Synthesis and antimicrobial studies of selenadiazolo benzimidazoles

Article abstract of DOI:10.1002/jhet.817

An efficient and eco-friendly method has been developed for the synthesis of selenadiazolo benzimidazoles by the condensation of N-benzylbenzo[c][1,2,5] selenadiazole-4,5-diamine with various aromatic aldehydes catalyzed by xanthan sulfuric acid. All the synthesized compounds 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j were evaluated for in vitro antibacterial activity against Gram-positive bacterial strains (Bacillus subtilis, Staphylococcus aureus, and Streptococcus pyogenes), and Gram-negative bacterial strains (Escherichia coli, Klebsiella pneumonia, and Salmonella typhimurium) and antifungal against Aspergillus niger, Candida albicans, and Aspergillus flavus (Fungi). Compound 5i emerged as the most interesting compound in this series exhibiting excellent antimicrobial activity.

Full text of DOI:10.1002/jhet.817

November 2013
Synthesis and Antimicrobial Studies of Selenadiazolo
Benzimidazoles
1337
B. Suresh Kuarm, J. Venu Madhav, and B. Rajitha*
Department of Chemistry, National Institute of Technology, Warangal, Andhra Pradesh, India
*
E-mail: rajithabhargavi@ymail.com
Received September 8, 2010
DOI 10.1002/jhet.817
Published online 12 September 2013 in Wiley Online Library (wileyonlinelibrary.com).
An efficient and eco‐friendly method has been developed for the synthesis of selenadiazolo benzimidazoles by
the condensation of N‐benzylbenzo[c][1,2,5]selenadiazole‐4,5‐diamine with various aromatic aldehydes catalyzed
by xanthan sulfuric acid. All the synthesized compounds 5a–j were evaluated for in vitro antibacterial activity
against Gram‐positive bacterial strains (Bacillus subtilis, Staphylococcus aureus, and Streptococcus pyogenes),
and Gram‐negative bacterial strains (Escherichia coli, Klebsiella pneumonia, and Salmonella typhimurium) and
antifungal against Aspergillus niger, Candida albicans, and Aspergillus flavus (Fungi). Compound 5i emerged
as the most interesting compound in this series exhibiting excellent antimicrobial activity.
J. Heterocyclic Chem., 50, 1337 (2013).
INTRODUCTION
attractive candidates in the search for such solid support cat-
alysts [23,24]. Among different biopolymers, xanthan is one
of the most common biopolymers and has some unique prop-
erties which make it an attractive alternative to conventional
organic or inorganic supports for catalytic applications. [25]
Recently, sulfonated xanthan has been used as a
biopolymeric solid support acid catalyst for the synthesis of
α‐amino nitriles [26]. This polymer has unlimited availability
as a renewable agro‐resource and is biodegradable. We
herein disclose a simple and efficient procedure for the
synthesis of selenadiazolo benzimidazoles catalyzed by
XSA at room temperature in excellent yield.
Benzimidazole and their derivatives are an important
class of bio‐active drug targets in the pharmaceutical indus-
try, as they are the core structure of numerous biologically
active compounds. For example, they represent potential
antitumor agents [1], antimicrobial agents [2], HIV [3,4],
herpes(HSV‐1) [5], RNA [6], influenza [7] and also act
as topoisomerase inhibitors [8], selective neuropeptide
YY1 receptor antagonists [9], angiotensin II inhibitors
[
10], and smooth muscle cell‐proliferation inhibitors [11].
Sulfur and selenium have many properties in common
and much sulfur chemistry is mirrored by selenium
chemistry. Selenium is the trace element controlled by
gene in human body [12]. In recent past, selenium chemis-
try was explored steadily and selenium‐based compounds
exhibited appreciable pharmacological properties [13–17].
In continuation of our work on benzimidazole moiety
18,19], we herein report for the first time, in vitro antimi-
crobial activity of selenadiazolo benzimidazoles.
The traditional synthesis of benzimidazoles includes the
condensation of o‐phenylenediamine with carboxylic acid
20], or its derivatives like nitriles, imidates, or orthoesters
RESULTS AND DISCUSSION
In our initial endeavor, we carried out the reaction of N‐
benzylbenzo[c][1,2,5]selenadiazole‐4,5‐diamine (3.0 mmol)
with various aldehydes (3.1 mmol) in presence of xanthan
sulfuric acid (0.08 g) in chloroform (5 mL) under conven-
tional and microwave irradiation conditions separately
(Scheme 1), and the results are tabulated in Table 3. In
method A [microwave (MW) irradiation], the reaction mix-
ture was irradiated in a domestic microwave oven at 300 W
over 30‐s intervals in an open vessel for 15 min. The progress
of the reaction was confirmed by thin‐layer chromatography
(TLC). At 300 W, only 50% of the reaction was completed,
whereas at 450 W, the reaction successfully completed
within 8 min. In method B [conventional], when the reaction
was carried out at room temperature, the reaction success-
fully completed within 4 h. With these optimistic results in
hand, further investigation was carried out for the catalytic
[
[
[
21] and the condensation of o‐phenylenediamine with
aldehyde in refluxing nitrobenzene [22] or in the presence of
various acidic catalysts. However, most of the methods suffer
from limitations such as moderate yields, long reaction times,
harsh reaction conditions, or tedious workup procedures.
Recently, the direction of science and technology has been
shifting more toward eco‐friendly, natural product resources,
and reusable catalysts. Thus, natural biopolymers are
©
2013 HeteroCorporation

1
338
B. S. Kuarm, J. V. Madhav, and B. Rajitha
Vol 50
Scheme 1
evaluation of XSA for the optimum reaction conditions. The
increase in the amount of XSA up to 0.1 g did not show much
difference in terms of yield or reaction time. However, in the
absence of XSA, only 10% of the product was obtained even
after stirring for 24 h. A range of aromatic and
heteroaromatic aldehydes were subjected to reaction with
N‐benzylbenzo[c][1,2,5]selenadiazole‐4,5‐diamine in the
presence of 0.08 g of XSA and chloroform as solvent. It
was found that both aromatic and heteroaromatic aldehydes
reacted equally good to afford the selenadiazolo benzimid-
azoles in excellent yields.
positive bacterial strains (Bacillus subtilis [BS],
Staphylococcus aureus [SA], and Streptococcus
pyrogenes [SP]), and Gram‐negative bacterial strains
(Escherichia coli [EI], Klebsiella pneumonia [KP], and
Salmonella typhimurium [ST]) using the agar‐diffusion
assay [28,29]. The antibiotic drug, ampicillin, was also
used as a positive control. Antibacterial screening for
analogs and positive control was performed at a fixed
concentration of 1000 μg/mL. All 10 compounds
represented in Table 1 exhibited antibacterial activity
against both Gram‐positive and Gram‐negative bacterial
strains with zones of inhibition (ZOI) ranging from 15 to
50 mm (Table 1). Analogs (5a–j) were also examined for
their antifungal activity against different fungal strains, i.
e., Aspergillus niger [AN], Candida albicans [CA], and
Aspergillus flavus [AF] (Table 1). The anti‐fungal drug,
ketoconazole, was used as a positive control. The fungal
strains were grown and maintained on Sabouraud glucose
agar plates. The plates were incubated at 26°C for 72 h
and resulting ZOIs were measured [30]. Antifungal
screening for analogs and positive control was performed
at a fixed concentration of 1000 μg/mL.
The minimum inhibitory concentration (MIC) of analogs
(5a–j) and the positive control drugs ampicillin and keto-
conazole was determined against the six bacterial strains
and the three fungal strains by the liquid dilution method
[31,32]. Concentrations of analogs and positive control
drugs at 2.5, 5, 10, 15, 20, 25, 30, 35, 40, 45, and 50 μg/mL
were prepared in an appropriate solvent. Inoculums of the
bacterial and fungal cultures were also prepared. Inoculum
(0.2 mL) and sterile water (3.8 mL) were added to a series
of tubes each containing 1 mL of test compound solution at
the 10 different concentrations. The tubes were incubated
for 24 h and carefully observed for the presence of turbid-
ity. The minimum inhibitory concentration at which no
growth was observed was taken as the MIC value. The
MIC values for all the analogs examined ranged from
2.5 to 50 μg/mL. Several analogs exhibited superior
We first tested the suitability of various solvents for the
transformation of the N‐benzylbenzo[c][1,2,5]selenadiazole‐
4,5‐diamine with various aldehydes to selenadiazolo benz-
imidazoles. Chloroform provided excellent yields (92%) and
proved to be the solvent of choice, whereas ethanol (87%),
methanol (79%), acetonitrile (73%), and water (59%) afforded
lower yields.
This method offers several advantages like milder reac-
tion conditions, shorter reaction times, cleaner reaction
profiles, high yields, and simple experimental and isolation
procedures making it an useful route to the synthesis of
selenadiazolo benzimidazoles. The structures of the com-
1
13
pounds 5a–j were confirmed by IR, H‐NMR, C‐NMR,
mass spectrometry, and elemental analysis.
At first, we synthesized the starting material (4) for the
formation of 5a–j. The first step involves the Hinsberg
reaction [27] for the synthesis of the corresponding 4‐chloro
selenadiazole in dry chloroform followed by nitration,
amination, and then treating the product with sodium
dithionate in boiled water to afford N‐benzylbenzo[c][1,2,5]
selenadiazole‐4,5‐diamine (4) in quantitative yield (Scheme 1).
BIOLOGICAL ACTIVITIES
Antibacterial and antifungal activities. All the newly
synthesized benzimidazole derivatives (5a–j) were tested
for their in vitro antibacterial activity against Gram‐
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2013
Synthesis and Antimicrobial Studies of Selenadiazolo Benzimidazoles
1339
Table 1
Zone of inhibition of selenadiazolo benzimidazoles (5a–j) analogs against different bacteria and fungi.
Zone of inhibition (mm)
a
b
c
Bacteria
Bacteria
Fungi
Analog
BS
SA
SP
EC
KP
ST
AN
CA
AF
5
5
5
5
5
5
5
5
5
5
a
b
c
d
e
f
g
h
i
21
29
35
29
30
25
30
25
40
25
35
–
24
39
40
35
25
24
20
25
50
32
44
–
26
28
38
30
30
23
25
30
39
26
33
–
29
15
36
35
25
38
25
38
44
20
37
–
34
30
36
40
25
30
25
25
47
30
40
–
27
20
35
42
26
25
19
25
46
35
42
–
25
35
25
35
27
20
20
30
38
24
–
29
29
23
35
32
15
25
30
35
35
–
30
32
29
38
35
25
35
34
38
25
–
j
d
AMPe
KET
41
38
33
a
Gram‐positive bacteria: BS, Bacillus subtilis; SA, Staphylococcus aureus; SP, Streptococcus pyogenes.
Gram‐negative bacteria: EC, Escherichia coli; KP, Klebsiella pneumonia; ST, Salmonella typhimurium.
b
c
AN, Aspergillus niger; CA, Candida albicans; AF, Aspergillus flavus.
d
AMP, ampicillin.
e
KET, ketoconazole
antimicrobial activity compared with the positive control
drugs, ampicillin and ketoconazole. The MIC data for all
the analogs against the different bacterial and fungal strains
is shown in Table 2.
ketoconazol were used as reference antimicrobial agents.
Antibacterial screening for analogs and positive control
was performed at a fixed concentration of 1000 μg/mL.
All 10 compounds exhibited antibacterial activity against
both Gram‐positive and Gram‐negative bacterial strains
with ZOI ranging from 15 to 50 mm (Table 1). Analog 5i
(ZOI[BS] = 40 mm, ZOI[SA] = 50 mm, ZOI[SP] = 39 mm,
ZOI[EC] = 44 mm, ZOI[KP] = 47 mm, and ZOI[ST] = 46 mm)
Antimicrobial activity.
The data of the antimicrobial
activity of the compounds and the control drugs as MIC
g/mL) values are given in Table 2. To observe the
efficiency of the antimicrobial activity, ampicillin and
(
Table 2
Minimum inhibitory concentration values for selenadiazolo benzimidazoles (5a–j) analogs and positive control drugs against different bacteria and fungi.
Minimum inhibitory concentration (μg/mL)
a
b
c
Bacteria
Bacteria
Fungi
Analog
BS
SA
SP
EC
KP
ST
AN
CA
AF
5
5
5
5
5
5
5
5
5
5
a
b
c
d
e
f
g
h
i
40
35
25
45
40
20
40
30
2.5
35
20
–
30
40
35
40
10
15
25
30
2.5
15
10
–
25
30
50
25
45
45
45
40
5
35
45
20
15
40
20
45
25
2.5
20
15
–
30
25
25
30
25
25
25
25
15
30
10
–
25
25
35
35
10
20
35
35
10
10
10
–
25
30
30
25
45
35
40
30
15
15
–
30
40
45
20
40
30
45
25
15
15
–
25
25
25
10
20
25
35
10
10
10
–
j
25
25
–
d
AMPe
KET
15
25
15
a
Gram‐positive bacteria: BS, Bacillus subtilis; SA, Staphylococcus aureus; SP, Streptococcus pyogenes.
Gram‐negative bacteria: EC, Escherichia coli; KP, Klebsiella pneumonia; ST, Salmonella typhimurium.
b
c
AN, Aspergillus niger; CA, Candida albicans; AF, Aspergillus flavus.
d
AMP, ampicillin.
e
KET, ketoconazole.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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340
B. S. Kuarm, J. V. Madhav, and B. Rajitha
Vol 50
was identified as a potent antibacterial agent against all
Gram‐positive and Gram‐negative bacterial strains (Table 1).
Analogs (5a–j) were also examined for their antifungal
activity against different fungal strains, i.e., Aspergillus niger
potential antimicrobial agent for the treatment of bacterial
and fungal infections.
[AN], Candida albicans [CA], and Aspergillus flavus [AF].
EXPERIMENTAL
The anti‐fungal drug, ketoconazole, was used as a positive
control. Antifungal screening for analogs and positive control
was performed at a fixed concentration of 1000 μg/mL.
Analog 5i (ZOI[AN] = 38 mm, ZOI[CA] = 35 mm, and ZOI
All the melting points were uncorrected. The progress of the
reaction was monitored by (TLC). IR spectra (KBr) were
recorded on Shimadzu FTIR model 8010 spectrometer and
1
the H‐NMR spectra on Varian Gemini 200 MHz spectrometer
=
38 mm), 5d (ZOI[CA] = 35 mm ZOI[AF] = 38 mm),
[AF]
using TMS as internal standard. The C, H, and N analysis of
the compound was done on a Carlo Erba model EA1108. Mass
spectra were recorded on a JEOL JMS D‐300 Spectrometer.
All solvents and reagents were purchased from Aldrich and
Fluka firms.
and 5j (ZOI[CA] = 35 mm) were identified as the most potent
antifungal agent against all three fungal strains (Table 1).
The MIC values for all the analogs examined ranged
from 2.5 to 50 μg/mL. Several analogs exhibited superior
antimicrobial activity compared with the positive control
drugs, ampicillin and ketoconazole. Analogs 5i (MIC[BS]
General procedure for the synthesis of selenadiazolo
benzimidazoles. Method A (microwave irradiation). A mixture
of N‐benzylbenzo[c][1,2,5]selenadiazole‐4,5‐diamine (3.0 mmol),
aldehyde (3.1 mmol), and xanthan sulfuric acid in chloroform (5
mL) was taken in an open vessel, placed in microwave oven and
irradiated at 450 W power for appropriate time (Table 3). After
completion of the reaction (confirmed by TLC), the solvent was
evaporated under vacuum on a rotary evaporator. The crude
product was purified by column chromatography on silica gel using
ethyl acetate‐hexane (2:8) as eluent to afford corresponding pure
products in good yields.
=
2.5 μg/mL, MIC[SA] = 2.5 μg/mL, MIC[SP] = 5 μg/mL,
MIC[EC] = 2.5 μg/mL, MIC[KP] = 15 μg/mL, MIC[ST]
=
1
0 μg/mL), 5e (MIC[ST] = 10 μg/mL), and 5j (MIC[ST]
=
1
0 μg/mL) were identified as potent anti‐bacterial agent,
and analogs 5i (MIC[AN] = 15 μg/mL, MIC[CA] = 15 μg/
mL, MIC[AF] = 10 μg/mL), 5j (MIC[AN] = 15 μg/mL,
MIC[CA] = 15 μg/mL, MIC[AF] = 10 μg/mL), 5h (MIC[AF]
=
10 μg/mL), and 5d (MIC[AF] = 10 μg/mL) were identified
Method B (conventional method). Mixture of N‐benzylbenzo
as potent anti‐fungal agents. Based on the MIC data, ana-
logs 5i was identified as the most potent antimicrobial
agent. The MIC data for all the analogs against the differ-
ent bacterial and fungal strains is shown in Table 2.
[c][1,2,5]selenadiazole‐4,5‐diamine (3.0 mmol), aldehyde (3.1
mmol), and xanthan sulfuric acid in chloroform (5 mL) was stirred
at room temperature for appropriate time (Table 3). After
completion of the reaction (confirmed by TLC), the solvent was
evaporated under vacuum on a rotary evaporator. The crude
product was purified by column chromatography on silica gel using
ethyl acetate‐hexane (2:8) as eluent to afford corresponding pure
products in good yields.
CONCLUSIONS
In summary, we have developed a convenient method to
synthesize selenadiazolo benzimidazoles with high yields
from N‐benzylbenzo[c][1,2,5]selenadiazole‐4,5‐diamine,
aldehydes, and XSA in chloroform, and evaluated for their
antimicrobial activity against different bacterial and fungal
strains. Analog 5i was considered lead compound worthy
of further structural optimization and development as
−1
1
Analog 5a. Mp: 230°C IR (KBr, cm ): 3064, 1621; H‐NMR
DMSO): δ = 4.03 (s, 2H), 7.08–7.34 (m, 10H), 7.37 (d, 1H), 7.69 (d,
(
1
3
1
1
1
H); C‐NMR (DMSO): δ = 43.2, 121.5, 121.7, 123.9, 127.2, 128.7,
28.8, 129.3, 129.4, 130.8, 133.9, 134.6, 135.7, 138.1, 138.5, 151.7,
60.1, 162.0; EIMS, 70 eV, m/z: 390 (M ); Anal. Calcd. for
+
C H N Se: C, 61.70; H, 3.62; N, 14.39. Found: C, 60.54; H,
20 14 4
4.29; N, 13.77.
Table 3
Synthesis of selenadiazolo benzimidazoles.
Method A
Method B
a
a
Analog
Aldehyde
Benzaldehyde
4‐Chlorobenzaldehyde
4‐Nitrobenzaldehyde
4‐Methylbenzaldehyde
4‐Methoxybenzaldehyde
4‐Hydroxybenzaldehyde
2‐Hydroxybenzaldehyde
2‐Naphthaldehyde
Time (min)
Yield (%)
Time (h)
Yield (%)
5
5
5
5
5
5
5
5
5
5
a
8
8
8
8
8
8
8
8
8
8
92
89
88
90
91
89
87
83
82
88
4
4
4
4
4
4
4
4
4
4
85
81
83
83
85
81
80
77
75
79
b
c
d
e
f
g
h
i
2‐Furaldehyde
4‐Ethoxybenzaldehyde
j
a
1
13
Yields refer to isolated products and all synthesized compounds were characterized by spectral data (IR, H‐NMR, C‐NMR, mass, and C, H, and N analysis).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2013
Synthesis and Antimicrobial Studies of Selenadiazolo Benzimidazoles
1341
−
1
1
Analog 5b.
Mp: 273°C IR (KBr, cm ): 3060, 1630; H‐
for C H N OSe: C, 60.97; H, 4.19; N, 12.93. Found: C, 61.82;
2
2 18 4
NMR (DMSO): δ = 4.09 (s, 2H), 7.06–7.40 (m, 9H), 7.47 (d,
H, 4.08; N, 2.72.
1
3
1
1
1
4
H), 7.79(d, 1H); C‐NMR (DMSO): δ = 43.1, 121.6, 121.4,
23.8, 127.3, 128.9, 129.0, 129.1, 129.5, 130.9, 133.5, 134.4,
35.8, 138.2, 143.5, 151.6, 160.2, 162.5; EIMS, 70 eV, m/z:
Acknowledgment. The author (B.S.K.) is grateful to Council of
Scientific and Industrial Research (CSIR), New Delhi, Republic
of India for providing financial support in the form of CSIR‐SRF.
+
24 (M ); Anal. Calcd. for C H ClN Se: C, 56.69; H, 3.09;
2
0
13
4
N, 13.22. Found: C, 58.23; H, 3.68; N, 12.64.
−
1
1
Analog 5c.
Mp: 196°C IR (KBr, cm ): 3049, 1640; H‐
NMR (DMSO): δ = 4.11 (s, 2H), 7.15–7.45 (m, 9H), 7.49 (d,
1
3
1
1
1
4
H), 7.85 (d, 1H), C‐NMR (DMSO): δ = 42.9, 120.8, 121.1,
23.7, 125.1, 125.6, 128.2, 129.4, 129.7, 130.4, 133.5, 134.1,
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H
13
N
5
O
2
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−
1
1
Analog 5d.
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1
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2
1 16 4
4
6
2.53; H, 4.00; N, 13.89. Found: C, 62.12; H, 3.65; N, 12.92.
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−
1
1
Analog 5e.
Mp: 276°C IR (KBr, cm ): 3059, 1628; H‐
NMR (DMSO): δ =3.63 (s, 3H), 4.08 (s, 2H), 7.07–7.39 (m,
1
3
9
5
1
H), 7.45 (d, 1H), 7.79 (d, 1H); C‐NMR (DMSO): δ = 43.4,
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8.2, 116.2, 121.6, 122.4, 124.2, 127.3, 128.9, 128.5, 129.1,
30.9, 133.5, 134.3, 135.5, 138.5, 152.0, 155.7, 160.3, 162.5;
EIMS, 70 eV, m/z: 420 (M ); Anal. Calcd. for C21
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H
16
N
4
OSe:
C, 60.15; H, 3.85; N, 13.36. Found: C, 61.22; H, 4.52; N, 13.96.
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−
1
Analog 5f.
Mp: 140–141°C IR (KBr, cm ): 3060, 1635;
5
1
H‐NMR (DMSO): δ = 3.99 (s, 2H), 5.21 (s, 1H), 6.99–7.37
[
1
3
(
m, 9H), 7.39 (d, 1H), 7.72 (d, 1H); C‐NMR (DMSO): δ =
4
3.4, 117.3, 121.2, 122.3, 124.5, 127.3, 128.9, 128.1, 129.0,
1
30.3, 133.5, 134.7, 135.2, 138.3, 152.1, 153.5, 160.5, 162.1;
+
EIMS, 70 eV, m/z: 406 (M ); Anal. Calcd. for C H N OSe:
2
0 14 4
[
C, 59.27; H, 3.48; N, 13.82. Found: C, 57.91; H, 3.90; N, 14.23.
−
1
1
Analog 5g.
Mp: 248°C IR (KBr, cm ): 3057, 1640; H‐
[
[
[
16] May, S. W. Expert Opin Invest Drugs 2002, 11, 1261.
17] Koketsu, M.; Ishihara, H. Curr Org Chem 2003, 7, 175.
18] Narasimha Reddy, P.; Thirupathi Reddy, Y.; Kanakalingeswara
NMR (DMSO): δ = 4.00 (s, 2H), 5.21 (s, 1H), 7.01–7.35 (m,
1
3
9
1
1
H), 7.40 (d, 1H), 7.74 (d, 1H); C‐NMR (DMSO): δ = 43.4,
17.0, 118.9, 121.1, 122.6, 124.3, 127.0, 128.7, 128.4, 129.3,
30.5, 133.6, 134.7, 135.2, 138.1, 152.0, 154.0, 160.4, 162.2;
EIMS, 70 eV, m/z: 406 (M ); Anal. Calcd. for C20
Rao, M.; Rajitha, B. Heterocycl Commun 2003, 9, 647.
[19] Venu Madhav, J.; Suresh Kuarm, B.; Rajitha, B. Arkivoc
+
2
008, xiii, 145.
20] Hisano, T.; Ichikawa, M.; Tsumoto, K.; Tasaki, M. Chem
Pharm Bull 1982, 30, 2996.
21] Tidwell, R. R.; Geratz, J. D.; Dann, O.; Volz, G.; Zeh, D.;
Loewe, H. J Med Chem 1978, 21, 613.
H
14
N
4
OSe:
[
C, 59.27; H, 3.48; N, 13.82. Found: C, 57.92; H, 3.88; N, 14.27.
−1
1
Analog 5h. Mp: 194–195°C IR (KBr, cm ): 3058, 1645; H‐
NMR (DMSO): δ = 4.13 (s, 2H), 7.15–7.44 (m, 12H), 7.51 (d,1H),
[
1
3
7
1
1
.82 (d, 1H); C‐NMR (DMSO): δ = 43.2, 121.7, 121.9, 123.5,
[
[
22] Sun, Q.; Yan, B. Bioorg Med Chem Lett 1998, 8, 361.
23] Breslow, R. Acc Chem Res 1980, 13, 170.
27.2, 128.2, 128.3, 128.5, 128.9, 129.0, 129.2, 130.3, 133.5,
34.2, 135.8, 136.2, 136.5, 138.0, 138.2, 152.1, 160.3, 162.5;
EIMS, 70 eV, m/z: 440 (M ); Anal. Calcd. for C H N Se: C,
[24] Clark, J. H.; Macquarrie, D. J. Green Chemistry and Technology;
Blackwell: Abingdon, 2002.
+
2
4 16 4
[
25] Huang, K.; Xue, L.; Hu, Y. C.; Huang, M.‐Y.; Jiang, Y. Y.
React Funct Polym 2002, 50, 199.
26] Shaabani, A.; Maleki, A.; Soudi, M. R.; Mofakham, H. Catal
Commun 2009, 10, 945.
27] Zhang, J. L.; Zheng, W. J.; Zou, J. H.; Yang, F.; Bai, Y.; Li, Y.
6
5.61; H, 3.67; N, 12.75. Found: C, 64.23; H, 3.11; N, 13.25.
−
1
1
Analog 5i.
Mp: 222°C IR (KBr, cm ): 3054, 1665; H‐
[
NMR (DMSO): δ = 4.08 (s, 2H), 6.65–7.11 (m, 3H), 7.20–7.41
1
3
(
m, 5H), 7.49 (d, 1H), 7.77 (d, 1H); C‐NMR (DMSO): δ =
[
4
1
7
5
0.8, 110.8, 112.5, 120.9, 121.5, 123.9, 127.2, 128.7, 129.3,
Q. Chem J Int 2004, 6, 97.
30.4, 134.6, 138.1,148.7, 150.1, 152.3, 160.1, 162.0; EIMS,
[28] Alam, S. J Chem Sci 2004, 116, 325.
[29] Reddy, P. M.; Ho, Y. P.; Shanker, K.; Rohini, R.; Ravinder, V.
Eur J Med Chem 2009, 44, 2621.
+
0 eV, m/z: 380 (M ); Anal. Calcd. for C18
H
12
N
4
OSe: C,
7.00; H, 3.19; N, 14.77. Found: C, 57.89; H, 3.27; N, 12.23.
−
1
[30] Cruickshank, R.; Duguid, J. P.; Marmion, B. P.; Swain, R. H. A.
Analog 5j. Mp: 196–197°C IR (KBr, cm ): 3058, 1633;
1
Medical Microbiology,12th ed.; Churchill Livingstone: New York, 1975;
Vol. 2.
H‐NMR (DMSO): δ = 1.45 (t, 3H), 3.97 (q, 2H), 4.06 (s, 2H),
13
7
.09–7.33 (m, 9H), 7.46 (d, 1H), 7.80 (d, 1H); C‐NMR
[
31] Omrum, U.; Arikan, S.; Kocago, S.; Semeak, B.; Unala, D.
Microbiol Infect Dis 2000, 38, 101.
32] Malue, M.; Bastide, J. M.; Biancard, A. Int J Antimicrob
Agents 2005, 25, 321.
(
DMSO): δ = 19.8, 43.8, 65.8, 116.9, 121.8, 122.7, 124.5, 127.3,
1
1
28.7, 128.0, 129.5, 130.7, 133.4, 134.5, 135.3, 138.4, 152.1,
55.5, 160.6, 162.2; EIMS, 70 eV, m/z: 434 (M ); Anal. Calcd.
[
+
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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