Potassium phthalimide-N-oxyl: A novel, efficient, and simple organocatalyst for the one-pot three-component synthesis of various 2-amino-4H-chromene derivatives in water

Article abstract of DOI:10.1016/j.tet.2012.11.068

A wide variety of 2-amino-4H-chromene derivatives with diverse substituents on the 4H-chromene ring were efficiently prepared via one-pot, three-component reaction of an aromatic aldehyde, malononitrile (or ethyl cyanoacetate), and diverse enolizable C-H activated acidic compounds in the presence of low loading of potassium phthalimide-N-oxyl (POPINO), as a new organocatalyst, in aqueous media. This procedure is a clean, transition metal-free, and environmentally friendly approach to prepare different 2-amino-4H-chromen derivatives that offers many advantages including short reaction time, high to quantitative yields, low cost, and straightforward work-up.

Full text of DOI:10.1016/j.tet.2012.11.068

Tetrahedron 69 (2013) 1074e1085
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Potassium phthalimide-N-oxyl: a novel, efficient, and simple
organocatalyst for the one-pot three-component synthesis
of various 2-amino-4H-chromene derivatives in water
*
Mohammad G. Dekamin , Mohammad Eslami, Ali Maleki
Pharmaceutical and Biologically-Active Compounds Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 August 2012
Received in revised form 2 November 2012
Accepted 20 November 2012
Available online 28 November 2012
A wide variety of 2-amino-4H-chromene derivatives with diverse substituents on the 4H-chromene ring
were efficiently prepared via one-pot, three-component reaction of an aromatic aldehyde, malononitrile
(or ethyl cyanoacetate), and diverse enolizable CeH activated acidic compounds in the presence of low
loading of potassium phthalimide-N-oxyl (POPINO), as a new organocatalyst, in aqueous media. This
procedure is a clean, transition metal-free, and environmentally friendly approach to prepare different
2-amino-4H-chromen derivatives that offers many advantages including short reaction time, high to
quantitative yields, low cost, and straightforward work-up.
Keywords:
Potassium phthalimide-N-oxyl (POPINO)
Transition metal-free catalysis
Multi-component reactions (MCRs)
2-Amino-4H-chromene
Ó 2012 Elsevier Ltd. All rights reserved.
Green chemistry
1. Introduction
biological and pharmacological activities of chromenes depend on
the nature of substituents being either on the 4H-pyran or the
Multi-component reactions (MCRs) have emerged as an attrac-
tive and powerful strategy for organic synthesis compared to multi-
step reactions due to the creation of several new bonds in a one-pot
reaction, low number of reaction and purification steps, selectivity,
syntheticconvergence, high atomeconomy, simplicity, andsynthetic
efficiency.1 Therefore, academic and industrial research groups have
increasingly focused on the use of MCRs to synthesize a broad range
of products.2 In fact, development of MCRs can lead to new efficient
synthetic methodologies to afford many small organic compounds in
the field of modern organic, bioorganic, and medicinal chemistry.1e3
Hence, MCRs are considered as a pivotal theme in the synthesis of
many important heterocyclic compounds such as chromene de-
rivatives nowadays. The chromene moiety, including that of 2H-
chromene and 4H-chromene, belongs to a major class of natural
oxygen-containing heterocycliccompounds, which arewidely found
in edible fruits and vegetables.4 These compounds have occupied an
important place in drug research because of their various biological
and pharmacological activities such as antioxidant, antileishmanial,
antibacterial, antifungal, hypotensive, anticoagulant, antiviral,
diuretic, antiallergenic, and antitumor activities.5 Generally, the
adjacent rings.
Especially, among various chromene derivatives, 2-amino-4H-
chromene with cyano-functionality has a potential applications in
the treatment of rheumatoid, psoriasis, and cancer.6 Other prop-
erties such as laser dyes,7 optical brighteners,8 fluorescence
markers,9 pigments,10 cosmetics, and potent biodegradable agro-
chemicals11 are well known for decades.
Due to the important aforementioned properties of chromene
derivatives, considerable attention has been focused on the de-
velopment of environmentally friendly methodologies to synthe-
size 2-amino-4H-chromene scaffold by cyclization of an aromatic/
aliphatic aldehyde, malononitrile (or ethyl cyanoacetate), and di-
verse enolizable CeH activated acidic compounds. Malononitrile or
ethyl cyanoacetate has been used as a nucleophile in organic syn-
theses.12 A literature survey shows that several modified methods
have been reported using different homogeneous or heterogeneous
catalysts such as cetyltrimethylammonium chloride/bromide13,14
tetrabutylammonium bromide,15 triethylbenzylammonium chlo-
ride,16 N,N-dimethylaminoethylbenzyldimethylammonium chlo-
ride,17 chitosan,18 KSF,19 K3PO4,20 K2CO3,21 Na2CO3 under
grinding,22 nano-sized MgO,23 heteropolyacid,24 Mg/Al hydro-
talcite,25 TiCl4,26 methane sulfonic acid,27 TMG-[bmim][x],28
[BMIm]BF4,29 [2-aemim][PF6],30 DBU,31 and piperidine under mi-
crowave irradiation.32,33 However, many proposed methods for the
* Corresponding author. Tel.: þ98 21 7724 0284; fax: þ98 21 7749 1204; e-mail
address: mdekamin@iust.ac.ir (M.G. Dekamin).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.068

M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
1075
Table 1
synthesis of these compounds suffer from disadvantages including
relying on multi-step conditions, the use of toxic organic solvents
or catalysts containing transition metals, tedious work-up pro-
cedure, troublesome waste discarding, high reaction time, and low
yields.33 Thus, obviation of these limitations is necessary to develop
a simple and green synthesis of 2-amino-4H-chromenes.
Optimization of the three-component reaction of dimedone (2), 4-
chlorobenzaldehyde (3a), and malononitrile (4a) under various conditionsa
In continuation of our interest to develop the catalytic scope of
phthalimide-N-oxyl (PINO) anion as an effective, easy to handle,
and readily available Lewis base for cyclotrimerization of iso-
cyanates,34 cyanosilylation of carbonyl compounds,35 and pro-
tection of alcohols and phenols with trimethylsilyl group,36 we
decided to investigate a transition metal-free route for synthesis of
2-amino-4H-chromene with diverse substituents in the presence of
potassium phthalimide-N-oxyl 1 (POPINO) in water. Furthermore,
the use of water, as a green, natural, and high abundance solvent,
strongly enhances the rate of reaction due to its strong hydrogen
bonding ability, hydrophobic effects and high polarity (Scheme 1).37
Entry Catalyst Catalyst Solvent Temperature Time Yieldb TON TOF
loading
(mol %)
(ꢀC)
(min) (%)
(hꢁ1
)
1
2
3
4
5
6
7
8
d
d
d
d
d
10
d
rt
100
rt
15
15
15
15
15
15
10
15
15
15
15
15
15
Trace
d
d
d
d
d
d
d
d
d
d
Trace
20
35
69
75
96
72
65
98
96
63
51
d
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
EtOH
d
LIPINOc
Reflux
Reflux
Reflux
Reflux
Reflux
rt
Reflux
Reflux
Reflux
6.9 27.6
7.5 30
9.6 57.6
7.2 28.8
6.5 26
13.1 52.4
19.2 76.8
12.6 50.4
10.2 40.8
NAPINOd 10
O
POPINO
10
MAPINOe 10
K+
N
O
R
O
9
POPINO
POPINO
POPINO
POPINO
POPINO
10
7.5
5
5
5
O
X
H
(1, 5 mol%)
10
11
12
13
O
R
H
X
NC
NH2
OH
ater
W
Reflux
,
MeCN Reflux
X = CN, COOEt
a
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), dimedone (1 mmol),
malononitrile (1.1 mmol), water (2 mL), and required amount of the catalysts.
Scheme 1. One-pot three-component reaction of different enols, aldehydes, and active
methylene nitriles catalyzed by POPINO in water.
b
The yields refer to the isolated product.
Lithium phthalimide-N-oxyl.
Sodium phthalimide-N-oxyl.
Magnesium phthalimide-N-oxyl.
c
d
e
2. Results and discussion
To find the optimized conditions, a systematic study considering
different variables affecting the reaction yield was carried out for
the reaction of dimedone (2), 4-chlorobenzaldehyde (3a), and
malononitrile (4a) (molar ratio: 1:1:1.1) as the model reaction
(Scheme 2). The results have been summarized in Table 1. Only
In order to generalize the optimum conditions, different de-
rivatives of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-benzo[b]pyran
(5aer) were prepared from the one-pot reaction mixture of
dimedone (2), appropriate aldehyde (3aen), and malononitrile (4a)
or ethyl cyanoacetate (4b) in the presence of a catalytic amount of
POPINO (5 mol %) in water under reflux conditions (Scheme 2). The
results have been summarized in Table 2.
O
R
O
O
O
O
POPINO
X
Water Reflux
,
R
H
X
NC
NH2
As shown in Table 2, aromatic aldehydes with electron-
withdrawing groups (entries 1e4 and 15, 16) accelerate the re-
action compared to the electron-donating groups (entries 6e10 and
18, Table 2). In addition to the aromatic aldehydes, the reaction was
also proceeded smoothly using heterocyclic, alkenyl, and aliphatic
aldehydes in high to excellent yields (entries 11e14, Table 2). It is
also noteworthy that ethyl cyanoacetate (4b) required longer re-
action time compared to malononitrile (4a) (entries 15e18,
Table 2). This may be attributed to the capability of the cyanide
group in stabilizing the reaction intermediates compared to the
ester group.
On the next step, various derivatives of 2-amino-5,10-dioxo-
5,10-dihydro-4H-benzo[g]chromene (7aeo) were synthesized from
the aqueous reaction mixture of 2-hydroxynaphthalene-1,4-dione
(6), aromatic aldehydes (3aep), and malononitrile (or ethyl cya-
noacetate) in the presence of catalytic amount of POPINO (5 mol %)
under reflux conditions (Scheme 3). The results have been sum-
marized in Table 3. The trend of reactivity for different aldehydes is
similar to the previous ones in the case of dimedone (2).
After that, 4-hydroxycoumarin (8) was used as enolic compo-
nent to synthesize 2-amino-3,4-dihydropyrano[3,2-c]chromene
(9aen) derivatives under the optimized conditions mentioned
above, which led to the advantage of a lower reaction time
(Scheme 4).
X = CN (4a)
= COOEt (4b)
2
3
5
Scheme 2. One-pot three-component reaction of dimedone (2a), different aldehydes
(3), and active methylene nitriles (4a,b) catalyzed by POPINO in water.
a trace amount of the desired 2-amino-4-(4-chlorophenyl)-3-cy-
ano-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene (5a) was
obtained under solvent-free conditions even at 100 ꢀC (entries 1
and 2). However, the use of water, as solvent, improved the yield of
the desired product 5a slightly (entries 3 and 4). Interestingly, the
use of PINO anion with different countercations, as soluble organic
salts in water, at 10 mol % loading afforded high to quantitative
yield of the desired product 5a in refluxing water. POPINO afforded
higher yield compared to other salts including Liþ, Naþ, and Mg2þ
(entries 5e8). Furthermore, the product of reaction is completely
precipitated out from the reaction mixture after cooling to rt.
Hence, filtering the reaction mixture simply afforded the pure de-
sired product 5a. Then, the effect of catalyst loading on the com-
pletion of the reaction was studied in the next step (entries 7, 10,
and 11, Table 1). As it can be seen, 5 mol % catalyst loading gave the
best results among all by considering the catalyst turnover number
(TON) and turnover frequency (TOF) values. On the other hand, the
use of other solvents such as EtOH and MeCN afforded lower yield
of the desired product 5a under similar conditions (entries 11e13,
Table 1).
In addition to the enolizable compounds such as dimedone,
2-hydroxynaphthalene-1,4-dione, and 4-hydroxycoumarin, acti-
vated phenols including resorcinol (10), 1-naphthol (11a), and

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M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
Table 2
Synthesis of derivatives of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-benzo[b]pyran (5) via condensation of dimedone (2), different aldehydes (3), and malononitrile or ethyl
cyanoacetate (4a,b) in the presence of POPINOa
Entry
RCHO (3)
Carbon acid (4) (X)
Productb
Time (min)
Yieldc (%)
Mp (obsd) (ꢀC)
Mp (lit.) (ꢀC)
1
4a (CN)
15
96
216e218
215e21738a
3a
5a
5b
2
3
4a (CN)
20
15
98
88
214e215
214e21538b
3b
4a (CN)
180e182
179e18038c
3c
5c
4
5
4a (CN)
10
15
92
95
217e219
234e236
214e21638a
3d
5d
5e
4a (CN)
234e23538d
3e
6
7
8
4a (CN)
4a (CN)
4a (CN)
20
20
25
94
92
89
219e221
226e228
201e203
220e22238e
224e22638d
201e20238d
3f
5f
3g
5g
3h
5h
9
4a (CN)
40
98
240e242
238e23038f
3i
5i

M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
1077
Table 2 (continued )
Entry
RCHO (3)
Carbon acid (4) (X)
Productb
Time (min)
Yieldc (%)
Mp (obsd) (ꢀC)
Mp (lit.) (ꢀC)
10
4a (CN)
30
95
210e212
210e21238g
3j
5j
11
4a (CN)
25
93
183e185
182e18438h
3k
5k
12
13
4a (CN)
4a (CN)
20
30
96
95
220e222
226e228
220e22338i
3l
5l
224e22638j
3m
5m
14
4a (CN)
35
88
203e205
199e20038k
3n
5n
15
4b (COOEt)
50
91
153e155
153e15438e
3a
5o
16
4b (COOEt)
4b (COOEt)
50
60
94
87
156e157
148e150
154e15638g
3d
5p
5q
17
151e15338e
3e
18
4b (COOEt)
60
90
153e155
151e15238g
3f
5r
a
Reaction conditions: dimedone (1 mmol), aldehyde (1mmol), malononitrile or ethyl cyanoacetate (1.1 mmol), water (2 mL, reflux), POPINO (5 mol %).
All compounds are known and their structures were established from their spectral data and melting points as compared with literature values.
The yields refer to isolated products.
b
c

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M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
O
R
O
2-naphthol (11b) were also used in the synthesis of 2-amino-4H-
chromene derivatives containing fused aromatic rings (12e14)
(Scheme 5). According to the data given in Table 5,
resorcinol reacted at position-6 instead of position-2 because of
the steric hindrance between two hydroxyl groups (entries 1e10,
Table 5).
O
O
X
OH
POPINO
R
H
NH2
X
NC
Water, Reflux
O
6
O
X = CN (4a)
=COOEt (4b)
3
7
Generally, the reactions described in Schemes 2e5 are
straightforward and the desired products are precipitated out
Scheme 3. One-pot three-component reaction of 2-hydroxynaphthalene-1,4-dione
(6), different aldehydes (3), and malononitrile or ethyl cyanoacetate (4a,b).
Table 3
Synthesis of derivatives of 2-amino-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene (7) via condensation of different aldehydes (3), malononitrile or ethyl cyanoacetate (4a,b),
and 2-hydroxynaphthalene-1,4-dione (6) in the presence of POPINOa
Entry
RCHO (3)
Carbon acid (4) (X)
Productb
Time (min)
Yieldc (%)
Mp (obsd) (ꢀC)
Mp (lit.) (ꢀC)
1
4a (CN)
30
98
243e244
240e24231
3a
7a
7b
2
4a (CN)
20
96
248e250
250e25239a
3b
3o
3
4a (CN)
25
97
244e246
240e24239a
7c
4
5
6
7
4a (CN)
4a (CN)
4a (CN)
4a (CN)
30
25
20
40
92
98
91
94
249e251
232e234
263e264
240e242
252e25431
236e23839a
260e26231
242e24431
3p
7d
3c
7e
3e
7f
3f
7g

M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
1079
Table 3 (continued )
Entry
RCHO (3)
Carbon acid (4) (X)
Productb
Time (min)
Yieldc (%)
Mp (obsd) (ꢀC)
Mp (lit.) (ꢀC)
8
4a (CN)
30
93
258e260
255e25739a
3g
7h
9
4a (CN)
30
90
243e245
244e24639a
3h
7i
10
4a (CN)
40
40
40
89
93
96
245e247
209e211
197e199
243e24539a
214e21631
194e19631
3i
7j
11
4b (COOEt)
3o
7k
12
4b (COOEt)
3c
7l
13
4b (COOEt)
50
94
185e187
18839b
3e
7m
7n
14
4b (COOEt)
50
90
207e209
211e21439a
3f
15
4b (COOEt)
50
89
224e226
220e22239b
3h
7o
a
Reaction conditions: aldehyde (1 mmol), 2-hydroxynaphthalene-1,4-dione (1 mmol), malononitrile or ethyl cyanoacetate (1.1 mmol), water (2 mL, reflux), POPINO
(5 mol %).
b
c
All compounds are known and their structures were established from their spectral data and melting points as compared with literature values.
The yields refer to isolated products.

1080
M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
from the reaction mixture. Therefore, simple filtration of the re-
action mixture affords essentially pure products without any la-
borious step for isolation of the catalyst or evaporation of organic
solvent. On the other hand, in some protocols for synthesis of 2-
amino-3-cyano-4H-chromenes, hydrolysis of cyano groups,
which produce undesirable side products have been re-
ported.24,26,27 Furthermore, acid sensitive aldehydes such as cin-
namaldehyde or electron-rich heterocyclic furfural and thiophene-
2-carbaldehyde (3kem) reacted smoothly under optimized re-
action conditions to afford desired products in all studied cases
without formation of any polymerization products.3b,c Fortunately,
the present methodology did not lead to any undesirable side
products.
Scheme 4. One-pot three-component reaction of 4-hydroxycoumarin (8), different
aldehydes (3), and malononitrile or ethyl cyanoacetate (4a,b).
R
C
N
HO
OH
12
HO
O
NH2
10
NH2
The mechanism suggested in Scheme 6 seems to be reasonable
for the one-pot three-component reaction of different enols, alde-
hydes, and active methylene nitriles catalyzed by POPINO (1) in
water. The first step includes cyanocinnamonitriles or ethyl cya-
nocinnamates (18) formation from the reaction between aldehyde
and malononitrile (or ethyl cyanoacetate). Then, Michael addition
of the enolizable component (2, 6, 8, 10 or 11) on the intermediate
(18), cyclization and final tautomerization of intermediates 19 and
20, respectively, in the presence of POPINO affords the desired
product (5, 7, 9, 12e14).
CN
R
OH
O
O
POPINO
Water Reflux
13
14
R
H
NC
C
N
,
11a
CN
O
a
4
3
OH
R
NH2
11b
Scheme 5. One-pot three-component reaction of activated phenols (10,11), different
aldehydes (3), and malononitrile or ethyl cyanoacetate (4a,b).
Table 4
Synthesis of derivatives of 2-amino-3,4-dihydropyrano[3,2-c]chromene (9) via condensation of different aldehydes (3), malononitrile or ethyl cyanoacetate (4a,b), and 4-
hydroxycoumarin (8) in the presence of POPINOa
Entry
1
RCHO (3)
Carbon acid (4) (X)
4a (CN)
Productb
Time (min)
Yieldc (%)
Mp (obsd) (ꢀC)
Mp (lit.) (ꢀC)
10
96
265e267
264e26638g
3a
9a
9b
9c
2
3
4a (CN)
4a (CN)
10
10
95
90
250e252
263e265
250e25240a
3c
264e26640b
3d
4
5
4a (CN)
12
12
97
88
261e263
257e259
260e26240c
3e
9d
4a (CN)
253e25531
3f
9e
6
4a (CN)
15
98
258e260
259e26040d
3g
9f

M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
1081
Table 4 (continued )
Entry RCHO (3)
Carbon acid (4) (X)
4a (CN)
Productb
Time (min)
Yieldc (%)
Mp (obsd) (ꢀC)
Mp (lit.) (ꢀC)
7
15
91
235e237
233e23640e
253e25440f
254e25740a
3h
3i
9g
9h
8
9
4a (CN)
4a (CN)
20
15
96
95
256e257
253e255
3l
9i
10
11
4b (COOEt)
4b (COOEt)
20
15
86
87
188e190
211e213
192e19431
3a
9j
209e21238g
3b
9k
12
13
4b (COOEt)
4b (COOEt)
15
20
95
90
232e233
209e211
232e23440g
3c
9l
210e21240h
3e
9m
14
4b (COOEt)
35
92
193e195
199e20140g
3f
9n
a
Reaction conditions: aldehyde (1 mmol), 4-hydroxycoumarin (1 mmol), malononitrile or ethyl cyanoacetate (1.1 mmol), water (2 mL, reflux), POPINO (5 mol %).
All compounds are known and their structures were established from their spectral data and melting points as compared with literature values.
The yields refer to isolated products.
b
c
A comparison of the catalytic efficiency of POPINO to pre-
4H-chromene derivatives, which are often encountered in bi-
ologically and pharmacologically actives compounds. The present
methodology requires low catalyst loading of POPINO as a mild
Lewis base organocatalyst. The most important advantages of this
method include the use of cost-effective and mild organocatalyst,
aqueous conditions, excellent yields, clean and simple work-up
procedure, and avoidance of using hazardous organic solvents
that makes this method an instrumental alternative to the previous
methodologies for the scale-up of these one-pot three-component
reactions.
pare the product of model reaction (5a) using the selected
previously known catalysts is shown in Table 6 to demonstrate
that the present protocol is indeed superior to several of the
others.
3. Conclusion
In summary, we have developed a highly efficient and green
one-pot methodology for the synthesis of a wide range of 2-amino-

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M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
Table 5
Synthesis of fused aromatic rings of 2-amino-7-hydroxy-4H-chromenes (12e14) via condensation of different aldehydes (3), malononitrile or ethyl cyanoacetate (4a,b), and
resorcinol (10) or naphthol isomers (11a,b) in the presence of POPINOa
Entry
RCHO (3)
Carbon acid (4) (X)
Productb
Time (min)
Yieldc (%)
Mp (ꢀC)
Mp (lit.) (ꢀC)
1
4a (CN)
15
92
162e163
16341a
3a
12a
2
4a (CN)
20
95
188e190
185e18741b
3b
12b
3
4a (CN)
22
87
190e192
187e18941c
3o
12c
4
5
6
4a (CN)
4a (CN)
4a (CN)
15
20
30
93
90
91
228e230
230e232
182e184
225e22741a
232e23441a
185e18741a
3p
12d
12e
3e
3f
12f
7
8
9
4a (CN)
4a (CN)
4a (CN)
20
30
25
88
86
89
252e254
190e192
185e187
24941d
3g
12g
12h
193e19541d
3j
189e19132
3l
12i

M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
1083
Table 5 (continued )
Entry
RCHO (3)
Carbon acid (4) (X)
4a (CN)
Productb
Time (min)
Yieldc (%)
Mp (ꢀC)
Mp (lit.) (ꢀC)
10
25
84
207e209
204e20532
3m
12j
11
4a (CN)
4a (CN)
4a (CN)
10
10
15
93
90
87
233e235
234e236
200e202
232e23441e
234e23541f
205e20631
3a
13a
13b
13c
12
3p
13
3f
14
4a (CN)
4a (CN)
12
15
88
92
207e208
238e240
206e20841g
3a
14a
14b
15
241e24317
3p
16
4a (CN)
15
83
185e187
182e18341g
3h
14c
a
Reaction conditions: aldehyde (1 mmol), resorcinol (1 mmol), malononitrile or ethyl cyanoacetate (1.1 mmol), water (2 mL, reflux), POPINO (5 mol %).
All compounds are known and their structures were established from their spectral data and melting points as compared with literature values.
The yields refer to isolated products.
b
c
4. Experimental
determined using an Electrothermal 9100 apparatus and are
uncorrected.
4.1. General
4.2. General procedure for preparation of POPINO (1)
All of the chemicals and laboratory grade reagents were
purchased from Merck and Aldrich without further purification,
except for benzaldehyde, which was used as a fresh distilled
sample. POPINO and other salts of PINO anion were synthesized
according to our previously reported experimental procedure.34a
Analytical thin layer chromatography (TLC) for monitoring re-
actions was performed using Merck 0.2 mm silica gel 60 F-254
Al-plates. Products were characterized by spectroscopy data (IR,
1H NMR, and 13C NMR spectra) and melting points. FTIR spectra
POPINO (1) was simply prepared in high yield and purity by the
reaction of N-hydroxyphthalimide (1.63 g, 10 mmol) with an
equivalent amount of the KOH in EtOH (20 mL) under reflux con-
ditions after 5 min. The obtained deep red salt was filtered, washed
with cold EtOH (5 mL), and characterized by FTIR spectroscopy.34a
4.3. Typical procedure for the synthesis of 2-amino-4H-
chromene derivatives (5, 7, 9, 12e14)
were recorded as KBr pellets on
a Shimadzu FT IR-8400S
spectrometer. 1H NMR (500 MHz) and 13C NMR (125 MHz)
spectra were recorded using Bruker DRX-500 Avance spec-
trometer in CDCl3 at ambient temperature. Melting points were
In a 5 mL round bottom flask equipped with a magnetic bar and
condenser, enolizable compound (2, 6, 8, 10 or 11, 1 mmol), alde-
hyde (3aep, 1 mmol), and malononitrile (or ethyl cyanoacetate)

1084
M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
Scheme 6. A plausible mechanism for the one-pot three-component reaction of different enols (2, 6, 8, 10, 11), aldehydes (3), and active methylene nitriles (4) catalyzed by POPINO
(1) in water.
Table 6
Comparative synthesis of compound 5a using the reported methods versus the present method
Entry
Catalyst
mol %
Solvent
Temp (ꢀC)
Time (min)
Yield (%)
TOF (hꢁ1
)
Reference
1
2
3
4
5
6
4-(Dimethylamino)pyridine (DMAP)
LiBr
Magnesium oxide
20
10
50
10
10
5
EtOH
H2O
d
Reflux
Reflux
rt
Reflux
Reflux
50
15
15
25
30
20
30
94
95
86
94
88
91
18.8
38
17.2
18.8
26.4
36.4
38g
42
5e
38d
43
17b
Tetrabutylammonium fluoride (TBAF)
Nickel nitrate hexahydrate (Ni(NO3)2$6H2O)
N,N-Dimethylaminoethylbenzyldimethylamm-
oniumchloride
H2O
H2O
d
([PhCH2Me2NþCH2CH2NMe2]Clꢁ)
Triethylbenzylammonium chloride (TEBA)
N-Methylimidazole
7
8
9
10
100
20
10
5
H2O
H2O
H2O
H2O
90
rt
Reflux
Reflux
420
90
120
15
94
90
94
95
0.13
3
4.7
44
45
46
This work
1,4-Diazabicyclo[2.2.2]octane (DABCO)
POPINO
78.6

M.G. Dekamin et al. / Tetrahedron 69 (2013) 1074e1085
1085
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Acknowledgements
We are grateful for the financial support from The Research
Council of Iran University of Science and Technology (IUST), Tehran,
Iran (grant no. 160/354).
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