Green and Sustainable Chemistry, 2013, 3, 1-8
doi:10.4236/gsc.2013.32A001 Published Online May 2013 (http://www.scirp.org/journal/gsc)
Silica-Grafted Ionic Liquids as Recyclable Catalysts for the
Synthesis of 3,4-Dihydropyrano[c]chromenes and
Pyrano[2,3-c]pyrazoles
Khodabakhsh Niknam*, Abolhassan Piran
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr, Iran
Email: *niknam@pgu.ac.ir, khniknam@gmail.com
Received February 10, 2013; revised March 12, 2013; accepted March 20, 2013
Copyright © 2013 Khodabakhsh Niknam, Abolhassan Piran. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
ABSTRACT
Silica-grafted N-propyl-imidazolium hydrogen sulfate ([Sipim]HSO4) is employed as a recyclable heterogeneous ionic
liquid catalyst for the synthesis of 3,4-dihydropyrano[c]-chromenes by the reaction of aromatic aldehydes, malononitrile
and 4-hydroxycoumarin at 100˚C under solvent-free conditions. Also, heterogeneous ionic liquid catalyst was used for
the synthesis of pyrano[2,3-c]-pyrazoles by the reaction of aromatic aldehydes, malononitrile and 3-methyl-l-phenyl5-pyrazolone at 110˚C under solvent-free conditions. The heterogeneous ionic liquid showed much the same efficiency
when used in consecutive reaction runs.
Keywords: Silica-Grafted N-Propyl-Imidazolium Hydrogen Sulfate; Aldehydes; Pyrano[2,3-c]-Pyrazoles;
3,4-Dihydropyrano[c]-Chromenes; Solvent-Free, Heterogeneous Ionic Liquid Catalysts
1. Introduction
In the recent years, ionic liquids were used as solvents
due to their particular properties, such as the ability to
dissolve many organic and inorganic substances and undetectable vapor pressure [1]. In addition, Brønsted acidic task-specific ionic liquids (BAILs), such as those possessing HSO 4 as a counter anion find a broad application in organic synthesis, acting as both solvents and
catalysts. Keim and co-workers reported the synthesis of
1-butyl-3-methylimidazolium hydrogen sulfate ([bmim]
HSO4) [2]. In addition, in the year of 2002 ([bmim]HSO4)
was used as a catalyst in the Friedel-Crafts alkylation [3].
The other applications of these acidic ionic liquids such
as acetalization and thioacetalization of carbonyl compounds [4], Fischer indole synthesis [5], acetylation of
alcohols and phenols [6], preparation of azides from alcohols [7], selective nitration of phenols [8], synthesis of
1,8-dioxo-octahydroxanthenes [9], formylation of alcohols [10], synthesis of polysubstituted quinolines [11],
have been proceeded with very good yields and selectivities. Recently, immobilization of acidic ionic liquids on
solid supports has been designed and it can offer important advantages in handling, separation and reuse proce*
Corresponding author.
Copyright © 2013 SciRes.
dures. 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, e.g., for esterification, nitration
reactions [12], acetal formation [13], Baeyer-Villiger
reaction [14], synthesis of α-aminonitriles [15] and bispyrazolones [16].
Dihydropyrano[c]chromenes and their derivatives are
of considerable interest as they possess a wide range of
biological properties [17], such as spasmolytic, diuretic,
anti-coagulant, anti-cancer, and anti-anaphylactic activity
[18,19]. In addition, they can be used as cognitive enhancers, for the treatment of neurodegenerative diseases,
including Alzheimer’s disease, Parkinson’s disease, AIDS
associated dementia and Down’s syndrome as well as for
the treatment of schizophrenia and myoclonus [20]. Also,
a number of 2-amino-4H-pyranes are useful as photoactive materials [21]. A number of methods have been
reported for the synthesis of 3,4-dihydropyrano[c] chromenes such as piperidine in organic solvent, i.e. ethanol
and pyridine [22], K2CO3 under microwave irradiation
[23], diammonium hydrogen phosphate [24], tetrabutylammonium bromide [25], sodium dodecyl sulfate [26],
DBU [27], morpholine [28], α-Fe2O3 nanopatricles [29],
CuO nanopatricles [30], and silica-bonded N-propylGSC
K. NIKNAM, A. PIRAN
2
piperazine sodium propionate [31].
In continuation of our studies on the design and application of acidic ionic liquids or silica-grafted ionic liquids as catalyst in organic transformations (Scheme 1)
[8-11,15,16], herein, we describe the application of silicagrafted N-propyl-imidazolium hydrogen sulfate ([Sipim]
HSO4) in the synthesis of pyrano[c]chromenes and pyrano[3,4c]pyrazoles.
Table 1. Investigation the effect of catalyst and solvent on
the reaction of 4-chlorobenzaldehyde, malononitrile and 4hydroxycoumarin.
Entry
2. Results and Discussion
2.1. Synthesis of Dihydropyrano[c]chromenes
To study the effect of catalyst loading on the synthesis of
2-amino-4-aryl-5-oxo-4H,5H-pyrano[3,2-c]chromene-3carbonitrile the condensation reaction of malononitrile,
4-chlorobenzaldehyde, and 4-hydroxycoumarin was chosen as a model reaction (Table 1). The results show
clearly that ionic liquids and silica-grafted ionic liquids
(SGILs) are effective catalysts for this condensation and
the optimal amount of SGILs was 0.1 g per 1 mmol of
aldehyde under solvent-free conditions at 100˚C. The
best result was obtained in the presence of [Sipim]HSO4.
This condensation was carried out with the lower amounts
of [Sipim]HSO4 0.05 g and 0.07 g and the corresponding
product was obtained in 88% and 91% yield (Table 1,
entries 4 and 5).
Also, this three-component condensation was accomplished in the presence of [Sipim]HSO4 in ethanol and
water at reflux conditions in longer reaction time and
lower yield (Table 1, entries 1 and 2). Moreover, the
model reaction was examined under solvent-free conditions at 80˚C gave 1b after 90 min in 80% yield (Table 1,
entry 8). The model reaction was reacted in the presence
of N-(3-silicapropyl) imidazolium chloride ([Sipim]Cl),
N-(3-silicapropyl) imidazolium dihydrogen phosphate
([Sipim]H2PO4), and N-(3-silicapropyl) imidazolium triflate ([Sipim]OTf), under solvent-free conditions at 100˚C
in 80%, 80%, and 75% yield respectively (Table 1, entries 10-12). In addition, the same model reaction was
carried out in the presence of ionic liquids such as imidazolium chloride, imidazolium hydrogen sulfate, methylimidazolium hydrogen sulfate, and imidazolium bromide under solvent-free and at 100˚C in 85%, 80%, 80%,
and 85% yield respectively (Table 1, entries 13-17).
SiO2
OH
OH
a
SiO2
OH
d
O
O Si
Cl
O
SiO2
O
O Si
b
c
SiO2
O
O Si
N
O
NH
Cl
([Sipim]Cl)
N
O
NH
HSO4
([Sipim]HSO4)
a) (MeO)3Si-(CH2)3-Cl, toluene(dry), Et3N, reflux, 48 h; b) Imidazole, toluene (dry), 24 h, reflux;
c) Dry under vaccum (50 oC), 4 h; d) dry CH2Cl2 , H2SO4 (97%), 48 h, reflux
Scheme 1. Preparation of silica-grafted propyl imidazolium
hydrogen sulfate ([Sipim]HSO4).
Copyright © 2013 SciRes.
1
SiO2
2
SiO2
3
SiO2
4
SiO2
5
SiO2
6
SiO2
7
SiO2
8
SiO2
9
SiO2
10
a
0.1
EtOH/Reflux
75
75
0.1
H2O/Reflux
75
75
0.1
EtOH/H2O
(1:1)/Reflux
60
86
0.05
Solvent-free/100
120
88
0.07
Solvent-free/100
90
91
0.1
Solvent-free/100
30
95
0.15
Solvent-free/100
30
95
0.1
Solvent-free/80
90
80
0.1
Solvent-free/120
30
95
0.1
Solvent-free/100
30
80
0.1
Solvent-free/100
30
80
0.1
Solvent-free/100
60
75
NH Cl
0.2
Solvent-free/100
120
85
NH HSO4
0.2
Solvent-free/100
150
80
NH HSO 4
0.2
Solvent-free/100
210
80
NH H 2PO4
0.2
Solvent-free/100
120
75
NH Br
0.2
Solvent-free/100
120
85
O
O Si
N
O
O Si
N
O
O
O Si
N
O
O
O Si
N
O
O
O Si
N
O
O
O Si
N
O
O
O Si
N
O
O
O Si
N
O
O
O Si
N
O
O
O Si
SiO2
N
O
SiO2
12
SiO2
O
O Si
N
O
O
O Si
N
NH
HSO4
NH
HSO4
NH
HSO4
NH
HSO4
NH
HSO4
NH
HSO4
NH
HSO4
NH
HSO4
NH
HSO4
NH
Cl
NH
H2PO4
NH
OTf
O
HN
14
HN
15
H 3CN
16
HN
17
Solvent/ Temp.
(˚C)
O
11
13
Catalyst
loading (g)
Catalyst
HN
Time Yield
(min) (%)a
Isolated Yield.
The synthesis of 2-amino-4-aryl-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile was achieved by the threecomponent condensation of an aromatic aldehyde, malononitrile, and 4-hydroxycoumarin in the presence of
[Sipim]HSO4 (0.1 g, 0.08 mmol of H+ [15]) under solventfree conditions at 100˚C (Table 2).
Thereafter, a series of different 3,4-dihydropyrano[c]chromene derivatives were prepared successfully from
different aromatic aldehydes bearing electron-withdrawing and electron donating groups, 4-hydroxycoumarin and malononitrile under solvent-free conditions.
Electron-withdrawing groups such as 3-nitro, 4-nitro, and
2-nitro-benzaldehyde reacted under optimized conditions
into corresponding 1f, 1g, and 1h in 93%, 90%, and 89%
yield after 30 min (Table 2, entries 6-8). ElectrondoGSC
K. NIKNAM, A. PIRAN
Table 2. [Sipim]HSO4 catalyzed synthesis of dihydropyrano
[c]chromene derivatives.a
NH2
OH
Ar-CHO +
O
O Si
N
O
CN
CN
2
SiO2
+
O
3
O
CN
O
NH
HSO4
Ar
Solvent-free, 100 oC
O
O
1
4
Entry
Ar
Product
Yield (%)b
1
C6H5-
1a
94
2
4-ClC6H4-
1b
95, 95, 93, 91, 90c
3
3-ClC6H4-
1c
93
4
4-BrC6H4-
1d
94
5
2,4-(Cl)2C6H3-
1e
90
6
3-O2NC6H4-
1f
93
7
4-O2NC6H4-
1g
90
8
2- O2NC6H4-
1h
89
9
4-MeC6H4-
1i
94
10
3,4,5-(CH3O)3C6H2-
1j
89
11
4-HO-C6H4-
1k
93
a
Reaction conditions: 4-hydroxycoumarin (1 mmol), malononitrile (1 mmol),
aldehyde (1 mmol), solvent-free conditions at 100˚C for 30 min. bIsolated
yield. cThe recovered [Sipim]HSO4 was used as catalyst.
3
phenyl-1H-pyrazol-5(4H)-one, aldehydes and malononitrile for the construction of 1,4-dihydropy-rano[2,3-c]
pyrazole derivatives has been reported under different
conditions [37-41]. However, most of the reported methods have their drawbacks. For example, hexadecyltrimethylammonium bromide (HTMAB) is a harmful and
irritant catalyst which is dangerous for the environment
[39]. In addition, the reusability of the catalysts such as
D,L-proline is not reported in a number of cases [40].
Heteropoly acids, silica-supported bases or acids have
been reported the synthesis of 1,4-dihydropyrano[2,3-c]
pyrazole derivatives via multi-component condensation
reaction [42-48].
The scope of this methodology was extended to the
synthesis of pyrano[2,3-c]pyrazols. Initially three-component condensation reaction of malononitrile, 4-chlorobenzaldehyde, and 3-methyl-1-phenyl-1H-pyrazol-5 (4H)one was chosen as a model reaction and the effect of different catalysts was investigated at 110˚C under solvent-free conditions (Table 3).
Again, the results show clearly that ionic liquids and
silica-grafted ionic liquids (SGILs) are effective catalysts
Table 3. Investigation the effect of catalyst on the reaction
of 4-chlorobenzaldehyde, malononitrile and 3-methyl-1phenyl-1H-pyrazol-5(4H)-one at 110˚C under solvent-free
conditions.
Entry
nating groups such as 4-Me, 3,4,5-(MeO)3-benzaldehyde
were treated with malononitrile and 4-hy- droxycoumarin
under optimized conditions gave corresponding products
1i and 1j in high yields (Table 2, entries 9 and 10). The
results clearly indicate that reactions can tolerate a wide
range of differently substituted aromatic aldehydes.
The possibility of recycling the catalyst was examined
using the reaction of malononitrle, 4-chlorobenzaldehyde
and 4-hydroxycoumarin under the optimized conditions.
Upon completion, the reaction mixture was washed with
warm ethanol (3 × 30 mL). The recovered catalyst was
dried and reused for subsequent runs. The recycled catalyst could be reused fourth times without any additional
treatment. No observation of any appreciable loss in the
catalytic activity of [Sipim]HSO4 was made (Table 2,
entry 2).
1
SiO2
2
SiO2
3
SiO2
4
SiO2
5
SiO2
6
7
8
O
O Si
120
80
0.07
120
85
0.1
90
90
0.15
90
95
0.2
90
95
0.15
100
90
0.15
100
90
0.15
120
70
NH Cl
0.2
120
85
NH HSO4
0.2
150
80
NH HSO 4
0.2
150
80
NH H 2PO4
0.2
150
70
NH Br
0.2
120
85
O
O Si
N
O
O
O Si
N
O
O
O Si
N
O
O
O Si
N
O
O
O Si
SiO2
N
O
SiO2
O
O Si
N
O
O
O Si
SiO2
HN
Condensed pyrazoles are also biologically interesting compounds and their chemistry has recently received considerable attention [32,33]. Several pyrano[2,3-c] pyrazoles are reported to have useful biological effects, such
as analgesic and anti-inflammatory activities [34]. Moreover, the biological activity of fused azoles has led to
intensive research on their synthesis [35,36]. Recently,
three component one-pot condensation of 3-methyl-1-
14
HN
15
H 3CN
16
HN
17
N
NH
HSO4
NH
HSO4
NH
HSO4
NH
HSO4
NH
HSO4
NH
Cl
NH
H2PO4
NH
OTf
O
13
Copyright © 2013 SciRes.
0.05
N
O
2.2. Synthesis of Pyrano[2,3-c]pyrazoles
a
Catalyst
Time (min) Yield (%)a
loading (g)
Catalyst
HN
Isolated Yield.
GSC
K. NIKNAM, A. PIRAN
4
for this condensation and the optimal amount of SGILs
was 0.15 g per 1 mmol of aldehyde under solvent-free
conditions at 110˚C.
A range of different substituted groups on aromatic
aldehydes involving electron-withdrawing groups such as
3-nitro, 4-nitro, and electron-donating groups such as 3,4dimethoxy-benzaldehyde reacted under optimized conditions into corresponding 5f, 5g, and 5h in 90%, 88%, and
90% yield after 90 min (Table 4, entries 6-8). 4-Hydroxy-benzaldehyde was treated with malononitrile and
3-methyl-1-phenyl-1H-pyrazol-5(4H)-one under optimized conditions gave corresponding products 5i in 90%
yield (Table 4, entry 9).
The possibility of recycling the catalyst was examined
using the reaction of malononitrle, 4-chlorobenzaldehyde
and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one under the
optimized conditions. Upon completion, the reaction mixture was washed with warm ethanol (3 × 30 mL). The
recovered catalyst was dried and reused for subsequent
runs. The recycled catalyst could be reused fourth times
without any additional treatment. No observation of any
appreciable loss in the catalytic activity of [Sipim]HSO4
was made (Table 4, entry 2).
3. Experimental Section
3.1. General
Chemicals were purchased from Fluka, Merck and Aldrich Chemical Companies. All the products were charTable 4. [Sipim]HSO4 catalyzed synthesis of dihydropyrano
[2,3-c]pyrazole derivatives.a
SiO2
Me
Ar-CHO
+
2
O
CN
+
CN
N
O
O Si
N
NH
HSO 4
Me
Ar
CN
N
N
Ph
3
O
Solvent-free, 110 oC
N
Ph
O
6
Entry
Ar
Product
Yield (%)b
1
C6H5-
5a
92
2
4-ClC6H4-
5b
95, 94, 92, 90, 89c
3
2,4-(Cl)2C6H3-
5c
89
4
4-BrC6H4-
5d
95
5
4-FC6H4-
5e
90
6
3-O2NC6H4-
5f
90
7
4-O2NC6H4-
5g
88
8
3,4-(CH3O)2C6H3-
5h
90
9
4-HO-C6H4-
5i
90
a
NH2
5
Reaction conditions: 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (1 mmol),
malononitrile (1 mmol), aldehyde (1 mmol), solvent-free conditions at 110
o
C for 90 min. bIsolated yield. cThe recovered [Sipim]HSO4 was used as
catalyst.
Copyright © 2013 SciRes.
pyl-imidazolium hydrogen sulfate ([Sipim]HSO4) was
acterized by comparison of their IR, 1H NMR and 13C
NMR spectroscopic data and their melting points with
the reported values [24-31,38-41]. Silica-grafted N-proprepared according to our previous reported procedure
[15].
3.2. General Procedure for the Synthesis of
3,4-Dihydropyrano[c]chromenes
To a mixture of aromatic aldehyde (1 mmol), malonitrile
(1 mmol), and 4-hydroxycoumarin (1 mmol), catalyst
[Sipim]HSO4 (0.1 g, 0.08 mmol of H+) was added and
the mixture was heated at 100˚C under solvent-free conditions. After completion of the reaction, as indicated by
TLC, ethanol (10 mL) was added and the reaction mixture was filtered. The remaining was washed with warm
ethanol (3 × 5 mL) in order to separate heterogeneous
catalyst. After cooling the crude products were precipitated. The crude products were purified by recrystallization from ethanol (95%). The recovered catalyst was
dried and reused for subsequent runs.
2-Amino-4-phenyl-4,5-dihydro-5-oxopyrano[3,2-c]c
hromene-3-carbonitrile 1a: mp 258˚C - 260˚C, (Lit.:
256˚C - 258˚C, [24]). 1H NMR (400 MHz, DMSO-d6): δ
(ppm) 4.46 (s, 1 H), 7.23 - 7.27 (m, 3 H), 7.31 - 7.35 (m,
2 H), 7.43 - 7.52 (m, 2H), 7.72 (dt, 1 H, J1 = 7.8 Hz, J2 =
1.6 Hz), 7.92 (dd, 1 H, J1 = 8.0 Hz, J2 = 0.8 Hz). 13C
NMR (100 MHz, DMSO-d6): δ (ppm) 58.41, 104.47,
113.42, 117.06, 119.68, 122.98, 125.18, 127.62, 128.10,
129.01, 133.45, 143.80, 152.60, 153.89, 158.36, 158.40,
160.05.
2-Amino-4-(4-chlorophenyl)-4,5-dihydro-5-oxopyra
no[3,2-c]chromene-3-carbonitrile 1b: mp 263˚C 265˚C, (Lit.: 252˚C - 255˚C, [28]). 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 4.49 (s, 1 H), 7.31 (d, 2 H, J = 8.4
Hz), 7.38 (d, 2H, J = 8.4 Hz), 7.45-7.51 (m, 2 H), 7.72 (t,
1 H, J = 7.8 Hz), 7.91 (d, 1 H, J = 8.0 Hz). 13C NMR
(100 MHz, DMSO-d6): δ (ppm) 57.94, 103.94, 113.39,
117.06, 119.54, 123.01, 125.18, 128.92, 130.12, 132.18,
133.51, 142.80, 152.64, 154.02, 158.34, 158.38, 160.03.
2-Amino-4-(3-chlorophenyl)-4,5-dihydro-5-oxopyra
no[3,2-c]chromene-3-carbonitrile 1c: mp 241˚C - 243˚C,
(Lit.: 246˚C - 248˚C, [26]). 1H NMR (400 MHz, DMSOd6): δ (ppm) 4.52 (s, 1 H), 7.26 (d, 1 H, J = 7.2 Hz), 7.31
- 7.38 (m, 3 H), 7.47 - 7.53 (m, 2 H), 7.73 (t, 1H, J = 7.6
Hz), 7.91 (d, 1H, J = 7.6 Hz). 13C NMR (100 MHz,
DMSO-d6): δ (ppm) 57.81, 103.63, 113.43, 117.02,
119.55, 123.06, 125.13, 127.03, 127.66, 128.06, 130.87,
133.48, 133.54, 146.26, 152.66, 154.19, 158.37, 158.42,
160.06.
2-Amino-4-(4-bromophenyl)-4,5-dihydro-5-oxopyra
no[3,2-c]chromene-3-carbonitrile (1d): mp 254˚C 256˚C, (Lit.: 247˚C - 249˚C, [26]). 1H NMR (400 MHz,
GSC
K. NIKNAM, A. PIRAN
DMSO-d6): δ (ppm) 4.48 (s, 1 H), 7.25 (d, 2 H, J = 8.0
Hz), 7.46 - 7.52 (m, 4 H), 7.73 (t, 1 H, J = 7.4 Hz), 7.91
(d, 1 H, J = 7.6 Hz). 13C NMR (100 MHz, DMSO-d6): δ
(ppm) 57.85, 103.88, 113.39, 117.08, 119.54, 120.71,
123.02, 125.20, 130.50, 131.85, 133.54, 143.23, 152.65,
154.03, 158.32, 160.04.
2-Amino-4-(2,4-dichloro-phenyl)-4,5-dihydro-5-oxo
pyrano[3,2-c]chromene-3-carbonitrile (1e): mp 258˚C
- 259˚C, (Lit.: 253˚C - 255˚C, [30]). 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 4.98 (s, 1 H), 7.35 - 7.41 (m, 2 H),
7.48 - 7.54 (m, 4 H), 7.60 (d, 1 H, J = 2.0 Hz), 7.74 (dt,
1H, J1 = 8.0 Hz, J2 = 1.6 Hz), 7.92 (dd, 1 H, J1 = 8.0 Hz,
J2 = 1.6 Hz). 13C NMR (100 MHz, DMSO-d6): δ (ppm)
34.33, 56.43, 102.96, 113.29, 117.12, 119.18, 123.04,
125.25, 128.36, 129.34, 132.56, 132.88, 133.61, 133.82,
139.91, 152.70, 154.62, 158.57, 159.94.
2-Amino-4-(3-nitrophenyl)-4,5-dihydro-5-oxopyran
o[3,2-c]chromene-3-carbonitrile (1f): mp 266˚C 267˚C, (Lit.: 262˚C - 264˚C, [24]). 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 4.74 (s, 1 H), 7.46 - 7.53 (m, 2 H),
7.58 (s, 2H, NH2), 7.64 (t, 1H, J = 8.0 Hz), 7.74 (dt, 1 H,
J1 = 7.9 Hz, J2 = 1.4 Hz), 7.82 (d, 1 H, J = 7.6 Hz), 7.93
(dd, 1 H, J1 = 8.0 Hz, J2 = 1.2 Hz), 8.12 - 8.15 (m, 2 H).
13
C NMR (100 MHz, DMSO-d6): δ (ppm) 57.36, 103.33,
113.39, 117.07, 119.45, 122.77, 122.93, 123.10, 125.19,
130.56, 133.61, 135.26, 145.96, 148.30, 152.73, 154.35,
158.52, 158.57, 160.10.
2-Amino-4-(4-nitrophenyl)-4,5-dihydro-5-oxopyran
o[3,2-c]chromene-3-carbonitrile (1g): mp 259˚C 261˚C, (Lit.: 258˚C - 260˚C, [24]). 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 4.68 (s, 1 H), 7.47 - 7.54 (m, 2 H),
7.58 - 7.61 (m, 2 H), 7.75 (dt, 1 H, J1 = 8.0 Hz, J2 = 1.2
Hz), 7.93 (dd, 1H, J1 = 8.0 Hz, J2 = 1.2 Hz), 8.21 (d, 2 H,
J = 8.4 Hz). 13C NMR (100 MHz, DMSO-d6): δ (ppm)
57.20, 103.27, 113.36, 117.13, 119.34, 123.09, 124.22,
125.26, 129.67, 133.69, 147.08, 151.23, 152.74, 154.42,
158.43, 158.47, 160.07.
2-Amino-4-(2-nitrophenyl)-4,5-dihydro-5-oxopyran
o[3,2-c]chromene-3-carbonitrile (1h): mp 258˚C 260˚C, (Lit.: 258˚C - 260˚C, [31]). 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 5.25 (s, 1 H), 7.46-7.59 (m, 6 H),
7.67 (t, 1 H, J = 7.6 Hz), 7.73 (t, 1 H, J = 7.8 Hz), 7.91 (d,
2 H, J = 7.6 Hz). 13C NMR (100 MHz, DMSO-d6): δ
(ppm) 56.52, 103.75, 113.27, 117.09, 119.22, 123.03,
124.45, 125.21, 128.93, 131.65, 133.57, 134.16, 137.83,
149.66, 152.63, 154.06, 159.08, 160.19.
2-Amino-4-p-tolyl-4,5-dihydro-5-oxopyrano[3,2-c]c
hromene-3-carbonitrile (1i): mp 253˚C - 255˚C, (Lit.:
259˚C - 260˚C, [28]). 1H NMR (400 MHz, DMSO-d6): δ
(ppm) 2.27 (s, 3H), 4.41 (s, 1 H), 7.11 - 7.15 (m, 4 H),
7.40 (s, 2 H, NH2), 7.46-7.52 (m, 2 H), 7.72 (dt, 1 H, J1 =
7.8 Hz, J2 = 1.6 Hz), 7.91 (dd, 1 H, J1 = 7.8 Hz, J2 = 1.4
Hz). 13C NMR (100 MHz, DMSO-d6): δ (ppm) 21.10,
58.53, 104.59, 113.42, 117.03, 119.71, 122.94, 125.15,
Copyright © 2013 SciRes.
5
128.00, 129.55, 133.38, 136.78, 140.86, 152.56, 153.72,
158.30, 160.01.
2-Amino-4-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-5
-oxopyrano[3,2-c]chromene-3-carbonitrile (1j): mp
236˚C - 238˚C, (Lit.: 236˚C - 238˚C, [31]). 1H NMR
(400 MHz, DMSO-d6): δ (ppm) 3.64 (s, 3 H), 3.72 (s, 6
H), 4.44 (s, 1 H), 6.53 (s, 2 H), 7.41 (s, 2 H, NH2),
7.47-7.52 (m, 2 H), 7.73 (dt, 1H, J1 = 8.0 Hz, J2 = 1.6
Hz), 7.91 (dd, 1 H, J1 = 8.0 Hz, J2 = 1.6 Hz). 13C NMR
(100 MHz, DMSO-d6): δ (ppm) 56.36, 58.32, 60.39,
104.11, 105.38, 113.54, 117.05, 119.71, 123.04, 125.11,
133.39, 137.03, 139.46, 152.64, 153.30, 153.98, 158.38,
160.14.
2-Amino-4-(4-hydroxy-phenyl)-4,5-dihydro-5-oxop
yrano[3,2-c]chromene-3-carbonitrile (1k): mp 266˚C 268˚C, (Lit.: 260˚C - 263˚C, [28]). 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 4.33 (s, 1 H), 6.71 (d, 2 H, J = 8.4
Hz), 7.06 (d, 0.72 H, J = 8.8 Hz), 7.36 (s, 2 H, NH2),
7.43 - 7.49 (m, 2 H), 7.69 (dt, 1H, J1 = 7.8 Hz, J2 = 1.6
Hz), 7.89 (dd, 1 H, J1 = 7.8 Hz, J2 = 1.4 Hz), 9.41 (s, 1H,
OH). 13C NMR (100 MHz, DMSO-d6): δ (ppm) 58.84,
104.92, 113.43, 115.59, 116.96, 119.87, 122.89, 125.09,
129.20, 133.25, 134.23, 152.48, 153.42, 156.80, 158.32,
160.02.
3.3. General Procedure for the Synthesis of
Dihydropyrano[2,3-c]pyrazoles
To a mixture of aromatic aldehyde (1 mmol), malonitrile
(1 mmol), and 3-methyl-1-phenyl-1H-pyrazol-5(4 H)-one
(1 mmol), catalyst [Sipim]HSO4 (0.15 g, 0.12 mmol of
H+) was added and the mixture was heated at 110˚C under solvent-free conditions. After completion of the reaction, as indicated by TLC, ethanol (10 mL) was added
and the reaction mixture was filtered. The remaining was
washed with warm ethanol (3 × 5 mL) in order to separate heterogeneous catalyst. After cooling the crude
products were precipitated. The crude products were purified by recrystallization from ethanol (95%). The recovered catalyst was dried and reused for subsequent
runs.
6-Amino-3-methyl-1,4-diphenyl-1,4-dihydro-pyran
o[2,3-c]pyrazol-5-carbonitrile (5a): mp 170˚C - 171˚C,
(Lit.: 168˚C - 170˚C, [38]). 1H NMR (400 MHz, CDCl3):
δ (ppm) 1.92 (s, 3 H), 4.69 (s, 1H), 4.71 (s, 2 H, NH2),
7.27 - 7.40 (m, 6 H), 7.49 (t, 2 H, J = 7.8 Hz), 7.68 (d,
2H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3): δ (ppm)
12.94, 37.44, 63.88, 98.36, 119.14, 121.22, 126.80,
127.62, 127.91, 128.83, 129.31, 137.57, 142.00, 143.84,
146.46, 158.17.
6-Amino-4-(4-chlorophenyl)-3-methyl-1-phenyl-1,4dihydro-pyrano[2,3-c]pyrazol-5-carbonitrile (5b): mp
174˚C - 176˚C, (Lit.: 174˚C - 177˚C, [43]). 1H NMR
(400 MHz, CDCl3): δ (ppm) 1.92 (s, 3 H), 4.68 (s, 1 H),
4.74 (s, 2 H, NH2), 7.22 (d, 2H, J = 8.4 Hz), 7.33-7.37 (m,
GSC
6
K. NIKNAM, A. PIRAN
3H), 7.49 (t, 2 H, J = 7.8 Hz), 7.67 (d, 2 H, J = 8.0 Hz).
C NMR (100 MHz, CDCl3): δ (ppm) 12.97, 36.91,
63.36, 97.87, 118.95, 121.25, 126.92, 129.06, 129.28,
129.34, 133.44, 137.45, 140.57, 143.80, 146.28, 158.23.
6-Amino-4-(2,4-dichlorophenyl)-3-methyl-1-phenyl1,4-dihydro-pyrano[2,3-c]pyrazol-5-carbonitrile (5c):
mp 183˚C - 185˚C, (Lit.: 182˚C - 184˚C, [38]). 1H NMR
(400 MHz, CDCl3): δ (ppm) 1.92 (s, 3 H), 4.78 (s, 2 H,
NH2), 5.29 (s, 1H), 7.17 (d, 1 H, J = 8.4 Hz), 7.26 - 7.28
(m, 1 H), 7.35 (t, 1 H, J = 7.2 Hz), 7.46-7.51 (m, 3 H),
7.67 (d, 2 H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3): δ
(ppm) 12.77, 33.53, 61.98, 97.58, 118.62, 121.28, 126.97,
128.04, 129.35, 129.68, 131.49, 133.95, 137.41, 137.86,
143.95, 146.04, 158.84.
6-Amino-4-(4-bromophenyl)-3-methyl-1-phenyl-1,4dihydro-pyrano[2,3-c]pyrazol-5-carbonitrile (5d): mp
182˚C - 184˚C, (Lit.: 176˚C - 177˚C, [40]). 1H NMR
(400 MHz, CDCl3): δ (ppm) 1.92 (s, 3H), 4.67 (s, 1 H),
4.73 (s, 2H, NH2), 7.17 (d, 2H, J = 8.0 Hz), 7.35 (t, 1 H,
J = 7.4 Hz), 7.48 - 7.53 (m, 4H), 7.67 (d, 2 H, J = 7.6 Hz).
13
C NMR (100 MHz, CDCl3): δ (ppm) 12.98, 36.98,
63.31, 97.78, 118.92, 121.26, 121.60, 126.93, 129.34,
129.63, 132.01, 137.45, 141.08, 146.28, 158.22.
6-Amino-4-(4-fluorophenyl)-3-methyl-1-phenyl-1,4dihydro-pyrano[2,3-c]pyrazol-5-carbonitrile (5e): mp
170˚C - 171˚C, (Lit.: 167˚C - 168˚C, [38]). 1H NMR
(400 MHz, CDCl3): δ (ppm) 1.91 (s, 3H), 4.69 (s, 1 H),
4.73 (s, 2 H, NH2), 7.07 (t, 2 H, J = 8.6 Hz), 7.24 - 7.28
(m, 2 H), 7.35 (t, 1 H, J = 7.4 Hz), 7.49 (t, 2H, J = 7.8
Hz), 7.67 (d, 2H, J = 8.0 Hz). 13C NMR (100 MHz,
CDCl3): δ (ppm) 12.94, 36.78, 63.69, 98.15, 115.86,
119.01, 121.24, 126.88, 129.33, 129.54, 137.49, 143.77,
146.32, 158.14, 162.17 (d, JC-F = 244.0 Hz).
6-Amino-3-methyl-4-(3-nitrophenyl)-1-phenyl-1,4-d
ihydro-pyrano[2,3-c]pyrazol-5-carbonitrile (5f): mp
190˚C - 191˚C, (Lit.: 190˚C - 192˚C, [43]). 1H NMR
(400 MHz, CDCl3): δ (ppm) 1.92 (s, 3 H), 4.84 (s, 3H,
CH & NH2), 7.37 (t, 1 H, J = 7.4 Hz), 7.51 (t, 2 H, J =
7.6 Hz), 7.60 (t, 1 H, J = 8.0 Hz), 7.67 - 7.70 (m, 3 H),
8.14 (s, 1 H), 8.21 (d, 1 H, J = 8.0 Hz). 13C NMR (100
MHz, CDCl3): δ (ppm) 13.01, 37.38, 62.11, 97.21,
118.76, 121.42, 122.87, 127.11, 129.37, 129.89, 134.17,
137.33, 144.49, 145.92, 148.76, 158.75.
6-Amino-3-methyl-4-(4-nitrophenyl)-1-phenyl-1,4-d
ihydro-pyrano[2,3-c]pyrazol-5-carbonitrile (5g): mp
194˚C - 196˚C, (Lit.: 195˚C - 197˚C, [43]). 1H NMR
(400 MHz, CDCl3): δ (ppm) 1.92 (s, 3 H), 4.83 (s, 3 H,
CH & NH2), 7.37 (t, 1 H, J = 7.4 Hz), 7.47 - 7.53 (m, 4
H), 7.78 (d, 2 H, J = 8.0 Hz), 8.27 (d, 2 H, J = 8.4 Hz).
13
C NMR (100 MHz, CDCl3): δ (ppm) 12.98, 37.33,
62.26, 97.07, 118.58, 121.35, 124.28, 127.16, 128.88,
129.40, 137.30, 143.83, 146.00, 147.46, 149.19, 158.56.
6-Amino-4-(3,4-dimethoxyphenyl)-3-methyl-1-phen
yl-1,4-dihydro-pyrano[2,3-c]pyrazol-5-carbonitrile
13
Copyright © 2013 SciRes.
(5h): mp 167˚C - 169˚C, (Lit.: 193˚C - 195˚C, [38]). 1H
NMR (400 MHz, CDCl3): δ (ppm) 1.91 (s, 3 H), 3.85 (s,
3 H), 3.87 (s, 3 H), 4.62 (s, 1 H), 4.73 (s, 2 H, NH2), 6,73
(d, 1H, J = 1.6 Hz), 6.79 - 6.85 (m, 2H), 7.31 (t, 1 H, J =
8.0 Hz), 7.45 (t, 2H, J = 8.0 Hz), 7.66 (d, 2 H, J = 8.4
Hz). 13C NMR (100 MHz, CDCl3): δ (ppm) 12.98, 37.06,
55.86, 55.98, 63.92, 98.29, 110.82, 111.12, 119.22,
120.18, 121.05, 126.71, 129.28, 134.56, 137.57, 143.80,
146.52, 148.41, 149.20, 158.02.
6-Amino-4-(4-hydroxyphenyl)-3-methyl-1-phenyl-1,
4-dihydro-pyrano[2,3-c]pyrazol-5-carbonitrile
(5i):
mp 206˚C - 208˚C, (Lit.: 206˚C - 207˚C, [40]). 1H NMR
(500 MHz, DMSO-d6): δ (ppm) 1.78 (s, 3 H), 4.55 (s, 1
H), 6.71 (d, 2 H, J = 7.8 Hz), 7.03 (d, 2 H, J = 7.8 Hz),
7.10 (s, 2 H, NH2), 7.31 (t, 1H, J = 7.0 Hz), 7.48 (t, 2 H,
J = 7.3 Hz), 7.77 (d, 2 H, J = 7.7 Hz), 9.31 (s, 1 H). 13C
NMR (125 MHz, DMSO-d6): δ (ppm) 13.45, 36.88,
59.68, 99.91, 116.07, 120.75, 120.96, 126.94, 129.62,
130.18, 134.79, 138.45, 144.65, 146.22, 157.15, 160.305.
4. Acknowledgements
We are thankful to Persian Gulf University Research
Council for partial support of this work.
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