Synthesis of Novel Benzofuran-Gathered C-2,4,6-substituted Pyrimidine Derivatives Conjugated by Sulfonyl Chlorides: Orally Bioavailable, Selective, Effective Antioxidants and Antimicrobials Drug Candidates

Article abstract of DOI:10.1002/jhet.2209

In the present study, we have made an effort to develop the novel synthetic antioxidants and antimicrobials with improved potency. The novel benzofuran-gathered C-2,4,6-substituted pyrimidine derivatives 5a, 5b, 5c, 5d, 5e, 5f, 6a, 6b, 6c, 6d, 6e, 6f, 7a, 7b, 7c, 7d, 7e, 7f, 8a, 8b, 8c, 8d, 8e, 8f, 9a, 9b, 9c, 9d, 9e, 9f were synthesized by simple and efficient four-step reaction pathway. Initially, o-alkyl derivative of salicylaldehyde readily furnish corresponding 2-acetyl benzofuran 2 in good yield, upon the treatment with potassium tertiary butoxide in the presence of molecular sieves. Further, Claisen-Schmidt condensation with aromatic aldehydes via treatment with thiourea followed by coupling reaction with different sulfonyl chlorides afforded target compounds. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, mass, and elemental analysis and further screened for their antioxidant and antimicrobial activities. The results showed that the synthesized compounds 8b, 8e, 9b, and 9e produced significant antioxidant activity with 50% inhibitory concentration higher than that of reference, whereas compounds 7d and 7c produced dominant antimicrobial activity at concentrations 1.0 and 0.5 mg/mL compared with standard Gentamicin and Nystatin, respectively.

Full text of DOI:10.1002/jhet.2209

Month 2014
Synthesis of Novel Benzofuran-Gathered C-2,4,6-substituted Pyrimidine
Derivatives Conjugated by Sulfonyl Chlorides: Orally Bioavailable,
Selective, Effective Antioxidants and Antimicrobials Drug Candidates
a
b
a
a
*
Javarappa Rangaswamy, Honnaiah Vijay Kumar, Salakatte Thammaiah Harini, and Nagaraja Naik
aDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, 570006, Karnataka, India
bDepartment of Organic Chemistry, Indian Institute of Science, Bangalore, 560012, Karnataka, India
*
E-mail: drnaikchem@gmail.com
Received October 20, 2013
DOI 10.1002/jhet.2209
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
In the present study, we have made an effort to develop the novel synthetic antioxidants and antimicro-
bials with improved potency. The novel benzofuran-gathered C-2,4,6-substituted pyrimidine derivatives
5–9(a–f) were synthesized by simple and efficient four-step reaction pathway. Initially, o-alkyl derivative
of salicylaldehyde readily furnish corresponding 2-acetyl benzofuran 2 in good yield, upon the treatment
with potassium tertiary butoxide in the presence of molecular sieves. Further, Claisen–Schmidt condensation
with aromatic aldehydes via treatment with thiourea followed by coupling reaction with different sulfonyl
chlorides afforded target compounds. The structures of newly synthesized compounds were confirmed by
IR, 1H NMR, 13C NMR, mass, and elemental analysis and further screened for their antioxidant and
antimicrobial activities. The results showed that the synthesized compounds 8b, 8e, 9b, and 9e produced
significant antioxidant activity with 50% inhibitory concentration higher than that of reference, whereas
compounds 7d and 7c produced dominant antimicrobial activity at concentrations 1.0 and 0.5 mg/mL
compared with standard Gentamicin and Nystatin, respectively.
J. Heterocyclic Chem., 00, 00 (2014).
also occupy a prominent place in the pharmaceutical arena.
Pyrimidine derivatives form a component in a number of
useful drugs and are associated with many biological, phar-
maceutical, and therapeutical activities [7]. Condensed
benzofuran-gathered pyrimidine heterocyclic derivatives
have been reported as antimicrobial, analgesic, anti-viral,
anti-inflammatory, anti-HIV, anti-tubercular, anti-tumor,
antioxidant, anti-neoplastic, anti-malarial, and diuretic
cardiovascular [8–15] agents. Pyrimidine compounds are
also used as hypnotic drugs for the nervous system [16],
calcium-sensing receptor antagonists [17]. On the other
hand, compounds containing sulfonyl groups have long been
a research focus as a result of their biological importance and
chemical applications.
It was envisaged that these three active pharmacophores,
if linked together would generate novel molecular tem-
plates, which are likely to exhibit interesting biological
properties. The aforementioned applications prompted us
to synthesize a series of new compounds, which are
reported in this article. Owing to the importance and in
continuation of our research work on synthesis of
INTRODUCTION
Heterocyclic compounds play an imperative role in an
untiring effort aimed at developing new biological agents
with new mechanism of action. Heterocyclic compounds
are also well known to possess diverse pharmacological
properties. Benzofurans are very interesting heterocycles,
which are ubiquitous in nature and show a wide range of
biological activities [1]. A wide variety of pharmacological
properties has been shown to be associated with
benzofuran [2]. The benzofuran ring system itself is a
common structural element that appears in a large number of
medicinally important compounds [3]. Benzofuran and its
heterocyclic systems are known to exhibit a wide range of
biological properties such as anti-hyperglycemic, analgesic,
anti-inflammatory, antimicrobial, and anti-tumor activities
[4–6]. Nitrogen containing heterocycles such as pyrimidine
and isoxazole is a promising structural moiety for drug de-
signing. They also play an essential role in several biological
processes, found in nucleoside antibiotics, antibacterials, car-
diovascular as well as considerable chemical reactions and
© 2014 HeteroCorporation

J. Rangaswamy, V. Kumar, S. T. Harini, and N. Naik
Vol 000
biologically active compounds [18–20], now, we wish to
describe the synthesis of new benzofuran-gathered C-2,
4,6-substituted pyrimidine derivatives containing sulfonyl
chlorides moiety and were screened for their antioxidant
and antimicrobial study. Thus, we have created new
avenues to explore the potent heterocyclic moieties for
the pharmacological activities in medicinal chemistry.
subsequently generates enolate anion (iii) undergoing intra-
molecular cyclocondensation reaction that afforded 2-acetyl
benzofuran (2) with improved yield Scheme 2. The resultant
starting material was subjected to Claisen–Schmidt conden-
sation reaction with different aromatic aldehydes in the
presence of zirconium chloride as a catalyst [26] afforded
corresponding chalcones 3(a–e). Generally, chalcones are
considered to be useful intermediates in several cyclisation
reactions to produce types of heterocyclic compounds of
diverse biological importance, according to the reactants
used and the reaction conditions [27]. Further, the com-
pounds 3(a–e) were treated with thiourea in DMF to yield
the corresponding pyrimidine derivatives 4(a–e) [28]. In
the final step, compounds 4(a–e) were coupled with
different substituted sulfonyl chlorides in the presence of
triethylamine as base accomplished the desired products
5–9(a–f) Scheme 3, Table 1. The structures of the com-
RESULTS AND DISCUSSION
In this present work, a series of 30 new benzofuran-
gathered C-2,4,6-substituted pyrimidine derivatives 5–9(a–f)
were synthesized by a four-step reaction. The desired
starting material 2-acetyl benzofuran (2) was obtained
by cyclocondensation reaction. At present, several general
methods for the preparation of 2-acetyl benzofuran are
known [21–24]. Very recently, we have reported 1,8-
diazabicyclo[5.4.0]undec-7-ene assisted one-pot synthesis
of benzofurans [25]. In this manuscript, we described
a mild variant potassium tertiary butoxide (t-BuOK)
that aided one-pot synthesis of 2-acetyl benzofuran in the
presence of molecular sieves Scheme 1. The synthetic route
involves, initially, o-alkylation of salicylaldehyde (1) with
chloroacetone (i) in the presence of t-BuOK as base-
furnished o-alkylated salicyaldehyde derivative (ii), which
1
pounds were elucidated by IR, H NMR, 13C NMR, mass,
and elemental analysis.
ANTIOXIDANT EVALUATION
Evaluation of antioxidant activity for the newly synthe-
sized analogs 5–9(a–f) was performed by using three
in vitro assays such as 2,2-diphenyl-1-picryl-hydrazyl
Scheme 1. Reaction lane for the synthesis of 2-acetyl benzofuran.
Scheme 2. Mechanism toward the synthesis of 2-acetyl benzofuran (2) by using t-BuOK.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Novel Benzofuran-Gathered C-2,4,6-substituted Pyrimidine Derivatives as a
Month 2014
Effective Antioxidants and Antimicrobials Drug Candidates
Scheme 3. Reaction pathway for the synthesis of benzofuran-gathered C-2,4,6-substituted pyrimidine derivatives 5–9 (a–f).
(DPPH) radical scavenging activity (RSA), N,N-dimethyl-
p-phenylenediamine (DMPD), and Ferric ion reducing
power assay. The antioxidant properties were expressed
as 50% inhibitory concentration (IC50) values and optical
density (OD) (Table 2).
Table 1
Sulfonyl linked phenyl ring (R2) in compounds 5–6(a–f).
Compounds
Entry R2
DPPH radical scavenging activity.
The DPPH radical
5a, 6a, 7a, 8a, 9a
5b, 6b, 7b, 8b, 9b
scavenging evaluation is a standard assay in antioxidant
activity studies and offers a rapid technique for screening
the RSA of specific compounds. The reaction of
synthesized compounds with stable DPPH free radical
indicates their free radical scavenging ability. In the present
study, different electron-withdrawing and electron-donating
groups attached to phenyl ring as substituent, which is
linked to sulfonyl groups were studied for antioxidant
efficacy. Among the synthesized analogs, compounds 8b
and 9b exhibited dominant antioxidant activity with IC50
value when compared with other compounds in the series,
this may be due to the presence of methoxy group in
addition to hydroxy moiety on C-6-substituted phenyl ring
and also the presence of hydroxy group at para position on
C-2-substituted phenyl ring in compound 8b. Compound
9b has a hydroxy group at para position on both C-6 and
C-2-substituted phenyl rings, which are accounted for
enhanced activity. Compounds 5b, 6b, and 7b having
hydroxy group on the sulfonyl-linked phenyl ring produce
better activity but slightly less than that of the standard
ascorbic acid (AA). The compounds in the series (5c–d,
6c–d, and 7c–d) at the para position emphasize that
the electron-withdrawing group (chloro and nitro) on the
sulfonyl-linked phenyl ring decreases the potency of the
activity, and compounds 8c–d and 9c–d also possess
electron-withdrawing group on sulfonyl-linked phenyl ring,
showing moderate activity in the presence of hydroxy
5c, 6c, 7c, 8c, 9c
5d, 6d, 7d, 8d, 9d
5e, 6e, 7e, 8e, 9e
5f, 6f, 7f, 8f, 9f
Journal of Heterocyclic Chemistry
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J. Rangaswamy, V. Kumar, S. T. Harini, and N. Naik
Vol 000
dark color of DMPD•+ radical cation solution becomes
lighter and absorbance of solution becomes lower in the
presence of an antioxidant compound. The DMPD•+ radical
cation solution shows a maximum absorbance at 505 nm.
Antioxidant compounds, which are hydrogen donors to
DMPD•+, quench the color of DMPD•+ solution. AA was
used as a standard for comparison. Among the synthesized
compounds 8b and 9b, possessed maximum radical activity
as well as more potent than the standard, and this is because
of the presence of 4-hydroxyphenyl pharmacophore at –S-
linked C-2 and C-6 positions of pyrimidine in compound
8b. Compound 9b emphasizes with 4-hydroxy 3-
methoxyphenyl at C-6 position of pyrimidine and as well as
4-hydroxyphenyl at sulfonyl-linked C-2 position of
pyrimidine nucleus, respectively. The presence of a strong
electron-withdrawing group such as nitro, chloro group on
the phenyl ring at para position did not favor the activity.
This might be the reason compounds 5–9(c–d) showed
considerable activity. In general, it appears that the presence
of electron-donating groups on the phenyl ring favors the
activity. This might be the reason for the enhancement of
activity of the other compounds, which showed moderate
RSA in compounds 5b, 6b, and 7b. Compounds 5–9(e–f)
showed good activity. The rest of the analogs showed weak
radical inhibition activity. The DMPD RSA results were
Table 2
Concentration required for 50% scavenging (IC50) of DPPH•, DMPD
radicals inhibition and absorbance of ferric ion reducing by the com-
pounds 5–6(a–f) and the standard antioxidant AA.
DPPH
DMPDx
Ferric re
Compounds
IC50
Absorbanceb
a
5a
5b
5c
5d
5e
5f
6a
6b
6c
6d
6e
6f
7a
7b
7c
7d
7e
7f
8a
8b
8c
8d
8e
8f
208
45
350
65
0.0812
0.3256
0.0701
0.0683
0.1201
0.0910
0.1025
0.3989
0.0962
0.0774
0.2937
0.2357
—
500
500
175
182
98
500
500
225
295
275
32
293
386
75
25
185
192
52
84
227
57
287
344
102
154
32
08
43
52
18
15
52
10
55
98
>500
79
0.2645
—
—
>500
>500
118
203
43
0.2156
0.1659
0.3677
0.4781
0.2235
0.3015
0.4567
0.3751
0.3098
0.4300
0.2935
0.2513
0.4256
0.3947
0.4135
15
91
74
29
42
74
18
76
89
22
33
20
presented in Table 2.
Ferric ion reducing power assay. In the ferric to ferrous
9a
9b
9c
9d
9e
9f
reduction assay, the yellow color of the test solution
changes to various shades of green and blue depending
upon the reducing power of each compound. The presence
of reducer (i.e., antioxidant) causes the reduction of the
Fe+3/Ferricyanide complex to the ferrous from giving, after
the addition of trichloroacetic acid and ferric chloride, the
Perls Prussian blue that can be monitored at 700nm. The
synthesized compounds 5–9(a–f) were screened to reduce
power ability, results revealed that the entire tested
compounds exhibited a certain degree of activity (Table 2)
compared with the reference drug. Compounds 5b, 6b, and
7b having hydroxy group, compounds 5e, 6e, and 7e were
possessing methoxy on sulfonyl–phenyl ring that exhibited
moderate to good activity. Compounds 8a, 8f, 9a, and 9f
incorporating with aromatic methyl and benzene sulfonyl
group linked at C-2 position of pyrimidine, produce
remarkable activity but less than that of the standard (AA).
The presence of hydroxy and methoxy substituents at the
para position of the phenyl ring, in compounds 8b, 8e, 9b,
and 9e exhibit more absorbance, indicates strong reducing
power than the standard, whereas compounds 5c–d, 6c–d,
and 7c–d having electron-withdrawing group (nitro and
chloro) on the SO2-linked phenyl ring at C-4 position
reveal lesser reducing ability. Compounds 5a, 6a, 7a do
not have any substituents on the 2-substituted phenyl ring
and displayed the weak reducing power compared with
other analogs.
62
24
45
11
AA
AA, ascorbic acid; DPPH, 2,2-diphenyl-1-picryl-hydrazyl; DMPD, N,N-
dimethyl-p-phenylenediamine.
aThe values are expressed as μM concentration. Lower IC50 values indi-
cate higher radical scavenging activity.
bHigher absorbance indicates higher reducing power.
group on the C-6-substituted phenyl ring; changing the
substituent on the –SO2– linked phenyl ring by electron-
donating group such as methyl and methoxy instead of
withdrawing group favors for antioxidant activity [29].
Thus, the compounds (5e–f, 6e–f, 7e–f, 8e–f, 9e–f) showed
relatively good RSA, respectively. The conjugation of
benzene sulfonyl chloride to scaffold (4a–e) revealed
considerable to moderate radical inhibition activity in
compounds 5a, 6a, 7a, 8a, and 9a. The aforementioned
SAR correlation study reveals that the nature of the
functional group present on the –SO2– linkage phenyl
ring as well as C-2 linked phenyl ring influences the
antioxidant activity.
DMPD radical scavenging activity. All the synthesized
benzofuran-gathered C-2,4,6-substituted pyrimidine derivatives
5–9(a–f) were evaluated for their antioxidant activity
employed by DMPD radical scavenging assay. The
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Novel Benzofuran-Gathered C-2,4,6-substituted Pyrimidine Derivatives as a
Month 2014
Effective Antioxidants and Antimicrobials Drug Candidates
ANTIMICROBIAL EVALUATION
The antibacterial activities of
the tested organisms, this could be due to the presence
electron-releasing substituents such as methoxy and
hydroxy on the 2-substituted sulfonyl–phenyl ring. In
general, the significant antibacterial activity attributed to
chloroaryl moiety [30]. Thus, compound 7d showed
dominant antibacterial activity against all the tested
organisms and even more than that of the standard, this
may be due to the presence of electron-withdrawing group
such as nitro on 6-substituted phenyl ring and chloro on
2-substituted sulfonyl–phenyl ring. Compound 7c showed
good activity but slightly less than the standard, and other
compounds in tested series 7a, 7b, 7e, and 7f showed
moderate inhibitory activity against all tested bacterial
strains. The results were compared with standard drug
Antibacterial activity.
newly synthesized compounds 5–9(a–f) were determined
by well plate method. In this study, Escherichia coli
ATCC 25922, Staphylococcus aureus ATCC 25923, and
Pseudomonas aeruginosa ATCC 27853 were used as
bacterial strains to investigate the activity. The test
compounds were dissolved in DMSO at concentrations 1
and 0.5 mg/mL. The investigation of antibacterial
screening data revealed that in all tested compounds,
some were showed good antibacterial activity against three
pathogenic bacterial strains. Among the tested series,
compound 5d exhibited a considerable antibacterial activity
against E. coli and P. Aeruginosa bacteria, this is because
of the presence of chloro substituents on the sulfonyl–
phenyl ring, and compounds 5a–c and 5e–f did not exhibit
any antibacterial activity. On the other hand, compounds,
6a–f, 8a–f, and 9a–f demonstrated less activity against all
Gentamicin as depicted in Table 3.
Antifungal activity. Newly synthesized compounds 5–9
(a–f) were also screened for their antifungal activity
against Aspergillus flavus MTCC 3306, Chrysosporium
keratinophilum MTCC 3017, and Candida albicans
Table 3
Inhibitory zone (diameter) millimeter of the synthesized compounds 5–6(a–f) against tested bacterial strains by well plate method. Each value represents
mean SD (n = 3).
Compounds no
Concentration in mg/mL
Control
Escherichia coli
Staphylococcus aureus
Pseudomonas aeruginosa
1
0.5
00
1
0.5
00
1
0.5
00
00
00
00
5a
5b
5c
5d
5e
1
2
1
5
1
2
3
3
2
3
5
4
0.03
—
0.17
—
0.21
—
0.17
0.12
0.11
0.18
0.13
0.10
0.44
0.15
0.13
0.24
2
1
1
4
1
1
2
2
3
2
4
2
0.01
—
—
0.10
0.23
—
—
1
1
2
4
2
1
3
4
2
3
7
6
0.03
—
—
0.25
0.14
0.21
—
0.25
0.26
0.32
0.21
0.20
0.08
0.33
0.24
0.10
0.12
0.33
0.24
0.30
0.32
0.35
0.25
0.42
1
4
0.15
0.43
0.20
0.10
0.10
0.13
0.19
0.14
0.18
0.04
0.88
0.06
0.24
0.34
0.23
0.21
0.24
0.25
0.26
0.27
0.75
0.12
1
3
1
3
1
5f
1
2
1
1
1
4
3
1
7
9
6a
6b
6c
6d
6e
1
1
2
1
2
1
7
0.14
2
2
1
2
4
4
0.19
0.16
0.13
0.34
0.10
0.11
6f
7a
7b
7c
7d
7e
13 0.34
12 0.11
16 0.32
20 0.30
15 0.32
12 0.23
2
2
3
3
2
2
2
3
2
4
3
3
12 0.15
13 0.10
8
13 0.26
15 0.32
17 0.22
21 0.65
10 0.36
12 0.54
14 0.10
17 0.95
0.10
10 0.09
10 0.17
0.14
6
9
6
6
1
1
3
1
2
2
1
1
2
2
1
1
0.24
0.48
0.36
0.24
0.11
0.13
0.05
0.15
0.13
0.11
0.12
0.28
0.27
0.16
0.13
0.42
13 0.05
14 0.35
9
9
1
1
1
2
1
1
1
2
1
3
2
2
0.24
0.10
0.16
0.13
0.11
0.11
0.11
0.10
0.37
0.29
0.27
0.16
0.15
0.73
8
7
2
2
4
2
4
3
2
2
3
4
3
2
0.45
0.14
0.16
0.10
0.14
0.22
0.11
0.15
0.24
0.28
0.17
0.29
0.13
0.33
9
0.12
7
7f
15 0.02
8a
8b
8c
8d
8e
0.21
0.65
0.21
0.15
0.34
0.18
0.26
0.24
0.14
0.21
0.10
0.67
5
5
3
4
4
2
3
2
1
5
3
2
0.18
0.24
0.15
0.14
0.16
0.18
0.11
0.13
0.20
0.11
0.14
0.16
3
3
3
2
3
1
1
1
0.10
0.45
0.04
0.14
0.10
0.10
0.19
0.27
8f
9a
9b
9c
9d
9e
—
3
1
1
0.12
0.14
0.83
9f
Gentamicin
18 0.33
11 0.41
14 0.21
09 0.36
20 0.70
17 0.41
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. Rangaswamy, V. Kumar, S. T. Harini, and N. Naik
Vol 000
MTCC 2827. The compounds were dissolved in DMSO
and antifungal activity was determined by well plate
method at concentrations 1 and 0.5 mg/mL. The results
indicated that among the tested compounds, 7d and 7c
produced significant antifungal activity when compared
with other compounds in the series against A. flavus and
the standard, Nystatin (Table 4), this would be possessing
of 4-chlorophenylsulfonyl and 4-nitrophenylsulfonyl at
C-2 position of pyrimidine and 4-nitrophenylsulfonyl at
C-6 position of pyrimidine. The compounds 5c, 5d, 6c,
and 6d were found to be moderately active against tested
C. albicans fungal strain. The remaining compounds 5b,
5e–f, 5a–b, 8a–f, and 9a–f demonstrated very least
activity against the three tested fungal strains compared
with other analogs. From the results, it is evident that in
both antibacterial and antifungal activities, two compounds
showed significant activity and few are moderately active.
The activity is considerably affected by halogens and
electron-withdrawing substituents present at the para
position of C-2 and C-6 pyrimidine-substituted phenyl rings.
In conclusion, a series of novel benzofuran-gathered
C-2,4,6-substituted pyrimidine derivatives conjugated by
sulfonyl chlorides 5–9(a–f) were synthesized and their anti-
oxidant and antimicrobial activities were evaluated. In
DPPH and DMPD assays, the presence of hydroxy and
methoxy substituents on both C-2 and C-6-substituted phe-
nyl rings, in compounds 8b and 9b, exhibits more antioxi-
dant activity than the standard. In Ferric ion reducing
power assay (FRAP) assay, compounds 8b, 8e, 9b, and 9e
containing hydroxy and methoxy on both phenyl rings
produced significant enhancement of reducing ability com-
pared with other compounds in the series and higher than
the standard. The antimicrobial activity results indicated that
among the tested compounds, 7d and 7c displayed signifi-
cant antimicrobial activity when compared with other
analogs in the series. This present studies revealed that the
nature of functional linkage –SO2– and C-6 phenyl ring)
and substituents (electron-withdrawing and electron-
donating groups) on phenyl ring is crucial for enhanced
antioxidant and antimicrobial activities. On the basis of their
Table 4
Inhibitory zone (diameter) millimeter of the synthesized compounds 5–9(a–f) against tested fungal strains by well plate method. Each value represents
mean SD (n = 3).
Compounds no
Aspergillus flavus
0.5
Chrysosporium keratinophilum
0.5
Candida albicans
1 0.5
Concentration in mg/mL
1
1
Control
5a
5b
5c
5d
5e
5f
6a
6b
6c
6d
6e
6f
7a
7b
7c
7d
7e
7f
8a
8b
8c
8d
8e
8f
00
0.01
0.06
0.41
0.36
0.45
0.06
0.02
0.72
0.15
0.21
0.16
0.02
0.42
0.11
00
—
00
00
0.13
—
00
0.27
0.43
00
0.01
0.21
1
2
9
8
2
3
2
2
6
9
2
2
2
4
2
1
9
6
3
2
1
2
7
8
2
3
1
3
0.06
0.71
0.31
0.16
0.73
0.77
0.01
0.24
0.35
0.06
0.74
0.33
0.07
0.02
1
2
3
1
2
1
6
7
1
2
1
1
5
8
1
1
1
2
0.45
0.43
0.02
0.21
0.43
0.41
0.22
0.62
0.16
0.31
0.07
0.36
0.13
8
6
1
1
0.70
0.42
0.46
0.09
—
0.13
0.72
0.21
0.63
0.41
—
11 0.23
10 0.10
10 0.11
7
2
1
2
2
8
5
2
2
1
3
0.33
0.02
0.03
0.14
0.06
0.46
0.25
0.06
0.14
0.17
0.01
3
2
3
3
9
7
3
4
2
4
0.17
0.12
0.13
0.33
0.11
0.32
0.09
0.22
0.63
0.16
2
5
6
2
1
2
0.07
21 0.45
22 0.13
19 0.65
20 0.15
16 0.43
17 0.37
15 0.09
16 0.06
22 0.78
24 0.05
20 0.88
21 0.43
2
2
2
2
2
3
3
2
1
3
4
3
3
3
0.05
0.43
0.03
0.01
0.43
0.11
0.42
0.46
0.21
0.16
0.02
0.01
0.49
0.21
1
1
0.47
0.65
—
0.23
0.05
0.24
0.61
0.73
—
0.21
0.01
0.02
0.17
0.46
2
3
3
2
3
2
2
2
2
4
4
2
2
2
0.36
0.12
0.12
0.02
0.08
0.35
0.01
0.33
0.63
0.41
0.02
0.01
0.13
0.12
1
2
1
0.08
0.38
0.41
—
0.70
0.42
—
0.40
0.06
0.73
0.02
—
2
3
1
2
4
2
3
3
0.23
0.01
0.02
0.05
0.04
0.74
0.45
0.75
—
0.02
0.02
0.21
0.42
0.04
1
2
0.76
0.09
—
0.41
0.02
0.01
0.02
0.01
—
1
1
2
1
1
1
2
1
1
2
1
1
2
1
2
3
9a
9b
9c
9d
9e
9f
1
2
2
1
2
2
4
2
3
2
—
3
1
1
1
0.01
0.11
0.65
0.43
—
0.01
3
Nystatin
21 0.05
18 0.41
16 0.33
14 0.25
22 0.23
19 0.57
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Novel Benzofuran-Gathered C-2,4,6-substituted Pyrimidine Derivatives as a
Month 2014
Effective Antioxidants and Antimicrobials Drug Candidates
177.5, 160.4, 159.4, 155.0, 145.1, 130.2, 127.6, 124.5, 123.0,
activity, these derivatives were identified as viable leads for
further studies.
121.6, 116.0, 114.2, 111.4, 55.7; MS (ESI) m/z: 278.09 (M+);
Anal. Calcd. for C18H14O3: C, 77.68; H, 5.07; found: C,
77.63; H, 5.14%.
EXPERIMENTAL
(E)-1-(benzofuran-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one
(3c).
Light brown solid, yield 56%, mp: 205–208°C,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3122–2961
(Ar–CH), 1629 (C═O); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 7.32–8.20 (m, 9H, Ar–H), 7.84 (d, 1H, J = 2.6 Hz,
β–CH), 6.95 (d, 1H, J = 3.5 Hz, α–CH); 13C NMR (DMSO-d6
100 MHz) δ ppm: 177.3, 160.2, 155.6, 145.1, 147.1, 141.3,
129.0, 127.8, 124.5, 123.6, 123.2, 121.0, 120.8, 116.2,
111.0; MS (ESI) m/z: 293.07 (M+); Anal. Calcd. for
C17H11NO4: C, 69.62; H, 3.78; N, 4.78; found: C, 69.60; H,
All reagents and solvents were purchased from Merck
(Darmstadt, Germany) chemical AR grade and were used as
provided. DPPH and AA were purchased from Sigma-Aldrich
chemical Co., (St. Louis, MO, USA). TLC analysis was performed
on alumina sheets precoated with silica gel 60 F-254 and SiO2, 200-
400mesh (Merck, Germany) was used for column chromatography.
1H NMR (400 MHz) and 13C NMR (100 MHz) were obtained from
AC Bruker spectrometer (Karlsruhe, Germany) in the appropriate
(DMSO-d6) solvent. Melting points were obtained on a Reichert
Thermopan melting point apparatus (Barnstead International, Du-
buque, IO, USA), equipped with a microscope and are uncorrected.
Mass spectra were obtained by Water-QTOF ultima spectrometer
(Milford, MA, USA). Micro analytical data were obtained by ele-
mental-Vario EL-III (Bombay, India).
3.82; N, 4.75%.
(E)-1-(benzofuran-2-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-
2-en-1-one (3d). Light yellow solid, yield, 78%, mp 192–195°C,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3130–2942
(Ar–CH), 1628 (C═O); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 6.70–7.90 (m, 8H, Ar–H), 7.65 (d, 1H, J = 4.5 Hz, β–CH),
6.72 (d, 1H, J = 3.8 Hz, α–CH), 5.32 (s, 1H, –OH), 3.83 (s, 3H,
OCH3); 13C NMR (DMSO-d6 100 MHz) δ ppm: 177.3, 160.5,
156.2, 149.0, 147.6, 145.1, 127.7, 124.7, 123.3, 122.9, 121.3,
120.9, 116.7, 111.9, 111.5, 56.1; MS (ESI) m/z: 294.09 (M+); Anal.
Synthesis of 2-acetyl benzofuran (2).
A mixture of
salicyaldehyde (1) (2 mmol), chloroacetone (2 mmol), and
potassium tert-butoxide (t-BuOK) (2 mmol) in 10 mL of dry
dichloromethane containing molecular sieves was reflux for 1 h.
Progress of the reaction was monitored by TLC using hexane/
ethyl acetate (8:2) mixture as mobile phase. After the
completion of the reaction, the reaction mixture was washed
with 10% HCl solution followed by water. The organics were
dried over anhydrous sodium sulfate. The yellow solid was
obtained by desolventizing in a rotary evaporator at room
temperature affords 2-acetyl benzofuran (2). mp 73–75°C [31],
Yield 94%, IR (KBr) νmax (cmꢀ1): 1674 (C═O), 1558 (C═C)
Calcd. for C18H14O4: C, 73.46; H, 4.79; found: C, 73.42; H, 4.75%.
(E)-1-(benzofuran-2-yl)-3-(4-hydroxyphenyl)prop-2-en-1-one
(3e). Dark brown semisolid, yield 65%, spectroscopic analysis:
IR (KBr) νmax (cmꢀ1): 3140–2960 (Ar–CH), 1630 (C═0); 1H
NMR (DMSO-d6 400 MHz) δ ppm: 6.65–7.88 (m, 9H, Ar–H),
7.70 (d, 1H, J=3.6Hz, β–CH), 6.65 (d, 1H, J= 2.6Hz, α–CH),
5.32 (s, 1H, –OH); 13C NMR (DMSO-d6 100 MHz) δ ppm: 177.2,
160.5, 157.9, 155.0, 144.9, 130.2, 127.6, 124.7, 123.3, 121.5,
120.5, 116.6, 115.8, 111.6; MS (ESI) m/z: 278.09 (M+); Anal.
Calcd. for C18H14O3: C, 77.68; H, 5.07; found: C, 77.63; H, 5.14%.
General procedure for synthesis of 4(a–e). Compounds 3
(a–e) (0.01 mol) and thiourea (0.01 mol) were dissolved in DMF
(20 mL). Few drops of concentrated HCl were added, the
reaction mixture was refluxed, and the reaction was monitored
by TLC. After completion of reaction, the reaction mixture was
poured onto 250 mL of ice cold water and kept aside for some
time. The crude solid was filtered and subjected to column
chromatography. Elution with solvent system ethyl acetate/
1
3087 (CH furan), 2900 (CH3). H NMR (DMSO-d6 400 MHz)
δ ppm: 6.80-7.70 (m, 5H, Ar–H), 2.60 (s, 3H, CH3); MS
(ESI) m/z: 161 (M+). Anal. Calcd. for C10H8O2, C, 74.99; H,
5.03; found: C, 74.95; H, 5.07%.
General procedure for synthesis of 3(a–e). Compound (2)
(1 mmol) in dichloromethane (5 mL) was treated with ZrCl4
(46.6 mg, 20 mol%) followed by addition-substituted benzaldehyde
(1 mmol). The solution was stirred at room temperature under an
air atmosphere for 1 h. After the completion of the reaction
monitored by TLC, the crude mixture was worked up in ice cold
brine solution and then extracted with ethyl acetate solution
(3 ꢁ 10 mL). The combined ethyl acetate extract was dried over
anhydrous Na2SO4 and concentrated in vacuo, and the resulting
products were purified by column chromatography using ethyl
acetate/n-hexane as mobile phase (7:3) to afford the pure products
3(a–e) as a solid. The product was recrystallized by methanol.
(E)-1-(benzofuran-2-yl)-3-phenylprop-2-en-1-one (3a). Light
yellow solid, yield 82%, mp 178–181°C, spectroscopic analysis: IR
hexane (20:80) gave pure compounds (4a–e).
4-(benzofuran-2-yl)-6-phenylpyrimidine-2-thiol (4a). Light
yellow solid, yield 82%, mp 238–241°C, spectroscopic analysis:
IR (KBr) νmax (cmꢀ1): 3130–2958 (Ar–CH), 1638 (C═N); 1H
NMR (DMSO-d6 400 MHz) δ ppm: 8.37 (s, 1H, CH of
pyrimidin), 7.14–7.92 (m, 10H, Ar–H), 12.3 (s, 1H, SH); 13C NMR
(DMSO-d6 100 MHz) δ ppm: 181.2, 166.0, 164.6, 155.2, 149.9,
135.8, 129.3, 128.7, 127.5, 124.7, 123.2, 120.9, 111.5, 103.4,
101.7; MS (ESI) m/z: 304.07 (M+); Anal. Calcd. for C18H12N2OS:
1
(KBr) νmax (cmꢀ1): 3138–2950 (Ar–CH), 1624 (C═O); H NMR
(DMSO-d6 400 MHz) δ ppm: 7.25–7.89 (m, 10H, Ar–H), 7.71 (d,
1H, J=3.5 Hz, β–CH), 6.69 (d, 1H, J=4.3Hz, α–CH); 13C NMR
(DMSO-d6 100 MHz) δ ppm: 177.6, 160.4, 155.0, 145.5, 135.7,
128.6, 127.8, 124.7, 123.3, 121.3, 120.9, 116.3, 111.2; MS (ESI)
m/z: 248.04 (M+); Anal. Calcd. for C17H12O2: C, 82.24; H, 4.87;
C, 71.03; H, 3.97; N, 9.20; found: C, 71.10; H, 3.91; N, 9.23%.
4-(benzofuran-2-yl)-6-(4-methoxyphenyl)pyrimidine-2-thiol
(4b).
Brown semisolid, yield 55%, mp: 402–405°C,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3148–2952
1
(Ar–CH), 1639 (C═N); H NMR (DMSO-d6 400 MHz) δ ppm:
found: C, 82.20; H, 4.90%.
(E)-1-(benzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one
8.39 (s, 1H, CH of pyrimidine), 7.12–8.32 (m, 9H, Ar–H), 12.5
(s, 1H, SH); 13C NMR (DMSO-d6 100 MHz) δ ppm: 181.0,
166.3, 164.5, 160.6, 155.4, 150.0, 129.3, 128.5, 128.1, 124.7,
123.0, 120.9, 114.8, 111.5, 103.2, 101.5, 55.7; MS (ESI) m/z:
334.08 (M+); Anal. Calcd. for C19H14N2O2S: C, 68.24; H, 4.22;
N, 8.38; found C, 68.20; H, 4.27; N, 8.42%.
(3b). Yellow semisolid, yield 73%, spectroscopic analysis: IR
1
(KBr) νmax (cmꢀ1): 3142–2963 (Ar–CH), 1634 (C═0); H NMR
(DMSO-d6 400MHz) δ ppm: 6.90–7.85 (m, 9H, Ar–H), 3.82 (s,
3H, OCH3), 7.68 (d, 1H, J = 3.0 Hz, β–CH), 6.70 (d, 1H,
J = 3.4 Hz, α–CH); 13C NMR (DMSO-d6 100 MHz) δ ppm:
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. Rangaswamy, V. Kumar, S. T. Harini, and N. Naik
Vol 000
4-(benzofuran-2-yl)-6-(4-nitrophenyl)pyrimidine-2-thiol
155.2, 150.0, 135.8, 131.0, 130.7, 129.8, 129.2, 128.7, 127.5,
124.8, 123.3, 120.9, 111.8, 103.8, 101.5; MS (ESI) m/z: 460.06
(M+); Anal. Calcd. for C24H16N2O4S2 : C, 62.59; H, 3.50; N, 6.08;
(4c).
Reddish brown solid, yield 74%, mp: 324–327°C,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3130–2946
1
(Ar–CH), 1625 (C═N); H NMR (DMSO-d6 400 MHz) δ ppm:
found: C, 62.54; H, 3.52; N, 6.12%.
S-4-(benzofuran-2-yl)-6-phenylpyrimidin-2-yl 4-nitrobenzene-
7.94 (s, 1H, CH of pyrimidin), 7.12–7.96 (m, 9H, Ar–H), 12.5 (s,
1H, SH); 13C NMR (DMSO-d6 100 MHz) δ ppm: 181.5, 166.2,
164.6, 155.4, 149.8, 147.9, 141.9, 129.3, 126.2, 124.7, 124.1,
123.4, 120.8, 111.2, 103.6, 101.9; MS (ESI) m/z : 349.05 (M+);
Anal. Calcd. for C18H11N3O3S: C, 61.88; H, 3.17; N, 12.03;
sulfonothioate (5c).
Light yellow solid, mp: 303–305°C,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3135–2943
(Ar–CH), 1619 (C═N); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 7.07–8.10 (m, 13H, Ar–H), 8.20 (s, 1H, CH of pyrimidin),
3.73 (s, 3H, OCH3); 13C NMR (DMSO-d6 100 MHz) δ ppm:
188.0, 166.3, 164.2, 155.2, 152.9, 149.8, 144.8, 135.7, 129.3,
128.7, 127.5, 124.8, 123.3, 120.9, 111.4, 103.5, 101.7; MS (ESI)
m/z: 489.05 (M+); Anal. Calcd. for C24H15N3O5S2: C, 58.89; H,
found: C, 61.92; H, 3.22; N, 11.99%.
4-(6-(benzofuran-2-yl)-2-mercaptopyrimidin-4-yl)-2-methoxy-
phenol (4d).
Yellow semisolid, yield 65%, spectroscopic
analysis: IR (KBr) νmax (cmꢀ1): 3140–2958 (Ar-CH), 1664
(C═N); 1H NMR (DMSO-d6 400 MHz) δ ppm: 12.40 (s, 1H,
SH), 7.98 (s, 1H, CH of pyrimidin), 6.65–7.85 (m, 9H, Ar–H),
5.30 (s,1H, OH), 3.82 (s, 3H, OCH3); 13C NMR (DMSO-d6
100MHz) δ ppm: 180.9, 165.8, 164.6, 155.0, 149.9, 148.7,
148.0, 130.5, 129.3, 124.7, 123.0, 121.2, 120.9, 115.8, 111.2,
108.8, 103.4, 101.3, 56.0; MS (ESI) m/z: 350.07 (M+); Anal.
Calcd. for C19H14N2O3S: C, 65.13; H, 4.03; N, 7.99; found: C,
65.18; H, 4.00; N, 8.05%.
3.09; N, 8.58; found: C, 58. 91; H, 3.08; N, 8.55%.
S-4-(benzofuran-2-yl)-6-phenylpyrimidin-2-yl 4-chlorobenzene-
sulfonothioate (5d). Brown solid, mp: 195–198°C, spectroscopic
analysis: IR (KBr) νmax (cmꢀ1): 3135–2963 (Ar–CH), 1643 (C═N);
1H NMR (DMSO-d6 400 MHz) δ ppm: 7.20–7.90 (m, 14H, Ar–H),
8.41 (s, 1H, CH of pyrimidin); 13C NMR (DMSO-d6 100 MHz) δ
ppm: 188.3, 166.0, 164.3, 155.0, 149.8, 139.2, 136.6, 135.8, 129.7,
129.2, 128.7, 127.3, 124.7, 123.0, 120.8, 111.2, 103.3, 101.7; MS
(ESI) m/z: 478.00 (M+); Anal. Calcd. for C24H15ClN2O3S2: C,
4-(6-(benzofuran-2-yl)-2-mercaptopyrimidin-4-yl)phenol
(4e).
Brown solid, yield 72%, mp: 194–197°C, spectroscopic
60.18; H, 3.16; N, 5.85; found: C, 60.20; H, 3.12; N, 5.82%.
analysis: IR (KBr) νmax (cmꢀ1): 3138–2975 (Ar–CH), 1634
(C═N) 1H NMR (DMSO-d6 400 MHz) δ ppm: 12.50 (s, 1H, SH),
8.24 (s, 1H, CH of pyrimidin), 6.68–7.85 (m, 9H, Ar–H), 5.35 (s,
1H, OH); 13C NMR (DMSO-d6 100 MHz) δ ppm: 181.3, 166.8,
164.2, 158.5, 155.3, 149.9, 129.3, 128.9, 128.3, 124.7, 123.3,
120.7, 116.2, 111.5, 103.4, 1017; MS (ESI) m/z: 320.06 (M+);
Anal. Calcd. for C18H12N2O2S: C, 67.48; H, 3.78; N, 8.74; found:
C, 67.45; H, 3.81; N, 8.70%.
S-4-(benzofuran-2-yl)-6-phenylpyrimidin-2-yl 4-methoxybenzene-
sulfonothioate (5e).
Dark brown solid, mp: 241–243°C,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3133–2975 (Ar–CH),
1628 (C═N, Pyrazole); 1H NMR (DMSO-d6 400 MHz) δ ppm:
7.15–7.95 (m, 14H, Ar–H), 7.94 (s, 1H, CH of pyrimidin), 3.83 (s,
3H, OCH3); 13C NMR (DMSO-d6 100 MHz) δ ppm: 188.5, 166.2,
165.6, 164.2, 155.5, 149.9, 135.7, 130.7, 129.3, 128.7, 127.5, 124.8,
123.5, 120.8, 115.2, 111.3, 103.4, 101.7, 55.8; MS (ESI) m/z: 474.09
(M+); Anal. Calcd. for C25H18N2O4S2: C, 63.27; H, 3.82; N, 5.90;
General procedure for the synthesis of benzofuran-gathered
C-2,4,6-substituted pyrimidine derivatives 5–9 (a–f).
4-
found: C, 63.19; H, 3.87; N, 5.85%.
(Benzofuran-2-yl)-6-phenylpyrimidine-2-thiol (4a) (1.2 mmol)
was suspended in dry THF (5 mL) in an inert atmosphere (N2). To
this suspension, at room temperature, triethylamine (1.5mmol)
followed by different sulfonyl chlorides (RSO2Cl) (1 mmol in
3 mL of THF) was added, and reaction mixture was stirred for
3–4 h. The progress of reaction mixture was monitored by TLC
using ethyl acetate/hexane (6:4). The reaction mixture was then
desolventized in rotary evaporator, and the compound was
extracted in ethyl acetate. The ethyl acetate layer was washed with
water and dried over anhydrous sodium sulfate. The products
were obtained by further desolventation in rotary evaporator at
50°C. The respective products were purified through column
chromatography using ethyl acetate/hexane (6:4) to furnish the
pure products (5a–f) as a solid. The same procedure was adopted
for synthesis of 6–9(a–f).
S-4-(benzofuran-2-yl)-6-phenylpyrimidin-2-yl 4-methylbenzene-
sulfonothioate (5f). Brown semisolid, spectroscopic analysis: IR
1
(KBr) νmax (cmꢀ1): 3132–2981 (Ar–CH), 1630 (C═N) H NMR
(DMSO-d6 400 MHz) δ ppm: 7.21–7.78 (m, 14H, Ar–H), 8.24 (s,
1H, CH of pyrimidin), 2.34 (s, 3H, CH3); 13C NMR (DMSO-d6
100 MHz) δ ppm: 188.2, 159.8, 164.5, 155.4, 149.8, 139.4, 135.8,
135.5, 130.0, 129.2, 128.7, 128.2, 127.4, 124.5, 123.3, 120.9,
111.4, 103.0, 101.5, 21.3; MS (ESI) m/z: 458.10 (M+); Anal.
Calcd. for C25H18N2O3S2: C, 65.48; H, 3.96; N, 6.11; found: C,
65.39; H, 4.05; N, 6.14%.
S-4-(benzofuran-2-yl)-6-(4-methoxyphenyl)pyrimidin-2-yl
benzenesulfonothioate (6a).
Reddish brown semisolid,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3130–2971 (Ar–CH),
1626 (C═N, Pyrazole); 1H NMR (DMSO-d6 400 MHz) δ ppm:
8.22 (s, 1H, CH of pyrimidin), 7.05–7.79 (m, 14H, Ar–H), 3.88 (s,
3H, OCH3),; 13C NMR (DMSO-d6 100 MHz) δ ppm: 188.6, 166.3,
164.0, 160.6, 155.4, 149.8, 129.2, 128.5, 126.1, 124.7, 123.3,
120.9, 114.8, 111.3, 103.4, 101.7, 55.8, 52.0; MS (ESI) m/z: 412.01
(M+); Anal. Calcd. for C25H18N2O4S2 : C, 58.24; H, 3.91; N, 6.79;
S-4-(benzofuran-2-yl)-6-phenylpyrimidin-2-yl methanesulfono-
thioate (5a).
Dark yellow semisolid; spectroscopic analysis IR
1
(KBr) νmax (cmꢀ1): 3128–2973 (Ar–CH), 1618 (C═N); H NMR
(DMSO-d6 400 MHz) δ ppm: 7.10–7.88 (m, 15H, Ar–H), 8.42 (m,
1H, CH of pyrimidin); 13C NMR (DMSO-d6 100 MHz) δ ppm:
188.3, 166.0, 164.6, 155.4, 149.2, 135.8, 129.3, 128.7, 127.4,
124.7, 123.3, 120.7, 111.5, 103.0, 101.6, 52.4; MS (ESI) m/z:
460.06(M+); Anal. Calcd. for C19H14N2O3S2 : C, 59.67; H, 3.69;
found: C, 58.20; H, 3.90; N, 6.83%.
S-4-(benzofuran-2-yl)-6-(4-methoxyphenyl)pyrimidin-2-yl
4-hydroxybenzenesulfonothioate (6b).
Light yellow solid,
mp: 282–285°C, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3123–2968 (Ar–CH), 1622 (C═N); 1H NMR (DMSO-d6
400 MHz) δ ppm: 8.33 (s, 1H, 1CH of pyrimidin), 7.10–7.93
(m, 13H, Ar–H), 5.35 (s, IH, OH), 3.80 (s, 3H, OCH3); 13C NMR
(DMSO-d6 100 MHz) δ ppm: 188.0, 166.2, 164.5, 163.4, 160.5,
155.5, 149.8, 131.1, 130.7, 129.6, 129.0, 128.4, 128.1, 124.7,
123.3, 120.9, 114.8, 111.5, 103.4, 101.6, 55.6; MS (ESI) m/z :
N, 7.32; found: C, 59.57; H, 3.62; N, 7.31%.
S-4-(benzofuran-2-yl)-6-phenylpyrimidin-2-yl 4-hydroxybenze-
nesulfonothioate (5b).
Brown solid, mp: 231-233°C;
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3131–2970 (Ar–CH),
1
1625 (C═N); H NMR (DMSO-d6 400 MHz) δ ppm: 7.12–7.92
(m, 14H, Ar–H), 5.32 (s, 1H, OH), 8.12 (s, 1H, CH of pyrimidin);
13C NMR (DMSO-d6 100 MHz) δ ppm: 188.6, 166.2, 164.8, 163.4,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Novel Benzofuran-Gathered C-2,4,6-substituted Pyrimidine Derivatives as a
Month 2014
Effective Antioxidants and Antimicrobials Drug Candidates
490.07 (M+). Anal. Calcd. for C25H18N2O5S2: C, 61.21; H, 3.70; N,
5.71; found: C, 61.32; H, 3.58; N, 5.65%.
ppm: 188.4, 166.2, 164.5, 163.3, 153.7, 149.8, 147.9, 141.9,
131.1, 130.7, 129.6, 129.2, 126.2, 124.7, 124.4, 123.2, 120.9,
111.5, 103.4, 101.6; MS (ESI) m/z: 505.04 (M+); Anal. Calcd. for
C24H15N3O6S2: C, 57.02; H, 2.99; N, 8.31; found: C, 57.10; H,
3.02; N, 8.38%.
S-4-(benzofuran-2-yl)-6-(4-methoxyphenyl)pyrimidin-2-yl
4-nitrobenzenesulfonothioate (6c).
Reddish brown solid,
mp: 258–261°C, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3129–2975 (Ar–CH), 1638 (C═N); 1H NMR (DMSO-d6
400 MHz) δ ppm: 7.24–8.35 (m, 13H, Ar–H), 8.40 (s, 1H,
CH of pyrimidin), 3.78 (s, 3H, OCH3); 13C NMR (DMSO-d6
100 MHz) δ ppm: 179.9, 165.8, 164.3, 160.6, 155.2, 152.9, 149.8,
144.6, 129.2, 128.5, 128.1, 124.9, 124.7, 123.3, 120.9, 114.8,
111.5, 103.4, 101.7, 55.8; MS (ESI) m/z: 519.09 (M+); Anal.
Calcd. for C25H17N3O6S2 : C, 57.79; H, 3.30; N, 8.09; found: C,
S-4-(benzofuran-2-yl)-6-(4-nitrophenyl)pyrimidin-2-yl 4-nitro-
benzenesulfonothioate (7c).
Yellow semisolid, spectroscopic
analysis: IR (KBr) νmax (cmꢀ1): 3261–2933 (Ar-CH), 1637
1
(C═N); H NMR (DMSO-d6 400 MHz) δ ppm: 8.41 (s, 1H, CH
of pyrimidin), 7.10–8.20 (m, 13H, Ar–H); 13C NMR (DMSO-d6
100 MHz) δ ppm: 188.6, 166.4, 164.6, 155.4, 152.9, 149.9, 147.9,
144.6, 141.9, 129.2, 126.2, 124.9, 124.4, 123.1, 120.7, 111.3,
103.3, 101.5; MS (ESI) m/z: 534.03 (M+); Anal. Calcd. for
C24H14N4O7S2: C, 53.93; H, 2.64; N, 10.48; found: C, 53.85; H,
2.71; N, 10.52%.
57.75; H, 3.27; N, 8.00%.
S-4-(benzofuran-2-yl)-6-(4-methoxyphenyl)pyrimidin-2-yl
4-chlorobenzenesulfonothioate (6d).
Brown semisolid,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3123–2982
(Ar–CH), (C═N,); 1H NMR (DMSO-d6 400 MHz) δ ppm:
8.39 (s, 1H, CH of pyrimidin), 7.02–7.85 (m, 13H, Ar–H),
3.85 (s, 3H, OCH3); 13C NMR (DMSO-d6 100 MHz) δ ppm:
188.4, 166.2, 164.1, 160.4, 155.3, 149.5, 139.2, 136.6, 129.8,
129.3, 128.5, 128.1, 124.7, 123.3, 120.9, 114.8, 111.5, 103.2,
101.7; MS (ESI) m/z: 508.03 (M+); Anal. Calcd. for
C25H17ClN2O4S2: C, 58.99; H, 3.37; N, 5.50; found: C, 58.95; H,
S-4-(benzofuran-2-yl)-6-(4-nitrophenyl)pyrimidin-2-yl 4-chloro-
benzenesulfonothioate (7d).
Reddish brown solid, mp:
272–275°C, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3135–2972 (Ar–CH), 1632 (C═N); 1H NMR (DMSO-d6
400 MHz) δ ppm: 8.35 (s, 1H, CH of pyrimidin), 7.14–7.98 (m,
13H, Ar–H); 13C NMR (DMSO-d6 100 MHz) δ ppm: 188.3,
166.1, 164.3, 155.5, 149.9, 147.9, 139.3, 136.6, 129.8, 129.3,
126.1, 124.5, 123.3, 120.9, 111.5, 103.4, 101.7; MS (ESI) m/z:
523.04 (M+); Anal. Calcd. for C24H14ClN3O5S2: C, 55.01; H,
2.69; N, 8.02; found: C, 55.09; H, 2.72; N, 8.12%.
3.30; N, 5.62%.
S-4-(benzofuran-2-yl)-6-(4-methoxyphenyl)pyrimidin-2-yl
S-4-(benzofuran-2-yl)-6-(4-nitrophenyl)pyrimidin-2-yl 4-methoxy-
4-methoxybenzenesulfonothioate (6e).
Brown semisolid,
benzenesulfonothioate (7e).
Brown semisolid, spectroscopic
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3122–2985
(Ar–CH), 1655 (C═N); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 7.02–7.75 (m, 13H, Ar–H), 3.84 (s, 6H, OCH3), 8.47
(s, 1H, CH of pyrimidin); 13C NMR (DMSO-d6 100 MHz) δ
ppm: 188.1, 166.2, 164.6, 165.6, 160.5, 155.4, 149.8, 130.8,
129.3, 128.5, 128.1, 124.7, 123.3, 120.9, 115.3, 114.8,
111.5, 103.1, 101.7, 55.8; MS (ESI) m/z: 504.08 (M+); Anal.
analysis: IR (KBr) νmax (cmꢀ1): 3133–2964 (Ar–CH), 1634 (C═N);
1H NMR (DMSO-d6 400 MHz) δ ppm: 8.35 (s, 1H, CH of
pyrimidin), 7.09–8.10 (m, 13H, Ar–H), 3.81 (s, 3H, OCH3); 13C
NMR (DMSO-d6 100 MHz) δ ppm: 188.4, 166.2, 165.1, 164.6,
155.6, 149.9, 147.9, 141.9, 130.8, 129.3, 126.2, 124.7, 124.4, 123.3,
120.9, 115.3, 111.5, 103.0, 101.6, 55.6; MS (ESI) m/z: 519.08 (M+);
Anal. Calcd. for C25H17N3O6S2: C, 57.79; H, 3.30; N, 8.09; found:
Calcd. for C26H20N2O5S2 : C, 61.89; H, 4.00; N, 5.55;
found: C, 61.80; H, 4.12; N, 5.53%.
S-4-(benzofuran-2-yl)-6-(4-methoxyphenyl)pyrimidin-2-yl
C, 57.74; H, 3.8; N, 8.15%.
S-4-(benzofuran-2-yl)-6-(4-nitrophenyl)pyrimidin-2-yl 4-methyl-
benzenesulfonothioate (7f).
Reddish brown semisolid,
4-methylbenzenesulfonothioate
(6f).
Light
brown
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3130–2946
(Ar–CH), 1625 (C═N); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 7.94 (s, 1H, CH of pyrimidin), 7.12–7.96 (m, 13H,
Ar–H), 2.84 (s, 3H, CH3); 13C NMR (DMSO-d6 100 MHz) δ
ppm: 188.3, 166.0, 164.8, 155.2, 149.8, 147.9, 141.9, 139.4,
135.5, 130.0, 129.3, 128.2, 126.2, 124.7, 124.4, 123.2, 120.9,
111.5, 103.2, 101.7, 21.3; MS (ESI) m/z: 503.06 (M+); Anal.
Calcd. for C25H17N3O5S2: C, 59.63; H, 3.40; N, 8.34; found: C,
semisolid, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3135–2943 (Ar–CH), 1619 (C═N); 1H NMR (DMSO-d6
400 MHz) δ ppm: 7.05–7.89 (m, 13H, Ar–H), 7.90 (s, 1H,
CH of pyrimidin), 2.82 (s, 3H, CH3); 13C NMR (DMSO-d6
100 MHz) δ ppm: 188.3, 166.0, 164.5, 160.3, 155.4, 149.8, 139.4,
135.5, 130.0, 129.3, 128.5, 128.2, 126.1, 124.7, 123.3, 120.9,
114.8, 111.5, 103.4, 101.7, 55.8, 21.3; MS (ESI) m/z : 488.11
(M+). Anal. Calcd. for C26H20N2O4S2: C, 63.92; H, 4.13; N, 5.73;
59.68; H, 3.34; N, 8.40%.
found: C, 63.90; H, 4.18; N, 5.68%.
S-4-(benzofuran-2-yl)-6-(4-nitrophenyl)pyrimidin-2-yl benze-
S-4-(benzofuran-2-yl)-6-(4-hydroxy-3-methoxyphenyl)pyrimidin-
2-yl benzenesulfonothioate (8a).
Light yellow solid. mp:
nesulfonothioate (7a).
Brown solid, mp: 325–328°C,
302–305°C, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3133–2964 (Ar–CH), 1634 (C═N); 1H NMR (DMSO-d6
400 MHz) δ ppm: 8.29 (s, 1H, CH of pyrimidin), 7.05–7.98 (m,
13H, Ar–H), 5.34 (s, 1H, OH), 3.83 (s, 3H, OCH3); 13C NMR
(DMSO-d6 100 MHz) δ ppm: 188.2, 166.5, 164.3, 155.0,
149.9, 148.7, 148.0, 130.5, 129.3, 124.7, 123.3, 121.2, 120.9,
115.8, 111.5, 108.8, 103.2, 101.6, 56.1, 52.0; MS (ESI) m/z:
428.05 (M+); Anal. Calcd. for C25H18N2O5S2: C, 56.06; H,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3138–2963
(Ar–CH), 1643 (C═N); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 8.30 (s, 1H, CH of pyrimidin), 7.09–7.90 (m, 14H, Ar–H);
13C NMR (DMSO-d6 100 MHz) δ ppm: 188.4, 166.5, 164.3,
155.5, 149.8, 147.9, 141.8, 129.3, 126.2, 124.7, 124.4, 123.3,
120.9, 111.5, 103.4, 101.6, 52.0; MS (ESI) m/z: 427.03 (M+).
Anal. Calcd. for C24H15N3O5S2: C, 53.39; H, 3.07; N, 9.83;
found: C, 53.32; H, 3.10; N, 9.75%.
S-4-(benzofuran-2-yl)-6-(4-nitrophenyl)pyrimidin-2-yl 4-hydro-
3.76; N, 6.54; found: C, 56.10; H, 3.68; N, 6.50%.
xybenzenesulfonothioate (7b).
Dark yellow solid, mp:
S-4-(benzofuran-2-yl)-6-(4-hydroxy-3-methoxyphenyl)pyrimidin-
238–241°C, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3128–2984 (Ar–CH), 1626 (C═N); 1H NMR (DMSO-d6
400 MHz) δ ppm: 8.41 (s, 1H, CH of pyrimidin), 7.12–8.30 (m,
13H, Ar–H), 5.34 (s, 1H, OH); 13C NMR (DMSO-d6 100 MHz) δ
2-yl 4-hydroxybenzenesulfonothioate (8b).
Yellow semisolid,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3128–2958 (Ar–CH),
1
1644 (C═N); H NMR (DMSO-d6 400 MHz) δ ppm: 8.41 (s, 1H,
CH of pyrimidin), 7.10–8.08 (m, 12H, Ar–H), 5.30 (s, 2H, OH),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. Rangaswamy, V. Kumar, S. T. Harini, and N. Naik
Vol 000
3.75 (s, 3H, OCH3); 13C NMR (DMSO-d6 100 MHz) δ ppm: 187.9,
166.1, 164.3, 163.5, 155.4, 149.8, 148.6, 148.0, 131.1, 130.7, 130.5,
129.7, 129.3, 124.7, 123.3, 121.2, 120.7, 115.8, 111.5, 108.7, 103.4,
101.7, 56.1; MS (ESI) m/z: 506.06 (M+); Anal. Calcd. for
C25H18N2O6S2: C, 59.28; H, 3.58; N, 5.53; found: C, 59.35; H,
3.46; N, 5.51%.
S-4-(benzofuran-2-yl)-6-(4-hydroxyphenyl)pyrimidin-2-yl
4-hydroxybenzenesulfonothioate (9b). Greenish black solid,
mp: 343–3346°C, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3138–2964 (Ar–CH), 1636 (C═N); 1H NMR (DMSO-d6
400 MHz) δ ppm: 8.35 (s, 1H, CH of pyrimidin), 7.02–7.95 (m,
12H, Ar–H), 5.29 (s, 2H, OH); 13C NMR (DMSO-d6 100 MHz) δ
ppm: 188.3, 166.0, 164.5, 163.5, 158.5, 155.4, 149.9, 131.1,
130.7, 129.6, 129.3, 128.7, 128.4, 124.7, 123.3, 120.9, 116.4,
111.5, 103.2, 101.7; MS (ESI, )m/z:476.05 (M+); Anal. Calcd. for
C24H16N2O5S2: C, 60.49; H, 3.38; N, 5.88; found: C, 60.51; H,
S-4-(benzofuran-2-yl)-6-(4-hydroxy-3-methoxyphenyl)pyrimidin-
2-yl 4-nitrobenzenesulfonothioate (8c).
Light yellow solid. mp:
265–268°C, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3135–2945 (Ar–CH), 1635 (C═N); 1H NMR (DMSO-d6 400 MHz)
δ ppm: 8.39 (s, 1H, CH of pyrimidin), 7.08–7.85 (m, 12H, Ar–H),
5.31(s,1H, OH), 3.78 (s, 3H, OCH3); 13C NMR (DMSO-d6
100 MHz) δ ppm: 188.6, 166.0, 164.6, 155.7, 152.9, 149.7, 148.7,
148.0, 144.6, 130.5, 129.3, 124.9, 124.7, 123.3, 121.2, 120.9, 115.8,
111.5, 108.6, 103.2, 101.6, 56.1; MS (ESI) m/z: 535.05 (M+); Anal.
Calcd. for C25H17N3O7S2: C, 56.07; H, 3.20; N, 7.85; found: C,
3.42; N, 5.84%.
S-4-(benzofuran-2-yl)-6-(4-hydroxyphenyl)pyrimidin-2-yl
4-nitrobenzenesulfonothioate (9c).
Yellow semisolid,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3140–2958
(Ar–CH), 1664 (C═N); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 7.98 (s, 1H, CH of pyrimidin), 6.98–7.85 (m, 12H,
Ar–H), 5.30(s,1H, OH); 13C NMR (DMSO-d6 100 MHz) δ
ppm: 188.3, 166.2, 164.6, 158.4, 155.5, 152.8, 149.9, 144.6,
129.3, 128.9, 128.4, 124.8, 123.3, 120.9, 116.4, 111.5, 103.1,
101.7; MS (ESI) m/z: 505.06 (M+); Anal. Calcd. for
C24H15N3O6S2: C, 57.02; H, 2.99; N, 8.31; found: C, 57.10; H,
56.01; H, 3.28; N, 7.75%.
S-4-(benzofuran-2-yl)-6-(4-hydroxy-3-methoxyphenyl)pyrimidin-
2-yl 4-chlorobenzenesulfonothioate (8d).
Reddish black
semisolid, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3135–2960 (Ar–CH), 1632 (C═N); 1H NMR (DMSO-d6
400 MHz) δ ppm: 8.25 (s, 1H, CH of pyrimidin), 7.10–7.90 (m,
12H, Ar–H), 5.28 (s, 1H, OH), 3.73(s, 3H, OCH3); 13C NMR
(DMSO-d6 100 MHz) δ ppm: 188.5, 166.3, 164.0, 155.4, 149.9,
148.6, 148.0, 139.3, 136.6, 130.5, 129.8, 129.2, 124.7, 123.3,
121.2, 120.9, 115.3, 111.2, 109.1, 101.3, 56.0; MS (ESI) m/z:
524.03 (M+); Anal. Calcd. for C25H18N2O6S2: C, 57.19; H, 3.26;
2.86; N, 8.36%.
S-4-(benzofuran-2-yl)-6-(4-hydroxyphenyl)pyrimidin-2-yl
4-chlorobenzenesulfonothioate (9d).
Brown semisolid,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3152–2948
(Ar–CH), 1639 (C═N); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 8.10 (s, 1H, CH of pyrimidin), 7.10–7.98 (m, 12H, Ar-
H), 5.31 (s, 1H, OH); 13C NMR (DMSO-d6 100 MHz) δ ppm:
188.2, 166.3, 164.6, 158.5, 155.5, 149.8, 139.3, 136.3, 129.8,
129.3, 128.9, 128.4, 124.7, 123.3, 120.9, 116.4, 111.5, 103.4,
101.5; MS (ESI) m/z: 494.02 (M+); Anal. Calcd. for
C24H15ClN2O4S2: C, 58.24; H, 3.05; N, 5.66 found C, 58.28;
N, 5.34; found C, 57.24; H, 3.20; N, 5.34%.
S-4-(benzofuran-2-yl)-6-(4-hydroxy-3-methoxyphenyl)pyrimidin-
2-yl 4-methoxybenzenesulfonothioate (8e).
Brown semisolid,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3130–2954 (Ar–CH),
1
1633 (C═N); H NMR (DMSO-d6 400 MHz) δ ppm: 8.24 (s, 1H,
CH of pyrimidin), 7.05–8.10 (m, 12H, Ar–H), 5.28 (s, 1H, OH),
3.78 (s, 6H, OCH3); 13C NMR (DMSO-d6 100 MHz) δ ppm: 188.3,
166.2, 165.3, 164.6, 155.5, 149.3, 148.7, 148.0, 130.8, 130.5, 129.3,
124.7, 123.3, 121.2, 120.9, 115.8, 115.3, 111.5, 108.7, 103.2, 101.7,
56.1, 55.8; MS (ESI) m/z: 520.08 (M+); Anal. Calcd. for
C26H20N2O6S2: C, 59.99; H, 3.87; N, 5.38; O, 18.44; S, 12.32;
found: C, 59.95; H, 3.91; N, 5.34; O, 18.49; S, 12.35%.
S-4-(benzofuran-2-yl)-6-(4-hydroxy-3-methoxyphenyl)pyrimidin-
2-yl 4-methylbenzenesulfonothioate (8f). Light yellow solid, mp:
H, 3.12; N, 5.59%.
S-4-(benzofuran-2-yl)-6-(4-hydroxyphenyl)pyrimidin-2-yl
4-methoxybenzenesulfonothioate (9e).
Brown semisolid,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3148–2960
(Ar–CH), 1642 (C═N); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 8.33 (s, 1H, CH of pyrimidin), 7.05–8.10 (m, 12H, Ar-H),
5.28 (s, 1H, OH), 3.83 (s, 6H, OCH3); 13C NMR (DMSO-d6
100 MHz) δ ppm: 188.4, 166.2, 165.5, 164.6, 158.7, 155.2, 149.7,
130.8, 129.3, 124.7, 123.3, 120.9, 116.4, 115.3, 111.5, 103.4,
101.7, 55.8; MS (ESI) m/z: 490.07 (M+); Anal. Calcd. for
C25H18N2O5S2: C, 61.21; H, 3.70; N, 5.71; found: C, 61.29; H,
358–361°C, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3136–2952 (Ar–CH), 1636 (C═N); 1H NMR (DMSO-d6 400 MHz)
δ ppm: 8.37 (s, 1H, CH of pyrimidin), 7.10–7.89 (m, 12H, Ar–H),
5.33 (s, 1H, OH), 3.82 (s, 3H, OCH3), 2.32 (s, 3H, CH3); 13C NMR
(DMSO-d6 100 MHz) δ ppm: 188.2, 166.0, 164.6, 155.5, 149.6,
148.5, 148.0, 139.2, 135.5, 130.5, 130.0, 129.3, 128.2, 124.7, 123.3,
121.2, 120.7, 115.6, 108.6, 103.1, 101.2, 56.1, 21.3; MS (ESI) m/z:
520.08 (M+); Anal. Calcd. for C26H20N2O6S2: C, 59.99; H, 3.87; N,
5.38; O, 18.44; S, 12.32; found: C, 59.95; H, 3.91; N, 5.34; O,
3.62; N, 5.63%.
S-4-(benzofuran-2-yl)-6-(4-hydroxyphenyl)pyrimidin-2-yl
4-methylbenzenesulfonothioate (9f).
Light yellow solid.
mp: 253–256°C, spectroscopic analysis: IR (KBr) νmax (cmꢀ1):
3138–2950 (Ar–CH), 1636 (C═N); 1H NMR (DMSO-d6
400 MHz) δ ppm: 7.98 (s, 1H, CH of pyrimidin), 7.05–7.94 (m,
12H, Ar–H), 5.30 (s, 1H, OH), 3.84 (s, 3H, OCH3), 2.34 (s, 3H,
CH3); 13C NMR (DMSO-d6 100 MHz) δ ppm: 188.4, 166.0,
164.5, 158.4, 155.5, 149.9, 139.4, 135.5, 130.0, 129.3, 128.9,
128.3, 128.2, 124.7, 123.3, 120.9, 116.4, 111.5, 103.2, 101.6,
21.3; MS (ESI) m/z: 474.07 (M+); Anal. Calcd. for
C25H18N2O4S2: C, 63.27; H, 3.82; N, 5.90; found: C, 63.27; H,
3.82; N, 5.90%.
18.49; S, 12.35%.
S-4-(benzofuran-2-yl)-6-(4-hydroxyphenyl)pyrimidin-2-yl
benzenesulfonothioate (9a).
Light yellow semisolid,
spectroscopic analysis: IR (KBr) νmax (cmꢀ1): 3140–2954
(Ar–CH), 1628 (C═N); 1H NMR (DMSO-d6 400 MHz) δ
ppm: 8.35 (s, 1H, CH of pyrimidin), 7.10–8.05 (m, 14H,
Ar–H), 5.35 (s, 1H, OH); 13C NMR (DMSO-d6 100 MHz) δ
ppm: 188.0, 166.3, 164.2, 158.5, 155.5, 149.8, 129.4, 128.9,
128.4, 124.7, 123.3, 120.8, 116.4, 111.5, 103.2, 101.9, 52.0;
MS (ESI) m/z: 398.04 (M+); Anal. Calcd. for
C24H16N2O4S2: C, 57.27; H, 3.54; N, 7.03; found: C, 57.30;
H, 3.60; N, 7.10%.
Antioxidant evaluation.
DPPH free radical scavenging assay.
antioxidant activity of newly synthesized compounds 5–9(a–f)
was carried out by DPPH RSA assay [32]. Internal standard
Butylated hydroxy anisole (BHA) and the synthesized compounds
of different concentrations were prepared in distilled ethanol,
The evaluation of
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Novel Benzofuran-Gathered C-2,4,6-substituted Pyrimidine Derivatives as a
Month 2014
Effective Antioxidants and Antimicrobials Drug Candidates
1 mL of each compound solutions having different concentrations
(10, 25, 50, 100, 200, and 500 μM) was taken in different test
tubes, 4 mL of 0.1mM ethanol solution of DPPH was added and
shaken vigorously. The tubes were then incubated in the dark
room at room temperature for 20min. A DPPH blank was
prepared without compound and ethanol was used for the baseline
correction. Changes (decrease) in the absorbance at 517 nm were
37°C. The inhibition zone that appeared after 24 h around
the well in each plate was measured as zone of inhibition in
millimeter. Experiments were triplicates and standard
deviation was calculated.
Antifungal activity.
Antifungal studies of newly
synthesized compounds were carried out against A. flavus, C.
keratinophilum, and C. albicans. Sabourands agar media was
prepared by dissolving peptone (10 g), D-glucose (40 g), and
agar (20 g) in distilled water (1000 mL) and adjusting the pH
to 5.7. Normal saline was used to make a suspension of
spore of fungal strains for lawning. A loopful of particular
measured using
a UV–visible spectrophotometer and the
remaining DPPH was calculated. The percent decrease in the
absorbance was recorded for each concentration and percent
quenching of DPPH was calculated on the basis of the observed
decreased in absorbance of the radical. The RSA was expressed as
the inhibition percentage and was calculated using the formula
fungal strain was transferred to 3 mL saline to get
a
suspension of corresponding species [38]. About 20 mL of
agar media was poured into each petri dish. Excess of
suspension was decanted and plates were dried by placing in
incubator at 37 ºC for 1 h. Using sterile cork borer punched
carefully, wells were made on these seeded agar plates
different concentrations of the test compounds in DMSO
were added into each labeled well. A control was also
prepared for the plates in the same way using solvent
DMSO. The Petri dishes were prepared in triplicate and
maintained at 25°C for 72 h. Antifungal activity was
determined by measuring the diameter of inhibition zone.
Activity of each compound was compared with fluconazole
as standard and zones of inhibition were determined for all
the synthesized compounds 5–9(a–f).
Radical scavenging activity ð%Þ ¼ ½ðA0 ꢀ A1Þ=A0 ꢁ 100ꢂ
where A0 is the absorbance of the control (blank, without compound)
and A1 is the absorbance of the compound.
DMPD radical scavenging activity.
The DMPD radical
scavenging ability of bromophenols was determined by the
method of Fogliano et al. [33] with slight modifications by
Gulcin [34]. This assay is based on the capacity of the extract to
inhibit DMPD+ cation radical formation. Briefly, 105 mg of
DMPD was dissolved in 5mL of distilled water. Then, 1 mL of
this solution was added to 100 mL of 0.1 M acetate buffer
(pH 5.3). DMPD+ was produced by adding 0.3 mL ferric chloride
(0.05 M) to this solution. Different concentrations of standard
antioxidants or synthesized compounds 5–9(a–f) (10–500 μM/mL)
were added, and the total volume was adjusted to 0.5 mL with
distilled water. One milliliter of the DMPD+ solution was directly
added to the reaction mixture. The reaction mixtures were
vortexed and incubated in the dark for 15 min. The absorbance
Acknowledgment. The authors would like to thank the NMR
Research Center, Indian Institute of Science, Bangalore for
providing the spectral data.
was measured at 505nm.
Ferric ion reducing power assay. The reducing power was
investigated by the Fe3+ to Fe2+ transformation in the presence of
synthesized compounds 5–9(a–f) as described by [35]. The Fe2+
can be monitored by measuring the formation of Perl’s Prussian
blue at 700 nm [36]. About 1 mL of the sample (10 μg/mL),
2.5 mL of phosphate buffer (pH 6.6), and 2.5 mL of 1%
potassium ferricyanide were incubated at 50°C for 30 min and
2.5 mL of 10% trichloroacetic acid was added to the mixture
and centrifuged for 10 min at 3000 rpm. About 2.5 mL of the
supernatant was diluted with 2.5 mL of water and shaken with
0.5 mL of freshly prepared 0.1% ferric chloride. The absorbance
was measured at 700 nm. BHA was used as the standard. All
tests were performed in triplicate.
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