Immobilized ionic liquid-catalyzed synthesis of pyrano[3, 2-b]indole derivatives

Article abstract of DOI:10.1155/2012/841632

An ionic liquid-catalyzed synthesis of 2-amino-4, 5-dihydro-4-arylpyrano[3, 2-b]indole-3-carbonitrile derivatives through a novel three-component condensation of 3-hydroxyindole, aromatic aldehydes and malononitrile in the presence of silica supported ion

Full text of DOI:10.1155/2012/841632

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(3), 1490-1493
Immobilized Ionic Liquid-Catalyzed Synthesis of
Pyrano[3,2-b]indole Derivatives
SAMAN DAMAVANDI
Department of Chemistry, Sarvestan Branch, Islamic Azad University, Sarvestan, Iran
saman_damavandi@yahoo.com
Received 14 October 2011; Accepted 20 December 2011
Abstract: An ionic liquid-catalyzed synthesis of 2-amino-4,5-dihydro-4-
arylpyrano[3,2-b]indole-3-carbonitrile derivatives through a novel three-
component condensation of 3-hydroxyindole, aromatic aldehydes and
malononitrile in the presence of silica supported ionic liquid of
[pmim]HSO4SiO2
(silica
supported
1-methyl-3-(triethoxysilylpropyl)
imidazolium hydrogensulfate) as an efficient catalyst is described.
Keywords: multicomponent, 2-amino-4,5-dihydro-4-arylpyrano[3,2-b]indole-3-carbonitriles,
hydrogensulfate ionic liquid.
Introduction
Ionic liquids have recently 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 Among these ionic liquids possessing
-
HSO4 as a counteranion find a broad application in organic synthesis, acting as both
solvents and catalysts. Recently, immobilization processes involving acidic ionic liquids on
solids supports have been designed.2-5 The heterogenization of catalysts and reagents can
offer important advantages in handling, separation and reuse procedures. Based on 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 range of
reactions.6-10
The anticancer potential of indole and α-pyrone derivatives have been reported already. 11,12
.
Accordingly, due to their significant biological activities as well as wide-ranging utility as
synthetic intermediates for alkaloids, drug candidates, and clinical harmaceuticals,13
a
number of synthetic methods have been developed in pursuit of this structure, including
intramolecular hetero-Diels-Alder cycloaddition14 and cycloisomerization. Moreover, based
catalyzed one-pot synthesis of pyrano[3,2-b ]indoles has been reported by our research
group.15
In continuation of our effort toward the development of new multi-component
condensation reactions,16 herein, we wish to report an efficient methodology for the
preparation of 2-amino-4,5-dihydro-4-arylpyrano[3,2-b]indole-3-carbonitrile derivatives
through a three-component condensation reaction of indolin-3-one, aryl aldehydes, and
malononitrile catalyzed by silica supported ionic liquid of [pmim]HSO4 SiO2 (silica supported
1-methyl-3-(triethoxysilylpropyl)imidazolium hydrogensulfate) (Figures 1).

Immobilized Ionic Liquid-catalyzed Synthesis of Pyrano[3,2-b]indole Derivatives 1491
N
HSO4
N
O
R
Si
OH
Si
O
O
OH
Si
CHO
OH
Si
Si
O
O
O
O
H
CN
+
+
N
CH2(CN)2
N
CH3CN
H
R
O
NH2
Ar = 4-CH3OC6H4 - (1)(84%); C6H5 - (2)(90%); 4-CH3C6H4 (3)(85%); 4-BrC6H4 (4)(90)
;
2-BrC6H4 - (5)(86%); 4-ClC6H4 (6)(90%); 2-ClC6H4 - (7)(86%); 4-CH3C6H4 - (8)(90%)
; 4-NO2C6H4 - (9) (85); 2-NO2OC6H4 - (10)(88%).
Figure 1. Synthesis of pyrano[3,2-b]indole derivatives 1-10.
Experimental
All the compounds are known and have been reported recently.15 [pmim]HSO4 SiO2 (extent of
labeling 0.25 mmol/gr loading) was prepared according to the literature.17
General Procedure for synthesis of pyranopyrrole derivatives 1-10
A mixture of aldehyde (1 mmol), 3-hydroxyindole (1 mmol), malononitrile (1.1 mmol) and
ionic liquid catalyst (0.1 mmol) in CH3CN (8 mml) was stirred at 80 °C for the appropriate
time (6-8 h). The reaction was monitored by TLC and after completion of the reaction, the
catalyst was simply recovered by filtration and washed by dichloromethane. The residue was
concentrated in vacuo and the crude product was purified by column chromatography on
silica gel eluting by n-hexane/ethyl acetate (9:1).
Entry 1. IR: 1665 (NH2), 2218 (-CN), 3224 & 3259 (asym. & sym. str. of -NH2). 1H NMR:
δH 3.63 (s, 3H, OCH3), 5.41 (s, 1H, CH), 6.89 (bs, 2H, NH2), 6.82-6.99 (m, 2 H); 7.04-7.13
(m, 4 H); 7.56 (d,1 H, J = 8.0); 7.87 (d, 1 H, J = 7.8), 10.14 (bs, 1H, NH). Anal Calcd for
C19H15N3O2: C, 71.91; H, 4.76; N, 13.24 %. Found: C, 71.75; H, 4.67; N, 13.11 %.
Entry 4. IR: 1670 (NH2), 2226 (-CN), 3240 & 3361 (asym. & sym. str. of -NH2). 1H NMR:
δH: 5.50 (s, 1H, CH), 6.70 (bs, 2 H, NH2), 7.07-7.16 (m, 2 H); 7.30-7.44 (m, 4 H); 7.68 (d, 1
H, J = 7.6); 8.01 (d, 1 H, J = 7.0), 11.02 (bs, 1H, NH). Anal Calcd for C18H12BrN3O: C,
59.03; H, 3.30; N, 11.47 %. Found: C, 58.76; H, 3.27; N, 11.40 %.
Entry 6. IR: 1667 (NH2), 2219 (-CN), 3202 & 3244 (asym. & sym. str. of -NH2). 1H NMR:
δH 5.49 (s, 1H, CH), 6.68 (s, 2H, NH2), 7.21-7.42 (m, 2 H); 7.46-7.59 (m, 4 H); 7.63 (d, 1 H,
J = 6.7); 8.01 (d, 1 H, J = 7.0), 10.54 (bs, 1H, NH). Anal Calcd for C18H12ClN3O: C, 70.81;
H, 3.96; N, 13.76 %. Found: C, 70.55; H, 3.90; N, 13.71 %.
Entry 9. IR: 1669 (NH2), 2225 (-CN), 3218 & 3231 (asym. & sym. str. of -NH2). 1H NMR:
δH 5.72 (s, 1H, CH), 6.71 (s, 2H, NH2), 7.22 (d, 1 H, J = 7.76); 7.26-7.42 (m, 3 H); 7.46-7.59
(m, 2 H); 7.76 (d, 1 H, J =7.6); 7.99 (d, 1 H, J = 6.9), 10.11 (bs, 1H, NH). Anal Calcd for
C18H12N4O3: C, 65.06; H, 3.64; N, 16.86 %. Found: C, 64.86; H, 3.53; N, 16.75 %.
Entry 10. IR: 1661 (NH2), 2200 (-CN), 3224 & 3262 (asym. & sym. str. of -NH2). 1H NMR:
δH 5.11 (s, 1H, CH), 6.75 (bs, 2H, NH2), 7.12-7.29 (m, 4 H); 7.38-7.52 (m, 2 H); 7.63 (d, 1

1492 SAMAN DAMAVANDI
H, J = 7.1); 8.20 (d, 1 H, J = 8.01), 10.24 (bs, 1H, NH). Anal Calcd for C18H12FN3O: C,
70.81; H, 3.96; N, 13.76 %. Found: C, 70.56; H, 3.91; N, 13.68 %.
Results and Discussion
Induced by significant advantages such as ease of separation from reaction mixture,
significant reduction in problems of waste disposal, and re-use applications by recycling,
[pmim]HSO4, was supported on the modified silica to obtain the immobilized catalyst of
[pmim]HSO4Sio2 (Figure 1). The reaction of 3-hydroxypyrrole (1.0 equiv.), benzaldehyde
(1.0 equiv.), malononitrile (1.0 equiv.) and 10 mol% of [pmim]HSO4 SiO2, using 8 mL of
acetonitrile at 80 °C was chosen as the model reaction and the corresponding product (2)
was obtained in 90% yield. Furthermor, the supported catalyst underwent only negligible
loss in its activity even after at least three recycles (Table 1).
a
Table 1. Reusability of [pmim]HSO4 SiO2
.
No. of Run
Yield
1
90
2
87
3
85
4
85
5
82
a
Reaction conditions: 1.0 equiv. of 3-hydroxypyrrole, 1.0 equiv. of benzaldehyde, 1.0
equiv. of malononitrile, 10 mol% of [pmim]HSO4 SiO2, 8 mL of solvent and at 80 °C.
We then successfully synthesized a variety of pyrano[3,2-b]indole derivatives and the
results were summarized in Figure 1. As shown, aromatic aldehydes carrying either electron-
donating or electron-withdrawing substituents reacted efficiently giving good to excellent
yields of the corresponding pyrano[3,2-b]indoles.
O
O
O
S
O
pmim
O
S
O
pmim
CN
CN
H
O
CN
CN
Ar
O
H
Ar
H
O
O
HN
HN
Ar
..
OH
O
O
Step 1
Step 2
A
N
H
Step 3
Ar
Ar
Ar
H
O
CN
C
CN
NH
CN
NH2
HN
Step 5 HN
Step 4
HN
N
OH
O
O
S
pmim
O
C
O
O
B
H
Figure 2. The proposed mechanism.
The proposed mechanism for the synthesis of pyrano[3,2-b]indoles is shown in Figure
2. The condensation of 3-hydroxyindole, arylaldehyde and malononitrile may occur by a
mechanism of Knoevenagel condensation, Michael addition, intramolecular cyclization, and
isomerization. Initially, by the aid of [pmim]HSO4 SiO2, intermediate A is formed through
condensation of 3-hydroxyindole and aromatic aldehyde. Michael-type addition of

Immobilized Ionic Liquid-catalyzed Synthesis of Pyrano[3,2-b]indole Derivatives 1493
malononitrile to the intermediate A gives B. Then, the proton of B is abstracted by
-
counteranion of HSO4 followed by heterocyclization and isomerization to furnish the
corresponding pyrano[3,2-b]indole product C (Figure 2).
Conclusion
In conclusion, we developed a novel, mild and effective one-pot method for the synthesis of
substituted pyrano[3,2-b]indole-3-carbonitrile derivatives utilizing silica supported ionic
liquid of [pmim]HSO4 SiO2
.
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