Synthesis and in vitro antimicrobial evaluation of 5-amino-7-aryl-6-cyano- 4H-pyrano[3,2,b]pyrrole derivatives catalyzed by reusable ZrOCl 2·8H2O

Article abstract of DOI:10.4314/bcse.v28i1.11

An efficient synthesis of a new series of 5-amino-7-aryl-6-cyano-4H- pyrano[3,2-b]pyrrole derivatives from the reaction of 3-hydroxypyrrole, malononitrile, and various aromatic aldehydes using ZrOCl₂· 8H₂O, an environmentally friendly catalyst under a thermal solvent-free green procedure is described. This simple protocol offer advantages such as shorter reaction times, simple work-up and excellent yield. The catalyst ZrOCl₂·8H₂O can be reused. The reusability of the catalyst has been studied for the synthesis of 5-amino-7-aryl-6-cyano- 4H-pyrano[3,2-b]pyrrole. All the compounds were screened for their antibacterial and antifungal activity.

Full text of DOI:10.4314/bcse.v28i1.11

Bull. Chem. Soc. Ethiop. 2014, 28(1), 91-100.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v28i1.11
ISSN 1011-3924
 2014 Chemical Society of Ethiopia
SYNTHESIS AND IN VITRO ANTIMICROBIAL EVALUATION OF
5-AMINO-7-ARYL-6-CYANO-4H-PYRANO[3,2,b]PYRROLE DERIVATIVES
CATALYZED BY REUSABLE ZrOCl2·8H2O
A. Mohammed Hussain, S. Sheik Mansoor*, K. Aswin, K. Logaiya and S.P.N. Sudhan
Bioactive Organic Molecule Synthetic Unit, Research Department of Chemistry,
C. Abdul Hakeem College, Melvisharam – 632 509, Tamil Nadu, India
(Received July 2, 2013; revised October 28, 2013)
ABSTRACT. An efficient synthesis of a new series of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole
derivatives from the reaction of 3-hydroxypyrrole, malononitrile, and various aromatic aldehydes using
ZrOCl2·8H2O, an environmentally friendly catalyst under a thermal solvent-free green procedure is described.
This simple protocol offer advantages such as shorter reaction times, simple work-up and excellent yield. The
catalyst ZrOCl2·8H2O can be reused. The reusability of the catalyst has been studied for the synthesis of 5-amino-
7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole. All the compounds were screened for their antibacterial and antifungal
activity.
KEY WORDS: ZrOCl2·8H2O, Pyranopyrrole, Malononitrile, 3-Hydroxypyrrole, Solvent-free
INTRODUCTION
Multi component reactions (MCRs) allow the creation of several bonds in a single operation and
are attracting increasing attention as one of the most powerful emerging synthetic tools for the
creation of molecular diversity and complexity [1-3].
One of the main challenges in medicinal chemistry is the design and synthesis of
biologically active molecules. 4H-pyran play an essential role as biologically active compounds
and represent an interesting template for medicinal chemistry. Many of these compounds are
known for their potential applications in pharmaceutical field. They exhibit a wide range of
biological activities like such as antimicrobial [4], antiviral [5], mutagenicity [6],
antiproliferative [7], sex pheromone [8], antitumor [9], cancer therapy [10] and central nervous
system activity [11]. Some of these compounds are widely employed as cosmetics and pigments
and as potential biodegradable agrochemicals [12]. Furthermore, they play a significant role as
potential calcium channel antagonists which are structurally similar to biologically active 1,4-
dihydropyridines [13]. Therefore, the synthesis of such compounds has attracted strong interest.
Recently, 4H-pyran derivatives were synthesized using different catalysts like magnesium
oxide [14], SB-DABCO [15], silica nanoparticles [16], ionic liquid [bmim]BF4 [17], Baker’s
yeast [18] and amino functionalized ionic liquid [19]. However, only few reports are available
for the synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole derivatives [20-24]. In
recent years, the synthesis of various 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole
derivatives have been reported by using various promoting agents, such as ferric
hydrogensulfate, Fe(HSO4)3 [20], 1-methyl-3-(triethoxysilylpropyl)-imidazolium hydrogen
sulfate anchored on silica support [pmim]HSO4 (1-propyl-3-methylimidazolium–HSO4) [21],
bis[N-(3,5-dicumylsalicylidene)anthracylaminato]zirconium(IV) dichloride as catalyst in the
presence of ultrasonic irradiation [22] and melamine trisulfonic acid (MTSA) catalyst under
solvent-free conditions [23]. Many of these methods however, suffer from drawbacks, such as
low yields of products, the requirement of longer reaction time and high temperature. Moreover,
__________
*Corresponding author. E-mail: smansoors2000@yahoo.co.in

92
A. Mohammed Hussain et al.
preparation of required catalysts is cumbersome in some cases. Thus, development of a facile,
atom-efficient, and eco-friendly method is highly desirable.
As part of our efforts to develop new synthetic methods in biologically active molecules,
such as 3,4-dihydropyrimidin-2(1H)-ones/-thiones/imines [24], β-amino ketone compounds [25]
and 2-amino-4,6-diphenylpyridine-3-carbonitrile derivatives [26] by one-pot synthesis, we
became interested in the possibility of developing a one-pot synthesis of 5-amino-7-aryl-6-
cyano-4H-pyrano[3,2-b]pyrrole derivatives catalyzed by ZrOCl2·8H2O. To the best of our
knowledge, 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole derivatives catalysed by
ZrOCl2·8H2O has not been reported.
In view of the inherent properties like environmental compatibility, reusability, greater
selectivity, operational simplicity, non corrosiveness and ease of isolation, we wish to describe
.
our results on ZrOCl2 8H2O catalyzed one pot synthesis of reactions of 3-hydroxy pyrrole,
aromatic aldehydes and malononitrile.
RESULTS AND DISCUSSIONS
Effect of solvent, temperature and catalysis
A mixture of 3-hydroxypyrrole, benzaldehyde and malononitrile with stoichiometic ratio of
1.0:1.0:1.1 and 0.05 mmol of ZrOCl2·8H2O was chosen as the model reaction to check the
feasibility of this synthesis. The solvents played an important role in the synthesis of 5-amino-7-
aryl-6-cyano-4H-pyrano[3,2-b]pyrrole derivatives. In order to optimize the reaction conditions,
various reaction media were screened (acetonitrile, cyclohexane, ethanol, benzene, toluene and
methanol) using the model reaction (Table 1, entries 1-6). It was found that the best results were
obtained with 0.05 mmol ZrOCl2·8H2O under solvent-free conditions (Table 1, entry 7). The
reaction was completed within 1.0 h and the expected product was obtained in a 94% yield.
Decreasing the quantity of the catalyst to 0.02 mmol and 0.03 mmol gave the corresponding
product in 55% and 73% yields in 1 h (Table 1, entries 8 and 9). The use of 0.08 mmol of
ZrOCl2·8H2O, there was no change in the yield (Table 1, entry 10). It was found that the best
results were obtained with 0.05 mmol ZrOCl2·8H2O under solvent-free conditions at 70 ºC
(Scheme 1).
Table 1. Synthesis of 5-amino-6-cyano7-phenyl-4H-pyrano[3,2-b]pyrrole derivatives from 3-hydroxy-
pyrrole, benzaldehyde and malononitrile catalysed by ZrOCl2·8H2O under various conditionsa.
Entry
Solvent
Acetonitrile
Cyclohexane
Ethanol
Benzene
Toluene
Methanol
None
Amount of catalyst (mmol)
Time (h)
1.0
Yield (%)
1
2
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.02
0.03
0.08
70
66
48
48
64
55
94
55
73
94
1.0
3
1.0
4
1.0
5
1.0
6
1.0
7
1.0
8
None
1.0
9
None
1.0
10
None
1.0
aReaction conditions: 3-hydroxypyrrole (1 mmol), benzaldehyde (1 mmol) and malononitrile (1.1 mmol), the
amount of solvent used for entries 1-6 was 5 mL.
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Synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2,b]pyrrole derivatives
93
R
CHO
OH
ZrOCl2.8H2O
0.05 mmol
H
N
CN
CN
CN
+
+
R
Solvent-free
70 oC
N
H
NH2
O
1
2a-l
3
4a-l
Scheme 1. Synthesis of various 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrroles.
The reusability of the catalyst is one of the most important benefits and makes it useful for
commercial applications. Thus the recovery and reusability of ZrOCl2·8H2O was investigated. In
these experiments, the reaction mixture was isolated with ethanol. The catalyst was easily reused
by filtration after washing with methanol and drying at 60 ºC. The catalyst could be reused four
times without any loss of its activity (Table 2 and Figure 1).
Table 2. The solvent-free synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole derivatives from
3-hydroxypyrrole, benzaldehydes and malononitrile catalysed by ZrOCl2·8H2O (0.05 mmol)a.
Entry
1
Aldehyde
Product
M.P. (ºC)
206–208
Time (h)
1.0
Yield (%)
94b
CHO
H
N
CN
O
NH2
4a
OH
CHO
2
224–226
1.0
83
H
N
CN
OH
O
NH2
4b
CN
CHO
3
4
5
217–219
198–200
216–218
1.5
1.5
1.0
76
83
89
H
N
CN
CN
O
NH2
4c
NO2
CHO
H
N
CN
NO
2
O
NH2
4d
CH3
CHO
H
N
CN
CH
3
O
NH2
4e
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A. Mohammed Hussain et al.
OCH3
CHO
OCH
6
7
8
9
212–214
1.5
89
H
N
CN
3
O
NH2
4f
Cl
CHO
196–198
1.0
88
H
N
CN
Cl
O
F
NH2
4g
CHO
208–210
1.0
89
88
H
N
CN
F
O
NH2
4h
Br
CHO
222–224
1.0
H
N
CN
Br
O
NH2
4i
CHO
Cl
10
11
202–204
210–212
1.5
1.0
84
87
Cl
H
N
CN
O
NH2
4j
CHO
F
F
H
N
CN
O
NH2
4k
CHO
Br
12
226–228
Br
H
N
CN
2.0
83
O
NH2
4l
aReaction conditions: 3-hydroxypyrrole (1 mmol), aromatic aldehyde (1 mmol) and malononitrile (1.1 mmol) at
70 ºC. bCatalyst can be reused four times. Yield (%) for the reaction was 94, 93, 92, 90.
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Synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2,b]pyrrole derivatives
95
98
96
Reusability of the catalyst
94%
94
93%
92%
92
90%
90
88
86
1
2
3
4
Number of Runs
Figure 1. The reusability of the catalyst ZrOCl2·8H2O for the synthesis of 5-amino-7-aryl-6-
cyano-4H-pyrano[3,2-b]pyrrole.
Synthesis of various 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole derivatives
To investigate the versatility of the catalyst, the reaction of 3-hydroxypyrrole and various
aromatic aldehydes and malononitrile was carried out under solvent-free conditions in 70 ºC
using 0.05 mmol of ZrOCl2·8H2O (Scheme 1). 5-Amino-7-aryl-6-cyano-4H-pyrano[3,2-
b]pyrrole derivatives containing both electron-withdrawing or electron-donating groups were
formed in a short experimental time (1.0–2.0 h) with high yields (76–94%) (Table 2).
Various aromatic aldehydes bearing different substitutes, such as para-OH, CN, NO2, CH3,
OCH3, Cl, F, Br were favorable to the reactions (4a–4i). The presence of more electron
releasing groups such as para-CH3, OCH3, Cl, F and Br to give the corresponding products in
high yield (Table 2, entries 5-9); however, the presence of more electron withdrawing groups
such as NO2 and CN adversely affected the results (Table 2, entries 3 and 4). We carried out a
study of sterically hindered ortho-substituted aromatic aldehydes bearing substitutes, such as Cl,
F and Br (Table 2, entries 10-12) (4j–4l). ortho-substituted aromatic aldehydes generally gave
very low yield. That is to say, steric factors played a key role in affecting the rate of reaction and
the reaction requires a longer time. In case of ortho-F substituted benzaldehyde, the reaction
time was less compared to other ortho-substituted benzaldehydes (Table 2, entry 11). The
reaction was compared with ortho-Cl and ortho-Br substituted benzaldehydes (Table 2, entries
10 and 12). It should be mentioned that as minor atomic radius of fluorine atom, ortho-F
substituted benzaldehyde displayed no above-mentioned steric hindered effect and reacted faster
than any other ortho-substituted benzaldehydes. The catalyst was easily regenerated by filtering
the reaction mixture after completion of reaction.
.
To explore the advantages of this ZrOCl2 8H2O catalyzed synthesized of 5-amino-7-aryl-6-
cyano-4H-pyrano[3,2-b]pyrrole, we compared the results we obtained under the optimized
conditions with results reported in the literature by other catalysts (Table 3). Among the
catalysts ferric hydrogensulfate, Fe(HSO4)3 [20], 1-methyl-3-(triethoxysilylpropyl)-imidazolium
hydrogen sulfate anchored on silica support [pmim]HSO4 (1-propyl-3-methyl- imidazolium–
HSO4) [21],
melamine trisulfonic acid (MTSA) [23], ZrOCl2 8H2O was found to be superior in terms of yield
and time of reaction.
bis[N-(3,5-dicumylsalicylidene)anthracylaminato] zirconium(IV) [22] and
.
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A. Mohammed Hussain et al.
.
Table 3. Comparison of catalytic activity of ZrOCl2 8H2O with other catalysts reported in the literature for
the synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole.
Entry Catalyst
Conditions
Time (h)
6.0
Yield (%)
Ref.
[20]
1
2
3
4
5
Fe(HSO4)3
EtOH/Reflux
CH3CN/50 oC
CH3CN/Ultrasonic 50 oC
86
89
86
92
94
[pmim]HSO4–SiO2
Zr-Catalyst
3.0
[21]
0.5
[22]
Melamine trisulfonic acid EtOH/Reflux
.
ZrOCl2 8H2O
1.5
[23]
Solvent-free/70 oC
1.0
This work
Biological activity
The antibacterial activity of compounds 4a-l were tested against two Gram-negative bacteria
(Escherichia coli and Pseudomonas aeruginosa), and two Gram-positive bacteria (Bacillus
subtilis and Staphylococcus aureus) and antifungal activity against Aspergillus flavus, Rhizopus
schipperae, Aspergillus niger and Candida albicans.
Antibacterial activity
Ciprofloxacin was used as the reference drug. The micro dilution susceptibility test in Muller-
Hinton broth was used for the determination of antibacterial activity. Serial dilutions of the drug
in Muller-Hinton broth were taken in tubes and their pH was adjusted to 5.0 using phosphate
buffer. A standardized suspension of the test bacterium was inoculated and incubated for 16-18
h at 37 oC. The minimum inhibitory concentration (MIC) was noted by seeing the lowest
concentration of the drug at which there was no visible growth. The observed MICs are given in
Table 4. In general all the synthesized compounds exert a wide range of modest antibacterial
activity in vitro against the tested organisms.
Table 4. In vitro antibacterial activity of compounds 4a–l.
Minimum inhibitory concentration (MIC) in µg/mL
Compound
E. coli
150
100
50
P. aeruginosa
B. subtilis
150
100
75
S. aureus
150
75
4a
100
75
50
75
75
75
50
50
50
75
50
50
25
4b
4c
75
4d
50
75
50
4e
100
100
100
50
100
100
75
75
4f
100
75
4g
4h
75
50
4i
100
100
50
75
75
4j
75
75
4k
4l
75
50
75
75
75
Ciprofloxacin
50
50
50
Antifungal activity
All the compounds were screened for their antifungal activity against each fungal strain in
DMSO by serial plate dilution method. Amphotericin B was used as the reference drug.
Sabourauds agar media was prepared by dissolving peptone (1 g), D-glucose (4 g) and agar (2 g)
in distilled water (100 mL) and adjusting the pH to 5.7. Normal saline was used to make a
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Synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2,b]pyrrole derivatives
97
suspension of sore of fungal strains for lawning. A loopful of particular fungal strain was
transferred to 3 mL saline to get a suspension of corresponding species. Twenty milliliters of
agar media was poured into each Petri dish. Excess of suspension was decanted and plates were
o
dried by placing in an incubator at 37 C for 1 h. Using a punch, wells were made on these
seeded agar plates. The observed MICs are given in Table 5.
Table 5. In vitro antifungal activity of compounds 4a–l.
Minimum inhibitory concentration (MIC) in µg/mL and zone of inhibition in mm
Compound
A. flavus
150
150
75
R. schipperae
A. niger
100
150
100
100
150
150
75
C. albicans
100
100
100
75
4a
100
100
75
4b
4c
4d
75
50
4e
150
150
100
75
100
100
75
100
100
75
4f
4g
4h
75
100
100
100
100
100
50
75
4i
150
100
75
75
100
75
4j
75
4k
4l
75
75
100
50
75
100
25
Amphoterecin-B
25
CONCLUSIONS
In conclusion, we have developed a very simple and efficient method for the high-yielding
synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole derivates by one-pot three-
component coupling of 3-hydroxypyrrole and various aromatic aldehydes and malononitrile
using ZrOCl2·8H2O as a catalyst. This method offers some advantages in terms of simplicity of
performance, low reaction times, solvent-free condition, low cost, and it follows along the line
of green chemistry. The catalyst is readily available and inexpensive and can conveniently be
handled and removed from the reaction mixture. All the compounds were screened for their
antibacterial and antifungal activities.
EXPERIMENTAL
Chemicals were purchased from Merck, Fluka and Aldrich Chemical Companies. All yields
1
refer to isolated products unless otherwise stated. H NMR (500 MHz) and 13C NMR (125
MHz) spectra were obtained using Bruker DRX- 500 Avance at ambient temperature, using
TMS as internal standard. FT-IR spectra were obtained as KBr discs on Shimadzu spectrometer.
Mass spectra were determined on a Varion-Saturn 2000 GC/MS instrument. Elemental analysis
was measured by means of Perkin Elmer 2400 CHN elemental analyzer flowchart.
General procedure for synthesis of pyranopyrrole derivatives (4a–4l)
A mixture of 3-hydroxypyrrole (1 mmol), aldehyde (1 mmol), malononitrile (1.1 mmol) and
ZrOCl2·8H2O catalyst (0.05 mmol) was stirred at 70 ºC in a 50 mL flask for the appropriate
time, as shown in Table 2. The reaction was monitored by TLC and after completion of the
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A. Mohammed Hussain et al.
reaction; the catalyst was simply recovered by filtration and washed by ethanol. The residue was
concentrated in vacuo and the crude product was purified by column chromatography on silica
gel.
Spectral data for the synthesized compounds
5-Amino-7-aryl-1,7-dihydropyrano[3,2-b]pyrrole-6-carbonitrile (4a). IR (KBr, cm-1): 3400,
1
3417, 3260, 2140, 1262. H NMR (500 MHz, DMSO-d6): δ = 5.42 (s, 1H, pyran H4), 6.30 (d,
1H, pyrrole H3), 6.72 (d, 1H, pyrrole H2), 6.73(s, 2H, NH2), 7.02-7.09 (m, 5H, Ar-H), 7.40 (s,
1H, pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 29.2, 55.1, 101.0, 105.0, 117.4,
121.8, 123.5, 127.4, 128.9, 129.9, 130.2, 174.7 ppm; MS (ESI): m/z 238 (M+H)+. Anal. calcd.
for C14H11N3O: C, 70.89; H, 4.64; N, 17.72%. Found: C, 70.62; H, 4.60; N, 17.60%.
5-Amino-7-(4-hydroxyphenyl)-1,7-dihydropyrano [3,2-b]pyrrole-6-carbonitrile (4b). IR (KBr,
cm-1): 3462, 3412, 3415, 3236, 2206, 2195, 1245. 1H NMR (500 MHz, DMSO-d6): δ = 10.16 (s,
1H, OH), 5.50 (s, 1H, pyran H4), 6.38 (d, 1H, pyrrole H3), 6.72 (d, 1H, pyrrole H2), 6.74 (s, 2H,
NH2), 7.10–7.20 (m, 4H, Ar-H), 7.45 (s, 1H, pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-
d6): δ = 28.3, 59.0, 110.3, 111.5, 115.6, 118.6, 120.6, 128.4, 130.2, 132.4, 134.8, 135.4, 142.0,
177.0 ppm; MS (ESI): m/z 254 (M+H)+. Anal. calcd. for C14H11N3O2: C, 66.40; H, 4.35; N,
16.60%. Found: C, 66.38; H, 4.28; N, 16.54%.
5-Amino-7-(4-cyanophenyl)-1,7-dihydropyrano[3,2-b]pyrrole-6-carbonitrile (4c). IR (KBr,
1
cm-1): 3409, 3412, 3240, 2210, 2188, 1260. H NMR (500 MHz, DMSO-d6): δ = 5.50 (s, 1H,
pyran H4), 6.10 (d, 1H, pyrrole H3), 6.40 (s, 2H, NH2), 6.63 (d, 1H, pyrrole H2), 7.21 (s, 1H,
pyrrole NH), 7.25-7.33 (m, 4H, Ar-H), ppm; 13C NMR (125 MHz, DMSO-d6): δ = 33.9, 62.3,
111.0, 113.4, 114.6, 122.3, 124.7, 126.8, 129.2, 133.7, 138.9, 139.6, 177.5 ppm; MS (ESI): m/z
263 (M+H)+. Anal. calcd. for C15H10N4O: C, 68.69; H, 3.84; N, 21.36%. Found: C, 67.74; H,
3.70; N, 21.12%.
5-Amino-1,7-dihydro-7-(4-nitrophenyl)pyrano[3,2-b]pyrrole-6-carbonitrile (4d). IR (KBr,
cm-1): 3408, 3420, 3228, 2168, 1372, 1558, 1247. 1H NMR (500 MHz, DMSO-d6): δ = 5.51 (s,
1H, pyran H4), 6.13 (d, 1H, pyrrole H3), 6.48 (s, 2H, NH2), 6.58 (d, 1H, pyrrole H2), 7.30 (s, 1H,
pyrrole NH), 7.30-7.44 (m, 4H, Ar-H), ppm; 13C NMR (125 MHz, DMSO-d6): δ = 30.1, 59.3,
107.6, 108.2, 120.3, 121.6, 124.0, 129.4, 136.6, 141.8, 145.7, 176.9 ppm; MS (ESI): m/z
283(M+H)+. Anal. calcd. for C14H10N4O3: C, 59.57; H, 3.57; N, 19.85%. Found: C, 59.42; H,
3.44; N, 19.76%.
5-Amino-1,7-dihydro-7-(4-methylphenyl)pyrano[3,2-b]pyrrole-6-carbonitrile (4e). IR (KBr,
1
cm-1): 3408, 3412, 3274, 2164, 1252. H NMR (500 MHz, DMSO-d6): δ =2.26 (s, 3H, CH3),
5.42 (s, 1H, pyran H4), 6.12 (d, 1H, pyrrole H3), 6.72 (s, 2H, NH2), 6.90 (d, 1H, pyrrole H2),
6.92–7.00 (m, 4H, Ar-H), 7.39 (s, 1H, pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-d6): δ =
24.3, 29.4, 54.02 100.4, 106.4, 116.3, 123.4, 128.4, 129.3, 131.7, 133.7, 137.9, 173.1 ppm; MS
(ESI): m/z 252 (M+H)+. Anal. calcd. for C15H13N3O: C, 71.71; H, 5.18; N, 16.73%. Found: C,
71.56; H, 5.14; N, 16.58%.
5-Amino-1,7-dihydro-7-(4-methoxyphenyl)pyrano[3,2-b]pyrrole-6-carbonitrile (4f). IR (KBr,
1
cm-1): 3410, 3399, 3278, 2163, 1252. H NMR (500 MHz, DMSO-d6): δ = 3.44 (s, 3H, OCH3),
5.41 (s, 1H, pyran H4), 6.14 (d, 1H, pyrrole H3), 6.80- 6.94 (m, 4H, Ar-H), 6.77 (d, 1H, pyrrole
H2), 6.80 (s, 2H, NH2), 7.49 (s, 1H, pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-d6): δ =
27.9, 54.9, 60.2, 101.5, 104.4, 119.0, 119.5, 121.5, 126.1, 127.4, 131.0, 153.9, 171.8 ppm; MS
Bull. Chem. Soc. Ethiop. 2014, 28(1)

Synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2,b]pyrrole derivatives
99
(ESI): m/z 268 (M+H)+. Anal. calcd. For C15H13N3O2: C, 67.42; H, 4.87; N, 15.73%. Found: C,
67.28; H, 4.82; N, 15.66%.
5-Amino-7-(4-chlorophenyl)-1,7-dihydropyrano[3,2-b]pyrrole-6-carbonitrile (4g). IR (KBr,
1
cm-1): 3408, 3422, 3256, 2154, 1266. H NMR (500 MHz, DMSO-d6): δ = 5.38 (s, 1H, pyran
H4), 6.09 (d, 1H, pyrrole H3), 6.42 (s, 2H, NH2), 6.59 (d, 1H, pyrrole H2), 7.03-7.10 (m, 4H, Ar-
H), 7.21 (s, 1H, pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 30.4, 60.4, 105.4,
108.3, 119.4, 124.6, 129.4, 129.9, 130.7, 132.2, 135.8, 177.7 ppm; MS (ESI): m/z 272.45
(M+H)+. Anal. calcd. for C14H10ClN3O: C, 61.89; H, 3.68; N, 15.47%. Found: C, 61.80; H,
3.55; N, 15.44%.
5-Amino-7-(4-fluorophenyl)-1,7-dihydropyrano[3,2-b]pyrrole-6-carbonitrile (4h). IR (KBr,
1
cm-1): 3406, 3430, 3278, 2211, 1239. H NMR (500 MHz, DMSO-d6): δ = 5.43 (s, 1H, pyran
H4), 6.13 (d, 1H, pyrrole H3), 6.44 (s, 2H, NH2), 6.97-7.15 (m, 4H, Ar-H), 6.76 (d, 1H, pyrrole
H2), 7.46 (s, 1H, pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 31.5, 65.3, 100.0,
109.0, 116.8, 123.0, 127.0, 127.5, 129.3, 130.4, 131.5, 131.9, 138.7, 142.8, 176.5 ppm; MS
(ESI): m/z 256 (M+H)+. Anal. calcd. for C14H10FN3O: C, 65.88; H, 3.92; N, 16.47%. Found: C,
65.75; H, 3.85; N, 16.44%.
5-Amino-7-(4-bromophenyl)-1,7-dihydropyrano[3,2-b]pyrrole-6-carbonitrile (4i). IR (KBr,
1
cm-1): 3404, 3414, 3300, 2186, 1260. H NMR (500 MHz, DMSO-d6): δ = 5.51 (s, 1H, pyran
H4), 6.09 (d, 1H, pyrrole H3), 6.97–7.09 (m, 4H, Ar-H), 6.61 (d, 1H, pyrrole H2), 7.48 (s, 1H,
pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 28.1, 56.3, 107.5, 108.5, 121.4, 122.3,
123.4, 127.3, 128.2,131.3, 132.4, 133.4, 141.5, 177.8 ppm; MS (ESI): m/z 316.9 (M+H)+. Anal.
calcd. for C14H10BrN3O: C, 53.18; H, 3.17; N, 13.29%. Found: C, 53.05; H, 3.10; N, 13.20%.
5-Amino-7-(2-chlorophenyl)-1,7-dihydropyrano[3,2-b]pyrrole-6-carbonitrile (4j). IR (KBr,
1
cm-1): 3412, 3433, 3250, 2150, 1258. H NMR (500 MHz, DMSO-d6): δ = 5.44 (s, 1H, pyran
H4), 6.11 (d, 1H, pyrrole H3), 6.44 (s, 2H, NH2), 6.66 (d, 1H, pyrrole H2), 7.03 -7.10 (m, 4H,
Ar-H), 7.22 (s, 1H, pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 30.2, 60.2, 105.3,
107.9, 119.5, 124.4, 129.2, 129.9, 130.5, 132.6, 135.9, 178.0 ppm; MS (ESI): m/z 272.45
(M+H)+. Anal. calcd. for C14H10ClN3O: C, 61.89; H, 3.68; N, 15.47%. Found: C, 61.77; H,
3.49; N, 15.38%.
5-Amino-7-(2-fluorophenyl)-1,7-dihydropyrano[3,2-b]pyrrole-6-carbonitrile (4k). IR (KBr,
1
cm-1): 3400, 3422, 3277, 2209, 1244. H NMR (500 MHz, DMSO-d6): δ = 5.40 (s, 1H, pyran
H4), 6.10 (d, 1H, pyrrole H3), 6.40 (s, 2H, NH2), 6.99-7.13 (m, 4H, Ar-H), 6.68 (d, 1H, pyrrole
H2), 7.44 (s, 1H, pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 31.3, 65.1, 100.4,
109.2, 116.2, 123.4, 127.3, 128.6, 129.5, 130.6, 131.5, 132.4, 138.8, 141.3, 177.0 ppm; MS
(ESI): m/z 256 (M+H)+. Anal. calcd. for C14H10FN3O: C, 65.88; H, 3.92; N, 16.47%. Found: C,
65.70; H, 3.89; N, 16.40%.
5-Amino-7-(2-bromophenyl)-1,7-dihydropyrano[3,2-b]pyrrole-6-carbonitrile (4l). IR (KBr,
1
cm-1): 3408, 3418, 3307, 2177, 1272. H NMR (500 MHz, DMSO-d6): δ = 5.44 (s, 1H, pyran
H4), 6.11 (d, 1H, pyrrole H3), 6.97–7.09 (m, 4H, Ar-H), 6.66 (d, 1H, pyrrole H2), 7.55 (s, 1H,
pyrrole NH) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 27.9, 56.0, 107.3, 108.7, 121.6, 122.7,
123.8, 127.7, 128.5,131.4, 132.8, 133.9, 141.9, 177.0 ppm; MS (ESI): m/z 316.9 (M+H)+. Anal.
calcd. for C14H10BrN3O: C, 53.18; H, 3.17; N, 13.29%. Found: C, 53.15; H, 3.14; N, 13.11%.
Bull. Chem. Soc. Ethiop. 2014, 28(1)

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A. Mohammed Hussain et al.
ACKNOWLEDGEMENTS
We sincerely thank the management of C. Abdul Hakeem College, Melvisharam – 632 509,
India, for providing the laboratory facilities. We are also thankful to Dr. A. Abdul Rahuman,
Unit of Nanotechnology and Bioactive Natural Products, for useful discussion and
encouragement.
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