An eco-friendly catalytic route for one-pot synthesis of 2-amino-6-(2-oxo-2Hchromen-3-yl)-4-arylnicotinonitrile derivatives by silica-supported perchloric acid (HClO4-SiO2) under solvent-free conditions

Article abstract of DOI:10.1007/s11164-013-1027-1

A facile and environmentally benign synthesis of some 2-amino-6-(2-oxo-2H- chromen-3-yl)-4-arylnicotinonitrile derivatives from the reaction of 3-acetylcoumarin, aromatic aldehydes, and malononitrile under solvent-free condition in the presence of silica-

Full text of DOI:10.1007/s11164-013-1027-1

Res Chem Intermed
DOI 10.1007/s11164-013-1027-1
An eco-friendly catalytic route for one-pot synthesis of
2-amino-6-(2-oxo-2Hchromen-3-yl)-4-arylnicotinonitrile
derivatives by silica-supported perchloric acid
(HClO4–SiO2) under solvent-free conditions
•
Majid Ghashang Krishnamoorthy Aswin
Syed Sheik Mansoor
•
Received: 24 November 2012 / Accepted: 4 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract A facile and environmentally benign synthesis of some 2-amino-6-(2-
oxo-2H-chromen-3-yl)-4-arylnicotinonitrile derivatives from the reaction of 3-ace-
tylcoumarin, aromatic aldehydes, and malononitrile under solvent-free condition in
the presence of silica-supported perchloric acid (HClO4–SiO2) is described. The
ability to reuse the catalyst, the high yields, and ease of purification are the
important features of this process.
Keywords 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitrile Á
Coumarin Á HClO4–SiO2 Á Solid support reagent Á 3-acetylcoumarin
Introduction
Over the years, coumarin (2-oxo-2H-chromene) derivatives have been established
as well-known naturally occurring oxygen-heterocyclic compounds isolated from
various plants which occupy a special role in nature [1]. The plant extracts
containing coumarin-related heterocycles are employed as herbal remedies in
traditional systems of medicine. They belong to the flavonoid class of plant
secondary metabolites. Coumarin derivatives constitute an important class of
heterocyclic compounds that have attracted significant attention in recent years [2,
3]. They have attracted intense interest because of their diverse pharmacological
M. Ghashang
Department of Chemistry, Faculty of Sciences, Najafabad Branch, Islamic Azad University,
Najafabad, Esfahan, Iran
K. Aswin Á S. S. Mansoor (&)
Bioactive Organic Molecule Synthetic Unit, Research Department of Chemistry, C. Abdul Hakeem
College, Melvisharam 632 509, Tamil Nadu, India
e-mail: smansoors2000@yahoo.co.in
123

M. Ghashang et al.
properties like anti-HIV [4], anticoagulant [5], antibacterial [6], antioxidant [7],
dyslipidemic [8], and anticancer agents [9], and antimicrobial activity [10].
In view of the pharmaceutical importance of heterocyclic compounds, various
methods have been developed for the synthesis of coumarin scaffolds [11, 12]. Of
these, the three-component coupling of 3-acetylcoumarin, an aromatic aldehyde,
and ammonium acetate is of great interest and was done by using acetic acid under
microwave irradiation [13, 14]. Although these procedures have some advantages
such as good yields, in the field of modern organic chemistry the discovery of new
synthetic methodologies to facilitate the preparation of organic compounds is a
demand point of research activity. Thus, the development of efficient synthetic
methods for coumarins of this type has become important in synthetic and medicinal
chemistry.
Therefore, considering the above and as a part of our ongoing programmed
synthesis of biologically active heterocyclic molecules [15–19], an efficient and
convenient synthesis of 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitrile
derivatives has been accomplished by the multi-component reaction of 3-acetyl-
coumarin, aromatic aldehydes, and malononitrile using silica-supported perchloric
acid (HClO4–SiO2) [20] as an efficient catalyst in good yields under solvent-free
condition (Scheme 1).
Results and discussion
3-Acetylcoumarin was synthesized by the reaction of salicylaldehyde with ethyl
acetoacetate in the presence of a catalytic amount of piperidine [21] (Scheme 2) to
undergo a condensation reaction with substituted benzaldehdyes, malononitrile, and
ammonium acetate to afford 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-phenylnicoti-
nonitrile derivatives.
To find out the suitable conditions for the reaction, a series of experiments were
performed with the standard reaction of 3-acetylcoumarin, benzaldehyde, malon-
onitrile, and ammonium acetate as a model reaction.
Effect of catalyst
Initially, a systematic study was carried out for catalytic evaluation of HClO4–SiO2
for the preparation of 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-phenylpyridine-3-
carbonitrile at a temperature of 60 °C (Table 1). Our studies showed that when
Ar
CN
O
O
HClO4 -SiO2 ( 0.8 mol %)
N
NH2
+ Ar-CHO + CH2(CN)2 + NH4OAc
Solvent-free; 60 o
C
O
O
O
4a - 4l
Scheme 1 Synthesis of various 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitrile derivatives
123

An eco-friendly catalytic route for one-pot synthesis
less than 0.8 mol% of HClO4–SiO2 was applied, lower yields of the corresponding
product (Table 1, Entries 2–4) resulted, whereas use of 0.8 mol% HClO4–SiO2
gives excellent results in terms of yield and time required for completion of the
reaction (Table 1, Entry 5). However, use of more than 0.8 mol% of catalyst did not
improve the yield (Table 1, Entry 6). In the absence of a catalyst, the product was
synthesized in low yield (Table 1, Entry 1).
Effect of temperature
In addition, the effect of temperature on rate of reaction was studied at different
temperatures for the preparation of 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-phenyl-
nicotinonitrile (4a) (Table 2). It was observed that the reaction is very slow at room
temperature. At 40 °C, the reaction proceeded smoothly and almost complete
conversion of product was observed. Further increases in temperature to 50, 60, 70,
and 80 °C increased the rate of reaction. However, at 70 and 80 °C, the reaction
time reduced and the yield of the product was also reduced. Therefore, we kept the
reaction temperature at 60 °C. At this temperature, the reaction is completed within
1.5 h with 92 % yield.
Finally, the optimum conditions selected were: 3-acetylcoumarin (1 mmol),
aldehyde (1 mmol), malononitrile (1 mmol), ammonium acetate (1 mmol), HClO4–
SiO2 (0.8 mol%), solvent-free condition and 60 °C as the reaction temperature.
To demonstrate the versatility of the developed protocol, several types of
aromatic aldehydes substituted with different groups possessing both electron-
O
N
CHO
OH
O
O
H
+
OEt
O
O
Scheme 2 Preparation of 3-Acetylcoumarin
Table 1 The reaction of 3-acetylcoumarin, benzaldehyde, malononitrile and ammonium acetate: Effect
of catalysis
Entry
Catalyst
Amount of catalyst (mol%)
Time (h)
Yield (%)a
1
2
3
4
5
6
HClO4–SiO2
HClO4–SiO2
HClO4–SiO2
HClO4–SiO2
HClO4–SiO2
HClO4–SiO2
0.0
0.2
0.4
0.6
0.8
1.0
3.0
3.0
3.0
2.0
1.5
1.2
28
55
69
81
92
84
Reaction conditions: 3-acetylcoumarin (1 mmol), benzaldehyde (1 mmol), malononitrile (1 mmol), and
ammonium acetate (2 mmol) under solvent-free condition at 60 °C
a
Isolated yields
123

M. Ghashang et al.
Yield (%)a
Table 2 Effect of temperature using HClO4–SiO2 (0.8 mol%)
Entry
Temperature (°C)
Time (h)
1
2
3
4
5
6
RT
40
50
60
70
80
4.0
4.0
3.5
1.5
1.2
1.2
39
72
82
92
85
80
Reaction conditions: 3-acetylcoumarin (1 mmol), benzaldehyde (1 mmol), malononitrile (1 mmol), and
ammonium acetate (2 mmol) in the presence of HClO4–SiO2 (0.8 mol %) under solvent-free condition
a
Isolated yields
withdrawing and electron-releasing groups were chosen and results are summarized
in Table 3. In all cases, aromatic aldehydes with substituents carrying either
electron-donating or electron-withdrawing groups reacted successfully and gave the
products in high yields. It was shown that the aromatic aldehydes with electron-
withdrawing groups reacted faster than the aromatic aldehydes with electron-
releasing groups as would be expected. The structures of isolated products 4a–4l
1
were deducted by physical and spectroscopic data such as: IR, H NMR and 13C
NMR spectroscopy, and elemental analysis.
Mechanism
On the basis of all our experimental results, together with a literature report [22], a
mechanistic rationale portraying the probable sequence of events is given in
Scheme 3. The reaction is believed to proceed through the formation of an enamine.
It is suggested that the 3-acetylcoumarin (ketone) is first reacted with ammonium
acetate to form enamine (a). In a second step, aromatic aldehyde undergoes
condensation with malononitrile to form arylidenemalononitrile (b). The enamine
(a) reacts with (b) to give intermediate (c). The intermediate (c) undergoes cyclo-
addition, isomerization, and aromatization to afford the final product.
Reusability of the catalyst
The reusability of the catalyst is one of the most important benefits and makes it
useful for commercial applications. Thus, the reusability of the catalyst was tested
in the synthesis of 2-amino-6-(2-oxo-2H-chromen3-yl)-4-phenylnicotinonitrile (4a),
as shown in Fig. 1 and Table 4. Interestingly, the heterogeneity of HClO4–SiO2
facilitates efficient recovery from the reaction mixture during the work-up
procedure by simple filtration and by washing the catalyst two times with an
aliquot of fresh CH2Cl2 (2 9 10 mL), then drying to make ready for a later run. The
catalyst was tested for four runs. It was seen that the recovered catalyst was
123

An eco-friendly catalytic route for one-pot synthesis
Table 3 Synthesis of various 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-phenylnicotinonitrile derivatives in
the presence of HClO4–SiO2
Entry Aldehyde
Product Time (h) Yield (%)a Mp (oC)
Found
Reported
232–234 234–236 [13]
1
4a
1.5
92
CHO
CHO
2
3
4b
1.2
95
242–244
224–226
–
–
Br
4c
1.2
1.5
96
90
CHO
Br
4
4d
287–289 286–288 [13]
CHO
NO2
5
4e
4f
1.5
1.2
93
94
250–252 252–254 [13]
CHO
O2N
6
248–250
–
CHO
F
7
4g
4h
1.2
1.5
92
90
232–234
238–240
–
–
CHO
F
8
CHO
OH
123

M. Ghashang et al.
Table 3 continued
Entry Aldehyde
Product Time (h) Yield (%)a Mp (oC)
Found
262–264 268–264 [13]
Reported
9
4i
1.5
91
CHO
HO
10
4j
1.2
96
254–256
–
CHO
Cl
11
12
4k
4l
2.0
2.0
86
88
270–272 271–273 [13]
266–268 268–270 [13]
CHO
CHO
H3C
H3CO
Reaction conditions: 3-Acetylcoumarin (1 mmol), benzaldehyde (1 mmol), malononitrile (1 mmol), and
ammonium acetate (2 mmol) in the presence of HClO4–SiO2 (0.8 mol%) under solvent-free condition
All reactions were carried out at 60 °C
a
Isolated yields
recycling in subsequent runs without observing significant decreases in activity even
after four runs.
Experimental
The general procedure for the synthesis of 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-
phenylnicotinonitrile derivatives was as follows. In a general experimental
procedure, a mixture of the 3-acetylcoumarin (1 mmol), aromatic aldehyde
(1 mmol), malononitrile (1 mmol), and ammonium acetate (1 mmol) in the presence
of HClO4–SiO2 (0.8 mol%) were taken into a 50-ml flask equipped with a reflux
condenser and heated at 60 °C for the appropriate time (Table 3). After completion
of the reaction (TLC monitoring), the reaction mixture was cooled to ambient
temperature, CH2Cl2 was added, and the HClO4–SiO2 was filtered off. The filtrate
was concentrated to dryness, and the crude solid product was crystallized from EtOH
to afford the pure 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-phenylnicotinonitrile.
123

An eco-friendly catalytic route for one-pot synthesis
O
NH
NH2
NH4OAc
R
HClO4 -SiO2
R
R
a
R
O
O
NC
Ar
CN
H
ArCHO + CH2(CN)2
b
-H2O
H
NH
NH2
NH
CN
R
NC
Ar
NC
Ar
NC
Ar
NH
H
a + b
R
R
NH
c
O2 (air)
-H2
Ar
CN
R
N
NH2
Scheme 3 Proposed mechanism for the synthesis of 2-amino-6-(2-oxo-2H-chromen-3-yl)-4-
arylnicotinonitrile derivatives
94
92
90
88
86
84
82
80
Reusability of the catalyst
92%
90%
88%
87%
1
2
3
4
Number of Runs
Fig. 1 Reusability of the catalyst HClO4–SiO2 for the synthesis of 2-amino-6-(2-oxo-2H-chromen-3-yl)-
4-phenylnicotinonitrile
123

M. Ghashang et al.
Table 4 The effect of recyclability of HClO4–SiO2 (0.8 mol%) catalyst on the product 4a yield
Entry
Cycle
Time (h)
Yield (%)a
1
2
3
4
0
1
2
3
1.5
1.5
1.5
1.5
92
90
88
87
Reaction conditions: 3-acetylcoumarin (1 mmol), benzaldehyde (1 mmol), malononitrile (1 mmol), and
ammonium acetate (2 mmol) in the presence of HClO4–SiO2 (0.8 mol%) under solvent-free condition at
60 °C
a
Isolated yields
Spectral data for the synthesized compounds
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-phenylnicotinonitrile (4a) IR (KBr, cm-1):
3,450 and 3,359 (NH2), 3,132 (ArH), 2,215 (CN), 1,725 (C=O), 1,612 (C–O); 1H NMR
(500 MHz, DMSO-d6) d: 8.82 (s, 1H, coumarin 4-H), 7.77 (s, 1H, PyrH), 7.88–7.54
(m, 9H, ArH), 7.02 (s, 2H, NH2);; 13C NMR (125 MHz, DMSO-d6) d: 86.4, 114.2,
117.8, 125.1, 125.6, 127.2, 127.6, 128.3, 129.4, 129.9, 130.3, 134.5, 136.1, 142.3,
147.2, 153.0, 158.9, 184.8 ppm; MS(ESI): m/z 340 (M ? H)?; Anal. Calcd. for
C21H13N3O2: C, 74.34; H, 3.83; N, 12.39 %. Found: C, 74.30; H, 3.80; N, 12.34 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(3-bromophenyl)nicotinonitrile (4b) IR
(KBr, cm-1): 3,453 and 3,344 (NH2), 3,120 (ArH), 2,218 (CN), 1,721 (C=O), 1,622
(C–O); 1H NMR (500 MHz, DMSO-d6) d: 8.77 (s, 1H, coumarin 4-H), 7.85 (s, 1H,
PyrH), 7.77–7.51 (m, 8H, ArH), 7.07 (s, 2H, NH2) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 85.8, 114.0, 117.4, 125.3, 125.8, 127.4, 127.8, 128.5, 129.5, 129.9,
130.5, 134.3, 136.3, 142.1, 147.5, 152.8, 158.7, 184.5 ppm; MS(ESI): m/z 418.9
(M ? H)?; Anal. Calcd. for C21H12BrN3O2: C, 60.30; H, 2.87; N, 10.05 %. Found:
C, 60.22; H, 2.85; N, 10.03 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(4-bromophenyl)nicotinonitrile (4c) IR
(KBr, cm-1): 3,54 and 3,342 (NH2), 3,128 (ArH), 2,216 (CN), 1,722 (C=O), 1,615
(C–O); 1H NMR (500 MHz, DMSO-d6) d: 8.81 (s, 1H, coumarin 4-H), 7.73 (s, 1H,
PyrH), 7.78–7.52 (m, 8H, ArH), 7.06 (s, 2H, NH2) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 86.2, 114.4, 117.5, 125.0, 125.4, 127.4, 127.7, 128.5, 129.6, 129.9,
130.3, 134.7, 136.0, 143.0, 147.4, 153.2, 158.8, 184.5 ppm; MS(ESI): m/z 418.90
(M ? H)?; Anal. Calcd. for C21H12BrN3O2: C, 60.30; H, 2.87; N, 10.05 %. Found:
C, 60.25; H, 2.80; N, 10.02 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(3-nitrophenyl)nicotinonitrile (4d) IR
(KBr, cm-1): 3,453 and 3,388 (NH2), 3,130 (ArH), 2,208 (CN), 1,718 (C=O),
1,609 (C–O); 3,452, 3,395, 3,130, 2,203, 1,723, 1,606; 1H NMR (500 MHz, DMSO-
d6) d: 8.80 (s, 1H, coumarin 4-H), 7.88 (s, 1H, PyrH), 7.82–7.40 (m, 8H, ArH), 7.12
(s, 2H, NH2) ppm; 13C NMR (125 MHz, DMSO-d6) d: 87.0, 114.0, 117.5, 125.0,
123

An eco-friendly catalytic route for one-pot synthesis
125.5, 127.0, 127.4, 128.0, 129.6, 129.9, 130.1, 134.3, 136.1, 142.0, 147.2, 153.5,
159.4, 186.2 ppm; MS(ESI): m/z 385 (M ? H)?; Anal. Calcd. for C21H12N4O4: C,
65.62; H, 3.12; N, 14.58 %. Found: C, 65.52; H, 3.11; N, 14.54 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(4-nitrophenyl)nicotinonitrile (4e) IR
(KBr, cm-1): 3,455 and 3,365 (NH2), 3,127 (ArH), 2,11 (CN), 1,724 (C=O),
1
1,628 (C–O); H NMR (500 MHz, DMSO-d6) d: 8.78 (s, 1H, coumarin 4-H), 7.75
(s, 1H, PyrH), 7.96–7.58 (m, 8H, ArH), 7.18 (s, 2H, NH2) ppm; 13C NMR
(125 MHz, DMSO-d6) d: 86.0, 114.0, 117.5, 125.0, 125.5, 127.1, 127.6, 128.3,
129.3, 129.8, 130.1, 134.5, 136.3, 142.1, 146.9, 152.5, 157.9, 186.0 ppm; MS(ESI):
m/z 385 (M ? H)?; Anal. Calcd. for C21H12N4O4: C, 65.62; H, 3.12; N, 14.58 %.
Found: C, 65.55; H, 3.09; N, 14.56 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(3-fluorophenyl)nicotinonitrile (4f) IR
(KBr, cm-1): 3,450 and 3,353 (NH2), 3,133 (ArH), 2,218 (CN), 1,722 (C=O), 1,616
(C–O); 1H NMR (500 MHz, DMSO-d6) d: 8.78 (s, 1H, coumarin 4-H), 7.71 (s, 1H,
PyrH), 7.83–7.54 (m, 8H, ArH), 7.03 (s, 2H, NH2) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 85.9, 113.9, 118.0, 124.9, 125.6, 127.2, 127.7, 128.6, 129.6, 129.9,
130.6, 134.6, 135.9, 142.4, 147.6, 152.9, 158.7, 185.1 ppm; MS(ESI): m/z 358
(M ? H)?; Anal. Calcd. for C21H12FN3O2: C, 70.59; H, 3.36; N, 11.76 %. Found:
C, 70.55; H, 3.32; N, 11.72 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(4-fluorophenyl)nicotinonitrile (4g) IR (KBr,
cm-1): 3,452 and 3,355 (NH2), 3,128 (ArH), 2,220 (CN), 1,718 (C=O), 1,622
(C–O); 1H NMR (500 MHz, DMSO-d6) d: 8.80 (s, 1H, coumarin 4-H), 7.86 (s, 1H,
PyrH), 7.75–7.48 (m, 8H, ArH), 7.00 (s, 2H, NH2) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 86.6, 114.7, 117.7, 125.0, 125.7, 127.4, 127.8, 128.1, 129.3, 129.9,
130.3, 134.2, 136.2, 141.9, 147.0, 152.7, 158.7, 184.5 ppm; MS(ESI): m/z 358
(M ? H)?;Anal. Calcd. for C21H12FN3O2: C, 70.59; H, 3.36; N, 11.76 %. Found:
C, 70.57; H, 3.29; N, 11.69 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(3-hydroxylphenyl)nicotinonitrile (4h) IR
(KBr, cm-1): 3,444 and 3,377 (NH2), 3,342 (OH), 3,133 (ArH), 2,211 (CN), 1,722
1
(C=O), 1,611 (C–O); H NMR (500 MHz, DMSO-d6) d: 8.64 (s, 1H, coumarin
4-H), 7.82 (s, 1H, PyrH), 7.89–7.65 (m, 8H, ArH), 7.15 (s, 2H, NH2), 9.89 (s, 1 H,
OH) ppm; 13C NMR (125 MHz, DMSO-d6) d: 85.3, 113.3, 118.2, 125.0, 125.4,
127.1, 127.6, 128.1, 129.4, 130.0, 130.5, 134.5, 136.1, 142.5, 147.0, 153.6, 159.7,
185.8 ppm; MS(ESI): m/z 408 (M ? H)?; Anal. Calcd. for C21H13N3O3: C, 70.98;
H, 3.66; N, 11.83 %. Found: C, 70.94; H, 3.64; N, 11.80 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(4-hydroxyphenyl)nicotinonitrile (4i) IR (KBr,
cm-1): 3,438 and 3,375 (NH2), 3,348 (OH), 3,128 (ArH), 2,216 (CN), 1,716 (C=O),
1
1,617 (C–O); H NMR (500 MHz, DMSO-d6) d: 8.58 (s, 1H, coumarin 4-H), 7.78
(s, 1H, PyrH), 7.94–7.68 (m, 8H, ArH), 7.14 (s, 2H, NH2), 9.94 (s, 1 H, OH) ppm;
13C NMR (125 MHz, DMSO-d6) d 85.9, 113.9, 117.9, 125.2, 125.7, 127.4, 127.7,
123

M. Ghashang et al.
128.1, 129.4, 130.2, 130.6, 134.7, 136.3, 142.2, 147.4, 153.5, 159.7, 186.2 ppm;
MS(ESI): m/z 408 (M ? H)?; Anal. Calcd. for C21H13N3O3: C, 70.98; H, 3.66; N,
11.83 %. Found: C, 70.90; H, 3.65; N, 11.84 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(3-chlorophenyl)nicotinonitrile (4j) IR
(KBr, cm-1): 3,458 and 3,347 (NH2), 3,126 (ArH), 2,212 (CN), 1,718 (C=O),
1
1,625 (C–O); H NMR (500 MHz, DMSO-d6) d: 8.79 (s, 1H, coumarin 4-H), 7.80
(s, 1H, PyrH), 7.80–7.56 (m, 8H, ArH), 7.07 (s, 2H, NH2) ppm; 13C NMR
(125 MHz, DMSO-d6) d: 86.3, 114.1, 117.7, 125.1, 125.6, 127.0, 127.5, 128.2,
129.5, 129.8, 130.6, 134.6, 136.2, 142.5, 147.5, 153.4, 159.2, 185.3 ppm; MS(ESI):
m/z 374.45 (M ? H)?; Anal. Calcd. for C21H12ClN3O2: C, 67.48; H, 3.21; N,
11.25 %. Found: C, 67.44; H, 3.20; N, 11.22 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(4-methylphenyl)nicotinonitrile (4k) IR
(KBr, cm-1): 3,440 and 3,376 (NH2), 3,130 (ArH), 2,210 (CN), 1,723 (C=O), 1,612
(C–O); 1H NMR (500 MHz, DMSO-d6) d: 8.61 (s, 1H, coumarin 4-H), 7.85 (s, 1H,
PyrH), 7.84–7.60 (m, 8H, ArH), 7.11 (s, 2H, NH2), 2.42 (s, 3H, CH3) ppm; 13C
NMR (125 MHz, DMSO-d6) d: 31.2, 85.5, 113.8, 118.1, 125.1, 125.5, 127.1, 127.5,
128.1, 129.2, 130.0, 130.3, 134.7, 136.1, 142.2, 146.9, 153.4, 159.4, 186.0 ppm;
MS(ESI): m/z 354 (M ? H)?; Anal. Calcd. for C22H15N3O2: C, 74.79; H, 4.25; N,
11.90 %. Found: C, 74.72; H, 4.26; N, 11.86 %.
2-Amino-6-(2-oxo-2H-chromen-3-yl)-4-(4-methoxyphenyl)nicotinonitrile (4l) IR
(KBr, cm-1): 3,416 and 3,352 (NH2), 3,118 (ArH), 2,216 (CN), 1,717 (C=O), 1,608
(C–O); 1H NMR (500 MHz, DMSO-d6) d: 8.74 (s, 1H, coumarin 4-H), 7.87 (s, 1H,
PyrH), 7.87–7.66 (m, 8H, ArH), 7.13 (s, 2H, NH2), 3.84 (s, 3H, OCH3) ppm; 13C
NMR (125 MHz, DMSO-d6) d: 86.1, 114.1, 117.4, 125.0, 125.4, 127.0, 127.7,
128.0, 129.7, 129.9, 130.1, 134.3, 136.3, 142.5, 147.6, 153.2, 158.5, 161.4,
184.7 ppm; MS(ESI): m/z 370 (M ? H)?; Anal. Calcd. for C22H15N3O3: C, 71.54;
H, 4.06; N, 11.38 %. Found: C, 71.44; H, 4.04; N, 11.33 %.
Conclusions
In summary, we have developed a simple and new procedure for the synthesis of
2-amino-6-(2-oxo-2H-chromen-3-yl)-4-arylnicotinonitrile by
a four-component
condensation of 3-acetylcoumarin, benzaldehyde, malononitrile, and ammonium
acetate in one-pot using HClO4–SiO2 as catalyst at 60 °C under solvent-free
condition. This method offers several advantages such as catalyst recyclability,
inexpensive catalyst, environmental friendly procedure, short reaction time, high
yields, simple work-up procedure, and easy isolation. We expect this method will
find extensive applications in the field of combinatorial chemistry, diversity-
oriented synthesis, and drug discovery.
123

An eco-friendly catalytic route for one-pot synthesis
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