Effective preparation of 2-amino-3-cyano-4-aryl-5,10-dioxo-5,10-dihydro-4H- benzo[g]chromene and hydroxyl naphthalene-1,4-dione derivatives under ambient and solvent-free conditions

Article abstract of DOI:10.1016/j.molliq.2012.10.012

The mild basic ionic liquids, 1,8-diazabicyclo[5.4.0]-undec-7-en-8-ium acetate, pyrrolidinium acetate, pyrrolidinium formate, piperidinium acetate, piperidinium formate, N-methylimidazolium formate, and 3-hydroxypropanaminium acetate catalyzed three-component synthesis of 2-amino-3-cyano-4-aryl-5,10- dioxo-5,10-dihydro-4H-benzo[g]chromene and hydroxyl naphthalene-1,4-dione derivatives under ambient and solvent-free conditions. Simple procedure, high yields, short reaction time and environmentally benign method are advantages of these protocols. The inexpensive and non-toxic ionic liquids can be reused several times without noticeable loss of their activities. The mentioned ionic liquids show priority relative to other catalysts in the literature.

Full text of DOI:10.1016/j.molliq.2012.10.012

Journal of Molecular Liquids 177 (2013) 353–360
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Liquids
journal homepage: www.elsevier.com/locate/molliq
Effective preparation of 2-amino-3-cyano-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo
[g]chromene and hydroxyl naphthalene-1,4-dione derivatives under ambient and
solvent-free conditions
⁎
Hamid Reza Shaterian , Majid Mohammadnia
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, PO Box 98135-674, Zahedan, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 March 2012
Received in revised form 5 October 2012
Accepted 8 October 2012
Available online 26 October 2012
The mild basic ionic liquids, 1,8-diazabicyclo[5.4.0]-undec-7-en-8-ium acetate, pyrrolidinium acetate,
pyrrolidinium formate, piperidinium acetate, piperidinium formate, N-methylimidazolium formate, and
3-hydroxypropanaminium acetate catalyzed three-component synthesis of 2-amino-3-cyano-4-aryl-5,
10-dioxo-5,10-dihydro-4H-benzo[g]chromene and hydroxyl naphthalene-1,4-dione derivatives under ambient
and solvent-free conditions. Simple procedure, high yields, short reaction time and environmentally benign
method are advantages of these protocols. The inexpensive and non-toxic ionic liquids can be reused several
times without noticeable loss of their activities. The mentioned ionic liquids show priority relative to other cat-
alysts in the literature.
Keywords:
Ionic liquids
Aldehyde
© 2012 Elsevier B.V. All rights reserved.
2-Hydroxynaphthalene-1,4-dione
Malononitrile
Amine
Solvent-free
1. Introduction
basic ionic liquids such as 1,8-diazabicyclo[5.4.0]-undec-7-en-8-ium
acetate (DBU[CH3COO]), pyrrolidinium acetate ([Pyrr][CH3COO]),
Due to their unique properties, ionic liquids (ILs) have become in-
creasingly popular over the last few years in the field of green organic
synthesis [1]. ILs can be used as reaction media and catalyst for organic
syntheses [2]. The greener Ils show several advantages including their
easy work-up by straightforward extraction, high-yield isolation and
purification, homogenous and mild reaction conditions, and efficient re-
usability [3]. The functionalized ionic liquids are used instead of classical
volatile organic compounds in organic reactions [4]. In a literature re-
view, researchers collect information about this topic [1–5] and use
ILs as environmental friendly solvents and catalysts in the green organic
chemistry field.
pyrrolidinium formate ([Pyrr][HCOO]), piperidinium acetate ([Pip]
[CH3COO]), piperidinium formate ([Pip][HCOO]), N-methylimidazolium
formate ([Hmim][HCOO]), and 3-hydroxypropanaminium acetate
(3-HPAA) as catalysts for condensation reaction of aromatic alde-
hydes, malononitrile, and 2-hydroxynaphthalene-1,4-dione under
ambient and solvent-free conditions for the first time (Scheme 1).
We also used these environmental friendly ionic liquids in con-
densation reaction of aromatic aldehydes, aromatic amines, and
2-hydroxynaphthalene-1,4-dione for preparation of hydroxyl
naphthalene-1,4-dione derivatives under ambient and solvent-free con-
ditions (Scheme 2).
Multi-component reactions (MCRs) have proven to be a valuable
asset in organic and medicinal chemistry; such protocols can be used
for drug design, and drug discovery because of their simplicity, efficien-
cy, and high selectivity [6,7]. Synthesis of bioactive and complex mole-
cules should be facile, fast, and efficient with minimal workup in this
methodology [6–8].
In continuation of our research on ionic liquids and their applications
as catalyst in green organic synthesis [9–11], herein, we reported an effi-
cient method for three component synthesis of 2-amino-3-cyano-4-aryl-
5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene derivatives using weak
Literature survey showed us that few research studies were done on
DBU[CH3COO], [Pyrr][CH3COO], [Pyrr][HCOO], [Pip][CH3COO], [Pip]
[HCOO], [Hmim][HCOO], and 3-HPAA. DBU[CH3COO] was used in aza-
conjugate addition of amines to various electron deficient alkenes [12].
[Pyrr][CH3COO] was applied in Knoevenagel condensation [13]. Synthe-
sis and characterization of [Pyrr][HCOO] [14] and its transport proper-
ties [15] were investigated. Piperidinium acetate was found to be a
tandem catalyst in Knoevenagel condensation, Nazarov cyclization,
and Conia-ene reactions [16]; this catalyst also was used in synthesis
of ethyl 6-substituted-2-hydroxy-2-(trifluoromethyl)-2H-chromene-
3-carboxylates [17]. Electrochemical and physicochemical proper-
ties of [Pip][HCOO] [18] were studied. “Living” radical polymeriza-
tion of methyl methacrylate [19] and also the atom transfer radical
polymerization (ATRP) of methyl methacrylate (MMA) employing
⁎
Corresponding author. Tel.: +98 541 2446565; fax: +98 541 2431067.
E-mail address: hrshaterian@chem.usb.ac.ir (H.R. Shaterian).
0167-7322/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molliq.2012.10.012

354
H.R. Shaterian, M. Mohammadnia / Journal of Molecular Liquids 177 (2013) 353–360
O
O
CHO
X
O
NH2
CN
OH
CN
CN
Ionic liquids (Catalyst)
+
+
Solvent-free
Room Temperature
O
O
X
Ionic Liquids = 1,8-diazabicyclo[5.4.0]-undec-7-en-8-ium acetate (DBU[CH3COO]), pyrrolidinium acetate ([Pyrr][CH3COO]),
pyrrolidinium formate ([Pyrr][HCOO]), piperidinium acetate ([Pip][CH3COO]), piperidinium formate ([Pip][HCOO]), N-
methylimidazolium formate ([Hmim][HCOO]), and 3-hydroxypropanaminium acetate (3-HPAA)
Scheme 1. Synthesis of 2-amino-3-cyano-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene derivatives.
ethyl 2-bromoisobutyrate (EBiB)/CuBr as the initiating system
using N-methylimidazolium formate ([Hmim][HCOO]) were reported
[20]. 3-HPAA as a new weak basic ionic liquid was used in the preparation
of 2-amino-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile de-
rivatives [11].
2-Amino-3-cyano-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo[g]
chromene derivatives show a variety of biological activities, includ-
ing anticancer [21], anti-inflammatory [22], antimalarial [23,24],
and pesticide activities [25]. Hydroxyl naphthalene-1,4-dione de-
rivatives are fluorescent heterocyclic compounds. These fluorescent
materials are of interest in many disciplines such as emitters for
electroluminescence devices [26], molecular probes for biochemical
research [27], in traditional textile and polymer fields [28], and fluo-
rescent whitening agents [29].
(15 mol%), [Pip][CH3COO] (10 mol%), [Pip][HCOO] (10 mol%), [Hmim]
[HCOO] (15 mol%), and 3-HPAA (15 mol%) as weak basic catalyst was
stirred under ambient and solvent-free conditions for the specific time.
After completion of the reaction, 5 mL of water was added to the mix-
ture. The ionic liquid was dissolved in water and filtered for separation
of the crude product. The separated product was washed twice with
water (2×5 mL). The solid product was purified by recrystallization pro-
cedure in ethanol. All of the desired product(s) were characterized by
comparison of their physical data with those of known compounds. For
recycling the catalysts, after washing solid products with water complete-
ly, the water containing ionic liquid (IL is soluble in water) was evaporat-
ed under reduced pressure and ionic liquid was recovered and reused.
Selected spectra for two known products are given below:
2-Amino-3-cyano-4-(2,4-dichlorophenyl)-5,10-dioxo-5,10-dihydro-
4H-benzo[g]chromene (Table 2, Entry 13): orange powder; mp=
288 °C; IR (KBr): νmax =3467, 3341, 3168, 2201, 1664, 1631, 1591,
1364, 1247, and 1200 cm−1.; 1H NMR (300 MHz, DMSO-d6): δ=
4.74 (1H, s, CH), 8.08–7.48 (9 H, m, Ar) and NH2) ppm.; 13C
NMR(75 MHz, DMSO-d6): δ=37.1, 56.9, 110.3, 119.2, 119.5, 121.1,
126.2 (2C), 126.5, 129.3, 131.2, 131.3, 133.1, 136.6 (2C), 136.9,
149.5, 158.1, 177.2, and 183.6 ppm.
2-Amino-3-cyano-4-(2-nitrophenyl)-5,10-dioxo-5,10-dihydro-4-
H-benzo[g]chromene (Table 2, Entry 15): orange powder; mp=
>243 °C; IR (KBr): νmax =3429, 3338, 2207, 1666, and 1631 cm−1.;
1H NMR (300 MHz, DMSO-d6): δ=5.94 (1H, s, CH), 8.27–7.46
(10 H, m, Ar and NH2) ppm.; 13C NMR(75 MHz, DMSO-d6): δ=31.5,
55.2, 119.2, 121.6, 124.5, 126.3, 127.0, 128.9, 131.0, 131.2, 131.8,
134.3, 134.7, 135.1, 138.3, 149.0, 149.5, 159.4, 177.2, and 183.2 ppm.
2. Experimental
All reagents were purchased from Merck and Aldrich and used with-
out further purification. The weak basic ionic liquids such as DBU
[CH3COO] [12], [Pyrr][CH3COO] [13], [Pyrr][HCOO] [14], [Pip][CH3COO]
[16], [Pip][HCOO] [18], [Hmim][HCOO] [20], and 3-HPAA [11] were pre-
pared according to the reported procedure. All yields refer to isolated
products after purification. The NMR spectra were recorded on a Bruker
Avance DPX 300 MHz instrument. The spectra were measured in
DMSO-d6 relative to TMS (0.00 ppm). IR spectra were recorded on a
JASCO FT-IR 460 plus spectrophotometer. Melting points were deter-
mined in open capillaries with a BUCHI 510 melting point apparatus.
TLC was performed on silica-gel Poly Gram SIL G/UV 254 plates.
2.1. General procedure for the synthesis of 2-amino-3-cyano-4-aryl-5,
10-dioxo-5,10-dihydro-4H-benzo[g]chromene under solvent-free and
ambient conditions
2.2. Synthesis of hydroxyl naphthalene-1,4-dione derivatives under ambient
and solvent-free conditions
The mixture of the aldehydes (10 mmol), malononitrile (10 mmol),
2-hydroxynaphthalene-1,4-dione (10 mmol) and ionic liquids containing
DBU[CH3COO] (10 mol%), [Pyrr][CH3COO] (15 mol%), [Pyrr][HCOO]
The mixture of the aldehydes (10 mmol), anilines (10 mmol), 2-
hydroxynaphthalene-1,4-dione (10 mmol) and ionic liquids containing
X
O
O
CHO
X
NH2
Y
OH
Ionic liquids (Catalyst)
O
O
+
+
Solvent-free
Room Temperature
N
Y
H
OH
Ionic Liquids = 1,8-diazabicyclo[5.4.0]-undec-7-en-8-ium acetate (DBU[CH3COO]), pyrrolidinium acetate ([Pyrr][CH3COO]),
yrrolidinium formate ([Pyrr][HCOO]), piperidinium acetate ([Pip][CH3COO]), piperidinium formate ([Pip][HCOO]), N-
p
methylimidazolium formate ([Hmim][HCOO]),and 3-hydroxypropanaminium acetate (3-HPAA)
Scheme 2. Synthesis of hydroxyl naphthalene-1,4-dione derivatives.

H.R. Shaterian, M. Mohammadnia / Journal of Molecular Liquids 177 (2013) 353–360
355
Table 1
Optimization amount of A: DBU[CH3COO], B: Pyrr[CH3COO], C: Pyrr[HCOO], D: Pip[CH3COO], E: Pip[HCOO], F: [Hmim][HCOO], and G: 3-HPAA as catalysts in three component syn-
thesis of 2-amino-3-cyano-4-(4-chlorophenyl)-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene from the reaction of 2-hydroxynaphthalene-1,4-dione, malononitrile, and
4-chlorobenzaldehyde under solvent-free and ambient conditions.
Entry
Catalyst (mol%)
Time (min)
Yield (%)a
A
B
C
D
E
F
G
A
B
C
D
E
F
G
A
B
C
D
E
F
G
1
2
3
4
5
5
5
5
5
5
5
10
5
5
20
15
12
11
21
18
15
14
15
10
10
9
16
11
11
10
20
14
12
12
16
13
12
11
79
90
91
91
71
80
90
91
74
83
91
91
80
91
92
92
79
90
91
91
73
79
90
91
71
80
91
92
10
15
20
10
15
20
10
15
20
10
15
20
10
15
20
10
15
20
10
15
20
4
a
Yields refer to pure isolated products.
Table 2
Three component synthesis of 2-amino-3-cyano-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene derivatives from the reaction of 2-hydroxynaphthalene-1,4-dione,
malononitrile, and aldehydes in the presence of A: DBU[CH3COO] (10 mol%), B: Pyrr[CH3COO] (15 mol%), C: Pyrr[HCOO] (15 mol%), D: Pip[CH3COO] (10 mol%), E: Pip[HCOO]
(10 mol%), F: [Hmim][HCOO] (15 mol%) and G: 3-HPAA (15 mol%) as catalysts under solvent-free and ambient conditions.
Entry
Aldehyde
Product
Time (min)
Yield (%)a
Melting point m.p (°C)/Lit. m.p (°C) [Ref]
A
6
B
C
D
E
F
G
A
B
C
D
E
F
G
1
Ph
12
11
10
9
11
9
88
89
87
90
89
88
90
260–261/(261–262) [30]
2
3
4-ClC6H4
5
7
12
14
11
14
11
13
10
13
10
14
9
90
85
90
85
90
85
90
88
89
85
89
86
89
84
250/(249–252) [30]
4-MeC6H4
10
241–243/(242–244) [30]
4
5
3-CH3OC6H4
4-BrC6H4
7
6
13
12
16
12
14
11
14
10
14
12
10
10
87
85
86
86
88
86
88
86
88
84
88
85
89
86
248–250/(247–248) [30]
252–253/(253–255) [30]
6
3-BrC6H4
5
12
13
12
12
13
9
85
87
87
87
88
89
89
260–262/(259–260) [30]
7
8
2-ClC6H4
6
8
14
15
14
16
13
15
12
14
13
15
9
88
80
89
83
88
82
90
84
89
82
89
84
90
85
237/(236–239) [30]
4-HOC6H4
12
254–256/(257–258) [30]
9
3-NO2C6H4
4-NO2C6H4
6
6
12
12
14
13
13
12
13
12
12
13
11
10
87
88
87
89
85
85
84
89
82
88
82
87
83
88
248–250/(247–249) [30]
233–234/(234–235) [30]
10
11
4-CH3OC6H4
7
13
13
13
13
12
10
84
82
82
84
83
83
84
248/(247–248) [30]
(continued on next page)

356
H.R. Shaterian, M. Mohammadnia / Journal of Molecular Liquids 177 (2013) 353–360
Table 2 (continued)
Entry
Aldehyde
Product
Time (min)
Yield (%)a
Melting point m.p (°C)/Lit. m.p (°C) [Ref]
A
7
B
C
D
E
F
G
A
B
C
D
E
F
G
12
3,4- (CH3O)2C6H3
10
12
12
12
11
10
87
87
88
88
89
90
88
272–273/(270–271) [31]
13
2,4-Cl2C6H3
5
6
12
11
12
13
14
13
14
13
13
12
9
9
90
88
91
89
90
89
90
90
88
89
87
88
87
89
288/(286–288) [32]
14
15
2,3,4-(CH3O)3C6H2
291–292/(290–293) [31]
2-NO2C6H4
6
12
13
12
12
13
10
86
87
86
91
89
89
90
243/(242–244) [32]
16
n-Heptanal
–
24 h
–
–
–
–
–
–
–
–
–
–
–
–
–
–
a
Yields refer to the isolated pure products. The desired known pure products were characterized by a comparison of their physical data (melting points, IR, 1H and 13C NMR) with
those of the known compounds.
DBU[CH3COO] (10 mol%), [Pyrr][CH3COO] (15 mol%), [Pyrr][HCOO]
(15 mol%), [Pip][CH3COO] (10 mol%), [Pip][HCOO] (10 mol%), [Hmim]
[HCOO] (15 mol%), and 3-HPAA (15 mol%) as weak basic catalyst was
stirred under ambient and solvent-free conditions for the specific time.
After completion of the reaction, 5 mL of water was added to the mixture.
The ionic liquid was dissolved in water and filtered for separation of the
crude product. The separated product was washed twice with water
(2×5 mL). The solid product was purified by recrystallization procedure
in ethanol. All of the desired product(s) were characterized by compari-
son of their physical data with those of known compounds. For recycling
the catalysts, after washing solid products with water completely, the
water containing ionic liquid (IL is soluble in water) was evaporated
under reduced pressure and ionic liquid was recovered and reused.
Selected spectra for two known products are given below.
2-Hydroxy-3-[(4-nitrophenyl)(phenylamino)methyl]naphthalene-1,
4-dione (Table 4, Entry 4): orange powder; mp 146–147 °C.; IR (KBr):
ν
max =3394, 3316, 1661, and 1631 cm−1.; 1H NMR (300 MHz,
DMSO-d6): δ=5.99 (1H, s, CH), 7.25–8.06, (14H, m, Ar and NH), 9.25
(1H, s, OH ppm.; 13C NMR(75 MHz, DMSO-d6): δ=37.8, 120.5,
122.7, 126.0, 126.1, 127.8, 128.3, 130.1, 130.3, 131.3, 132.6, 133.0,
135.1, 144.4, 156.9, 181.6, and 183.8 ppm.
3. Results and discussions
First, to find optimization conditions, the solvent-free reaction of
4-chlorobenzaldehyde, malononitrile, 2-hydroxynaphthalene-1,4-dione
in the presence of ionic liquid, 1,8-diazabicyclo[5.4.0]-undec-7-en-8-ium
acetate, as catalyst under ambient and solvent-free conditions was select-
ed as a model. The reaction was carried out with different 1,8-diazabicyclo
[5.4.0]-undec-7-en-8-ium acetates as catalysts (5, 10, 15, 20 mol%)
(Table 1). As it was shown from Table 1, 10 mol% of DBU[CH3COO] as cat-
alyst afforded 2-amino-3-cyano-4-(4-chlorophenyl)-5,10-dioxo-5,10-
dihydro-4H-benzo[g]chromene in 5 min with 91% of yield. In continua-
tion of our study, application of ionic liquids, [Pyrr][CH3COO], [Pyrr]
[HCOO], [Pip][CH3COO], [Pip][HCOO], [Hmim][HCOO], and 3-HPAA, as
catalysts in the preparation of 2-amino-3-cyano-4-(4-chlorophenyl)-
5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene were investigated in
the model. According to the Table 1 and its general optimization proce-
dure, 15 mol% of [Pyrr][CH3COO], 15 mol% of [Pyrr][HCOO], 10 mol% of
[Pip][CH3COO], 10 mol% of [Pip][HCOO], 15 mol% of [Hmim][HCOO],
and 15 mol% of 3-HPAA as catalysts under solvent-free and ambient con-
ditions were chosen (Table 1).
Next, three-component condensation reaction of aromatic aldehydes,
malononitrile and 2-hydroxynaphthalene-1,4-dione under optimized
conditions for preparation of 2-amino-3-cyano-4-aryl-5,10-dioxo-5,10-
dihydro-4H-benzo[g]chromene derivatives was investigated (Table 2).
The efficiency and versatility of the seven weak basic ionic liq-
uids, DBU[CH3COO] (10 mol%), [Pyrr][CH3COO] (15 mol%), [Pyrr]
[HCOO] (15 mol%), [Pip][CH3COO] (10 mol%), [Pip][HCOO] (10 mol%),
[Hmim][HCOO] (15 mol%), and 3-HPAA (15 mol%), as catalysts demon-
strated by the wide range of substituted and structurally diverse alde-
hydes to synthesize the corresponding products in high to excellent
yields (Table 2). There was no effect in the reaction time and the
yield of the corresponding products when electron donating groups
2-Hydroxy-3-[phenyl(phenylamino)methyl]naphthalene-1,4-dione
(Table 4, Entry 1): orange powder, mp 144–146 °C; IR (KBr): νmax
=
3434, 3321, 1660, and 1636 cm−1.; 1H NMR (300 MHz, DMSO-d6):
δ=5.98 (1H, s, CH), 7.25–8.07 (15H, m, Ar and NH), 9.26 (1H, s, OH
ppm.; 13C NMR(75 MHz, DMSO-d6): δ=37.3, 113.4, 123.9, 125.9,
125.9, 126.4, 128.5, 129.6, 130.3, 132.6, 133.1, 133.5, 135.0, 138.1,
146.0, 156.8, 157.6, 181.8, and 184.0 ppm.
O
N
O
N
O
H
CHO
O
N
CN
O
4
+
H
N
O
CN
2
Basic ionic Liquids
as catalyst
1
3
5
O
O
O
O
NH2
N
O
6
NH
Tautomerism
N
O
7
Scheme 3. Suggested mechanism for the formation of 2-amino-3-cyano-4-phenyl-5,
10-dioxo-5,10-dihydro-4H-benzo[g]chromene.

H.R. Shaterian, M. Mohammadnia / Journal of Molecular Liquids 177 (2013) 353–360
357
100
90
80
70
60
50
40
30
20
10
0
93 93
93
92 92
92
92
91 91 91
91
91
90
90
90
90
88
89
89
89
89
87
88
87 87
87
86
86
DBU[CH3COO]
Pyrr[CH3COO]
Pyrr[HCOO]
Pip[CH3COO]
Pip[HCOO]
[Hmim][HCOO]
3-HPAA
1
2
3
4
Reaction cycles
Fig. 1. The recycling of ionic liquids such as DBU[CH3COO], [Pyrr][CH3COO], [Pyrr][HCOO], [Pip][CH3COO], [Pip][HCOO], [Hmim][HCOO], and 3-HPAA as catalysts under solvent-free
conditions using a model reaction of 4-chlorobenzaldehyde, malononitrile, 2-hydroxynaphthalene-1,4-dione.
and electron-withdrawing groups on banzaldehydes were used.
Furthermore, we examined aliphatic aldehyde such as heptanal in-
stead of benzaldehydes in the reaction. The all starting materials
in the reaction were intact without formation of any desired prod-
uct and side products after 24 h (Table 2, Entry 16). Our observation
can be confirmed with other catalysts reported in the literature [30].
The proposed mechanism for the preparation of 2-amino-3-
cyano-4-phenyl-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene from
bezaldehyde, malononitrile and 2-hydroxynaphthalene-1,4-dione using
weak basic ionic liquids as catalyst is described in Scheme 3. According
to literature report [30], 2-benzylidenemalononitrile, containing the
electron-poor C\C double bond, is formed quantitatively by Knoevenagel
addition of malononitrile to the benzaldehyde in the presence ionic liq-
uids as catalyst. Then, the 2-benzylidenemalononitrile has been attacked
by the 2-hydroxynaphthalene-1,4-dione (4) in the presence of weak
basic ionic liquids, which leads to the intermediate (5). Tautomerization
and cyclization by the nucleophilic attack of OH group on the cyano
(CN) moiety gave the intermediate (6). The subsequent tautomerization
produced the desired product.
We also investigated the recycling of the ionic liquids under
solvent-free conditions using a model reaction of 4-chlorobenzaldehyde,
malononitrile, and 2-hydroxynaphthalene-1,4-dione in the presence of
DBU[CH3COO] (10 mol%), [Pyrr][CH3COO] (15 mol%), [Pyrr][HCOO]
(15 mol%), [Pip][CH3COO] (10 mol%), [Pip][HCOO] (10 mol%), [Hmim]
[HCOO] (15 mol%), and 3-HPAA (15 mol%) (Table 2, Entry 2). After
completion of the reaction, water was added and the precipitated mix-
ture was filtered off for separation of crude products. After washing the
solid products with water completely, the water containing ionic liquid
(IL is soluble in water) was evaporated under reduced pressure and
ionic liquid was recovered and reused (Fig. 1). The recovered catalysts
were reused four runs without any loss of its activities.
Six papers were published about the synthesis of this class of
compounds [30–35]. In order to show the accessibility of the
present work in comparison with these six reported results in the litera-
ture, we summarized some of the results for the preparation of 2-amino-
3-cyano-4-(4-chlorophenyl)-5,10-dioxo-5,10-dihydro-4H-benzo[g]
chromene in Table 3. The results show that weak basic ionic liquids
such as DBU[CH3COO] (10 mol%), [Pyrr][CH3COO] (15 mol%), [Pyrr]
Table 3
Comparison the results of DBU[CH3COO], [Pyrr][CH3COO], [Pyrr][HCOO], [Pip][CH3COO], [Pip][HCOO], [Hmim][HCOO], and 3-HPAA with other catalysts in the literature such
as Et3N, CH3CN [30], HOAC/DMF [31], [bmim]OH [32], triethylbenzylammonium chloride (TEBA) [33], DBU [34], Et3N, EtOH [35] in the synthesis of 2-amino-3-cyano-4-
(4-chlorophenyl)-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene.
Entry
Catalyst (mol%)
Conditions
Time
Yield (%)a [Ref]
1
2
Et3N (10 mol%)
HOAC
CH3CN (5 mL), room temperature
DMF
24 h
5 min
80 [30]
93 [31]
MWI at 150 W
3
[bmim]OH (10 mol%)
EtOH (5 mL)
48 min
92 [32]
room temperature
Solvent-free, 85 °C
Water, reflux
EtOH/reflux
Solvent-free, room temperature
4
5
6
7
TEBA (10 mol%)
DBU (10 mol%)
Triethylamine (10 mol%)
DBU[AC] (10 mol%)
3.5 h
90 min
3 h
93 [33]
85 [34]
82 [35]
90
5 min
(Present work)
8
Pyrr[CH3COO] (15 mol%)
[Pyrr][HCOO] (15 mol%)
[Pip][CH3COO] (10 mol%)
[Pip][HCOO] (10 mol%)
[Hmim][HCOO] (15 mol%)
3-HPAA (15 mol%)
Solvent- free, room temperature
Solvent-free, room temperature
Solvent-free, room temperature
Solvent-free, room temperature
Solvent-free, room temperature
Solvent-free, room temperature
12 min
11 min
11 min
10 min
10 min
9 min
90
(Present work)
90
(Present work)
90
(Present work)
89
(Present work)
89
(Present work)
89
9
10
11
12
13
(Present work)
a
Yields refer to isolated pure products.

358
H.R. Shaterian, M. Mohammadnia / Journal of Molecular Liquids 177 (2013) 353–360
Table 4
Three component synthesis of hydroxyl naphthalene-1,4-dione derivatives from the reaction of 2-hydroxynaphthalene-1,4-dione, anilines, and aldehydes in the presence of A: DBU
[CH3COO] (10 mol%), B: Pyrr[CH3COO] (15 mol%), C: Pyrr[HCOO] (15 mol%), D: Pip[CH3COO] (10 mol%), E: Pip[HCOO] (10 mol%), F: [Hmim][HCOO] (15 mol%) and G: 3-HPAA
(15 mol%) as catalysts (Scheme 2) under solvent-free and ambient conditions.
Entry
X
Y
Product
Time (min)
Yield (%)a
Melting point m.p (°C)/Lit. m.p (°C) [Ref]
A
5
B
6
C
6
D
7
E
8
F
G
8
A
B
C
D
E
F
G
1
H
H
9
90
90 89 90 91 89 90 144–146/(143–146) [36]
2
3
4-HO
4-F
4-Me
4-Me
8
8
7
8
7
8
8
8
8
7
8
8
8
9
91
91
88 90 91 89 90 89 151–152/(149–152) [36]
91 90 88 90 88 89 146–147/(143–146) [36]
4
5
4-NO2
4-HO
H
H
5
5
6
7
7
6
7
7
8
8
8
9
9
8
88
89
89 88 89 88 89 88 146–147/(145–148) [36]
90 90 90 89 89 90 189–190/(185–190) [36]
6
7
4-MeO
4-Me
4-F
5
5
7
7
7
6
8
7
7
7
8
8
9
8
88
91
88 89 89 90 88 90 148–149/(144–147) [36]
H
90 90 89 91 91 90 151/(150–153) [36]
8
9
2-Cl
4-Me
4-F
10
5
11 10 11 11 12 12 89
89 90 91 90 91 89 151–152/(149–152) [36]
89 88 89 89 89 90 148–151/(149–152) [36]
4-NO2
7
7
8
8
8
9
87
10
2,4-Cl2
4-Me
9
10
9
10 10 10 11 88
90 89 90 90 90 89 146/(144–147) [36]
11
n-Heptanal 4-F
–
8 h
–
–
–
–
–
–
Trace
–
–
–
–
–
–
–
a
Yields refer to the isolated pure products. The desired known pure products were characterized by a comparison of their physical data (melting points, IR, 1H and 13C NMR) with
those of the known compounds.
[HCOO] (15 mol%), [Pip][CH3COO] (10 mol%), [Pip][HCOO] (10 mol%),
[Hmim][HCOO] (15 mol%), and 3-HPAA (15 mol%) are the most efficient
catalysts with respect to the reaction time, ambient and solvent-free con-
ditions, and exhibit broad applicability in terms of yield relative to other
catalysts in the literature such as Et3N, CH3CN [30], HOAC/DMF [31],
[bmim]OH [32], triethylbenzylammonium chloride [33], DBU [34], Et3N,
and EtOH [35].
condensation reaction of aromatic aldehydes, aromatic amines, and
2-hydroxynaphthalene-1,4-dione for preparation of hydroxyl
naphthalene-1,4-dione derivatives under ambient and solvent-free
conditions. As,we described optimization procedure, the reaction of
benzaldehyde, 4-fluoroaniline, and 2-hydroxynaphthalene-1,4-dione
was selected as a model. The reaction was carried out in the presence
of different catalysts, DBU[CH3COO] (5, 10, 15, and 20 mol%), [Pyrr]
[CH3COO] (5, 10, 15, and 20 mol%), [Pyrr][HCOO] (5, 10, 15, and
20 mol%), [Pip][CH3COO] (5, 10, 15, and 20 mol%), [Pip][HCOO] (5, 10,
We also applied DBU[CH3COO], [Pyrr][CH3COO], [Pyrr][HCOO],
[Pip][CH3COO], [Pip][HCOO], [Hmim][HCOO], and 3-HPAA in

H.R. Shaterian, M. Mohammadnia / Journal of Molecular Liquids 177 (2013) 353–360
359
O
O
CHO
H
NH2
H
O
H
C
C
H
NH
-H2O
O
4
+
N
Basic ionic Liquids
as catalyst
O
8
10
9
O
11
Tautomerism
O
C
H
NH
OH
12
O
Product
Scheme 4. Suggested mechanism for the formation of 2-hydroxy-3-(phenyl(phenylamino)methyl)naphthalene-1,4-dione.
100
90
80
70
60
50
40
30
20
10
0
93
93
91
92 92
92
92
90 90
91
90 90 90
90
89
89
89
88 88
88
87
85 85
87
87
86
86 86
DBU[CH3COO]
Pyrr[CH3COO]
Pyrr[HCOO]
Pip[CH3COO]
Pip[HCOO]
[Hmim][HCOO]
3-HPAA
1
2
3
4
Reaction cycles
Fig. 2. The recycling of DBU[CH3COO], Pyrr[CH3COO], Pyrr[HCOO], Pip[CH3COO], Pip[HCOO], [Hmim][HCOO], 3-HPAA as catalyst under ambient and solvent-free conditions using a
model reaction of benzaldehyde, 4-fluoroaniline, and 2-hydroxynaphthalene-1,4-dione.
15, and 20 mol%), [Hmim][HCOO] (5, 10, 15, and 20 mol%), and 3-HPAA
(5, 10, 15, and 20 mol%) under solvent-free and ambient conditions.
The best results were obtained when the amount of catalysts was cho-
sen as DBU[CH3COO] (10 mol%), [Pyrr][CH3COO] (15 mol%), [Pyrr]
[HCOO] (15 mol%), [Pip][CH3COO] (10 mol%), [Pip][HCOO] (10 mol%),
[Hmim][HCOO] (15 mol%), and 3-HPAA (15 mol%). Then, three-
component condensation reaction of aromatic aldehydes, anilines,
and 2-hydroxynaphthalene-1,4-dione under optimized conditions
for preparation of hydroxyl naphthalene-1,4-diones was investigat-
ed (Table 4). A wide range of substituted and structurally diverse
Table 5
Comparison the results of DBU[CH3COO], [Pyrr][CH3COO], [Pyrr][HCOO], [Pip][CH3COO], [Pip][HCOO], [Hmim][HCOO], and 3-HPAA with InCl3 [36] in the synthesis
2-hydroxy-3-(phenyl(phenylamino)methyl)naphthalene-1,4-dione.
Entry
Catalyst (mol%)
Conditions
Time
Yield (%)a [Ref]
1
2
InCl3 (20 mol%)b
H2O (Reflux)
Solvent-free, room temperature
8 h
5 min
85 [36]
91
DBU[CH3COO] (10 mol%)c
(Present work)
90
(Present work)
90
(Present work)
89
(Present work)
91
(Present work)
91
3
4
5
6
7
8
Pyrr[CH3COO](15 mol%)c
[Pyrr][HCOO](15 mol%)c
[Pip][CH3COO] (10 mol%)c
[Pip][HCOO](10 mol%)c
[Hmim][HCOO](15 mol%)c
3-HPAA (15 mol%)c
Solvent-free, room temperature
Solvent-free, room temperature
Solvent-free, room temperature
Solvent-free, room temperature
Solvent-free, room temperature
Solvent-free, room temperature
7 min
6 min
7 min
7 min
8 min
8 min
(Present work)
90
(Present work)
a
Yields refer to isolated pure products.
InCl3 as catalyst isn't reusable.
The weak basic ionic liquids are recyclable catalysts.
b
c

360
H.R. Shaterian, M. Mohammadnia / Journal of Molecular Liquids 177 (2013) 353–360
[3] J. Dupont, R.F. Souza, P.A.Z. Suarez, Chemical Reviews 102 (2002) 3667–3692.
[4] J.S. Wilkes, Green Chemistry 4 (2002) 73–80.
[5] A. Chrobok, S. Baj, W. Pudło, A. Jarzebski, Applied Catalysis A: General 366 (2009)
aldehydes and anilines were used and the corresponding products
were synthesized in high to excellent yields (Table 4). Heptanal as
aliphatic aldehydes produced trace of desired compounds and al-
most all of starting materials were intact.
22–28.
[6] A. Nefzi, J.M. Ostresh, R.A. Houghten, Chemical Reviews 97 (1997) 449–472.
[7] L.A. Thompson, Current Opinion in Chemical Biology 4 (2000) 324–337.
[8] A. Dömling, Current Opinion in Chemical Biology 6 (2002) 306–313.
[9] H.R. Shaterian, M. Arman, F. Rigi, Journal of Molecular Liquids 158 (2011)
145–150.
[10] H.R. Shaterian, M. Ranjbar, K. Azizi, Journal of Molecular Liquids 162 (2011)
95–99.
[11] H.R. Shaterian, A.R. Oveisi, Journal of the Iranian Chemical Society 8 (2011)
545–552.
[12] A.G. Ying, L. Liu, G.F. Wu, G. Chen, X.Z. Chen, W.D. Ye, Tetrahedron Letters 50
(2009) 1653–1657.
[13] A.M. Dumas, A. Seed, A.K. Zorzitto, E. Fillion, Tetrahedron Letters 48 (2007)
7072–7074.
[14] M. Anouti, M. C-Caravanier, Y. Dridi, H. Galiano, A. Lemordant, Journal of Physical
Chemistry 112 (2008) 13335–13343.
[15] M. Anouti, J. Jacquemin, D. Mordant, Fluid Phase Equilibria 297 (2010) 13–22.
The proposed mechanism for the preparation of 2-hydroxy-3-
(phenyl(phenylamino)methyl)naphthalene-1,4-diones from the re-
action of benzaldehyde, aniline and 2-hydroxynaphthalene-1,4-dione
using weak basic ionic liquid as catalyst is described in Scheme 4.
According to literature report [36], imine was formed by condensation re-
action of benzaldehyde with aniline. Then, the 2-hydroxynaphthalene-1,
4-dione has been attacked to imine in the presence of basic catalyst.
Tautomerization converts intermediate (11) to the desired product.
The recycling of the ionic liquids was studied such as the above
procedure using a model reaction of benzaldehyde, 4-fluoroaniline,
and 2-hydroxynaphthalene-1,4-dione. The recovered catalysts were
reused four runs without any loss of its activities (Fig. 2).
[16] L. Liu, L. Wei, Y. Lu, J. Zhang, Chemistry
A European Journal 16 (2010)
11813–11817.
In order to show the accessibility of the present work in compar-
ison with only one reported results [36] in the literature, we sum-
marized some of the results for the preparation of 2-hydroxy-3-
(phenyl(phenylamino)methyl)naphthalene-1,4-dione in Table 5.
The results show that weak basic ionic liquids such as DBU
[CH3COO] (10 mol%), [Pyrr][CH3COO] (15 mol%), [Pyrr][HCOO]
(15 mol%), [Pip][CH3COO] (10 mol%), [Pip][HCOO] (10 mol%),
[Hmim][HCOO] (15 mol%), and 3-HPAA (15 mol%) are the most ef-
ficient catalysts with respect to the reaction time and yields of the
product relative to catalytic amount of InCl3 under reflux condi-
tions in water [36].
[17] D.L. Chizhov, V.Ya. Sosnovskikh, M.V. Pryadeina, Y.V. Burgart, V.I. Saloutin,
V.N. Charushin, Synlett 2 (2008) 281–285.
[18] T.-Y. Wu, S.-G. Su, Y.-C. Lin, H.P. Wang, M.-W. Lin, S.-T. Gung, I.-W. Sun,
Electrochimica Acta 56 (2010) 853–862.
[19] G. Lai, Z. Hu, J. Wu, L. Wu, Y. Li, Acta Polymerica Sinica 3 (2006) 549–552.
[20] H. Ziqiang, Z. Fang, Q. Huayu, L. Guoqiao, W. Jirong, L. Wenqing, Journal of Wuhan
University of Technology-Materials Science Edition 25 (2010) 785–788.
[21] M. Ough, A. Lewis, E.A. Bey, J. Gao, J.M. Ritchie, W. Bornmann, D.A. Boothman, L.W.
Oberley, J.J. Cullen, Cancer Biology and Therapy 4 (2005) 95–102.
[22] D.O. Moon, Y.H. Choi, N.D. Kim, Y.M. Park, G.Y. Kim, International
Immunopharmacology 7 (2007) 506–514.
[23] V.F. De Andrade-Neto, M.O.F. Goulart, J.F. Da Silva Filho, M.J. Da Silva, M.D.C.F.R.
Pinto, A.V. Pinto, M.G. Zalis, L.H. Carvalho, A.U. Krettli, Bioorganic & Medicinal
Chemistry Letters 14 (2004) 1145–1149.
[24] P.S. Elisa, E.B. Ana, A.G. Ravelo, D.J. Yapu, A.G. Turba, Chemistry and Biodiversity 2
(2005) 264–274.
[25] A.M. Shestopalov, Y.M. Emelianova, V.N. Nesterov, Russian Chemical Bulletin 52
(2003) 1164–1171.
4. Conclusion
Seven mild basic ionic liquids, 1,8-diazabicyclo[5.4.0]-undec-7-en-8-
ium acetate, pyrrolidinium acetate, pyrrolidinium formate, piperidinium
acetate, piperidinium formate, N-methylimidazolium formate, and
3-hydroxypropanaminium acetate catalyzed three-component
synthesis of 2-amino-3-cyano-4-aryl-5,10-dioxo-5,10-dihydro-4
H-benzo[g]chromene and hydroxyl naphthalene-1,4-dione derivatives
under ambient and solvent-free conditions. The main advantages of
the present synthetic protocol are mild, solvent-free conditions, eco-
friendly catalysts and easy reaction work-up procedure. It is expected
that the present methodology will find application in organic synthesis.
[26] K. Hunger, Industrial Dyes, WILEY-VCH Verlag, Gmbh & Co. KGaA, Weinheim,
Germany, 2003.
[27] A. Dmitry, A. Pavel, Chemical Communications 12 (2003) 1394–1395.
[28] H. Gold, in: K. Venkataraman (Ed.), Pergamon, Academic Press, New York, USA,
1971.
[29] E. Belgodere, R. Bossio, S. Chimichi, V. Passini, R. Pepino, Dyes and Pigments 4
(1985) 59–71.
[30] A. Shaabani, R. Ghadari, S. Ghasemi, M. Pedarpour, A.H. Rezayan, A. Sarvary, S.W.
Ng, Journal of Combinatorial Chemistry 11 (2009) 956–959.
[31] X.-H. Wang, X.-H. Zhang, S.-J. Tu, F. Shi, X. Zou, S. Yan, Z.-G. Han, W.-J. Hao, X.-D.
Cao, S.-S. Wua, Journal of Heterocyclic Chemistry 46 (2009) 832–836.
[32] Y. Yu, H. Guo, X. Li, Journal of Heterocyclic Chemistry 48 (2011) 1264–1268.
[33] Y. Changshenga, Y. Chenxiaa, L. Tuanjiea, T. Shujiang, Chinese Journal of Chemis-
try 27 (2009) 1989–1994.
[34] J.M. Khurana, B. Nand, P. Saluja, Tetrahedron 66 (2010) 5637–5641.
[35] M. Khodeir, F. El-Taweel, A. Elagamey, Pharmazie 47 (1992) 486–487.
[36] M. Dabiri, Z.N. Tisseh, A. Bazgir, Dyes and Pigments 89 (2011) 63–69.
Acknowledgments
We are thankful to the University of Sistan and Baluchestan Re-
search Council for the partial support of this research.
References
[1] P. Wasserscheid, T. Welton, Ionic Liquids in Synthesis, Wiley-VCH, Weinheim,
Germany, 2008.
[2] P. Wasserscheid, W. Keim, Angewandte Chemie, International Edition 39 (2000)
3773–3789.