An efficient method for the one-pot, three-component synthesis of 3,4-dihydropyrano[c]chromenes catalyzed by nano Al2O3

Article abstract of DOI:10.13005/ojc/300355

Nano Al₂O₃ efficiently catalyzed the one-pot, three-component reaction of 4-hydroxycoumarin, aromatic aldehydes and malononitrile to yield 3,4-dihydropyrano[c]chromene derivatives in high yields. The features of this procedure are mi

Full text of DOI:10.13005/ojc/300355

ISSN: 0970-020 X
CODEN: OJCHEG
014, Vol. 30, No. (3):
Pg. 1361-1364
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
2
www.orientjchem.org
An Efficient Method for the One-pot,Three-Component
Synthesis of 3,4-Dihydropyrano[c]chromenes
Catalyzed by Nano Al O
2
3
ALIREZA MONTAGHAMI and NASER MONTAZERI*
Department of Chemistry, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran.
*
Corresponding author E-mail: Montazer1350@gmail.com
http://dx.doi.org/10.13005/ojc/300355
(Received: May 21, 2014; Accepted: June 17, 2014)
ABSTRACT
Nano Al O efficiently catalyzed the one-pot, three-component reaction of 4-hydroxycoumarin,
2
3
aromatic aldehydes and malononitrile to yield 3,4-dihydropyrano[c]chromene derivatives in high yields.
The features of this procedure are mild, reaction conditions, short reaction time and operational
simplicity.
Keywords: Nano Al O , 3,4-Dihydropyrano[c]chromene,
2
3
4-Hydroxycoumarin, Malononitrile, Aromatic aldehydes.
INTRODUCTION
3,4-dihydropyrano[c]chromenes will be interesting
in both synthetic organic and medicinal chemistry.
3,4-Dihydropyrano[c] chromene derivatives are
generally synthesized via one-pot reaction of an aryl
aldehydes, malononitrile and 4-hydroxycoumarin in
the presence of several catalysts such as sodium
4
H-Chromene and its derivatives have been
studied due to a variety of chemical and biological
significance . The importance of chromenes as
1
biologically active compounds includes their use
2
3
4
1
14
15
16
as emetic , anti-HIV , anti-tumor , anti-cancer ,
dodecyl sulfate (SDS) , DBU , morpholine ,
1
5
6
17
18
anti-coagulant , anti-alzheimer , anti-bacterial ,
piperidine , K CO under microwave irradiation ,
2 3
7
8
9
19
anti-malaria , diuretic , spasmolytic , anti-
sulfonic acid functionalized silica (SiO PrSO H) ,
2 3
trisodium citrate , silica gel , inorganic-organic
hybrid magnetic nanocatalyst , nano ZnO ,
10,11
12
20
21
leukemic , anti-anaphylactic activities .Moreover,
chromene derivatives such as 3,4-dihydropyrano[c]
chromenes are of importance as they have
various industrial, pharmaceutical and biological
applications . Therefore, the development of new
and efficient methodologies for the synthesis of
2
2
23
2
4
25
26
27
KAl(SO ) .12H O , TBAB , TMGT , MgO ,
4
2
2
28
diammonium hydrogen phosphate and heteropoly
acids . However, in spite of their potential utility,
1
3
29
some difficulties still exist, such as expensive or

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MONTAGHAMI & MONTAZERI, Orient. J. Chem., Vol. 30(3), 1361-1364 (2014)
3
1
toxic reagent. Therefore, the development of new, of heterocyclic compounds , herein, we wish to
simple and cheap methods for the synthesis of report an efficient synthesis of 3,4-dihydropyrano[c]
3,4-dihydropyrano[c] chromene derivatives is of main chromenes by cyclocondensation reaction of
importance. In continuation of our efforts to develop 4-hydroxycoumarin, aryl aldehydes and malononitrile
novel synthetic routes using solid catalysts in organic using nano Al O as a solid catalyst (Scheme 1).
2
3
3
0
reactions , and due to our interest in the synthesis
NH2
CN
Ar
OH
O
O
Nano Al O
2
3
CH (CN)2
ArCHO
+
O
2
+
O
O
1
2
3a-h
4a-h
Scheme 1: Synthesis of 3,4- dihydropyrano[c]chromene by nano Al O3
2
EXPERIMENTAL
reaction conditions, 4-hydroxycoumarin (1 mmol),
malononitrile (1.5 mmol), and 3-nitrobenz aldehyde
All of the chemical material used in this (1 mmol) in ethanol (5 mL) was mixed in the presence
work purchased from Fluka or Merk and without of nano Al O (25 mol%) as catalyst for 5h. The
2
3
further purification. Melting points were recorded on reaction proceeds very cleanly at room temperature
an Electrothermal type 9100 melting point apparatus. and was free of side products.After completion of the
The IR spectra were obtained on a 4300 Shimadzu reaction (monitored byTLC), a simple workup affords
1
spectrophotometer in KBr disks. The H NMR (500 the products in high yields (Scheme 1). Among the
MHz) spectra were recorded on a Bruker-Ac-500 solvents tested, the reaction in H O, CH CN and
2
3
spectrophotometer.
CHCl using 25 mol% of the catalyst gave a moderate
3
yield of the desired product at room temperature.
General procedure for the synthesis of However in the EtOH relatively high yield of product
,4-dihydropyrano[c]chromenes (4a-h). is obtained at room temperature after 5h. Without
A solution of 4-hydroxycoumarin 1(1 mmol), catalyst, in refluxing EtOH, H O, CHCl and CH CN
3
2
3
3
malononitrile 2(1.5 mmol), an aromatic aldehydes or at room temperature in this solvents the reaction
3
4
a-h(1 mmol) and nano Al O (25 mol% based on times are prolonged and the yields are poor. In the
-hydroxycoumarin) in EtOH (5 mL) was stirred solvent-free conditions, even in the presence of 35
2 3
at room temperature for 5h. The progress of the mol% of the catalyst at room temperature, 60 °C,
reaction was monitored by TLC. After completion of 70 °C, 80 °C and 90 °C, the yields are moderate.
the reaction, boiling ethanol (20 mL) was added and The results are summarized in Table 1. We also
catalyst was filtrated. The filtrate was concentrated evaluated the amount of nano Al O required for this
2
3
to give the solid product that washed with water, and transformation. It was found that the yield of product
recrystallized in the ethanol to give pure products was affected by the catalyst amount. Increasing the
(
4a-h).The structures of the products were confirmed amount of the catalyst up to 25 mol% in the EtOH at
1
by H NMR, IR spectroscopies and comparison with room temperature increased the yield of the product.
authentic samples prepared by reported methods.
Further increase in the catalyst amount did not
increase the yield noticeably.
RESULTS AND DISCUSSION
In order to show generality and scope of this
In order to optimize the reaction conditions, new protocol, we used various substituted aromatic
including solvents and temperature, the reaction aldehydes and the results obtained are summarized
was conducted under various conditions and in Table 2. In all cases, aromatic aldehydes with
the results are listed in Table 1. In an optimized substitutes carrying either electron-donating or

MONTAGHAMI & MONTAZERI, Orient. J. Chem., Vol. 30(3), 1361-1364 (2014)
1363
electron- withdrawing group reacted successfully
and gave the expected products in high yields. The
type of aldehyde had no significant effect on the
reaction.
a
Table 1: Effect of nano Al O amount on the model reaction
2
3
Entry
Catalyst (mol%)
Solvent
Condition
Time (h) Yield (y)b
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
-
-
-
-
-
-
-
-
35
35
35
35
35
20
25
30
35
25
25
25
25
25
25
25
EtOH
Reflux
Reflux
Reflux
Reflux
r.t
r.t
r.t
r.t
r.t
60 °C
70 °C
80 °C
90 °C
r.t
r.t
r.t
r.t
r.t
18
15
12
12
-
-
-
-
45
43
40
35
32
72
88
85
82
65
55
45
85
70
68
65
H O
2
CHCl3
CH CN
3
EtOH
H O
2
CHCl3
CH CN
3
-
-
-
-
-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
EtOH
EtOH
EtOH
EtOH
H O
2
CHCl3
r.t
r.t
Reflux
Reflux
Reflux
Reflux
CH CN
3
EtOH
H O
2
CHCl3
CH CN
3
a
b
4
-Hydroxycoumarin (1mmol), 3-nitrobenzaldehyde (1 mmol) and malononitrile (1.5 mmol). Isolated yields.
Table 2: Synthesis of 3,4-dihydropyrano[c]chromenes (4a-h)a
Entry
Ar
Product
Yield(%)b
m.p(°C)
Reported
Found
1
2
3
4
5
6
7
8
3-NO C H
4a
4b
4c
4d
4e
4f
88
80
75
84
89
82
77
87
260-261
263-265
245-247
259-260
263-265
247-248
250-252
246-248
257-258 [22]
260-262 [15]
242-243 [15]
256-258 [15]
259-261 [21]
248-250 [15]
253-255 [15]
242-244 [19]
2
6
4
4-ClC H4
6
3-ClC H4
6
C H5
6
4-NO C H
2
6
4
4-MeOC H4
6
4-MeC H4
4g
4h
6
3-MeOC H4
6
a
1
mmol 4-hydroxycoumarin, 1 mmol 3-nitrobenzaldehyde, 1.5 mmol malononitrite and 25 mol%
b
nano Al O in the EtOH after 5h. Isolated yields.
2
3

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MONTAGHAMI & MONTAZERI, Orient. J. Chem., Vol. 30(3), 1361-1364 (2014)
CONCLUSIONS
ACKNOWLEDGMENTS
In conclusion we have successfully
demonstrated the catalytic activity of nano Al O3
We gratefully acknowledgments the
financial support of this research by Islamic Azad
University, Tonekabon Branch.
2
in the synthesis of 3,4-dihydropyrano[c]chromene
derivatives. Easy simple work-up and high yields of
products are some advantages on this method.
REFERENCES
1
2
3
.
.
.
Foye, W. O. Principidi Chimica Farmaceutica
Piccin- Padova, Italy, 1991.
Cannon, J. G.; Khonji, R. R. J. Med. Chem.
2010, 7, 890-894.
Khurana,J.M.;Nand,B.;Saluja,P. Tetrahedron
2010, 66, 5637-5641.
Heravi, M. M.; Zaheri, M.; Mohammadi, N.
Chin. J. Chem. 2011, 29, 1163-1166.
Shaker, R. M. R. Pharmazie. 1996, 51, 148-
151.
15.
16.
1
975, 18, 110-112.
Tanabe, A.; Nakashima, H.; Yoshida, O.;
Yamamoto, N.;Tenmyo, O; Oki, T. J. Antibiot. 17.
988, 41, 1708-1710.
1
4
5
.
.
Shijay, G.; Cheng, H. T.; Chi, T.; Ching-Fa, Y. 18.
Tetrahedron 2008, 64, 9143-9149.
Bayer, T. A.; Schafer, S.; Breyh, H.; Breyhan, 19.
O.;Wirths, C.;Treiber, G. A.Clin Neuropathol.
Kidwai, M.;Saxena, S. Synth.Commun.2006,
36, 2737-2742.
Mohammadi ziarani, G.; Badiei, A.; Azizi, M.;
Zarabadi, P. Iran. J. Chem. Chem. Eng. 2011,
2, 59-65.
2006, 25, 163-171.
6
7
.
.
Morgan, L. R.; Jursic, B. S.; Hooper, C. L.; 20.
Neumann, D. M.; Thangaraj, K.; Leblance,
B. Bioorg. Med. Chem. Lett. 2002, 12, 3407- 21.
Zheng, J.; Yi-Qun, Li. Scholars Res. Libr.
2011, 2, 381-388.
Prasanna,T.S.R.;Mohana Raju, K. J.Korean
Chem. Soc. 2011, 4, 662-665.
Khoobi, M.; Mamani, L.; Rezazadeh, F.;
Zareie, Z.; Foroumadi, A.; Ramazani, A.;
Shafiee, A. J. Mol. Cat. A: Chem. 2012, 359,
74-80.
3411.
Bolognese, A.; Correale, G.; Manfra, M.; 22.
Levecchia, A.; Mazzoni, O.; novellino, E.;
Lacolla, P.; Sanna, G.; Loddo, R. J. Med.
Chem. 2004, 47, 849-858.
8
9
.
.
Hafez, E.A.A.;Elnaghi, M.H.;Elagamey, A.G. 23.
A.; El-Taweel, F. M. A. A. Heterocycles. 1987,
Paul, S.; Bhattacharyya, P.; Das, A. R.
Tetrahedron Lett. 2011, 52, 4636-4641.
Karimi, A. R.; Sedaghatpour, F. Synthesis.
2010, 1731-1735.
26, 903-907.
24.
Ellis, G. P. The Chemistry of Heterocyclic
Compounds.In Chromenes;Chromenes, and 25.
Chromenes; Weissberger; Taylor, A.; Eds, E.
Khurana, J. M.; Kumar, S. Tetrahedron Lett.
2009, 50, 4125-4127.
C.; John Wiley; NewYork. 1977.
Beagley, P.; Blackic, M. A. L.; Chibale, K.;
Clarkson, C.;Meijboom, R.;Moss, J.R.;Smith, 27.
P.; Su, H. Dalton Trans. 2003, 3046-3051.
26.
Shaabani, A.;Samadi, S.;Badri, Z.;Rahmati,
A. Catal. Lett. 2005, 104, 39-43.
Seifi, M.; Sheibani, H. Catal. Lett. 2008, 126,
275-279.
1
1
1
0.
1.
2.
Fokialakis, n.;Magiatis, P.;Chinou, L.;Mitaka, 28.
S.;Tillequin, F. Chem. Pharm. Bull. 2002, 50,
Abdolmohammadi,S.;Balalaie,S. Tetrahedron
Lett. 2007, 48, 3299-3303.
Heravi, M.M.;Sadjadi, S.;Haj, N.M.;Oskooie,
H. A.; Bamoharram, F. F. Catal. Commun.
2009, 10, 1643-1646.
413-414.
29.
Biot, O.; Blampain, G.; Blampain, G.;
Blampain, P.; Georges, A. F.; Abessolo, H.;
Dive, D.; Lebibi, J. J. Med. Chem. 1997, 40, 30.
715-3718.
Konkoy, C.S.;Fick, D.B.;Cai, S.X.;Lan, N.C.; 31.
Keana, J. F. W.; PCT Int. Appl. Wo 0075123,
Montazeri, N.; Rad-Moghadam, K. Chine
Chem. Lett. 2008, 19, 1143-1146.
Montazeri, N.; Pourshamsian, K.; Khoddadi,
M.; Khddadi, K. Oriental J. Chem. 2011, 27,
1023-1027.
3
1
1
3.
4.
2000; Chem. Abstr. 2001, 134, 293130.
Mehrabi, H.; Abusaidi, H. J. Iran. Chem. Soc.