Cu(II) immobilized on Fe3O4–diethylenetriamine: A new magnetically recoverable catalyst for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones and oxidative coupling of thiols

Article abstract of DOI:10.1002/aoc.3596

Cu(II) immobilized on Fe₃O₄–diethylenetriamine was designed as a new, inexpensive and efficient heterogeneous catalyst for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones and the oxidative coupling of thiols. The structure of the nanomagnetic catalyst was comprehensively characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, vibrating sample magnetometry, thermogravimetric analysis, X-ray diffraction and atomic absorption spectroscopy. Simple preparation of the catalyst from commercially available materials, high catalytic activity, simple operation, high yields, use of green solvents, easy magnetic separation and reusability of the catalyst with unaltered activity make our protocol a green and feasible synthetic strategy.

Full text of DOI:10.1002/aoc.3596

Received: 25 July 2016
DOI 10.1002/aoc.3596
Revised: 29 July 2016
Accepted: 2 August 2016
F U L L PA P E R
Cu(II) immobilized on Fe3O4–diethylenetriamine: A new
magnetically recoverable catalyst for the synthesis of 2,3‐
dihydroquinazolin‐4(1H)‐ones and oxidative coupling of thiols
*
Lotfi Shiri | Arash Ghorbani‐Choghamarani | Mosstafa Kazemi
Department of Chemistry, Faculty of Basic
Cu(II) immobilized on Fe3O4–diethylenetriamine was designed as a new,
inexpensive and efficient heterogeneous catalyst for the synthesis of
Sciences, Ilam University, PO Box 69315‐516,
Ilam, Iran
Correspondence
Lotfi Shiri, Department of Chemistry, Faculty of
2,3‐dihydroquinazolin‐4(1H)‐ones and the oxidative coupling of thiols. The
structure of the nanomagnetic catalyst was comprehensively characterized using
Fourier transform infrared spectroscopy, scanning electron microscopy,
Basic Sciences, Ilam University, PO Box 69315‐
516, Ilam, Iran.
Email: lshiri47@gmail.com
energy‐dispersive X‐ray spectroscopy, vibrating sample magnetometry,
thermogravimetric analysis, X‐ray diffraction and atomic absorption spectroscopy.
Simple preparation of the catalyst from commercially available materials, high
catalytic activity, simple operation, high yields, use of green solvents, easy magnetic
separation and reusability of the catalyst with unaltered activity make our protocol a
green and feasible synthetic strategy.
KEYWORDS
2,3‐dihydroquinazolin‐4(1H)‐ones, Cu(II) immobilized on Fe3O4–DETA, magnetic
separation, oxidative coupling
1
|
INTRODUCTION
Compared with heterogeneous catalysts, homogeneous
catalysts exhibit high catalytic activities in chemical
processes due to their solubility in reaction media, which
increases catalytic site accessibility for the substrate.[13]
However, separating them from the reaction mixture to avoid
contamination of the product requires expensive and tedious
purification steps.[14] Immobilization of homogeneous
catalysts on heterogeneous supports is in fact a nice response
to this problem, because this catalytic strategy provides
several notable advantages such as simple catalyst separation,
long catalytic life, high reusability and thermal stability.[15]
From an economic point of view, the designing and devel-
oping of copper‐catalysed strategies for organic reactions is a
hot research topic in modern catalysis research, because, com-
pared to other transition metals, copper is less toxic, readily
available and inexpensive.[16] Over the last decade, the
catalytic activity of copper complexes heterogenized on solid
supports such as silica, alumina, zeolites and mesoporous
materials in various chemical reactions were extensively
studied by organic chemists.[17] Although these procedures
are valuable, but most of them suffer a series of substantial
2,3‐Dihydroquinazolin‐4(1H)‐ones have been recognized as a
key and supplementary blocks in agro‐chemistry, medicinal
chemistry
and
organic
chemistry.[1]
Also,
2,3‐dihydroquinazolin‐4(1H)‐ones and their analogous are
found widely in nature, especially in biologically and pharma-
ceutically active molecules, and can act as key structural
motifs for the design of new category of highly valuable syn-
thetic drug candidates owing to their important pharmacolog-
ical properties.[2–4] Recent literature studies clearly show that
a variety of molecules containing 2,3‐dihydroquinazolin‐4
(1H)‐one structural units exhibit a series of significant biolog-
ical activities such as antitumor, anticancer, antibiotic,
antibacterial, antidefibrillatory, antipyretic and anticonvulsant
properties.[5,6] The condensation of aryl, alkyl and hetroaryl
aldehydes or ketones with anthranil amide in the presence of
acidic catalysts is the most well‐known approach for the syn-
thesis of 2,3‐dihydroquinazolin‐4(1H)‐ones.[7] In recent
times, a variety of catalysts and reagents for the synthesis of
these compounds have been reported in the literature.[8–12]
Appl. Organometal. Chem. 2016; 1–9
wileyonlinelibrary.com/journal/aoc
Copyright © 2016 John Wiley & Sons, Ltd.
1

2
SHIRI ET AL.
drawbacks such as high reaction temperature, low reaction
rate, tedious work‐up procedures, low yields and the usual
requirement of stoichiometric copper salts. Furthermore, in
these catalytic strategies, fewer sites on the surface are
accessible for catalysis; the catalytic system is less reactive
and selective, and sometimes the support itself can act as a
catalyst for side reactions. Therefore, the development of
new support materials and heterogenization strategies for
organic synthesis has recently become a major area of
research in modern catalysis science.
In this respect, as an important class of separable
materials, magnetic nanoparticles (MNPs), especially Fe3O4
nanoparticles, have received special attention in modern
catalysis research because of their advantages such as simple
preparation and functionalization, large surface area ratio,
low toxicity and cost, high dispersion and reactivity as well
as high chemical stability.[18–20] Despite those important
advantages, the most valuable advantage of MNPs is their
simple separation from a reaction mixture using an external
magnet, without the need for filtration, centrifugation or other
tedious work‐up processes.[21,22] Also, most MNP‐supported
catalysts can be reused many times while keeping their initial
activity. In recent times, catalysis processes using
eco‐friendly solvents have received considerable attention in
green organic synthesis.[23] More recently, copper complexes
supported on Fe3O4 nanoparticles have emerged as efficient
catalysts for a range of organic transformations such as
oxidation, C─C coupling and condensation reactions.[24]
Inspired by this catalytic strategy, in this paper, we report a
simple and efficient synthesis of a catalyst, namely Cu(II)
immobilized on Fe3O4–diethylenetriamine (DETA), and its
application in the one‐pot cyclocondensation of
anthranilamide with aldehydes or ketones for the synthesis
of 2,3‐dihydroquinazolin‐4(1H)‐ones.
of the catalyst were measured using vibrating sample
magnetometry (VSM; MDKFD).
2.2 | 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 mechanical
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.
2.3 | Preparation of Fe3O4–3‐
chloropropyltrimethoxysilane (CPTMS)
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 CPTMS (2.5 ml) was added to the mixture. The
reaction mixture was stirred using mechanical stirring under
nitrogen atmosphere at 40°C for 8 h. Then, the nanoparticles
were re‐dispersed in ethanol by sonication five times and
separated through magnetic decantation. The nanoparticle
product (Fe3O4–CPTMS) was dried at room temperature.
2.4 | Preparation of Fe3O4–DETA
Fe3O4–CPTMS (1.5 g) was dispersed in toluene (50 ml) in an
ultrasonic bath for 10 min. DETA (2 ml) was added and
stirred at 100°C for 30 h under nitrogen atmosphere. Then,
the prepared functionalized MNPs were separated by
magnetic decantation and washed three times with ethanol
to remove the unattached substrates. The resulting product
was dried at room temperature.
2
| EXPERIMENTAL
2.1 | Materials
2.5 | Preparation of Cu(II) immobilized on Fe3O4–
DETA
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
powder X‐ray diffraction (XRD) with a Holland Philips
X'pert X‐ray diffractometer (Co Kα radiation,
λ = 0.154056 nm), at a scanning speed of 2° min−1 from
10° to 100°. The particle size and morphology were
investigated using scanning electron microscopy (SEM)
with a JEOL JEM‐2010 instrument at an accelerating
voltage of 200 kV. Fourier transform infrared (FT‐IR)
spectra of samples were recorded in KBr discs using a
Nicolet Impact 410 spectrometer. Thermogravimetric
analysis (TGA) curves were recorded using a PL‐STA
1500 device (Thermal Sciences). Supermagnetic properties
In the last step, Cu(NO3)2⋅3H2O (0.25 g) was added to
Fe3O4–DETA (0.5 g) in absolute ethanol (30 ml) and the
resultant mixture was refluxed for 24 h. Finally, the
synthesized nanosolid (Cu(II) immobilized on Fe3O4–DETA)
was separated by magnetic decantation. The nanomagnetic
catalyst was washed several times with absolute ethanol,
and dried under vacuum at room temperature (Scheme 1).
2.6 | General procedure for synthesis of 2,3‐
dihydroquinazolin‐4(1H)‐ones
A mixture of anthranilamide (1.05 mmol, 142 mg), aldehyde
or ketone (1 mmol) and Cu(NO3)2/Fe3O4–DETA (10 mg) in
water (2 ml) was stirred at reflux temperature. Reaction

SHIRI ET AL.
3
2.8.2
(3c)
| 2‐(4‐Methylphenyl)‐2,3‐dihydroquinazolin‐4(1H)‐one
1H NMR (400 MHz, DMSO‐d6, δH, 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, δC, 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.
SCHEME 1 General route for the synthesis of Cu(II) immobilized on
Fe3O4–DETA (Cu(NO3)2/Fe3O4–DETA)
2.8.3
(3e)
| 2‐(4‐Nitrophenyl)‐2,3‐dihydroquinazolin‐4(1H)‐one
1H NMR (400 MHz, DMSO‐d6, δH, 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, δC, ppm): 66.8, 115, 115.4, 118, 124.1,
127.9, 128.5, 134.1, 147.7, 147.9, 149.8, 163.8.
progress was monitored by TLC (acetone–n‐hexane, 2:8).
After the required time, the 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 get the
pure 2,3‐dihydroquinazolin‐4(1H)‐ones in 83–98% yields.
2.8.4
| 2‐Phenyl‐2,3‐dihydroquinazolin‐4(1H)‐one (3i)
1H NMR (400 MHz, DMSO‐d6, δH, 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, N‐H). 13C
NMR (DMSO, 100 MHz, δC, ppm): 67.1, 114.9, 115.4,
117.6, 127.4, 127.9, 128.8, 129, 133.8, 142.1, 148.4, 164.1.
2.7 | General procedure for oxidative coupling of thiols
to disulfides
A mixture of thiol (1 mmol), hydrogen peroxide (0.5 ml) and
Cu(NO3)2/Fe3O4–DETA (10 mg) in ethanol (2 ml) was
stirred at ambient temperature. Reaction progress was moni-
tored by TLC (acetone–n‐hexane, 2:8). After completion of
the reaction, the catalyst was separated using an external
magnet and washed with ethyl acetate. The product was then
extracted with ethyl acetate (4 × 5 ml). The organic layer was
dried over anhydrous Na2SO4 (1.5 g). Finally, the organic
solvents were evaporated, and the corresponding disulfides
were obtained in high to excellent yields (89–98%).
2.8.5
(3 k)
| 2‐(3‐Nitrophenyl)‐2,3‐dihydroquinazolin‐4(1H)‐one
1H NMR (400 MHz, DMSO‐d6, δH, 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, δC, 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.
2.8 | Spectroscopic data
All the products reported here are known compounds and the
spectroscopic data were matched with literature values. Data
for the some of the compounds are given below.
2.8.1
(3a)
| 2‐(4‐Chlorophenyl)‐2,3‐dihydroquinazolin‐4(1H)‐one
2.8.6
| 1,2‐Bis(4‐fluorophenyl)disulfane (5 g)
1H NMR (400 MHz, CDCl3, δH, ppm): 7.47 (d, J = 8.8 Hz,
4H), 7.56 (t, J = 8.8 Hz, 4H). 13C NMR (100 MHz, CDCl3,
δC, ppm): 119.46, 129.48, 132.27, 145.32.
1H NMR (400 MHz, DMSO‐d6, δH, 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,
δC, ppm): 66.3, 114.9, 115.4, 117.8, 127.9, 128.8, 129.2,
133.5, 133.9, 141.1, 148.1, 164.
2.8.7
| 1,2‐Dibenzyldisulfane (5 k)
1H NMR (400 MHz, CDCl3, δH, ppm): 3.75 (s, 4H),
7.03–7.15 (m, 10H). 13C NMR (100 MHz, CDCl3, δC,
ppm): 43.35, 128.34, 128.51, 129.13, 137.49.

4
SHIRI ET AL.
3
|
RESULTS AND DISCUSSION
the Cu(NO3)2/Fe3O4–DETA catalyst shows two characteristic
peaks at 1621 and 3432 cm−1, which correspond to N─H
stretching and bending modes, respectively. Therefore, it
can be concluded that the Cu(II) complex was immobilized
successfully on the surface of Fe3O4–DETA nanoparticles.
The morphology and size of the catalyst were studied
using SEM (Figure 2). From the SEM images, it can be seen
that the catalyst is made up uniformly and the average size of
Cu(NO3)2/Fe3O4–DETA is about 18 nm.
The magnetic property of the nanomagnetic catalyst was
investigated using VSM at ambient temperature. Figure 3
exhibits the magnetization curves of Fe3O4 MNPs and Cu
(NO3)2/Fe3O4–DETA. It can be seen that the saturation
magnetization decreases from 55.1 emu g−1 for the Fe3O4
MNPs to 38.25 emu g−1 for the catalyst. As a result of this
analysis, the superparamagnetic properties of the prepared
Cu(NO3)2/Fe3O4–DETA are attractive for its application.
TGA was used to determine the percentage of functional
groups chemisorbed onto the surface of MNPs. Figure 4
shows the TGA curves for bare Fe3O4 MNPs, Fe3O4–DETA
and Cu(NO3)2/Fe3O4–DETA. The TGA curves of all samples
show a small amount of weight loss below 200°C, due to
3.1 | Preparation and characterization of Cu(NO3)2/
Fe3O4–DETA
Cu(NO3)2/Fe3O4–DETA was successfully synthesized using
a surface modification strategy as depicted in Scheme 1.
Fe3O4 MNPs were prepared by a chemical co‐precipitation
method[24] and coated with CPTMS via covalent bonds.[25]
The reaction of the supported CPTMS with DETA in toluene
under reflux conditions for 42 h produced DETA‐functional-
ized Fe3O4 nanoparticles (Fe3O4–DETA). Finally, Fe3O4–
DETA was treated with Cu(NO3)2⋅3H2O in ethanol at reflux
temperature for 24 h to provide Cu(II) immobilized on
Fe3O4–DETA.
The prepared magnetic nanocatalyst was comprehen-
sively characterized using FT‐IR, TGA, XRD, SEM, atomic
absorption spectroscopy (AAS) and VSM techniques.
The FT‐IR spectra of Fe3O4 MNPs, Fe3O4–CPTMS,
Fe3O4–DETA and Cu(NO3)2/Fe3O4–DETA are displayed in
Figure 1. The FT‐IR spectrum of the Fe3O4 MNPs exhibits
a characteristic peak at 579 cm−1, which is attributed to the
Fe─O stretching vibration. Also the broad band at around
3400 cm−1 is attributed to bound water O─H stretching
vibration. CPTMS anchored on Fe3O4 MNPs is confirmed
by a characteristic peak at 996 cm−1, which is attributed to
Fe─O─Si stretching vibration. In the spectrum of Fe3O4–
DETA, three obvious peaks at 1040, 1119 and 1203 cm−1
are characteristic of C─N bonds. The FT‐IR spectrum of
desorption of physically adsorbed solvents and surface
[6]
hydroxyl groups.
Organic groups have been reported to
desorb at temperatures above 260°C. The organic groups on
Fe3O4–DETA are found to have a mass percentage loss of
about 9%, while the Cu(NO3)2/Fe3O4–DETA catalyst shows
a greater mass loss, about 32%. As a result of this analysis,
it can be concluded that the good grafting of Cu(II) complex
on Fe3O4–DETA is verified.
XRD is an effective technique for investigating the
reorganization 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 using XRD. The XRD pattern of Cu
(NO3)2/Fe3O4–DETA is displayed in Figure 5. Several char-
acteristic peaks at 2θ = 35.2°, 41.3°, 50.5°, 63.3°, 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 data reported in the literature).[24]
The AAS data for the catalyst show that the amount of
copper loaded on the surface of Fe3O4 MNPs is about
0.15 mmol g−1
.
3.2 | Catalytic study
After successful characterization of the prepared
nanocatalyst, the catalytic activity of Cu(NO3)2/Fe3O4–
DETA was studied in the one‐pot cyclocondensation of
anthranilamide with various aldehydes or ketones. At first,
the
cyclocondensation
of
anthranilamide
with
4‐chlorobenzaldehyde was chosen as a model reaction and
the effect of various parameters such as solvent type, temper-
ature and catalyst amount on this reaction was studied. To
FIGURE 1 Ft‐IR spectra of (a) Fe3O4 MNPs, (b) Fe3O4–CPTMS, (c)
Fe3O4–DETA and (d) Cu(NO3)2/Fe3O4–DETA

SHIRI ET AL.
5
FIGURE 2 Sem images of Cu(NO3)2/Fe3O4–DETA
FIGURE 5 Xrd pattern of Cu(NO3)2/Fe3O4–DETA
temperature (Table 1, entries 1–6). As evident from
Table 1, the best results (with respect to yield and reaction
time) are obtained when the reaction is performed in water
at reflux temperature. Next, the effect of catalyst amount on
the model reaction in water at reflux temperature was studied
and it is found that the catalyst amount plays a key role in
product yield and conversion time. When the amount of
nanocatalyst is increased from 3 to 10 mg (Table 1, entries 7
and 8) a significant improvement is observed in both reaction
time and product yield. On the other hand, higher amounts of
catalyst do not improve the yield or reaction time (Table 1,
entry 9). In order to elucidate the role of the catalyst, the pro-
cess was conducted in the absence of the catalyst, and only a
trace amount of the product is observed on the TLC plate after
180 min (Table 1, entry 10). Therefore, 10 mg of the catalyst
is considered as the ideal amount (Table 1, entry 8). Finally,
the effect of temperature was studied by performing the model
reaction at 90 and 80°C in water in the presence of 10 mg of
the catalyst (Table1, entries 11 and 12). When the reaction
temperature decreases from reflux to 80°C, product yields
decrease from 98 to 90% and reaction times increase from
30 to 55 min. Accordingly, after a comprehensive screening
of the process parameters, the highest yield and shortest
FIGURE 3 Magnetization curves for Fe3O4 MNPs (blue curve) and Cu
(NO3)2/Fe3O4–DETA (green curve) at room temperature
FIGURE 4 Tga curves of Fe3O4 MNPs (black curve), Fe3O4–DETA
(green curve) and Cu(NO3)2/Fe3O4–DETA (red curve)
check the effect of solvent on the reaction time and product
yield, the model reaction was carried out with 5 mg of the
Cu(NO3)2/Fe3O4–DETA catalyst in common organic
solvents such as toluene, EtOH, CH3CN, water, tetrahydrofu-
ran (THF) and dimethylformamide (DMF) at reflux

6
SHIRI ET AL.
TABLE 1 Optimization of reaction conditionsa
reaction time for product 3a occur in the presence of 10 mg of
the Cu(NO3)2/Fe3O4–DETA catalyst in water at reflux tem-
perature (Table 1, entry 8).
Next, to check the efficiency of the catalytic system, the
cyclocondensation of anthranilamide with aromatic alde-
hydes and ketones was studied under the optimized condi-
tions (Scheme 2). The results are summarized in Table 2.
All aromatic aldehydes are successfully converted to the
desired products in high to excellent yields. Substrates with
either electron‐withdrawing or electron‐donating groups also
react smoothly to afford the corresponding products in
satisfactory yields. It is noteworthy that when ketones are
used as substrates, products 3q and 3r are afforded in
satisfactory yields and with longer reaction times because
of the steric effect (Table 2, entries 17 and 18). Therefore,
the results demonstrate well that the catalytic system is very
efficient for the cyclocondensation of anthranilamide with
aromatic aldehydes and ketones.
Oxidative coupling of thiols is a key and valuable
transformation in organic synthesis, because their products,
namely disulfides, are prevalent in nature and present in the
structural backbones of a broad spectrum of biologically
and pharmaceutically active molecules.[19,28,29] Owing to
the significance of disulfides from the biological and
medicinal points of view, we decided to study the catalytic
activity of Cu(NO3)2/Fe3O4–DETA in the oxidative
coupling of thiols to disulfides. To determine the optimum
reaction conditions, the effect of various parameters (such
as solvent type and amounts of catalyst and hydrogen
peroxide) on the room temperature oxidative coupling of
benzo[d]thiazole‐2‐thiol (as a model substrate) was studied.
The results are summarized in Table 3. The highest yield
The amount of
catalyst (mg)
Entry
Solvent (Temp.°C)
Time/min
Yieldb%
1
5
5
toluene (reflux)
EtOH (reflux)
CH3CN (reflux)
H2O (reflux)
THF (reflux)
DMF (reflux)
H2O (reflux)
H2O (reflux)
H2O (reflux)
H2O (reflux)
H2O (90°C)
120
75
75
92
2
3
5
105
45
90
4
5
95
5
5
120
100
65
70
6
5
86
7
3
91
8
10
15
—
10
10
30
98*
98
9
30
10
11
12
180
40
trace
95
H2O (80°C)
55
90
aReaction conditions: 1.05 mmol of 1 and 1 mmol of 2a in the presence of catalyst
and solvent (2 ml).
bIsolated yield.
SCHEME
2
Cu(NO3)2/Fe3O4–DETA‐catalysed cyclocondensation of
anthranilamide (1) with aldehydes/ketones (2)
TABLE 2 Cu(NO3)2/Fe3O4–DETA‐catalysed one‐pot synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones in H2O at reflux temperature
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
—
Me
3a
3b
3c
30
25
50
20
65
35
30
25
50
45
80
45
85
45
30
25
155
180
98
93
94
96
93
98
94
95
97
92
90
93
85
88
91
95
84
83
199–201[2]
185–187[6]
220–222[6]
197–199[6]
200–201[26]
201–202[6]
171–173[2]
209–211[26]
218–220[6]
192–193[27]
190–191[27]
184–186[27]
189–190[6]
174–176[27]
174–175[27]
210–212[6]
220–221[6]
219–221[27]
2
3
4
3d
3e
5
4‐NO2C6H5CHO
4‐BrC6H5CHO
4‐EtOC6H5CHO
4‐(Me2)NC6H5CHO
C6H5CHO
6
3f
7
3 g
3 h
3i
8
9
10
11
12
13
14
15
16
17
18
3‐ClC6H5CHO
3‐NO2C6H5CHO
3‐BrC6H5CHO
2‐NO2C6H5CHO
2‐BrC6H5CHO
2‐OMe C6H5CHO
3,4‐(OMe)2C6H5CHO
Cyclohexanone
Ph
3j
3 k
3 l
3 m
3n
3o
3p
3q
3r
aIsolated yield.

SHIRI ET AL.
7
TABLE 3 Optimization of reaction conditionsa
After optimization of the reaction parameters, to gener-
alize the catalytic efficiency of Cu(NO3)2/Fe3O4–DETA,
various thiols were subjected to oxidation to the corre-
sponding disulfides (Scheme 3). The results of this study
are summarized in Table 4. A variety of aliphatic, aromatic
and heteroaromatic thiols are successfully converted to the
corresponding disulfides in short to suitable reactions times
and excellent yields. Aromatic and hetroaromatic thiols
with electron‐donating as well as electron‐withdrawing
substituents at ortho and para positions are well tolerated
and do not exert any tangible effect on the yield of
reactions.
In order to investigate the efficiency of the present
synthetic methodology, the collected results for the synthesis
of products 3a and 5f (as typical examples) were compared
with protocols previously reported in the literature (Table 5).
It is obvious that the catalytic system in the present research
demonstrates suitable reaction time and higher yields than
other catalytic systems. Also, this new nanomagnetic catalyst
is comparable in terms of price, non‐toxicity, stability and
ease of separation.
Catalyst
(mg)
H2O2
(ml)
Time
(min)
Yield
(%)b
Entry
Solvent
1
5
5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.3
0.4
0.6
CH3CN
Acetone
H2O
45
40
90
91
2
3
5
100
70
30
4
5
CH2Cl2
n‐Hexane
EtOH
88
5
5
85
75
6
5
25
94
7
3
EtOH
40
91
8
10
15
—
10
10
10
EtOH
10
98
9
EtOH
10
98
10
11
12
13
EtOH
120
45
Trace
90
EtOH
EtOH
25
94
EtOH
10
97
aReaction conditions: oxidative coupling of benzo[d]thiazole‐2‐thiol (1 mmol)
using H2O2 in the presence of catalyst and solvent (2 ml).
bIsolated yield.
3.3 | Reusability of Cu(NO3)2/Fe3O4–DETA catalyst
and shortest reaction time for product 5d is obtained in the
presence of 10 mg of Cu(NO3)2/Fe3O4–DETA and 0.5 ml
of hydrogen peroxide in EtOH (2 ml) at ambient tempera-
ture (Table 3, entry 8).
The recovery and reusability of a catalyst are important
aspects in catalytic processes. To address this issue, after
the successful utilization of Cu(NO3)2/Fe3O4–DETA as
catalyst for the synthesis of 2,3‐dihydroquinazolin‐4(1H)‐
ones and oxidative coupling of thiols, we decided to check
the recyclability of the nanomagnetic catalyst in the
synthesis of products 3a and 5d. After completion of the
reaction, the catalyst was separated easily and rapidly from
the product using an external magnet, and the reaction
solution was decanted, magnetically. The remaining
nanomagnetic catalyst was washed several times with ethyl
acetate and dried to remove residual product, and subjected
SCHEME 3 Cu(NO3)2/Fe3O4–DETA‐catalysed oxidative coupling of
thiols to disulfides
TABLE 4 Cu(NO3)2/Fe3O4–DETA‐catalysed oxidative coupling of thiols into disulfides in ethanol at room temperature
Entry
R
Product
Time (min)
Yield (%)a
M.p. (°C)
1
Benzenethiol
5a
5b
5c
45
20
40
10
50
15
20
30
25
45
60
40
30
92
94
93
98
89
98
93
96
94
90
95
92
93
60–61[30]
133–134[31]
58–59[32]
171–173[31]
93–94[31]
40–41[31]
Oil[33]
90–91[32]
283–286[33]
161–163[34]
70–71[33]
Oil[33]
2
Naphthalene‐2‐thiol
3
Pyridine‐2‐thiol
4
Benzo[d]thiazole‐2‐thiol
Benzo[d]oxazole‐2‐thiol
4‐Methylbenzenethiol
4‐Fluorobenzenethiol
4‐Bromobenzenethiol
2‐Mercaptobenzoic acid
4,6‐Dimethylpyrimidine‐2‐thiol
Phenylmethanethiol
5d
5e
5
6
5f
7
5 g
5 h
5j
8
9
10
11
12
13
2i
5 k
5 l
5 m
2‐Mercaptoethanol
2‐Mercaptoacetic acid
Oil[33]
aIsolated yield.

8
SHIRI ET AL.
TABLE 5 Comparison of activity of various catalysts in the synthesis of products 3a (entries 1–6) and 5f (entries 7–12)
Entry
Catalyst
Conditions
Time (min)
Yield (%)
Ref.
[35]
[36]
[37]
[7]
1
KAl(SO4)2.E12H2O
Glycerosulfonic acid
Silica sulfuric acid
EtOH, reflux
Glycerol, 80°C
H2O,80°C
300
360
180
150
120
30
80
97
81
87
85
98
95
94
98
94
97
98
2
3
4
SBNPSA
EtOH, reflux
[8]
5
Dodecylbenzenesulfonic acid
Cu(NO3)2/Fe3O4–DETA
Ni‐salen‐MCM‐41
EtOH, US, 40°C
EtOH, reflux
6
This work
[38]
7
UHP/EtOH, r.t.
H2O2/CH3CN, r.t.
H2O2/solvent‐free, r.t.
UHP/EtOH, r.t.
H2O2/EtOH, r.t.
H2O2/EtOH, r.t.
25
[39]
[33]
[32]
[40]
8
Fe NPs@SBA‐15
45
9
Zr‐oxide@MCM‐41
Cu(II) Schiff base MCM‐41
DSA@MNPs
30
10
11
12
50
15
Cu(NO3)2/Fe3O4–DETA
15
This work
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ACKNOWLEDGMENTS
This work was supported by the research facilities of Ilam
University, Ilam, Iran.

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