Preparation, characterization and catalytic application of nano-Fe3O4-DOPA-SnO2 having high TON and TOF for non-toxic and sustainable synthesis of dihydroquinazolinone derivatives

Article abstract of DOI:10.1039/c7nj01208j

A novel class of heterogeneous magnetically separable nano catalysts was designed by encapsulating SnO₂ on nano-Fe₃O₄-DOPA. After the successful characterization of the synthesized catalyst by FT-IR, SEM, TEM, EDX, TGA, po

Full text of DOI:10.1039/c7nj01208j

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Preparation, characterization and catalytic application of nano-Fe3O4-DOPA-SnO2
having high TON and TOF for non-toxic and sustainable synthesis of
dihydroquinazolinone derivatives
Binoyargha Dam, a Ranjit A. Patil, b Yuan-Ron Ma, b and Amarta Kumar Pal a*
aDepartment of Chemistry, Centre for Advanced Studies, NorthꢀEastern Hill University, Shillongꢀ793022,
India, E-mail: amartya_pal22@yahoo.com, akpal@nehu.ac.in
b Department Physics, National Dong Hwa University, Hualienꢀ97401, Taiwan
Introduction:
Major attention in catalytic routes for the synthesis of complex organic molecules has been
determined by the economically favourable and environment aware market. Discovery of
selective and efficient catalysts in industrial and academic field have gained lots of attention.
An efficient catalyst shows enormous influence on minimizing the manufacturing costs as
well as waste disposal. Practical application of catalysts in aqueous medium is limited
because of difficulties in catalyst separation and recycling. Several approaches like
nanofiltration, centrifugation, and newer separation techniques based on liquid-liquid phase
separation, including supercritical solvents, polymeric supports, ionic liquids have been
applied since years to evade difficulties in catalyst separation.1 Each separation technique has
its own limitations like higher cost, less efficiency, generation of unwanted wastes etc.
Because of these issues, heterogenization of homogeneous catalysts on solid supports has
gained tremendous attention.2 Magnetic nanoparticles (NPs) because of its higher surface
area and tremendous response to an applied magnetic field have achieved incredible attention
as catalyst supports. 3
Post synthetic surface modifications of magnetic nanoparticles provide enviable chemical
functionality and leads to generation of catalytic sites on the surface of nanoparticles.
Moreover their insoluble and magnetic nature leads to a trouble free separation of the
nanocatalysts from the reaction vessel by using an external magnetic field. These surface

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modified nanocatalysts acts as bridge between homogenesous and heterogeneous catalysis,
thus conserving the advantageous attributes of both the systems. This application requires
specific ligand to be immobilized on the surface of the nanoparticles. We have chosen
dopamine as desired ligand mainly because of two reasons: i) according to Langmuir
isotherms, desorption of dopamine molecules from metal oxide surface is less favourable
4
than its absorption thereby reducing the chances of its leaching from the surface and ii)
dopamine transforms the un-coordinated iron surface sites back to bulk-like lattice site with
octahedral geometry for oxygen coordinated iron which leads to a tight binding with iron
oxide.5 Previously many research groups have incorporated many metals and metal salts like
Pd, Cu, Ni, RuCl3 etc following these techniques and applied that in various organic
transformations.6 Among various metals that have been applied in organic synthesis, tin
received tremendous attention due to its low cost, suitable activity and lower toxicity.7
Moreover tin dioxide (SnO2) is a resourceful metal oxide because of its two exclusive
characteristics; which are, existence of oxygen vacancy defects and variation in valence
state.8 Because of these reasons SnO2 has found extensive applications in catalysis,
electrochromic devices, transparent conductive electrodes, antistatic coating and solar energy
conversion.9 However, owing to poor thermal stability of the pure tin oxide, its application is
restricted to a greater extent in catalysis.10 So, several amendments have been proposed, of
which addition of metal and non-metal oxides to tin oxide is an effectual strategy.11 We
herein, incorporated SnO2 on the surface of magnetic nanoparticles which not only makes its
handling easier but also increases its catalytic activity thereby increasing its recyclability and
reusability.
Nitrogen containing heterocycles like quinazolinones are pivotal sub-units of a large number
of biologically active compounds which possess several medicinal activities like
antihypertensive, antiinflamatory, antibacterial, anticancer, antimicrobial, antitumour etc.12

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Although many methodologies for the synthesis of dihydroquinazolinone derivatives have
13
been already developed
but most of these methodologies suffer certain drawbacks like
multi-step process, elongated time, costly catalyst, tedious workup procedure, costly
syntheses.14
As a part of our continuing efforts towards synthesis of heterocycles using heterogeneous
recyclable catalyst15 we herein discuss a procedure for the synthesis of novel nano-Fe3O4-
DOPA-SnO2 catalyst and applied that in aqueous medium for the synthesis of biologically
active dihyroquinazolinone derivatives. We also carried out a gram scale reaction to verify
the industrial scope of our methodology.
Results and discussions:
Preparation of catalyst:
Firstly we focused towards synthesis of Fe3O4 nanoparticles (NPs) by co-precipitation method
using Fe+2 and Fe+3salts.16 Characterization of the synthesized nanoparticles was then carried
out by SEM, TEM, EDX and powder XRD analyses (Fig. SI 1). Following that Fe3O4 NPs
were coated with dopamine by simply ultrsonicating a mixture of dopamine hydrochloride
and Fe3O4 NPs in water for 2 h.17 Final encapsulation of SnO2 on synthesized nano-Fe3O4-
DOPA was done by stirring an aqueous solution of SnCl2.2H2O with nano-Fe3O4-DOPA at
room temperature for 24 h (Scheme 1).
Fe+2
Dopamine
hydrochloride,
H2O, (((, 2h
NH4OH (25%)
60 0C, H2O, 1h
SnCl2.2H2O,
H2O, r.t, 24h
SnO2
=
= Dopamine
Fe+3
nano -Fe O
nano -Fe O -DOP A
3
4
nano -Fe O -DOP A-S nO
2
3
4
3
4
Scheme 1: Synthetic scheme for the synthesis of nano-Fe3O4-DOPA-SnO2

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Characterization of catalyst:
Fe
O Nps
4
3
Nano-Fe
O
-DOPA
3
3
4
Nano-Fe
O
-DOPA-SnO
4
2
45
40
35
30
25
20
15
10
5
1632.10
3423.07
595.31
1631.10
1631.10
576.08
607.69
0
673.08
500
3423.24
3440.18
-5
4000
3500
3000
2500
2000
1500
-1
1000
Wavenumber (cm )
Fig. 1: Comparative FT-IR spectra of nano-Fe3O4, nano-Fe3O4-DOPA and nano-Fe3O4-
DOPA-SnO2
Firstly to get information regarding functional groups, FT-IR analyses of nano-Fe3O4, nano-
Fe3O4-DOPA and nano-Fe3O4-DOPA-SnO2 were carried out and compared with each other.
Comparative FT-IR spectra of nano-Fe3O4, nano-Fe3O4-DOPA and nano-Fe3O4-DOPA-SnO2
-1
-1
(Fig. 1) shows prominent peaks above 3400 cm and 1631-1632 cm which was found in
all three spectra. These peaks correspond to –OH stretching and H-O-H bending vibrations of
moisture absorbed on the surface of materials. 18 Peak at around 1631 cm -1 became more
intense in spectra of nano-Fe3O4-DOPA and nano-Fe3O4-DOPA-SnO2, this may be because
of the aromatic -C=C- stretching of benzene ring present in dopamine molecule. Peaks in
region of 670-595 cm-1 correspond to Fe-O stretching frequency proving presence of Fe3O4
NPs in all the three catalysts. On careful surveillance of FT-IR spectra of nano-Fe3O4-DOPA-
-1
SnO2 a peak at around 576 cm
vibration.19
was observed which is because of Sn-O stretching
After getting information regarding functional groups, in order to gather information
regarding size and morphology of nano-Fe3O4-DOPA-SnO2, TEM (Transmission Electron
Microscopy) analysis of synthesized catalyst was carried out. From TEM image [Fig 2(a)] we
observed that NPs are spherical in shape along with rod like shapes. The average size of NPs

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was found to be ~20 nm. In order to confirm the chemical composition, a high-resolution
TEM (HRTEM) image was taken and is shown in Fig. 2 (b). The HRTEM image consists of
the high-resolution images of NPs and a portion of the rod-like shapes. In both spherical and
rod shaped nanoparticles, the inter planer spacing (d) of the crystal planes was found to be
same (0.24 nm). The values of d spacing correspond to the (222) plane of Fe3O4. Therefore,
HRTEM analysis confirms that spherical as well as rod like NPs are composed of Fe3O4. The
selected area electron diffraction (SAED) pattern of the NPs is shown in Fig. 2(c). Due to
diffraction from various planes of NPs, SAED showed various diffraction spots. We have
assigned a set of the diffraction pattern (highlighted using yellow circles) to the diffraction
planes of Fe3O4, corresponding to the zone axis [111]. This proves that nano-Fe3O4-DOPA-
SnO2 is crystalline in nature.
Fig. 2: (a) TEM image of nano-Fe3O4-DOPA-SnO2 (b) HRTEM images of NP’s and (c)
SAED pattern
Elemental investigation of synthesized catalyst was estimated by Energy dispersive X-ray
(EDX) analysis (Fig. 3). EDX spectrum clearly showed presence of iron (Fe), tin (Sn),
oxygen (O), nitrogen (N) and carbon (C). Peaks of gold (Au) are present in spectrum because
while doing analyses coating of sample was done with gold. Scanning electron microscopy

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(SEM) image (Fig. 4) of synthesized nano-Fe3O4-DOPA-SnO2 was also taken and it was
found to be in accordance with that of TEM image thereby showing spherical shape.
Fig. 3: EDX of nano-Fe3O4-DOPA-SnO2
Fig. 4: SEM image
After concluding successful incorporation of tin (Sn) on metal nanoparticles it is very
important to know in what form it got attached? For this an XPS (X-ray Photo electron
Spectroscopy) analysis of synthesized catalyst was carried out. Overall survey spectrum
indicated presence of iron (Fe), Oxygen (O) and tin (Sn) [Fig. 5 (a)]. Fig. 5(b) and 5 (c)
shows the binding energy curve for O1s, Sn 3d5/2 and Sn 3d3/2 at around 430.5 eV, 495.3 and
486.9 eV respectively. From literature survey it was found that the values are specific for
SnO2.20 This lead us to the conclusion that tin (Sn) is bonded to nano-Fe3O4-DOPA as SnO2.
120000
Sn
3d
100000
O
1s
80000
Fe
2p
60000
40000
20000
0
800
600
400
200
0
Binding energy (eV)
(a)
(b)

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(c)
Fig. 5: XPS spectra of nano-Fe3O4-DOPA-SnO2 (a) Survey spectra (b) 1s peak of O and (c)
Sn 3d5/2 and Sn 3d3/2 peaks
Prepared nano-Fe3O4-DOPA-SnO2 was also characterized by Powder XRD (PXRD)
analysis. Fig. 6 shows the PXRD pattern of the nano-Fe3O4-DOPA-SnO2. The XRD pattern
consist a two sets of diffraction peaks. One set is at (2θ =) 30.17°, 35.63°, 37.18°, 43.02°,
53.35°, 57.20°, and 62.83° which are indexed to the (220), (311), (400), (422), (511) and
(440) planes of cubic structure of Fe3O4, having lattice indices of a = b= c = 8.38 Å (JCPDS
19-629).21 Another set of diffraction peaks at (2θ =) 34.6°, 53.36°, 59.06°, and 61.20°
corresponds to the (101), (21 1), (002), and (310) planes of tetragonal rutile structure of SnO2
having lattice constants of a = b = 4.737 Å and c = 3.186 Å (JCPDS 41-1445).22 The strong
peaks prove that nano-Fe3O4-DOPA-SnO2 is crystalline in nature which agrees with TEM
results.
Fig. 6: Room temperature XRD pattern of the NP’s of Fe3O4-DOPA-SnO2

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23
VSM analysis indicated ferromagnetic nature of nano-Fe3O4-DOPA-SnO2. Its saturation
magnetization was found to be 32.077 emu/g (Fig.7). Even though it is less than that of bare
nano-Fe3O4 24 because of surface coating but still it is appreciably magnetic for catalyst to be
recycled by an external magnet.
30
20
10
0
-10
-20
-30
0
Field (G)
Fig. 7: Room temperature VSM results of the nano-Fe3O4-DOPA-SnO2 (inset picture is a
zoomed portion of VSM data showing the hysteresis loop)
At last, to gain information regarding thermal stability of SnO2 incorporated nanoparticles, a
TGA (Thermo Gravimetric Analysis) was also performed. TGA curve (Fig. 8) indicated
weight loss which starts at around 42 0C and it may correspond to loss of moisture trapped on
0
catalyst surface. There is also another degradation which starts around 209 C and may
correspond to the loss of SnO2 molecule. This proves that the synthesized catalyst is
0
thermally stable below 200 C and can be easily applied in any reactions below this
temperature.
TGA curve of nano-Fe
O -DOPA-SnO
4
3
2
102
100
98
96
94
92
90
88
86
84
82
0
42.1
C
0
209
C
100
200
300
400
500
600
700
800
900
1000
Temperature (0C)

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Fig. 8: TGA curve of nano-Fe3O4-DOPA-SnO2
An ICP-AES (Inductively coupled plasma atomic emission spectroscopy) analysis was also
performed to determine the amount of tin (Sn) attached on the surface of nano-Fe3O4-DOPA
and it was found to be 1.027 %.
Standardization of reaction parameters:
After synthesis and characterization of nano-Fe3O4-DOPA-SnO2, we applied it for the
synthesis of dihydroquinazolinone derivatives. In order to confirm nano-Fe3O4-DOPA-SnO2
to be crucial for rendering the above said reaction we set up a reaction with isotoic anhydride
(1, 1mmol), NH4OAc (2, 1.5 mmol) and 4-chlorobenzaldehyde (5a, 1 mmol) in ethanol under
refluxing condition without any catalyst. It failed to produce the target molecule in good yield
and only trace amount of dihydroquinazolinone was isolated (8%) after 5h of refluxing. Then
keeping other components in fixed amount we added externally our catalyst (10 mg) and
good amount of product (90 %) was isolated after 3h. Firstly to investigate effect of solvent,
we had set pilot reaction in 5 ml of different non-polar and polar solvents like benzene,
toluene, THF, MeOH, CHCl3, EtOH, acetonitrile, and water. All reactions were refluxed for
3h and it was observed that in non-polar solvents like benzene and toluene, reaction was very
sluggish and conversion of starting materials to desired product was very less. However, in
presence of polar solvents like MeOH, EtOH, acetonitile, THF, chloroform and H2O
conversions were excellent (Table 1). But we decided to choose water as our desired solvent
because its nature’s own reaction medium, easily available and cheap.
Then taking water as solvent we shifted our focus towards standardization of temperature.
Firstly we carried out reaction at room temperature (20 0C) and observed that after 3 h of
vigorous stirring, desired product was not forming and only starting materials were left in the
reaction (from TLC). After getting no positive result at room temperature we applied heat to

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the reaction and carried out four sets of reactions at 40 0C, 60 0C, 80 0C and 100 0C. After
carrying reaction for 3h, we observed that on increasing the temperature, desired product
0
yield was also increasing (Table 1). Maximum yield was obtained at 80 C and on further
increasing the temperature beyond 80 0C showed no significant effect on product yield.
Table 1: Standardization of solvent and temperature a :
Sl. Solvent b Temperature(0
Time
(min)
180
180
180
180
180
180
180
180
180
180
180
180
Yield
c (%)
21
No.
1
C)
80
Benzene
Toluene
THF
2
110
66
30
3
81
4
CHCl3
MeCN
MeOH
EtOH
H2O
62
79
5
82
83
6
65
87
7
82
90
8
100
80
92
9
H2O
92
10
11
12
H2O
60
75
H2O
40
52
H2O
20 (r.t)
-
a Isotoic anhydride (1, 1mmol), NH4Oac (2, 1.5 mmol) and 4-Chlorobenzaldehyde (5a, 1 mmol), nano-Fe3O4-DOPA-SnO2 (10 mg)
b Amount of solvent taken was 5ml; c isolated yield
Catalyst concentration possesses large effect on yield and cost of the process. So, screening
of catalysts concentration was also carried out. We had set up several sets of reaction
containing 0, 2, 4, 6, 8, 10 and 12 mg of catalysts at 80 0C in water. It is important to mention
that without any catalyst showed no positive result even after 3 h of stirring and to our delight
we found that on increasing the catalyst concentration till 10 mg reaction was showing steady
increase in the rate, though on increasing the amount of catalyst beyond 10 mg showed no

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significant effect on the product yield (Fig. 9). So, 10 mg was chosen as optimum catalyst
concentration for getting maximum yield.
After finalizing solvent, temperature and catalyst concentration, standardization of time was
done. For that we took starting materials, 10 mg of catalyst and carried out the reaction using
water as solvent at 80 0C. It was observed that with time, yield was increasing and best result
was observed in 50 min. No more improvement was observed beyond this time frame (Fig.9).
Finally turn over number (TON) and turn over frequency (TOF) of the present catalyst were
also calculated for the pilot reaction based on the amount of the active metal used (Sn) and
they were found to be 1057.47 and 3204.45 h-1.
10 min
100
90
80
70
60
50
40
30
20
10
0
20 min
30 min
40 min
50 min
60 min
0
2
4
6
8
10
12
Catalyst concentration (mg)
Fig. 9: Optimization of catalyst loading with respect to time and yield
We also compared the efficiency and recoverability of nano-Fe3O4-DOPA-SnO2 catalyst with
other conventional catalyst under the standardised reaction condition. Likewise Fe2SO4,
FeCl3, SnCl2 were applied in the pilot reaction and they also showed efficient catalyses but
being hygroscopic and water soluble in nature, their handling and separation from reaction
mixture was difficult. Fe3O4 NP was showing good result but the reaction was sluggish and
when Fe3O4 NP coated with dopamine (DOPA), the catalytic activity decreased drastically
(Table 2).
Table 2: Standardization of catalyst a :

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Sl. No.
Catalysts (10 mg)
Time (min)
Yield (%) b
1
Fe2SO4
FeCl3
50
50
50
50
50
50
73
75
81
53
16
92
2
3
4
5
6
SnCl2
Fe3O4 NP
nano-Fe3O4-DOPA
nano-Fe3O4-DOPA-SnO2
aIsotoic anhydride (1, 1mmol), NH4Oac (2, 1.5 mmol) and 4-chlorobenzaldehyde (5a, 1 mmol), cataylts (10 mg), 5ml water, 80 0C, b isolated
yield
Synthetic application of nano-Fe3O4-DOPA-SnO2 :
With standardized conditions in our hand, to explore further this approach, the generality and
scope of this protocol was examined. For this, we employed various amine sources like
NH4Oac (2) and 4-Methyl aniline (3). Among aldehydes, aromatic (5a-f, 5i, 5k-l), aliphatic
(5h), tricyclic (5g) as well as hetroaromatic aldehyde (5j) were used (Fig. 11) and all of them
afforded brilliant yields within a short period of time as shown in table 3. Aromatic aldehydes
possessing both electron donating as well as electron withdrawing groups in ortho or para
position of the benzene ring, converted into desired products without any difficulties. To
further expand scope of our methodology, application of bulky heteroarmatic amine source
like 2-aminobenzimidazole (4) was also investigated and to our outmost delight, this reaction
also went smoothly there by showing a very good positive result (Scheme 2). Structures of all
synthesized compounds were identified by analyzing spectral data. Structures of 6f, 6k and
6m were also analyzed by single crystal X-ray crystallography (CCDC numbers 1063941,
1524323, 1535780 respectively) and shown in the ORTEP diagrams (Fig. 10).

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(a)
(b)
(c)
Fig 10. ORTEP diagrams of (a) 6f, (b) 6k, (c) 6m
O
O
R
Nano-Fe3O4-DOPA-SnO2
10 mg, H2O (5 ml)
80 0C, 45-90 min
R= p-methylphenyl; 3
N
NH4OAc
O
2
R1CHO
N
H
R1
RNH2
N
H
O
5
6a-p
3/4
1
R= benzimidazole; 4
R1 = various aromatic, alliphatic and heteroaromatic and tricyclic aldehydes.
Scheme 2: Synthetic scheme for the synthesis of dihydroquinazolinone derivatives using nano-Fe3O4-DOPA-SnO2 catalyst
Cl
CN
Br
OCH3
CHO
CHO
O2N
CHO
CHO
CHO
CHO
CHO
5a
5c
5g
5b
5d
5e
5f
O
O
CHO
OCH3
CHO
5k
CHO
5l
CHO
5i
5h
5j
Fig. 11: Various aldehydes used in the reaction

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Table 3:
O
O
O
O
NH
NH
NH
NH NO2
N
H
N
H
N
H
N
H
Cl
CN
Br
6b,
6a,
6c,
6d,
45 min;Yield: 90%
50 min;Yield: 92%
55 min;Yield: 91%
50 min;Yield: 87%
O
O
O
O
H
N
NH
NH
NH
N
H
N
H
N
H
N
H
O
6g,
6h,
6e,
6f,
85 min;Yield: 82%
90 min;Yield: 86%
55 min;Yield: 85%
60 min;Yield: 86%
O
N
O
N
O
N
O
N
N
N
H
O
N
N
H
N
H
N
H
H
Cl
6l,
6j,
6k,
6i
70 min;Yield: 91%
70 min;Yield: 87%
80 min;Yield: 84%
55 min;Yield: 90%
O
N
O
N
O
N
O
N
N
N
N
H
O
N
N
N
O
N
N
H
H
H
N
H
N
H
N
H
N
H
CN
O
6o
6n
75 min;Yield: 86%
6p
6m
80 min;Yield: 85%
90 min;Yield: 82%
60 min;Yield:90%
Isotoic anhydride (1, 1mmol), NH4Oac (2, 1.5 mmol) or amine source (3/4, 1 mmol) and aldehydes (5, 1 mmol), nano-Fe3O4-DOPA-SnO2
(10 mg), 5ml water, 80 0C, Yield = isolated yield.
Speedy creation of molecular diversity in a predictable and controlled way from simple and
easily available starting materials is an exciting topic in modern day organic synthesis. In
short, importance of creating complex molecules relies mainly on combination of individual
transformations in to one synthetic procedure. Following these lines, we cogitated that the use
of 1,4-dialdehydes (5m) and aldehydes possessing multiple functional groups (5n) would
lead to the formation of complex molecules thereby doubling the effectiveness of the above
methodology. Reaction of 1,4-dibenzaldehyde with NH4OAc and isotoic anhydride furnished
desired bis-dihydroquinazolinone (6q) compound after 90 min of heating (scheme 3), which

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effectively leads to the formation of six new C-N bonds, two new C-C bonds, two
stereocentres and two dihydroquinazolinone moieties in a single step. However when bulky
amine group (4-methyl aniline) was taken in place of NH4OAc, it was observed that instead
of bis-product mono-substituted dihydroquinazolinones (6r, 6s) were formed (scheme 4).
O
CHO
NH
*
O
Nano-Fe3O4-DOPA-SnO2
(10 mg)
Water (5 ml), 80 0C, 90 min
N
O
H
H
NH4OAC
N
O
*
N
H
1
O
CHO
5m
HN
2
6q
Yield: 87%
= 6 New C-N bonds
= 2 new C-C bonds
Scheme 3: Synthetic scheme for the formation of bis-dihydroqunazolinone compounds.
O
CHO
OHC
N
5m
N
H
NH2
O
6r
CHO
Nano-Fe3O4-DOPA-SnO2
(10 mg)
H2O (5 ml), 80 0C, 90 min
Yield: 88 %
O
N
H
O
1
2
O
N
O
O
N
H
C
CHO
O
C
O
6s
5n
Yield: 85 %
Scheme 4: Nano-Fe3O4-DOPA-SnO2 catalysed synthesis of quinazolinone derivatives using terephthalaldehyde (5m)
and methyl 4-formylbenzoate (5n)
Plausible Mechanism:
O
O
NH2
R
2 or 3 or 4
SnO2
O
N
O
1 H
O
O
N
SnO2
R
N
O
O
N
H
a
O2
Sn
O2Sn
O2Sn
R1
O
O
N
O
R
H
6
H
N
R
R
N
NH
R
H
N
NH
C
R1
H
N
R1
SnO2
g
Hydrogen
transfer
NH2
h
c
O
O
O2Sn
H
O
O2Sn
O
N
R
R
N
H
b
NH
SnO2
N
H
O
R1
R1
H
OH
e
f
H
R1
O
d
SnO2
CO2
H2O
H
R1
5
= Fe3O4 NPs
O
O
NH2
=
Scheme 5: Plaussible mechanistic pathway catalysed by nano-Fe3O4-DOPA-SnO2

New Journal of Chemistry
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DOI: 10.1039/C7NJ01208J
From experimental results and after referring literature25 we proposed a plausible mechanistic
pathway for the synthesis of dihydroquinazolinone derivatives with nano-Fe3O4-DOPA-SnO2
(scheme 5). In this catalyst, tin (Sn) is the reactive site and it acts a Lewis acid. The carbonyl
groups of isotoic anhydride (1) are activated by co-ordination with tin. Which in turn
facilitates the nucleophilic attack of primary amines (3 or 4) or ammonium acetate (2) to
form a new C-N bond and leads to formation of intermediate b. Intermediate b undergoes
decarboxylation to form another intermediate c. Nano-Fe3O4-DOPA-SnO2 also activates
aldehydes and they react with intermediate c to give a new intermediate e which undergoes
dehydration to form imine intermediate f. Then nano-Fe3O4-DOPA-SnO2 facilitates
intramolecular nucleophilic attack of amide nitrogen to imine and forms acyclic intermediate
h which ultimately undergoes intra-molecular hydrogen transfer to form desired product (6).
Nano-Fe3O4-DOPA-SnO2 being let off from the reaction re-enters the catalytic cycle.
Application of procedure:
To highlight industrial applicability of the present protocol a gram scale reaction was
performed (scheme 6). For this isotoic anhydride (10 mmol, 1), ammonium acetate (15 mmol,
2), 4-chlorobenzaldehyde (10 mmol, 5a) and nano-Fe3O4-DOPA-SnO2 (100 mg) was taken
0
and heated in 50 ml of water at 80 C with constant stirring for 50 min. After completion of
the reaction nano-Fe3O4-DOPA-SnO2 was separated from the reaction mixture by applying an
external magnet and pure product was obtained by using column chromatography (4:6
EtOAc:Hexane). Reaction furnished a good yield (86 %) in the gram scale reaction thereby
proving its industrial applicability.
O
CHO
O
nano-Fe3O4-DOPA-SnO2
(100 mg)
Water (50 ml), 80 0C, 50 min
NH
O
NH4OAC
N
H
N
H
1
O
Cl
5a
Cl
2
6a
Scheme 6: Gram Scale reaction for the formation of dihydroqunazolinone derivative using nano-Fe3O4-DOPA-SnO2

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Application of Compound:
After detailed literature survey it was established that the most biologically active or naturally
occurring quinazolinones are in its oxidised form. Therefore we embarked towards the
functional group transformation of synthesized dihydroquinazolinones to quinazolinones by
using MgO2 as an oxidant (scheme 7). Structures of synthesized quinazolinone derivatives
are shown in Fig. 12.
O
O
R
R
N
1. MnO2, EtOH
N
2. reflux, 15-20 min
R= H; 6c
N
R1
N
R1
H
7a,7b
6c, 6i
p-methylphenyl; 6i
R=
R1= aromatic aldehydes
Scheme 7: Oxidation of didroquinazolinones to quinazolinones
O
O
H
N
N
N
N
Br
Cl
7b
7a
Yield: 85 %
Yield: 87 %
Fig. 12: Structures of quinazolinones prepared
Catalyst stability and recyclability:
For validating recyclability of synthesized catalyst, a re-use investigation of model reaction
involving isotoic anhydride (1) (1 mmol), ammonium acetate (2) (1.5 mmol) and 4-
chlorobenzaldehyde (5a) (1 mmol) along with the catalyst (10 mg) in water was carried out.
After completion of reaction, we recycled back the catalyst simply by using an external
magnet. Following that, catalyst was washed with ethyl acetate and acetone and dried.
Recovered catalyst was reused for five consecutive runs without much decrease in catalyst
activity (Fig.13). Then to check the nature and morphology of catalyst after five consecutive

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runs, TEM (Fig. 14), EDX, SEM, TGA (Fig. 15) analyses of reused catalyst were performed
and those analyses showed no significant changes from that of freshly prepared catalyst.
80
60
40
20
0
1
2
3
4
5
No. of runs
Fig. 13: Catalyst recyclability
A leaching test for synthesised catalyst was also performed. For this, catalyst (10 mg) and
0
water (5 ml) was stirred at 80 C for 2h and then catalyst was separated from the solvent. In
this solvent isotoic anhydride (1) (1 mmol), ammonium acetate (2) (1.5 mmol) and 4-
0
chlorobenzaldehyde (5a) (1 mmol) were added and stirred for 50 min at 80 C. Reaction
showed only 7% conversion of starting materials to product proving negligible amount of
catalyst leaching. To prove it more precisely, after completion of reaction we carried out an
ICP-AES analysis. For that, model reaction was carried out under standardised condition. On
completion of reaction (50 min), catalyst was separated from the reaction mixture and an
ICP-AES analysis of the solvent was performed. It showed very less existence of tin (Sn)
(less than 0.01 ppm) indicating negligible leaching.
(a)
(b)
(c)
Fig. 14: TEM of recycled nano-Fe3O4-DOPA-SnO2 after five runs (a) at 2 nm, (b) at 10 nm
and (c) SAED pattern.

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New Journal of Chemistry
-DOPAV-SniOew Article Online
TGA of reused nano-Fe3O4
2
DOI: 10.1039/C7NJ01208J
100
95
90
85
80
200
400
600
0
800
1000
Temperature ( C)
(a)
(b)
(c)
Fig. 15: (a) EDX of recycled nano-Fe3O4-DOPA-SnO2 (b) SEM of recycled nano-Fe3O4-
DOPA-SnO2, (c) TGA of recycled nano-Fe3O4-DOPA-SnO2 after five runs.
Conclusion:
In conclusion, an efficient, ferromagnetic nano-Fe3O4-DOPA-SnO2 was developed from
easily available starting materials under sustainable conditions. The catalyst was fully
characterized by FT-IR, TEM, EDX, SEM, XPS, powder XRD, VSM, TGA and ICP-AES
analyses. Then the catalyst was exploited in one-pot synthesis of dihydroquinazolinone
derivatives. Merits and novelty of nano-Fe3O4-DOPA-SnO2 does not end here since it is also
applied in the synthesis of bis-dihydroquinazolinone compound thereby leading to the
formation of six new C-N bonds, two new C-C bonds, formation of two new stereocentres
and two new dihydroquinazolinone moieties in one step within a shorter period of time.
Present methodology also highlighted easy separation and reusability of catalyst for five
consecutive runs, higher selectivity of desired product, good application in gram scale
reaction, shorter reaction time, column free purification and easy workup procedures thereby
addressing issues of sustainability. Further biologically more important quinazolinones were
synthesized from dihydroquinazolinone derivatives.
Experimental:
Design and synthesis of nano-Fe3O4-DOPA-SnO2:
Preparation of nano-Fe3O4:
A mixture of ferric nitrate (3.4 g) and ferrous sulphate (3 g) was added in 100 ml of deionised
water and stirred at r.t. (room temperature) for 15 min. Ammonium hydroxide (25%) was

New Journal of Chemistry
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then added till pH of the solution became 10. After that the stirring was continued for another
0
1 h at 60 C. A black precipitate appeared which was separated by external magnet, washed
with water until the pH became neutral and dried in oven.
Post-synthetic modification of nano-Fe3O4 with dopamine (DOPA):
To accomplish this step, we first took 25 ml of deionized water and added 2g of Fe3O4
nanoparticles in it. Then the reaction mixture was dispersed for 30 min by ultrasonication at
room temperature. Following this dopamine hydrochloride (2g) was dissolved separately in 5
ml of deionized water and added to the previous mixture. Resultant mixture was then
ultrasonicated for 2 more hours. This lead to the surface modification of Fe3O4 nanoparticles
with dopamine (DOPA). Synthesized nano-Fe3O4-DOPA was then precipitated by using
acetone, isolated by using an external magnet and washed several times with water and
acetone and dried.
Encapsulation of SnO2 on the surface of nano-Fe3O4-DOPA:
Nano-Fe3O4-DOPA (1g) was dispersed in water (80 ml) and then a solution of tin (II)
chloride dehydrate (1% w/v, 200 mg) in water was added to it. The resulting solution was
then stirred for 24h at room temperature. Following that the product was allowed to settle
down, separated my magnet and washed several times with water and acetone and dried at 50
0C.
Synthesis of dihydroquinazolinone derivatives:
Isotoic anhydride (1) (1 mmol), ammonium acetate (2) (1.5 mmol) or amines (3 or 4) (1
mmol), aldehydes (5) (1 mmol) nano-Fe3O4-DOPA-SnO2 (10 mg), water (5 ml) were taken in
a round-bottom flask. Then the reaction mixture was placed on a pre-heated oil bath
accompanied with a magnetic stirrer (IKA C-MAG, HS4 Digital) at 80 0C and stirred for time
mentioned in table 3. After completion of reaction (monitored by TLC), the reaction mixture

Page 21 of 25
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was cooled at room temperature. Catalyst was then separated by external magnet, washed
with ethyl acetate, acetone and dried. This recovered catalyst was used in another set of
reaction. After that the reaction mixture was extracted with ethylacetate (3x 5 ml) and
combined organic extract was washed with water (3x 10 ml), brine solution (1x 10 ml) and
dried (anhydrous sodium sulphate). Following that the solvent was evaporated and pure
products (6a-s) were obtained by recrystallization from ethanol.
Conversion of dihydroquinazolinones to quinazolinones:
Synthesized dihydroquinazolinones (6e, 6i) (1 mmol), Mn2O (1 mmol) and water 5 ml
were taken in a 25 ml round bottom flask. This was then refluxed for 20-30 min.
Finally after full conversion of dihydroquinazolinones to quinazolinones (TLC), the
reaction mixture was extracted with ethylacetate (3x 5ml) washed with water (3x 10
ml), brine solution (10 ml) and dried over anhydrous sodium sulphate. Pure products
were obtained after recrystallization from ethanol.
Acknowledgment:
We would like to thank Department of Chemistry, North-Eastern Hill University
(NEHU) and the University Grant Commission (UGC) for supporting this work under
the Special Assistance Programme (SAP) (sanctioned no. SERC/F/0293/2012-13) and
DST-Purse programme. We are thankful to the Sophisticated Analytical and
Instrumentation Facility (SAIF) of North-Eastern Hill University and IIT-Bombay, the
central instruments facility (CIF) of IIT-Guwahati. We also take this opportunity to
thank the Institute of Advanced Study in Science and Technology (IASST), Guwahati.
Our sincere thanks go to Mr. Kundan Saha of IIT Guwahati and Mr. Sanjay Adhikary of
NEHU, Shillong, India.

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Table of content
Preparation, characterization and catalytic application of nano-Fe3O4-DOPA-SnO2 having
high TON and TOF for non-toxic and sustainable synthesis of dihydroquinazolinone
derivatives
Binoyargha Dam a, Ranjit A. Patil b, Yuan-Ron Ma b and Amarta Kumar Pal a *
aDepartment of Chemistry, Centre for Advanced Studies
North-Eastern Hill University
Shillong-793022, India
Email: amartya_pal22@yahoo.com (Dr.Amarta Kumar pal)
b Department Physics, National Dong Hwa University, Hualien-97401, Taiwan
CCDC 1535780
O
O
O
O
O
N
R
O
H
N
R1
R
MnO2
R1
R
H
N
+
N
R1NH3
N
H
Fe
3
O
4
Nps
TGA curve of nano-Fe
O -DOPA-SnO
3 4 2
Fe
O
-DOPA
3
4
45
40
35
30
102
100
98
96
94
92
90
88
86
84
82
0
Fe
3
O
4
-DOPA-SnO
2
42.1
C
1632.10
0
209
C
3423.07
25
20
15
10
5
595.31
1631.10
1631.10
576.08
607.69
0
673.08
3423.24
3440.18
nano -Fe O
-5
3
4
100 200 300 400 500 600 700 800 900 1000
4000 3500 3000 2500 2000 1500 1000 500
0
Temperature ( C)
-1
+
Wavenumber (cm
)
O
O
NH2
=
120000
100000
80000
60000
40000
20000
0
+
Sn
3d
O
2p
1s
SnCl2.2H2O,
H2O, r.t, 24h
Fe
SnO
=
nano -F3e O -DOP 2A-S nO
4
2
800
600
400
200
0
Binding energy (eV)
Aqueous reaction medium
Wide substrate variability
High atom economy
Cost effective magnetically recyclable tin catalyst
Column chromatography free
Catalyst reused in 5 runs
High catalyst TON and TOF Gram Scale application