Basic magnetic nanoparticles as efficient catalysts for the preparation of naphthopyrane derivatives

Article abstract of DOI:10.3184/174751912X13264750348839

Aminosilane-functionalised spinel ferrite oxide (Fe₂O ₃ ) magnetic nanoparticles have been synthesised and used as efficient heterogeneous base catalysts for the condensation of aromatic aldehydes with malonitrile and α (or β) naphth

Full text of DOI:10.3184/174751912X13264750348839

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 49
JANUARY, 49–51
Basic magnetic nanoparticles as efficient catalysts for the preparation of
naphthopyrane derivatives
Hossein Yarahmadi and Hamid Reza Shaterian*
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, PO Box 98135-674, Zahedan, Iran
Aminosilane-functionalised spinel ferrite oxide (Fe2O3) magnetic nanoparticles have been synthesised and used
as efficient heterogeneous base catalysts for the condensation of aromatic aldehydes with malonitrile and α (or β)
naphthole via a three-component reaction under solvent-free conditions at 80 °C. Quantitative conversion of the
reactants is achieved under mild conditions. Recovery of the catalyst is easily achieved by magnetic decantation.
The supported catalyst is reused four times without significant degradation in catalytic activity. Naphthopyrans are
polyfunctionalised benzopyran derivatives that have many biological and pharmacological properties.
Keywords: multi-component reactions, magnetic nanoparticles, naphthopyran, green chemistry
In recent years, research has moved towards the development
of environmentally benign reactions. One of the tools used to
combine the economic aspects of new reactions with green
chemistry and environmental aspects is the multi-component
reaction (MCR) strategy.1 Recently, MCRs have emerged as a
valuable synthetic tool in modern drug discovery.2,3 Another
tool is heterogeneous catalysis. These concepts are at the
centre of chemical activity, and the research on high selectivity
is the driving force for the conception of all new catalytic
processes.1,4
Naphthopyrans are polyfunctionalised benzopyran deriva-
tives which constitute structural units of several natural
products. The biological and pharmacological properties of
naphthopyrans include anticoagulant, spasmolytic, diuretic,
anticancer and antianaphylactin activities.5–8 The most straight-
forward synthesis of this heterocyclic system involves a three-
component coupling of aromatic aldehyde, malononitrile and
activated phenol. Traditionally, this reaction was catalysed by
acidic or basic catalysts such as ammonium salts,9–12 TiCl4,13
K2CO3,14 Et3N,15 InCl3,16 I2/K2CO3,17 heteropolyacid18 and 4A°
MS.19 However, some of the reported methods require pro-
longed reaction time, reagents in stoichiometric amounts, toxic
solvents, and generate moderate yields in the final product.
However, a few heterogeneous catalysts have been used for
this transformation. Recently, nano-sized catalysts have also
been shown to be effective catalysts for this reaction.20–22
Good biocompatibility and biodegradability as well as basic
magnetic characteristics can be denoted for surface functional
organic materials grafted to iron oxide magnetic nanoparticles
(MNPs).23–25 These catalysts can be easily separated and
recycled from the products by an external magnet. The silane
agents such as 3-aminopropyltriethyloxysilane (APTES) and
4-aminophenyl trimethoxysilane (APTS) are often considered
as potential candidates for modifying the surface of MNPs
directly.26,27
new selective and synthesis methods based on the use of
APTES functionalised magnetic nanoparticles as catalysts.
In this work, we have considered the MCR strategy for the
synthesis of substituted naphthopyrans using the basic nano-
magnetic catalyst under solvent-free conditions (Scheme 1).
Result and discussion
Our initial study focused on the development of the optimal
reaction conditions for this transformation. To determine the
best weight of the catalyst and temperature, the synthesis of 6
was carried out in presence of different amounts of catalyst
and at different temperatures. Initially, the reaction could
start without any catalyst at 100 °C leading to poor yield (23%)
of the final product 6 (Table 1, Entry 1). Table 1 shows a
remarkable increase in outputs according to the increase in the
quantity of the catalyst.
In order to use the minimum mass of the catalyst and
temperature, we determined the optimum conditions to be
15 mg mol−1 of catalyst at 80 °C (Table 1, entry 12) for the
synthesis of a variety of substrates (Table 2).
A heterogeneous catalyst is more interesting when it can be
easily recovered and re-used. For this purpose, the synthesis of
6 was carried out using fresh and recovered MNPs catalyst
for a four-cycle run. After 20 min reaction, the product 6 was
isolated and identified. The recovered catalyst was washed
with acetone and dried at 100 °C. The obtained yield after
the four-cycle run is almost stable and unchangeable (92, 89,
86 and 85%) which demonstrates that MNPs can be easily
recovered and re-used without any loss of its activity.
As can be seen from Table 2, electronic effects and the
nature of substituent on the aromatic rings showed strong
effects in terms of reaction time under the reaction conditions
mentioned above. Aromatic aldehydes substituted by electron-
donating groups (Table 2, entries f–i) require a longer reaction
time than those of electron-withdrawing groups (Table 2,
entries b–e).
The basic magnetic catalyst could be easily isolated from
the reaction mixture by simple magnetic decantation using a
permanent magnet and it could be reused several times without
significant degradation in activity.
Existence of many hydroxyl groups on the MNPs’ surface
leads to a reaction with alkoxysilane reagents and formation
of Si–O bonds which support terminal functional groups
available for the immobilisation of other substances.28 In con-
tinuation of our works on the application of heterogeneous
catalysts,29–34 as part of our program aimed at developing useful
Experimental
Amino coated magnetic nanoparticles were produced according to
reported procedure.26
Synthesis of 2-amino-2-chromenes; general procedure
An equimolar (1 mmol) mixture of an aromatic aldehyde (1), malono-
nitrile (2), α (or β) -naphthol (3) and 15 mg of catalyst were vigor-
ously stirred at 80 °C for the specified time. The end of the reaction
was monitored by TLC. After completion, the mixture reaction was
diluted by 5 mL dichloromethane; then the catalytic system was
* Correspondent. E-mail: hshaterian@yahoo.com;
hshaterian@chem.usb.ac.ir

50 JOURNAL OF CHEMICAL RESEARCH 2012
Scheme 1 Synthesis of naphthopyranes using MNPs under solvent-free conditions.
removed by an external magnet and reused as such for the next exper-
iment. The organic layer was washed with aq. solution 10% NaHCO3
and water, dried with Na2SO4 and concentrated to give the crude prod-
ucts. Consequently the desired naphthopyran recrystallised in ethanol:
water (25% v/v). The desired pure product(s) were characterised by
comparison of their physical data with those of known compounds.9–22
The spectral data of some representative naphthopyranes are as
follows.
3-Amino-1-(3,4-dimethoxyphenyl)-1H-benzo[f]chromene-2-carbonitrile
(12): H NMR (400 MHz, CDCl3): δ = 3.8 (s, 6H), 4.7 (S, 2H), 5.2
1
(s, 1H), 6.7 (d, J = 7.6 Hz, 1H), 6.8 (d, J = 7.6 Hz, 2H), 7.3 (d, J =
8.8 Hz, 1H), 7.4 (2H, br), 7.7 (br, 1H), 7.8 (d, J = 6.8 Hz, 2H) ppm;
13C NMR (100 MHz, CDCl3): 38.5, 55.8, 55.9, 62.4, 110.5, 111.4,
115.0, 116.6, 119.3, 120.1, 123.9, 125.2, 127.2, 128.5, 129.6, 130.9,
131.49, 137.2, 147.1, 148.0, 149.3, 158.6 ppm; FT-IR (KBr, cm−1):
3428 (N–H), 3336 (N–H), 3193, 3065, 2955, 2184 (CN), 1649; Anal.
Calcd for C22H18N2O3: C, 73.73; H, 5.06; N, 7.82. Found: C, 73.70;
H, 5.02; N, 7.79%. 2-amino-4-(3,4,5-trimethoxyphenyl)-4H-benzo[h]
2-Amino-4-(3,4-dimethoxy phenyl)-4H-benzo[h]chromene-3-carbonitrile
1
(11): H NMR (400 MHz, CDCl3): δ = 3.8 (S, 3H), 3.9 (s, 3H), 4.8
1
(s, 2H), 4.9 (s, 1H), 6.8 (d, J = 1.2 Hz, 1H), 6.8–6.9 (m, 2H), 7.1 (d,
J = 8.8 Hz, 1H), 7.5–7.6 (m, 3H), 7.8 (d, J = 7.6 Hz, 1H), 8.2 (d, J =
8.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): 41.1, 55.1, 56.0, 61.5,
111.2, 117.3, 119.9, 120.5, 120.8, 123.2, 124.6, 126.2, 126.7, 126.8,
127.8, 133.3, 137.1, 143.2, 148.4, 149.3, 158.8 ppm; FT-IR (KBr,
cm−1): 3382 (N–H), 3326 (N–H), 3211, 3056, 2934, 2192 (CN), 1661;
Anal. Calcd for C22H18N2O3: C, 73.73; H, 5.06; N, 7.82. Found: C,
73.69; H, 5.01; N, 7.84%.
chromene-3-carbonitrile (13): H NMR (400 MHz, CDCl3): δ = 3.8
(s, 6H), 3.8 (s, 3H), 4.8 (s, 1H), 4.9 (s, 2H), 6.5 (s, 2H), 7.1 (d, J =
8.8 Hz,1H), 7.5–7.6 (m, 3H), 7.8 (dd, J = 1.2, 7.2 Hz, 1H), 8.2 (d, J =
8 Hz, 1H,) ppm; 13C NMR (100 MHz, CDCl3): 41.8, 45.0, 56.1, 60.8,
105.3, 116.9, 119.9, 120.8, 123.2, 124.6, 126.2, 126.7, 126.8, 127.8,
133.4, 137.2, 140.1, 143.2, 153.5, 159.1 ppm; FT-IR (KBr, cm−1):
3485, 3331, 3203, 3066, 2187, 1664; Anal. Calcd for C23H20N2O4: C,
71.12; H, 5.19; N, 7.21. Found: C, 71.08; H, 5.15; N, 7.24%.
Table 1 Catalyst and temperature screening for the synthesis
of 6a,b
Table
2
Synthesis of naphthopyrane derivatives (1–18)
produced via Scheme 1a
Entry
X
A/B Product Time (min)
M.p. (lit.)ref.
/ Yield (%)b
a
b
c
d
e
f
H
2-Cl
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
1
2
25/88
25/89
20/87
20/90
15/93
15/92
12/94
15/94
20/92
15/90
16/90
18/88
22/91
25/92
40/84
205–208 (207–210)10
276–279 (278–279)19
235–238 (236–237)10
265–268 (265–267)19
230–232 (231–232)10
209–211 (210–211)19
222–225 (222–224)10
236–239 (239–240)19
230–233 (231–234)10
185–188 (185–186)19
187–190
Entry
Temperature /°C
Catalyst /mg
Yield of 6 /%c
3
1
2
100
35
50
65
80
100
120
80
80
80
80
80
80
80
80
-
26
41
53
78
93
94
94
95
93
91
92
92
83
80
71
4
200
200
200
200
200
200
150
100
50
4-Cl
5
3
6
4
2,4-Cl
4-NO2
3,4-OMe
3,4,5-OMe
4-Me
7
5
8
6
9
7
10
11
12
13
14
15
8
9
198–201
10
11
12
13
14
15
g
h
140–144
25
184–186
204–206 (205–206)10
15
10
B
A
B
16
17
18
40/82
60/80
70/79
252–255 (253–254)11
180–183 (182–184)22
192–195 (194)19
5
1
i
4-OMe
a All reactions were conducted with the 4-chlorobenzaldehyde
c (1 mmol), 2-naphthol 2 (1 mmol), malonitrile (1 mmol) and
basic nanomagnetic catalyst in solvent-free conditions.
b The time of all reactions is 1 h.
a All reactions were conducted with the arylaldehyde a–i
(1 mmol), naphthol A or B (1 mmol), malonitrile (1 mmol), and
nanomagnetic catalyst (20 mg) in solvent-free conditions at
80 °C.
c Isolated yields.
b Yield of isolated product afther recrystalisation.

JOURNAL OF CHEMICAL RESEARCH 2012 51
9
R. Ballini, G. Bosica, M.L. Conforti, R. Maggi, A. Mazzacanni, P. Righi
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7.7–7.8 (m, 1H), 7.8–7.9 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3):
39.1, 44.9, 56.1, 60.8, 61.9, 104.2, 114.7, 116.6, 120.1, 123.8, 125.2,
127.3, 128.5, 129.8, 130.9, 131.3, 136.8, 140.2, 147.2, 153.5, 158.8
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Conclusion
In conclusion, we have developed a simple, efficient, and green
methodology for the synthesis of naphthopyranes using MNPs
under solvent-free conditions. The simple experimental proce-
dure, solvent-free reaction conditions, good yields, short time
reaction and utilisation of an efficient, easily recoverable and
reusable catalyst are the advantages of the present method.
20 D. Kumar, V.B. Reddy, B.G. Mishra, R.K. Rana, M.N. Nadagaouda and
R.S. Varma, Tetrahedron, 2007, 63, 3093.
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22 A. Solhy, A. Elmakssoudi, R. Tahir, M. Karkouri, M. Larzek, M. Bousmina
and M. Zahouily, Green Chem., 2010, 12, 2261.
We thank the Sistan and Baluchestan University Research
Council for partial support of this work.
23 A.H. Lu, E.L. Salabas and F. Schuth, Angew. Chem. Int. Ed. 2007, 46,
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24 B. Hu, J. Pan, H.L. Yu, J.W. Liu and J.H. Xu, Process Biochem. 2009, 44,
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Received 20 November 2011; accepted 9 January 2012
Paper 1100994 doi: 10.3184/174751912X13264750348839
Published online: 31 January 2012
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Chem. Int. Ed., 2004, 43, 5645.
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