Heterogeneous magnetic catalyst for S-arylation reactions

Article abstract of DOI:10.1016/j.apcata.2012.05.026

A convenient method for the synthesis of monodisperse, superparamagnetic copper ferrite (CuFe₂O₄) nanoparticles with high surface area has been described. The synthesized material was characterized by various techniques. XRD showed the nanocrystalline nature of CuFe₂O ₄ with a crystallite size of 6 nm. TEM analysis showed that uniform spherical CuFe₂O₄ particles are formed with a size of 55 ± 5 nm. N₂ adsorption/desorption measurements confirmed the mesoporous nature of the sample with surface area >216 m² g ^-1. The field dependent magnetization, illustrated by VSM and saturation magnetization was found to be 44 emu g^-1. The catalytic applications of the synthesized CuFe₂O₄ nanoparticles were explored for the cross-coupling of thiols with diverse range of aryl halides. Aryl iodides and bromides result in biarylsulfides in good to excellent yields (62-98%) whereas aryl chlorides gave significant amount of diaryldisulfide. Scope of this catalytic protocol further extended to one-pot synthesis of biologically important tricyclic dibenzothiazepines. The superparamagnetic nature of CuFe₂O₄ nanoparticles was found to be advantageous for their easy, quick and quantitative separation from the reaction mixture. Negligible leaching of Cu and Fe in consecutive cycles makes the catalyst economical and environmentally benign.

Full text of DOI:10.1016/j.apcata.2012.05.026

Applied Catalysis A: General 433–434 (2012) 258–264
Contents lists available at SciVerse ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Heterogeneous magnetic catalyst for S-arylation reactions
Niranjan Panda∗, Ashis Kumar Jena, Sasmita Mohapatra∗∗
Department of Chemistry, National Institute of Technology, Rourkela-769008, Odisha, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient method for the synthesis of monodisperse, superparamagnetic copper ferrite (CuFe2O4)
nanoparticles with high surface area has been described. The synthesized material was characterized by
various techniques. XRD showed the nanocrystalline nature of CuFe2O4 with a crystallite size of 6 nm.
TEM analysis showed that uniform spherical CuFe2O4 particles are formed with a size of 55 5 nm.
N2 adsorption/desorption measurements confirmed the mesoporous nature of the sample with surface
area >216 m2 g−1. The field dependent magnetization, illustrated by VSM and saturation magnetization
was found to be 44 emu g−1. The catalytic applications of the synthesized CuFe2O4 nanoparticles were
explored for the cross-coupling of thiols with diverse range of aryl halides. Aryl iodides and bromides
result in biarylsulfides in good to excellent yields (62–98%) whereas aryl chlorides gave significant amount
of diaryldisulfide. Scope of this catalytic protocol further extended to one-pot synthesis of biologically
important tricyclic dibenzothiazepines. The superparamagnetic nature of CuFe2O4 nanoparticles was
found to be advantageous for their easy, quick and quantitative separation from the reaction mixture.
Negligible leaching of Cu and Fe in consecutive cycles makes the catalyst economical and environmentally
benign.
Received 3 January 2012
Received in revised form 18 May 2012
Accepted 20 May 2012
Available online 28 May 2012
Keywords:
Superparamagnetic nanoparticles
Heterogeneous catalyst
Cross-coupling
S-arylation
Dibenzothiazepines
Dibenzothiazepinones
Aryl halides
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
neocuproine, N-methylglycine, oxime-phosphine oxide ligand, tri-
pod ligand, benzotriazole, 1,2-diaminocyclohexane, ␤-ketoester,
Transition-metal-catalyzed cross-coupling reaction presents
one of the robust methods for the formation of carbon–carbon
and/or carbon–heteroatom bonds [1–3]. Among the various cross-
coupling reactions, metal-catalyzed S-arylation has received less
attention as compared with N- or O-arylation reactions until very
recent times. This is because (i) thiols are prone to undergo oxida-
tive S S coupling reactions to undesired disulfides, and (ii) strong
coordinating properties of organic sulfur compounds, often make
the catalyst ineffective (catalyst poison) [4]. Usually, palladium,
copper and nickel-based catalysts are extensively used for various
l-proline, BINAM, polyethylene glycol, and ethylene diammine, are
used as chelating agents in the copper-catalyzed cross-coupling
reactions [10]. On the other hand, the simple separation and
regeneration of the catalyst from the reaction mixture are in
strong demand for the cost-effective process of molecular syn-
thesis. In pharmaceutical industries, it is also essential to remove
all traces of metal residues, which frequently interfere with the
subsequent reactions and contaminate the final products. In con-
trast, developments of reusable heterogeneous catalytic systems
for cross-coupling reactions have been received less attention
although the situation is changing in recent years [11]. Evidently,
certain heterogeneous catalytic system for the cross coupling of
arylthiols with aryl halides have been reported. For instance, CuI-
catalyzed cross coupling of arylthiols with aryl iodide was reported
by van Koten [12] and Li [13] individually. Luque and co-workers
developed a microwave-assisted, Fe-Cu co-catalyzed heteroge-
neous catalytic system for the cross-coupling of thiols with aryl
iodides [14]. More importantly, Punniyamurthy and co-workers
exploited the high surface area and reactive morphology of the CuO
nanoparticles for successful C S cross-coupling reactions under
ligand free conditions [15]. Ranu and co-workers also employed
copper nanoparticles for the cross-coupling of aryl iodides and bro-
mides with thiophenols at 110 ◦C [16,17]. Although these results
are promising, the small size of nanoparticles often makes their
separation and recycling difficult, which impedes their use in indus-
trial processes [18,19]. In order to circumvent such problems, we
C
S cross-coupling reactions [5–9]. In spite of having wide scope
and excellent compatibility with many functional groups, these
protocols, often suffer from the disadvantages resulting from (i)
the high cost of the palladium precursors, (ii) the need for ancillary
ligands rendering the catalysts sufficiently reactive, (iii) concerns
about the toxicity of these metal salts, and (iv) the extended reac-
tion times, which are necessary in many cases. Considering the
cost and environmental factor, the use of Cu catalysts for various
cross-coupling reactions is attractive one from industrial perspec-
tives. Moreover, ligands such as phosphazene, ethylene glycol,
∗
Corresponding author. Tel.: +91 661 2462653.
Corresponding author.
∗∗
E-mail addresses: npanda@nitrkl.ac.in, niranjanpanda@gmail.com (N. Panda),
sasmitam@nitrkl.ac.in (S. Mohapatra).
0926-860X/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.apcata.2012.05.026

N. Panda et al. / Applied Catalysis A: General 433–434 (2012) 258–264
259
envision that single component superparamagnetic nanocatalysts
with high surface area, whose flocculation and dispersion can be
controlled reversibly by application of a magnetic field, may be
employed as a heterogeneous catalyst for cross-coupling reactions.
Indeed, in recent years, magnetic nanoparticles have been exten-
sively studied for various biological applications, such as magnetic
resonance imaging [20], drug delivery [21,22], biomolecular sen-
sors [23,24], bioseparation [25,26] and magneto-thermal therapy
[27,28]. Despite their wide use in biological systems, much less
attention has been focused on the catalytic behavior of magnetic
nanoparticles in organic transformations [29–35]. Here, we report
the detailed synthesis, characterizations of mesoporous superpara-
magnetic copper ferrite (CuFe2O4) nanoparticles and their efficient
catalytic activity toward the S-arylation reactions. One-pot synthe-
sis of biologically important tricyclic dibenzothiazepines was also
demonstrated.
30 min at 80 ◦C followed by addition of 15 mL of ethanolamine. The
entire solution was heated at 150 ◦C for 6 h during which fine black
colloidal particles appeared in the reaction mixture. Then it was
cooled down to room temperature. The particles were recovered
using a magnetic separator (DynaMag2, Invitrogen), washed with
millipore water and dried in a hot air oven at 80 ◦C. The dried sam-
ples were calcined at 500 ◦C for 5 h to get mesoporous CuFe2O4
powders.
2.4. General procedure for S-arylation reactions
For S-arylation reactions, CuFe2O4 (10 mol%) nanoparticles were
added to a solution of thiol (1 eq.), aryl halide (2 equiv.) and tBuOK
(2 equiv.) in dry 1,4-dioxane. The reaction mixture was heated
under reflux for 24 h under N2 atmosphere. Then, it was cooled
to room temperature, diluted with ethyl acetate and catalyst was
separated by magnetic separator. The catalyst was washed with
ethyl acetate. The combined ethyl acetate layers were washed with
water (twice), dried over anhydrous Na2SO4 and concentrated to
yield the crude products, which on further purification by silica gel
column chromatography using petroleum ether/ethyl acetate lead
to the desired S-arylated products.
2. Experimental
2.1. Materials
All chemicals are of reagent grade and used without further
purification. FeCl3, CuCl2·2H2O, ethylene glycol and ethanolamine
were purchased from Merck specialities, India. N-heterocycles,
thiols and aryl halides were obtained from Spectrochem, India.
Petroleum ether, ethyl acetate and other organic solvents were
procured from Rankem, India.
3. Results and discussions
3.1. Catalyst characterizations
The X-ray diffraction pattern of the calcined sample (Fig. 1) per-
fectly matches with the expected cubic spinel structure of CuFe2O4.
The position and relative intensities match well with those from
JCPDS card (77-0010) for CuFe2O4. The broadening of peaks indi-
cates nanocrystalline nature of the sample. The crystallite size was
calculated using Scherer equation taking into account broaden-
ing of each diffraction peak and was found to be 9 nm. Copper
and iron content in CuFe2O4 nanoparticles were estimated to be
4.15 mmol/g and 8.30 mmol/g respectively by ICP-MS.
2.2. Instrumentations
The phase formation and crystallographic state of the sample
was studied by X-ray diffraction (XRD) analysis using Philips PW
1830 X-ray diffractometer with CuK␣ source. Nitrogen adsorp-
tion/desorption isotherm was obtained at 77 K on a Quantachrome
Autosorb 3-B apparatus. The specific surface area and pore size
distribution were obtained by following BET equation and BJH
method respectively. The morphology of the catalyst was stud-
ied by scanning electron microscopy (HITACHI COM-S-4200) and
Transmission electron microscopy (JEOL 3010, Japan) operated at
300 kV. Atomic Weight Percentage of the catalyst (CuFe2O4) was
determined by an inductively coupled plasma-mass spectrometry
(ICP-MS). Leaching of heavy metals after S-arylation was analyzed
by AAS (Perkin Elmer A Analyst 200 Spectrometer).
The synthesized cross-coupled products were characterized by
IR, NMR spectroscopy and MS spectrometry. Chemical composi-
tions of the products were determined by C, H, N, S elemental
analyzer. IR spectra were recorded on Perkin Elmer (BX 12) spec-
trophotometer on KBR discs. All NMR spectra were recorded on
Bruker Avance III (400 MHz for 1H NMR, 100 MHz for 13C NMR)
spectrometer; chemical shifts were expressed in ı units (ppm)
relative to TMS signal as internal reference in CDCl3 (7.28 ppm).
Multiplicity was indicated as follows: s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet) and bs (broad singlet). Elemen-
tal analyses were carried out with a Vario EL Elemental Analyzer.
Mass spectra were taken by EI (70 eV) technique on Shimadzu QP
2010 PLUS GC–MS system.
Fig. 2a shows typical SEM image of the CuFe2O4 powder. It
is interesting to observe that CuFe2O4 nanoparticles own quasi
monodisperse size. TEM was used to further characterize the mor-
phology and crystal structure. Fig. 2b and c represents TEM images
at different magnifications. It can be noticed that CuFe2O4 parti-
cles are spherical, almost monodisperse and own an average size of
about 55 5 nm. An image at higher magnification (Fig. 2c) shows
that each spherical particle is an assembly of primary cubic CuFe2O4
nanocrystals having a size of 3–4 nm and worm like pores with size
of 2–3 nm. The HRTEM image (Fig. 2d) of a single aggregate shows
that the parallel lattice fringe is extended over primary nanocrys-
tals and pores. From this observation, oriented attachment growth
mechanism may be proposed for the formation of such porous
assembly [37–39]. This mesoporous structure has been formed
from the self-assembly of ultrafine particles by sharing common
crystallographic orientations. From thermodynamic point of view
it can be explained that the driving force for such spontaneous
arrangement is that the elimination of pairs of high energy surfaces
which leads to the reduction of surface free energy. The marked
region in Fig. 2d shows an interplanner spacing of 0.25 nm, corre-
sponding to [3 1 1] plane of the cubic CuFe2O4 nanoparticle. The
selected area electron diffraction (inset in Fig. 2b) pattern is also
consistent with the cubic phase of CuFe2O4 nanoparticles.
2.3. Synthesis of the catalyst
Superparamagnetic CuFe2O4 nanoparticles were prepared by
thermal decomposition of CuCl2 and FeCl3 in ethylene glycol
in presence of sodium acetate and ethanolamine following the
method recently reported by Mohapatra et al. [36]. Anhydrous
FeCl3 (0.683 g, 4.2 mmol) and CuCl2·2H2O (0.358 g, 2.1 mmol) were
taken in 30 mL ethylene glycol and 0.5 gm of sodium acetate was
added to it. The black color solution thus obtained was stirred for
Nitrogen sorption experiment further supports the porous
nature of CuFe2O4 nanoparticles. Fig. 3 represents nitrogen adsorp-
tion/desorption isotherms and BJH pore size distribution curve
(inset in Fig. 3). The isotherm is of type IV and displays H3 hysteresis
loop. Generally, such type of hysteresis loop is observed in case of
aggregates of plate like particles which give rise to slit shaped pores

260
N. Panda et al. / Applied Catalysis A: General 433–434 (2012) 258–264
Fig. 1. XRD pattern of CuFe2O4 sample (a) freshly prepared; (b) recovered sample after S-arylation reaction.
[40]. The BJH pore size distribution clearly indicates that mesopores
of size 2–3 nm are formed among the ultrafine nanoparticles within
the aggregate, which is in accordance with the TEM result. The BET
surface area was found to be 216 m2 g−1. The high surface area
and narrow pore size distribution is advantageous in improving
catalytic performance toward cross-coupling reactions.
Field dependent magnetization curve of CuFe2O4 catalyst at
room temperature has been illustrated in Fig. 4. The magnetization
value increased rapidly as the applied field increased up to 1 T and
reached at a saturation point at 2 T. The saturation magnetization
(Ms) displays higher value for synthesized nano-assemblies than
the corresponding nanodots. Ms value for CuFe2O4 nanoparticles
was found to be 23 emu g−1 against the corresponding bulk value
of 83 emu g−1 [41]. This decrease in Ms could mainly be attributed
to the small particle surface effect that becomes more prominent
as the particle size decreases [42]. The curve shows almost no
hysteresis and is completely reversible at room temperature. As
observed by TEM, the size of primary nanocrystal is 3–4 nm, which
is below the superparamagnetic critical size of CuFe2O4. Thus it
is logical that the synthesized clusters show superparamagnetic
behavior even though their sizes exceed the critical size and at
the same time the improved coalescence of the crystallites in the
Fig. 2. (a) SEM image of fresh CuFe2O4 catalyst and recovered catalyst (inset); (b) and (c) TEM images of discrete and monodisperse CuFe2O4 nanoparticles with porous
structure, inset is the SAED pattern; (d) high resolution TEM image showing lattice imaging of [3 1 1] plane.

N. Panda et al. / Applied Catalysis A: General 433–434 (2012) 258–264
261
SH
S
Me
O
catalyst
base, solvent,
reflux
I
COMe
1a
Scheme 1. S-arylation reaction.
the solvent, DMF, and base, tBuOK, required higher temperature
to afford 1a in quantitative yield (90%). In contrast, solvents such
as methanol, toluene, CH3CN and DMSO, in presence of base,
tBuOK, resulted 1a in poor yield (8–48%). Similarly, other bases
like, Cs2CO3, K2CO3, NaOAc, NaHCO3 and Et3N leads <30% yield of
the desired product 1a. Having the suitable solvent and the base
for C S cross-coupling reaction, next we have examined the effi-
cacy of other magnetic ferrite nanoparticles MFe2O4 (M = Fe+2, Co+2
and Ni+2). We observed that other ferrite nanoparticles, i.e. Fe3O4,
CoFe2O4 and NiFe2O4 resulted 0–15% of the S-arylated product.
Moreover, CuFe2O4 nanoparticles not only give excellent yield of
the product, but also magnetic nature of the catalyst facilitates
its easy and quantitative removal from the reaction medium in
the presence of an external magnetic field for subsequent use.
When the reaction was conducted in presence of ambient air or
in presence of atmospheric oxygen, 25–39% of 1a was isolated
(Table 1, entries 18 and 19). The poor yield of 1a is attributed to
the formation of unidentified polymeric residue. It is worth men-
tioning that when 10 mol% of CuO were used for the reaction, in
addition to the S-arylated product (59%), diphenyldisulfide (24%)
was obtained from the homocoupling of thiophenol. In contrast,
under our optimum conditions 10 mol% of CuFe2O4 nanoparticle
furnished significantly higher yield (95%) of S-arylated product
and no trace of diphenyl disulfide was detected (from TLC). Thus,
it may be concluded that the synergistic effects of Fe and Cu
in CuFe2O4 co-catalyze the S-arylation reactions and presumably
this is due to the reducing nature of Fe, which restricts the for-
mation of the undesired diaryl disulfide in C S cross-coupling
reactions.
Fig. 3. Nitrogen adsorption-desorption isotherm of CuFe2O4 nanoparticles.
nanostructure results in enhanced magnetic coupling and higher
magnetization.
3.2. Catalytic applications of copper ferrite nanoparticles in
cross-coupling reactions
Recently, we have shown the utility of magnetically separable
CuFe2O4 nanoparticles for N-arylation and alkynylation reactions
[34,35]. Our results suggested to us that similar catalytic protocol
for C S couplings might be tolerant of a wide variety of func-
tional groups. Thus, to study the efficacy of magnetic nanocatalyst
in the C S cross-coupling reactions, we use 4-iodoacetophenone
and thiophenol as model substrates (Scheme 1). The optimiza-
tion of the reaction conditions were carried out using different
bases and solvents at their boiling temperature (Table 1). The
best result was obtained when the reaction was conducted using
10 mol% of copper ferrite nanoparticles in the presence of 2 equiv.
of tBuOK as base in 1,4-dioxane affording the desired 1-(4-
(phenylthio)phenyl)ethanone (1a) (95% yield). The reactions with
With the optimized reaction conditions we then extended the
scope of this catalytic protocol for the cross-coupling of a diverse
range of halides with thiophenol (Table 2). We noticed that CuFe2O4
catalyzes the cross-coupling reactions of thiophenol with several
aryl iodides in excellent yield. We have not detected any trace of
Table 1
Optimization of reaction conditions for S-arylation reaction.a
Entry
Catalyst
Solvent
Base
Yield [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18b
19c
CuFe2O4
CuFe2O4
CuFe2O4
CuFe2O4
CuFe2O4
CuFe2O4
CuFe2O4
CuFe2O4
CuFe2O4
CuFe2O4
CuFe2O4
Fe3O4
CoFe2O4
NiFe2O4
CuO
CuFe2O4
–
DMF
1,4-Dioxane
MeOH
Toluene
CH3CN
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
Cs2CO3
K2CO3
NaOAc
NaHCO3
Et3N
90
95
8
24
18
48
30
20
≤5
10
18
≤5
10
15
59
00
00
39
25
DMSO
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
–
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
CuFe2O4
CuFe2O4
a
Reaction conditions: 0.90 mmol of thiophenol, 1.80 mmol of 4-iodo acetophe-
none, 10 mol% of catalyst, 2.0 equiv. of base, 5 mL of solvent, 24 h reflux under N2
atmosphere.
b
Reaction carried out under O2 atmosphere.
Reaction carried out in open air.
Fig. 4. Field-dependent magnetization of (a) fresh CuFe2O4 catalyst and (b) recov-
ered sample.
c

262
N. Panda et al. / Applied Catalysis A: General 433–434 (2012) 258–264
Table 2
CuFe2O4 catalyzed C-S cross-coupling of thiophenol with aryl halides.a
SH
X
10 mol% CuFe2O4
2 equiv. tBuOK
S S
S
+
1,4-dioxane,reflux
24h
R
R
1
Dipheneyl disulfide
Entry
Aryl halide
Yield of 1 (%)
1
2
3
X = I, R = 4-COMe
X = I, R = H
X = I, R = 4-NO2
X = I, R = 4-COOH
X = I, R = 2-COOH
X = I, R = 4-Cl
95 (1a)
98 (1b)
86 (1c)
87 (1d)
90 (1e)
88 (1f)
83 (1g)
4
5b
6
7
X = I, R = 4-OMe
8
9
10
11
12
13c
X = Br, R = 4-COMe
X = Br, R = H
X = Br, R = 4-NO2
X = Br, R = 4-COOEt
X = Br, R = 2-CHO
X = Br, R = 4-OMe
87 (1a)
85 (1b)
62 (1c)
76 (1h)
72 (1i)
62 (1g)
14c
15c
16c
17c
X = Cl, R = H
48 (1b)
45 (1h)
42 (1c)
47 (1j)
X = Cl, R = 4-COOEt
X = Cl, R = 4-NO2
X = Cl, R = 4-Me
a
Reaction conditions: 0.90 mmol of thiophenol, 1.80 mmol of halide, 10 mol% of catalyst, 2.0 equ. of tBuOK, 5 mL of 1,4-dioxane, 24 h reflux under N2 atmosphere.
Reaction was carried out in DMF instead 1,4-dioxane.
Entries 13–17 result 14, 20, 22, 25 and 17% of disulfide respectively along with biaryl sulfide.
b
c
homocoupling product (e.g. diphenyl disulfide) from TLC. Coupling
At the onset of our investigation to the one-pot synthesis
of dibenzo-fused thiazepines, we have taken 2-aminothiophenol
as the starting material and 2-bromobenzaldehyde as the cou-
pling partner (Scheme 3). After 24 h, under the optimized reaction
of thiophenol with different aryl bromides having both electron-
donating and -withdrawing groups resulted in products with good
yields 62–87% (Table 2, entries 8–13). Moderated yield in case of
4-nitrobromobenzene and 2-bromobenzaldehyde is accounted for
the possible decomposition where as p-bromoanisole results com-
petitive homocoupled diphenyl disulfide (14%). More interestingly,
our catalytic system was also found to be efficient in yielding the
cross-coupled products with the comparatively less reactive aryl
chlorides although a reasonable amount (17–25%) of disulfide was
Table 3
Cross-coupling of bromobenzene and chlorobenzene with thiophenol in presence
of different catalysts.
SH
X
S
Catalyst
isolated (Table 2, entries 14–17). It may be note worthy that, C
S
coupling reactions of aryl bromides and chlorides with thiophenol
reported earlier, gave poor yield or no yield of the S-aryl prod-
ucts even under Cu-catalyzed-ligand-assisted conditions (Table 3)
[12,14,32,43–47].
X = Br / Cl
1a
.
Catalyst
Aryl halide Yield of 1a (%) References
Having the proved cross-coupling efficiency of our catalytic pro-
tocol with aryl iodides, the scope of the reaction was subsequently
extended to a range of aryl and alkyl thiols. As summarized in
Scheme 2, a number of biarylsulfides were obtained in moderate
to excellent yields. Next, we deem for the one-pot synthesis of
X = I
X = Cl, X= Br
91
0
FeCl3/DMEDA
[43]
X = I
X = Br
X = Cl
95
37
<5
CuO (nano)
[32]
diaryl-fused thiazepine derivatives by the tandem C S and C
N
X = I
X = Br
X = Cl
95
70
48
Fe2O3/Cu(OAc)2/L/MW
Cu-MW-HMS
[44]
[14]
[12]
[45]
[46]
[47]
bond forming reactions. It is worthy to mention that dibenzo-fused
thiazepines having medium-ring (6–7–6) structures show pro-
nounced therapeutic effect on the central nervous system and are
particularly active as antidepressants, antimetics, analgesiscs and
sedatives [48,49]. Successful examples include dibenzothiazepine
drugs (3 and 4), which are clinically used for the treatment of
bipolar and psychiatric disorders (Fig. 5). Very recently, Garat-
tini and co-workers reported the anti-tumor potential of the
dibenzothazopine-11-one derivatives (5) in animals [50]. Pet-
terssons and co-workers also reported the selective CBI inverse
agonist behavior of dibenzothiazepine derivative (6) [51]. The
emerging pharmacological potential of dibenzothiazepine ring sys-
tems makes them a valuable target and thus short and efficient
routes for their synthesis are desired. In contrast, to the best of our
knowledge one-pot synthesis of such tricyclic nucleus has not been
reported till date although limited literature on multistep synthe-
ses is precedented [50–53].
X = I
X = Br
X = Cl
95
nd
nd
X = I
X = Br
X = Cl
99
5
4
CuI/NMP
X = I
X = Br
X = Cl
86
32
00
CuL/L/MW
X = I
X = Br
X = Cl
97
66
00
Cu(OTf)2/BINAM
CuI(nano)/nBu4NOH
X = I
X = Br
X = Cl
93
61
Trace

N. Panda et al. / Applied Catalysis A: General 433–434 (2012) 258–264
263
10 mol% CuFe2O4.
I
2 equiv. tBuOK
S
R
+
HSR
1,4-dioxane, reflux
24h
EtO
O
NH2
H
N
S
S
S
S
S
S
N
N
2a; 78%
2b; 85%
2e; 86%
2d; 88%
2c; 82%
COOH
S
S
S
S
S
COOH
OCH3
CH3
1e;, 60%
2g; 80%
2f; 40%
1j;, 80%
1g; 60%
Scheme 2. Cross-coupling of thiols with iodobenzene. Reaction conditions: 0.90 mmol of thiol, 1.80 mmol of iodobenzene, 10 mol% of CuFe2O4, 2.0 equ. of tBuOK, 5 mL of
1,4-dioxane, 24 h reflux under N2 atmosphere.
Table 4
N
Reusability and leaching experiment over multiple run.
O
N
Cycle
Recovered
CuFe2O4 (%)
Yield of 1a (%)
Cu leakage
(in ppm)
Fe leakage
(in ppm)
N
N
OH
N
N
Cl
1
2
3
4
5
–
95
93
93
92
90
0.25
0.22
0.20
0.06
0.05
0.08
0.02
0.02
0.01
0.01
96
95
95
94
S
S
Clothiapine (4)
Quetiapine (3)
R
H
N
S
S
N
OEt
C S and C N coupling was further extended for the synthesis
of other dibenzothiazepines such as 8 and 11 in moderate yield
(Scheme 3).
N
O
N
O
HOHNOC
5
O
5; R = OMe, Cl
6
4. Recovery and reusability of the catalyst
Fig. 5. Some biologically potent dibenzo-fused thiazepines.
After completion of the cross-coupling reaction of thiophenol
with 4-iodoacetophenone, the catalyst was separated quantita-
tively (>95%) by using a magnetic separator and washed with ethyl
acetate followed by distilled water and acetone. Then, it was dried
in hot air oven at 150 ◦C for 2 h and reused for the cross-coupling
of thiophenol with 4-iodoacetophenone under our optimized reac-
tion conditions. The catalytic behavior of CuFe2O4 was found to be
unaltered (up to five consecutive cycles) with negligible leaching
of Fe and Cu to the reaction medium (Table 4). The weight per-
centage of copper and iron in the recovered catalyst was measured
to be 4.08 mmol/g and 8.21 mmol/g, respectively (from ICP-MS). It
was found from the XRD pattern of the recovered catalyst (Fig. 1b)
that although there is no change in phase but the crystallite size
increases from 9 nm to 27 nm. As a result of which the saturation
magnetization (Ms) at room temperature (Fig. 4b) increases from
23 emu g−1 to 32 emu g−1. This increase in Ms could be attributed
to the partial agglomeration of nanoparticles during catalytic reac-
tion [54]. The SEM image (inset Fig. 2a) of the recovered catalyst
shows that the morphology as well as the dispersity of the catalyst
is not affected even after the successful catalytic cycles.
conditions, tricyclic dibenzo[b,f][1,4]thiazepine (7) was resulted in
moderate (65%). Encouraged by this interesting result, we insisted
to synthesize functionalized dibenzothiazepines (e.g. dibenzoth-
iazepinones). Thus, when methyl 2-iodobenzoate was employed,
methyl 2-(2-aminophenylthio)benzoate (9) was obtained as the
major product (86%) and traces of dibenzothiazepine-11-one (10,
from TLC). However, on heating 9 at 135 ◦C in acetic acid we got
quantitative yield of the desired product 10 (72%). In order to access
10 directly from 2-aminothiophenol and ethyl 2-iodobenzoate,
reaction mixture was heated under reflux in DMF for 24 h during
which moderated yield (60%) was obtained. Scope of the tandem
S
Cl
R
CHO
Br
N
7; R = H, 65%
8; R = Cl, 59%
SH
NH2
5. Conclusion
CO2Me
R
R
S
CO2Me
I
R
S
We have synthesized mesoporous copper ferrite nanoparticles
with a size of 55 5 nm by thermal decomposition method. Syn-
thesized CuFe2O4 nanoparticles were found to be efficient for the
S-arylation reactions under ligand-free conditions whereas other
ferrite nanoparticles were found to be ineffective. Our protocol was
found to be tolerant to the cross-coupling of thiols with halides
having different functional groups. Scope of this methodology has
been extended to the one pot synthesis of dibenzothiazepines for
N
H
NH2
O
10; R = H, 60%
11; R = Cl, 53%
9; R = H (86%)
Scheme 3. Synthesis of dibenzothiazepines. Reaction conditions: 0.90 mmol of o-
aminothiol, 1.80 mmol of halide, 10 mol% of CuFe2O4, 2.0 equ. of tBuOK, 24 h reflux
under N2 atmosphere.

264
N. Panda et al. / Applied Catalysis A: General 433–434 (2012) 258–264
the first time. The magnetic nature of CuFe2O4 nanoparticles offers
an advantage for easy, quick and quantitative separation of the het-
erogeneous catalyst from the reaction mixture. The use of CuFe2O4
nanoparticles for above cross-coupling reactions is found to be eco-
nomic. Furthermore, the negligible leaching of Fe and Cu to reaction
medium makes the reaction environmentally safe and thus may be
adopted by the industries for large-scale syntheses.
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