Organocatalytic approach toward the green one-pot synthesis of novel benzo[f]chromenes and 12H-benzo[5,6]chromeno[2,3-b]pyridines

Article abstract of DOI:10.1007/s11164-017-3145-7

An efficient tandem reaction approach is described to prepare novel benzo[f]chromenes from 2,3-dihydroxynaphthalene, malononitrile and aldehydes using 10?mol% guanidine hydrochloride as the catalyst under solvent-free conditions. The method was also exten

Full text of DOI:10.1007/s11164-017-3145-7

Res Chem Intermed
DOI 10.1007/s11164-017-3145-7
Organocatalytic approach toward the green one-pot
synthesis of novel benzo[f]chromenes and 12H-
benzo[5,6]chromeno[2,3-b]pyridines
Abolfazl Olyaei1 Mohammad Sadegh Shahsavari1
•
•
Mahdieh Sadeghpour2
Received: 5 July 2017 / Accepted: 7 September 2017
Ó Springer Science+Business Media B.V. 2017
Abstract An efficient tandem reaction approach is described to prepare novel
benzo[f]chromenes from 2,3-dihydroxynaphthalene, malononitrile and aldehydes
using 10 mol% guanidine hydrochloride as the catalyst under solvent-free condi-
tions. The method was also extended to the preparation of novel 12H-benzo[5,6]-
chromeno[2,3-b]pyridines from 2-aminoprop-1-ene-1,1,3-tricarbonitrile instead of
malononitrile under the same reaction conditions. The described one-pot three-
component reaction is characterized by short reaction times, high-product yield,
mild reaction conditions, simple workup procedure, and simple purification.
Keywords Benzo[f]chromene Á Benzo[5,6]chromeno[2,3-b]pyridine Á
2,3-Dihydroxynaphthalene Á Malononitrile Á 2-Aminoprop-1-ene-1,1,3-
tricarbonitrile
Introduction
Benzochromenes are an important group of heterocyclic compounds being the main
components of many naturally occurring products. These molecules are biologically
active and find application in pharmacological properties such as anti-inflammatory
[1], anti-microbial [2], anticancer [3], mutagenicitical, antiviral and central nervous
system activities [4]. They can also be employed in industry as antioxidants [5], as
cosmetics and pigments and as potential biodegradable agrochemicals [6]. Several
conventional protocols have been well developed for the syntheses of these
&
Abolfazl Olyaei
Olyaei_a@pnu.ac.ir
1
2
Department of Chemistry, Payame Noor University, PO Box 19395-3697, Tehran, Iran
Department of Chemistry, Takestan Branch, Islamic Azad University, Takestan, Iran
123

A. Olyaei et al.
polyfunctionalized chromenes involving the three-component, one-pot condensation
of malononitrile, aldehyde and phenol or naphthol with the use of various catalysts,
such as methanesulfonic acid [7], H14[NaP5W30O110] [8], poly(4-vinylpyridine) [9],
ionic liquid [10], piperidine [11], CaO–ZrO2 nanocomposite oxides [12], Ni–Al2O3
[13], potassium phthalimide-N-oxyl [14], diammonium hydrogen phosphate [15],
thiourea dioxide [16], sodium malonate [17], nanozeolite clinoptilolite [18], and
potassium hydrogen phthalate [19]. However, they are mostly suffer from one or
more drawbacks including the use of expensive reagents, toxic metals, the use of
volatile organic solvents, drastic reaction conditions, tedious work-up procedures,
high cost and low product yields.
Chromenopyridines have biological properties such as antiproliferative [20],
cancer chemopreventive [21], antibacterial [22, 23], antimyopic [24], hypotensive
[25], hypotensive [26], antirheumatic [27], and antiasthmatic activities [28]. A few
methods have been reported for the synthesis of chromeno[2,3-b]pyridine deriva-
tives by a MCR of 2-amino-1,1,3-tricyanopropene or malononitrile and aldehydes
with secondary cyclic amines [29], 3-phenylisoxazol-5(4H)-one [30], 4-hydroxy-
carbazole [31], thiols [32, 33], and naphthols [34, 35] in the presence of different
catalysts under different reaction conditions.
Organocatalysts have been used widely in many reactions as mono and
bifunctional catalysts due to economic and environmental considerations. Among
many organocatalysts, hydrogen bonding compounds such as guanidine derivatives
are becoming powerful tools for activation of the carbonyl functionality in organic
transformations. Recently, guanidinium salts have been successfully employed as
novel chiral phase-transfer catalysts in the conjugate addition of nitroalkanes with
enones [36, 37]. Moreover, these organocatalysts provide an environment for the
process activating the nucleophile, the electrophile or both reagents through weak
interactions, such as hydrogen bonding or ion pairing or much stronger interactions
such as covalent bonding.
However, there are no reports available for the synthesis of benzo[f]chromenes
and 12H-benzo[5,6]chromeno[2,3-b]pyridines from 2,3-dihydroxynaphthalene in
the literature. Hence, our attention was devoted toward the reactions involving 2,3-
dihydroxynaphthalene and aldehydes with malononitrile or 2-aminoprop-1-ene-
1,1,3-tricarbonitrile using guanidine hydrochloride as the organocatalyst under
solvent-free conditions.
Results and discussion
In continuation of our investigations on the synthesis of organic compounds in the
presence of guanidine hydrochloride [38–42], initially we examined the three-
component condensation reaction of 2,3-dihydroxynaphthalene (1, 1 mmol),
benzaldehyde (2, 1 mmol), malononitrile (3, 1 mmol) and guanidine hydrochloride
(10 mol%) in the different solvents such as EtOH, MeOH, CH3CN, THF and
toluene (Table 1, entries 1–6). However, no desired product was detected even after
a long reaction time (5 h) under reflux conditions.
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Organocatalytic approach toward the green one-pot synthesis…
Table 1 Optimization of reaction conditions in the presence of guanidine hydrochloride (10 mol%) as
catalyst
CN
NH2
CHO
OH
OH
CN
O
conditions
+
+
CN
3
OH
1
2
4a
Entry
Solvent
Temp. (°C)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
a
EtOH
MeOH
CH3CN
THF
78
64
5
NRb
NR
NR
NR
NR
60
5
81
5
66
5
Toluene
H2O
110
100
70
5
2
Neat
2
64
Neat
100
120
0.75
0.75
85
Neat
70
Isolated yield
No reaction
b
The above reaction was performed in water under reflux conditions. Interestingly,
product 4a was obtained in moderate yield (60%, entry 6) after 2 h. Also, the
solvent-free condition was further used to optimize these reaction conditions
(Table 1, entries 7–9). It was observed that as the temperature rises from 70 to
100 °C, both the reaction speed and the product yield increased. It is noteworthy
that, increasing the temperature to 120 °C,the yield of the corresponding product
was slightly decreased from 85 to 70% (entry 9) (Table 1).
Moreover, the optimal molar loading of guanidine hydrochloride as the catalyst
was determined by performing the model reaction using 5, 10, 15 and 20 mol% of
catalyst under solvent-free condition at 100 °C. The results show that in the absence
of catalyst, the reaction did not proceed to completion even after 80 min and
Table 2 The optimization of
catalyst loading for the synthesis
of benzo[f]chromenes 4a
Entry Catalyst (mol%) Temp. (°C) Time (min) Yielda (%)
1
2
3
4
5
None
5
100
100
100
100
100
80
80
40
40
40
20
72
85
86
85
10
15
20
aIsolated yield
123

A. Olyaei et al.
CN
Ar
NH2
NH2Cl
NH2
O
OH
OH
CN
H2N
ArCHO
+
+
solvent-free
100 oC
CN
3
OH
1
2
4a-i
Scheme 1 Three-component synthesis of benzo[f]chromenes 4
Table 3 One-pot synthesis of benzo[f]chromene derivatives 4
Entry
Aldehyde
Product
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
Benzaldehyde
4a
4b
4c
4d
4e
4f
40
45
55
30
60
60
70
45
60
85
81
78
83
81
84
79
80
81
2-Nitrobenzaldehyde
3-Nitrobenzaldehyde
2-Chlorobenzaldehyde
4-Chlorobenzaldehyde
3-Bromobenzaldehyde
4-Bromobenzaldehyde
4-Fluorobenzaldehyde
3-Hydroxybenzaldehyde
4g
4h
4i
resulted in the isolation of product 4a in 20% yield (Table 2, entry 1). However,
increasing the amount of catalyst from 5 to 10 mol% led to an increase in the yield
from 72 to 85% (Table 2, entries 2–3). The use of 15 and 20 mol% catalyst was
identified as the most effective way of pushing this reaction toward completion and
did not further improve the yield (Table 2, entry 5). The results of these screening
experiments show that the optimum reaction conditions are 10 mol% guanidine
hydrochloride at 100 °C under solvent-free conditions (Table 2).
With the optimum reaction conditions in hand, we evaluated the scope of the
transformation using various substituted benzaldehyde 2. A wide range of aldehydes
2, which bear different substituent groups on the aryl ring, were utilized to react
with 2,3-dihydroxynaphthalene and malononitrile under the optimal conditions
(Scheme 1; Table 3).
The results show that all reactions of various substituted benzaldehydes
proceeded smoothly to give the corresponding benzo[f]chromenes in high yields
(Fig. 1). However, when some aliphatic aldehydes such as acetaldehyde, propi-
onaldehyde and 3-phenylpropanaldehyde were used in this protocol under the above
optimized conditions, unfortunately, the expected products could not be obtained.
Encouraged by the successful condensation of 2,3-dihydroxynaphthalene,
aldehydes and malononitrile under solvent-free conditions to give benzo[f]chro-
mene derivatives, we next attempted on the formation of novel bis-condensation
products by executing the reaction of 2,3-dihydroxynaphthalene with double molar
123

Organocatalytic approach toward the green one-pot synthesis…
NO2
NO2
CN
Cl
CN
CN
CN
NH2
NH2
NH2
NH2
O
O
O
O
OH
CN
OH
OH
OH
4c
4a
4b
4d
Br
Cl
Br
F
CN
CN
CN
NH2
NH2
NH2
NH2
O
O
O
O
OH
OH
OH
OH
OH
4e
4f
4g
4h
CN
NH2
O
OH
4i
Fig. 1 Products 4a–i
OH
CN
CN
Cat.
OH
2
Cat.
ArHC
CN
ArCHO +
NC
-H2O
3
5
2
CN
CN
CN
H
Ar
NH2
Ar
H
Ar
NH
C
O
N
O
O
OH
OH
OH
6
4
7
Scheme 2 Plausible mechanism for the organo catalyzed synthesis of benzo[f]chromenes 4
ratios of benzaldehyde and malononitrile under similar reaction conditions. The
result showed that the product 4a was obtained as only product instead of the
expected bis-condensed product (Table 3; Fig. 1). A plausible mechanism for the
formation of the product 4 is proposed in Scheme 2. We assume that guanidine
hydrochloride is an effective catalyst for the formation of olefin 5, which is formed
123

A. Olyaei et al.
in situ by Knoevenagel condensation of aryl aldehyde 2 and the active methylene
compound 3. Olefin 5 subsequently reacts with 2,3-dihydroxynaphthalene to give
intermediate 6. Further, the cyclization of 6 gives intermediate 7 which
subsequently tautomerizes to yield the corresponding benzo[f]chromene 4
(Scheme 2).
Encouraged by the successful condensation of 2,3-dihydroxynaphthalene,
aldehydes, and malononitrile under solvent-free conditions to give benzo[f]chro-
mene derivatives, we next attempted the reaction with 2,3-dihydroxynaphthalene,
aldehydes and 2-aminoprop-1-ene-1,1,3-tricarbonitrile (8) under the same reaction
conditions, which led to the formation of novel 12H-benzo[5,6]chromeno[2,3-
b]pyridines 9a–f in good yields (Scheme 3; Fig. 2). The results are shown in
Table 4.
Inspired by the optimization of the reaction conditions, we continued to
investigate the applicable scope of the methodology of this one-pot three-
component heterocyclization using 2,3-dihydroxynaphthalene (1 mmol),
2-chlorobenzaldehyde (2 mmol) and 2-aminoprop-1-ene-1,1,3-tricarbonitrile
(2 mmol). It is observed that the product 9a was obtained as the only product
NH2Cl
Ar
CN
NH2
N
OH
OH
CN
CN
CN
H2N
NH2
+
ArCHO
+
H2N
solvent-free
100 oC
O
NH2
1
8
2
OH
9a-f
Scheme 3 Three-component synthesis of 12H-benzo[5,6]chromeno[2,3-b]pyridines 9
Cl
Br
Cl
NH2
N
NH2
NH2
N
CN
CN
CN
NH2
O
O
O
N
NH2
NH2
OH
OH
OH
9a
9b
F
9c
Br
NO2
NH2
N
NH2
N
NH2
N
CN
CN
CN
2NH
O
O
O
NH2
NH2
OH
OH
OH
9f
9e
9d
Fig. 2 Products 9a–f
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Organocatalytic approach toward the green one-pot synthesis…
Table 4 One-pot synthesis of
Entry Aldehyde
Product Time (min) Yield (%)
12H-benzo[5,6]chromeno[2,3-
b]pyridine derivatives 9
1
2
3
4
5
6
2-Chlorobenzaldehyde 9a
60
120
100
90
75
78
81
79
78
88
4-Chlorobenzaldehyde 9b
3-Bromobenzaldehyde 9c
4-Bromobenzaldehyde 9d
4-Fluorobenzaldehyde 9e
100
40
3-Nitrobenzaldehyde
9f
OH
OH
Ar
O
NH2
NC
NC
NH2
H
NC
NH2
CHAr
NC
10
CN
Cat.
ArCHO +
C
N
CN
NC
NC
Cat.
2
8
OH
11
Ar
NH2
NH2
N
Ar
H
Ar NH2
CN
CN
CN
NH
C
O
NH
NH2
O
N
O
N
H
OH
OH
12
OH
9
13
Scheme 4 Plausible mechanism for the synthesis of 12H-benzo[5,6]chromeno[2,3-b]pyridines 9
instead of the expected bis-condensed product. Furthermore, we also carried out a
one-pot pseudo four-component reaction of 2,3-dihydroxynaphthalene (1 mmol),
2-chlorobenzaldehyde (1 mmol) and malononitrile (2 mmol) under the same
reaction conditions for the synthesis of compound 9a. However, the reaction
provided benzo[f]chromene 4d as the only product instead of an expected 12H-
benzo[5,6]chromeno[2,3-b]pyridine 9a (Table 4; Fig. 2).
A mechanistic rationale portraying the probable sequence of events is given in
Scheme 4. The first stage of this process is the Knoevenagel condensation promoted
between 2-aminoprop-1-ene-1,1,3-tricarbonitrile 8 and aldehyde 2 in the presence
of guanidine hydrochloride to give rise to intermediate 10. Next, the Michael
addition of 2,3-dihydroxynaphthalene to intermediate 10 provides the intermediate
11 which then undergoes tautomerization and subsequent intramolecular cyclization
twice, to afford final the corresponding 12H-benzo[5,6]chromeno[2,3-b]pyridines 9
(Scheme 4).
Conclusion
In summary, we have introduced a one-pot three-component condensation reaction
leading to a new class of benzo[f]chromene derivatives starting from 2,3-
dihydroxynaphthalene, malononitrile and aldehydes using guanidine hydrochloride
123

A. Olyaei et al.
as organo catalyst. Further investigation in our laboratory will focus on evaluating
the process with 2-aminoprop-1-ene-1,1,3-tricarbonitrile instead of malononitrile
for the synthesis of 12H-benzo[5,6]chromeno[2,3-b]pyridine derivatives. These
reactions can be regarded as a new approach for the preparation of synthetically and
pharmaceutically relevant heterocyclic systems. This approach includes some
important aspects such as high atom economy, mild reaction conditions, high yields
of the products, short reaction times, solvent-free nature of the reaction, ease of
work-up and clean procedure, and involving no chromatography.
Experimental section
General information
All commercially available chemicals and reagents were used without further
purification. Melting points were determined with an Electrothermal model 9100
apparatus and are uncorrected. IR spectra were recorded on a Shimadzu 4300
1
spectrophotometer. The H and 13C NMR spectra were recorded in DMSO-d6 on
Bruker DRX-300 Avance spectrometers. Chemical shifts (d) are reported in parts
per million and are referenced to the NMR solvent. Mass spectra of the products
were obtained with a HP (Agilent technologies) 5973 mass selective detector.
Elemental analyses were carried out by a CHN–O–Rapid Heraeus elemental
analyzer (Wellesley, MA).
General procedure for the synthesis of benzo[f]chromens 4a–f and 12H-benzo[5,
6]chromeno[2,3-b]pyridines 9a–f
In a 25 mL round bottom flask, a mixture of 2,3-dihydroxynaphthalene (1 mmol),
aldehyde (1 mmol), malononitrile (1 mmol) or 2-aminoprop-1-ene-1,1,3-tricarboni-
trile (1 mmol) and guanidine hydrochloride (10 mol%) were taken, and the mixture
was stirred at 100 °C in an oil bath for an appropriate amount of time as indicated in
Tables 3 and 4. The progress of the reaction was monitored by thin-layer
chromatography (TLC). After completion, the reaction mixture was cooled to room
temperature and CH3CN (5 mL) was added, and then a precipitate was allowed to
form. The precipitate was filtered, washed with CH3CN and dried. The crude
product was stirred for 5 min in boiling EtOH,and the resulting precipitate was
1
filtered. The product 4 and 9 thus obtained was found to be pure upon H and 13C
NMR, mass spectra, elemental analyses, and TLC examination.
3-Amino-5-hydroxy-1-phenyl-1H-benzo[f]chromene-2-carbonitrile (4a)
Cream solid; mp 287–288 °C; IR (KBr, cm-1): 3487, 3375, 3249, 3061, 2995, 2188,
1648, 1621, 1570, 1454, 1421, 1254, 1180; H NMR (300 MHz, DMSO-d6): 5.22
1
(s, 1H, methine-H), 6.93 (s, 2H, NH2), 7.10–7.32 (m, 8H, Ar–H), 7.65–7.72 (t, 2H,
1
J = 9.0 Hz, Ar–H), 10.32 (s, 1H, OH), H NMR (300 MHz ? D2O, DMSO-d6):
5.22 (s, 1H, methine-H), 7.10–7.31 (m, 8H, Ar–H), 7.63–7.68 (t, 2H, J = 7.8 Hz,
123

Organocatalytic approach toward the green one-pot synthesis…
Ar–H), 13C NMR (75 MHz, DMSO-d6): 58.42, 110.32, 117.75, 120.93, 123.87,
124.15, 124.75, 125.56, 125.98, 126.89, 127.04, 127.35, 129.15, 131.73, 139.56,
145.47, 146.11, 160.18; MS m/z (%): 314 (M?), 297, 247, 238, 237 (100), 208, 191,
164, 153, 127, 114, 77, 51; Anal. calcd. for C20H14N2O2: C, 76.43; H, 4.45; N, 8.91.
Found: C, 76.50; H, 4.39; N, 8.94.
3-Amino-5-hydroxy-1-(2-nitrophenyl)-1H-benzo[f]chromene-2-carbonitrile (4b)
Pale green solid; mp 274–275 °C; IR (KBr, cm-1): 3482, 3381, 3239, 3068, 2995,
2192, 1658, 1623, 1584, 1522, 1426, 1335, 1255, 1187; 1H NMR (300 MHz,
DMSO-d6): 6.10 (s, 1H, methine-H), 6.99 (d, 1H, J = 6.9 Hz, Ar–H), 7.10 (s, 2H,
NH2), 7.20–7.46 (m, 4H, Ar–H), 7.51–7.56 (t, 1H, J = 6.3 Hz, Ar–H), 7.62 (d, 1H,
J = 8.4 Hz, Ar–H), 7.72 (d, 1H, J = 7.5 Hz, Ar–H), 7.98 (d, 1H, J = 6.9 Hz, Ar–
H), 10.46 (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6): 56.66, 111.07, 115.65,
120.07, 122.92, 124.66, 124.73, 125.21, 125.83, 127.17, 128.66, 130.37, 131.75,
134.80, 139.68, 140.40, 145.43, 147.78, 160.28; MS m/z (%): 359 (M?), 342 (100),
311, 284, 255, 237, 227, 201, 191, 164, 127, 114, 105, 77, 57, 43; Anal. calcd. for
C20H13N3O4: C, 66.85; H, 3.62; N, 11.70. Found: C, 66.81; H, 3.69; N, 11.76.
3-Amino-5-hydroxy-1-(3-nitrophenyl)-1H-benzo[f]chromene-2-carbonitrile (4c)
Yellow solid; mp 285–287 °C; IR (KBr, cm-1): 3441, 3334, 3215, 3068, 2924,
2182, 1660, 1637, 1592, 1526, 1464, 1413, 1318, 1262, 1116; 1H NMR (300 MHz,
DMSO-d6): 5.58 (s, 1H, methine-H), 7.10 (s, 2H, NH2), 7.19–7.34 (m, 3H, Ar–H),
7.56–7.74 (m, 4H, Ar–H), 8.03–8.05 (m, 2H, Ar–H), 10.43 (s, 1H, OH); 13C NMR
(75 MHz, DMSO-d6): 57.39, 110.83, 116.67, 120.62, 121.66, 122.30, 123.74,
124.46, 125.79, 127.02, 130.92, 131.76, 134.11, 139.66, 139.71, 145.38, 145.66,
148.31, 148.45, 160.44; MS m/z (%): 359 (M?), 342, 311, 237 (100), 208, 191, 164,
153, 126, 105, 77, 57, 43; Anal. calcd. for C20H13N3O4: C, 66.85; H, 3.62; N, 11.70.
Found: C, 66.82; H, 3.67; N, 11.76.
3-Amino-5-hydroxy-1-(2-chlorophenyl)-1H-benzo[f]chromene-2-carbonitrile (4d)
Yellow solid; mp 286–287 °C; IR (KBr, cm-1): 3490, 3381, 3258, 3079, 2916,
21.94, 1653, 1610, 1578, 1420, 1356, 1261, 1186, 1116; 1H NMR (300 MHz,
DMSO-d6): 5.70 (s, 1H, methine-H), 7.02 (s, 2H, NH2), 7.17–7.33 (m, 6H, Ar–H),
7.45–7.52 (m, 2H, Ar–H), 7.69 (d, 1H, J = 7.8 Hz, Ar–H), 10.40 (s, 1H, OH); 13C
NMR (75 MHz, DMSO-d6): 56.81, 110.67, 116.86, 120.29, 122.90, 124.51, 124.70,
125.68, 127.12, 128.68, 128.93, 129.97, 130.34, 131.38, 131.66, 139.98, 143.12,
145.45, 147.33, 160.34; MS m/z (%): 350 (M ? 2)?, 348 (M?), 313, 238, 237
(100), 188, 164, 153, 126, 114, 100, 75, 57, 43; Anal. calcd. for C20H13ClN2O2: C,
68.86; H, 3.73; N, 8.03. Found: C, 68.90; H, 3.68; N, 8.00.
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A. Olyaei et al.
3-Amino-5-hydroxy-1-(4-chlorophenyl)-1H-benzo[f]chromene-2-carbonitrile (4e)
Cream solid; mp 275–276 °C; IR (KBr, cm-1): 3408, 3357, 3223, 3034, 2936, 2186,
1655, 1621, 1578, 1488, 1351, 1247, 1149, 1115; 1H NMR (300 MHz, DMSO-d6):
5.32 (s, 1H, methine-H), 6.99 (s, 2H, NH2), 7.19–7.35 (m, 7H, Ar–H), 7.68 (d, 2H,
J = 8.4 Hz, Ar–H), 10.35 (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6): 57.94,
110.51, 117.23, 120.77, 123.80, 124.24, 124.62, 125.63, 126.94, 129.16, 129.21,
129.49, 131.62, 131.75, 139.56, 145.09, 145.46, 160.20; MS m/z (%): 350
(M ? 2)?, 348 (M?), 311, 238, 237 (100), 208, 191, 164, 153, 127, 114, 81, 69,
55, 43; Anal. calcd. for C20H13ClN2O2: C, 68.86; H, 3.73; N, 8.03. Found: C, 68.90;
H, 3.68; N, 8.09.
3-Amino-5-hydroxy-1-(3-bromophenyl)-1H-benzo[f]chromene-2-carbonitrile (4f)
Yellow solid; mp 262–264 °C; IR (KBr, cm-1): 3490, 3382, 3171, 3072, 2977,
2189, 1655, 1621, 1574, 1427, 1362, 1151, 1114; 1H NMR (300 MHz, DMSO-d6):
5.35 (s, 1H, methine-H), 7.03 (s, 2H, NH2), 7.16–7.38 (m, 7H, Ar–H), 7.67–7.72 (t,
2H, J = 7.8 Hz, Ar–H), 10.38 (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6): 57.85,
110.64, 117.05, 120.70, 122.37, 123.30, 123.77, 124.34, 124.58, 125.71, 126.48,
126.97, 129.88, 130.04, 131.49, 131.74, 139.61, 145.43, 148.81, 160.33; MS m/
z (%): 394 (M ? 2)?, 392 (M?), 348, 238, 237 (100), 208, 191, 164, 153, 127, 114,
97, 83, 69, 57, 43; Anal. calcd. for C20H13BrN2O2: C, 61.06; H, 3.30; N, 7.12.
Found: C, 61.01; H, 3.25; N, 7.18.
3-Amino-5-hydroxy-1-(4-bromophenyl)-1H-benzo[f]chromene-2-carbonitrile (4g)
Cream solid; mp 276–278 °C; IR (KBr, cm-1): 3497, 3387, 3225, 3076, 2938, 2183,
1660, 1622, 1584, 1506, 1424, 1351, 1248, 1220, 1181; 1H NMR (300 MHz,
DMSO-d6): 5.31 (s, 1H, methine-H), 6.96 (s, 2H, NH2), 7.06–7.33 (m, 7H, Ar–H),
7.66–7.71 (t, 2H, J = 7.5 Hz, Ar–H), 10.33 (s, 1H, OH); 13C NMR (75 MHz,
DMSO-d6): 58.17, 110.35, 115.77, 116.05, 117.58, 120.89, 123.85, 124.19, 124.61,
125.60, 126.92, 129.15, 129.26, 131.73, 139.48, 142.42, 145.47, 160.16; MS m/
z (%): 394 (M ? 2), 392 (M?), 348, 338, 332, 327 (100), 208, 191, 164, 153, 127,
114, 95, 83, 69, 57, 43; Anal. calcd. for C20H13BrN2O2: C, 61.06; H, 3.30; N, 7.12.
Found: C, 61.09; H, 3.37; N, 7.13.
3-Amino-5-hydroxy-1-(4-flourophenyl)-1H-benzo[f]chromene-2-carbonitrile (4h)
Cream solid; mp 282–283 °C; IR (KBr, cm-1): 3497, 3388, 3222, 3075, 2938, 2183,
1660, 1622, 1603, 1506, 1424, 1351, 1248, 1220, 1150; 1H NMR (300 MHz,
DMSO-d6): 5.32 (s, 1H, methine-H), 6.96 (s, 2H, NH2), 7.06–7.33 (m, 7H, Ar–H),
7.66–7.71 (t, 2H, J = 7.5 Hz, Ar–H), 10.34 (s, 1H, OH); 13C NMR (75 MHz,
DMSO-d6): 58.20, 110.39, 115.77, 116.09, 117.58, 120.91, 123.85, 124.21, 124.62,
125.62, 126.93, 129.16, 129.27, 131.75, 139.50, 142.39, 142.42, 145.49, 160.18;
MS m/z (%): 332 (M?), 303, 238, 237 (100), 208, 191, 164, 153, 127, 114, 95, 75,
123

Organocatalytic approach toward the green one-pot synthesis…
57, 43; Anal. calcd. for C20H13FN2O2: C, 72.29; H, 3.91; N, 8.43. Found: C, 72.33;
H, 3.86; N, 8.49.
3-Amino-5-hydroxy-1-(3-hydroxyphenyl)-1H-benzo[f]chromene-2-carbonitrile (4i)
Cream solid; mp 262–263 °C; IR (KBr, cm-1): 3477, 3305, 3153, 3061, 2946, 2196,
1651, 1624, 1610, 1531, 1485, 1411, 1331, 1295, 1246, 1209, 1113; H NMR
1
(300 MHz, DMSO-d6): 5.15 (s, 1H, methine-H), 6.50–6.55 (m, 2H, Ar–H), 6.68 (d,
1H, J = 7.5 Hz, Ar–H), 6.91 (s, 2H, NH2), 7.03–7.33 (m, 4H, Ar–H), 7.66–7.71 (t,
2H, J = 8.4 Hz, Ar–H), 9.32 (s, 1H, OH), 10.32 (s, 1H, OH), 13C NMR (75 MHz,
DMSO-d6): 58.35, 110.20, 114.12, 117.84, 117.87, 118.13, 121.04, 123.32, 123.89,
124.13, 124.82, 125.57, 126.86, 130.03, 131.70, 139.50, 145.48, 147.54, 158.05,
160.19; MS m/z (%): 332 (M ? 2), 330 (M?), 238, 237 (100), 208, 191, 164, 153,
127, 95, 83, 69, 57, 55, 43; Anal. calcd. for C20H14N2O3: C, 72.72; H, 4.24; N, 8.48.
Found: C, 72.69; H, 4.20; N, 8.53.
9,11-Diamino-6-hydroxy-12-(2-chlorophenyl)-12H-benzo[5,6]chromeno[2,3-
b]pyridine-10-carbonitrile (9a)
Cream solid; mp [ 300 °C; IR (KBr, cm-1): 3476, 3363, 3193, 3054, 2206, 1646,
1580, 1473, 1400, 1322, 1263, 1218; H NMR (300 MHz, DMSO-d6): 6.13 (s, 1H,
1
methine-H), 6.38 (s, 2H, NH2), 6.56 (s, 2H, NH2), 7.13–7.35 (m, 6H, Ar–H), 7.55
(d, 1H, J = 7.5 Hz, Ar–H), 7.66 (d, 1H, J = 5.1 Hz, Ar–H), 8.07–8.09 (m, 1H, Ar–
H), 10.23 (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6): 71.67, 90.61, 110.58,
116.77, 117.66, 123.28, 124.05, 125.29, 125.35, 125.99, 127.08, 128.36, 129.12,
130.42, 131.19, 131.33, 132.06, 141.19, 141.74, 145.98, 157.21, 159.06, 159.99;
MS m/z (%): 416 (M ? 2)?, 414 (M?), 342, 330, 303, 238, 237 (100), 208, 191,
164, 127, 114, 75, 57, 43; Anal. calcd. for C23H15ClN4O2: C, 66.58; H, 3.61; N,
13.51. Found: C, 66.52; H, 3.67; N, 13.48.
9,11-Diamino-6-hydroxy-12-(4-chlorophenyl)-12H-benzo[5,6]chromeno[2,3-
b]pyridine-10-carbonitrile (9b)
Pale green solid; mp [ 300 °C; IR (KBr, cm-1): 3498, 3351, 3243, 3070, 2973,
2202, 1623, 1555, 1473, 1403, 1322, 1207, 1149; 1H NMR (300 MHz, DMSO-d6):
6.05 (s, 1H, methine-H), 6.50 (s, 2H, NH2), 6.85 (s, 2H, NH2), 7.19–7.46 (m, 7H,
Ar–H), 7.65–7.68 (m, 1H, Ar–H), 8.11–8.14 (m, 1H, Ar–H), 10.22 (s, 1H, OH); 13
C
NMR (75 MHz, DMSO-d6): 71.42, 91.76, 110.28, 117.01, 119.57, 123.44, 124.07,
125.07, 125.39, 127.02, 128.80, 129.56, 131.47, 131.54, 140.81, 144.19, 146.14,
147.31, 157.09, 159.37, 160.06; MS m/z (%): 416 (M ? 2)?, 414 (M?), 342, 304,
303 (100), 238, 237, 189, 160, 127, 105, 77, 57, 43; Anal. calcd. for C23H15ClN4O2:
C, 66.58; H, 3.61; N, 13.51. Found: C, 66.62; H, 3.57; N, 13.58.
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A. Olyaei et al.
9,11-Diamino-6-hydroxy-12-(3-bromophenyl)-12H-benzo[5,6]chromeno[2,3-
b]pyridine-10-carbonitrile (9c)
Cream solid; mp [ 300 °C; IR (KBr, cm-1): 3494, 3355, 3239, 3062, 2900, 2202,
1623, 1605, 1469, 1400, 1322, 1253, 1079; H NMR (300 MHz, DMSO-d6): 6.04
1
(s, 1H, methine-H), 6.52 (s, 2H, NH2), 6.88 (s, 2H, NH2), 7.17–7.41 (m, 6H, Ar–H),
7.68 (s, 1H, Ar–H), 8.12 (d, 1H, J = 8.4 Hz, Ar–H), 10.25 (s, 1H, OH); 13C NMR
(75 MHz, DMSO-d6): 71.44, 91.56, 109.96, 116.46, 116.94, 119.36, 122.04, 123.31,
124.19, 125.02, 125.46, 126.82, 127.07, 129.83, 130.24, 131.18, 131.54, 140.88,
146.11, 147.83, 157.06, 159.39, 160.10; MS m/z (%): 460 (M ? 2), 458 (M?), 405,
391, 330, 303, 275, 237, 189, 164, 139 (100), 119, 111, 105, 91, 77; Anal. calcd. for
C23H15BrN4O2: C, 60.13; H, 3.26; N, 12.20. Found: C, 60.11; H, 3.30; N, 12.27.
9,11-Diamino-6-hydroxy-12-(4-bromophenyl)-12H-benzo[5,6]chromeno[2,3-
b]pyridine-10-carbonitrile (9d)
Yellow solid; mp [ 300 °C; IR (KBr, cm-1): 3498, 3351, 3239, 3077, 2969, 2202,
1623, 1565, 1473, 1400, 1322, 1257, 1149; H NMR (300 MHz, DMSO-d6): 6.04
1
(s, 1H, methine-H), 6.50 (s, 2H, NH2), 6.86 (s, 2H, NH2), 7.19–7.41 (m, 7H, Ar–H),
7.66–8.13 (m, 2H, Ar–H), 10.24 (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6):
71.42, 91.69, 110.28, 117.00, 119.49, 120.01, 123.42, 124.07, 125.07, 125.39,
125.98, 127.01, 129.94, 131.71, 140.80, 144.60, 146.13, 147.31, 157.09, 159.34,
160.05; MS m/z (%): 460 (M ? 2)?, 458 (M?), 405, 391, 330, 303, 275, 237, 219,
191, 160, 139, 119, 111, 105 (100), 91, 77, 57, 43; Anal. calcd. for C23H15BrN4O2:
C, 60.13; H, 3.26; N, 12.20. Found: C, 60.11; H, 3.25; N, 12.28.
9,11-Diamino-6-hydroxy-12-(4-flourophenyl)-12H-benzo[5,6]chromeno[2,3-
b]pyridine-10-carbonitrile (9e)
Green solid; mp [ 300 °C; IR (KBr, cm-1): 3498, 3351, 3243, 3077, 2923, 2202,
1623, 1566, 1511, 1469, 1403, 1257; H NMR (300 MHz, DMSO-d6): 6.04 (s, 1H,
1
methine-H), 6.48 (s, 2H, NH2), 6.85 (s, 2H, NH2), 6.99–7.67 (m, 7H, Ar–H),
7.98–8.16 (m, 2H, Ar–H), 10.21 (s, 1H, OH); 13C NMR (75 MHz, DMSO-d6):
71.41, 92.08, 110.16, 115.39, 115.66, 115.97, 116.26, 119.92, 123.50, 124.01,
125.08, 126.98, 129.49, 129.59, 131.54, 132.64, 140.77, 146.14, 157.04, 159.39;
MS m/z (%): 398 (M?), 391, 330, 303, 275, 237, 191, 164, 151, 141, 139 (100), 119,
111, 105, 91, 77, 57, 43; Anal. calcd. for C23H15FN4O2: C, 69.34; H, 3.76; N, 14.07.
Found: C, 69.30; H, 3.71; N, 14.11.
9,11-Diamino-6-hydroxy-12-(3-nitrophenyl)-12H-benzo[5,6]chromeno[2,3-
b]pyridine-10-carbonitrile (9f)
White solid; mp [ 300 °C; IR (KBr, cm-1): 3490, 3359, 3243, 3081, 2927, 2206,
1623, 1565, 1523, 1469, 1400, 1346, 1263, 1203; 1H NMR (300 MHz, DMSO-d6):
6.22 (s, 1H, methine-H), 6.56 (s, 2H, NH2), 6.96 (s, 2H, NH2), 7.22 (s, 7H, Ar–H),
7.32–8.15 (m, 7H, Ar–H), 8.43 (s, 1H, Ar–H), 10.31 (s, 1H, OH); 13C NMR
123

Organocatalytic approach toward the green one-pot synthesis…
(75 MHz, DMSO-d6): 71.46, 91.24, 110.67, 116.89, 118.95, 122.07, 122.17, 122.28,
123.17, 124.33, 124.94, 125.53, 127.13, 130.59, 131.55, 134.33, 141.02, 146.15,
147.23, 148.10, 157.14, 159.41, 160.22; MS m/z (%): 444 (M?), 398, 330, 303
(100), 274, 237, 191, 164, 151, 139, 127, 105, 77, 75, 43; Anal. calcd. for
C23H15FN5O4: C, 64.94; H, 3.53; N, 16.47. Found: C, 64.98; H, 3.59; N, 16.42.
Acknowledgements The authors thank the Research Council of Payame Noor University for financial
support.
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