Aqua-mediated multicomponent synthesis of various 4H-pyran derivatives catalyzed by poly(4-vinylpyridine)-supported copper iodide nanoparticle catalyst

Article abstract of DOI:10.1007/s11164-015-2400-z

A green and efficient approach for synthesis of some new 4H-pyran derivatives is reported, catalyzed by green recyclable poly(4-vinylpyridine)-supported copper iodide nanoparticle catalyst in water. This procedure has many advantages such as operational s

Full text of DOI:10.1007/s11164-015-2400-z

Res Chem Intermed
DOI 10.1007/s11164-015-2400-z
Aqua-mediated multicomponent synthesis of various
4H-pyran derivatives catalyzed by poly
(4-vinylpyridine)-supported copper iodide nanoparticle
catalyst
Jalal Albadi1 Azam Mansournezhad1
•
Received: 8 September 2015 / Accepted: 16 December 2015
Ó Springer Science+Business Media Dordrecht 2016
Abstract A green and efficient approach for synthesis of some new 4H-pyran
derivatives is reported, catalyzed by green recyclable poly(4-vinylpyridine)-sup-
ported copper iodide nanoparticle catalyst in water. This procedure has many
advantages such as operational simplicity, short reaction time, clean procedure, and
high product yield.
Keywords 4H-pyran derivatives Á Malononitrile Á Aldehyde Á Poly
(4-vinylpyridine)-supported copper iodide nanoparticles
Introduction
Pyran and chromene derivatives are an important class of oxygen-containing
heterocycles, being the main components of many naturally occurring products and
exhibiting a wide spectrum of biological activities [1, 2]. These compounds are
widely employed as cosmetics, pigments, and potential biodegradable agrochem-
icals [3, 4]. Pyrans and chromenes can also serve as useful building blocks for
production of a range of natural products showing molluscicidal, antibacterial,
anticancer, anticoagulant, antiallergic, antibiotic, hypolipidemic, and immunomod-
ulating activities [5, 6]. Because of these properties, pyran and chromene derivatives
have received significant attention from many pharmaceutical scientists and
chemists. Consequently, several catalysts have been reported for promoting
synthesis of pyran and chromene derivatives [7–25].
Electronic supplementary material The online version of this article (doi:10.1007/s11164-015-2400-z)
contains supplementary material, which is available to authorized users.
&
Jalal Albadi
Chemalbadi@gmail.com; Albadi@bkatu.ac.ir
1
College of Science, Behbahan Khatam Alanbia University of Technology, Behbahan, Iran
123

J. Albadi, A. Mansournezhad
The multicomponent reaction approach has attracted attention from synthetic
organic chemists for building up highly functionalized organic molecules and
pharmacologically important heterocyclic compounds. These reactions present wide
potential for efficient construction of highly complex molecules in a single
procedural step, avoiding difficult purification operations and allowing savings of
both solvents and reagents. Due to their atom economy, simplicity, high product
yield, and time-saving nature, multicomponent reactions (MCRs) provide a simple
and useful route for synthesis of various heterocyclic compounds [26, 27].
CuI, as a Lewis acid catalyst, promotes organic synthesis reactions effectively.
However, it is a toxic compound and suffers from thermodynamic instability,
nonrecyclability, and difficulty in separation of the products from the reaction
mixture. Such drawbacks could be obviated by using polymer-supported CuI. The
best supports are those which have nitrogen or oxygen binding sites and are chelated
with copper catalysts. Nitrogen-based polymers have been shown to protect the
metal center from oxidation and disproportionation, while enhancing the catalytic
activity [28]. In previous research, we reported preparation and application of
poly(4-vinylpyridine)-supported copper iodide nanoparticles (P4VPy-CuI) in some
organic reactions [29–33]. P4VPy-CuI possesses increased advantages over CuI,
being a safe, stable, easy to handle, and recyclable catalyst. It can be recovered
simply by filtration and can be reused in subsequent runs without significant loss in
catalytic activity. In continuation of our studies on synthesis of benzopyrans and
chromene derivatives [34–37], we report herein synthesis of various 4H-pyran
derivatives catalyzed by P4VPy-CuI as an efficient recyclable catalyst in water.
Experimental
All known products were characterized by comparison of their spectroscopic
[nuclear magnetic resonance (NMR) and infrared (IR)] data and physical properties
with those reported in literature. The new compounds were identified by elemental
analysis, physical properties, and IR and NMR spectra. IR spectra were recorded on
a PerkinElmer 781 spectrophotometer. NMR spectra were recorded on a Bruker
Advance 400 MHz. Yields refer to isolated pure products. P4VPy-CuI was prepared
according to the our previous articles [29, 30].
Determination of copper content in P4VPy-CuI
P4VPy-CuI (100 mg) was extracted with concentrated HCl (5 9 2 mL) in a screw-
capped vessel, followed by treatment with concentrated nitric acid (2 mL) to digest
the metal complex. The mixture was then transferred into a volumetric flask
(100 mL), diluted 1:50 for a second time, and analyzed by inductively coupled
plasma (ICP) analysis. The copper concentration was determined from atomic
emission (324.754 nm) with reference to a linear (R = 0.99) calibration curve of
(1–4 ppm) CuI prepared in a manner identical to the sample preparation. The
loading of the supported catalyst was calculated to be 1.32 mmol CuI g-1 of
prepared catalyst.
123

Aqua-mediated multicomponent synthesis of various 4H…
General procedure
A mixture of aldehyde (1 mmol), malononitrile (1 mmol), resorcinol or 3-methyl-1-
phenyl-2-pyrazolin-5-one (1 mmol) or 1,3-dicarbonyl compounds (1 mmol), and
P4VPy-CuI (0.07 g) in water (10 mL) was stirred at reflux conditions. After reaction
completion as monitored by thin-layer chromatography (TLC), the reaction mixture
was cooled to room temperature and filtered, and hot ethanol was added. Then, the
catalyst was recovered for subsequent use by filtration. Evaporation of the solvent
from the filtrate and recrystallization of the solid residue from hot ethanol afforded
pure products in high yields. The spectral and analytical data for the new
compounds are as follows:
Table 2, entry 13: White solid, m.p.: 196–198 °C; IR (KBr) mmax/cm-1: 3450,
1
3300, 3200, 2200, 1640, 1590, 1540, 1395, 1340, 1120, 1060, 1040, 1020, 750. H
NMR (DMSO-d6, 400 MHz), d (ppm): 1.82 (s, 3H, CH3), 4.91 (s, 1H, CH), 7.31 (t,
1H, J = 7.41 Hz, Ar), 7.37 (s, 2H, NH2), 7.48 (t, 2H, J = 8.16 Hz, Ar), 7.65 (d, 1H,
J = 8.32 Hz, Ar), 7.78 (t, 3H, J = 8.26 Hz, Ar), 8.04 (s, 1H, Ar). 13C NMR
(DMSO-d6, 100 MHz), d (ppm): 12.5, 35.7, 56.7, 97.2, 119.7, 120.1, 123.3, 124.5,
126.2, 129.2, 131.7, 133.2, 137.4, 144.0, 144.9, 145.0, 147.8, 159.7, 159.7. Elem.
Anal. Found: C, 58.99 %; H, 3.51 % N, 17.23 % (calculated for C20H14N5O2Cl: C,
58.90 %; H, 3.46 %; N, 17.17 %).
Table 2, entry 14: White solid, m.p.: 257–259 °C; IR (KBr) mmax/cm-1: 3500,
3400, 3200, 3100, 2200, 1650, 1600, 1540, 1510, 1410, 1320, 1240, 1080, 1040,
960, 840, 810. 1H NMR (DMSO-d6, 400 MHz), d (ppm): 2.00 (s, 3H, CH3), 2.31 (s,
3H, CH3), 4.90 (s, 1H, CH), 7.16 (d, 2H, J = 8.38 Hz, Ar), 7.23 (t, 1H,
J = 7.29 Hz, Ar), 7.41–7.46 (m, 6H, Ar, NH2), 7.70 (d, 2H, J = 8.08 Hz, Ar), 9.85
(s, 1H, NH). 13C NMR (DMSO-d6, 100 MHz), d (ppm): 11.6, 23.8, 32.6, 54.8, 95.6,
118.9, 119.0, 120.5, 125.5, 127.3, 128.8, 136.7, 137.1, 137.2, 146.2, 155.2, 167.9,
168.0. Elem. Anal. Found: C, 68.61 %; H, 5.02 % N, 18.23 % (calculated for
C21H16N4: C, 68.55 %; H, 4.96 %; N, 18.17 %).
Table 2, entry 15: Yellow solid, m.p.: 202–204 °C; IR (KBr) mmax/cm-1: 3466,
3340, 2191, 1641, 1587, 1505, 1459, 1406, 1344, 1309, 1247, 1155, 1111, 1056,
1
1012, 964. H NMR (CDCl3, 400 MHz), d (ppm): 2.10 (s, 3H, CH3), 4.74 (s, 1H,
CH), 4.98 (s, 2H, NH2), 5.16 (s, 2H, CH2), 6.83 (d, 2H, J = 8.68 Hz, Ar), 7.09–7.12
(m, 4H, Ar), 7.25–7.39 (m, 4H, Ar), 7.60 (d, 4H, J = 7.91 Hz, Ar). 13C NMR
(CDCl3, 100 MHz), d (ppm): 11.6, 32.3, 57.8, 69.1, 97.3, 114.3, 119.8, 120.4, 125.5,
127.5, 127.7, 128.1, 128.4, 128.9, 137.2, 146.2, 156.6, 157.1, 158.3, 158.4, 164.1.
Elem. Anal. Found: C, 74.71 %; H, 5.17 % N, 13.07 % (calculated for C27H22N4O2:
C, 74.63 %; H, 5.10 %; N, 12.98 %).
Table 4, entry 11: White solid, m.p.: 200–202 °C; IR (KBr) mmax/cm-1: 3425,
3312, 3186, 2961, 2183, 1655, 1381, 1251, 1215, 1161, 1043. 1H NMR (DMSO-d6,
400 MHz), d (ppm): 1.03 (s, 6H, 2CH3), 1.66–1.71 (m, 1H), 1.83–1.88 (m, 1H),
2.12 (d, 1H, J = 16 Hz), 2.24 (d, 1H, J = 16 Hz), 2.33 (d, 1H, J = 17.6 Hz), 2.40
(d, 1H, J = 18.4 Hz), 2.43–2.49 (m, 1H), 3.29 (t, 1H, J = 4.4 Hz), 7.01 (s, 2H),
7.11–7.18 (t, 1H, J = 7.6, d, 2H, J = 7.6, Ar), 7.27 (t, 2H, J = 7.6, Ar). 13C NMR
(DMSO-d6, 100 MHz), d (ppm): 27.4, 28.7, 29.7, 31.1, 32.0, 36.5, 50.5, 55.5, 112.7,
120.6, 126.1, 128.5, 128.8, 142.1, 160.4, 160.5, 163.7, 196.7. Elem. Anal. Found: C,
123

J. Albadi, A. Mansournezhad
74.57 %; H, 6.92 % N, 8.73 % (calculated for C20H22N2O2: C, 74.50 %; H, 6.88 %;
N, 8.69 %).
Table 4, entry 12: Yellow solid, m.p.: 244–246 °C; IR (KBr) mmax/cm-1: 3453,
3334, 2961, 2193, 1681, 1657, 1353, 1247, 1211, 1145, 1038, 725. 1H NMR
(DMSO-d6, 400 MHz), d (ppm): 1.05 (s, 3H, CH3), 1.07 (s, 3H, CH3), 1.89 (d, 1H,
J = 16 Hz), 2.13 (d, 1H, J = 16 Hz), 2.63 (t, 2H, J = 18 Hz), 6.01 (s, 1H, CH),
7.07 (s, 2H, NH2), 7.43–7.49 (m, 2H, Ar), 7.52–7.60 (m, 2H Ar), 8.09 (d, 3H,
J = 8.1 Hz, Ar), 8.54 (s, 1H), 8.66 (d, 1H, J = 8.8 Hz, Ar). 13C NMR (DMSO-d6,
100 MHz), d (ppm): 27.2, 28.9, 29.8, 32.0, 50.4, 58.6, 114.3, 119.7, 123.6, 124.9,
125.1, 125.4, 125.5, 126.4, 127.8, 129.2, 129.3, 130.2, 131.2, 131.4, 132.0, 135.0,
158.4, 158.5, 162.4, 196.1. Elem. Anal. Found: C, 79.27 %; H, 5.71 % N, 7.19 %
(calculated for C26H22N2O2: C, 79.16 %; H, 5.62 %; N, 7.10 %).
Table 4, entry 13: White solid, m.p.: 218–220 °C; IR (KBr) mmax/cm-1: 3456,
3387, 3317, 3254, 3208, 2958, 2898, 2191, 1686, 1658, 1601, 1507, 1461, 1367,
1
1241, 1140, 1030, 842, 747. H NMR (CDCl3, 400 MHz), d (ppm): 1.03 (s, 3H,
CH3), 1.10 (s, 3H, CH3), 2.19 (d, 1H, J = 16 Hz), 2.23 (d, 1H, J = 16 Hz), 2.43 (s,
2H), 4.36 (s, 1H), 4.50 (s, 2H, NH2), 5.01 (s, 2H), 6.88 (d, 2H, J = 8.6 Hz, Ar),
7.14–7.16 (d, 2H, J = 8.6 Hz, Ar), 7.31–7.42 (m, 5H). 13C NMR (CDCl3,
100 MHz), d (ppm): 26.8, 28.3, 31.7, 34.7, 50.0, 58.5, 69.2, 112.9, 114.4, 119.7,
127.6, 127.8, 128.2, 128.4, 137.1, 137.1, 157.1, 158.3, 158.4, 162.1, 195.6. Elem.
Anal. Found: C, 75.07 %; H, 6.09 % N, 7.08 % (calculated for C25H24N2O3: C,
74.97 %; H, 6.04 %; N, 6.99 %).
Table 4, entry 14: White solid, m.p.: 199–201 °C; IR (KBr) mmax/cm-1: 3456,
3330, 3206, 2941, 2195, 1681, 1601, 1509, 1457, 1418, 1368, 1245, 1198, 1171,
1
1136, 1067, 1005, 835. H NMR (CDCl3, 400 MHz), d (ppm): 1.96–2.03 (m, 2H),
2.31–2.37 (m, 2H), 2.53–258 (m, 2H), 4.38 (s, 1H), 4.56 (s, 2H, NH2), 5.00 (s, 2H),
6.88 (d, 2H, J = 8.6 Hz, Ar), 7.15 (d, 2H, J = 8.6 Hz, Ar), 7.31–7.41 (m, 5H). 13
C
NMR (CDCl3, 100 MHz), d (ppm): 19.8, 26.4, 34.6, 36.3, 58.4, 69.2, 114.5, 119.8,
127.6, 127.8, 128.2, 128.4, 137.1, 137.1, 157.1, 158.3, 158.4, 164.1, 195.8. Elem.
Anal. Found: C, 74.26 %; H, 5.48 % N, 7.59 % (calculated for C23H20N2O3: C,
74.17 %; H, 5.41 %; N, 7.52 %).
Table 4, entry 17: White solid, m.p.: 128–130 °C; IR (KBr) mmax/cm-1: 3376,
1
3326, 3194, 2959, 2189, 1680, 1657, 1603, 1383, 1209, 1176, 1137, 1005, 743. H
NMR (DMSO-d6, 400 MHz), d (ppm): 1.63–1.70 (m, 1H), 1.75–192 (m, 3H),
2.25–2.29 (m, 2H), 2.38–2.49 (m, 3H), 3.28 (t, 1H, CH, J = 4.4 Hz), 6.99 (s, 2H,
NH2), 7.11–7.18 (m, 3H, 3H, Ar), 7.26 (t, 2H J = 7.6 Hz, Ar). 13C NMR (DMSO-
d6, 100 MHz), d (ppm): 20.2, 26.9, 29.7, 30.9, 36.3, 36.8, 55.4, 113.8, 120.6, 126.1,
128.5, 128.7, 142.2, 160.3, 160.4, 165.4, 196.9. Elem. Anal. Found: C, 73.53 %; H,
6.22 % N, 9.59 % (calculated for C18H18N2O2: C, 73.44 %; H, 6.16 %; N, 9.51 %).
Table 4, entry 18: Yellow solid, m.p.: 248–250 °C; IR (KBr) mmax/cm-1: 3451,
3337, 2949, 2192, 1678, 1656, 1352, 1244, 1203, 1139, 997, 724. 1H NMR (DMSO-
d6, 400 MHz), d (ppm): 1.78–181 (m, 1H), 1.93–2.08 (m, 2H), 2.15–2.22 (m, 1H),
2.69–2.76 (m, 2H), 6.00 (s, 1H), 7.06 (s, 2H, NH2), 7.46–7.48 (m, 2H, Ar),
7.52–7.60 (m, 2H, Ar), 8.08 (d, 3H, J = 8.8 Hz, Ar), 8.54 (s, 1H), 8.67 (d, 1H,
J = 8.8 Hz, Ar). 13C NMR (DMSO-d6, 100 MHz), d (ppm): 20.4, 27.1, 29.9, 36.8,
58.5, 115.2, 119.7, 123.4, 124.9, 125.1, 125.4, 125.5, 126.4, 127.8, 129.2, 129.3,
123

Aqua-mediated multicomponent synthesis of various 4H…
130.3, 131.2, 131.4, 132.0, 134.9, 158.3, 158.3, 164.2, 196.1. Elem. Anal. Found: C,
78.75 %; H, 5.02 % N, 7.71 % (calculated for C24H18N2O2: C, 78.67 %; H, 4.95 %;
N, 7.64 %).
Table 6, entry 14: White solid, m.p.: 151–152 °C; IR (KBr) mmax/cm-1: 3444,
3337, 3217, 2193, 1645, 1587, 1408, 1156, 1114. 1H NMR (DMSO-d6, 400 MHz), d
(ppm): 4.69 (s, 1H), 6.43 (d, 1H, J = 2.4), 6.51–6.53 (dd, 1H, J = 2.4), 6.83 (d, 1H,
J = 8.4), 6.98 (s, 2H, NH2), 7.19 (d, 1H, J = 7.6), 7.29 (t, 1H, J = 7.6), 7.35–7.36
(m, 1H), 7.41–7.44 (m, 1H), 9.78 (s, 1H). 13C NMR (DMSO-d6, 100 MHz), d
(ppm): 38.3, 56.1, 102.7, 113.0, 113.4, 120.9, 122.3, 127.0, 130.0, 130.4, 130.4,
131.3, 149.3, 149.5, 157.7, 160.8. Elem. Anal. Found: C, 54.48 %; H, 3.41 % N,
8.53 % (calculated for C15H11N2O2Br: C, 54.40 %; H, 3.34 %; N, 8.45 %).
Results and discussion
P4VPy-CuI was prepared by a coprecipitation method and characterized by
Brunauer–Emmett–Teller (BET) surface area, Fourier-transform infrared (FT-IR)
spectroscopy (Fig. 1), energy-dispersive x-ray spectroscopy (EDS), X-ray diffrac-
tion (XRD) analysis (Fig. 2), scanning electron microscopy (SEM) analysis (Fig. 3),
and ICP analysis [29, 30]. SEM imaging of the prepared catalyst indicated that CuI
nanoparticles were homogeneously immobilized on poly(4-vinylpyridine) surface.
According to SEM images of P4VPy-CuI, the average size of copper nanoparticles
was estimated to be 75–100 nm. Sharp peaks were observed in the XRD pattern of
Fig. 1 FT-IR spectrum of poly(4-vinylpyridine)-supported copper iodide nanoparticles
123

J. Albadi, A. Mansournezhad
Fig. 2 XRD pattern of poly(4-vinylpyridine)-supported copper iodide nanoparticles
Fig. 3 SEM image of poly(4-
vinylpyridine)-supported copper
iodide nanoparticles
P4VPy-CuI, and their positions were consistent with metallic copper and copper
iodide nanocrystals. The size of copper nanoparticles was also determined from
X-ray line broadening using the Debye–Scherrer formula (obtained size: 75 nm).
This catalyst is safe, easy to handle, and can be used as an efficient Lewis acid in
synthesis of 4H-pyran derivatives. First, we examined the catalytic application of
P4VPy-CuI in synthesis of 4H-pyran derivatives via three-component reaction of
aldehydes, malononitrile, and 3-methyl-1-phenyl-2-pyrazolin-5-one or 1,3-dicar-
bonyl compounds (Scheme 1). For optimization of reaction conditions, the reaction
of benzaldehyde, malononitrile, and 3-methyl-1-phenyl-2-pyrazolin-5-one was
investigated in a variety of conditions.
The effect of various factors such as catalyst loading, solvents, and temperature
was investigated. The reaction was evaluated in the presence of different amounts of
P4VPy-CuI. It was observed that use of 0.07 g P4VPy-CuI was sufficient for
reaction completion after 22 min. Increase in the amount of catalyst (0.1 g) did not
123

Aqua-mediated multicomponent synthesis of various 4H…
Ar
Me
N
CN
Me
NH2
N
O
N
N
O
Ph
CN
CN
P4VPy-CuI
Ph
O
+
ArCHO
O
Ar
O
+
water, reflux
CN
R
R
R
R
NH2
O
R: Me, H
Scheme 1 Synthesis of 4H-pyran derivatives catalyzed by P4VPy–CuI
significantly affect reaction yield or time (Table 1). To study the solvent effect, the
model reaction was carried out in various solvents. As shown in Table 1, the best
results were obtained in water as solvent under reflux conditions. Finally, the best
Table 1 Optimization of reaction conditions in synthesis of 4H-pyran derivatives from aldehyde,
3-methyl-1-phenyl-2-pyrazolin-5-one, and malononitrile
Entry
Conditionsa
Catalyst amount (g)
Time (min)
Yield (%)b
1
H2O/reflux
–
180
180
180
180
45
–
2
EtOH/reflux
H2O/r.t.
–
–
3
0.03
0.05
0.03
0.05
0.07
0.03
0.05
0.05
0.05
0.03
0.05
0.05
–
4
H2O/r.t.
–
5
H2O/reflux
75
6
H2O/reflux
22
93
7
H2O/reflux
20
93
8
EtOH/reflux
EtOH/reflux
CH3OH/reflux
CH3CN/reflux
Solvent free/80 °C
Solvent free/80 °C
Solvent free/100 °C
60
Trace
60
9
60
10
11
12
13
14
a
60
Trace
Trace
Trace
65
60
60
60
60
50
Reaction conditions: aldehyde (1 mmol), 3-methyl-1-phenyl-2-pyrazolin-5-one (1 mmol), malononi-
trile (1 mmol)
b
Yields refer to isolated pure products
123

J. Albadi, A. Mansournezhad
results were obtained in presence of P4VPy-CuI (0.07 g) in water under reflux
conditions with relative ratio of benzaldehyde:malononitrile:3-methyl-1-phenyl-2-
pyrazolin-5-one of 1:1:1.
Using these optimized conditions, the reactions of various aromatic aldehydes
including electron-withdrawing groups such as nitro, nitrile, and aldehyde moieties
and electron-donating groups such as methyl and methoxy moieties with malonon-
itrile and 3-methyl-1-phenyl-2-pyrazolin-5-one were investigated (Table 2). It was
observed that the desired products were obtained in short reaction times and high
yields.
Moreover, synthesis of 4H-pyran derivatives via three-component reaction of
aldehydes, malononitrile, and 1,3-dicarbonyl compounds (dimedone or 1,3-cyclo-
hexandione) was investigated. To optimize the reaction conditions, the reaction of
benzaldehyde, malononitrile, and dimedone was studied under a variety of
conditions. The best result was achieved by running the reaction of each substrate
(with 1 mmol) in the presence of 0.05 g P4VPy-CuI (Table 3, entry 6).
After that, the reaction of various aromatic aldehydes was studied (Table 4). The
evaluation showed that electron-withdrawing groups such as nitro on aromatic ring
decreased the reaction time, whereas electron-releasing groups such as methoxy and
methyl increased it. Furthermore, in the presence of P4VPy-CuI, aliphatic aldehydes
Table 2 Synthesis of 4H-pyran derivatives from aldehyde, 3-methyl-1-phenyl-2-pyrazolin-5-one, and
malononitrile catalyzed by CuO P4VPy-CuI
Entry
Aldehyde
Time (min)
Yield (%)a
M.p. (°C)b
1
C6H5CHO
22
12
15
12
16
16
14
35
25
20
40
15
12
20
35
93
93
92
91
91
93
92
90
90
92
90
89
92
89
90
169–170
192–194
190–191
183–185
175–177
145–146
157–159
173–175
177–179
168–169
209–211
217–219
196–198c
257–259c
202–204c
2
4-O2NC6H4CHO
3-O2NC6H4CHO
2,4-Cl2C6H4CHO
4-ClC6H4CHO
3
4
5
6
2-ClC6H4CHO
7
3-ClC6H4CHO
8
4-MeOC6H4CHO
4-MeC6H4CHO
4-FC6H4CHO
9
10
11
12
13
14
15
a
4-HOC6H4CHO
4-CNC6H4CHO
4-Cl-3-O2NC6H3CHO
4-MeCONHC6H4CHO
4-C6H5CH2OC6H4CHO
Yields refer to isolated pure products
b
Products characterized by comparison of their spectroscopic (NMR and IR) data and melting points
with those reported in literature [8, 24, 25]
c
New compounds
123

Aqua-mediated multicomponent synthesis of various 4H…
Table 3 Optimization of reaction conditions in synthesis of 4H-pyran derivatives from aldehyde, 1,3-
dicarbonyl compounds, and malononitrile
Entry
Conditionsa
Catalyst amount (g)
Time (min)
Yield (%)b
1
H2O/reflux
–
180
180
180
180
30
–
2
EtOH/reflux
H2O/r.t.
–
–
3
0.03
0.05
0.03
0.05
0.07
0.03
0.05
0.05
0.05
0.03
0.05
0.05
–
4
H2O/r.t.
–
5
H2O/reflux
60
6
H2O/reflux
15
92
7
H2O/reflux
15
92
8
EtOH/reflux
EtOH/reflux
CH3OH/reflux
CH3CN/reflux
Solvent free/80 °C
Solvent free/80 °C
Solvent free/100 °C
60
Trace
50
9
60
10
11
12
13
14
a
60
Trace
Trace
50
60
30
30
70
30
75
Reaction conditions: aldehyde (1 mmol), dimedone (1 mmol), malononitrile (1 mmol)
b
Yields refer to isolated pure products
such as 3-propianaldehyde were also converted to benzopyran derivatives in high
yields (Table 4).
Similarly, 2-amino-4H-chromenes were obtained by condensation of aromatic
aldehydes, malononitrile, and resorcinol under reflux conditions in water
(Scheme 2).
To optimize these reaction conditions, the reaction of benzaldehyde, malonon-
itrile, and resorcinol was investigated. It was observed that the best result was
obtained by reaction of substrates (with 1:1:1 mol ratio) in the presence of 0.07 g
P4VPy-CuI under reflux conditions in water (Table 5).
Various aromatic aldehydes were investigated using the optimized conditions.
From Table 6, it is clear that different aromatic aldehydes with either electron-
donating or electron-withdrawing groups efficiently reacted to afford the desired
products in good to high yields. We also observed that aliphatic aldehydes remained
intact under the reaction conditions. Therefore, this method could be useful for
chemoselective synthesis of 2-amino-4H-chromenes from aromatic aldehydes in the
presence of aliphatic ones.
The activity of the recovered catalyst was also examined in three reactions under
optimized conditions. In the synthesis of 4H-pyrans from 3-methyl-1-phenyl-2-
pyrazolin-5-one or 1,3-dicarbonyl compounds, it was found that the catalyst could
be recycled up to five times with desired products obtained in high yields after each
run (Table 7). To explore this property, reaction of benzaldehyde, malononitrile,
and 3-methyl-1-phenyl-2-pyrazolin-5-one or dimedone was again studied under
123

J. Albadi, A. Mansournezhad
Table 4 Synthesis of 4H-pyran derivatives from aldehyde, 1,3-dicarbonyl compounds, and malononitrile
catalyzed by P4VPy-CuI
Entry
Aldehyde
R
Time (min)
Yield (%)a
M.p. (°C)b
1
C6H5CHO
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
15
12
10
12
12
30
20
45
60
45
35
22
92
94
92
92
93
91
91
90
88
88
90
90
230–232
209–210
180–182
207–208
228–230
205–207
212–214
213–215
192–194
207–209
200–202c
244–246c
2
3-O2NC6H4CHO
4-O2NC6H4CHO
4-ClC6H4CHO
3-ClC6H4CHO
4-MeOC6H4CHO
4-MeC6H3CHO
4-HOC6H4CHO
CH3CH2
3
4
5
6
7
8
9
10
11
12
C6H4CH=CHCHO
C6H4CH2CH2CHO
CHO
13
14
15
16
17
18
4-C6H5CH2OC6H4CHO
4-C6H5CH2OC6H4CHO
4-ClC6H4CHO
Me
H
35
42
15
30
35
25
89
89
91
90
90
90
218–220c
199–201c
227–229
196–198
128–130c
248–250c
H
4-MeOC6H4CHO
H
C6H4CH2CH2CHO
H
CHO
H
a
Yields refer to isolated pure products
b
Products characterized by comparison of their spectroscopic (NMR and IR) data and melting points
with those reported in literature [12]
c
New compounds
Ar
O
CN
CN
CN
P4VPy-CuI
H2O, reflux
+
+
ArCHO
HO
NH2
HO
OH
Scheme 2 Synthesis of 2-amino-4H-chromenes catalyzed by P4VPy–CuI
optimized conditions (Table 7). After reaction completion, the catalyst was filtered,
washed with hot ethanol, and after dryness reused in the next similar process.
Moreover, in the synthesis reaction of 2-amino-4H-chromenes, the recyclability
of the catalyst in the reaction of benzaldehyde, malononitrile, and resorcinol was
123

Aqua-mediated multicomponent synthesis of various 4H…
Table 5 Optimization of reaction conditions in synthesis of 2-amino-4H-chromenes from aldehyde,
resorcinol and malononitrile
Entry
Conditionsa
Catalyst amount (g)
Time (min)
Yield (%)b
1
H2O/reflux
–
180
180
180
180
30
–
2
EtOH/reflux
H2O/r.t.
–
–
3
0.03
0.05
0.03
0.05
0.03
0.05
0.05
0.05
0.03
0.05
0.05
Trace
Trace
70
4
H2O/r.t.
5
H2O/reflux
6
H2O/reflux
20
92
7
EtOH/reflux
EtOH/reflux
CH3OH/reflux
CH3CN/reflux
Solvent free/80 °C
Solvent free/80 °C
Solvent free/100 °C
60
Trace
70
8
60
9
60
50
10
11
12
13
a
60
Trace
50
60
60
70
60
80
Reaction conditions: aldehyde (1 mmol), resorcinol (1 mmol), malononitrile (1 mmol)
b
Yields refer to isolated pure products
Table 6 Synthesis of 2-amino-4H-chromenes from aldehyde, resorcinol, and malononitrile catalyzed by
P4VPy-CuI
Entry
Aldehyde
Time (min)
Yield (%)a
M.p. (°C)b
1
C6H5CHO
15
17
15
12
8
94
92
91
92
93
91
91
92
92
91
90
90
92
92
232–234
189–191
103–105
162–163
257–259
163–165
170–172
224–226
188–190
184–186
111–113
250–252
208–209
151–152c
2
2-ClC6H4CHO
3-ClC6H4CHO
4-ClC6H4CHO
2,4-ClC6H3CHO
2-NO2C6H4CHO
3-NO2C6H4CHO
4-BrC6H4CHO
4-FC6H4CHO
3
4
5
6
15
16
20
20
18
25
32
45
20
7
8
9
10
11
12
13
14
a
4-MeC6H4CHO
4-MeOC6H4CHO
4-HOC6H4CHO
3,4,5-(MeO)3C6H2CHO
3-BrC6H4CHO
Yields refer to isolated pure products
b
Products characterized by comparison of their spectroscopic (NMR and IR) data and melting points
with those reported in literature [13, 16, 36]
c
New compound
123

J. Albadi, A. Mansournezhad
123

Aqua-mediated multicomponent synthesis of various 4H…
investigated. It was observed that the catalyst could be recycled up to six times with
consistent activity (Table 7).
Conclusions
A mild, efficient, and green procedure for synthesis of various 4H-pyran derivatives
in the presence of recyclable P4VPy-CuI at reflux conditions in water is reported.
Moreover, high product yield, short reaction time, easy workup, and clean
procedure are the most important advantages of this method, making this procedure
a useful addition to available methods. We are exploring further applications of
P4VPy-CuI for other types of organic reactions in our laboratory.
Acknowledgments We are grateful to Behbahan Khatam Alanbia University of Technology for support
of this research.
References
1. W.P. Smith, L.S. Sollis, D.P. Howes, C.P. Cherry, D.I. Starkey, N.K. Cobley, J. Med. Chem. 41, 787
(1998)
2. A.G. Martinez, L.J. Marco, Bioorg. Med. Chem. Lett. 7, 3165 (1997)
3. D.M. Pore, K.A. Undale, B.B. Dongare, U.V. Desai, Catal. Lett. 132, 104 (2009)
4. N.M.A. El-Rahmana, A.A. El-Kateba, M.F. Mady, Synth. Commun. 37, 3961 (2007)
5. M. Darbarwar, V. Sundarmurthy, Synthesis 1982, 337 (1982)
6. N.R. Kamdar, D.D. Haveliwala, P.T. Mistry, S.K. Patel, Eur. J. Med. Chem. 45, 5056 (2010)
7. M.M. Heravi, Y.S. Beheshtiha, Z. Pirnia, S. Sadjadi, M. Adibi, Synth. Commun. 39, 3663 (2009)
8. S.B. Gou, S.-X. Wang, J.T. Li, Synth. Commun. 37, 2111 (2007)
9. S. Khaksar, A. Rouhollahpour, S. Mohammadzadeh Talesh, J. Fluorine Chem. 141, 11 (2012)
10. H.R. Shaterian, M. Mohammadnia, Res. Chem. Intermed. 41, 1301 (2015)
11. J. Safari, Z. Zarnegar, J. Mol. Struct. 1072, 53 (2014)
12. S. Nemouchi, R. Boulcina, B. Carboni, A. Debache, C. R. Chim. 15, 394 (2012)
13. J. Safari, L. Javadian, Ultrason. Sonochem. 22, 341 (2015)
14. A. Banerjee, A. Saha, New J. Chem. 37, 4170 (2013)
15. M. Khoobi, L. Ma’mani, F. Rezazadeh, Z. Zareie, A. Foroumadi, A. Ramazani, A. Shafiee, J. Mol.
Catal. A Chem. 359, 74 (2012)
16. H. Eshghi, S. Damavandi, G.H. Zohouri, Synth. React. Inorg. Met. Org. Nano-Met. Chem. 41, 1067
(2011)
17. M.A. Bodaghifard, M. Soleimannejad, S. Asadbegi, S. Doiatabadi Farahani, Res. Chem. Intermed.
(2015). doi:10.1007/s11164-015-2079-1
18. K. Santosh Shriram, L. Machhindra Karbhari, A. Balasaheb Ramrao, G. Suresh Tukaram, Chin.
J. Chem. 29, 199 (2011)
19. S. Rathod, B. Arbad, M. Arbad, Chin. J. Catal. 31, 631 (2010)
20. M. Hosseini-Sarvari, S. Shafiei-Haghighi, Chem. Heterocycl. Comp. 48, 1307 (2012)
21. S.B. Semilane, H.H. Knife, A. Muller, D.B. Williams, Org. Lett. 16, 4543 (2014)
22. D. Shi, J. Mou, Q. Zhuang, L. Niu, N. Wu, X. Wang, Synth. Commun. 34, 4557 (2004)
23. T.S. Jin, A.Q. Wang, Z.L. Cheng, J.S. Zhang, T.S. Li, Synth. Commun. 35, 137 (2005)
24. J. Zheng, Y.Q. Li, Arch. Appl. Sci. Res. 3, 381 (2011)
25. M.G. Dekamin, M. Eslami, A. Maleki, Tetrahedron 69, 1074 (2013)
26. A. Domling, I. Ugi, Angew. Chem. Int. Ed. 39, 3168 (2000)
27. G. Balme, E. Bossharth, N. Monteiro, Eur. J. Org. Chem. 2003, 4101 (2003)
28. B. Gerard, J. Ryan, A.B. Beeler, J.A. Porco, Tetrahedron 62, 6405 (2006)
29. J. Albadi, M. Keshavarz, F. Shirini, M. Vafaie-nezhad, Catal. Commun. 27, 17 (2012)
30. J. Albadi, N. Iravani, M. Khoshakhlagh, Iran. J. Catal. 2, 85 (2012)
123

J. Albadi, A. Mansournezhad
31. J. Albadi, M. Keshavarz, M. Abedini, M. Vafaie-nezhad, Chin. Chem. Lett. 23, 297 (2012)
32. J. Albadi, M. Keshavarz, M. Abedini, M. Khoshakhlagh, J. Chem. Sci. 125, 295 (2013)
33. J. Albadi, J. Abbasi Shiran, A. Mansournezhad, Acta Chim. Slov. 61, 900 (2014)
34. J. Albadi, A. Mansournezhad, Z. Derakhshandeh, Chin. Chem. Lett. 24, 821 (2013)
35. J. Albadi, A. Mansournezhad, F. Akbari Balout-Bangan, Acta Chim. Slov. 61, 185 (2014)
36. J. Albadi, A. Razeghi, A. Mansournezhad, Z. Azarian, J. Nanostruct. Chem. 3, 85 (2013)
37. J. Albadi, A. Alihoseinzadeh, A. Mansournezhad, L. Kaveiani, Synth. Commun. 45, 495 (2015)
123