Microwave-assisted Fe3O4 nanoparticles catalyzed synthesis of chromeno[1,6]naphthyridines in aqueous media

Article abstract of DOI:10.1016/j.catcom.2014.12.015

Fe₃O₄ nanocatalyst was prepared by co-precipitation method and characterized by XRD, FT-IR, TEM, VSM and BET analyses. The particles have an average size of 7 nm and possess highly open mesopores, moderate surface area, and uniform morphology with superparamagnetic behavior. Activity of catalyst was probed through the synthesis of chromeno[1,6]naphthyridines in water under microwave irradiation (MW) and it was about 7-fold higher as compared to conventional method. Nanocatalyst plays a dual role of catalyst as well as susceptor, and enhances the overall capacity to absorb MW. Fe₃O₄ NPs easily recovered by simple magnetic separation and recycled at least 5 times.

Full text of DOI:10.1016/j.catcom.2014.12.015

Microwave-assisted Fe3O4 nanoparticles catalyzed synthesis of
chromeno[1,6]naphthyridines in aqueous media
Anshu Dandia, Vijay Parewa, Shyam L. Gupta, Amit Sharma, Kuldeep
S. Rathore, Astha Jain
PII:
DOI:
Reference:
S1566-7367(14)00517-2
doi: 10.1016/j.catcom.2014.12.015
CATCOM 4169
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
14 November 2014
15 December 2014
18 December 2014
Please cite this article as: Anshu Dandia, Vijay Parewa, Shyam L. Gupta, Amit Sharma,
Kuldeep S. Rathore, Astha Jain, Microwave-assisted Fe3O4 nanoparticles catalyzed syn-
thesis of chromeno[1,6]naphthyridines in aqueous media, Catalysis Communications (2014),
doi: 10.1016/j.catcom.2014.12.015
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Microwave-assisted Fe3O4 nanoparticles catalyzed synthesis of
chromeno[1,6]naphthyridines in aqueous media
Anshu Dandia,*a Vijay Parewa,a Shyam L. Gupta,a Amit Sharma,a Kuldeep S. Rathoreb, Amit
Sharma,b Astha Jainb
aCentre of Advanced Studies, Department of Chemistry,
University of Rajasthan, Jaipur, India.
bSemiconductor and Polymer Science Laboratory, Department of Physics, University of
Rajasthan, Jaipur, India.
E-maila: dranshudandia@yahoo.co.in E-mailb: kuldeep_ssr@yahoo.com
ABSTRACT
Fe3O4 nanocatalyst was prepared by co-precipitation method and characterized by XRD,
FT-IR, TEM, VSM and BET analyses. The particles have an average size of 7 nm and possess
highly open mesopores, moderate surface area, and uniform morphology with superparamagnetic
behavior. Activity of catalyst was probed through the synthesis of chromeno[1,6]naphthyridines
in water under microwave irradiation (MW) and it was about 7-fold higher as compared to
conventional method. Nanocatalyst plays a dual role of catalyst as well as susceptor, and
enhances the overall capacity to absorb MW. Fe3O4 NPs easily recovered by simple magnetic
separation and recycled at least 5 times.
Keywords: Fe3O4 nanocatalyst, Microwave radiation, Water, Heterogeneous catalyst,
Chromeno[1,6]naphthyridines.
1. Introduction
The applications of iron-based materials as catalysts in organic synthesis has attracted a
lot of attention during the last decade [1]. Iron is most widely recommended due to its low cost,
abundance, environmentally benign and non-toxic nature [2-3] for industrial scale synthesis of
fine chemicals [4]. Iron oxides have been frequently used as catalysts and supports in bulk
industrial processes, usually at high temperature and pressure [5]. However, Fe has a great deal

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to offer at the nanoscale, including potent magnetic and catalytic properties [6]. The strategy of
magnetic separation of magnetic nanoparticles is typically more effective than filtration or
centrifugation as it prevents loss of the catalyst. Furthermore, Fe3O4 nanoparticles have showed
potential applications in many other fields [7-8].
Chromenes and 1,6-naphthyridines are associated with a wide spectrum of biological
activities [9-11]. Consequently, integration of chromene moieties with naphthyridines in a single
molecular-framework may increase their biological and fluorescence properties [12]. While a
considerable number of naphthyridines fused with five-membered rings has been described in
literature [13-14], corresponding derivatives condensed with six-membered heterocycles have
been less investigated [15-16]. There are also few synthetic methods available in literature for
the synthesis of chromeno[1,6]naphthyridines [17-20].
A vigilant scrutiny described that most of the methodologies endure some setbacks owing
to their limited utility i.e. usage of corrosive catalysts [17], multistep process [18], high
temperature, long reaction time, non-compatible solvent [19], low yields and unavailable starting
materials [20]. Although, some strategically sound modifications have been documented [21] for
upliftment of reaction condition, but somewhere down the line it still lack the versatility. The
employed catalytic systems are more often non-recoverable [21], thus plummeting the turn over
frequency (TOF), which is significant from industrial point of view. As a result, the development
of new synthetic methods for this purpose remains an attractive goal.
The use of nanomaterial as efficient catalysts in aqueous medium has attracted
considerable interest [22-23]. The coupling of nanocatalyst with aqueous medium and MWs can
offer an astonishing synergistic effect with superior potential than these components in solitude

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[24]. In continuation of our efforts towards the development of newer nanocatalytic processes
[25-27], herein, we wish to report the synthesis of magnetically recoverable Fe3O4 nanoparticles
and their catalytic applications in the synthesis of chromeno[1,6]naphthyridines in water.
2. Experimental
General part including used instruments is provided in ESI.
2.1 Catalyst preparation
A mixture of ferric chloride (2.7 g) and ferrous chloride (0.99 g) in a fixed molar ratio of
2:1 (Fe+3:Fe+2) in 30 mL of ethylene glycol was introduced in a 50 mL heavy walled pear-shaped
two necked flask with non-standard tapered outer joint. The flask was attached to a 12 mm tip
diameter probe and the reaction mixture was sonicated at ambient temperature for the specified
period at 50% power of the processor and in a 4 s pulse mode. After proper sonication of the
mixture, sodium acetate was added and sonication was continued until a fine dispersion was
seen. This assembly was then subjected to an oil bath where the temperature was increased to
190 °C. For uniform heating of the broth, oil was constantly stirred. After 6 hours of stirring, the
temperature was lowered to room temperature and the nanoparticles were separated magnetically
and washed repeatedly with isopropanol followed by centrifugation at 8000 rpm for 20 minutes.
Drying in a vacuum oven at 60 °C for two hours gave a brown coloured fine powder.
2.2 Catalyst activity measurement
Aromatic aldehyde (1 mmol), malononitrile (2 mmol), 2-hydroxyacetophenone (1 mmol)
and 5 mol% of Fe3O4 NPs in water (10 mL) was introduced in a 50 mL round-bottom flask. The
flask was placed in the microwave cavity and subjected to irradiation for appropriate time at 70

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°C using a power of 400W. On the completion of reaction, Fe3O4 NPs were separated by using
external magnet and crude product was purified by crystallization from ethanol.
3. Results and discussion
3.1 Synthesis and characterization of catalyst
Fe3O4 NPs have been synthesized via co-precipitation method [28] with excellent
catalytic properties and high stability. The morphology, behavior and structure of Fe3O4
nanoparticles were characterized by XRD, FT-IR, TEM, VSM and BET analyses. In FT-IR, the
adsorption band of the Fe–O bonds in tetrahedral sites was observed at 606 cm−1. In XRD
patterns, characteristic peaks appeared at 2θ = 30.15, 35.48, 43.2, 56.83 and 62.64 correspond to
the major planes (220), (311), (400), (511) and (440) respectively, confirmed the inverse spinel
structure. TEM image showed that average diameter of Fe3O4 NPs is about 7 nm with a square
shaped morphology. The excellent magnetically controllable behavior of Fe3O4 NPs was
investigated by VSM. The hysteresis loops exhibit a superparamagnetic behavior with the
saturation magnetization of about 67 emu/g (Fig 1).
(Fig. 1)
In the N2 adsorption–desorption isotherm sample showed a typical type IV isotherm with
‘a’ type hysteresis loop. The isotherm accounts for the relatively ordered mesopores and the
hysteresis loop. The BET surface area for the Fe3O4 NPs is 39 m2g-1 with pore dimensions of 3.6
nm (Fig. 2).
(Fig. 2)
3.2 Assessment of catalytic activity

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We began our study by evaluating the efficiency of MW (400 W) at 70 °C for 60 min. for
the model reaction of 3-phenoxybenzaldehyde (1.0 mmol), malononitrile (2.0 mmol) and 2-
hydroxyacetophenone (1.0 mmol) in aqueous medium without using any catalyst. Under these
conditions the reaction did not proceed. In order to optimize the reaction conditions, different
iron catalysts in water were examined (Table 1).
(Table 1)
When FeCl2.4H2O was used as a catalyst the product were obtained in low yields. When
FeCl3.6H2O was used, the yield was still lower, whereas with Fe(NO3)3.9H2O the yield of 4h is
36% with no reusability of catalyst (Table 1). However, reaction occurred smoothly in the
presence of Fe3O4 NPs affording product in 88 % yield. Fe3O4 NPs exhibit higher TOF value
than corresponding bulk iron oxide. These results proved the superiority of this method in terms
of yield and reaction time. The presence of Fe2+/Fe3+species in reaction mixture alone cannot
drive the reaction adequately to produce 4h; it should be in a definite structure, shape and size
(Fe3O4 NPs). As indicated from Table 1, 5 mol % of catalyst loading was adequate to catalyze
the reaction, excessive amount of catalyst did not increase the yield remarkably. Furthermore,
water was proved as a superior solvent as compared to commonly employed organic solvents
(See ESI).
The model reaction was also investigated under different nonconventional and
conventional conditions (See ESI). Under MW, the catalytic activity of Fe3O4 NPs was found to
be 7-fold higher than conventional method. To interpret the enhanced catalytic activity under
MW, two hypotheses were proposed. First one assumes the existence of thermal effect only, i.e.
a different temperature regime and second theory assumes that non-thermal effects can also exist.

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But, the theory behind non-thermal effect is controversial [29]. If non-thermal effects are ruled
out, then the enhanced catalytic activity must be due to a different temperature regime.
Since, it is well known that for a given temperature for both heating techniques
(conventional and microwave), nanocatalyst can be heated up more selectively by MW [30-33].
The selective heating may be created by the difference in dielectric properties of materials, by
the uneven distribution of electromagnetic field strength, or by the volumetric dielectric heating
under MW [34]. It suggested that temperature of nanoparticles was much higher than the average
temperature measured. Thus, nanocatalysts can act as a susceptor [24, 26, 35] and serve as an
internal heating source for the reaction by transferring heat to the reactants and prevent their own
deactivation.
To study the scope and limitations of this protocol, we have employed a wide range of
aromatic aldehydes (Table 2). Catalytic efficiency was not significantly affected by the
substituents on the aromatic ring. Both electron-rich and electron-deficient substituents were
highly effective, although slightly lower yields were obtained when ortho substituted aromatic
substrates were employed. Further, at the expense of time up to 40 min, heterocyclic aldehydes
also afforded good yields.
(Table 2)
A plausible mechanistic insight of the reaction involves consequent aldol, Knoevenagel
condensation and intra molecular ring closure followed by aromatization leading to the formation
of chromeno[1,6]naphthyridines catalyzed by Fe3O4 NPs (See ESI).
Recyclability
When reaction was completed, Fe3O4 NPs were collected on the side wall of the reaction
vessel with the aid of an external magnet and water was removed from the mixture to leave a

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residue (including the product and catalyst). Then, the residue was dissolved in ethanol and
catalyst was easily separated from the product by attaching an external magnet onto the reaction
vessel, followed by decantation of product solution. Remaining catalyst was washed with ethanol
to remove the residual product, dried under vacuum and reused for five subsequent reaction
cycles without any significant loss in catalytic activity (Fig. 3).
(Fig. 3)
The characteristics obtained from TEM of fresh and used catalysts are almost similar,
which suggest the retention of structure and morphology of Fe3O4 NPs after repeated use as
catalyst. According to ICP-AES results, there was no nanocatalyst present in the final product
and water.
4. Conclusions
The present work illustrates the advantages of microwave-assisted nano-catalysis in
aqueous medium. Fe3O4 NPs have been synthesized, characterized and probed as a catalyst for
the synthesis of chromeno[1,6]naphthyridines in water. Under MW, catalytic activity of Fe3O4
NPs was about 7-fold higher as compared to the conventional method. MW energy can be
focused on the surface of the nanocatalyst and rapidly transferred to the reactants, the residence
time of nano-catalyst at this high temperature is minimum. In this way, thermal decomposition
and deactivation of the catalyst can be avoided by shorter reaction time and it can acts as
susceptor. Formation of water as the only by-product is additional advantages of present
methodology.
Acknowledgments

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Financial assistance from CSIR [02(0143)/13/EMR-II] and UGC, New Delhi is gratefully
acknowledged. We are also thankful to Central Drug Research Institute (CDRI), Lucknow and
IIT Delhi for the spectral analyses.
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Fig. 1 (a) FT-IR spectra (b) XRD pattern (c) TEM image and (d) Magnetic hysteresis loops of
Fe3O4 NPs

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Fig. 2 (a) N2 adsorption–desorption isotherm and (b) Pore dimensions of Fe3O4 NPs
Fig. 3 Recyclability of Fe3O4 NPs

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Table 1 Comparison of catalytic activity of Fe3O4 NPs with other iron catalysts for the synthesis
of chromeno[1,6]naphthyridine derivatives (4h)a
OPh
O
CH
3
O
H
OH
CN
CN
N
O
Fe3O4 NPs
water/MW
+
2
+
N
OPh
NC
NH2
1
2h
3
4h
Entry
Condition
Time
Yield (%)*
TOF(h-1)
1.
2.
3.
4.
5.
6.
FeCl2.4H2O (10 mol %)
FeCl3.6H2O (10 mol %)
Fe(NO3)3.9H2O (10 mol %)
Bulk Iron oxide (10 mol %)
Fe3O4 NPs (10 mol %)
Fe3O4 NPs (5 mol %)
45 min
38 min
34 min
30 min
25 min
25 min
17
28
36
62
88
88
51
99
143
279
475
1003
* Isolated yield
aReactions performed on a 1:2:1 ratio of 3-phenoxybenzaldehyde, malononitrile and 2- hydroxyacetophenone in aqueous medium
under microwave irradiation.

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Table 2 Synthesis of chromeno[1,6]naphthyridines
R
O
CH
3
O
H
OH
N
O
CN
Fe3O4 NPs
water/MW
+
2
+
N
CN
NC
R
1
2a-n
3
NH
2
4a-n
O2N
H3CO
H3C
N
O
N
O
N
O
N
O
N
N
NH2
4a
N
N
NC
NC
NC
NC
NH2
NH2
NH2
4b
85%
4c
88%
4d
83%
82%
OCH3
Cl
OPh
H3CO
H3CO
Cl
N
O
N
O
O2N
N
O
N
O
N
N
NC
NC
N
N
NC
NC
NH2
NH2
NH2
NH2
4e
80%
4h
88%
4f
81%
4g
80%
Cl
HO
S
O
N
H
O
N
O
N
O
N
O
N
N
N
N
NC
NC
NC
NH2
H2N
CN
NH2
NH2
4k
81%
4l
83%
4i
82%
4j
84%
HN
N
N
O
N
O
N
NC
N
NC
NH2
4m
80%
NH2
4n
82%

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Microwave-assisted Fe3O4 nanoparticles catalyzed synthesis of
chromeno[1,6]naphthyridines in aqueous media
Anshu Dandia,*a Vijay Parewa,a Shyam L. Gupta,a Amit Sharma,a Kuldeep S. Rathoreb Amit
Sharma,b Astha Jainb
aCentre of Advanced Studies, Department of Chemistry,
University of Rajasthan, Jaipur, India.
bSemiconductor and Polymer Science Laboratory, Department of Physics, University of
Rajasthan, Jaipur, India.
E-maila: dranshudandia@yahoo.co.in E-mailb: kuldeep_ssr@yahoo.com
Graphical Abstract
R
O
H
R
O
CH3
OH
CN
CN
s
+
2
MW
P
N
O
+
N
4
O
N
3
e
NC
Fe3O4 NPs
F
NH2
4a-n

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Highlights



Fe3O4 NPs was prepared by co-precipitation method.
Fe3O4 NPs catalyzed efficient synthesis of chromeno[1,6]naphthyridines.
Reaction takes place via MW-assisted nano-catalysis in aqueous medium.


The catalyst can be simply recovered by magnetic separation.
High TOF value, recycling and economic viability of the catalyst.