Ultrasound-assisted one-pot synthesis of disubstituted and trisubstituted 1H-benzo[f]chromene derivatives catalyzed by 4-nitro-2,6-diacetylpyridinebis(2, 4,6-trimethylaniline)FeCl2

Article abstract of DOI:10.1007/s11164-012-0933-y

1,3-Diaryl-1H-benzo[f]chromenes and 1,3-diaryl-1H-benzo[f]chromen-2-yl) (phenyl)methanones have been synthesized by one-pot three-component reaction of naphthols, aromatic aldehydes, and acetophenone or 1,3-diphenylpropane-1,3- dione, with the bis(imino)p

Full text of DOI:10.1007/s11164-012-0933-y

Res Chem Intermed
DOI 10.1007/s11164-012-0933-y
Ultrasound-assisted one-pot synthesis of disubstituted
and trisubstituted 1H-benzo[f]chromene derivatives
catalyzed by 4-nitro-2,6-diacetylpyridinebis
(2,4,6-trimethylaniline)FeCl2
•
Reza Sandaroos Saman Damavandi
Received: 7 July 2012 / Accepted: 17 November 2012
Ó Springer Science+Business Media Dordrecht 2012
Abstract 1,3-Diaryl-1H-benzo[f]chromenes and 1,3-diaryl-1H-benzo[f]chromen-2-
yl)(phenyl)methanones have been synthesized by one-pot three-component reaction of
naphthols, aromatic aldehydes, and acetophenone or 1,3-diphenylpropane-1,3-dione,
with the bis(imino)pyridine iron-based catalyst 4-nitro-2,6-diacetylpyridinebis(2,4,6-
trimethylaniline)FeCl2. This novel, efficient, and rapid method is performed under
solvent-free conditions with ultrasonic irradiation.
Keywords Benzo[f]chromene Á One-pot Á Ultrasonication Á Catalyst
Introduction
Recently, ‘‘ideal synthesis’’ has been defined as one in which the target compound is
generated in one step, in quantitative yield, from readily available and inexpensive
starting materials in a resource-effective and environmentally acceptable process
[1, 2]. One-pot multicomponent condensations are possible means of performing
near ideal synthesis because they have one of the aforementioned qualities, namely
the possibility of building-up complex molecules with maximum simplicity and
diversity [1–3].
Ultrasound is increasingly being used in organic synthesis. Many ultrasound-
assisted reactions can be carried out in higher yield, shorter reaction time, or under
milder conditions [4–7]. The temperature of hot spots caused by the collapse of
acoustic caves can be absorbed by organic molecules to dramatically raise their
R. Sandaroos (&)
Department of Chemistry, Faculty of Science, University of Birjand, Birjand, Iran
e-mail: r_sandaroos@yahoo.com; r_sandaroos@birjand.ac.ir
S. Damavandi (&)
Young Researchers Club, Sarvestan Branch, Islamic Azad University, Sarvestan, Fars, Iran
e-mail: saman_damavandi@yahoo.com
123

R. Sandaroos, S. Damavandi
intrinsic energy leading to the apparent improvement of the reaction efficiency with
increased rates and reduced reaction time.
Chromene derivatives are a class of important compounds with wide application
in medicinal chemistry [8]. They have antihyperglycemic and antidyslipidemic [9],
cytotoxic [10], molluscicidal [11], anti-inflammatory [12], and antifungal activity
[13]. In addition, chromenes are components of numerous natural products [14].
Nowadays there is increasing awareness of the urgent need to limit, as far as
possible, any source of pollution. In response to this, chemists have devoted much
effort to the development of clean techniques [15]. This new challenge has led to
growing interest in organic reactions performed in aqueous media and under solvent
free conditions [15, 16].
Schiff bases are versatile catalysts which have been used in many and various
fields of organic chemistry. Recently, we have studied the catalytic activity and
application of novel 2,6-bis(imino)pyridine catalysts, based on iron(II), with
different substituents [17]. In continuation of our study on the development of new
syntheses of heterocyclic compounds via novel one-pot MCRs [18–23], a novel
three-component reaction for synthesis of disubstituted and trisubstituted 1H-
benzo[f]chromene derivatives is reported herein. Although a few procedures have
been reported for synthesis of 1,3-diaryl-3H-benzo[f]chromene compounds, for
example, acid catalyzed Claisen rearrangement of alkynyl aryl ethers from
propargylic alcohols and naphthols [24, 25], to the best of our knowledge there is
no literature report of preparation of 1,3-diaryl-3H-benzo[f]chromenes and 1,3-
diaryl-1H-benzo[f]chromen-2-yl)(phenyl)methanones by one-pot condensation of
naphthols, aldehydes, and acetophenone or 1,3-diphenylpropane-1,3-dione using
4-nitro-2,6-diacetylpyridinebis(2,4,6-trimethylaniline)FeCl2 as catalyst, ultrasonic
irradiation, and solvent-free conditions (Scheme 1).
Experimental
Chemicals wereeitherpreparedin our laboratoriesorpurchased fromMerck, Fluka, and
Aldrich.Allyieldsrefertoisolatedproducts. IRspectrawererecordedonaShimadzu-IR
1
470 spectrophotometer at room temperature. H NMR spectra were recorded on a
Bruker 100-MHz spectrometer at room temperature in chloroform as solvent and with
TMS as internal standard. Flash column chromatography was performed with 300 and
400 mesh silica gel and analytical thin-layer chromatography was performed on
R
H
NO2
O
O
Ph
O
N
H
H
R
N
N
H
R
Fe
R
O
Cl
O
Cl
Ultrasonic irradiation
Solvent-free, 60 o
H
O
+
2 H2O
+
C
R= H or CH2COPh
Scheme 1 Synthetic route to disubstituted and trisubstituted 1H-benzo[f]chromene derivatives
123

Ultrasound-assisted one-pot synthesis
pre-coatedsilica gel plates (60F-254). Elemental analysis was performed with a Thermo
Finnigan EA1112 elemental analyzer. Sonication was performed in a Kunshan KQ-
250B ultrasonic cleaner with a frequency of 40 kHz and 250 W power. The reaction
flasks were located in the maximum energy area in the cleaner, and the temperature
of the water bath was controlled by addition or removal of water. 4-Nitro-2,6-
diacetylpyridinebis(2,4,6-trimethylaniline)FeCl2 was prepared in accordance with
method reported elsewhere [17].
General procedure for synthesis of 1,3-diaryl-3H-benzo[f]chromene derivatives
In a round-bottomed flask a mixture of naphthol (1 mmol), aromatic aldehyde
(1.1 mmol), and acetophenone or 1,3-diphenylpropane-1,3-dione (1 mmol) was mixed
with 4-nitro-2,6-diacetylpyridinebis(2,4,6-trimethylaniline)) FeCl2 (0.1 mmol) and the
mixture was irradiated with ultrasonic waves at 60 °C for an appropriate time, as
indicated in Table 1. The progress of the reaction was monitored by TLC. After
completion of the reaction, the mixture was cooled to room temperature and extracted
with dichloromethane (10 mL), and the catalyst was isolated by filtration. The organic
layer was then washed with water and dried over anhydrous Na2SO4. Organic solvent
was evaporated under reduced pressure and the product obtained was purified by short-
column chromatography on silica gel (ethyl acetate–hexane, 4:1) to afford the pure
product in good yield. Representative spectral data for the selected products are as
follows:
1,3-Diphenyl-3H-benzo[f]chromene (entry 1)
1H NMR (100 MHz, CDCl3): d 6.90–7.10 (m, 7H, Ar), 7.25–7.40 (m, 5H, Ar),
7.40–7.55 (m, 4H, Ar), 5.9 (d, 1H, J = 1.5 Hz), 4.90 (d, 1H, J = 1.5 Hz). Ms (m/z):
336, 335, 334, 128, 105, 106, 77. Anal. Calcd. for C25H18O: C, 89.79; H, 5.43;
Found: C 88.63, H 5.35.
3-(4-Chlorophenyl)-1-phenyl-3H-benzo[f]chromene (entry 2)
1H NMR (100 MHz, CDCl3): d 7.10–7.22 (m, 6H, Ar), 7.25–7.55 (m, 9H, Ar), 5.76
(d, 1H, J = 3.2 Hz), 4.84 (d, 1H, J = 3.2 Hz). Ms (m/z): 370, 369, 368, 139 105,
106, 77. Anal. Calcd. for C25H17ClO: C 81.41, H 4.65, Found: C 81.53, H 4.69.
3-(4-Methoxyphenyl)-1-phenyl-3H-benzo[f]chromene (entry 3)
1H NMR (100 MHz, CDCl3): d 7.46–7.55 (m, 10H, Ar), 6.96–7.25 (m, 5H, Ar),
5.80 (d, 1H, J = 3.5 Hz), 4.80 (d, 1H, J = 3.5 Hz), 3.75 (s, 3H). Ms (m/z): 366,
365, 364, 349, 333, 322, 135, 106, 77. Anal. Calcd. for C26H20O2: C 85.69, H 5.53,
Found: C 85.51, H 5.48.
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R. Sandaroos, S. Damavandi
Table 1 Results of
benzo[f]chromenes synthesis
using iron (II)-based catalyst
a
Entry
Product
Time (min)
Yield (%)
1
55
54
85
O
Cl
2
3
88
82
O
O
57
58
58
O
Br
4
5
84
85
O
O
6
7
52
50
87
90
O
O
Cl
8
9
O
52
58
82
80
O
O
O
Ph
O
10
11
12
62
65
65
81
80
82
O2
N
O
Ph
O
Br
O
Ph
O
Reaction conditions: 1.0 equiv.
of naphthol, 1.0 equiv. of
aldehyde, 1 equiv. of diketone,
10 mol% catalyst, under
ultrasonication
O
O
Ph
13
65
80
O
a
Isolated yields
123

Ultrasound-assisted one-pot synthesis
3-(2-Bromophenyl)-1-phenyl-3H-benzo[f]chromene (entry 4)
1H NMR (100 MHz, CDCl3): d 7.55–7.70 (m, 7H, Ar), 7.20–7.50 (m, 8H, Ar), 6.10
(d, 1H, J = 5 Hz), 4.85 (d, 1H, J = 5 Hz). Ms (m/z): 414, 413, 412, 182, 127, 105,
77. Anal. Calcd. for C25H17BrO: C 72.65, H 4.15, Found: C 72.49, H 4.09.
3-(4-Methylphenyl)-1-phenyl-3H-benzo[f]chromene (entry 5)
1H NMR (100 MHz, CDCl3): d 7.30–7.48 (m, 10H, Ar), 7.10–7.22 (m, 5H, Ar),
6.14 (d, 1H, J = 3.7 Hz), 4.85 (d, 1H, J = 3.7 Hz), 2.22 (s, 3H). Ms (m/z): 350,
349, 348, 182, 119, 105, 77. Anal. Calcd. for C26H20O: C, 89.62; H, 5.79; Found: C
89.38, H 5.68.
2,4-Diphenyl-4H-benzo[h]chromene (entry 6)
1H NMR (100 MHz, CDCl3): d 7.75–7.70 (m, 2H, Ar), 7.60–7.45 (m, 7H, Ar),
7.42–7.16 (m, 7H, Ar), 6.03 (d, 1H, J = 6.2 Hz), 4.92 (d, 1H, J = 6.5 Hz). Ms (m/
z): 336, 335, 334, 128, 105, 106, 77. Anal. Calcd. for C25H18O: C, 89.79; H, 5.43;
Found: C 89.56, H 5.48.
4-(4-Chlorophenyl)-2-phenyl-4H-benzo[h]chromene (entry 7)
1H NMR (100 MHz, CDCl3): d 7.84 (d, 1H, Ar), 7.63–7.55 (m, 5H, Ar), 7.35–7.10
(m, 9H, Ar), 5.92 (d, 1H, J = 5 Hz), 4.53 (d, 1H, J = 5.2 Hz). Ms (m/z): 370, 369,
368, 139 105, 106, 77. Anal. Calcd. for C25H17ClO: C, 81.41; H, 4.65; Found: C
81.52, H 4.69.
4-(4-Methoxyphenyl)-2-phenyl-4H-benzo[h]chromene (entry 8)
1H NMR (100 MHz, CDCl3): d 7.82 (d, J = 7.4 Hz, 1H), 7.25–7.62 (m, 9H, Ar),
7–7.25 (m, 6H, Ar), 6.12 (d, 2H, J = 3.5 Hz), 6.05 (d, 1H, J = 3.5 Hz), 4.90 (d,
1H, J = 5 Hz). Ms (m/z): 366, 365, 364, 349, 333, 322, 135, 106, 77. Anal. Calcd.
for C26H20O2: C 85.69, H 5.53, Found: C 85.12, H 5.44.
2-Phenyl-4-p-tolyl-4H-benzo[h]chromene (entry 9)
1H NMR (100 MHz, CDCl3): d 7.90–7.75 (m, 3H, Ar), 7.65–7.55 (m, 3H, Ar),
7.50–7.32 (m, 6H, Ar), 7.30–7.05 (m, 3H, Ar), 5.92 (d, 1H, J = 6.5 Hz), 4.96 (d,
1H, J = 6.5 Hz), 2.27 (s, 3H, Me). Ms (m/z): 350, 349, 348, 182, 119, 105, 77.
Anal. Calcd. for C26H20O: C 89.62, H 5.79, Found: C 88.57, H 5.83.
Phenyl(3-phenyl-1-p-tolyl-1H-benzo[f]chromen-2-yl)methanone (entry 10)
1H NMR (100 MHz, CDCl3): d 7.85–7.45 (m, 12H, Ar), 7.35–6.90 (m, 8H, Ar),
6.14 (s, 1H, CH), 2.25 (s, 3H, Me). Ms (m/z): 354, 353, 352, 347, 119, 105, 77. Anal.
Calcd. for C33H24O2: C, 87.58; H, 5.35; Found: C 86.22, H 5.16.
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R. Sandaroos, S. Damavandi
(1-(4-Nitrophenyl)-3-phenyl-1H-benzo[f]chromen-2-yl)(phenyl)methanone
(entry 11)
1H NMR (100 MHz, CDCl3): d 8.02 (m, 2H, Ar), 7.80–7.62 (m, 7H, Ar), 7.55–7.42
(m, 6H, Ar), 7.35–7.10 (m, 5H, Ar), 5.65 (s, 1H, CH). Ms (m/z): 485, 484, 483, 453,
437, 127, 104, 105. Anal. Calcd. for C32H21NO4: C, 79.49; H, 4.38; Found: C 80.11,
H 4.44.
(1-(4-Bromophenyl)-3-phenyl-1H-benzo[f]chromen-2-yl)(phenyl)methanone
(entry 12)
1H NMR (100 MHz, CDCl3): d 7.77–7.67 (m, 3H, Ar), 7.60–7.45 (m, 8H, Ar),
7.37–7.28 (m, 5H, Ar), 7.21–7.02 (m, 4H, Ar), 4.90 (s, 1H, CH). Ms (m/z): 518, 517,
516, 347, 119, 105, 77. Anal. Calcd. for C32H21BrO2: C, 74.28; H, 4.09; Found: C
75.02, H 4.17.
(1-(4-Methoxyphenyl)-3-phenyl-1H-benzo[f]chromen-2-yl)(phenyl)methanone
(entry 13)
1H NMR (100 MHz, CDCl3): d 7.40–7.75 (m, 11H, Ar), 6.70–7.25 (m, 9H, Ar),
5.65 (s, 1H, CH), 3.65 (s, 3H, OMe). Ms (m/z): 470, 469, 468, 453, 437, 127, 104,
105. Anal. Calcd. for C33H24O3: C, 84.59; H, 5.16; Found: C 83.44, H 5.06.
Results and discussion
First, one-pot reaction of acetophenone, 2-naphthol, and benzaldehyde was performed
under solvent-free conditions with ultrasonic irradiation. This reaction was regarded as
the model reaction. To evaluate the effect of ultrasonic irradiation (Table 1, compound
1), first the model reaction was conducted in the presence of 10 mol% catalyst, without
ultrasound, at 60 °C. With prolonged reaction time (5 h) a moderate yield (68 %) was
obtained, whereas when the reaction was performed with ultrasonication, good yield
(85 %) of the corresponding 1,3-diaryl-3H-benzo[f]chromene was obtained within a
short reaction time(55 min). Furthermore, nobyproduct was detectedwhen the reaction
was performed with ultrasonic irradiation. The scope and generality of this process was
illustrated by use of different aromatic aldehydes. Aromatic aldehydes substituted with
either electron-donating or electron-withdrawing groups underwent the reaction
smoothly and gave the corresponding 1,3-diaryl-3H-benzo[f]chromene in good yields.
Although differences between reaction times were small, electron-deficient substituents
were usually superior to electron-rich substituents in this regard. In addition to
2-naphthol, 1-naphthol was used and the corresponding disubstituted benzo[h]chro-
mene derivatives were obtained in good yields (Table 1, entries 6–9).
Toextendourresearch,weusedanotherenolizableketone,1,3-diphenylpropane-1,3-
dione, and one-pot cyclocondensations of 1,3-diphenylpropane-1,3-dione, aromatic
aldehydes, and 2-naphthol were performed under identical reaction conditions. As is
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Ultrasound-assisted one-pot synthesis
apparent from Table 1, the corresponding 1,3-diaryl-1H-benzo[f]chromen-2-yl)-
(phenyl)methanone derivatives were synthesized in good yields.
The mechanism suggested for synthesis of 1,3-diaryl-1H-benzo[f]chromen-2-
yl)(phenyl)methanones is given in Scheme 2. The reaction probably proceeds via
in-situ generation of ortho-quinone methides, followed by Michael-type addition of
the enolized 1,3-diphenylpropane-1,3-dione to the methides, dehydration, and
heterocyclization leading to synthesis of the 1,3-diaryl-1H-benzo[f]chromen-2-
yl)(phenyl)methanones product. The iron(II)-based Schiff base catalyst used is a
strong Lewis acid because iron has an empty 3d orbital and because it is chelated
with three nitrogen ligands which lead to substantial electron deficiency on the
central metal. It can activate the carbonyl groups (C=O) of intermediates, thus
facilitating the reaction.
Conclusion
A novel three-component synthesis of 1,3-diaryl-1H-benzo[f]chromene and 1,3-
diaryl-1H-benzo[f]chromen-2-yl)(phenyl)methanone derivatives in the presence of
(4-nitro-2,6-diacetylpyridinebis(2,4,6-trimethylaniline)FeCl2, under ultrasonic irra-
diation and solvent free conditions, is described. The catalyst had high activity and
the reactions were highly selective affording exclusively disubstituted and
trisubstituted benzo[f]chromenes in high yield.
O
O
OH
O
..
Fe(II)
R
H
R
O
..
OH
-H2O
+
O
Fe(II)
R
R
R
O
O
O
O
..
OH
O
O
Fe(II)
O
-H2O
Scheme 2 Proposed mechanism for synthesis of 1,3-diaryl-1H-benzo[f]chromen-2-yl)(phenyl)methanones
123

R. Sandaroos, S. Damavandi
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