Trichloroacetic acid as a solid heterogeneous catalyst for the rapid synthesis of dihydropyrano[2,3-c]pyrazoles under solvent-free conditions

Article abstract of DOI:10.1515/HC.2011.046

A one-pot, three-component reaction of an aromatic aldehyde, malononitrile and 3-methyl-1-phenyl-2-pyrazolin-5-one in the presence of a catalytic amount of trichloroacetic acid produces a 6-amino-4-aryl-5-cyano-3-methyl-1-phenyl-1,4- dihydropyrano[2,3-c]p

Full text of DOI:10.1515/HC.2011.046

Heterocycl. Commun., Vol. 17(5-6), pp. 177–179, 2011 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/HC.2011.046
Trichloroacetic acid as a solid heterogeneous catalyst
for the rapid synthesis of dihydropyrano[2,3-c]pyrazoles
under solvent-free conditions
for several important organic transformations (Karimi-
Jaberi and Amiri, 2010; Karimi-Jaberi and Keshavarzi,
2010; Karimi-Jaberi et al., 2010, Karimi-Jaberi and
Arjmandi, 2011), we now describe a simple and efficient
protocol for the synthesis of 1,4-dihydropyrano[2,3-c]pyra-
zoles (Scheme 1). The approach is based on a three-com-
ponent reaction of an aromatic aldehyde, malononitrile and
3-methyl-1-phenyl-2-pyrazolin-5-one in the presence of
trichloroacetic acid as a solid heterogeneous catalyst under
solvent-free conditions. Heterogeneous catalysts are advan-
tageous over conventional homogeneous catalysts in that
they can be easily recovered from the reaction mixture by
simple filtration and can be reused after activation (Thomas
and Thomas, 1997). Trichloroacetic acid is a readily avail-
able and inexpensive reagent and can conveniently be han-
dled and removed from the reaction mixture (Karimi-Jaberi
et al., 2011).
Zahed Karimi-Jaberi* and Mohammad Mehdi
ReyazoShams
Department of Chemistry, Firoozabad Branch, Islamic
Azad University, P.O. Box 74715-117 Firoozabad, Fars,
Iran
*Corresponding author
e-mail: z.karimi@iauf.ac.ir
Abstract
A one-pot, three-component reaction of an aromatic alde-
hyde, malononitrile and 3-methyl-1-phenyl-2-pyrazolin-5-
one in the presence of a catalytic amount of trichloroacetic
acid produces a 6-amino-4-aryl-5-cyano-3-methyl-1-phenyl-
1,4-dihydropyrano[2,3-c]pyrazole in excellent yield and in a
short reaction time.
The conditions were optimized using benzaldehyde for
the reaction with 3-methyl-1-phenyl-2-pyrazolin-5-one
and malononitrile. The reaction proceeded smoothly under
solvent-free conditions in the presence of 10 mol% trichlo-
roacetic acid as a solid heterogeneous catalyst. The yield of
1 was 98% after 3 min at 100°C. Various aldehydes were
allowed to react following the optimization to prepare a series
of 1,4-dihydropyrano[2,3-c]pyrazoles 1–12 (Scheme 1).
In all cases, the corresponding products were obtained
in low reaction times with good to excellent yields. The
reaction was successful with many common aldehydes.
However, 4-dimethylaminobenzaldehyde failed to react. It
can be suggested that the strongly electron donating dim-
ethylamino group diminishes reactivity of the aldehyde (Jin
et al., 2006). It is important to note that the synthesis of
dihydropyrano[2,3-c]pyrazoles could not be achieved in the
absence of trichloroacetic acid. The structures of all prod-
Keywords: aldehyde; dihydropyranopyrazoles; malono-
nitrile; trichloroacetic acid.
Introduction
Dihydropyrano[2,3-c]pyrazole derivatives show useful bio-
logical and pharmacological properties (Witte et al., 1986;
Bonsignore et al., 1993; Zaki et al., 2006; Abdelrazek et al.,
2007). Some 2-amino-4H-pyrans can be used as photoactive
materials (Armetso et al., 1989). Furthermore, polysubstituted
4H-pyrans constitute a structural unit of a series of natural
products (Hatakeyama et al., 1988; Kamaljit and Harjit, 1996).
Synthesis of 4H-pyrano[2,3-c]pyrazole from 3-methyl-3-
pyrazolin-5-one and arylidenemalononitrile using base cata-
lyst has been attempted (Otto, 1974; Otto and Schmelz, 1979).
Recently, three-component one-pot condensation of 3-methyl-
1-phenyl-2-pyrazolin-5-one, aldehydes and malononitrile for
the construction of 1,4-dihydropyrano[2,3-c]pyrazole deriva-
tives has been reported under different conditions (Shi et al.,
2004; Jin et al., 2005, 2006; Heravi et al., 2010; Khurana
et al., 2011; Kshirsagar et al., 2011). These approaches require
harsh reaction conditions, expensive reagents, toxic organic
solvents and long reaction times.
1
ucts 1–12 were confirmed by IR, H NMR, 13C NMR, and
elemental analysis.
Conclusion
Trichloroacetic acid is a simple and efficient solid catalyst for
the synthesis of 1,4-dihydropyrano[2,3-c]pyrazoles through
one-pot, three-component reaction of 3-methyl-1-phenyl-2-
pyrazolin-5-one, aldehydes and malononitrile under solvent-
free conditions. This acid is as an effective catalyst with
respect to reaction times and yields when compared to other
catalysts used for similar transformations (Shi et al., 2004; Jin
et al., 2005, 2006; Heravi et al., 2010; Khurana et al., 2011;
Kshirsagar et al., 2011).
Results and discussion
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178 Z. Karimi-Jaberi and M.M. ReyazoShams
Ar
O
H3C
H3C
N
CN
Cl3CCOOH
CH2(CN)2
+
ArCHO
+
N
Solvent-free, 100°C
O
N
N
NH2
Ph
Ph
1-12
1: Ar=C6H5; 2: Ar=4-ClC6H4; 3: Ar=4-BrC6H4; 4: Ar=4-FC6H4; 5: Ar= 4-CNC6H4; 6: Ar=4-NO2C6H4; 7: Ar=3-NO2C6H4;
8: Ar=2,6-Cl2C6H3; 9: Ar=2,4-Cl2C6H3; 10: Ar=4-CH3C6H4; 11: Ar=4-CH3OC6H4; 12: Ar=4-OHC6H4
Scheme 1 Synthesis of dihydropyrano[2,3-c]pyrazoles.
6-Amino-4-(3-nitrophenyl)-5-cyano-3-methyl-1-phenyl-1,4-di-
hydropyrano[2,3-c]pyrazole (7) Reaction time 3 min; yield 96%;
mp 188–191°C; reported mp 188–190°C (Jin et al., 2006).
Experimental
General procedure for the synthesis of
1,4-dihydropyrano[2,3-c]pyrazoles 1–12
6-Amino-4-(2,6-dichlorophenyl)-5-cyano-3-methyl-1-phenyl-
1,4-dihydropyrano[2,3-c]pyrazole (8) Reaction time 8 min; yield
70%; mp 205–207°C; IR (KBr) νmax 3321, 3200, 2192, 1654, 1522,
To a mixture of aldehyde (2 mmol), malononitrile (132 mg, 2 mmol)
and 3-methyl-1-phenyl-2-pyrazolin-5-one (384 mg, 2 mmol), trichlo-
roacetic acid (32 mg, 10 mol%) was added and the mixture was
stirred at 100°C for the period of time indicated below. The progress
of the reaction was monitored by TLC (ethyl acetate/n-hexane, 1:4).
After completion of the reaction, the mixture was cooled to 25°C,
treated with water (10 mL), and stirred for 10 min. The obtained solid
was collected by filtration and crystallized from ethanol to afford
pure product 1–12.
1
1394, 1269, 1028, 753 cm-1; H NMR (250 MHz, CDCl3): δ 1.90
(s, 3H, CH3), 5.80 (s, 1H, C-H), 4.80 (s, 2H, NH2), 7.14–7.64 (m, 8H,
ArH); 13C NMR (62.5 MHz, CDCl3): δ 12.4, 33.2, 59.4, 96.1, 118.6,
121.3, 126.8, 129.2, 130.77, 134.4, 135.6, 136.4, 137.5, 144.4, 145.7,
159.9. Anal. Calcd for C20H14Cl2N4O: C, 60.47; H, 3.55; N, 14.10.
Found: C, 60.42; H, 3.51; N, 14.13.
6-Amino-4-(2,4-dichlorophenyl)-5-cyano-3-methyl-1-phenyl-
1,4-dihydropyrano[2,3-c]pyrazole (9) Reaction time 3 min; yield
87%; mp 182–184°C; reported mp 182–184°C (Jin et al., 2006).
6-Amino-5-cyano-3-methyl-1,4-diphenyl-1,4-dihydro-
pyrano[2,3-c]pyrazole (1) Reaction time 3 min; yield 98%; mp
168–170°C; reported mp 168–170°C (Jin et al., 2005).
6-Amino-4-(4-methylphenyl)-5-cyano-3-methyl-1-phenyl-1,4-
dihydropyrano[2,3-c]pyrazole (10) Reaction time 5 min; yield
88%; mp 172–174°C; reported mp 176–178°C (Jin et al., 2005).
6-Amino-4-(4-chlorophenyl)-5-cyano-3-methyl-1-phenyl-1,4-
dihydropyrano[2,3-c]pyrazole (2) Reaction time 3 min; yield
85%; mp 175–177°C; reported mp 174–175°C (Jin et al., 2005).
6-Amino-4-(4-methoxyphenyl)-5-cyano-3-methyl-1-phenyl-
1,4-dihydropyrano[2,3-c]pyrazole (11) Reaction time 9 min; yield
91%; mp 172–174°C; reported mp 174–176°C (Jin et al., 2005).
6-Amino-4-(4-bromophenyl)-5-cyano-3-methyl-1-phenyl-1,4-
dihydropyrano[2,3-c]pyrazole (3) Reaction time 1 min; yield
90%; mp 182–184°C; reported mp 183–184°C (Khurana et al.,
2011).
6-Amino-4-(4-hydroxyphenyl)-5-cyano-3-methyl-1-phenyl-1,4-
dihydropyrano[2,3-c]pyrazole (12) Reaction time 4 min; yield
95%; mp 210–212°C; reported mp 211–212°C (Heravi et al., 2010).
6-Amino-4-(4-flourophenyl)-5-cyano-3-methyl-1-phenyl-1,4-
dihydropyrano[2,3-c]pyrazole (4) Reaction time 2 min; yield
84%; mp 169–171°C; reported mp 167–168°C (Shi et al., 2004).
Acknowledgments
6-Amino-4-(4-cyanophenyl)-5-cyano-3-methyl-1-phenyl-1,4-
dihydropyrano[2,3-c]pyrazole (5) Reaction time 2 min; yield
90%; mp 197–199°C; IR (KBr) νmax 3400, 3305, 2234, 2189,
The authors gratefully acknowledge the partial financial support
from the Firoozabad Branch, Islamic Azad University. The authors
would also like to thank Ms. Baharak Pooladian for all of her superb
help.
1
1649, 1491, 1262, 1024, 753 cm-1; H NMR (250 MHz, CDCl3): δ
1.88 (s, 3H, CH3), 4.74 (s, 1H, C-H), 4.76 (s, 2H, NH2), 7.26–7.69
(m, 9H, ArH); 13C NMR (62.5 MHz, CDCl3): δ 12.9, 37.5, 62.5,
97.1, 111.7, 118.5, 121.3, 127.1, 128.3, 128.71, 129.3, 131.9, 132.3,
132.8, 146.0, 147.2, 158.4. Anal. Calcd for C21H15N5O: C, 71.38;
H, 4.28; N, 19.82. Found: C, 71.30; H, 4.25; N, 19.78.
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dihydropyrano[2,3-c]pyrazole (6) Reaction time 3 min; yield
88%; mp 192–195°C; reported mp 194–196°C (Jin et al., 2006).
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Received October 16, 2011; accepted November 15, 2011
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