Efficient and eco-friendly synthesis of 2-amino-4H-chromene derivatives using catalytic amount of tetrabutylammonium chloride (TBAC) in water and solvent-free conditions

Article abstract of DOI:10.1007/s13738-012-0073-8

A simple, efficient and eco-friendly procedure has been developed using tetrabutylammonium chloride as catalyst for the synthesis of 2-amino-4H-chromene derivatives in water and solvent-free neat conditions. The present methodology offers several advantag

Full text of DOI:10.1007/s13738-012-0073-8

J IRAN CHEM SOC (2012) 9:599–605
DOI 10.1007/s13738-012-0073-8
ORIGINAL PAPER
Efficient and eco-friendly synthesis of 2-amino-4H-chromene
derivatives using catalytic amount of tetrabutylammonium
chloride (TBAC) in water and solvent-free conditions
•
Hossein Mehrabi Nafiseh Kamali
Received: 6 February 2011 / Accepted: 9 December 2011 / Published online: 25 February 2012
Ó Iranian Chemical Society 2012
Abstract A simple, efficient and eco-friendly procedure
has been developed using tetrabutylammonium chloride as
catalyst for the synthesis of 2-amino-4H-chromene deriv-
atives in water and solvent-free neat conditions. The
present methodology offers several advantages such as
excellent yields, short reaction time and environmentally
benign milder reaction conditions.
reagents to facilitate the ion-exchange process until an
aqueous phase discretely appears in the system [5, 6].
2-Aminochromenes are an important class of compounds
found as the main components of many naturally occurring
products employed as cosmetics and pigments and utilized
as potential biodegradable agrochemicals [7–10]. Thus, the
synthesis of 2-aminochromenes is of much importance to
organic chemists. These compounds are generally prepared
by reacting aldehydes, activated methylene compounds and
activated phenols in organic solvents (i.e., ethanol [11],
acetonitrile) and in the presence of organic bases like
piperidine, which are frequently utilized in stoichiometric
amounts [12–14]. A literature survey revealed several
modified procedures using cetyltrimethylammonium chlo-
ride (CTAC) [15], cetyltrimethylammonium bromide
(CTAB) coupled with ultrasound [16], c-alumina [17],
K2CO3 [7], nanosize MgO [18], heteropolyacid [19],
hexadecyltrimethylammonium bromide (HTMAB) [20],
triethylbenzylammonium chloride (TEBA) [21], TiCl4 [22],
N,N-dimethylaminoethylbenzyldimethylammonium chloride
[23], sodium carbonate [24], NaOAc/KF [25], NaBr [26]
and NaI [27]. However, the applications of some of these
methods are limited due to the moderate yields of the
product, longer reaction time and toxic solvents.
Keywords Tetrabutylammonium chloride ꢀ
Phase-transfer catalysis ꢀ One-pot synthesis ꢀ
Solvent-free ꢀ 2-Amino-4H-chromenes
Introduction
The technique of phase-transfer catalysis (PTC) using
quaternary salts as catalysts has been established as one of
the most useful methods for the acceleration of heteroge-
neous reactions [1, 2]. The recent trend toward ‘‘green and
sustainable chemistry’’ has again attracted a strong atten-
tion to its significance for organic syntheses. Water
sometimes interferes with the desired reaction through
suppression or diversion. Thus, PTC was often carried out
with solid reagent salts in the absence of water (solid–
liquid PTC). In many solid–liquid systems, however, small
quantities of water play an important role in the catalytic
processes [3, 4]. The catalytic reactions hardly proceeded
under anhydrous conditions. Though the role of water is
still ambiguous, it has been often assumed that water
hydrates the surface of the crystal lattice of inorganic
In view of the above observation, we decided to develop
an environmentally and green approach for the synthesis of
some 2-amino-4H-chromenes catalyzed by tetrabutylam-
monium chloride (TBAC) in water and solvent-free neat
conditions (Scheme 1).
Experimental
H. Mehrabi (&) ꢀ N. Kamali
Department of Chemistry, Rafsanjan Vali-e-Asr University,
77176 Rafsanjan, Iran
e-mail: mehraby_h@yahoo.com
All chemicals were purchased from Aldrich and Merck
with high-grade quality, and used without any purification.
123

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J IRAN CHEM SOC (2012) 9:599–605
NH2
CN
2
3
3
X
CN
Ar
4
Ar
NH2
1
O
2
1
Y
10
7
4
5
CN
O
9
8
TBAC (10 mol%)
Water / Neat
6
7
ArCHO
+
+
5
+
10
CN
6
8
9
X, Y= H or OH
1
4
2
3
5
Scheme 1 Synthesis of 2-amino-4H-chromenes by condensation of aldehydes, malononitrile and a- or b-naphthol
126.50, 127.50, 132.50, 138.10, 142.50, 147.80, 148.70,
160.00 ppm (Found: C, 73.54; H, 5.07; N, 7.84
C22H18N2O3: calculated C, 73.73; H, 5.06; N, 7.82%].
All melting points were obtained by Bamslead Electro-
thermal 9200 apparatus and are uncorrected. The reactions
were monitored by TLC and all yields refer to isolated
products. 1H and 13C NMR spectra were recorded in
DMSO on a Bruker 500 and 400 MHz spectrometer.
Infrared spectra were recorded on a Bruker FT-IR Equinax-
55 spectrophotometer in KBr with absorption in cm-1. All
products were characterized by their spectra and physical
data.
2-Amino-4-phenyl-4H-benzo[h]chromene-3-carbonitrile
(4a) [16] Mp: 210–212 °C, [210–211 °C]. IR (KBr):
3,454, 3,318, 3,020, 2,932, 2,205, 1,656, 1,600, 1,572,
1,450, 1,372, 1,267, 1,100, 1,022, 811, 744 cm-1. 1H NMR
(400 MHz, DMSO): d = 4.90 (1H, s, H-4), 7.10 (2H, s,
NH2), 7.07–7.12 (6H, m, H-5,20,30,40,50,60), 7.56–7.66 (3H,
m, H-6,8,9), 7.94 (1H, d, J = 8.4, H-7), 8.23 (1H, d,
J = 8.4, H-10) ppm. 13C NMR (100 MHz, DMSO):
d = 41.3, 54.3, 115.5, 120.8, 121.3, 121.7, 122.4, 123.0,
125.4, 126.3, 127.4, 127.8, 128.4, 130.5, 131.7, 140.4,
142.7, 158.3 ppm.
General procedure
Method A A mixture of a-naphtol or b-naphtol (1 mmol),
malononitrile (1.5 mmol), an aromatic aldehyde (1 mmol)
and TBAC (10 mol%) in H2O (5 mL) for the synthesis of
2-amino-4H-chromenes were stirred at 100 °C for appro-
priate time. Upon completion, monitored by TLC, the
reaction mixture was allowed to cool at room temperature.
The solid was filtered off and washed with water and
purified by recrystallization from ethanol.
2-Amino-4-(3-chlorophenyl)-4H-benzo[h]chromene-3-car-
bonitrile (4e) [16] Mp: 218–220 °C, [229–230 °C]. IR
(KBr): 3,455, 3,340, 3,023, 2,930, 2,210, 1,645, 1,600,
1
1,580, 1,470, 1,378, 1,266, 1,030, 816, 750, 700 cm-1. H
NMR (400 MHz, DMSO): d = 4.98 (1H, s, H-4), 7.24
(2H, s, NH2), 7.13 (1H, d, J = 8.4, H-5), 7.32–7.38 (3H, m,
H-40,50,60), 7.23 (1H, s, H-20), 7.56–7.66 (3H, m, H-6,8,9),
7.89 (1H, d, J = 8.4, H-7), 8.26 (1H, d, J = 8.4, H-10)
ppm. 13C NMR (100 MHz, DMSO): d = 42.7, 55.2, 118.6,
120.4, 120.7, 121.5, 122.6, 124.4, 125.1, 126.2, 127.1,
127.3, 128.1, 129.2, 130.6, 131.7, 135.9, 141.4, 145.6,
161.4 ppm.
Method B A mixture of a-naphthol or b-naphthol
(1 mmol), malononitrile (1.5 mmol), an aromatic aldehyde
(1 mmol) and TBAC (10 mol%) were under solvent-free
and heated in an oil bath maintained at 100 °C for appro-
priate time. Upon completion, monitored by TLC, the
reaction mixture was allowed to cool at room temperature.
The reaction was worked up as in method A.
2-Amino-4-(2,4-dichlorophenyl)-4H-benzo[h]chromene-3-
carbonitrile (4g) [16] Mp: 223–225 °C, [212–214 °C]. IR
(KBr): 3,454, 3,336, 3,022, 2,182, 1,667, 1,600, 1,572,
Spectroscopic data
2-Amino-4-(3,4-dimethoxyphenyl)-4H-benzo[h]chromene-
3-carbonitrile (4k) Mp: 206–208 °C, IR (KBr): 3,381,
3,326, 3,211, 2,192, 1,661, 1,617, 1,510, 1,411, 1,376,
1,260, 1,228, 1,138, 1,028, 749 cm-1. 1H NMR (500 MHz,
DMSO): d = 3.69 (6H, s, 2-OCH3), 4.83 (1H, s, H-4), 6.73
(1H, m, H-60), 6.86 (1H, s, H-10), 6.88 (1H, m, H-50), 7.09
(2H, br s, NH2), 7.12 (1H, d, J = 8.7, H-5), 7.52–7.62 (3H,
m, H-6,8,9), 7.85 (1H, d, J = 8.4, H-7), 8.24 (1H, d,
J = 8.4, H-10) ppm. 13C NMR (125 MHz, DMSO):
d = 40.40, 55.47, 55.49, 56.50, 111.60, 112.10, 118.00,
119.80, 120.40, 120.60, 122.70, 123.60, 126.10, 126.40,
1
1,500, 1,466, 1,378, 1,200, 1,050, 860, 811, 755 cm-1. H
NMR (400 MHz, DMSO): d = 5.47 (1H, s, H-4), 7.30 (2H,
s, NH2), 6.98 (1H, d, J = 8.4, H-60), 7.59–7.61 (2H, m,
H-30,50), 7.39 (1H, d, H-5), 7.69–7.89 (3H, m, H-6,8,9), 8.03
(d, 1H, J = 8.4, H-7), 8.25 (d, 1H, J = 8.4, H-10) ppm. 13
C
NMR (100 MHz, DMSO): d = 43.7, 56.7, 117.5, 119.8,
120.2, 121.9, 123.2, 124.8, 125.0, 125.3, 127.8, 128.0, 128.6,
129.7, 131.4, 133.6, 135.2, 141.5, 146.2, 158.7 ppm.
2-Amino-4-(4-nitrophenyl)-4H-benzo[h]chromene-3-carbo-
nitrile (4b) [16] Mp: 235–236 °C, [239–241 °C]. IR
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J IRAN CHEM SOC (2012) 9:599–605
601
(KBr): 3,460, 3,335, 2,196, 1,665, 1,600, 1,575, 1,536,
1,500, 1,346, 1,270, 1,195, 1,100, 805, 770 cm-1. 1H NMR
(400 MHz, DMSO): d = 5.12 (1H, s, H-4), 7.29 (2H, s,
NH2), 7.05 (1H, d, J = 8.4, H-5), 7.5–7.7 (3H, m, H-6,8,9),
7.52 (d, 2H, H-20,60), 7.90 (1H, d, J = 8.4, H-7), 8.15 (2H,
d, H-30,50), 8.27 (1H, d, J = 8.4, H-10) ppm. 13C NMR
(100 MHz, DMSO): d = 43.1, 54.8, 119.3, 125.7, 121.1,
122.6, 123.6, 124.9, 126.5, 127.2, 128.6, 129.3, 130.6,
133.7, 136.3, 140.9, 146.2, 160.7 ppm.
2-Amino-4-(4-fluorophenyl)-4H-benzo[h]chromene-3-car-
bonitrile (4d) [21] Mp: 229–231 °C, [230–232 °C]. IR
(KBr): 3,385, 3,147, 2,217, 1,658, 1,593, 1,446, 1,105,
1
803 cm-1. H NMR (400 MHz, DMSO): d = 4.82 (1H, s,
H-4), 6.86 (2H, s, NH2), 7.08 (1H, d, H-5, J = 8.0),
7.32–7.43 (4H, m, Ar), 7.90–7.55 (3H, m, Ar), 7.72 (1H, d,
H-7, J = 8.0), 8.05 (1H, d, H-10, J = 8.0) ppm. 13C NMR
(100 MHz, DMSO): d = 46.3, 57.2, 120.3, 122.5, 122.7,
123.7, 124.8, 125.6, 126.0, 126.2, 127.2, 128.4, 131.6,
132.7, 134.3, 141.7, 146.8, 159.4 ppm.
2-Amino-4-(4-bromophenyl)-4H-benzo[h]chromene-3-car-
bonitrile (4h) [16] Mp: 240–241 °C, [242–244 °C]. IR
(KBr): 3,472, 3,329, 2,194, 1,669, 1,601, 1,410, 1,376,
2-Amino-4-(4-methylphenyl)-4H-benzo[h]chromene-3-
carbonitrile (4j) [21] Mp: 202–204 °C, [205–206 °C]. IR
(KBr): 3,394, 3,268, 2,210, 1,654, 1,592, 1,436, 1,383,
1
1,103, 780 cm-1. H NMR (500 MHz, DMSO): 4.91 (1H,
1
s, H-4), 7.06 (1H, d, H-5), 7.19 (2H, m, H-20,60), 7.23 (2H,
s, NH2), 7.48 (2H, d, H-30,50), 7.51–7.63 (3H, m, H-6,8,9),
7.85 (1H, d, H-7), 8.26 (1H, d, H-10) ppm. 13C NMR
(125 MHz, DMSO): d = 40.2, 55.8, 117.2, 120.0, 120.2,
120.6, 122.7, 123.9, 125.9, 126.6, 126.7, 127.5, 129.8,
131.5, 132.6, 142.7, 144.9, 160.1 ppm.
1,127 cm-1. H NMR (500 MHz, DMSO): d = 2.25 (3H,
s, CH3), 4.53 (1H, s, H-4), 6.90 (2H, s, NH2), 7.08 (1H, s,
H-5, J = 8), 7.15–7.26 (4H, m, Ar), 7.34–7.41 (3H, m, Ar),
7.66 (1H, d, H-7, J = 8), 8.04 (1H, d, H-10, J = 8) ppm.
13C NMR (125 MHz, DMSO): d = 31.4, 43.7, 55.9, 119.7,
120.3, 122.0, 122.7, 123.8, 124.0, 125.6, 126.2, 127.4,
128.7, 130.5, 132.7, 133.7, 141.6, 145.2, 160.6 ppm.
2-Amino-4-(4-methoxyphenyl)-4H-benzo[h]chromene-3-
carbonitrile (4l) [19] Mp: 188–190 °C, [182–183 °C]. IR
(KBr): 3,430, 3,337, 2,200, 1,678, 1,592, 1,436, 1,383,
1,123, 794 cm-1. 1H NMR (500 MHz, DMSO): d = 3.90
(3H, s, OCH3), 4.54 (1H, s, H-4), 6.82 (2H, s, NH2), 7.0
(1H, s, H-5, J = 8), 7.10–7.22 (4H, m, Ar), 7.40–7.45
(3H, m, Ar), 7.56 (1H, d, H-7, J = 8), 8.15 (1H, d, H-10,
J = 8) ppm. 13C NMR (125 MHz, DMSO): d = 40.8,
55.1, 56.3, 118.7, 121.9, 122.2, 122.8, 123.5, 124.7,
125.1, 126.9, 127.7, 128.2, 129.4, 131.7, 133.4, 143.5,
148.3, 161.2 ppm.
2-Amino-4-(2-methylphenyl)-4H-benzo[h]chromene-3-
carbonitrile (4i) Mp: 246–248 °C. IR (KBr): 3,374,
3,224, 2,279, 1,662, 1,600, 1,586, 1,543, 1,357, 1,265,
1
1,165 cm-1. H NMR (500 MHz, DMSO): d = 2.28 (3H,
s, CH3), 5.04 (1H, s, H-4), 7.07 (2H, s, NH2), 7.27 (1H, d,
J = 8.2, H-5), 7.29–7.38 (3H, m, Ar), 7.42 (1H, d, J = 8.2,
H-6), 7.50–7.62 (3H, m, Ar), 7.82 (1H, d, J = 8.4, H-7),
8.17 (1H, d, J = 8.4, H-10) ppm. 13C NMR (125 MHz,
DMSO): d = 30.5, 43.6, 56.7, 119.8, 120.5, 121.3, 122.9,
123.5, 124.7, 125.0, 126.7, 128.2, 128.9, 129.8, 131.3,
132.8, 133.1, 135.6, 141.9, 142.2, 159.7 ppm.
2-Amino-4-(4-chlorophenyl)-4H-benzo[h]chromene-3-car-
bonitrile (4f) [19] Mp: 284–286 °C, [231–232 °C]. IR
(KBr): 3,421, 3,253, 2,208, 1,662, 1,596, 1,436, 1,380,
2-Amino-4-(4-dimethylaminophenyl)-4H-benzo[h]chro-
mene-3-carbonitrile (4m) [16] Mp: 181–184 °C,
[179–180 °C]. IR (KBr): 3,415, 3,278, 2,186, 1,656, 1,599,
1
1,139, 805 cm-1. H NMR (400 MHz, DMSO): d = 4.55
1
(1H, s, H-4), 6.70 (2H, s, NH2), 7.1 (1H, d, H-5, J = 8),
7.21–7.33 (4H, m, Ar), 7.40–7.45 (3H, m, Ar), 7.56 (1H, d,
H-7, J = 8), 8.15 (1H, d, H-10, J = 8) ppm. 13C NMR
(100 MHz, DMSO): d = 42.6, 55.6, 119.8, 120.6, 122.1,
122.4, 123.7, 125.4, 125.9, 126.5, 127.6, 128.8, 130.2,
132.8, 133.9, 142.4, 147.6, 160.8 ppm.
1,456, 1,397, 1,184 cm-1. H NMR (500 MHz, DMSO):
d = 3.15 (6H, s, NMe2), 4.57 (1H, s, H-4), 6.97 (2H, s,
NH2), 7.17 (1H, s, H-5, J = 8), 7.19–7.25 (4H, m, Ar),
7.33–7.47 (3H, m, Ar), 7.72 (1H, d, H-7, J = 8), 8.23 (1H,
d, H-10, J = 8 Hz) ppm. 13C NMR (125 MHz, DMSO):
d = 43.7, 45.7, 58.3, 117.4, 121.5, 122.5, 123.2, 123.8,
124.6, 125.2, 126.7, 127.2, 128.6, 131.6, 132.3, 134.4,
140.2, 144.6, 158.9 ppm.
2-Amino-4-(3-nitrophenyl)-4H-benzo[h]chromene-3-car-
bonitrile (4c) [24] Mp: 210–212 °C, [210–213 °C]. IR
(KBr): 3,404, 3,237, 2,206, 1,674, 1,610, 1,572, 1,521,
1,507, 1,356, 1,261, 1,128, 805 cm-1. 1H NMR (500 MHz,
DMSO): d = 5.24 (1H, s, H-4), 7.17 (2H, s, NH2), 7.22
(1H, d, J = 8.4, H-5), 7.29–7.37 (3H, m, H-6,8,9), 7.45
(1H, s, H-20), 7.52–7.63 (3H, m, H-40,50,60), 7.82 (1H, d,
J = 8.4, H-7), 8.17 (1H, d, J = 8.4, H-10) ppm. 13C NMR
(125 MHz, DMSO): d = 42.7, 55.7, 120.7, 121.5, 121.8,
122.4, 123.3, 124.2, 125.6, 126.1, 128.2, 128.7, 129.8,
130.3, 132.4, 133.9, 135.7, 141.6, 145.4, 158.3 ppm.
2-Amino-4-(4-fluorophenyl)-4H-benzo[f]chromene-3-car-
bonitrile (5d) Mp: 229–230 °C; IR (KBr): 3,460, 3,358,
2,186, 1,661, 1,592, 1,506, 1,403, 1,234, 1,221, 838,
1
804 cm-1. H NMR (500 MHz, DMSO): d = 5.34 (1H, s,
H-4), 7.00 (2H, br s, NH2), 7.06 (2H, m, H-6,7), 7.22 (2H,
m, H-5,8), 7.33 (1H, d, J = 8.7, H-9), 7.41 (2H, m,
H-20,60), 7.81 (1H, d, J = 8.7, H-10), 7.89 (2H, m, H-30,50)
ppm. 13C NMR (125 MHz, DMSO): d = 37.20, 57.80,
115.30, 116.70, 120.29, 123.40, 124.80, 127.00, 128.40,
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128.70, 129.50, 130.01, 130.70, 141.80, 146.70, 159.70,
161.70 ppm. [Found: C, 75.86; H, 4.13; N, 8.87
C20H13FN2O: calculated C, 75.94; H, 4.14; N, 8.86%].
(2H, s, NH2), 7.23 (1H, d, J = 8.4, H-9), 7.32–7.50 (2H, m,
Ar), 7.61 (1H, s, H-20), 7.67–7.81 (2H, m, Ar), 7.92 (1H, d,
J = 9.2, H-10), 7.95–8.13 (3H, m, Ar) ppm. 13C NMR
(100 MHz, DMSO): d = 42.7, 57.2, 117.7, 118.6, 121.8,
122.3, 123.5, 124.7, 125.3, 127.6, 128.1, 129.0, 129.7,
131.3, 133.8, 141.6, 145.4, 146.3, 153.8, 158.4 ppm.
2-Amino-4-(phenyl)-4H-benzo[f]chromene-3-carbonitrile
(5a) [19] Mp: 282–284 °C, [280 °C]. IR (KBr): 3,435,
3,208, 2,185, 1,669, 1,560 cm-1 1H NMR (400 MHz,
.
DMSO): d = 5.24 (1H, s, H-4), 7.11 (2H, s, NH2),
7.06–7.15 (3H, m, Ar), 7.23–7.28 (2H, m, Ar), 7.38 (1H, d,
J = 8.4, H-9), 7.45–7.67 (2H, m, Ar), 7.79 (1H, d, J = 8.4,
H-10), 7.80–7.95 (2H, m, Ar) ppm. 13C NMR (100 MHz,
DMSO): d = 40.4, 55.7, 117.9, 119.7, 121.0, 122.6, 123.7,
124.6, 125.3, 127.6, 128.3, 129.4, 130.8, 132.7, 137.4,
144.9, 155.4, 158.6 ppm.
2-Amino-4-(2,4-dichlorophenyl)-4H-benzo[f]chromene-3-
carbonitrile (5g) Mp: 219–222 °C. IR (KBr): 3,390,
2,272, 1,652, 1,590, 1,578, 1,526, 1,381, 1,205,
1
1,058 cm-1. H NMR (400 MHz, DMSO): d = 5.36 (1H,
s, H-4), 7.14 (2H, s, NH2), 7.27 (1H, d, J = 8.4, H-9),
7.38–7.50 (2H, m, Ar), 7.70 (1H, s, H-30), 7.61–7.76 (2H,
m, Ar), 7.95 (1H, d, J = 8.4, H-10), 7.98–8.10 (2H, m, Ar)
ppm. 13C NMR (100 MHz, DMSO): d = 41.5, 59.7, 117.2,
119.4, 121.2, 121.8, 123.4, 124.5, 125.7, 126.1, 128.8,
129.1, 130.6, 132.7, 135.4, 142.8, 145.9, 147.3, 152.8,
159.6 ppm.
2-Amino-4-(4-nitrophenyl)-4H-benzo[f]chromene-3-car-
bonitrile (5b) [16] Mp: 184–185 °C, [185–186 °C]. IR
(KBr): 3,430, 3,325, 2,190, 1,650, 1,610, 1,582, 1,540,
1,502, 1,340, 1,244, 1,200, 1,070 cm-1
.
1H NMR
(400 MHz, DMSO): d = 5.45 (1H, s, H-4), 7.20 (2H, s,
NH2), 7.38 (1H, d, J = 8.4, H-9), 7.40–7.52 (2H, m,
H-6,7), 7.69–7.86 (2H, m, H-5,8), 7.92 (1H, d, J = 9.2,
H-10), 7.98 (2H, m, H-20,60), 8.15 (2H, m, H-30,50) ppm.
13C NMR (100 MHz, DMSO): d = 38.7, 55.3, 117.9,
119.6, 120.8, 122.4, 123.5, 124.8, 127.3, 128.6, 128.8,
129.5, 130.6, 132.6, 143.6, 147.6, 155.8, 159.7 ppm.
2-Amino-4-(4-bromophenyl)-4H-benzo[f]chromene-3-car-
bonitrile (5h) [24] Mp: 239–241 °C, [241–243 °C]. IR
(KBr): 3,427, 3,215, 2,268, 1,654, 1,603, 1,507, 1,255,
1,274, 844, 800 cm-1 1H NMR (500 MHz, DMSO):
.
d = 5.26 (1H, s, H-4), 6.92 (2H, s, NH2), 7.13–7.19 (2H,
m, Ar), 7.23–7.30 (2H, m, Ar), 7.32 (1H, d, J = 8.0, H-9),
7.37–7.42 (2H, d, J = 8.2, H-20,60), 7.73 (1H, d, J = 8.0,
H-10), 7.82–7.91 (2H, d, J = 8.2, H-30,50) ppm. 13C NMR
(125 MHz, DMSO): d = 39.7, 58.3, 118.4, 119.3, 121.0,
122.4, 123.7, 125.3, 126.6, 127.8, 128.3, 129.2, 130.6,
133.6, 139.2, 143.5, 157.6, 159.2 ppm.
2-Amino-4-(4-chlorophenyl)-4H-benzo[f]chromene-3-car-
bonitrile (5f) [24] Mp: 204–206 °C, [203–205 °C]. IR
(KBr): 3,453, 3,318, 2,194, 1,674, 1,595, 1,516, 1,422,
1,248, 1,211, 838, 802 cm-1
.
1H NMR (500 MHz,
DMSO): 5.37 (1H, s, H-4), 6.94 (2H, s, NH2), 7.06–7.15
(2H, m, H-6,7), 7.20–7.29 (2H, m, H-5,8), 7.35 (1H, d,
J = 8.4, H-9), 7.40–7.48 (2H, m, H-20,60), 7.81 (1H, d,
J = 8.4, H-10), 7.83–7.95 (2H, m, H-30,50) ppm. 13C NMR
(125 MHz, DMSO): d = 36.2, 56.8, 116.7, 118.4, 121.1,
122.7, 123.1, 124.5, 127.0, 128.4, 128.8, 129.8, 130.2,
133.5, 140.8, 145.7, 156.2, 160.8 ppm.
2-Amino-4-(4-methylphenyl)-4H-benzo[f]chromene-3-car-
bonitrile (5j) Mp: 193–195 °C. IR (KBr): 3,436, 2,228,
1,648, 1,598, 1,523, 1,263, 1,249, 851 cm-1 1H NMR
.
(500 MHz, DMSO): d = 2.33 (3H, s, CH3), 5.41 (1H, s,
H-4), 6.97 (2H, s, NH2), 7.17–7.23 (2H, m, Ar), 7.28–7.34
(2H, d, J = 8.0, H-30,50), 7.49 (1H, d, J = 8.0, H-9),
7.54–7.69 (2H, m, Ar), 7.73 (1H, d, J = 8.0, H-10),
7.79–7.87 (2H, d, J = 8.0, H-20,60) ppm. 13C NMR
(125 MHz, DMSO): d = 32.4, 40.4, 57.6, 117.6, 119.7,
121.8, 122.2, 123.5, 124.8, 126.5, 127.4, 128.8, 129.6,
130.3, 132.9, 137.4, 144.6, 156.8, 158.6 ppm.
2-Amino-4-(3-nitrophenyl)-4H-benzo[f]chromene-3-car-
bonitrile (5c) [16] Mp: 189–190 °C, [188–189 °C]. IR
(KBr): 3,326, 2,284, 1,643, 1,583, 1,582, 1,545, 1,507,
.
1,365, 1,244, 1,206, 1,075 cm-1 1H NMR (400 MHz,
DMSO): d = 5.37 (1H, s, H-4), 7.12 (2H, s, NH2), 7.26
(1H, d, J = 8.4, H-9), 7.36–7.52 (2H, m, Ar), 7.57 (1H, s,
H-20), 7.66–7.83 (2H, m, Ar), 7.86 (1H, d, J = 9.2, H-10),
7.98–8.15 (3H, m, Ar) ppm. 13C NMR (100 MHz, DMSO):
d = 41.4, 56.7, 118.5, 119.4, 120.7, 122.7, 123.6, 124.2,
125.8, 126.3, 128.2, 129.3, 129.7, 130.3, 132.7, 144.1,
145.8, 147.8, 155.2, 159.3 ppm.
2-Amino-4-(2-methylphenyl)-4H-benzo[f]chromene-3-car-
bonitrile (5i) Mp: 203–205 °C. IR (KBr): 3,425, 2,268,
1
1,649, 1,583, 1,529, 1,374, 1,229, 1,138 cm-1. H NMR
(400 MHz, DMSO): d = 2.27 (3H, s, CH3), 5.54 (1H, s,
H-4), 7.06 (2H, s, NH2), 7.22 (1H, d, J = 8.2, H-9),
7.36–7.49 (2H, m, Ar), 7.59–7.76 (3H, m, Ar), 7.86
(1H, d, J = 8.2, H-10), 7.90–8.02 (3H, m, Ar) ppm. 13C
NMR (100 MHz, DMSO): d = 31.4, 40.7, 57.8, 117.9,
120.6, 121.7, 122.7, 123.3, 124.1, 125.5, 126.8, 127.3,
129.8, 129.9, 131.7, 134.8, 140.6, 143.6, 145.2, 151.4,
158.7 ppm.
2-Amino-4-(3-chlorophenyl)-4H-benzo[f]chromene-3-car-
bonitrile (5e) Mp: 211–213 °C. IR (KBr): 3,394, 2,264,
1
1,643, 1,594, 1,563, 1,550, 1,373, 1,206, 1,042 cm-1. H
NMR (400 MHz, DMSO): d = 5.59 (1H, s, H-4), 7.10
123

J IRAN CHEM SOC (2012) 9:599–605
603
2-Amino-4-(3,4-dimethoxyphenyl)-4H-benzo[f]chromene-
3-carbonitrile (5k) [14] Mp: 273–275 °C, [270–272 °C].
IR (KBr): 3,405, 3,211, 2,212, 1,652, 1,510, 1,411, 1,376,
Table 1 Evaluation of catalytic activity of different catalysts for the
condensation of 4-nitrobenzaldehyde and a-naphtol
Entry Catalyst Mol% Solvent
Time (h) Yield (%)a
1
1,260, 1,228, 1,138 cm-1. H NMR (500 MHz, DMSO):
1
2
3
4
5
6
7
8
9
10
a
Non
–
H2O
24
1
25
85
96
90
60
70
94
93
50
75
d = 3.54 (6H, s, 2-OCH3), 5.03 (1H, s, H-4), 7.08 (2H, br
s, NH2), 7.12–7.24 (3H, m, Ar), 7.39–7.52 (3H, m, Ar),
7.70–7.85 (3H, m, Ar) ppm. 13C NMR (125 MHz, DMSO):
d = 40.49, 56.17, 57.49, 57.52, 117.34, 122.84, 123.63,
125.13, 125.76, 126.10, 126.49, 126.92, 127.51, 128.27,
129.72, 131.18, 132.54, 138.19, 142.29, 147.83, 148.03,
160.08 ppm.
TBAF
TBAC
TBAB
TBAC
TBAC
TBAC
TBAC
TBAC
TBAC
10
10
10
2.5
5
H2O
H2O
0.5
1
H2O
H2O
2
H2O
2
15
20
10
10
H2O
1
H2O
1
2-Amino-4-(4-methoxyphenyl)-4H-benzo[f]chromene-3-
carbonitrile (5l) [24] Mp: 190–192 °C, [188–189 °C]. IR
(KBr): 3,387, 3,209, 2,329, 1,641, 1,512, 1,442, 1,361,
H2O ? EtOH
EtOH
1
1
1
1,251, 1,225, 1,130 cm-1. H NMR (500 MHz, DMSO):
Yield are related to isolated pure products
d = 3.62 (3H, s, OCH3), 5.26 (1H, s, H-4), 7.11 (2H, br s,
NH2), 7.15–7.31 (4H, m, Ar), 7.36–7.51 (3H, m, Ar),
7.68–7.87 (3H, m, Ar) ppm. 13C NMR (125 MHz, DMSO):
d = 39.52, 57.26, 58.23, 118.93, 121.41, 123.33, 124.83,
125.17, 126.52, 127.37, 128.43, 129.11, 130.71, 133.44,
137.04, 138.19, 144.73, 148.83, 158.47 ppm.
of the TBAC did not improve the yields. Under the opti-
mized reaction conditions, a series of 2-amino-4H-chro-
mene derivatives 4 were synthesized (Scheme 1; Table 2).
We also investigated the synthesis of our target com-
pounds under solvent-free neat conditions, since a number
of reactions have been reported to proceed efficiently and
with higher selectivity under such conditions [28, 29].
Therefore, 4-nitrobenzaldelyde, a-naphthol and TBAC
were mixed thoroughly in a round-bottomed flask and the
mixture was heated in an oil bath maintained at 100 °C.
Interestingly, the reaction was complete in 15 min and 90%
of pure 4b was obtained. Under the optimized reaction
conditions, a series of 2-amino-4H-chromene derivatives 4
were synthesized (Scheme 1; Table 2).
2-Amino-4-(4-dimethylaminophenyl)-4H-benzo[f]chro-
mene-3-carbonitrile (5m) Mp: 244–245 °C. IR (KBr):
3,387, 3,209, 2,329, 1,641, 1,512, 1,442, 1,361, 1,251,
1,225, 1,130 cm-1
.
1H NMR (500 MHz, DMSO):
d = 3.26 (6H, s, NMe2), 5.18 (1H, s, H-4), 6.74 (2H, br s,
NH2), 7.11–7.29 (3H, m, Ar), 7.38–7.55 (4H, m, Ar),
7.62–7.86 (3H, m, Ar) ppm. 13C NMR (125 MHz, DMSO):
d = 40.17, 42.82, 56.39, 120.41, 122.63, 123.26, 124.38,
124.71, 126.54, 127.66, 128.84, 130.23, 132.68, 134.62,
137.73, 140.69, 145.80, 147.57, 156.45 ppm.
As can be seen from Table 2, electronic effects and the
nature of substituents on the aromatic ring did show effects
in terms of reaction time. When aromatic aldehydes con-
taining electron-donating groups (such as methyl, meth-
oxyl, or dimethylamino group) were employed, a longer
reaction time was required than those of electron-with-
drawing groups (such as nitro, or halides group) on aro-
matic rings.
Results and discussion
In order to optimize the reaction conditions, we studied the
synthesis of 2-amino-4H-chromene 4b from the conden-
sation of a-naphthol, 4-nitrobenzaldehyde and malononit-
rile in the presence of a variety of catalysts (Table 1).
We examined this reaction in the absence and presence
of several catalysts. It was found that when the reaction
occurred without any catalysts, it resulted in poor yield
(Table 1, entry 1). Tetrabutylammonium halides could
push the reaction forward with good yields (Table 1,
entries 2–4). Among when TBAC was used in this reaction
system, the yield of product was improved with lower time
(Table 1, entry 3).
We also tried to extend the scope of the present protocol
for condensation of aldehydes, b-naphthol and malononit-
rile. Therefore, a series of substituted 2-amino-4H-chro-
mene derivatives 5 were prepared successfully from
different aromatic aldehydes bearing electron-withdrawing
and electron-donating groups in water and under solvent-
free neat conditions (Scheme 1; Table 3).
The comparison reaction of a-naphthol and b-naph-
thol with aromatic aldehydes and malononitrile gave
different results. For instance, benzaldehyde reacted with
malononitrile and a-naphthol or b-naphthol and gave
products of 4a (30 min) and 5a (120 min), respectively.
It showed that a-naphthol reveals higher reactivity than
b-naphthol.
We evaluated the amount of TBAC required for this
transformation. It was found that when increased the
amount of the TBAC from 2.5 to 20 mol%, the yields
increased from 60 to 93%. Using 10 mol% TBAC in water
was sufficient to push the reaction forward. Extra amounts
123

604
J IRAN CHEM SOC (2012) 9:599–605
Method B
Table 2 Synthesis of 2-amino-
4H-chromenes by condensation
of aldehydes, a-naphtol and
malononitrile using TBAC
(10 mol%) as catalyst
Entry
Ar
Product
Method A
Time (min)
Yield (%)a
Time (min)
Yield (%)a
1
C6H5
4a
4b
4c
4d
4e
4f
30
30
95
96
98
97
95
96
97
94
96
95
94
96
85
15
15
15
15
15
15
15
25
25
30
30
35
35
93
90
94
90
92
92
95
91
90
88
94
90
88
2
4-O2NC6H4
3-O2NC6H4
4-FC6H4
3
30
4
30
5
3-ClC6H4
30
6
4-ClC6H4
30
7
2,4-Cl2C6H3
4-BrC6H4
4g
4h
4i
30
8
60
9
2-CH3C6H4
4-CH3C6H4
3,4-(CH3O)2C6H3
4-CH3OC6H4
4-(CH3)2NC6H4
60
Method A: reaction carried out
in water; Method B: reaction
carried out under solvent-free
conditions
10
11
12
13
4j
90
4k
4l
90
150
150
a
Yield are related to isolated
pure products
4m
Table 3 Synthesis of 2-amino-
4H-chromenes by condensation
of aldehydes, b-naphtol and
malononitrile using TBAC
(10 mol%) as catalyst
Entry
Ar
Product
Method A
Method B
Time (min)
Yield (%)a
Time (min)
Yield (%)a
1
C6H5
5a
5b
5c
5d
5e
5f
120
60
80
90
93
88
94
90
95
93
80
82
80
77
70
35
25
30
25
35
30
25
30
35
35
35
40
40
82
88
90
90
92
93
93
90
89
85
86
82
80
2
4-O2NC6H4
3-O2NC6H4
4-FC6H4
3
60
4
60
5
3-ClC6H4
120
60
6
4-ClC6H4
7
2,4-Cl2C6H3
4-BrC6H4
5g
5h
5i
60
8
60
9
2-CH3C6H4
4-CH3C6H4
3,4-(CH3O)2C6H3
4-CH3OC6H4
4-(CH3)2NC6H4
120
120
140
180
180
Method A: reaction carried out
in water; Method B: reaction
carried out under solvent-free
conditions
10
11
12
13
5j
5k
5l
a
Yield are related to isolated
pure products
5m
Table 4 Comparison of catalytic activity ammonium salts of previous reports with present work for preparation of 2-amino-4H-chromene
derivatives
Reference number
Catalyst
Reaction conditions
Time (h)
Yield (%)
15
Cetyltrimethylammonium chloride (CTAC)
Cetyltrimethylammonium bromide (CTAB)
Hexadecyltrimethylammonium bromide (HTMAB)
Triethylbenzylammonium chloride (TEBA)
N,N,dimethylaminoethylbenzyldimethylammonium chloride
Tetrabutylammonium chloride (TBAC)
H2O, 110 °C
H2O, us, rt
6.0
60–94
72–94
68–95
90–94
62–95
70–95
80–93
16
2.5
20
H2O, 100 °C
H2O, 90 °C
Solvent-free, 80 °C
H2O, 100 °C
Solvent-free, 100 °C
4.0–6.0
4.0
21
23
0.5–2.0
0.5–1.5
0.25–0.58
Present work
Tetrabutylammonium chloride (TBAC)
Also, the comparison of catalytic activity ammonium
salts of previous reports with present work for prepa-
ration of 2-amino-4H-chromene derivatives has shown
in Table 4. It was found that shorter reaction times are
the main advantageous of these reactions in present
work.
123

J IRAN CHEM SOC (2012) 9:599–605
605
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Acknowledgments We are thankful to the Office of Graduate
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