2-Arylation/alkylation of benzothiazoles using superparamagneticgraphene oxide-Fe3O4 hybrid material as a heterogeneous catalystwith diisopropyl azodicarboxylate (DIAD) as an oxidant

Article abstract of DOI:10.1002/aoc.3971

In this report, we introduced Graphene oxide-iron oxide (GO-Fe₃O₄) nanocomposites as a heterogeneous catalyst for arylation/alkylation of benzothiazoles with aldehydes and benzylic alcohols in the presence of diisopropyl azodicarboxylate (DIAD) as an oxidant which exclusively produced 2-aryl (alkyl)-1H–benzothizoles in moderate to excellent yields. The absence of precious metals and toxic solvent, easy product isolation, and recyclability of the GO-Fe₃O₄ with no loss of activity are notable advantages of this method.

Full text of DOI:10.1002/aoc.3971

Received: 18 April 2017
DOI: 10.1002/aoc.3971
Revised: 1 June 2017
Accepted: 20 June 2017
F U L L P A P E R
2‐Arylation/alkylation of benzothiazoles using
superparamagneticgraphene oxide‐Fe3O4 hybrid material as
a heterogeneous catalystwith diisopropyl azodicarboxylate
(DIAD) as an oxidant
Dariush Khalili1
| Elham Etemadi‐Davan1 | Ali Reza Banazadeh2
1 Department of Chemistry, College of
Sciences, Shiraz University, Shiraz 71454,
Iran
2 Department of Chemistry and
Biochemistry, Texas Tech. University,
Lubbock, Texas, 79409, USA
In this report, we introduced Graphene oxide‐iron oxide (GO‐Fe3O4) nanocom-
posites as a heterogeneous catalyst for arylation/alkylation of benzothiazoles
with aldehydes and benzylic alcohols in the presence of diisopropyl
azodicarboxylate (DIAD) as an oxidant which exclusively produced 2‐aryl
(alkyl)‐1H–benzothizoles in moderate to excellent yields. The absence of pre-
cious metals and toxic solvent, easy product isolation, and recyclability of the
GO‐Fe3O4 with no loss of activity are notable advantages of this method.
Correspondence
Dariush Khalili, Department of Chemistry,
College of Sciences, Shiraz University,
Shiraz 71454, Iran.
KEYWORDS
Email: khalili@shirazu.ac.ir
Benzothiazoles, DIAD, heterogeneous, hybrid material, magnetic graphene oxide
Funding information
Shiraz University, Grant/Award Number:
95GRD1M235307
1 | INTRODUCTION
developed.[21–24] Although these problems still represent
a real challenge, exploration of clean and effective routes
Benzothiazoles are heterocyclic compounds which can be
found in numerous pharmaceuticals and natural prod-
ucts.[1–3] Owing to the interesting properties of their
derivatives, functionalization of benzothiazoles to give
2‐substituted benzothiazoles have attracted much atten-
tion in recent years. The conventional methods for
synthesis of 2‐substituted benzothiazoles includes using
metals as catalysts for intramolecular cyclization reac-
tions[4,5] and also the condensation of 2‐aminothiophenol
with alcohols,[6] aldehydes,[7–9] ketones,[10] carboxylic
acids,[11] halides,[12,13] ammonium triflates,[14] β‐
oxodithioesters[15] and amines.[16] However, having
harsh and hazardous reaction conditions,[17] use of
expensive reagents and metal catalysts[18] or strong acidic
or oxidative conditions,[19] and also tedious workup
procedures for separation of the pure products are the
disadvantages for most of these transformations.[20] Con-
sidering these limitations, several catalytic systems
starting directly from benzothiazoles were also
by using renewable and stable reagents and catalysts for
the synthesis of such compounds is of great value. To
overcome these limitations, the concept of heterogeneous
systems have been used by chemists.[25,26] Carbon mate-
rials with unique physicochemical properties such as
adjustable surface peculiarities and excellent chemical
and thermal stability can be good candidates as a
heterogeneous catalyst for this purpose.[27] Graphene
oxide (GO) is an oxide‐functionalized derivative of
graphene,[28] has received much interest for scientists.
Its adjustable and full accessible surface properties
provide it a high surface area for the immobilization of
magnetic nanoparticles (MNPs). The immobilization of
MNPs improves the catalytic activity of GO owing to
the synergistic interaction between both components.[29]
As a nontoxic carbon source, magnetic graphene oxide
can be used as a heterogeneous catalyst for various organic
transformations.[30–32] Despite this potential activity, mag-
netic GO still remain largely unexplored in catalytic
Appl Organometal Chem. 2017;e3971.
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Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.3971

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KHALILI ET AL.
SCHEME 1 Synthesis of GO‐Fe3O4 nanocomposites. Red dots indicate Fe3O4 nanoparticles
reactions. As a continuing interest in expanding the cata-
lytic application of GO in organic transformations,[33,34]
we report herein a heterogeneous catalytic system for the
arylation/alkylation of benzothiazoles with aldehydes
and benzylic alcohols using GO‐Fe3O4 nanocomposites as
a catalyst and diisopropyl azodicarboxylate (DIAD) as an
available and useful oxidant.
Fe3O4.[37] The characteristic peak corresponding to the
stretching vibration of Fe‐O bond is also shifted toward
a higher wavenumber 615 cm−1 compared to 570 cm−1
which was reported for bulk Fe3O4 suggesting that mag-
netic Fe3O4 is bound to the ‐COO− on the GO surface.[38]
Figure 2 shows X‐ray diffraction (XRD) patterns of the
GO and GO‐Fe3O4 samples. GO shows a sharp diffraction
peak centered at 2θ = 10.7, corresponding to the (002)
inter‐planar spacing of 0.82 nm, indicating the formation
of GO. The XRD pattern of the GO‐Fe3O4 composites indi-
cates six characteristic peaks of Fe3O4 at about 2θ = 30.1
(220), 35.8 (311), 43.3 (400), 53.7 (422), 57.1(511) and
63.2 (440) planes of the magnetite (JCPDS no. 19–629),
being similar to the previously reported data.[39–41] These
results indicate that the Fe3O4 nanoparticles are deposited
onto the surface of the GO sheets.
2 | RESULTS AND DISCUSSION
GO was prepared using harsh oxidation of graphite based
on a modified Hummers method,[35] followed by exfolia-
tion in an aqueous solution by ultrasonication. The pre-
pared GO was characterized using FT‐IR, UV/Vis, XRD
and also with cyclic voltammetry (CV) measurements to
establish its characteristics (see ESI).
Magnetically active GO‐Fe3O4 nanocomposites were
synthesized by the da Costa group via co‐precipitating
iron salts onto GO sheets in basic solution (Scheme 1).[36]
The synthesized nanocomposites were characterized
by, FT‐IR, powder XRD, VSM, TEM and thermogravimet-
ric analysis. The FTIR spectrum of GO‐Fe3O4 hybrid is
shown in Figure 1. The C¼O stretching peak of ‐COOH
on the GO (see supporting information) in the medium
frequency area at 1724 cm−1 is shifted to 1633 cm−1 indi-
cating the formation of ‐COO− after coating with
FIGURE 1 FT‐IR spectra of the Fe3O4‐GO nanocomposites
FIGURE 2 XRD patterns of GO (down) and GO‐Fe3O4 (up)

KHALILI ET AL.
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The thermal behavior of GO‐Fe3O4 was further inves-
tigated by thermogravimetric analysis. As shown in
Figure 3, TGA curve of GO‐Fe3O4 sample showed a 5.8%
weight loss up to 150°C, which can be assigned to the loss
of the residual or absorbed solvent.Then two stages of
weight loss observed around 240°C (3.4%) and a slow loss
of 2% at 350°C, indicating the decomposition and vapori-
zation of various functional groups at different positions
on the surface of the GO‐Fe3O4 hybrid composite. A
3.8% weight loss between 350°C and 650°C may be
attributed to the breakdown of the carboxylate group
(−COO−) coordinated with magnetic Fe3O4 nanoparticles
in the GO‐Fe3O4 composites.[38,42]
The morphology of the obtained GO‐Fe3O4 hybrid
composites was also characterized with transmission elec-
tron microscopy (TEM). The typical TEM image of the
prepared GO‐Fe3O4 composites revealed that Fe3O4 nano-
particles distributed homogeneously in the GO surfaces of
the nanocomposites. A minor degree of aggregation of
Fe3O4 was also observed (Figure 4).
FIGURE 4 TEM image of GO‐Fe3O4 nanocomposites
Next, the magnetic properties of GO‐Fe3O4 hybrid
were investigated using VSM at room temperature
(Figure 5). The GO‐Fe3O4 nanocomposites showed a typ-
ical S‐like magnetic hysteresis loop with the specific satu-
ration magnetization (Ms) of ~16 emu/g. This value
exhibits superparamagnetic behavior.[42] The reduction
in the value of Ms of the GO‐Fe3O4 hybrid compared
to ~60 emu/g reported for Fe3O4 nanoparticles, is due to
the low loading amount of Fe3O4 NPs, which is found to
be as 25 wt% by ICP analysis.
Raman spectroscopy is a suitable tool which is widely
used to characterize carbonaceous materials. The well‐
known characteristics of graphitic carbon‐based materials
FIGURE
nanocomposites
5
Magnetic hysteresis loops of GO‐Fe3O4
FIGURE 3 TGA curve of GO‐Fe3O4 hybrid composite

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KHALILI ET AL.
which interestingly results in the formation of 3c in 70%
yield (entry 8). Furthermore, increasing the amount of
catalyst improves the yield up to 84% (entries 9 and 10).
Changing the ratio of PEG‐200 against H2O, dropped the
yields (entries 11 and 12). Moreover, the combination of
PEG‐200/DMSO and PEG‐200/CH3CN were also tested
but poor yields of 3c were gained (entries 13 and 14).
Then the reaction was run without catalyst which gives
3c in 10% yield after 24 h and suggests that the presence
of the catalyst is crucial for the reaction to proceed (entry
15). In order to investigate the effect of temperature, we
decreased the temperature to 80°C which decreased the
yield of the product (74%, entry 16). To check the
efficiency of other azo compounds as oxidants, 4,4′‐
azopyridine (4,4′‐azpy), 3,3′‐azopyridine (3,3′‐azpy), 2,2′‐
azopyridine (2,2′‐azpy), 2,2′‐azobenzimidazole (azbi),
2,2′‐azobenzothiazole (azbt) and 5,5′‐dimethyl‐3,3′‐
azoisoxazole (azbio) were employed (Figure 8) but they
were found to be fruitless (entries 17–19). Performing
the reaction using other carbon based materials such as
activated carbon, natural flake graphite, hydrazine‐
reduced graphene oxide and magnetic reduced graphene
oxide, lead to a sharp decrease in the yield of 3c even after
a 24 h reaction time (entries 19–21). We also studied the
scope of this reaction with other oxidants such as oxone,
O2 and 30% hydrogen peroxide (entries 23–25). Replace-
ment of DIAD by these oxidants resulted in a lower yield
of the product 3c and DIAD was found to be the most
effective one.
FIGURE 6 Raman spectrum of the GO
in Raman spectra are the G and D bands. The spectrum of
GO shows a strong G band at 1590 cm−1, with a disor-
dered‐induced peak (D band) at 1366 cm−1 (Figure 6).
The Raman spectrum of the GO‐Fe3O4 shows charac-
teristic peaks of Fe3O4 in the range of 200–600 cm−1 and
typical peaks of GO at around 1357 cm−1 and 1587 cm−1
,
corresponding to the D and G bands respectively
(Figure 7). It can also be observed that the ID/IG ratio
increased from 1.38 for GO to 1.90 for GO‐Fe3O4. This
occurrence could be attributed to the introducing
of Fe3O4 which increased the defects and disorders in
GO sheets.
Then, we commenced our study by examining the
reaction of benzothiazole (1a) (1.2 mmol, 162 mg),
4‐methylbenzaldehyde (2c) (1.0 mmol, 120 mg), and
GO‐Fe3O4 (12 mg) as the catalyst in the presence of DIAD
(94%, 1.1 mmol, 0.23 ml) as an oxidant at 100°C under sol-
vent‐free condition (Table 1). Under this condition, the
arylation product (3c) was obtained in 34% yield (entry 1).
Next, we screen the effect of different solvents such as
H2O, PEG‐200, EtOH, toluene, CH3CN, and THF which
provide moderate yields and were not effective (entries
2–7). Considering the results of arylation of benzothiazole
in a mixture of two solvents which are noticeable,[21,23]
made us focus on using a mixture of solvents to see
whether it affects the efficiency of this transformation or
not. The combination of PEG‐200/H2O (2:1) was used
With the optimal condition in hand, the versatility
and scope of the reaction were explored (Table 2). A wide
variety of aldehydes were used to react with benzothiazole
derivatives under the stipulated conditions to afford the
desired products 3a–u in reasonably moderate to excel-
lent yield.
These results illustrate that electron deficient benzal-
dehydes undergo reaction with preference to their elec-
tron rich counterparts. This trend can be attributed to a
low electrophilicity of electron‐rich substrates. The reac-
tions worked smoothly with benzaldehydes having an
electron‐donating substituent on the aryl ring such as ‐
OCH3, −OCH2C≡CH, −CH3 and ‐OH to provide 2‐aryl
benzothiazoles 3b–i in 70–82% yields (entries 2–9). Prom-
ising reactivity was observed with electron‐deficient benz-
aldehydes and provided the corresponding products in
good to excellent yields (83–90%, entries 10–13). In the
case of hindered aldehydes such as 2,5‐dimethoxy (entry 3)
and 2‐chlorobenzaldehyde (entry 12) high yields were
obtained which indicates that steric hindrance is not evi-
dent in this reaction.
Aliphatic aldehydes are one of the most challenging
substrates in this condensation reaction perhaps due to
their rapid oxidation to carboxylic acids.[20,21,23] It was
FIGURE 7 Raman spectrum of the Fe3O4‐GO nanocomposite

KHALILI ET AL.
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TABLE 1 Optimization of the reaction conditions for the condensation of benzothiazole (1a) with 4‐methylbenzaldehyde (2c)a
Entry
Oxidant
Catalyst (mg)
Solvent (condition)
Time (h)
Yield (%)b
1c
DIAD
GO‐Fe3O4 (12)
None, 100 °C
24
34
2
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
DIAD
4,4′‐azpy
3,3′‐azpy
2,2′‐azpy
Azbi
GO‐Fe3O4 (12)
GO‐Fe3O4 (12)
GO‐Fe3O4 (12)
GO‐Fe3O4 (12)
GO‐Fe3O4 (12)
GO‐Fe3O4 (12)
GO‐Fe3O4 (12)
GO‐Fe3O4 (18)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
‐
H2O, reflux
12
12
12
12
12
12
12
12
12
12
12
12
12
24
12
12
12
12
12
12
12
24
24
24
24
12
12
12
48
55
59
22
46
41
70
76
84
74
78
32
28
10
74
65
40
53
69
62
60
12
21
30
40
71
65
77
3d
Peg, 100 °C
4
EtOH, reflux
5
Toluene, reflux
6
CH3CN, reflux
7
THF, reflux
8d
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (1:2), 100°C
PEG + H2O (1:1), 100°C
PEG + DMSO (2:1), 100°C
PEG + CH3CN (2:1), 100°C
None, 100 °C
9
10e
11
12
13
14
15c
16
17
18
19
20
21
22
23
24f
25
26
27
28
29
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
Graphite (24)
r‐GO (24)
PEG + H2O (2:1), 80°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
PEG + H2O (2:1), 100°C
Azbt
Aziox
DIAD
DIAD
DIAD
DIAD
Oxone
O2
r‐GO‐ Fe3O4 (24)
Activated carbon (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
GO‐Fe3O4 (24)
H2O2
aReaction condition: 1a (1.2 mmol, 162 mg, 0.13 ml), 2c (1 mmol, 120 mg, 0.12 ml), carbon promoter (type and amount indicated), DIAD (94%, 1.1 mmol,
0.23 ml), solvent (3 ml).
bIsolated yield.
csolvent‐free condition.
dPEG‐200.
eBold value signifies the best reaction conditions.
fr‐GO = reduced graphene oxide.
worth noting that this methodology could also be applied
for aliphatic aldehydes as well to afford the corresponding
2‐alkylbenzothiazoles in moderate yields (entries 14–16)
which represents an advantage of this catalytic system
over the reported protocols in literature.[21,22] Besides,
benzothiazoles bearing electron‐donating (−OMe) and
electron deficient (−Cl) substituents at the phenyl ring
proved to be suitable substrates for this transformation,

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KHALILI ET AL.
4‐methylbenzaldehyde and GO‐Fe3O4/DIAD which
forms 2‐(4‐methylphenyl)benzothiazole (3c) in 76% yield
(equation 2). Besides, the direct reaction of bis(2‐
aminophenyl) disulfide (5) with 4‐methylbenzaldehyde
also afforded benzothiazole (3c) in 61% yield (equation 3).
This observation clearly is in accordance with the
previously reported data for similar arylation of
benzothiazoles.[20]
FIGURE 8 Heterocyclic azo compounds
providing the corresponding products 3q–u in good yields
(entries 17–21).
Additionally, oxidation of alcohols to their correspond-
ing aldehydes using an appropriate oxidant and its further
condensation with benzothiazoles is an appealing
approach for the arylation of benzothiazoles since alcohols
are commercially available starting materials. Recently,
oxidation of alcohols to carbonyl compounds by diethyl
azodicarboxylate (DEAD) has been reported by Grée.[43]
As far as we know, there is only one report on the synthesis
of 2‐arylbenzothiazole directly through sequential oxida-
tion and condensation of alcohols with benzothiazole.[20]
In order to extend the scope of our methodology, we
examined the reaction of various benzylic alcohols instead
of aldehydes under the previously optimized reaction con-
dition for the synthesis of 2‐substituted benzothiazoles.
The representative results are listed in Table 3. As the
results show, benzylic alcohols with either electron‐donat-
ing (entries 2–4) or electron‐withdrawing substituents
(entries 5–7) in the presence of benzothiazole derivatives
(entries 8–10) delivered the expected products in moderate
to good yields which indicated the potential utility of our
protocol for using alcohols as the starting material. To
investigate the mechanistic pathway, several controlled
experiments were conducted under the optimized reaction
conditions. In the absence of aldehyde, benzothiazole was
converted into the 2‐amino thiophenol (63%) and its dimer
(5: 33%) (equation 1) which suggests the ring opening of
the starting material takes place.
Although the exact mechanism is still not clear at
present, but these results showed that the reaction goes
through the oxidative benzothiazole ring opening path-
way and then oxidative condensation of the resultant 2‐
amino thiophenol (or disulfide 5) with the aldehyde
(Scheme 2). In the proposed mechanism, magnetic GO
can act as a solid acid catalyst and also can activate the
aldehyde.
We also studied the effect of adding a mixture
of GO and Fe3O4 nanoparticles, instead of the
nanocomposite, for the reaction of benzothiazole (1a)
and 4‐methylbenzaldehyde (2c) under optimized condi-
tions. It was found that the absence of nanocomposite
affects the reaction greatly and a lower yield of 3c was
obtained (59%). This difference may be due to the strong
synergistic interaction between both components GO
and Fe3O4 in the nanocomposite.[29]
Moreover, the potential recyclability of the catalytic
system was tested using benzothiazole with 4‐methyl
benzaldehyde. After the first run, GO‐Fe3O4 was filtered,
washed with diethyl ether (2 × 10 ml) and warm EtOH
several times and then dried under vacuum. In the
recycling experiment, the recovered GO‐Fe3O4 catalyst
was recharged with fresh reactants for the next run under
similar conditions. The results indicate that the catalyst
still remained catalytically active after being reused seven
times (Figure 9).
In order to investigate whether these two intermediates
can form the corresponding 2‐substituted benzothiazole in
the presence of aldehyde, we conduct the reaction of 2‐
amino thiophenol under our standard condition applying
In order to check the applicability of using
benzoxazoles and benzimidazoles instead of benzothia-
zoles, we conduct their reaction in the presence of 4‐

KHALILI ET AL.
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TABLE 2 Arylation of benzothiazoles with various aldehydesa
Entry 1: 3a, 82%
Entry 5: 3e, 84%
Entry 2: 3b, 76%
Entry 6: 3f, 77%
Entry 3: 3c, 73%
Entry 7: 3 g, 81%
Entry 4: 3d, 79%
Entry 8: 3 h, 70%
Entry 9: 3i, 74%
Entry 10: 3j, 90%
Entry 14: 3n, 58%
Entry 18: 3r, 77%
Entry 11: 3 k, 87%
cEntry 15: 3o, 46%
Entry 19: 3 s, 72%
Entry 12: 3 l, 83%
cEntry 16: 3p, 40%
Entry 20: 3 t, 87%
Entry 13: 3 m, 88%
Entry 17: 3q, 84%
Entry 21: 3u, 73%
aReaction condition: benzothiazoles (1.2 mmol), aldehydes (1 mmol), GO‐Fe3O4 (24 mg), PEG‐H2O (3 ml, 2:1), DIAD (94%, 1.1 mmol, 0.23 ml), 100 °C, 12 h.
bIsolated yields after flash column chromatography on silica gel.
cReaction was performed in a sealed tube.
methylbenzaldehyde (2a) under the same reaction condi-
tions. Unfortunately, our attempts to incorporate the
benzoxazole and benzimidazole failed to produce
The failure of the benzimidazole might be due to the fact
that this substrate is not able to undergo oxidative ring open-
ing to produce o‐phenylenediamine which can undergo
the desired products under our conditions (equation 4
the reaction with the activated aldehyde (equation 6).
and 5).[21] Controlled experiments showed that benzimid-
azole remained intact under the reaction condition
whereas benzoxazoles were converted to unidentified
products in the reaction.[44]
Moreover, 2‐aminophenol did not undergo oxidative
condensation with benzaldehyde to form 2‐phenyl
benzoxazoles under the optimized reaction condition
(equation 7).

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KHALILI ET AL.
TABLE 3 GO‐Fe3O4 catalyzed coupling of benzylic alcohols with benzothiazoles in a one‐pot oxidation/condensation tandem processa
Entry 1: 3a, 66%
Entry 2: 3b, 57%
Entry 3: 3c, 58%
Entry 7: 3i, 60%
Entry 4: 3e, 49%
Entry 8: 3n, 66%
Entry 5: 3 g, 69%
Entry 9: 3o, 58%
Entry 6: 3 h, 66%
Entry 10: 3q, 62%
aReaction condition: benzothiazoles (1.2 mmol), benzylic alcohol (1 mmol), GO‐Fe3O4 (24 mg), PEG‐H2O (3 ml, 2:1), DIAD (94%, 1.1 mmol, 0.23 ml), 100 °C, 12 h.
bIsolated yields.
SCHEME 2 Plausible mechanism
effectively separated from the reaction mixture via an
external permanent magnet and the resulting material
was characterized by TEM analysis. TEM image of the
recovered catalyst after the 7th reaction run indicated that
the Fe3O4 NPs were agglomerated (Figure 10), evidenced
by the formation of large clusters in 7 consecutive conden-
sation reaction.
The use of o‐ phenylenediamine in the condensation
reaction is also feasible but produces the products in
lower yields.
Furthermore, Raman spectroscopy was taken in order
to evaluate the structure of the GO‐Fe3O4 after 7 runs. The
obtained Raman spectrum of GO‐Fe3O4 indicates the par-
tial reduction of recovered magnetic GO after the last run.
No obvious shifts in the D and G bands of the recovered
magnetic GO were observed with respect to pristine GO‐
Fe3O4, but the intensity ratio of the D to G band (ID/IG)
is decreased to 1.63, which demonstrates a slight restora-
tion of the conjugated C¼C bonds (Figure 11).
To determine the fate of the GO‐Fe3O4 catalyst which
used in these condensation reactions, a control experi-
ment was carried out using benzothiazole 1a (1.2 mmol)
and 4‐methylbenzaldehyde 2c (1 mmol) in PEG‐H2O in
the presence of GO‐Fe3O4 (24 mg) at 100°C. This reaction
was repeated seven times with the same catalyst sample,
which was recovered after each reaction. After the com-
pletion of the reaction, the residual catalyst was

KHALILI ET AL.
9 of 11
(PEG‐H2O). A variety of 2‐aryl/alkyl benzothiazoles
were obtained by the present methodology. In addition,
high stability and activity of the catalyst, operational
simplicity, convenience in product isolation and also
the possibility to perform the transformation in a safe
and green medium are also the attractive features of
this protocol.
4 | EXPERIMENTAL
4.1 | Synthesis of graphene oxide (GO)
FIGURE 9 Catalyst reusability study
Graphene oxide (GO) was prepared from graphite using
modified Hummer's and Offeman method. As a typical
run, 1.0 g of natural flake graphite (particle size:
<50 μm; from Merck) and 1.0 g of NaNO3 (fine mesh,
1.0 g) were mixed together followed by the addition of
48 mL of H2SO4 (48 ml, 98%) by stirring in an ice bath
(0°C) for 15 min. KMnO4 powder (3.0 g) was added
slowly to the above solution and the rate of addition
was controlled to prevent the mixture temperature from
exceeding 20°C. After 1.5 h, the mixture was transferred
to a 35 3°C water bath with constant stirring (30 min).
Subsequently, the resulting solution was diluted by
adding 180 ml of water, the temperature rose gradually
and was kept in 90–100°C for another 30 min. The mix-
ture was further treated with 400 ml de‐ionized water
and 35% of the hydrogen peroxide solution (10 ml). After
being continuously stirred for 1.5 h, the yellow mixture
was filtered and the precipitate washed with 5% HCl
aqueous solution (5%, 200 ml). The synthesized GO was
dialyzed in a dialysis bag for 1 week to ensure the
complete removal of any metal ions and acid. The
obtained brown precipitate was dried under vacuum
and kept in the dark until further use. For use in the
reactions, the graphite oxide aqueous suspension was
sonicated (200 ml, 10 mg ml−1) for nearly 1 h to obtain
graphene oxide.
FIGURE 10 TEM image of recycled GO‐Fe3O4 nanocomposite
after 7th run
4.2 | Preparation of GO‐Fe3O4
nanocomposites
FIGURE 11 Raman spectrum of the recovered Fe3O4‐GO
nanocomposite after 7 run
The GO‐Fe3O4 hybrid composites were prepared by
co‐precipitating pre‐hydrolysed ferric and ferrous salts
in the presence of GO nanosheets. Typically, an aqueous
solution (150 mL) containing FeCl3.6H2O (6 mmol) and
FeCl2.4H2O (3 mmol) was prepared with an initial pH
of 1.5. The solution was adjusted to pH 4 by adding
sodium hydroxide (1.0 M) and further stirred for
30 min. After that, the GO solution (75 ml, 0.5 mg/ml)
was gradually added into this solution at a fixed pH = 10
by adjusting with 1.0 M NaOH. The mixture was
stirred for a further 30 min at room temperature.
3 | CONCLUSION
In summary, we have successfully developed a practical
magnetic graphene oxide‐catalyzed oxidative condensa-
tion protocol for the arylation and alkylation of
benzothiazoles starting from aldehydes or benzylic
alcohols using DIAD as an oxidant in a safe medium

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KHALILI ET AL.
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The resulting dark black precipitate was collected by an
external magnet and washed thoroughly with
deionized water and ethanol prior drying in an oven
at 60°C for 48 h.
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4.3 | Typical procedure for the synthesis of
2‐aryl (alkyl) benzothiazole
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A
25‐ml round‐bottom flask was charged with
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benzothiazole 1a (1.2 mmol, 0.13 ml), aldehyde 2c (1.0
mmol, 0.12 ml) or benzylic alcohol 4a (1.0 mmol, 0.1 ml),
DIAD (94%, 1.1 mmol, 0.23 ml), GO‐Fe3O4 (24 and
21.6 mg for aldehydes and benzylic alcohols, respectively)
and PEG‐200/H2O (2:1 ml). The reaction was stirred at
100°C for 12 h until TLC analysis showed the completion
of the reaction. Upon completion of the reaction, the mix-
ture was diluted with EtOAc (10 ml) and magnetic
graphene oxide was removed by an external magnetic field.
The organic phase was dried over Na2SO4, and concen-
trated to yield the crude product, which was further puri-
fied by flash chromatography on silica gel
(eluent: petroleum ether/ethyl acetate) to give the pure
product. All the compounds are known and were charac-
terized by the comparison of their spectral data with those
reported in the literature.
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ACKNOWLEDGMENT
This research was financially supported by the Shiraz
University – Iran research council.
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How to cite this article: Khalili D, Etemadi‐
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Davan E, Banazadeh AR. 2‐Arylation/alkylation of
benzothiazoles using superparamagneticgraphene
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catalystwith diisopropyl azodicarboxylate (DIAD)
as an oxidant. Appl Organometal Chem. 2017;e3971.
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