Synthesis and characterization of bromine source supported on magnetic Fe3O4 nanoparticles: A new, versatile and efficient magnetically separable catalyst for organic synthesis

Article abstract of DOI:10.1002/aoc.3634

Tribenzylammonium tribromide supported onto magnetic nanoparticles (Br₃-TBA-Fe₃O₄) as a bromine source was successfully synthesized and characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy and vibrating sample magnetometry. The synthesized catalyst is shown to be a versatile and highly efficient heterogeneous catalyst for the Knoevenagel condensation and synthesis of 2,3-dihydroquinazolin-4(1H)-one and polyhydroquinoline derivatives. To the best of the authors' knowledge, this is the first report of the use of a bromine source immobilized on Fe₃O₄ nanoparticles as a magnetically separable catalyst for these reactions. The nanosolid catalyst can be magnetically recovered and reused readily several times without significant loss in catalytic efficiency.

Full text of DOI:10.1002/aoc.3634

Received: 10 August 2016
DOI 10.1002/aoc.3634
Accepted: 21 August 2016
F U L L PA P E R
Synthesis and characterization of bromine source supported on
magnetic Fe3O4 nanoparticles: A new, versatile and efficient
magnetically separable catalyst for organic synthesis
Lotfi Shiri | Arash Ghorbani‐Choghamarani | Mosstafa Kazemi
Department of Chemistry, Faculty of Basic
Tribenzylammonium tribromide supported onto magnetic nanoparticles (Br3‐TBA‐
Fe3O4) as a bromine source was successfully synthesized and characterized using
Sciences, Ilam University, PO Box 69315‐516,
Ilam, Iran
Correspondence
Lotfi Shiri, Department of Chemistry, Faculty of
Fourier transform infrared spectroscopy, thermogravimetric analysis, X‐ray diffrac-
tion, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy and
vibrating sample magnetometry. The synthesized catalyst is shown to be a versatile
Basic Sciences, Ilam University, PO Box 69315‐
516, Ilam, Iran.
Email: lshiri47@gmail.com
and highly efficient heterogeneous catalyst for the Knoevenagel condensation and
synthesis of 2,3‐dihydroquinazolin‐4(1H)‐one and polyhydroquinoline derivatives.
To the best of the authors' knowledge, this is the first report of the use of a bromine
source immobilized on Fe3O4 nanoparticles as a magnetically separable catalyst for
these reactions. The nanosolid catalyst can be magnetically recovered and reused
readily several times without significant loss in catalytic efficiency.
KEYWORDS
Br3‐TBA‐Fe3O4, 2,3‐dihydroquinazolin‐4(1H)‐one, Knoevenagel condensation,
magnetically separable catalyst, polyhydroquinoline
1
|
INTRODUCTION
reagents such as ammonium chloride,[11] iodine,[12] ionic
liquids,[13,14] Brønsted acids,[15] phosphoric acid,[16] copper
chloride,[17] tetrabutylammonium bromide,[18] TMSCl‐
Among the various classes of nitrogen‐containing hete-
rocyclic compounds endowed with numerous biological
activities, 2,3‐dihydroquinazolin‐4(1H)‐one and poly-
hydroquinoline structural motifs have attracted much
attention because they not only possess a broad spectrum of
biological activities but also are extensively employed in
medicinal industry for the design of new categories of active
molecules with valuable antioxidant and pharmacological
properties.[1–4] Recent literature clearly shows that 2,3‐
dihydroquinazolin‐4(1H)‐ones and polyhydroquinolines have
been clinically used as antitumor, anticancer, antibiotic,
antidiabetic, antibacterial, antidefibrillatory, antipyretic and
anticonvulsant agents.[4–8] Furthermore, polyhydroquinoline
derivatives also are well known as calcium channel blockers,
and have emerged as one of the most important class of drugs
for the treatment of cardiovascular disease and Alzheimer's
disease.[9,10] In view of their tremendous significance, for
the synthesis of 2,3‐dihydroquinazolin‐4(1H)‐one and
polyhydroquinoline frameworks, a variety of catalysts and
NaI,[19] hetrapolyacid,[20] nickel nanoparticles,[21] MCM‐
41,[22] ZrCl4
and p‐TSA[24] have been recently reported
[23]
in the literature. Despite the great importance of the
above strategies, most of them suffer from a series of draw-
backs such as unsatisfactory yields, formation of undesirable
di‐substituted product, long reaction times, high tempera-
tures, tedious work‐up, use of hazardous and carcinogenic
solvent as reaction medium as well as use of toxic, expensive
and non‐reusable catalysts. Therefore, the development of
new, clean and efficient synthetic procedures (using reusable
catalysts and green solvents) for the synthesis of these
valuable derivatives is still an important challenge from
environmental, practical and economical points of view.
The first 15 years of the twenty‐first century witnessed a
rapid and considerable growth in the utilization of
nanomaterials as catalyst supports. Among these
nanomaterials, magnetic nanoparticles (MNPs) have received
much attention due to their unique advantages such as high
Appl Organometal Chem 2016; 1–12
wileyonlinelibrary.com/journal/aoc
Copyright © 2016 John Wiley & Sons, Ltd.
1

2
SHIRI ET AL.
surface area to bulk ratios, low toxicity, high activity and
thermal stability and the capability of surface modifications
and easy dispersion.[25,26] MNPs can be readily separated
from a reaction medium using an external magnet, without
the need for filtration, centrifugation or other tedious work‐
up processes.[27,28] In fact, use of magnetically separable cat-
alysts is a well‐favoured and fascinating strategy to bridge the
split between heterogeneous and homogenous catalysis.[29]
Among the various MNPs employed as core magnetic sup-
port, Fe3O4 nanoparticles have been widely studied for both
their scientific interest and technological applications.[30]
Up to now, a diverse range of synthetic protocols have
been developed for the construction of organic compounds
and synthetic intermediates using molecular bromine.[31] To
decrease the toxicity of these processes (since molecular bro-
mine is toxic), during recent decades, a number of
tribromide‐containing compounds have been prepared and
successfully applied as catalysts for a range of organic trans-
formations to reach the corresponding target synthetic prod-
ucts.[32,33] The immobilization of N‐tribromide reagents on
Fe3O4 nanoparticles can be considered as an efficient and fas-
cinating catalytic system, and the nanosolid catalyst can be
readily separated from the reaction medium using an external
magnet. Considering this topic, from the economic and envi-
ronmental points of view, we became interested in synthesiz-
ing tribenzylammonium tribromide immobilized on Fe3O4
nanoparticles (Br3‐TBA‐Fe3O4) and studying its catalytic
activity in the synthesis of 2,3‐dihydroquinazolin‐4(1H)‐one
and polyhydroquinoline derivatives.
supported APTMS with tribenzyl bromide in the presence
of K2CO3 in dimethylformamide (DMF) under reflux condi-
tions for 30 h. Finally, the reaction of Br‐TBA‐Fe3O4 with
Br2 in carbon tetrachloride at ambient temperature for 8 h
led to the generation of Br3‐TBA‐Fe3O4.
The synthesized nanomagnetic catalyst was com-
prehensively characterized using Fourier transform infrared
(FT‐IR) spectroscopy, thermogravimetric analysis (TGA),
X‐ray diffraction (XRD), scanning electron microscopy
(SEM), energy‐dispersive X‐ray spectroscopy (EDX) and
vibrating sample magnetometry (VSM).
The successful formation of Br3‐TBA‐Fe3O4 was con-
firmed from FT‐IR spectra. The FT‐IR spectra for Fe3O4
MNPs, APTMS‐Fe3O4, Br‐TBA‐Fe3O4 and Br3‐TBA‐Fe3O4
are shown in Figure 1. The FT‐IR spectrum of Fe3O4 MNPs
shows a strong peak at 579 cm−1, which it is attributed to the
presence of Fe─O bond and it confirms the formation of
Fe3O4 MNPs. A broad peak is observed at 3400 cm−1, which
is characteristic of both symmetric and unsymmetric modes
of O─H bonds linked to the surface of iron atoms. Also,
the appearance of a stretching peak at 1624 cm−1 is attributed
to an adsorbed water layer. The presence of APTMS moieties
on the surface of the Fe3O4 MNPs is confirmed by a charac-
teristic peak at 1001 cm−1 which is ascribed to the Fe─O─Si
stretching vibration. The FT‐IR spectrum of APTMS‐Fe3O4
exhibits a broad band at 3334 cm−1 assigned to NH2 group
and two weak peaks at 2922 and 2854 cm−1 which are
ascribed to the C─H stretching vibration of alkyl chain of
amine. In the spectrum of Br‐TBA‐Fe3O4, the characteristic
weak peaks at 2925 and 1640 cm−1 are attributed to C─H
and C═C stretching vibrations. Also the broad peak at about
1370–1400 cm−1 in the spectrum of Br‐TBA‐Fe3O4 is attrib-
uted to C─N+ stretching vibration.[34] But, Br3 exhibits a
2
| RESULTS AND DISCUSSION
signal between 180 and 200 cm ,
−1 [35] which is not recogniz-
able in the FT‐IR spectrum.
2.1 | Preparation and characterization of Br3‐TBA‐
Fe3O4
Br3‐TBA‐Fe3O4 was successfully synthesized using a
surface modification strategy, as depicted in Scheme 1.
The Fe3O4 nanoparticles were prepared using the chemical
co‐precipitation method[2] and coated with 3‐amino-
propyltrimethoxysilane (APTMS) by covalent bonds.[2]
Ammonium bromide immobilized on Fe3O4 nanoparticles
(Br‐TBA‐Fe3O4) was prepared through the reaction of the
SCHEME
1
General route for the synthesis of tribenzyl ammonium
FIGURE 1 FT‐IR spectra of (a) Fe3O4 MNPs, (b) APTMS‐Fe3O4, (c) Br‐
TBA‐Fe3O4 and (d) Br3‐TBA‐Fe3O4
tribromide immobilized on Fe3O4 nanoparticles (Br3‐TBA‐Fe3O4)

SHIRI ET AL.
3
The morphology and particle size of the catalyst were
investigated using SEM, as shown in Figure 2. From the
SEM images, it can be seen that the catalyst is made up of
uniformly particles and the average size of Br3‐TBA‐Fe3O4
is about 15 nm.
The components of Br3‐TBA‐Fe3O4 were analysed using
EDX (Figure 3). As shown in Figure 3, the characteristic
peaks of Fe, O, C, N, Si and Br indicate well that
tribenzylammonium tribromide is successfully immobilized
on the Fe3O4 nanoparticles. As a result of this analysis, it
can be concluded that the Br3‐TBA‐Fe3O4 catalyst has been
successfully synthesized.
The magnetic property of the catalyst was investigated
using VSM at ambient temperature. The magnetization
curves for the Fe3O4 nanoparticles and Br3‐TBA‐Fe3O4 are
FIGURE 3 EDX spectrum of Br3‐TBA‐Fe3O4
depicted in Figure 4. As can be seen, the saturation magneti-
zation of Br3‐TBA‐Fe3O4 is about 38 emu g−1, which is much
lower than that of bare Fe3O4 MNPs (about 55 emu g−1). As
expected, the saturation magnetization of Br3‐TBA‐Fe3O4 is
decreased due to the silica coating and the layer of the grafted
catalyst.
TGA is an effective and fascinating technique for inves-
tigating the thermal stability of the immobilized catalyst
relative to that of MNPs. Furthermore, bond formation
between the MNPs and the catalyst can also be interpreted
and verified using TGA. The overlaid TGA curves of
Fe3O4 nanoparticles, APTMS‐Fe3O4 and Br3‐TBA‐Fe3O4
are displayed in Figure 5. The initial mass loss at tempera-
tures below 200°C is due to the removal of physically
adsorbed solvent and surface hydroxyl groups. Organic
groups have been reported to desorb at temperatures above
260°C. The mass loss of about 5% between 240 and 420°C
for APTMS‐Fe3O4 is ascribed to the thermal decomposition
of the 3‐aminopropylsilane groups. In the curve of Br3‐
TBA‐Fe3O4, a weight loss of about 8% over the range
FIGURE 4 Magnetization curves for Fe3O4 MNPs (red) and Br3‐TBA‐
FIGURE 2 SEM images of Br3‐TBA‐Fe3O4
Fe3O4 (green) at room temperature

4
SHIRI ET AL.
2.2 | Catalytic Studies
After characterization of the catalyst, the catalytic activity
of Br3‐TBA‐Fe3O4 in the one‐pot synthesis of 2,3‐
dihydroquinazolin‐4(1H)‐ones was investigated. In this
respect, the cyclocondensation of 4‐chlorobenzaldehyde and
anthranilamide was selected as a model reaction to optimize
the reaction condition by varying catalyst amount, solvent
and reaction temperature. The results are summarized in
Table 1. First, the impact of different amounts of Br3‐TBA‐
Fe3O4 (3, 5, 10, 15 and 20 mg) on the reaction was studied
and it is found that the amount plays a key role in the product
yield and conversion time (Table 1, entries 1–5). Second,
with optimal catalytic amount (5 mg of Br3‐TBA‐Fe3O4),
the effect of solvent on the process was studied. In this
respect, a series of polar and non‐polar solvents at reflux tem-
perature were examined (Table 1, entries 6–10). The best
results are obtained when the reaction is conducted in ethanol
and water. Compared to ethanol, water ias found to be the
best solvent with respect yield and reaction time. From com-
parison of the obtained results in entry 10 with entry 4,
FIGURE 5 TGA curves of Fe3O4 MNPs (green), APTMS‐Fe3O4 (red) and
Br3‐TBA‐Fe3O4 (blue)
250–600°C is also observed, which is attributed to the
breakdown of the tribenzylammonium tribromide moieties.
As a result of this analysis, it can be concluded that the
grafting of bromine source on the surface of Fe3O4
nanoparticles is verified.
TABLE 1 Optimization of reaction conditionsa
XRD is an effective technique for investigation of the reor-
ganization of the major properties of magnetite structures. In
fact, the formation of magnetite crystal phase in the
nanomagnetic catalyst in aggregate powder form can also be
identified by XRD. The XRD diffraction pattern of the
prepared Br3‐TBA‐Fe3O4 is shown in Figure 6. Several
characteristic peaks at 2θ = 35.1°, 41.4°, 50.6°, 63.2°, 67.5°
and 74.5° are observed, which are assigned to the (220),
(311), (400), (422), (511) and (440) crystallographic faces of
magnetite (in good agreement with the standard Fe3O4 XRD
spectrum reported in the literature).[4] This analysis clearly
indicates that the surface modification and conjugation of the
Fe3O4 nanoparticles do not lead to phase change.
Amount of
catalyst (mg)
Solvent
(Temp., °C)
Time
(min)
Yield
(%)b
Entry
1
3
H2O (70)
110
90
84
90
2
5
H2O (70)
3
10
15
20
15
15
15
15
15
15
—
H2O (70)
60
94
4
H2O (70)
40
97
5
H2O (70)
40
97
6
CH3CN (reflux)
EtOH (reflux)
THF (reflux)
PhMe (reflux)
H2O (reflux)
H2O (60)
90
87
7
75
90
8
130
155
40
79
9
73
10
11
12
96
65
92
H2O (70)
120
Trace
aReaction conditions: anthranilamide (1.05 mmol) and 4‐chlorobenzaldehyde
(1 mmol) in the presence of catalyst and solvent (2 ml).
bIsolated yield.
SCHEME
2
Br3‐TBA‐Fe3O4‐catalysed
cyclocondensation
of
FIGURE 6 XRD pattern of Br3‐TBA‐Fe3O4
anthranilamide with aldehydes/ketones

SHIRI ET AL.
5
wefind that the product yield and reaction time are not
improved when the reaction temperature id increased from
70°C to reflux temperature. Finally, to clarify the role of
Br3‐TBA‐Fe3O4, the process was conducted under catalyst‐
free conditions (Table 1, entry 12), and only a trace amount
of the product is observed on the TLC plate after 120 min.
Accordingly, after a comprehensive screening of the process
parameters, the highest yield and shortest reaction time for
product 3a are obtained with 15 mg of Br3‐TBA‐Fe3O4 in
water (2 ml) at 70°C (Table 1, entry 4).
Next, with the optimized reaction conditions in hand, the
scope and generality of this process were further studied
TABLE 2 Br3‐TBA‐Fe3O4‐catalysed one‐pot synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones in H2O at 70°C
Entry
R
R′
Product
Time (min)
Yield (%)a
M.p. (°C)
1
4‐ClC6H5CHO
4‐OMeC6H5CHO
4‐MeC6H5CHO
4‐FC6H5CHO
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
—
Me
2a
2b
2c
40
25
60
20
60
45
35
30
65
40
45
70
50
35
90
50
60
30
40
35
45
30
140
165
97
92
93
97
91
98
95
94
92
93
94
89
91
90
86
89
90
90
89
94
91
93
82
80
198–200[7]
185–186[6]
221–223[6]
196–198[6]
199–201[33]
202–203[6]
170–172[7]
209–211[19]
276–278[6]
217–219[6]
191–192[36]
190–191[36]
184–186[36]
145–147[37]
188–190[6]
175–176[36]
203–205[38]
174–175[36]
185–187[39]
209–211[6]
168–169[36]
187–189[6]
219–220[6]
221–222[36]
2
3
4
2d
2e
5
4‐NO2C6H5CHO
4‐BrC6H5CHO
4‐EtOC6H5CHO
4‐(Me2)NC6H5CHO
4‐OHC6H5CHO
C6H5CHO
6
2f
7
2 g
2 h
2i
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2j
3‐ClC6H5CHO
3‐NO2C6H5CHO
3‐BrC6H5CHO
3‐OMeC6H5CHO
2‐NO2C6H5CHO
2‐BrC6H5CHO
2‐ClC6H5CHO
2‐OMeC6H5CHO
2‐MeC6H5CHO
3,4‐(OMe)2C6H5CHO
2,4‐(Cl)2C6H4CHO
2,4‐(OMe)2C6H4CHO
Cyclohexanone
Ph
2 k
2 l
2 m
2n
2o
2p
2q
2r
2 s
2 t
2u
2v
2w
2×
aIsolated yield.
TABLE 3 Optimization of reaction conditionsa
Entry
Catalyst (mg)
Solvent
Temperature (°C)
Time (min)
Yield (%)b
1
3
3
CH3CN
Reflux
Reflux
Reflux
Reflux
Reflux
90
180
240
200
240
180
65
72
64
75
35
76
81
84
90
95
95
91
98
97
10
2
THF
3
3
DMF
4
3
H2O
5
3
EtOH
6
3
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
Solvent‐free
7
5
90
55
8
10
15
20
15
15
15
—
90
35
9
90
20
10
11
12
13
14
90
20
80
35
100
10
110
10
100
240
aReactions conditions: aldehyde (1 mmol), dimedone (1 mmol), ethyl acetoacetate (1 mmol) and ammonium acetate (1.2 mmol).
bIsolated yield.

6
SHIRI ET AL.
ammonium acetate was studied under the optimized reaction
conditions (Scheme 3). The results are summarized in Table 4.
A range of polyhydroquinoline derivatives are obtained in
TABLE 5 Optimization of reaction conditionsa
SCHEME 3 Br3‐TBA‐Fe3O4‐catalysed synthesis of polyhydroquinolines
with a diverse range of aldehydes and ketones (Scheme 2).
The results of this study are summarized in Table 2.
The electronic effect on the aromatic ring of aldehydes has
Amount of
catalyst (mg)
Solvent
(Temp, °C)
Time
(min)
Yield
(%)b
Entry
a
notable impact on the productivity and reaction
1
3
H2O (70)
65
50
87
91
times, because 4‐substituted 2,3‐dihydroquinazolin‐4(1H)‐
ones (Table 2, entries 1–9) are achieved in shorter reaction
times and higher yields than 3‐ or 2‐substituted 2,3‐
dihydroquinazolin‐4(1H)‐ones (Table 2, entries 11–19).
High reaction yields are obtained when disubstituted
aromatic aldehydes are used as substrate (Table 2, entries
20–22). It is noteworthy that when ketones are used as sub-
strate, the products 2w and 2× are afforded in satisfactory
yields and with longer reaction times because of the steric
effect (Table 2, entries 23 and 24).
2
5
H2O (70)
3
10
15
10
10
10
10
10
10
—
H2O (70)
30
98
4
H2O (70)
30
98
5
CH3CN (reflux)
EtOH (reflux)
THF (reflux)
PhMe (reflux)
H2O (reflux)
H2O (60)
105
95
91
6
93
7
150
150
30
73
8
68
9
97
10
11
45
93
H2O (70)
120
Trace
In the next part of our study, the catalytic activity of
Br3‐TBA‐Fe3O4 in the synthesis of polyhydroquinolines
was investigated. First, to determine the optimum reaction
conditions and understand the effect of various parameters
(such as solvent type, catalyst and amount of hydrogen
peroxide) on multicomponent reactions, the reaction of 4‐
aReaction conditions: malononitrile (1.05 mmol) and 4‐chlorobenzaldehyde
(1 mmol) in the presence of catalyst and solvent (2 ml).
bIsolated yield.
cholorobenzaldehyde,
ethyl
acetoacetate,
dimedone
and ammonium acetate was chosen as a model reaction.
Accordingly, as evident from Table 3, 15 mg of Br3‐
TBA‐Fe3O4 in the absence of solvent at 100°C were chosen
as the ideal reaction conditions for the synthesis of
polyhydroquinoline derivatives (Table 3, entry 12).
To establish the generality of this protocol, the reaction of
various aldehydes with dimedone, ethyl acetoacetate and
SCHEME 4 Knoevenagel condensation of active methylene compounds
with aromatic aldehydes catalysed by Br3‐TBA‐Fe3O4
TABLE 4 Br3‐TBA‐Fe3O4‐catalysed synthesis of polyhydroquinolines at 100°C under solvent‐free conditions
Entry
Aldehyde
Product
Time (min)
Yield (%)a
M.p. (°C)
1
4‐ClC6H5CHO
4‐OMeC6H5CHO
4‐MeC6H5CHO
4‐FC6H5CHO
4a
4b
4c
10
15
20
10
25
15
40
35
25
30
20
40
98
91
93
95
94
99
92
97
96
95
92
93
237–239[40]
251–253[40]
252–254[40]
180–182[40]
241–243[41]
249–252[40]
230–233[40]
233–235[41]
179–180[40]
215–217[40]
202–204[40]
234–236[41]
2
3
4
4d
4e
5
4‐NO2C6H5CHO
4‐BrC6H5CHO
4‐OHC6H5CHO
4‐(Me2)NC6H5CHO
4‐OEtC6H5CHO
C6H5CHO
6
4f
7
4 g
4 h
4i
8
9
10
11
12
4j
3,4‐(OMe)2C6H5CHO
3‐BrC6H5CHO
4 k
4 l
aIsolated yield.

SHIRI ET AL.
7
short times with excellent yields. It is noteworthy that the type
of aldehyde has no significant effect on the reaction, because
the desired products are obtained in high yields in relatively
short reaction times.
Knoevenagel condensation is still one of the well‐known
reactions in organic synthetic chemistry because
Knoevenagel products, namely α,β‐unsaturated products or
synthesized alkenes, play a key role in the synthesis of fine
chemicals,[42] therapeutic drugs,[43] natural products,[44]
functional polymers,[45] cosmetics[46] and perfumes,[47] in
hetero Diels–Alder reactions[48] and in the synthesis of carbo-
cyclic as well as heterocyclic compounds of biological
TABLE 6 Br3‐TBA‐Fe3O4‐catalysed one‐pot Knoevenagel condensation of malononitrile with aldehydes in H2O at 70°C
Entry
Substrate
Product
Time (min)
Yield (%)a
M.p. (°C)
1
4‐ClC6H5CHO
4‐OMeC6H5CHO
4‐MeC6H5CHO
4‐FC6H5CHO
6a
6b
6c
30
45
40
20
25
30
55
45
20
50
45
65
70
65
35
35
98
93
94
96
94
97
92
95
94
89
90
87
88
89
91
93
159–161[51]
110–111[51]
129–131[51]
120–122[52]
160–162[51]
158–160[52]
171–173[18]
177–179[52]
81–83[51]
101–102[52]
107–109[53]
157–160[54]
139–140[54]
158–160[54]
93–96[55]
2
3
4
6d
6e
5
4‐NO2C6H5CHO
4‐BrC6H5CHO
4‐OEtC6H5CHO
4‐(Me2)NC6H5CHO
C6H5CHO
6
6f
7
6 g
6 h
6i
8
9
10
11
12
13
14
15
16
3‐NO2C6H5CHO
3‐OMeC6H5CHO
3‐OHC6H5CHO
2‐NO2C6H5CHO
2‐OHC6H5CHO
2‐ClC6H5CHO
C6H5CH═CH
6j
6 k
6 l
6 m
6n
6o
6p
124–127[54]
aIsolated yield.
TABLE 7 Br3‐TBA‐Fe3O4‐catalysed one‐pot Knoevenagel condensation of ethyl cynoacetate with aldehydes in H2O at 70°C
Entry
Substrate
Product
Time (min)
Yield (%)a
M.p. (°C)
1
4‐ClC6H5CHO
4‐OMeC6H5CHO
4‐MeC6H5CHO
4‐FC6H5CHO
8a
8b
8c
55
75
97
92
91
93
90
95
90
94
93
88
85
86
91
91–93[52]
78–81[56]
90–92[52]
88–90[57]
168–170[52]
88–91[52]
170–172[52]
121–124[52]
50–52[51]
128–130[52]
100–102[58]
130–132[56]
115–117[56]
2
3
85
4
8d
8e
45
5
4‐NO2C6H5CHO
4‐BrC6H5CHO
4‐OHC6H5CHO
4‐(Me2)NC6H5CHO
C6H5CHO
70
6
8f
55
7
8 g
8 h
8i
115
95
8
9
50
10
11
12
13
3‐NO2C6H5CHO
2‐NO2C6H5CHO
2‐OHC6H5CHO
C6H5CH═CH
8j
110
155
160
65
8 k
8 l
8 m
aIsolated yield.

8
SHIRI ET AL.
significance.[49] In general, this type of condensation is
catalysed by organic bases and their salts such as
ethylenediamine, dimethylaminopyridine and guanidine in
an organic solvent or a liquid‐phase system.[50] In these
cases, the recovery of the catalysts is very difficult and their
utilization is not ideal from the economic point of view.
Owing to the significance of Knoevenagel products from
the biological and medicinal points of view, we decided to
study the catalytic activity of Br3‐TBA‐Fe3O4 in the
Knoevenagel condensation of aldehydes and active methy-
lene compounds. In this respect, the condensation of
malononitrile with 4‐chlorobenzaldehyde was chosen as a
model reaction to optimize the reaction conditions by vary-
ing catalyst amount, solvent and reaction temperature. The
results are summarized in Table 5. The highest yield and
shortest reaction time for product 6a are obtained when
10 mg of Br3‐TBA‐Fe3O4 is used in water at 70°C (Table 5,
entry 3).
In order to explore the scope and generality of this cat-
alytic system, the Knoevenagel condensations of two types
of active methylene compounds (namely malononitrile and
ethyl cynoacetate) with various aldehydes were tested under
the optimized conditions (Scheme 4). The results of this
study are summarized in Tables 6 and 7. The obtained data
demonstrate well that a broad spectrum of aldehydes can
successfully participate in the process and the desired prod-
ucts are obtained in high to excellent yields. As evident
from Tables 6 and 7, aromatic aldehydes bearing either
electron‐donating or electron‐withdrawing groups readily
react with malononitrile and ethyl cynoacetate and the
desired products are obtained in high yields. These results
demonstrate well that malononitrile (Table 6) is more reac-
tive than ethyl cyanoacetate (Table 7), because the reactions
proceed faster and the products achieved in higher yields
when malononitrile is used as an active methylene
compound.
In order to show the efficiency of the present system, the
results obtained for the synthesis of products 2a, 4a and
6a are compared with those of previously reported proce-
dures (Table 8). The present protocol is superior to some of
the previously reported procedures in terms of product yield,
reaction time and reaction conditions.
The recovery and reusability of catalysts are valuable
advantages in modern catalysis research, which make them
very notable from commercial and economic points of view.
In this respect, the reusability of Br3‐TBA‐Fe3O4 in the
synthesis of products 2a, 4a and 6a (as model reactions) was
investigated. At the end of the process, Br3‐TBA‐Fe3O4 was
readily separated from the reaction mixture using an external
magnet, washed several times with ethyl acetate and dried to
remove residual product. Then, the recovered catalyst was
reused for a subsequent fresh batch of the reaction. The cata-
lytic activity was studied for six successive times, showing
similar activity in each run (Figure 7). Accordingly, one of
the fascinating advantages of this new catalytic system is its
simple, rapid and efficient separation using a suitable external
magnet, which minimizes the loss of catalyst during
separation.
FIGURE 7 Reusability of Br3‐TBA‐Fe3O4 in the synthesis of products 2a,
4a and 6a
TABLE 8 Comparison of activity of various catalysts in the synthesis of products 2a (entries 1–5), 4a (entries 6–10) and 6a (entries 11–15)
Entry
Catalyst
Conditions
Time (min)
Yield (%)
Ref.
[59]
[60]
[61]
[62]
1
2
KAl(SO4)2⋅E12H2O
Glycerosulfonic acid
Silica sulfuric acid
SBNPSA
EtOH, reflux
glycerol, 80°C
H2O, 80°C
300
360
180
150
40
80
97
81
87
97
87
80
98
95
98
90
88
94
95
98
3
4
EtOH, reflux
H2O, 70°C
5
Br3‐TBA‐Fe3O4
PdCl2
This work
[3]
6
THF, reflux
240
30
[63]
[40]
[64]
7
K7[PW11CoO40
Cu‐SPATB/Fe3O4
[TBA]2[W6O19
]
CH3CN, reflux
PEG‐400, 80°C
Solvent‐free, 110°C
Solvent‐free, 100°C
EtOH, reflux
Solvent‐free, reflux
DMSO, 35°C
Acetone, r.t.
8
65
9
]
20
10
11
12
13
14
15
Br3‐TBA‐Fe3O4
PVC‐TEPA
SO42−/ZrO2
Lipase
10
This work
[65]
60
[66]
[67]
[51]
120
720
60
NP‐SnO2
Br3‐TBA‐Fe3O4
H2O, 70°C
30
This work

SHIRI ET AL.
9
3
|
CONCLUSIONS
4.3 | Preparation of APTMS‐Fe3O4
The obtained Fe3O4 nanoparticles (1.5 g) were dispersed in
250 ml of ethanol–water (1:1 v/v) by sonication for 30 min,
and then APTMS (2.5 ml) was added to the mixture. The
reaction mixture was mechanically stirred under nitrogen
atmosphere at 40°C for 8 h. Then, the nanoparticles were
redispersed in ethanol by sonication five times and separated
through magnetic decantation. The nanoparticle product
(APTMS‐Fe3O4) was dried at room temperature.
From the experimental results obtained we can conclude that
Br3‐TBA‐Fe3O4 is a versatile and highly efficient bromine
source catalyst for organic synthesis. It is noteworthy that a
broad spectrum of 2,3‐dihydroquinazolin‐4(1H)‐ones,
polyhydroquinolines and Knoevenagel products (α,β‐unsatu-
rated products) was obtained in high to excellent yields. The
nanosolid catalyst with high activity could be readily recov-
ered from the reaction medium using an external magnet
and reused for at least six cycles without significant loss in
its catalytic efficiency. To the best of our knowledge, this is
the first report of the use of a bromine source immobilized
on Fe3O4 nanoparticles as a magnetically separable catalyst
for the synthesis of 2,3‐dihydroquinazo‐lin‐4(1H)‐ones and
polyhydroquinolines as well as Knoevenagel condensation
products. As a result of this study, we believe that this
protocol will open up a new practical and efficient synthetic
strategy for the preparation of pharmaceutically and biologi-
cally active molecules.
4.4 | Preparation of Br‐TBA‐Fe3O4
The obtained APTMS‐Fe3O4 (1 g) was added to a mixture of
K2CO3 (2 mmol) and benzyl bromide (2.5 ml) in DMF. The
mixture was then stirred at 80°C for 30 h under N2
atmosphere. The resulting powder was separated by magnetic
decantation. The magnetic powder was washed with ethanol
and dried at room temperature.
4.5 | Preparation of Br3‐TBA‐Fe3O4 Catalyst
Br‐TBA‐Fe3O4 (1 g) was dispersed in CCl4 (10 ml) using an
ultrasonic bath for 20 min. Subsequently, Br2 (4 ml) was
added and the mixture was stirred for 8 h at room tempera-
ture. Then, the final product was separated by magnetic
decantation and washed with CCl4 to remove the unattached
substrates. The product (Br3‐TBA‐Fe3O4) was stored in a
refrigerator prior to use as catalyst.
4
| EXPERIMENTAL
4.1 | Materials
Chemicals were purchased from Fisher and Merck. The
reagents and solvents used in this work were obtained from
Sigma‐Aldrich, Fluka or Merck and used without further
purification. Nanostructures were characterized using a
Holland Philips X'pert powder X‐ray diffractometer (Co Kα
radiation, 0.154056 nm), at a scanning speed of 2° min−1
from 10° to 100°. The particle size and morphology were
investigated with a JEOL JEM‐2010 scanning electron micro-
scope, at an accelerating voltage of 200 kV. The FT‐IR
spectra of samples were recorded in KBr discs using a
Nicolet Impact 410 spectrometer. TGA curves were recorded
4.6 | General procedure for synthesis of 2,3‐
dihydroquinazolin‐4(1H)‐ones
A mixture of anthranilamide (1.05 mmol, 142 mg), aldehyde
or ketone and Br3‐TBA‐Fe3O4 (15 mg) in water (2 ml) was
stirred at 70°C. Reaction progress was monitored by TLC
(acetone–n‐hexane, 2:8). After the time specified in Table 2,
reaction mass was allowed to cool to room temperature.
CH2Cl2 (3 × 5 ml) was added to the reaction mixture and
the catalyst was separated using an external magnet. CH2Cl2
was evaporated under reduced pressure to afford the crude
products. The obtained crude products were further
recrystallized from ethanol to afford the pure 2,3‐
dihydroquinazolin‐4(1H)‐ones (80–98%).
using
a
PL‐STA 1500 device (Thermal Sciences).
Supermagnetic properties of the catalyst were measured with
an MDKFD VSM instrument.
4.2 | Preparation of Fe3O4 MNPs
A mixture of FeCl3⋅6H2O (5.838 g, 0.0216 mol) and
FeCl2⋅4H2O (2.147 g, 0.0108 mol) was dissolved in 100 ml
of deionized water in a three‐necked flask (250 ml)
under nitrogen atmosphere. After that, under rapid mechani-
cal stirring, 10 ml of NH3 was added into the solution within
30 min with vigorous mechanical stirring. After being rapidly
stirred for 30 min, the resultant black dispersion was heated
to 80°C for 30 min. The black precipitate formed was isolated
by magnetic decantation, washed with double‐distilled water
until neutrality, further washed twice with ethanol and dried
at room temperature.
4.7 | General procedure for synthesis of
polyhydroquinolines
A mixture of aldehyde (1 mmol), dimedon (1 mmol), ethyl
acetoacetate (1 mmol), ammonium acetate (1.2 mmol) and
Br3‐TBA‐Fe3O4 (15 mg) was stirred at 100°C under sol-
vent‐free conditions. Reaction progress was monitored by
TLC (acetone–n‐hexane, 3:7). After completion of the
reaction, the catalyst was separated using an external magnet
and washed with ethyl acetate. Then, the solvent was evapo-
rated and all products were recrystallized from ethanol. The

10
SHIRI ET AL.
pure polyhydroquinoline derivatives were obtained in excel-
lent yields (91–99%).
N‐H). 13C NMR (DMSO, 100 MHz, δ, ppm): 67.1, 114.9,
115.4, 117.6, 127.4, 127.9, 128.8, 129, 133.8, 142.1, 148.4,
164.1.
2‐(3‐Nitrophenyl)‐2,3‐dihydroquinazolin‐4(1H)‐one (2 l).
1H NMR (400 MHz, DMSO‐d6, δ, ppm): 5.98 (s, 1H), 6.72
(t, J = 8 Hz, 1H, Ar‐H), 6.82 (d, J = 8 Hz, 1H, Ar‐H), 7.29
(td, J = 6.8, 1.6 Hz, 1H, Ar‐H), 7.38 (brs, 1H, N‐H), 7.65
(dd, J = 8, 1.6 Hz, 1H, Ar‐H), 7.71 (t, J = 8 Hz, 1H, Ar‐
H), 7.97 (d, J = 7.6 Hz, 1H, Ar‐H), 8.23 (dq, J = 8,
1.6 Hz, 1H, Ar‐H), 8.39 (t, J = 2 Hz, 1H, Ar‐H), 8.57 (brs,
1H, N‐H). 13C NMR (DMSO, 100 MHz, δ, ppm): 65.7,
115.1, 115.4, 118, 122.1, 123.8, 127.9, 130.5, 133.8, 134.1,
144.7, 147.8, 148.2, 163.9.
Ethyl‐4‐(4‐methoxyphenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,
6,7,8‐hexahydroquinolin‐3‐carboxylate (4b). 1H NMR
(400 MHz, DMSO‐d6, δ, ppm): 0.87 (s, 3H), 1.02 (s, 3H),
1.15 (t, J = 6.8 Hz, 3H), 1.99 (d, J = 16.4 Hz, 1H), 2.18
(d, J = 16 Hz, 1H), 2.28–2.32 (m, 4H), 2.43 (d,
J = 16.8 Hz, 1H), 3.68 (s, 3H), 3.99 (q, J = 6.8 Hz, 2H),
4.82 (s, 1H), 6.76 (d, J = 8.4 Hz, 2H, Ar‐H), 7.08 (d,
J = 8.8 Hz, 2H, Ar‐H), 9.03 (brs, 1H, N‐H). 13C NMR
(DMSO, 100 MHz, δ, ppm): 14.6, 18.8, 27, 29.6, 32.6,
35.4, 50.8, 55.3, 59.5, 104.4, 110.7, 113.5, 128.9, 140.5,
145.1, 149.7, 157.8, 167.4, 194.7.
Ethyl‐4‐(4‐fluorophenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,
8‐hexahydroquinolin‐3‐carboxylate (4d). 1H NMR (400 MHz,
DMSO‐d6, δ, ppm): 0.85 (s, 3H), 1.02 (s, 3H), 1.13 (t,
J = 7.2 Hz, 3H), 1.99 (d, J = 16 Hz, 1H), 2.18 (d,
J = 16 Hz, 1H), 2.28–2.32 (m, 4H), 2.43 (d, J = 16.8 Hz,
1H), 3.98 (q, J = 7.2 Hz, 2H), 4.87 (s, 1H), 6.99–7.20 (m,
4H, Ar‐H), 9.11 (brs, 1H, N‐H). 13C NMR (DMSO,
100 MHz, δ, ppm): 14.6, 18.8, 26.7, 29.6, 32.6, 35.8, 50.7,
59.5, 103.9, 110.4, 114.7, 129.6, 144.3, 145.7, 149.95,
159.7, 167.2, 194.7.
Ethyl‐4‐(4‐bromophenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,
7,8‐hexahydroquinolin‐3‐carboxylate (4f). 1H NMR
(400 MHz, DMSO‐d6, δ, ppm): 0.85 (s, 3H), 1.02 (s, 3H),
1.13 (t, J = 7.2 Hz, 3H), 1.99 (d, J = 16 Hz, 1H), 2.18 (d,
J = 16 Hz, 1H), 2.27–2.31 (m, 4H), 2.43 (d, J = 17.2 Hz,
1H), 3.98 (q, J = 7.2 Hz, 2H), 4.85 (s, 1H), 7.11–7.14 (m,
2H, Ar‐H), 7.38, 7.41 (m, 2H, Ar‐H), 9.13 (brs, 1H, N‐H).
13C NMR (DMSO, 100 MHz, δ, ppm): 14.6, 18.8, 26.9,
29.6, 32.6, 36.2, 50.6, 59.6, 103.5, 110.1, 119.19, 130.2,
131.1, 145.9, 147.5, 150.1, 167.1, 194.7.
4.8 | General procedure for Br3‐TBA‐Fe3O4‐catalysed
Knoevenagel condensation
A mixture of aldehyde (1 mmol), activated methylene com-
pounds (1.05 mmol) and Br3‐TBA‐Fe3O4 (10 mg) in water
(2 ml) was stirred at 70°C. Reaction progress was monitored
by TLC (acetone–n‐hexane, 3:7). After the time specified in
Tables 6 and 7, the reaction mass was allowed to cool to room
temperature. Ethyl acetate (3 × 5 ml) was added to the reac-
tion mixture and the catalyst was separated using an external
magnet. Ethyl acetate was evaporated under reduced pressure
to afford the crude products. The obtained crude products
were further recrystallized from ethanol to afford the pure
final products (85–98%).
4.9 | Spectroscopic data
All the products reported here are known compounds and the
spectroscopic data matched with literature values. Data for
some of the compounds are given below.
2‐(4‐Chlorophenyl)‐2,3‐dihydroquinazolin‐4(1H)‐one (2a).
1H NMR (400 MHz, DMSO‐d6, δ, ppm): 5.79 (s, 1H), 6.70
(t, J = 7.6 Hz, 1H, Ar‐H), 6.76 (d, J = 8 Hz, 1H, Ar‐H),
7.16 (brs, 1H, N‐H), 7.24–7.29 (td, J = 7.6, 1.6 Hz, 1H,
Ar‐H), 7.46–7.49 (dt, J = 8.8, 2 Hz, 2H, Ar‐H), 7.51–7.53
(dt, J = 8.4, 2 Hz, 2H, Ar‐H), 7.62 (dd, J = 7.6, 1.6 Hz,
1H, Ar‐H), 8.35 (brs, 1H, N‐H). 13C NMR (DMSO,
100 MHz, δ, ppm): 66.3, 114.9, 115.4, 117.8, 127.9, 128.8,
129.2, 133.5, 133.9, 141.1, 148.1, 164.
2‐(4‐Methylphenyl)‐2,3‐dihydroquinazolin‐4(1H)‐one (2c).
1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.31 (s, 3H, CH3),
5.73 (s, 1H), 6.68 (t, J = 7.6 Hz, 1H, Ar‐H), 6.75 (d,
J = 8.4 Hz, 1H, Ar‐H), 7.07 (brs, 1H, N‐H), 7.20–7.27 (m,
3H, Ar‐H), 7.39 (d, J = 8 Hz, 2H, Ar‐H), 7.62 (dd, J = 7.6,
1.2 Hz, 1H, Ar‐H), 8.25 (brs, 1H, N‐H). 13C NMR (DMSO,
100 MHz, δ, ppm): 21.2, 66.9, 114.9, 115.5, 117.5, 127.3,
127.8, 129.3, 133.7, 138.2, 139.1, 148.4, 164.1.
2‐(4‐Nitrophenyl)‐2,3‐dihydroquinazolin‐4(1H)‐one (2e).
1H NMR (400 MHz, DMSO‐d6, δ, ppm): 5.94 (t, J = 2 Hz,
1H, CH), 6.71 (t, J = 7.6 Hz, 1H, Ar‐H), 6.79 (d, J = 7.6 Hz,
1H, Ar‐H), 7.26–7.30 (td, J = 7.6, 1.6 Hz, 1H, Ar‐H), 7.35
(brs, 1H, N‐H), 7.62–7.65 (dd, J = 8, 1.6 Hz, 1H, Ar‐H),
7.75–7.79 (dt, J = 8.8, 2 Hz, 2H, Ar‐H), 8.26–8.30 (dt,
J = 9.2, 2 Hz, 2H, Ar‐H), 8.55 (brs, 1H, N‐H). 13C NMR
(DMSO, 100 MHz, δ, ppm): 66.8, 115, 115.4, 118, 124.1,
127.9, 128.5, 134.1, 147.7, 147.9, 149.8, 163.8.
Ethyl‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquino-
1
lin‐3‐carboxylate (4j). H NMR (400 MHz, DMSO‐d6, δ,
ppm): 0.86 (s, 3H), 1.02 (s, 3H), 1.14 (t, J = 7.2 Hz, 3H),
1.99 (d, J = 16 Hz, 1H), 2.18 (d, J = 16 Hz, 1H),
2.29–2.33 (m, 4H), 2.44 (d, J = 17.2 Hz, 1H), 3.99 (q,
J = 7.2 Hz, 2H), 4.88 (s, 1H), 7.06–7.21 (m, 5H, Ar‐H),
9.07 (brs, 1H, N‐H). 13C NMR (DMSO, 100 MHz, δ,
ppm): 14.6, 18.8, 26.9, 29.6, 32.6, 36.4, 50.7, 59.5, 104.1,
110.5, 126.1, 127.9, 128.145.5, 148.1, 150, 167.3, 194.7.
Ethyl‐4‐(3‐bromophenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,
8‐hexahydroquinolin‐3‐carboxylate (4 l). 1H NMR (400 MHz,
2‐Phenyl‐2,3‐dihydroquinazolin‐4(1H)‐one (2j). 1H
NMR (400 MHz, DMSO‐d6, δ, ppm): 5.77 (s, 1H), 6.69 (t,
J = 8 Hz, 1H, Ar‐H), 6.77 (d, J = 7.6 Hz, 1H, Ar‐H), 7.13
(brs, 1H, N‐H), 7.26 (td, J = 8, 1.6 Hz, 1H, Ar‐H),
7.34–7.43 (m, 3H, Ar‐H), 7.51 (dd, J = 6.8, 1.2 Hz, 2H,
Ar‐H), 7.63 (dd, J = 7.6, 1.2 Hz, 1H, Ar‐H), 8.31 (brs, 1H,

SHIRI ET AL.
11
[11] A. Shaabani, A. Maleki, H. Mofakham, Synth. Commun. 2008, 38, 3751.
[12] L.‐Y. Zeng, C. J. Cai, Heterocycl. Chem. 2010, 47, 1035.
DMSO‐d6, δ, ppm): 0.87 (s, 3H), 1.03 (s, 3H), 1.14 (t,
J = 7.2 Hz, 3H), 2.01 (d, J = 16 Hz, 1H), 2.19 (d,
J = 16 Hz, 1H), 2.31–2.34 (m, 4H), 2.45 (d, J = 17.2 Hz,
1H), 4.0 (q, J = 7.2 Hz, 2H), 4.85 (s, 1H), 7.15–7.31 (m,
4H, Ar‐H), 9.16 (brs, 1H, N‐H). 13C NMR (DMSO,
100 MHz, δ, ppm): 14.6, 18.8, 26.8, 29.6, 32.6, 36.6, 50.6,
59.6, 103.5, 109.9, 121.5, 127, 129, 130.6, 130.9, 146.1,
150.3, 150.7, 167, 194.8.
[13] J. X. Chen, W. K. Su, H. Y. Wu, M. C. Liu, C. Jin, Green Chem. 2007, 9,
972.
[14] S. J. Ji, Z. Q. Jiang, J. Lu, T. P. Loh, Synlett 2004, 831.
[15] M. Rueping, A. P. Antonchick, E. Sugiono, K. Grenader, Angew. Chem. Int.
Ed. 2009, 48, 908.
[16] X. Cheng, S. K. Vellalath, R. Goddard, J. Am. Chem. Soc. 2008, 130, 15786.
[17] R. J. Abdel‐Jalil, W. Voelter, M. Saeed, Tetrahedron Lett. 2004, 45, 3475.
2‐(4‐Chlorobenzylidene)malononitrile (6a). 1H NMR
(400 MHz, DMSO‐d6, δ, ppm): 7.74 (d, J = 8.8 Hz, 2H),
7.97 (d, J = 8.8 Hz, 2H), 8.73 (s, 1H). 13C NMR
(100 MHz, DMSO, δ, ppm): 82.7, 113.5 (CN), 114.5 (CN),
115.7 (2C), 130.5, 132.6 (2C), 139.5, 160.6.
[18] A. Davoodnia, S. Allameh, A. R. Fakhari, N. Tavakoli‐Hoseini, Chin. Chem.
Lett. 2010, 21, 550.
[19] G. Sabitha, G. S. K. K. Reddy, C. S. Reddy, J. S. Yadav, Tetrahedron Lett.
2003, 44, 4129.
[20] M. M. Heravi, K. Bakhtiari, V. Zadsirjan, M. Saeedi, F. F. Bamoharram,
1
Iran. J. Org. Chem. 2010, 2, 298.
2‐(4‐Methoxybenzylidene)malononitrile (6b). H NMR
[21] S. B. Sapkal, K. F. Shelke, B. B. Shingate, M. S. Shingare, Tetrahedron Lett.
2009, 50, 1754.
(400 MHz, DMSO‐d6, δ, ppm): 7.21 (d, J = 7.2 Hz, 2H),
7.99 (d, J = 7.2 Hz, 2H), 8.41 (s, 1H). 13C NMR
(100 MHz, DMSO, δ, ppm): 56.4, 114.4 (CN), 115.3 (CN),
115.7 (2C), 124.6, 133.8 (2C), 160.9, 164.8.
[22] L. Nagarapu, M. D. Kumari, N. V. Kumari, S. Kantaveri, Catal. Commun.
2007, 8, 1871.
[23] C. S. Reddy, M. Raghu, Indian J. Chem. 2008, 47, 1578.
[24] A. Kumar, R. A. Maurya, Synlett 2008, 883.
2‐(4‐Nitrobenzylidene)malononitrile (6e). 1H NMR
(400 MHz, DMSO‐d6, δ, ppm): 8.15 (d, J = 8.8 Hz, 2H),
8.44 (d, J = 8.8 Hz, 2H), 8.57 (s, 1H). 13C NMR
(100 MHz, DMSO, δ, ppm): 86.3, 112.9 (CN), 114.1 (CN),
124.8 (2C), 131.9 (2C), 137.1, 150.1, 159.7.
[25] L. Shiri, A. Ghorbani‐Choghamarani, M. Kazemi, Aust. J. Chem. 2016,
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335, 253.
2‐(4‐Ethoxybenzylidene)malononitrile (6 g). 1H NMR
(400 MHz, DMSO‐d6, δ, ppm): 1.37 (t, J = 7.2 Hz, 3H),
4.19 (q, J = 7.2 Hz, 2H), 7.19 (d, J = 9.2 Hz, 2H), 7.98 (d,
J = 9.2 Hz, 2H), 8.41 (s, 1H). 13C NMR (100 MHz, DMSO,
δ, ppm): 14.8, 64.5, 77.1, 114.4 (CN), 115.3 (CN), 116 (2C),
124.5, 133.9 (2C), 160.9, 164.2.
Ethyl (E)‐2‐cyano‐3‐(4‐methylphenyl)‐2‐propenoate (8c).
1H NMR (400 MHz, DMSO‐d6, δ, ppm): 1.26 (t, J = 7.2 Hz,
3H), 2.4 (S, 3H), 3.54 (q, J = 7.2 Hz, 2H) 7.1 (d, J = 8 Hz,
2H), 7.45–7.47 (d, J = 8 Hz, 2H), 8.03 (s, 1H). 13C NMR
(100 MHz, DMSO, δ, ppm): 15.24 (CH3), 55.31 (CH3O),
65.39 (O─CH2), 102.33 (C─CN), 113.77 (CN), 121.36,
126.51, 132.22, 139.33, 152.57, 162.26 (C═O).
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