Facile one-pot synthesis of 5-amino-7-aryl-6-cyano-4Hpyrano[ 3,2-b]pyrroles using supported hydrogen sulfate ionic liquid

Article abstract of DOI:10.1007/s00706-012-0744-2

Twelve new derivatives of 5-amino-7-aryl-6- cyano-4H-pyrano[3,2-b]pyrrole were prepared by one-pot acid-catalyzed cyclocondensation reaction of 3-hydroxypyrrole, malononitrile, and various aldehydes in the presence of the silica-supported ionic liquid 1-m

Full text of DOI:10.1007/s00706-012-0744-2

Monatsh Chem
DOI 10.1007/s00706-012-0744-2
ORIGINAL PAPER
Facile one-pot synthesis of 5-amino-7-aryl-6-cyano-4H-
pyrano[3,2-b]pyrroles using supported hydrogen
sulfate ionic liquid
•
Reza Sandaroos Saman Damavandi
•
Mehri Salimi
Received: 4 July 2011 / Accepted: 26 February 2012
Ó Springer-Verlag 2012
Abstract Twelve new derivatives of 5-amino-7-aryl-6-
cyano-4H-pyrano[3,2-b]pyrrole were prepared by one-pot
acid-catalyzed cyclocondensation reaction of 3-hydroxy-
pyrrole, malononitrile, and various aldehydes in the
presence of the silica-supported ionic liquid 1-methyl-3-
(triethoxysilylpropyl)imidazolium hydrogen sulfate as cat-
alyst. The reaction efficiencies were enhanced by moderate
electron-withdrawing groups, such Cl and Br, on benzal-
dehyde, but decreased as substituents became more
electron-withdrawing. Among the solvents and catalysts
screened for the model reaction, acetonitrile and the silica-
supported hydrogen sulfate ionic liquid were found to be
the best choices.
readily recycled and tunable to specific chemical tasks. One
type is Brønsted acidic task-specific ionic liquids (BAILs).
-
Among these, ionic liquids possessing HSO4 as a count-
eranion find a broad application in organic synthesis, acting
as both solvents and catalysts. Recently, immobilization
processes involving acidic ionic liquids on solid supports
have been designed [2–8]. The heterogenization of catalysts
and reagents can offer important advantages in handling,
separation, and reuse procedures. On the basis of economic
criteria, it is desirable to minimize the amount of ionic
liquid utilized in a potential process. Immobilized acidic
ionic liquids have been used as novel solid catalysts for a
wide spectrum of reactions [9–13].
Homogeneous catalysts could be heterogenized through
covalent and non-covalent attachment to either inorganic or
organic materials, such as silica [14, 15], layered clay
[16, 17], and polymers [18, 19]. Compared with organic
supports, higher chemical and thermal stability are the
most important advantages which are offered by inorganic
supports. Despite having advantages, such as the increased
flexibility in the choice of the support material, reaction
conditions, and work-up strategies, non-covalent attach-
ment enhances leaching of the catalyst from the support,
leading to higher losses in activity of non-covalent cata-
lysts in comparison with covalent analogues [20].
Keywords Supported ionic liquids Á Supported catalysts Á
One-pot synthesis Á 5-Amino-7-aryl-6-cyano-4H-pyrano-
[3,2-b]pyrrole Á Hydrogen sulfate ionic liquid
Introduction
In recent years, ionic liquids have become a powerful
alternative to conventional molecular organic solvents due
to their particular properties, such as undetectable vapor
pressure and the ability to dissolve many organic and
inorganic substances [1]. In addition, ionic liquids are
4H-Pyran derivatives are of interest in the area of
synthesizing various drugs owing to their various phar-
macological and biological activities, such as antimicrobial
[21], mutagenicity [22, 23], antiproliferative [24], sex
pheromone [25], antitumor [26], cancer therapy [27–29],
and central nervous system activity [30]. Some of these
compounds are widely employed as cosmetics and pig-
ments and as potentially biodegradable agrochemicals [31].
Accordingly, the synthesis of such compounds is an
interesting challenge.
R. Sandaroos (&) Á M. Salimi
Department of Chemistry, Faculty of Science,
University of Birjand, Birjand, Iran
e-mail: R_Sandaroos@yahoo.com
S. Damavandi
Department of Chemistry, Sarvestan Branch,
Islamic Azad University, Sarvestan, Iran
123

R. Sandaroos et al.
Scheme 1
Ar
OH
O
H
CN
CN
CN
[pmim]HSO4-SiO2
N
+
+
H
Ar
N
O
NH2
H
With the aim of obtaining more biologically potent
heterocyclic systems, many efforts have recently been
undertaken for the preparation of various pyran derivatives,
such as benzopyrans [32, 33], naphthopyrans [34–36], and
4-substituted pyrans [37], but to the best of our knowledge,
the synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]-
pyrrole derivatives has never been communicated until
now. With these considerations in mind, we now report
the synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]-
pyrroles by one-pot cyclocondensation reaction of
3-hydroxypyrrole, substituted benzaldehydes, and malono-
nitrile in the presence of 1-methyl-3-(triethoxysilylpropyl)-
imidazolium hydrogen sulfate ([pmim]HSO4–SiO2) as a
silica-supported ionic liquid with an acidic counteranion
N
HSO4
N
N
X
O
N
Si
O
OH
Si
O
O
Si
OH
Si
Si
O
O
O
[pmim]HSO4-SiO2
(a)
[pmim]X
X = (b): Cl; (c): BF3; (d): HSO4
Fig. 1 Silica-supported ionic liquid catalyst (a), and unsupported
ionic liquid catalysts (b–d)
-
HSO4 (Scheme 1; Fig. 1).
Table 1 Comparison of the catalytic efficiency of various ionic
liquids
Results and discussion
Entry
Catalyst
Time/h
Yield/%a
A mixture of benzaldehyde, 3-hydroxypyrrole, and mal-
ononitrile with a stoichiometric ratio of 1.0:1.0:1.1 and
10% mol of ionic liquid catalyst was chosen as the model
reaction. To find the most efficient catalyst, three ionic liq-
uids [pmim]HSO4 (1-propyl-3-methylimidazolium–HSO4),
[pmim]BF4 (1-propyl-3-methylimidazolium–BF4), and
[pmim]Cl (1-propyl-3-methylimidazolium–Cl), possessing
different counteranions (Fig. 1), were comparatively used
for catalyzing the model reaction (Table 1, entries 2–5). As
can be seen in Table 1, among the ionic liquid catalysts
employed, only [pmim]HSO4 showed a desirable catalytic
efficiency (entry 3).
1
2
3
4
5
6
–
24
3
0
89
76
8
[pmim]HSO4–SiO2
[pmim]HSO4
[pmim]BF4
[pmim]Cl
7
6
24
20
3
Silica support
11
Reaction conditions: 1.0 equiv. of 3-hydroxypyrrole, 1.0 equiv. of
benzaldehyde, 1.0 equiv. of malononitrile, 10% mol of catalyst,
4 cm3 CH3CN, 50 °C
a
Isolated yields
attributed to the participation of SiO2 in the catalytic pro-
cess. In order to support this hypothesis, we used the silica
support as catalyst under the same reaction conditions and
showed that it improved the efficiency of the reactions
compared with the non-catalytic system (Table 1, compare
entries 1 and 6).
Induced by the significant advantages offered by sup-
ported catalysts, such as the ease of separation from the
reaction mixture, significant reduction in problems of waste
disposal, and reuse applications by recycling, much effort
has been devoted by many research groups to their prep-
aration in the area of transition metal catalyst mediated
organic reactions in recent decades [38–40]. Therefore,
among the prepared catalysts, the most active one,
[pmim]HSO4, was supported on modified silica to obtain
the immobilized catalyst [pmim]HSO4–SiO2 (Fig. 1).
Immobilization on silica support slightly enhanced the
activity of the corresponding catalyst and shortened the
reaction time significantly (Table 1, entry 1). The higher
activity of the immobilized catalyst [pmim]HSO4–SiO2
compared with its unsupported analogue could be
Although the results in Table 2 show good yields for
reused catalyst, there is an observable trend in the results
that indicates deactivation of the catalyst with repeated use.
One possible reason for this loss in activity might be due to
the dissociation of the ionic liquid catalyst from the silica
support surface.
To delineate the effect of solvent on the catalytic effi-
ciency of [pmim]HSO4–SiO2, several solvents were
examined for the model reaction (Table 3). As a result of
123

Facile one-pot synthesis
yields and reaction times were improved in apolar solvents,
such as toluene and benzene, to some extent, but acetoni-
trile still remained the best solvent.
Table 2 Reusability of [pmim]HSO4–SiO2
Run
Time/h
Yield/%a
1
2
3
4
3
3
3
3
89
87
88
83
On the basis of recent reports which have proposed
ortho-quinone methides (OQMs) as in situ intermediates in
the one-pot three-component synthesis of naphthopyran
derivatives [41, 42], we envisioned a mechanism with
a similar intermediate (intermediate A) for the one-pot
three-component synthesis of pyranopyrrole derivatives
(Scheme 2). After Michael-type addition of malononitrile
to intermediate A, the reaction is followed by attack of an
hydroxyl group on one of two cyano groups to afford the
final product.
Reaction conditions: 1.0 equiv. of 3-hydroxypyrrole, 1.0 equiv. of
benzaldehyde, 1.0 equiv. of malononitrile, 10% mol of
[pmim]HSO4–SiO2, 4 cm3 solvent, 50 °C
a
Isolated yields
Table 3
[pmim]HSO4–SiO2
Effect of solvents on the catalytic efficiency of
To explore the scope of this reaction, we extended the
model reaction using different derivatives of benzaldehyde.
This revealed that the electronic nature of substituted
groups on benzaldehyde could immensely affect the reac-
tion times and chemical yields. Reaction efficiencies
increased on changing the substituent groups from methoxy
to Br and then Cl; however, the presence of more electron-
withdrawing groups such as NO2 and CN adversely
affected the results (Table 4). This paradoxical behavior
could be the result of a change in the rate-limiting step. In
the case of electron-releasing or poorly electron-with-
drawing groups, the first step, a nucleophilic attack of
pyrrole on aldehyde, which is accelerated by electron-
withdrawing groups, may be rate-limiting. On the other
hand, the second step (dehydroxylation step) would prob-
ably become rate-limiting as the substituents become more
electron-withdrawing. Because the second step proceeds
Entry
Solvent
Time/h
Yield/%a
1
2
3
4
5
Benzene
CH3CN
MeOH
EtOH
4
3
7
6
5
63
89
34
36
69
Toluene
Reaction conditions: 1.0 equiv. of 3-hydroxypyrrole, 1.0 equiv. of
benzaldehyde, 1.0 equiv. of malononitrile, 10% mol of [pmim]HSO4–
SiO2, 4 cm3 solvent, 50 °C
a
Isolated yields
this investigation, protic solvents such as ethanol and
methanol led to the worst results. Conversely, application
of polar aprotic solvents such as acetonitrile significantly
improved the chemical yields and reaction times. Com-
pared with those obtained in protic solvents, chemical
O
[pmim]
O
O
O
S
[pmim]
Step 1
H
O
S
O
O
H
O
O
O
OH
O
H
Step 2
Ar
Intermediate A
CN
CN
Ar
H
Ar
N
N
H
N
H
CN
CN
O
H
H
O
S
O
O
O
Step 3
O
S
[pmim]
O
O
H
O
H
O
N
NH2
CN
NH
CN
O
O
C
Step 5
Step 4
CN
N
H
N
N
H
Ar
H
Ar
H
Ar
Scheme 2
123

R. Sandaroos et al.
1
on a Shimadzu-IR 470 spectrophotometer. H NMR and
Table 4 One-pot three-component synthesis of 5-amino-7-aryl-6-
cyano-4H-pyrano[3,2-b]pyrroles (Scheme 1)
13C NMR spectra were recorded on a Bruker 400 MHz
spectrometer in chloroform as the solvent and TMS as
internal standard. Elemental analysis (C, H, N) was carried
out by a PerkinElmer 2400 series-II elemental analyzer.
The silica support, 1-methyl-3-(triethoxysilylpropyl)imi-
dazolium chloride, [pmim]Cl–SiO2, and [pmim]HSO4–
SiO2 (extent of labeling 0.25 mmol/g loading) were pre-
pared according to the literature (Scheme 3) [43].
Product
Ar
Time/h
Yield/%a
5a
5b
5c
5d
5e
5f
4-CH3O–C6H4
C6H5
4
3
3
2
2
1
1
5
5
7
8
8
62
89
80
91
89
88
88
70
67
61
69
31
4-CH3–C6H4
4-Br–C6H4
2-Br–C6H4
4-Cl–C6H4
2-Cl–C6H4
4-CN–C6H4
2-CN–C6H4
4-NO2–C6H4
2-NO2–C6H4
2-Furanyl
5g
5h
5i
Synthesis of silica support with extensive system
of meso- and macropores
5j
In a typical procedure 25 cm3 1 M HNO3 was dissolved in
2.3 g of polyethylene glycol (PEG) with molecular weight
of 35,000 g/mol. The resultant sol was stirred until a clear
solution was obtained. Then 22 cm3 tetraethoxysilane
(TEOS) was added slowly and after that 1 g of cetyltri-
methylammonium bromide (CTAB). This solution was
sonicated for 5 min, left to gel at 40 °C, and aged for
6 days at 40° C. Next the white alcogels obtained were
impregnated in a 1 M NH4OH solution for 10 h at 90 °C,
washed with deionized water, dried for 4 days at 60 °C,
and then calcined at 550 °C for 6 h under air (heating ramp
0.5 K/min). The size and shape of the monoliths were
determined by the size and shape of the vessel used.
Composition led to the formation of a macroporous,
interconnected, open network with bimodal system of
macropores of micrometer size. Apart from the macrop-
ores, the material also exhibited textural mesopores, with a
BET surface area of 550 m2/g, total pore volume 3.5 cm3/
g, and mean pore diameter of about 20 nm.
5k
5l
Reaction conditions: 1.0 equiv. of 3-hydroxypyrrole, 1.0 equiv. of
aldehyde, 1.0 equiv. of malononitrile, 10% mol of [pmim]HSO4–
SiO2, 4 cm3 CH3CN, 50 °C
a
Isolated yields
better with electron-releasing groups, the presence of CN
and NO2 groups increases the reaction time and decreases
the chemical yield.
Experimental
All chemicals and accessible ionic liquids were purchased
from Merck, Fluka, and Aldrich chemical companies. All
yields refer to isolated products. The products were char-
acterized by their spectral data. IR spectra were recorded
Scheme 3
EtO
OEt
Si
Cl
+
N
N
EtO
Si-OH
Si-OH
Si-OH
Si-OH
Si-OH
Si-OH
Si-OH
Si-OH
Si-OH
Si-OH
Si-OH
Si-OH
Si-OH
OEt
EtO
+
Si
EtO
N
N
+
Cl
+
+
N
N
N
O
N
Si-OH
Cl
HSO4
H2SO4
-HCl
Silica support
OEt
O
OEt
O
Si
O
Si
O
OH
O
OH
Si
OH
Si
O
OH
Si
Si
Si
Si
O
Si
Si
O
O
O
O
123

Facile one-pot synthesis
Synthesis of 1-methyl-3-(triethoxysilylpropyl)-
imidazolium chloride
The residue was concentrated in vacuo and the crude
product was purified by column chromatography on silica
gel (Table 4).
A mixture of 0.12 mol (3-chloropropyl)triethoxysilane and
0.12 mol of 1-methylimidazole (freshly distilled) was
refluxed at 78 °C for 24 h under nitrogen atmosphere. The
reaction mixture was cooled and any remaining volatile
substances were removed by rotary evaporation. The crude
product was additionally washed with Et2O (5 9 5 cm3)
and dried under vacuum. The product (slightly yellow
viscous oil) was obtained in 98% yield.
5-Amino-1,7-dihydro-7-(4-methoxyphenyl)pyrano-
[3,2-b]pyrrole-6-carbonitrile (5a, C15H13N3O2)
ꢀ
IR (KBr): m = 3,411 and 3,279 (asym. and sym. str. of
-NH2), 3,400 (NH), 2,160 (-CN str.), 1,251 (asym. str. of
cyclic ArC–O–C ether) cm-1
;
1H NMR (400 MHz,
CDCl3): d = 3.37 (s, 3H, OCH3), 5.43 (s, 1H, pyran H4),
6.11 (d, 1H, pyrrole H3), 6.63 (d, 2H, Ar–H), 6.68 (d, 1H,
pyrrole H2), 6.89 (s, 2H, D2O exch., NH2), 7.05 (d, 2H, Ar–
H), 7.54 (s, 1H, pyrrole NH) ppm; 13C NMR (100 MHz,
CDCl3): d = 28.6 (pyran C4), 55.2 (O–CH3), 59.5 (pyran
C3), 101.5 (pyran C6), 104.9 (pyrrole C3), 119.3 (pyrrole
C1), 122.0 (CN), 126.1 (pyran C5), 119.2, 127.4, 130.3,
154.6 (Ar–C), 171.4 (pyran C2) ppm.
Synthesis of 1-methyl-3-(triethoxysilylpropyl)-
imidazolium chloride anchored on silica support
([pmim]Cl–SiO2)
[Pmim]Cl (1 g, 2.7 mmol) was dissolved in 25 cm3 of dry
toluene and treated with 2 g of the previously prepared
silica support. The slurry was heated at 90 °C for 16 h,
after which the solid was isolated by filtration and washed
with 100 cm3 of dichloromethane. In the following step,
the unreacted ionic liquid was removed by 24 h extraction
with boiling dichloromethane. The material was then dried
under high vacuum to give a white powder of [pmim]Cl–
SiO2 in 92% yield.
5-Amino-1,7-dihydro-7-phenylpyrano[3,2-b]-
pyrrole-6-carbonitrile (5b, C14H11N3O)
ꢀ
IR (KBr): m = 3,405 and 3,283 (asym. and sym. str. of
-NH2), 3,405 (NH), 2,157 (-CN str.), 1,247 (asym. str. of
cyclic ArC–O–C ether) cm-1
;
1H NMR (400 MHz,
CDCl3): d = 5.51 (s, 1H, pyran H4), 6.25 (d, 1H, pyrrole
H3), 6.73 (d, 1H, pyrrole H2), 6.75 (s, 2H, D2O exch.,
NH2), 7.09–7.15 (m, 5H, Ar–H), 7.50 (s, 1H, pyrrole NH)
ppm; 13C NMR (100 MHz, CDCl3): d = 30.6 (pyran C4),
55.8 (pyran C3), 101.6 (pyran C6), 106.4 (pyrrole C3),
117.9 (pyrrole C1), 123.5 (CN), 129.7 (pyran C5), 122.8,
129.1, 127.9, 130.8 (Ar–C), 173.7 (pyran C2) ppm.
Synthesis of 1-methyl-3-(triethoxysilylpropyl)-
imidazolium hydrogen sulfate anchored on silica
support ([pmim]HSO4–SiO2)
5-Amino-1,7-dihydro-7-(4-methylphenyl)pyrano-
[3,2-b]pyrrole-6-carbonitrile (5c, C15H13N3O)
In a three-necked round-bottom flask equipped with a
stirrer, ice bath condenser, and thermometer, 3 g of
[pmim]Cl–SiO2 was suspended in 20 cm3 of dry CH2Cl2.
Under vigorous stirring 2.9 mmol of concentrated H2SO4
(97%) was added dropwise at 0 °C. The mixture was then
warmed to room temperature and heated under reflux for
48 h. When the formed HCl was completely distilled off
the solution was cooled and CH2Cl2 was removed under
vacuum. To remove any water from the reaction mixture
10 cm3 of benzene was added to the crude ionic liquid and
stirred for 3 h with a magnetic stirrer at 50 °C. The formed
azeotrope was distilled off yielding [pmim]HSO4–SiO2 in
93% yield.
ꢀ
IR (KBr): m = 3,422 and 3,272 (asym. and sym. str. of
-NH2), 3,419 (NH), 2,189 (-CN str.), 1,252 (asym. str. of
cyclic ArC–O–C ether) cm-1
;
1H NMR (400 MHz,
CDCl3): d = 2.31 (s, 3H, Ar–CH3), 5.60 (s, 1H, pyran
H4), 6.18 (d, 1H, pyrrole H3), 6.80 (s, 2H, D2O exch.,
NH2), 6.89 (d, 1H, pyrrole H2), 6.98–7.07 (m, 4H, Ar–H),
7.38 (s, 1H, pyrrole NH) ppm; 13C NMR (100 MHz,
CDCl3): d = 24.7 (-CH3), 29.2 (pyran C4), 54.6 (pyran
C3), 100.1 (pyran C6), 107.3 (pyrrole C3), 115.7 (pyrrole
C1), 126.5 (CN), 131.4 (pyran C5), 128.3, 129.1, 133.6,
137.9 (Ar–C), 169.1 (pyran C2) ppm.
5-Amino-7-(4-bromophenyl)-1,7-dihydropyrano[3,2-b]-
pyrrole-6-carbonitrile (5d, C14H10BrN3O)
General procedure for synthesis of pyranopyrrole
derivatives 5a–5l
ꢀ
IR (KBr): m = 3,425 and 3,269 (asym. and sym. str. of
-NH2), 3,434 (NH), 2,201 (-CN str.), 1,242 (asym. str. of
cyclic ArC–O–C ether) cm-1
;
1H NMR (400 MHz,
A
mixture of aldehyde (1 mmol), 3-hydroxypyrrole
(1 mmol), malononitrile (1.0 mmol) and ionic liquid cata-
lyst (0.1 mmol) in 4 cm3 CH3CN was stirred at 50 °C for
the appropriate time. The reaction was monitored by TLC
and after completion of the reaction the catalyst was simply
recovered by filtration and washed with dichloromethane.
CDCl3): d = 5.40 (s, 1H, pyran H4), 6.11 (d, 1H, pyrrole
H3), 6.49 (s, 2H, D2O exch., NH2), 7.06 (d, 2H, Ar–H),
6.70 (d, 1H, pyrrole H2), 7.25 (d, 2H, Ar–H), 7.39 (s, 1H,
pyrrole NH) ppm; 13C NMR (100 MHz, CDCl3): d = 31.4
(pyran C4), 64.9 (pyran C3), 100.5 (pyran C6), 109.5
123

R. Sandaroos et al.
(pyrrole C3), 117.3 (pyrrole C1), 127.2 (CN), 130.3 (pyran
C5), 123.6, 129.4, 130.9, 138.4 (Ar–C), 179.7 (pyran C2)
ppm.
d = 34.6 (pyran C4), 62.8 (pyran C3), 111.7 (pyran C6),
114.5 (pyrrole C3), 122.4 (pyrrole C1), 124.8 (CN), 126.5
(CN), 139.4 (pyran C5), 114.8, 129.9, 133.5, 139.5 (Ar–C),
176.3 (pyran C2) ppm.
5-Amino-7-(2-bromophenyl)-1,7-dihydropyrano[3,2-b]-
pyrrole-6-carbonitrile (5e, C14H10BrN3O)
5-Amino-7-(2-cyanophenyl)-1,7-dihydropyrano-
[3,2-b]pyrrole-6-carbonitrile (5i, C15H10N4O)
ꢀ
IR (KBr): m = 3,415 and 3,298 (asym. and sym. str. of
-NH2), 3,411 (NH), 2,187 (-CN str.), 1,257 (asym. str. of
ꢀ
IR (KBr): m = 3,421 and 3,248 (asym. and sym. str. of
cyclic ArC–O–C ether) cm-1
;
1H NMR (400 MHz,
-NH2), 3,416 (NH), 2,201 (-CN str.), 2,190 (-CN str.),
1,250 (asym. str. of cyclic ArC–O–C ether) cm-1; 1H NMR
(400 MHz, CDCl3): d = 5.59 (s, 1H, pyran H4), 6.31 (d,
1H, pyrrole H3), 6.60 (d, 1H, pyrrole H2), 6.81 (s, 2H, D2O
exch., NH2), 7.23–7.39 (m, 4H, Ar–H), 7.43 (s, 1H, pyrrole
NH) ppm; 13C NMR (100 MHz, CDCl3): d = 29.2 (pyran
C4), 59.6 (pyran C3), 110.3 (pyran C6), 110.9 (pyrrole C3),
118.1 (pyrrole C1), 120.3 (CN), 121.5 (CN), 134.2 (pyran
C5), 115.0, 128.2, 130.6, 132.5, 133.9, 141.3 (Ar–C), 174.8
(pyran C2) ppm.
CDCl3): d = 5.58 (s, 1H, pyran H4), 6.19 (d, 1H, pyrrole
H3), 6.73 (d, 1H, pyrrole H2), 6.79 (s, 2H, D2O exch.,
NH2), 6.97–7.11 (m, 4H, Ar–H), 7.58 (s, 1H, pyrrole NH)
ppm; 13C NMR (100 MHz, CDCl3): d = 28.3 (pyran C4),
57.5 (pyran C3), 108.6 (pyran C6), 108.9 (pyrrole C3),
121.6 (pyrrole C1), 127.5 (CN), 131.5 (pyran C5), 122.8,
122.4, 128.9, 132.7, 133.0, 141.6 (Ar–C), 179.0 (pyran C2)
ppm.
5-Amino-7-(4-chlorophenyl)-1,7-dihydropyrano-
[3,2-b]pyrrole-6-carbonitrile (5f, C14H10ClN3O)
5-Amino-1,7-dihydro-7-(4-nitrophenyl)pyrano-
[3,2-b]pyrrole-6-carbonitrile (5j, C14H10N4O3)
ꢀ
IR (KBr): m = 3,414 and 3,259 (asym. and sym. str. of
-NH2), 3,415 (NH), 2,156 (-CN str.), 1,256 (asym. str. of
ꢀ
IR (KBr): m = 3,413 and 3,240 (asym. and sym. str. of
-NH2), 3,414 (NH), 2,178 (-CN str.), 1,360 and 1,548
cyclic ArC–O–C ether) cm-1
;
1H NMR (400 MHz,
CDCl3): d = 5.48 (s, 1H, pyran H4), 6.16 (d, 1H, pyrrole
H3), 6.42 (s, 2H, D2O exch., NH2), 6.64 (d, 1H, pyrrole
H2), 7.06 (d, 2H, Ar–H), 7.21 (d, 2H, Ar–H), 7.29 (s, 1H,
pyrrole NH) ppm; 13C NMR (100 MHz, CDCl3): d = 30.7
(pyran C4), 60.2 (pyran C3), 106.5 (pyran C6), 108.4
(pyrrole C3), 119.0 (pyrrole C1), 124.8 (CN), 136.1 (pyran
C5), 129.5, 129.4, 130.5, 132.8 (Ar–C), 179.7 (pyran C2)
ppm.
(asym. and sym. str. of -NO2), 1,249 (asym. str. of cyclic
ArC–O–C ether) cm-1 1H NMR (400 MHz, CDCl3):
;
d = 5.50 (s, 1H, pyran H4), 6.17 (d, 1H, pyrrole H3), 6.40
(s, 2H, D2O exch., NH2), 6.57 (d, 1H, pyrrole H2), 7.31 (s,
1H, pyrrole NH), 7.37 (d, 2H, Ar–H), 8.03 (d, 2H, Ar–H)
ppm; 13C NMR (100 MHz, CDCl3): d = 30.4 (pyran C4),
59.7 (pyran C3), 107.8 (pyran C6), 108.2 (pyrrole C3),
120.5 (pyrrole C1), 124.3 (CN), 136.8 (pyran C5), 121.5,
129.1, 141.6, 145.3 (Ar–C), 177.4 (pyran C2) ppm.
5-Amino-7-(2-chlorophenyl)-1,7-dihydropyrano-
[3,2-b]pyrrole-6-carbonitrile (5g, C14H10ClN3O)
5-Amino-1,7-dihydro-7-(2-nitrophenyl)pyrano-
[3,2-b]pyrrole-6-carbonitrile (5k, C14H10N4O3)
ꢀ
IR (KBr): m = 3,458 and 3,256 (asym. and sym. str. of
-NH2), 3,397 (NH), 2,167 (-CN str.), 1,248 (asym. str. of
ꢀ
IR (KBr): m = 3,413 and 3,240 (asym. and sym. str. of
-NH2), 3,414 (NH), 2,178 (-CN str.), 1,381 and 1,547
cyclic ArC–O–C ether) cm-1
;
1H NMR (400 MHz,
CDCl3): d = 5.51 (s, 1H, pyran H4), 6.28 (d, 1H, pyrrole
H3), 6.64 (d, 1H, pyrrole H2), 6.84 (s, 2H, D2O exch.,
NH2), 7.09–7.19 (m, 4H, Ar–H), 7.43 (s, 1H, pyrrole NH)
ppm; 13C NMR (100 MHz, CDCl3): d = 26.2 (pyran C4),
55.6 (pyran C3), 113.9 (pyran C6), 114.2 (pyrrole C3),
118.6 (pyrrole C1), 129.1 (CN), 137.2 (pyran C5), 125.4,
127.3, 128.9, 132.7, 133.0, 139.6 (Ar–C), 173.7 (pyran C2)
ppm.
(asym. and sym. str. of -NO2), 1,253 (asym. str. of cyclic
ArC–O–C ether) cm-1 1H NMR (400 MHz, CDCl3):
;
d = 5.51 (s, 1H, pyran H4), 6.28 (d, 1H, pyrrole H3), 6.57
(d, 1H, pyrrole H2), 6.86 (s, 2H, D2O exch., NH2), 7.33–
7.39 (m, 2H, Ar–H), 7.44 (s, 1H, pyrrole NH), 7.56 (dd,
1H, Ar–H), 8.01 (d, 1H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 26.0 (pyran C4), 54.3 (pyran C3), 110.9
(pyran C6), 112.2 (pyrrole C3), 121.2 (pyrrole C1), 121.9
(CN), 137.7 (pyran C5), 122.0, 128.4, 133.5, 134.9, 136.0,
148.8 (Ar–C), 177.0 (pyran C2) ppm.
5-Amino-7-(4-cyanophenyl)-1,7-dihydropyrano-
[3,2-b]pyrrole-6-carbonitrile (5h, C15H10N4O)
ꢀ
IR (KBr): m = 3,401 and 3,248 (asym. and sym. str. of
5-Amino-7-(2-furanyl)-1,7-dihydropyrano-
[3,2-b]pyrrole-6-carbonitrile (5l, C12H9N3O2)
-NH2), 3,418 (NH), 2,210 (-CN str.), 2,181 (-CN str.),
1,257 (asym. str. of cyclic ArC–O–C ether) cm-1; 1H NMR
(400 MHz, CDCl3): d = 5.51 (s, 1H, pyran H4), 6.10 (d,
1H, pyrrole H3), 6.48 (s, 2H, D2O exch., NH2), 6.60 (d, 1H,
pyrrole H2), 7.24 (s, 1H, pyrrole NH), 7.26 (d, 2H, Ar–H),
7.38 (d, 2H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3):
ꢀ
IR (KBr): m = 3,418 and 3,234 (asym. and sym. str. of
-NH2), 3,419 (NH), 2,166 (-CN str.), 1,252 (asym. str. of
cyclic ArC–O–C ether) cm-1
;
1H NMR (400 MHz,
CDCl3): d = 5.47 (s, 1H, pyran H4), 5.87 (dd, 1H, furan
H3), 6.19 (m, 2H, pyrrole H3, furan H4), 6.59 (d, 1H,
123

Facile one-pot synthesis
21. Khafagy MM, Abd El-Wahab AHF, Eid FA, El-Agrody AM
(2002) Farmaco 57:715
pyrrole H2), 6.78 (s, 2H, D2O exch., NH2), 7.24 (d, 1H,
furan H2), 7.40 (s, 1H, pyrrole NH) ppm; 13C NMR
(100 MHz, CDCl3): d = 29.4 (pyran C4), 56.4 (pyran C3),
106.9 (pyran C6), 107.0 (furan C3), 110.3 (pyrrole C3),
110.8 (furan C4), 119.5 (pyrrole C1), 116.4 (CN), 141.9
(furan C2), 143.2 (pyran C5), 150.9 (furan C1), 167.4 (pyran
C2) ppm.
´
22. Martınez-Grau A, Marco JL (1997) Bioorg Med Chem Lett
7:3165
23. Smith PW, Sollis SL, Howes PD, Cherry PC, Starkey ID, Cobley
KN, Weston H, Scicinski J, Merritt A, Whittington A, Wyatt P,
Taylor N, Green D, Bethell R, Madar S, Fenton RJ, Morley PJ,
Pateman T, Beresford A (1998) J Med Chem 41:787
24. Hiramoto K, Nasuhara A, Michikoshi K, Kato T, Kikugawa K
(1997) Mutat Res 395:47
25. Dell CP, Smith CW (1993) Eur Patent Appl 537949
26. Mohr SJ, Chirigos MA, Fuhrman FS, Pryor JW (1975) Cancer
Res 35:3750
References
27. Anderson DR, Hegde S, Reinhard E, Gomez L, Vernier WF, Lee
L, Liu S, Sambandam A, Snider PA, Masih L (2005) Bioorg Med
Chem Lett 15:1587
¨ ¨
28. Skommer J, Wlodkowic D, Matto M, Eray M, Pelkonen J (2006)
J Leukemia Res 30:322
29. Wang JL, Liu D, Zhang ZJ, Shan S, Han X, Srinivasula SM,
Croce CM, Alnemri ES, Huang Z (2000) Proc Natl Acad Sci U S
A 97:7124
30. Eiden F, Denk F (1991) Arch Pharm 324:353
31. Hafez EAA, Elnagdi MH, Ali Elagamey AG, El-Taweel FMAA
(1987) Heterocycles 26:903–907
1. Wasserscheid P, Welton T (2007) Ionic liquids in synthesis, 2nd
edn. Wiley-VCH, Weinheim
2. Du Y, Tian F, Zhao W (2006) Synth Commun 36:1661
3. Gupta N, Sonu, Kad GL, Singh J (2007) Catal Commun 8:1323
4. Hajipour AR, Rajaei A, Ruoho AE (2009) Tetrahedron Lett
50:708
5. Khosropour AR (2008) Can J Chem 86:264
6. Wang W, Cheng W, Shao L, Yang J (2008) Catal Lett 121:77
7. Wasserscheid P, Sesing M, Korth W (2002) Green Chem 4:134
8. Xu DQ, Yang WL, Luo SP, Wang BT, Wu J, Xu ZY (2007) Eur J
Org Chem 2007:1007
32. Jones RM, Selenski C, Pettus TRR (2002) J Org Chem 67:6911
33. Hong Nguyen VT, Langer P (2005) Tetrahedron Lett 46:815–817
34. Ichihara A, Ubukata M, Oikawa H (1980) Tetrahedron Lett
21:4469
35. Kometani T, Takeuchi Y, Yoshii E (1983) J Org Chem 48:2630
36. Li TT, Ellison RH (1978) J Am Chem Soc 100:6263
37. Thumar NJ, Patel MP (2009) Arkivoc 13:363
38. Rechavi D, Lemaire M (2002) Chem Rev 102:3467
39. De Vos DE, Dams M, Sels BF, Jacobs PA (2002) Chem Rev
102:3615
40. De Miguel YR (2000) J Chem Soc Perkin Trans 1:4213
41. Eshghi H, Zohuri GH, Damavandi S, Vakili M (2010) Chin Chem
Lett 21:1423
42. Khodaei MM, Khosropour AR, Moghanian H (2006) Synlett
37:916–920
¨
9. Fischer J, Holderich WF (1999) Appl Catal A: Gen 180:435
´
´
10. Gonzalez-Nun˜ez ME, Mello R, Olmos A, Asensio G (2005) J Org
Chem 70:10879
´
´
11. Gonzalez-Nun˜ez ME, Mello R, Olmos A, Asensio G (2006) J Org
Chem 71:6432
12. Qiao K, Hagiwara H, Yokoyama C (2006) J Mol Catal A: Chem
246:65
13. Sugimura R, Qiao K, Tomida D, Yokoyama C (2007) Catal
Commun 8:770
14. Joseph T, Hartmann M, Ernst S, Halligudi SB (2004) J Mol Catal
A: Chem 207:129
15. Zhou XG, Yu XQ, Huang JS, Li SG, Li LS, Che CM (1999)
Chem Commun 1789
16. Barloy L, Battioni P, Mansuy D (1990) J Chem Soc Chem
Commun 1365
43. Chrobok A, Baj S, Pudło W, Jarzebski A (2009) Appl Catal A
Gen 366:22
17. Bowers C, Dutta PK (1990) J Catal 122:271
18. Sutra P, Brunel D (1996) J Chem Soc Chem Commun 2485
19. Mimitolo F, Pini D, Salvadori P (1996) Tetrahedron Lett 37:3375
20. Horn J, Michalek F, Tzschucke C, Bannwarth W (2004) In:
Kirschning A (ed) Immobilized catalysts, 3rd edn. Springer,
Berlin
123