine and quinolone moieties.
*Corresponding author
e-mail: premlatakumari1@gmail.com
Abstract
A series of 1,3,5-triazine derivatives that contain aniline,
4-hydroxy-N-methylquinolone and different piperazine and
piperidine moieties as substituents on the carbon atoms of the
triazine ring has been synthesized by a simple and efficient
synthetic protocol. Comparative studies were performed on
the compounds, which were synthesized with conventional
and microwave heating methods. The microwave method
was observed to be more beneficial as it provides an increase
in yield and 90%–95% reduction time. The antimicrobial
activity of the compounds was tested against seven bacteria
(Staphylococcus aureus, Bacillus cereus, Escherichia coli,
Pseudomonas aeruginosa, Klebsiella pneumonia, Salmonella
typhi, Proteus vulgaris) and two fungi (Aspergillus niger,
Candida albicans). The results indicate that some of the novel
s-triazines have noteworthy activity in MIC and agar diffu-
sion tests.
Keywords: antimicrobial activity; microwave irradiation;
piperazine; piperidine; quinolone; s-triazine.
Microwave technology has become a powerful tool in
organic synthesis, since by employing this technique it is gen-
erally possible to prepare organic compounds very quickly,
with high purity and better yields compared to other more con-
ventional methods (Kayes, 2002; Kappe and Stadler, 2005).
In particular, we carried out the reaction of 4-(4-chloro-6-
phenylamino-[1,3,5]triazin-2-yloxy)-1-methyl-1H-quinolin-
2-one (3) with different amines under microwave irradiation.
This method proved to be superior to the traditional heating.
Introduction
Controlling the deadliest infectious diseases in the world is
seriously threatened by the sharpening increase in the multi-
drug resistance of human pathogenic strains to a wide range
of currently available antimicrobial agents. Worryingly,
in most of the developing countries, this problem is at an
alarming level, where resistant infections lead to increased
mortality. Furthermore, an increased number of immunocom-
promised patients attributable to the ongoing HIV epidemic
can further increase the burden of antimicrobial resistance
in human civilization by facilitating the spread of resistant
pathogens (Nathan, 2004). Significant impact of the affliction
of infectious disease in developing countries due to multidrug
resistance posed by bacteria, has driven us to examine newly
synthesized derivatives against the representative panel of
Results and discussion
Compounds 5a-u have been synthesized according to the
Scheme 1. Two basic approaches, conventional heating and
microwave irradiation, were applied for the final nucleo-
philic substitution reactions of the intermediate product 3
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34 D. Patel et al.
Cl
N
NH2
NH
N
N
THF
NaH
+
N
N
Cl
Cl
Phenylamine
Cl
Cl
2,4,6-Trichloro-[1,3,5]triazine
N
(4,6-Dichloro-[1,3,5]triazin-2-yl)-phenyl-amine
1
NH
OH
N
N
THF
NaH
O
Cl
Compound 1
+
N
O
N
CH3
4-Hydroxy-1-methyl-1H-quinolin-2-one
O
N
2
CH3
4-(4-Chloro-6-phenylamino-[1,3,5]triazin-2-yloxy)-1-methyl-1H-
quinolin-2-one
3
11
10
9
12
13
NH
7
8
4
3
N
N5
6
2
1,4-dioxane
MW
O
N
R
24
23
N
19
16
1
Compound 3
+
4a-u (R)
18
17
K2CO3
14
15
22
O
21
25
20
CH3
26
5a-u
Amines 4a-u (R-H) coupled to compound 3
O
HN
N
C
h
o
HN
N
CH
HN
N
CH5
a
CH3
CH3
CH
CH3
HN
N
C2H5
N
HN
b
I
p
HN
N
CH
Cl
Scheme 1 (Continued)
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Quinolone based s-triazines 35
F
Cl
Cl
N
HN
HN
N
N
c
j
q
r
N
N
HN
HN
N
N
HN
HN
Cl
N
N
d
k
F
CF3
e
f
l
s
t
N
HN
NH
HN N CH2
OCH3
H3CO
CH2
NH
m
O
CH2
HN
HN
N
N
OCH3
HN
HN
CH3
OCH3
g
n
u
N
HN
CH3
Scheme 1 Synthesis of target compounds.
with amines 4a-u to furnish the desired products 5a-u. A
comparative study of the yields of products under micro-
wave irradiation and conventional heating showed that the
use of microwave irradiation substantially reduced the reac-
tion times from h to min and appreciably increased the yields
(Table 1). The disubstituted s-triazine intermediate 3, in
turn, was obtained by the reaction between N-(4,6-dichloro-
[1,3,5]-triazin-2-yl)aniline (1) and 4-hydroxy-N-methyl-2
-quinolone 2 in the presence of 60% NaH at 45–50°C. As
already mentioned, substitution reaction of 3 with appro-
priate piperazines and piperidines 4a–u provided the target
compounds 5a–u.
towards Gram-negative strain E. coli, while compounds
5d, 5p, 5s, and 5t demonstrated 25 µg/ml of inhibitory
concentration level against E. coli. Compounds 5i and 5s
(26 mm – zone of inhibition) as well as 5n (25 mm – zone
of inhibition) appeared with remarkable activity against
Gram-negative P. aeruginosa at 6.25 µg/ml of MIC, where
the 0.5-fold activity was observed (MIC, 12.5 µg/ml) for
compounds 5d and 5t against the same bacteria. Inhibition
of Gram-negative bacteria K. pneumoniae was also noted
for s-triazine derivatives 5t and 5u at 12.5 µg/ml as well
as 5s with quite reduced zone diameter (23 mm). Another
five derivatives 5c, 5d, 5n, 5p and 5s exhibited 0.5-fold
growth inhibition of the same bacteria (MIC, 25 µg/ml).
Compound 5h, 5i and 5u (26 mm – zone of inhibition), and
compound 5t (25 mm – zone of inhibition) possessed the
highest activity (MIC, 12.5 µg/ml) against Gram-negative
S. typhi along with 0.5-fold activity profile of compounds
5b and 5n (MIC, 25 µg/ml). Final s-triazine derivatives 5m,
5p, and 5s (27 mm – zone of inhibition) and 5n (26 mm –
zone of inhibition) were superior in inhibiting the growth
of Gram-negative P. vulgaris (MIC, 6.25 µg/ml), whereas
0.5-fold activity was observed in the case of compounds 5h
and 5t at 12.5 µg/ml.
The antifungal bioassay results revealed that s-triazine
derivative 5p, 5r, 5s, and 5u displayed excellent antigrowth
activity (MIC, 12.5 µg/ml) against A. niger, which was found
to be equivalent to the standard drug tested. Compounds 5c,
5d and 5t appeared with 0.5-fold inhibitory action against
the same fungi at MIC, 25 µg/ml. Compounds 5d, 5h, 5t and
5u appeared with excellent inhibition of C. albicans at
25 µg/ml. Compound 5s displayed similar MIC µg/ml but
the zone of inhibition was reduced to 1 mm. Compounds 5p,
5q, and 5r indicated 0.5-fold activity (50 µg/ml) of the most
active analogues towards C. albicans.
All the synthesized compounds were tested against seven
bacteria, namely E. coli, P. aeruginosa, K. pneumoniae,
S. typhi, P. vulgaris, S. aureus, B. cereus and two fungi
C. albicans and A. niger.
The results of antimicrobial data are shown in Table 2.
Final s-triazinyl compounds 5d, 5n, and 5s showed substan-
tial activity (MIC, 6.25 µg/ml) against Gram-positive strain
S. aureus. Compound 5u exhibited a similar inhibitory con-
centration of 6.25 µg/ml against S. aureus with 1 mm of
lesser zone of inhibition. Compounds 5p and 5t were found
half as active (MIC, 12.5 µg/ml) against S. aureus as com-
pared to most active analogues tested against the same strain.
Final s-triazinyl analogues 5s and 5t displayed strong inhib-
itory profile at 6.25 µg/ml against Gram-positive B. cereus,
while compounds 5h and 5r exhibited a similar inhibitory
concentration of 6.25 µg/ml against B. cereus with 1 mm of
lesser zone of inhibition along with 0.5-fold comparative
activity of compounds 5p and 5n (MIC, 12.5 µg/ml) against
the same bacterial strain. Compounds 5c and 5q (26 mm
of zone of inhibition) were found to have good activity
(MIC, 12.5 µg/ml) along with similar inhibitory concentra-
tion level of compound 5r (25 mm of zone of inhibition)
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36 D. Patel et al.
Table 1 Comparison of the synthesis of 5a-u using microwave irradiation and conventional heating (see Scheme 1 for the structures of
5a-u).
Entry
R
Microwave method
Reaction time (min) Yield (%)
Conventional method
Reaction time (h) Yield (%)
5a
5b
5c
5d
5e
5f
5g
5h
5i
N-methylpiperazino
N-ethylpiperazino
4-(3-chlorophenyl)piperazino
4-(2,3-dichlorophenyl)piperazino
Piperidino
Morpholino
4-phenylpiperazino
4-acetylpiperazino
4-isopropylpiperazino
2
2
3
4
5
4
6
4
7
8
8
3
2
4
2
5
6
6
7
5
4
79
81
77
83
87
89
84
80
75
85
82
87
86
90
72
77
92
90
87
80
74
9
9
10
10
8
60
72
61
70
64
62
65
63
60
73
71
79
77
75
66
63
78
81
61
65
60
9
9
11
10
12
12
11
13
8
5j
5k
5l
4-(2-pyridyl)piperazino
4-(2-pyrimidyl)piperazino
4-benzylpiperazino
5m
5n
5o
5p
5q
5r
5s
5t
4-benzylpiperidino
3,5-dimethylpiperidino
4-benzhydrylpiperazino
4-chlorobenzhydrylpiperazino
4-(2-fluorophenyl)piperazino
4-(4-fluorophenyl)piperazino
4-(3-(trifluoromethyl)phenyl)piperazino
4-(2,3,4-trimethoxybenzyl)piperazino
4-(4-methoxyphenyl)piperazino
9
12
12
11
12
10
11
5u
Table 2 In vitro antibacterial activity of compounds 5a-u. For structures, see Table 1 and Scheme 1.
Compound
(100 µg/disc)
Zone of inhibition [mm (MIC in µg/ml)]
Gram (-)
Gram (+)
S. aureus
B. cereus
E. coli
P. aeruginosa
K. pneumoniae
S. typhi
P. vulgaris
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
19 (100)
20 (100)
23 (25)
28 (6.25)
22 (100)
21 (100)
19 (100)
24 (25)
23 (100)
21 (100)
20 (100)
21 (100)
23 (50)
21 (100)
22 (25)
25 (25)
18 (100)
20 (100)
26 (12.5)
25 (25)
16 (100)
16 (100)
15 (100)
23 (50)
19 (100)
19 (100)
24 (25)
25 (12.5)
16 (100)
19 (100)
16 (100)
23 (25)
26 (6.25)
20 (100)
20 (100)
20 (100)
17 (100)
25 (6.25)
18 (100)
21 (50)
20 (100)
19 (100)
23 (25)
21 (50)
23 (25)
23 (100)
23 (50)
19 (100)
20 (100)
22 (50)
23 (12.5)
16 (100)
16 (100)
16 (100)
24 (12.5)
22 (50)
17 (100)
21 (100)
20 (100)
27 (6.25)
26 (6.25)
21 (100)
27 (6.25)
23 (50)
26 (6.25)
20 (100)
20 (100)
17 (100)
26 (6.25)
22 (50)
18 (100)
21 (100)
19 (100)
19 (100)
26 (12.5)
20 (100)
25 (12.5)
23 (25)
22 (25)
17 (100)
16 (100)
19 (100)
22 (50)
21 (100)
19 (100)
17 (100)
18 (100)
18 (100)
22 (25)
17 (100)
18 (100)
16 (100)
26 (12.5)
26 (12.5)
19 (100)
19 (100)
17 (100)
20 (100)
24 (25)
18 (100)
22 (100)
24 (50)
23 (50)
24 (50)
22 (50)
16 (100)
18 (100)
17 (100)
17 (100)
23 (50)
19 (100)
25 (25)
26 (12.5)
25 (12.5)
25 (25)
28 (6.25)
22 (50)
25 (12.5)
24 (25)
19 (100)
22 (25)
23 (12.5)
22 (50)
5q
5r
5s
5t
21 (50)
22 (25)
26 (6.25)
24 (12.5)
21 (25)
25 (25)
26 (6.25)
27 (6.25)
27 (6.25)
24 (25)
22 (25)
28 (6.25)
26 (12.5)
27 (6.25)
30 (1.0)
23 (25)
27 (6.25)
25 (12.5)
23 (25)
24 (25)
22 (50)
32 (1.0)
25 (12.5)
25 (12.5)
33 (1.0)
25 (12.5)
26 (12.5)
30 (1.0)
5u
Ciprofloxacin
(100 µg/disc)
DMSO
31 (1.0)
33 (1.0)
31 (1.0)
–
–
–
–
–
–
–
The MIC values were evaluated at concentration range of 3.12–100 µg/ml.
Each value is the mean of three independent experiments.
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Quinolone based s-triazines 37
Table 3 In vitro antifungal activity of compounds 5a-u. For
structures, see Table 1 and Scheme 1.
subjected to elemental analysis using a Heraeus Carlo Erba 1180
CHN analyzer.
Compound
(100 µg/disc)
Zone of inhibition in [mm (MIC in µg/ml)]
N-(4,6-Dichloro-[1,3,5,]triazin-2-yl)aniline (1)
A. niger
C. albicans
To a stirred solution of 2,4,6-trichloro-1,3,5-triazine (15 g, 0.081 mol)
in anhydrous tetrahydrofuran (THF) (150 ml) aniline (7.97 g,
0.081 mol) was added dropwise at 0–5°C. The resulting mixture was
stirred at this temperature for 2 h, then treated with triethylamine
(8.28 g, 0.081 mol), and stirring was continued for another 4 h. The
mixture was then treated with crushed ice, neutralized with dilute HCl
and the precipitate was filtered, dried, and crystallized from acetone to
afford 17.0 g (87%) of 1; mp 191–194°C; IR: 3296.5 cm−1 (-NH); 1H
NMR: δ 9.15 (s, 1H, NH), 6.93–7.69 (m, 5H, Ar-H); 13C NMR 117.9,
122.8, 128.8, 139.6, 165.4, 171.2.Analysis: calculated for C9H6Cl2N4:
C, 44.84; H, 2.51; N, 23.24. Found: C, 44.76; H, 2.40; N, 23.29.
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
16 (100)
20 (100)
24 (25)
16 (100)
17 (100)
24 (100)
28 (25)
17 (100)
15 (100)
17 (100)
28 (25)
20 (100)
17 (100)
17 (100)
16 (100)
20 (100)
24 (100)
21 (100)
26 (50)
26 (50)
27 (50)
27 (25)
28 (25)
28 (25)
33 (1.0)
24 (25)
16 (100)
19 (100)
21 (100)
23 (50)
21 (100)
18 (100)
16 (100)
17 (100)
17 (100)
24 (50)
19 (100)
25 (12.5)
24 (50)
25 (12.5)
25 (12.5)
25 (25)
4-(4-Chloro-6-anilino-[1,3,5]triazin-2-yl)oxy)-1-methyl-
1H-quinolin-2-one (3)
To a stirred mixture of 4-hydroxy-N-methylquinolone (2, 8.63 g,
0.05 mol) and 60% NaH (1.18 g, 0.05 mol) in anhydrous THF
(150 ml), compound 1 (11.89 g, 0.05 mol) was added. The mixture
was stirred for 1 h at room temperature and then for another 14 h
at 45–50°C, after which time it was treated with crushed ice, and
the solid precipitate was filtered, dried, and crystallized from THF
to afford 7.53 g (86%) of 3; mp 265–269°C; IR: 1243–1251 cm-1
5q
5r
5s
5t
5u
25 (12.5)
30 (≤3)
Ketoconazole
(100 µg/disc)
DMSO
1
(C-O-C), 1700.4 cm-1 (C=O); H NMR: δ 9.17 (s, 1H, NH), 7.10–
7.82 (m, 9H, Ar-H), 6.47 (s, 1H, H at C-22 of quinolone), 3.25 (s, 3H,
CH3 of quinolone); 13C NMR 32.5, 97.2, 115.5, 118.7, 122.5, 123.1,
123.8, 126.6, 132.0, 140.1, 141.2, 151.7, 165.6, 172.4. Analysis:
calculated for C19H14ClN5O2: C, 60.09; H, 3.72; N, 18.44. Found: C,
60.17; H, 3.59; N, 18.37.
–
–
The MIC values were evaluated at concentration range of
3.12–100 µg/ml.
Each value is the mean of three independent experiments.
General procedures for preparation of compounds 5a-u
Conclusions
Conventional method To a solution of 3 (3.79 g, 0.01 mol) in
1,4-dioxane (30 ml), piperazine or piperidine derivative was added.
For example, 1-benzyl piperazine (4i, 1.57 g, 0.01 mol) was added
and the mixture was heated under reflux for 10–15 h as per TLC
monitoring. Potassium carbonate was used for the neutralization of
the reaction mixture. After completion of the reaction, it was treated
with crushed ice, neutralized by dilute HCl, and the precipitate thus
obtained was filtered, dried and crystallized from THF (15 ml) to
give 4.19 g (79%) of 5i as light brown solid. The same procedure was
applied for the synthesis of other final compounds.
This study indicates that the developed procedure for synthe-
sis of title compounds using microwave-assisted synthesis is
much more simple, easier to work with, and safer compared
to the conventional method. From the bioassay results, it is
clear that substituents on the s-triazine ring strongly affect
the antimicrobial activity. Some modifications to improve the
potency of the series by changing the position and the type
of substituents are currently under investigation and will be
reported in future.
Microwave method The microwave irradiation of the final nu-
cleophilic substitution mixtures were carried out on the same scale,
using the same solvent (1,4-dioxane) and under similar concentration
conditions as indicated above. The reaction time was found to be dra-
matically reduced for each substitution from 10 to 15 h (conventional
heating method) to 2–6 min under microwave irradiation. Microwave
assisted reactions of 3 with various amines were conducted in sep-
tum-sealed reaction vessels in a microwave reactor. For example,
compound 3 (3.79 g, 0.01 mol) in the presence of K2CO3 (1.41 g)
was condensed with 4-benzylpiperidine (4m, 1.74 g, 0.01 mol) us-
ing 1,4-dioxane (30 ml) as a solvent under microwave irradiation at
180 W power for 2–6 min. The mixture was heated until completion
as determined by silica gel TLC analysis (1:1 chloroform/methanol
developing system). After completion of reaction the solvent was re-
moved by using vacuum solvent recovery module. The residue was
Experimental section
Microwave assisted reactions were carried out on a microwave reac-
tor model-Roto Synth Terminal-640. The melting points were deter-
mined in open capillaries on a Veego VMP-D electronic apparatus
and are uncorrected. The IR spectra were recorded on a Shimadzu
8400-S FT-IR spectrophotometer in KBr pellets. Thin layer chro-
matography was performed on microscopic glass slides (2×7.5 cm)
coated with silica gel-G, using appropriate mobile phase system
and spots were visualized under UV radiation. 1H NMR and 13C
NMR spectra were recorded on a Varian 400 MHz spectrometer at
400 MHz and 100 MHz, respectively, in CDCl3 using TMS as inter-
nal standard. The 19F spectra were recorded on the same instrument
in CDCl3 using CFCl3 as internal standard. All new compounds were
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38 D. Patel et al.
treated with crushed ice, neutralized with diluted HCl, filtered, and
the solid material was dried and crystallized from THF to give 4.46 g
(86%) of compound 5m. The same procedure was applied for synthe-
sis of the other final compounds. The conventional method and the
microwave assisted methods are compared in Table 1.
C=O of quinolone), 152.8 (C-23, C-O-C at quinolone), 148.6, 132.7,
130.5, 129.5, 128.8, 128.5, 123.7, 123.5, 122.7, 120.2, 119.7, 118.8,
118.6, 116.1 (14C, Ar-C), 110.4 (C-22, C-C=O of quinolone), 50.2,
46.8 (4C, piperazine), 32.4 (C-26, -CH3 of quinolone). Analysis:
calculated for C29H25Cl2N7O2: C, 60.63; H, 4.39; N, 17.07. Found:
C, 60.51; H, 4.47; N, 17.15.
Characterization of compounds 5a-u
[4-(4-Anilino-6-piperidino-[1,3,5]triazin-2-yl)oxy]-1-methyl-1H-
quinolin-2-one (5e): mp 262–265°C; IR: 3297.1 (N-H str.), 1694.3
(C=O of quinolone), 1261.4 (C-O-C), 812.1 cm-1 (s-triazine C-N
str.); 1H NMR: δ 9.22 (s, 1H, -NH), 7.01–8.17 (m, 9H, Ar-H), 6.41
(s, 1H, H at C-22 of quinolone), 3.40 (s, 3H, CH3 of quinolone),
2.57–3.16 (m, 10H, piperidine); 13C NMR: δ 171.8 (C-6, C-N at
piperazine linkage), 171.3 (C-2, C-O-C at quinolone linkage),
165.4 (C-4, C-NH at aniline linkage), 159.1 (C-21, C=O of qui-
nolone), 152.6 (C-23, C-O-C at quinolone), 1422, 140.0, 132.6,
128.8, 128.4, 123.7, 123.4, 122.7, 117.8, 118.5, 116.7, 115.8 (12C,
Ar-C), 109.3 (C-22, C-C=O of quinolone), 46.8, 31.3, 34.7 (5C,
piperidine), 32.4 (C-26, CH3 of quinolone). Analysis: calculated for
C24H24N6O2: C, 67.27; H, 5.65; N, 19.61. Found: C, 67.21; H, 5.52;
N, 19.50.
1-Methyl-[4-[4-(4-methylpiperazino)-6-anilino-[1,3,5]triazin-2-yl]
oxy]-1H-quinolin-2-one (5a): mp 258–261°C; IR: 3296.4 (N-H str.),
1712.2 cm-1 (C=O of quinolone), 1463.0 (CH3), 1260.5 (C-O-C),
811.2 cm-1 (s-triazine C-N str.); 1H NMR: δ 9.17 (s, 1H, -NH), 6.97–
8.21 (m, 9H, Ar-H), 6.45 (s, 1H, H at C-22 of quinolone), 3.60 (s,
3H, CH3 of quinolone), 3.19 (br-s, 8H, piperazine), 2.57 (s, 3H, CH3
of piperazine); 13C NMR: δ 171.9 (C-6, C-N at piperazine linkage),
171.3 (C-2, C-O-C at quinolone linkage), 165.4 (C-4, C-NH at ani-
line linkage), 159.2 (C-21, C=O of quinolone), 152.8 (C-23, C-O-C
at quinolone), 142.6, 140.1, 132.7, 128.8, 128.8, 123.7, 123.6, 122.7,
118.8, 1188, 116.8, 115.9 (12 C, Ar-C), 110.1 (C-22, C-C=O of qui-
nolone), 64.1, 45.0 (4C, piperazine), 32.7 (C-26, CH3 of quinolone).
Analysis: calculated for C24H25N7O2: C, 65.00; H, 5.68; N, 22.11.
Found: C, 65.17; H, 5.61; N, 22.02.
4-[(6-Anilino-4-morpholino-[1,3,5]triazin-2-yl)oxy]-1-methyl-1H-
quinolin-2-one (5f): mp 216–266°C; IR: 3296.2 (N-H str.), 1705.1
(C=O of quinolone), 1260.2 (C-O-C), 814.2 cm-1 (s-triazine C-N
str.); 1H NMR: δ 9.05 (s, 1H, -NH), 6.97–8.17 (m, 9H, Ar-H), 6.53 (s,
1H, H at C-22 of quinolone), 3.80–3.82 (m, 8H, morpholine), 3.34 (s,
3H, -CH3 of quinolone); 13C NMR: δ 171.9 (C-6, C-N at piperazine
linkage), 171.2 (C-2, C-O-C at quinolone linkage), 165.3 (C-4, C-NH
at aniline linkage), 159.3 (C-21, C=O of quinolone), 152.8 (C-23, C-
O-C at quinolone), 143.9, 132.5, 132.5, 129.9, 128.7, 123.5, 122.3,
120.2, 119.66, 116.5, 115.0, 112.4 (12C, Ar-C), 109.9 (C-22, C-C=O
of quinolone), 64.4, 52.3 (4C, morpholine), 32.2 (C-26, CH3 of qui-
nolone). Analysis: calculated for C23H22N6O3: C, 64.17; H, 5.15; N,
19.52. Found: C, 64.10; H, 5.26; N, 19.39.
[4-[4-(4-Ethylpiperazino)-6-anilino-[1,3,5]triazin-2-yl]oxy]-1-meth-
yl-1H-quinolin-2-one (5b): mp 253–258°C; IR: 3296.5 (N-H str.),
1694.4 (C=O of quinolone), 1490.3 (CH2CH3), 1256.3 (C-O-C),
806.2 cm-1 (s-triazine C-N str.); 1H NMR: δ 9.12 (s, 1H, -NH),
6.85–8.19 (m, 9H, Ar-H), 6.47 (s, 1H, H at C-22 of quinolone), 3.31
(s, 3H, CH3 of quinolone), 3.57 (br-s, 8H, piperazine), 2.60 (s, 3H,
CH2-CH3 of piperazine), 1.90 (s, 2H, CH2-CH3 of piperazine); 13C
NMR 171.9 (C-6, C-N at piperazine linkage), 171.3 (C-2, C-O-C
at quinolone linkage), 165.4 (C-4, C-NH at aniline linkage), 159.23
(C-21, C=O of quinolone), 152.8 (C-23, C-O-C at quinolone), 142.7,
140.2, 132.7, 128.8, 128.7, 123.7, 123.5, 122.7, 118.6, 118.9, 116.8,
115.9 (12 C, Ar-C), 110.1 (C-22, C-C=O of quinolone), 58.2, 46.9
(4C, piperazine), 51.7 (C-34, CH2-CH3 of piperazine), 32.6 (C-26,
CH3 of quinolone), 15.4 (C-33, CH2-CH3 of piperazine). Analysis:
calculated for C25H27N7O2: C, 65.63; H, 5.95; N, 21.43. Found: C,
65.51; H, 5.88; N, 21.56.
4-[(4-Anilino-6-(4-phenylpiperazino)-[1,3,5]triazin-2-yl)oxy]-1-
methyl-1H-quinolin-2-one (5g): mp 273–276°C; IR: 3298.4 (N-H
str.), 1697.2 (C=O of quinolone), 1260.3 (C-O-C), 817.14 cm-1
1
(s-triazine C-N str.); H NMR: δ 9.11 (s, 1H, -NH), 6.82–8.21 (m,
14H, Ar-H), 6.57 (s, 1H, H at C-22 of quinolone), 3.56 (br-s, 8H,
piperazine), 3.29 (s, 3H, CH3 of quinolone); 13C NMR: δ 172.21
(C-6, C-N at piperazine linkage), 171.45 (C-2, C-O-C at quinolone
linkage), 165.26 (C-4, C-NH at aniline linkage), 159.30 (C-21, C=O
of quinolone), 152.72 (C-23, C-O-C at quinolone), 150.9, 132.9,
130.1, 129.9, 128.8, 128.7, 123.9, 123.5, 122.8, 119.5, 118.8, 118.4,
116.9, 116.3, 116.3, 115.2 (16C, Ar-C), 110. (C-22, C-C=O of qui-
nolone), 50.4, 46.1 (4C, piperazine), 32.1 (C-26, -CH3 of quinolone).
Analysis: calculated for C29H27N7O2: C, 68.89; H, 5.38; N, 19.39.
Found: C, 68.81; H, 5.50; N, 19.32.
4-[4-[4-(3-Chlorophenyl)piperazino]-6-anilino-[1,3,5]triazin-2-yl]-
oxy]-1-methyl-1H-quinolin-2-one (5c): mp 230–236°C; IR: 3293.1
(N-H str.), 1697.5 (C=O of quinolone), 1270.1 (C-O-C), 816.91
(Cl), 814.2 cm-1 (s-triazine C-N str.); 1H NMR: δ 9.14 (s, 1H, -NH),
6.62–8.24 (m, 13H, Ar-H), 6.41 (s, 1H, H at C-22 of quinolone), 3.39
(s, 3H, CH3 of quinolone), 3.31 (br-s, 8H, piperazine); 13C NMR
172.1 (C-6, C-N at piperazine linkage), 171.8 (C-2, C-O-C at qui-
nolone linkage), 165.3 (C-4, C-NH at aniline linkage), 159.3 (C-21,
C=O of quinolone), 152.7 (C-23, C-O-C at quinolone), 152.8, 152.0,
132.6, 131.1, 128.8, 128.7, 123.9, 122.7, 119.1, 118.6, 118.8, 117.5,
115.8, 115.2 (14C, Ar-C), 110.2 (C-22, C-C=O of quinolone), 53.1,
47.51 (4C, piperazine), 31.8 (C-26, -CH3 of quinolone). Analysis:
calculated for C29H26ClN7O2: C, 64.50; H, 4.85; N, 18.16. Found:
C, 64.56; H, 4.72; N, 18.27.
4-[(4-(4-Acetylpiperazino)-6-anilino-[1,3,5]triazin-2-yl)oxy]-1-
methyl-1H-quinolin-2-one (5h): mp 266–271°C; IR: 3297.5 (N-H
str.), 1696.3 (C=O of quinolone), 1258.2 (C-O-C), 1692.1 (C=O of
1
COCH3), 1491.4 (CH3 of COCH3), 810.2 (s-triazine C-N str.); H
4-[4-[4-(2,3-Dichlorophenyl)piperazino]-6-anilino-[1,3,5]triazin-
2-y]oxy]-1-methyl-1H-quinolin-2-one (5d): mp 249–254°C; IR:
3298.4 (N-H str.), 1695.3 (C=O of quinolone), 1262.4 (C-O-C), 817.0
(s-triazine C-N str.), 804.2 cm-1 (-Cl); 1H NMR: δ 9.19 (s, 1H, -NH),
6.80–8.14 (m, 12H, Ar-H), 6.47 (s, 1H, H at C-22 of quinolone), 3.35
(s, 3H, CH3 of quinolone), 3.62 (br-s, 8H, piperazine); 13C NMR
171.7 (C-6, C-N at piperazine linkage), 171.3 (C-2, C-O-C at qui-
nolone linkage), 166.1 (C-4, C-NH at aniline linkage), 1601 (C-21,
NMR: δ 9.15 (s, 1H, NH), 6.96–8.17 (m, 9H, Ar-H), 6.52 (s, 1H,
H at C-22 of quinolone), 3.62 (br-s, 8H, piperazine), 3.32 (s, 3H,
CH3 of quinolone), 2.36 (s, 3H, COCH3); 13C NMR: δ 172.2 (C-6,
C-N at piperazine linkage), 171.8 (C-2, C-O-C at quinolone link-
age), 169.77 (C-33, COCH3), 166.1 (C-4, C-NH at aniline linkage),
160.3 (C-21, C=O of quinolone), 152. 6 (C-23, C-O-C at quinolone),
141.1, 140.2, 132.8, 128.9, 128.8, 123.8, 123.5, 122.7, 118.9, 118.6,
116.8, 115.3 (12C, Ar-C), 109.5 (C-22, C-C=O of quinolone), 49.6,
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Quinolone based s-triazines 39
47.1 (4C, piperazine), 31.2 (C-26, -CH3 of quinolone), 24.2 (C-35,
COCH3). Analysis: calculated for C25H25N7O3: C, 63.68; H, 5.34;
N, 20.79. Found: C, 63.60; H, 5.27; N, 20.85.
quinolone). Analysis: calculated for C30H29N7O2: C, 69.35; H, 5.63;
N, 18.87. Found: C, 69.21; H, 5.56; N, 18.97.
4-[(4-Anilino-6-(4-benzylpiperidino)-[1,3,5]triazin-2-yl)oxy]-1-
methyl-1H-quinolin-2-one (5m): mp 278–284°C; IR: 3296.2 (N-H
str.), 1694.3 (C=O of quinolone), 1262.2 cm-1 (C-O-C); 1H NMR: δ
9.07 (s, 1H, NH), 7.03–8.11 (m, 14H, Ar-H), 6.49 (s, 1H, H at C-22
of quinolone), 3.83 (t, 4H, piperidine), 3.65 (t, 4H, piperidine), 3.39
(s, 3H, CH3 of quinolone), 2.58 (d, 2H, CH2 at piperidine linkage),
1.83 (t, 1H, CH, piperidine); 13C NMR: δ 171.9 (C-6, C-N at piperi-
dine linkage), 171.4 (C-2, C-O-C at quinolone linkage), 165.4 (C-4,
C-NH at aniline linkage), 159.3 (C-21, C=O of quinolone), 152.8
(C-O-C at quinolone), 140.8, 139.1, 132.8, 129.1, 129.1, 128.9,
128.8, 128.6, 128.4, 125.6, 123.9, 123.6, 122.5, 118.7, 118.4, 115.3
(16C, Ar-C), 109.6 (C-22, C-C=O of quinolone), 63.7 (C-33, -CH2),
41.6, 39.8, 35.1 (5C, piperidine), 31.4 (C-26, CH3 of quinolone).
Analysis: calculated for C31H30N6O2: C, 71.79; H, 5.83; N, 16.20.
Found: C, 71.60; H, 5.71; N, 16.28.
4-[(4-Anilino-6-isopropylpiperazino-[1,3,5]triazin-2-yl)oxy]-1-
methyl-1H-quinolin-2-one (5i): mp 271–279°C; IR: 3297.9 (N-H
str.), 1697.5 (C=O of quinolone), 1261.2 (C-O-C), 1490.4 (-CH3),
809.9 cm-1 (s-triazine C-N str.); 1H NMR: δ 9.10 (s, 1H, -NH),
7.01–8.12 (m, 9H, Ar-H), 6.49 (s, 1H, H at C-22 of quinolone), 3.54
(br-s, 8H, piperazine), 3.34 (s, 3H, CH3 of quinolone), 2.57 (s, 1H,
CH3-CH-CH3), 1.75 (s, 6H, -CH3)2; 13C NMR: δ 171.8 (C-6, C-N at
piperazine linkage), 171.2 (C-2, C-O-C at quinolone linkage), 165.8
(C-4, C-NH at aniline linkage), 159.4 (C-21, C=O of quinolone),
152.4 (C-23, C-O-C at quinolone), 141.2, 140.1, 132.8, 128.8, 128.1,
123.8, 123.4, 122.6, 118.9, 118.5, 116.7, 115.1 (12C, Ar-C), 110.3
(C-22, C-C=O of quinolone), 57.2 (C-33, CH3-CH-CH3), 49.9, 46.2
(4C, piperazine), 32.5 (C-26, -CH3 of quinolone), 26.7 (C-34, C-35,
CH3-CH-CH3). Analysis: calculated for C26H29N7O2: C, 66.22; H,
6.20; N, 20.79. Found: C, 66.10; H, 6.27; N, 20.68.
4-[(4-Anilino-6-(3,5-dimethylpiperidino)-[1,3,5]triazin-2-yl)oxy]-
1-methyl-1H-quinolin-2-one (5n): mp 271–274°C; IR: 3296.4
(N-H str.), 1705.1 (C=O of quinolone), 1455.2 (CH3), 1260.3 cm-1
4-[(4-Anilino-6-(4-pyridin-2-yl-piperazino)-[1,3,5]triazin-2-yl)-
oxy]-1-methyl-1H-quinolin-2-one (5j): mp 277–286°C; IR: 3297.3
(N-H str.), 1696.5 (C=O of quinolone), 1257.1 (C-O-C), 820.0 cm-1
1
(C-O-C); H NMR: δ 9.04 (s, 1H, -NH), 7.02–8.06 (m, 9H, Ar-H),
1
(s-triazine C-N str.); H NMR: δ 9.14 (s, 1H, -NH), 6.70–8.20 (m,
6.41 (s, 1H, H at C-22 of quinolone), 3.68–3.75 (m, 4H, piperidine),
2.41 (br-s, 2H, CH2, piperidine), 1.93 (q, 2H, piperidine), 1.84 (6H,
d, 2-CH3); 13C NMR: δ 172.1 (C-6, C-N at piperidine linkage), 171.5
(C-2, C-O-C at quinolone linkage), 165.2 (C-4, C-NH at aniline
linkage), 159.2 (C-21, C=O of quinolone), 152.8 (C-23, C-O-C at
quinolone), 140.1, 139.1, 132.7, 128.8, 128.6, 123.9, 123.6, 122.6,
118.8, 118.3, 116.5, 114.2 (12C, Ar-C), 109.3 (C-22, C-C=O of qui-
nolone), 45.4, 42.3, 33.3 (5C, piperidine ring carbons), 32.5 (C-26,
-CH3 of quinolone), 23.8 (C-33, C-34, -CH3). Analysis: calculated
for C26H28N6O2: C, 68.40; H, 6.18; N, 18.41. Found: C, 68.29; H,
6.30; N, 18.46.
13H, Ar-H), 6.55 (s, 1H, H at C-22 of quinolone), 3.56 (br-s, 8H,
piperazine), 3.41 (s, 3H, CH3 of quinolone); 13C NMR: δ 171. 9 (C-6,
C-N at piperazine linkage), 171.4 (C-2, C-O-C at quinolone linkage),
165.1 (C-4, C-NH at aniline linkage), 159.7 (C-21, C=O of quinolo-
ne), 152.8 (C-23, C-O-C at quinolone), 148.7, 140.1, 140.1, 132.69,
128.8, 128.64, 123.9, 123.4, 122.4, 118.9, 118.9, 116.8, 115.0, 114.7,
114.2 (15C, Ar-C), 109.65 (C-22, C-C=O of quinolone), 50.7, 47.2
(4C, piperazine), 32.5 (C-26, CH3 of quinolone). Analysis: calcu-
lated for C28H26N8O2: C, 66.39; H, 5.17; N, 22.12. Found: C, 66.44;
H, 5.30; N, 22.03.
4-[(4-Anilino-6-(4-pyrimidin-2-yl-piperazino)-[1,3,5]triazin-2-yl)-
oxy]-1-methyl-1H-quinolin-2-one (5k): mp >300°C; IR: 3298.5
(N-H str.), 1698.2 (C=O of quinolone), 1263.4 (C-O-C), 810.3 cm-1
4-[(4-Anilino-6-(4-benzhydrylpiperazino)-[1,3,5]triazin-2-yl)oxy]-1-
methyl-1H-quinolin-2-one (5o): mp >300°C; IR: 3298.2 (N-H str.),
1710.1 (C=O of quinolone), 1261.5 cm-1 (C-O-C); 1H NMR: δ 9.13
(s, 1H, -NH), 6.91–8.30 (m, 19H, Ar-H), 6.39 (s, 1H, H at C-22 of
quinolone), 5.26 (s, H, N-CH at piperazine linkage), 3.34 (s, 3H, CH3
of quinolone), 3.60 (br-s, 8H, piperazine); 13C NMR: δ 172.1 (C-6,
C-N at piperazine linkage), 171.5 (C-2, C-O-C at quinolone linkage),
164.9 (C-4, C-NH at aniline linkage), 160.3 (C-21, C=O of quinolo-
ne), 152.9 (C-23, C-O-C at quinolone), 141.7, 139.4, 139.1, 132.8,
128.9, 128.9, 128.9, 128.8, 128.8, 128.8, 128.5, 128.5, 128.4, 128.4,
126.6, 126.5, 123.7, 123.5, 122.7, 118.8, 118.6, 114.1 (22C, Ar-C),
110.3 (C-22, C-C=O of quinolone), 72.9 (C-33, N-CH at piperazine
linkage), 51.2, 46.9 (4C, piperazine), 32.5 (C-26, CH3 of quinolone).
Analysis: calculated for C36H33N7O2: C, 72.59; H, 5.58; N, 16.46.
Found: C, 72.64; H, 5.70; N, 16.49.
1
(s-triazine C-N str.); H NMR: δ 9.10 (s, 1H, -NH), 6.85–8.40 (m,
12H, Ar-H), 6.45 (s, 1H, H at C-22 of quinolone), 3.58 (br-s, 8H,
piperazine), 3.39 (s, 3H, CH3 of quinolone); 13C NMR: δ 172.1 (C-6,
C-N at piperazine linkage), 171.4 (C-2, C-O-C at quinolone link-
age), 165.3 (C-4, C-NH at aniline linkage), 159.6 (C-21, C=O of
quinolone), 153.1 (C-23, C-O-C at quinolone), 157.4, 157.1, 152.4,
141.2, 140.1, 132.7, 128.8, 128.6, 123.8, 123.5, 122.7, 118.8, 118.5,
116.8, 115.8, 113.9 (16C, Ar-C), 109.5 (C-22, C-C=O of quinolone),
50.2, 46.3 (4C, piperazine), 31.3 (C-26, CH3 of quinolone). Analysis:
calculated for C27H25N9O2: C, 63.89; H, 4.96; N, 24.84. Found: C,
63.94; H, 5.10; N, 24.77.
4-[4-Anilino-6-((4-chlorophenyl)-phenyl-methylpiperazino)[1,3,5]-
triazin-2-yl)oxy]-1-methyl-1H-quinolin-2-one (5p): mp >300°C; IR:
3292.4 (N-H str.), 1696.9 (C=O of quinolone), 1262.3 (C-O-C), 820.1
(-Cl); 1H NMR: δ 9.17 (s, 1H, -NH), 6.87–8.22 (m, 18H, Ar-H), 6.45
(s, 1H, H at C-22 of quinolone), 5.31 (s, H, N-CH at piperazine link-
4-[(4-Anilino-6-(4-benzylpiperazino)-[1,3,5]triazin-2-yl)oxy]-1-
methyl-1H-quinolin-2-one (5l): mp 282–287°C; IR: 3296.4 (N-H
str.), 1706.4 (C=O of quinolone), 1262.5 (C-O-C); 1H NMR: δ 9.16
(s, 1H, -NH), 6.96–8.31 (m, 14H, Ar-H), 6.52 (s, 1H, H at C-22 of
quinolone), 3.75 (s, 2H, CH2 at piperazine linkage), 3.54 (br-s, 8H,
piperazine), 3.36 (s, 3H, CH3 of quinolone); 13C NMR: δ 171.7 (C-6,
C-N at piperazine linkage), 171.3 (C-2, C-O-C at quinolone link-
age), 164.9 (C-4, C-NH at aniline linkage), 159.5 (C-21, C=O of
quinolone), 152.6 (C-23, C-O-C at quinolone), 141.2, 139.2, 132.7,
128.7, 128.7, 128.2, 128.3, 128.3, 127.2, 123.7, 123.4, 122.6, 118.7,
118.2, 116.7, 115.3 (16C, Ar-C), 109.7 (C-22, C-C=O of quinolone),
65.2 (C-33, -CH2) 509, 47.1 (4C, piperazine), 31.4 (C-26, CH3 of
age), 3.42 (s, 3H, CH3 of quinolone), 3.60 (br-s, 8H, piperazine); 13
C
NMR: δ 171.8 (C-6, C-N at piperazine linkage), 171.2 (C-2, C-O-C
at quinolone linkage), 165.1 (C-4, C-NH at aniline linkage), 160.1
(C-21, C=O of quinolone), 151.6 (C-23, C-O-C at quinolone), 141.3,
32.5, 130.2, 129.0, 128.93, 128.90, 128.87, 128.83, 128.0, 127.5,
127.4, 126.6, 123.6, 122.7, 122.5, 118.70, 118.3, 115.2 (18C, Ar-C),
109.32 (C-22, C-C=O of quinolone), 74.6 (C-33, N-CH at piperazine
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40 D. Patel et al.
linkage), 50.9, 47.4 (4C, piperazine), 31.4 (C-26, CH3 of quinolone).
Analysis: calculated for C36H32ClN7O2: C, 68.62; H, 5.12; N, 15.56.
Found: C, 68.57; H, 5.22; N, 15.67.
4-[(4-Anilino-(6-(4-methoxyphenyl)piperazino)-[1,3,5]triazin-2-
yl)oxy]-1-methyl-1H-quinolin-2-one (5u): mp >300°C; IR: 3296.2
(N-H str.), 1697.4 (C=O of coumarin), 1270.3 (-OCH3), 1265.4 cm-1
(C-O-C); 1H NMR: δ 9.21 (s, 1H, -NH), 6.77–8.11 (m, 13H, Ar-H),
6.47 (s, 1H, H at C-22 of quinolone), 3.78 (s, 3H, -OCH3), 3.39 (s, 3H,
CH3 of quinolone), 3.63 (br-s, 8H, piperazine); 13C NMR: δ 171. 9
(C-6, C-N at piperazine linkage), 171.1 (C-2, C-O-C at quinolone
linkage), 164.3 (C-4, C-NH at aniline linkage), 161.3 (C-21, C=O of
quinolone), 152.8 (C-23, C-O-C at quinolone), 152.4, 152.4, 140.2,
132.1, 128.8, 128.6, 123.9, 123.6, 122.7, 118.8, 118.6, 117.5, 117.4,
116.9, 116.0, 115.12 (16C,Ar-C), 110.1 (C-22, C-C=O of quinolone),
62.4 (C-40, -OCH3), 49.3, 46.8 (4C, piperazine), 32 (C-26, CH3 of
quinolone). Analysis: calculated for C30H29N7O3: C, 67.27; H, 5.46;
N, 18.31. Found: C, 67.15; H, 5.56; N, 18.44.
4-[(4-Anilino-6-(4-(2-fluorophenyl)piperazino)-[1,3,5]triazin-2-yl)-
oxy]-1-methyl-1H-quinolin-2-one (5q): mp 295–298°C; IR: 3298.2
(N-H str.), 1697.2 (C=O of quinolone), 1268.1 (C-O-C), 1157.32
(C-F); 1H: δ 9.09 (s, 1H, -NH), 6.49–8.14 (m, 13H, Ar-H), 6.41 (s, 1H,
H at C-22 of quinolone), 3.36 (s, 3H, -CH3 of quinolone), 3.64 (br-s,
8H, piperazine); 19F NMR: δ -122.14; 13C NMR: δ 171.8 (C-6, C-N at
piperazine linkage), 171.4 (C-2, C-O-C at quinolone linkage), 164.6
(C-4, C-NH at aniline linkage), 159.3 (C-21, C=O of quinolone), 151.7
(C-23, C-O-C at quinolone), 156.1, 151.8, 140.1, 132.9, 128.9, 128.4,
125.7, 123.7, 123.5, 122.7, 118.7, 118.4, 116.9, 115.1 (14C, Ar-C),
110.1 (C-22, C-C=O of quinolone), 50.9, 46.3 (4C, piperazine), 32.3
(C-26, -CH3 of quinolone). Analysis: calculated for C29H26FN7O2: C,
66.53; H, 5.01; N, 18.73. Found: C, 66.42; H, 5.12; N, 18.78.
Antimicrobial activity
The s-triazinyl piperazine and piperidine compounds 5a-u were ex-
amined for antimicrobial activity against five Gram-negative bac-
teria (E.coli MTCC 739, P. aeruginosa MTCC 741, K. pneumonia
MTCC 109, S. typhi MTCC 733, P. vulgaris MTCC 1771), two
Gram-positive bacteria (S. aureus MTCC 96 and B. cereus MTCC
619), and two fungal species (C. albicans MTCC 183 and A. niger
MTCC 282) using disc diffusion sensitivity test (Cruickshank et al.,
1975). The Mueller-Hinton agar media were sterilized (autoclaved at
120°C for 30 min), poured at a uniform depth of 5 mm and allowed
to solidify. The microbial suspension (105 CFU/ml) (0.5 McFarland
Nephelometery Standards) was streaked over the surface of media
using a sterile cotton swab (15 min at 180°C) to ensure even growth
of the organisms. The tested compounds were dissolved in dimethyl
sulfoxide to get a solution of 3–100 µg/ml concentration. Sterile filter
paper discs measuring 6.25 mm in diameter (Whatman no. 1 filter
paper), previously soaked in a known concentration of the test com-
pounds in dimethyl sulfoxide were placed on the solidified nutrient
agar medium that had been inoculated with the microbials, and the
plates were incubated for 24 h at 37°C. A control disc impregnated
with an equivalent amount of dimethyl sulfoxide without any sample
was also used and did not reveal any inhibition. Ciprofloxacin and
ketoconazole (100 µg/disc) were used as control drugs for antibacte-
rial and antifungal activity, respectively.
To determine the minimum inhibitory concentration (MIC), a
stock solution of the synthesized compound (100 µg/ml) in dim-
ethyl sulfoxide was prepared and graded quantities of the test com-
pounds were incorporated in specified quantity of molten sterile
agar, nutrient agar for antibacterial, and sabouraud dextrose agar
for antifungal activity evaluation. The medium containing the test
compound was poured into a Petri dish at a depth of 4–5 mm and
allowed to solidify under aseptic conditions. Suspension of the
micro-organism was prepared to contain approximately 105 CFU/ml
and applied to plates with serially diluted compounds with required
concentration of 3.12–100 µg/ml in dimethyl sulfoxide to be tested
and incubated at (37 1)°C for 24 and 48 h for bacteria and fungi,
respectively.
4-[(4-Anilino-6-(4-(4-fluorophenyl)piperazino)-[1,3,5]triazin-2-yl)-
oxy]-1-methyl-1H-quinolin-2-one (5r): mp >300°C; IR: 3298.2
(N-H str.), 1696.4 (C=O of quinolone), 1266.4 (C-O-C), 1161.26
1
(C-F); H NMR: δ 9.12 (s, 1H, -NH), 6.49–8.17 (m, 13H, Ar-H),
6.37 (s, 1H, H at C-22 of quinolone), 3.30 (s, 3H, -CH3 of quinolone),
3.57 (br-s, 8H, piperazine); 19F NMR: δ -119.47; 13C NMR: δ 171.9
(C-6, C-N at piperazine linkage), 171.3 (C-2, C-O-C at quinolone
linkage), 164.5 (C-4, C-NH at aniline linkage), 159.4 (C-21, C=O of
quinolone), 151.7 (C-23, C-O-C at quinolone), 156.2, 151.6, 139.9,
132.8, 128.9, 128.3, 125.7, 123.7, 123.6, 122.7, 118.9, 118.5, 116.8,
115.2 (14C, Ar-C), 110.3 (C-22, C-C=O of quinolone), 50.9, 46.4
(4C, piperazine), 32.4 (C-26, -CH3 of quinolone). Analysis: calcu-
lated for C29H26FN7O2: C, 66.53; H, 5.01; N, 18.73. Found: C, 66.45;
H, 5.08; N, 18.81.
4-[(4-Anilino-6-(4-(3-trifluoromethylphenyl)piperazino)-[1,3,5]-
triazin-2-yl)oxy]-1-methyl-1H-quinolin-2-one (5s): mp >300°C;
IR: 3298.1 (N-H str.), 1697.2 (C=O of quinolone), 1264.3 (C-O-C),
1
1161.2 (C-F); H NMR: δ 9.19 (s, 1H, -NH), 7.02–8.10 (m, 13H,
Ar-H), 6.41 (s, 1H, H at C-22 of quinolone), 3.46 (s, 3H, CH3 of qui-
nolone), 3.52 (br-s, 8H, piperazine); 19F NMR: δ -65.10; 13C NMR:
δ 171.8 (C-6, C-N at piperazine linkage), 171.2 (C-2, C-O-C at qui-
nolone linkage), 165.4 (C-4, C-NH at aniline linkage), 160.3 (C-21,
C=O of quinolone), 152.2 (C-23, C-O-C at quinolone), 151.1, 141.2,
140.1, 132.6, 128.8, 128.7, 123.9, 123.5, 122.7, 118.9, 118.8, 116.9,
116.6, 115.9 (14C, Ar-C), 109.5 (C-22, C-C=O of quinolone), 50.2,
47.1 (4C, piperazine), 31.4 (C-26, CH3 of quinolone). Analysis:
calculated for C30H26F3N7O2: C, 62.82; H, 4.57; N, 17.09. Found: C,
62.88; H, 4.45; N, 17.20.
4-[(4-Anilino-6-(4-(2,3,4-trimethoxybenzyl)piperazino)-[1,3,5]-
triazin-2-yl)oxy]-1-methyl-1H-quinolin-2-one (5t): mp 292–296°C;
IR: 3297.5 (N-H str.), 1697.3 (C=O of quinolone), 1269.2 (-OCH3),
1264.6 (C-O-C); 1H NMR: δ 9.10 (s, 1H, -NH), 6.68–8.13 (m, 11H,
Ar-H), 6.44 (s, 1H, H at C-22 of quinolone), 3.36 (s, 3H, -CH3 of
quinolone), 3.62–3.69 [m, 9H, (OCH3)3], 3.67 (br-s, 8H, piperazine),
2.60 (s, 2H, -CH2); 13C NMR: δ 172.0 (C-6, C-N at piperazine link-
age), 171.4 (C-2, C-O-C at quinolone linkage), 164.2 (C-4, C-NH
at aniline linkage), 160.2 (C-21, C=O of quinolone), 152.7 (C-23,
C-O-C at quinolone), 152.2, 141.1, 139.3, 132.5, 128.9, 128.7, 124.4,
123.9, 123.5, 123.4, 122.7, 118.9, 118.6, 116.4, 106.2 (15C, Ar-C),
109.3 (C-22, C-C=O of quinolone), 58.7, 58.1, 60.3 (C-40, C-42,
C-44, -OCH3), 50.2, 47.1 (4C, piperazine), 31.7 (C-26, CH3 of qui-
nolone). Analysis: calculated for C33H35N7O5: C, 65.01; H, 5.79; N,
16.08. Found: C, 65.11; H, 5.60; N, 16.01.
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Received April 5, 2011; accepted April 19, 2011
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