Synthesis of novel bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-dione) and its derivatives: Evaluation of their antioxidant properties

Article abstract of DOI:10.1016/j.bmcl.2013.04.068

One pot cyclocondensation reaction of barbituric/thiobarbituric acid with aromatic aldehydes and p-phenylenediamine/2,6-diaminopyridine by refluxing in glacial acetic acid afforded novel bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)- diones)/pyrido bis(pyrimido

Full text of DOI:10.1016/j.bmcl.2013.04.068

Bioorganic & Medicinal Chemistry Letters 23 (2013) 3873–3878
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Bioorganic & Medicinal Chemistry Letters
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Synthesis of novel bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-dione)
and its derivatives: Evaluation of their antioxidant properties
⇑
Kandasamy Parameswaran, Paramasivam Sivaguru, Appaswami Lalitha
Department of Chemistry, Periyar University, Periyar Palkalai Nagar, Salem 636 011, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
One pot cyclocondensation reaction of barbituric/thiobarbituric acid with aromatic aldehydes and
p-phenylenediamine/2,6-diaminopyridine by refluxing in glacial acetic acid afforded novel bis(pyrimi-
do[5,4-c]quinoline-2,4(1H,3H)-diones)/pyrido bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-diones. All the
synthesized compounds were screened for their antioxidant activities using FRAP and DPPH methods.
Compounds with chloro substituents showed relatively good antioxidant properties.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 26 December 2012
Revised 16 April 2013
Accepted 26 April 2013
Available online 9 May 2013
Keywords:
One-pot cyclocondensation
p-Phenylenediamine
Barbituric/thiobarbituric acid
Bis(pyrimido[5,4-c]quinoline-
2,4(1H,3H)-dione)
Antioxidant activity
Heterocyclic ring systems remain part of many powerful scaf-
folds holding several pharmacopores that can act as potent and
selective drugs for many diseases.1,2 Pyrimido[4,5-b]quinoline-
2,4(1H,3H,5H,10H)-dione is one of the important class of heterocy-
clic moiety that possesses biological properties such as antitumor,
anticancer, antihypertensive and antibacterial.3 It has also been re-
ported to have potential inhibition property against Kaposi’s sar-
coma-associated herpesvirus (KSHV).4 Bond et al. studied the
inhibitory effect of pyrimido[4,5-b]quinoline against topoisomer-
ase and their associated diseases and disorders.5
lines to afford functionalized pyrimido-[4,5-b]quinoline-
2,4(1H,3H,5H,10H)-dione as one of the products.9 Majority of the
diseases such as ischemia, cataract, atherosclerosis, inflammation,
ageing, carcinogenesis and even AIDS are proved to be associated
with oxidative stress arising from the imbalance between the for-
mation and detoxification of free radicals and reactive oxygen spe-
cies (ROS) such as superoxide anion, hydrogen peroxide, and
hydroxyl radical formed as by-products of a variety of pathways
of aerobic metabolism.10–17 As they are unstable and highly reac-
tive, they can interact with a wide range of biological substrates
such as, lipids, DNA and proteins resulting in cell damage.18–20 Nat-
urally occurring antioxidants such as vitamin C, vitamin E, sele-
nium, b-carotene, lycopene, lutein and other carotenoids could
fight with such species and suppress the concentration of free rad-
icals. Apart from these, there are number of literature reports
revealing the efficiency of polyphenolic compounds and thiols in
the defense against free radicals.21 Recently, heterocyclic com-
pounds such as quinolines, pyrazoles and isoxazoles, 1,4-thiaze-
pine, Mannich bases and piperamides have been screened for
their antioxidant properties.22
In the last few decades, construction of highly functionalized
pyrimido[4,5-b]quinoline-2,4(1H,3H,5H,10H)-diones
have
at-
tracted both synthetic and medicinal chemists. Dow et al. have
reported the synthesis of 7,8-dimethoxy-5,10-dihydropyrimi-
do[4,5-b]quinolin-4(1H)-one compounds that act as selective inhib-
itor of the tyrosine-specific kinase enzyme.6 Microwave-assisted
synthesis
of
pyrimido[5,4-b][4,7]phenanthroline-9,11(7H,8H,
10H,12H)-dione derivatives, which are obtained by the incorpora-
tion of pyrimido-[4,5-b]quinoline-2,4(1H,3H,5H,10H)-dione and
[4,7]-phenanthroline motifs via three-component reactions has
been reported by Shi et al.7 Bazgir et al. have also reported a one-
pot synthesis of pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidine-dione
derivatives.8 Recently, Aknin et al. have performed one-pot three
component reaction involving barbituric acid, aldehydes and ani-
In our effort of designing novel heterocyclic compounds with
potential antioxidant properties, herein we describe a simple and
efficient synthesis of some novel bis(dihydropyrimido[5,4-c]quino-
line-2,4-dione) derivatives (4) by one pot multicomponent reaction
of barbituric acid/thiobarbituric acid with aromatic aldehydes and
p-phenylenediamine by refluxing in glacial acetic acid (Scheme 1).
To find the suitable reaction medium for this cyclocondensa-
tion, initially we have carried out the one pot cyclocondensation
⇑
Corresponding author.
E-mail addresses: lalitha2531@yahoo.co.in, lalitha253@rediffmail.com (A. Lalitha).
0960-894X/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bmcl.2013.04.068

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K. Parameswaran et al. / Bioorg. Med. Chem. Lett. 23 (2013) 3873–3878
X
protons in barbituric acid moiety appeared as two singlets at d
11.09 and 11.12 ppm.
HN
NH
OH
CHO
NH2
NH2
H
N
R
When we tried to recrystalize the Mannich base 6 for further
purification in glacial acetic acid, unexpectedly a small amount of
compound 4c was obtained as product, which was confirmed by
1H NMR spectrum, in which, the two singlets appeared at d 5.01
and 8.75 ppm, corresponding to the methine proton (–CH–) and
the cyclic amine proton (–NH). Impressed by this result, compound
6 was refluxed in glacial acid for 7 h expecting the formation of 4c
and its regioisomer RI (Scheme 2).
Glacial CH3COOH
Reflux, 4-7h
O
HN
X
+
+
O
O
N
H
N
H
R
R
HN
NH
2 equiv 2 equiv 1 equiv
X
2
3
4
1
Scheme 1. Synthesis of bis(dihydropyrimido[5,4-c]quinoline-2,4-dione).
1H and 13C NMR spectra of compound obtained from one pot
synthesis and that from acid treatment of Mannich base 6 were
found to be similar. Moreover, to elucidate the structure of the
compounds obtained by these two routes, the 2D-HMBC and HSQC
were recorded from which we observed that, six correlations were
found for both compounds instead of nine correlations expected
for the regioisomer RI (Scheme 3) thereby confirming the structure
of both the compounds are identical and 4c is the formed product.
Perhaps, the formation of 4c would have taken place via proton-
ation of 6 in acidic medium. This protonated form underwent
intermolecular cyclization to afford exclusively compound 4c as
product with 82% yield (Scheme 4).
of barbituric acid, p-chlorobenzaldehyde and p-phenylenediamine
as a model reaction in polar protic solvents such as methanol, eth-
anol and isopropanol in the presence of
reflux condition.
L-proline as catalyst under
This cyclocondensation reaction in methanol, ethanol and iso-
propanol yielded 5 as the only product where, 4c was not formed
in 5 h. The lesser reactivity of barbituric acid might be attributed
to the heterogeneity of the reaction mixture. To improve the reac-
tivity and increase the homogeneity, we have carried out the same
reaction in high polar protic solvents such as ethyeneglycol and
diethyleneglycol at 120 °C in the presence of 30% L-proline where,
The cylcocondensation reaction involving aldehydes with elec-
tron withdrawing group in para-position afforded the correspond-
ing products (Table 2, entries 6, 14) in lesser time with better
yields. Similarly, chloro substituent in para-position also led to les-
ser reaction time with better yields. In the cases of aldehydes with
electron donating groups such as 4-hydroxy and 4-methoxyben-
zaldehydes, products were not at all formed (Table 2, entries 7, 8,
15, 16). Aromatic aldehydes with either electron releasing groups
or electron withdrawing groups in ortho-position needed longer
reaction times compared to that in meta- or para-positions which
may be due to steric hindrance (Table 2).
we observed moderate yields of 4c (60–65%), (Table 1, entries 4, 5),
which may be due to the high polar nature of the solvents that
might hold the product by hydrogen bonding. Refluxing in glacial
CH3COOH in the absence of L-proline yielded exclusively 4c in 5h
with 85% yield (Table 1, entry 6).
Though, we got 5 as the product while refluxing in alcoholic sol-
vents for 5 h, it was possible to obtain the Mannich base 6 when
the reaction time was extended to 10 h (Table 1, entries 1, 2, 3).
1H NMR spectrum of compound 6 showed two doublets in the re-
gion of d 4.2-4.3 and 4.72–4.73 ppm that correspond to –CH–CH–
NH– group, which indicated the formation of C–C bond. Amide
Table 1
Cyclocondensation reaction of barbituric acid, p-chlorobenzaldehyde and p-phenylenediamine in various reaction media
X
Cl
HN
NH
H
N
R
N
O
O
or
Cl
N
H
N
R
HN
NH
X
O
H
4c
5
OH
NH2
RM/ cat. L-Proline
HN
+
+
10
O
N
H
O
h
,
R
e
f
l
Cl
NH2
Cl
O
u
x
H
N
O
O
1
2
3
H
N
NH
O
RM = Reaction Medium
O
HN
N
H
O
N
H
6
Cl
Entry
Reaction mediuma
Temperature (°C)
Reaction time (h)
Product
Yieldc (%)
1
2
3
4
5
6
Methanol
Ethanol
Isopropanol
Ethyleneglycol
Diethyleneglycol
Acetic acidb
Reflux
Reflux
Reflux
120
120
Reflux
5 (10)
5 (10)
5 (10)
5
5
5
5 (6)
5 (6)
5 (6)
4c
4c
4c
92 (72)
95 (81)
96 (84)
65
60
85
a
Cyclocondensation reaction of barbituric acid (2 mmol), aromatic aldehydes (2 mmol) and p-phenylenediamine (1 mmol) in the presence of 30%
reaction media.
L
-proline in various
b
Reflux in absence of
L-proline.
c
Isolated yield. Products and yields in parentheses correspond to reaction times given in parentheses.

K. Parameswaran et al. / Bioorg. Med. Chem. Lett. 23 (2013) 3873–3878
3875
Cl
Cl
O
X
H
N
O
O
Cl
HN
NH
O
H
N
H
N
H
N
H
N
NH
O
Gla. CH3COOH
Reflux, 7h
O
HN
O
or
O
NH
O
HN
N
O
N
H
N
H
N
H
H
HN
NH
O
O
N
H
Cl
4c
6
Cl
X
Cl
Possible Regioisomer
RI
Scheme 2. Acid treatment of Mannich base 6.
Cl
Table 2
One pot synthesis of bis(dihydropyrimido[5,4-c]quinoline-2,4-dione) derivatives23
O
Cl
Entry
X
R
Producta
Time (h)
Yieldb (%)
O
HN
NH
H
N
H
N
H
O
N
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
O
O
O
O
O
O
O
O
S
S
S
S
S
H
2-Cl
4-Cl
2-NO2
3-NO2
4-NO2
4-OH
4-OMe
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
6.0
6.5
5.0
6.0
5.0
4.0
7.0
7.0
6.0
6.5
5.0
6.0
5.0
4.0
7.0
7.0
80
75
85
78
HN
O
NH
O
O
N
H
N
H
N
H
O
HN
NH
Cl
81
O
87
NRc
NRc
78
RI
Cl
4c
Scheme 3. Possible HMBC correlation for compound 4c and RI.
2-Cl
4-Cl
72
83
75
82
2-NO2
3-NO2
4-NO2
4-OH
4-OMe
The 1H NMR spectrum of each compound in the series 4a–f and
4i–n showed a singlet at d 5.01–5.26, which revealed the methine
proton (–CH) and a singlet at d 8.72–8.91 ppm due to cyclic amine
proton (–NH). The two singlets appeared at d 10.22–10.50 ppm and
11.44–11.62 ppm, could be accounted for cyclic amide protons
S
S
S
86
NRc
NRc
a
Cyclocondensation reaction of barbituric/thiobarbituric acid (2 mmol), aromatic
aldehydes (2 mmol) and p-phenylenediamine (1 mmol) refluxing in glacial
CH3COOH.
(–NH). Aromatic protons appeared as multiplet at
d 6.80–
b
8.43 ppm. The mass spectra of compounds are in agreement with
their assigned structures. All the spectra exhibit parent peaks due
to molecular ions (M+). The mass spectrum of 4c showed molecu-
lar ion peak (M+) at 574 in accordance with its molecular formula.
Next, we have planned to synthesize another similar heterocylic
derivative 8, where, o-phenylenediamine 7 was utilized in the
place of p-phenylenediamine in the above cyclocondensation. In
this case, an unexpected product namely, 4-chlorobenzyl barbitu-
ric acid 9 was obtained with 73% yield instead of bis(dihydropy-
rimido[5,4-c]quinoline-2,4-dione) compound 8 (Scheme 5).
The formation of 9 instead of 8 may be attributed to the 1,4-
nucleophilic addition of 7 at the –C@C– bond of intermediate C,
which might have transformed into 9 after hydride transfer
(Schemes 5 and 6). The 1,2-nuclephilic addition of 7 might not
Isolated yield.
No reaction.
c
be possible due to the other amino group present in the next posi-
tion. The characterization of remaining products is under progress.
In the 1H NMR spectrum, one doublet appeared at d 3.24–
3.25 ppm for methylene protons (–CH2) and one triplet at d 3.95–
3.97 ppm for methine proton (–CH), confirming the hydride
transfer that has occurred at –C@C– in intermediate C. Peak for
cyclic amide proton at d 11.21 ppm also supported the formation
of compound 9.
Furthermore, we explored the same reaction conditions for the
synthesis of pyrido bis(dihydropyrimido[5,4-c]quinoline-2,4-
H
O
N
O
O
Ar
O
Ar
H
H
H
N
NH
HN
NH
OH
O
Ar
O
HN
NH
H
Ar
O
O
N
H
HN
N
O
N
H
OH
H
NH
O
N
H
6
HN
-H
-H2O
O
Ar
HN
NH
O
N
H
HN
Ar = 4-Cl-phenyl
Scheme 4. Proposed mechanism for the formation of 4c from 6.

3876
K. Parameswaran et al. / Bioorg. Med. Chem. Lett. 23 (2013) 3873–3878
O
O
NH
HN
HN
O
NH
O
NH HN
O
H
OH
8
Cl
Cl
H2N
+
H2N
Glacial CH3COOH
Reflux, 4h
HN
+
O
O
N
H
O
Cl
HN
7
1
2
+
Others
O
N
H
O
Cl
9
Scheme 5. One pot reaction of barbituric acid, p-chlorobenzaldehyde and o-phenylenediamine.
dione) derivatives using barbituric acid/thiobarbituric acid with
H
aromatic aldehydes and 2,6-diaminopyridine 10 as amine part by
refluxing in glacial CH3COOH,24 where the corresponding products
were obtained in good yields (Table 3).
H
H
OH
O
O
O
OH
NH
OH
H
Ar
Ar
NH
Ar
H
O
O
The 1H NMR spectrum of each compound in the series 11a–f
and 11i–n showed a singlet at d 5.01–5.31 which revealed methine
proton (–CH) and a singlet at d 8.97–9.12 ppm due to cyclic amine
proton (–NH). The two singlets appeared at d 10.51–10.72 ppm and
11.52–11.71 ppm, could be accounted for cyclic amide protons
N
H
O
N
H
O
HO
NH
O
O
HN
HN
HO
NH
O
O
Ar
OH Ar
OH Ar
(–NH). Aromatic protons appeared as multiplet at
d 6.94–
HN
Ar
H
NH
7.95 ppm. The mass spectrum of 11a showed the molecular ion
peak (M+) at 505, which matches with its molecular formula. The
mass spectra of other compounds are in agreement with their as-
signed structures.
In the present study, antioxidant potential of synthesized
bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-dione compounds (4a–f,
HN
O
HN
O
N
H
O
H2N
NH2
N
H
O
O
N
H
O
9
+
H2N
Ar = 4-Cl-phenyl
D
C
Others
Scheme 6. Proposed mechanism for the formation of 9.
Table 3
One pot reaction of barbituric/thiobarbituric acid, aromatic aldehydes and 2,6-diaminopyridinea
X
X
HN
NH
HN
NH
OH
CHO
Glacial CH3COOH
Reflux, 4.5-8h
O
O
HN
+
+
H2N
N
NH2
N
H
N
N
H
X
N
H
O
R
R
R
11(a-p)
10
1 equiv
X = O or S
2
1
2 equiv
2 equiv
R = H, 2-Cl, 4-Cl, 2-NO2, 3-NO2, 4-NO2, OH, OMe
Entry
X
R
Product
11a
11b
11c
11d
11e
11f
11g
11h
11i
11j
11k
11l
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
O
O
O
O
O
O
O
O
S
S
S
S
S
H
2-Cl
4-Cl
2-NO2
3-NO2
4-NO2
4-OH
4-OMe
H
6.0
7.0
5.0
6.5
6.0
4.5
8.0
7.0
6.0
7.0
5.0
6.5
6.0
4.5
8.0
8.0
76
70
83
74
77
85
NRc
NRc
74
2-Cl
4-Cl
71
81
75
78
2-NO2
3-NO2
4-NO2
4-OH
4-OMe
11m
11n
11o
11p
S
S
S
84
NRc
NRc
a
Cyclocondensation reaction barbituric/thiobarbituric acid (2 mmol), aromatic aldehydes (2 mmol) and 2,6-diaminopyridine (1 mmol) by
refluxing in glacial CH3COOH.
b
Isolated yield.
No reaction.
c

K. Parameswaran et al. / Bioorg. Med. Chem. Lett. 23 (2013) 3873–3878
3877
Table 4
Radical scavenging activities of all compounds were determined
from the interacting ability of compounds with DPPH as stable free
radical. Compound 4a, that is not having any substituents on the
phenyl ring, was selected as a model compound for evaluating its
DPPH radical scavenging activity. Compound 4a has been tried in
DPPH radical scavenging activity and ferric ion reducing antioxidant power of
compounds 4a–f and 4i–n
Compounds
DPPH RSAa (20
(%)
l
g/ml)
FRAP IC50 value (60 lg/ml)
IC50 value (lg)
five different concentrations such as 20, 40, 60, 80, 100
and sufficient activity was observed in 20 g/mL concentration.
All other compounds in these series were screened for their antiox-
idant activity in 20 g/mL concentration. The antioxidant activities
were expressed as the percentage of inhibition and 50% inhibitory
concentration values in Tables 4 and 5 and compared with that of
standard BHA. The results in percentage are expressed as the ratio
of absorbance decrease at 517 nm, and the absorbance of DPPH
solution in the absence of bis(pyrimido[5,4-c]quinoline-
2,4(1H,3H)-dione compounds.
The hydrogen donating ability of cyclic amide groups present as
part of all synthesized compounds in the series 4a–p and 11a–p
might be responsible for their antioxidant properties (Scheme 7).
To investigate the structure activity relationship in the series
4a–p and 11a–p, the radical scavenging activity of 4a was studied
and compared with 12 using DPPH radical. The radical scavenging
activity of 4a was found to be higher than 12 (Fig. 1), which may be
attributed to the increase in the number of cyclic amide groups
capable of donating hydrogen.
The FRAP assay is based on measuring the reducing ability of a
compound that reduce the ferric ion to the colored ferrous ion
complex. FRAP values are measured spectrophotometrically at
700 nm. To investigate the reducing ability of synthesized com-
pounds, compound 4a was selected as model compound and to
fix optimum concentration required for the reducing ability, this
lg/mL
4a
4b
4c
4d
4e
4f
82.0 2.62
84.0 0.82
85.2 1.04
82.7 1.05
81.7 1.30
80.9 1.12
79.6 1.00
84.1 1.08
84.4 1.20
82.0 0.96
79.3 1.00
82.3 0.30
87.1 0.89
12.15
12.05
11.80
12.07
12.39
12.44
12.62
11.99
11.93
12.15
12.68
12.17
11.55
32.76
24.01
23.21
29.08
33.28
25.01
32.10
24.46
24.11
29.50
33.70
25.21
20.76
l
l
4i
4j
4k
4l
4m
4n
BHA
a
Antioxidant activities were expressed in percentage compared with standard
BHA. The data represent mean value (SEM) of three duplicates.
Table 5
DPPH radical scavenging activity and Ferric ion reducing antioxidant power of
compounds 11a–f and 11i–n
Compounds
DPPH RSAa (20
(%)
l
g/ml)
FRAP IC50 value (60 lg/ml)
IC50 value (lg)
11a
11b
11c
11d
11e
11f
70.6 1.16
80.8 1.50
81.1 1.35
74.0 1.16
70.2 1.23
74.2 1.68
70.4 1.62
80.6 1.21
80.9 0.57
73.6 1.66
70.1 1.96
74.0 1.08
87.1 0.89
14.21
12.42
12.35
13.56
14.24
13.48
14.25
12.41
12.36
13.60
14.34
13.56
11.55
33.91
25.51
24.41
31.39
34.90
26.06
33.50
25.07
25.00
30.47
34.93
26.25
20.76
11i
11j
11k
11l
11m
11n
BHA
X
O
HN
NH
H
N
HN
O
O
O
N
H
N
H
N
H
a
Antioxidant activities were expressed in percentage compared with standard
BHA. The data represent mean value (SEM) of three duplicates.
HN
NH
X
12
4a
IC50 Value = 12.15 µg/mL
IC50 Value = 18.91 g/mL
4i–n and 11a–f, 11i–n) were studied using DPPH radical scaveng-
ing technique by spectrophotometrically according to Shimada
et al.25 and ferric reducing antioxidant power (FRAP) assay.26
Fig. 1. Structures of compound 12 and 4a.
X
X
X
RH
R
N
NH
N
NH
HN
NH
H
N
H
N
H
N
O
O
O
O
O
O
N
H
N
H
N
H
HN
NH
HN
NH
HN
NH
X
X
X
R
RH
X
X
N
NH
N
NH
H
H
N
N
O
O
O
O
N
H
N
H
HN
N
HN
N
X
X
Scheme 7. Plausible mechanism for all synthesized compounds interacting with DPPH radical.

3878
K. Parameswaran et al. / Bioorg. Med. Chem. Lett. 23 (2013) 3873–3878
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compound has been tried in five different concentrations such as
20, 40, 60, 80, 100 g/mL and sufficient activity was observed in
60 g/mL concentration. All other compounds in these series were
screened for their antioxidant activity in 60 g/mL concentration.
According to the data presented in (Tables 4 and 5), compounds
with chloro-substituent on the phenyl ring such as 4b, 4c, 4j, 4k,
11b, 11c, 11j and 11k showed better antioxidant power in FRAP as-
say. Generally, all compounds exhibited comparable or more po-
tent antioxidant potential in FRAP assay in comparison with
synthetic antioxidant, BHA.
The analysis of Tables 4 and 5 leads to conclude that the radical
scavenging activity of bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-
dione on DPPH radical and ferric ion reducing power has been
found to be maximum for all compounds. Especially, compounds
with chloro-substituent on the phenyl ring (4b, 4c, 4j, 4k, 11b,
11c, 11j and 11k) have enhanced and exhibited maximum radical
scavenging activities (Tables 4 and 5).
In conclusion, bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-dione
derivatives have been successfully synthesized by one pot cyclo-
condensation of barbituric/thiobarbituric acid, aromatic aldehydes
and p-phenylenediamine/2,6-diaminopyridine by refluxing in gla-
cial acetic acid. Radical scavenging abilities of all synthesized com-
pounds were evaluated with the stable DPPH radical and FRAP
methods and the chloro containing bis(pyrimido[5,4-c]quinoline-
2,4(1H,3H)-dione derivatives have enhanced and shown maximum
radical inhibitory effect and ferric ion reducing antioxidant power.
l
l
l
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Acknowledgments
We acknowledge the SIF-NMR Research Centre, IISc, Bangalore,
India and SAIF-IITM, Chennai, India for NMR data. We thank Dr. V.
Sujatha for providing UV–vis spectral facilities.
Supplementary data
23. Procedure for the synthesis of Bis(dihydropyrimido[5,4-c]quinoline-2,4
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.bmcl.2013.
04.068.
(1H,3H)-diones) (4c):
A mixture of p-phenylenediamine (0.925 mmol),
p-chlorobenzaldehyde (1.85 mmol) and barbituric acid (1.85 mmol) was
refluxed in glacial acetic acid until the completion of reaction as evidenced
by TLC. After completion, the reaction mixture was cooled to room
temperature. The yellow color solid separated was washed with hot ethanol
and dried.
References and notes
24. Procedure for the synthesis of pyrido bis(dihydropyrimido[5,4-c]quinoline-
2,4(1H,3H)-diones) (11c): A mixture of 2,6-diaminopyridine (0.925 mmol), p-
chlorobenzaldehyde (1.85 mmol) and barbituric acid (1.85 mmol) was refluxed
in glacial acetic acid until the completion of reaction monitored by TLC. After
completion, the reaction mixture was cooled to room temperature. The yellow
color solid separated was washed with hot ethanol and dried.
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