Recyclable superparamagnetic Fe3O4 nanoparticles for efficient catalysis of thiolysis of epoxides

Article abstract of DOI:10.1016/j.molcata.2012.05.004

An efficient and rapid procedure is developed for room-temperature ring opening of various epoxides with thiols under solvent-free conditions in the presence of catalytic amount of superparamagnetic Fe₃O₄ nanoparticles. As a result,

Full text of DOI:10.1016/j.molcata.2012.05.004

Journal of Molecular Catalysis A: Chemical 361–362 (2012) 68–71
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Recyclable superparamagnetic Fe3O4 nanoparticles for efficient catalysis of
thiolysis of epoxides
Mohammad M. Mojtahedi∗, M. Saeed Abaee∗, Azam Rajabi, Peyman Mahmoodi, Saeed Bagherpoor
Chemistry and Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and rapid procedure is developed for room-temperature ring opening of various epoxides
with thiols under solvent-free conditions in the presence of catalytic amount of superparamagnetic Fe3O4
nanoparticles. As a result, high conversion of reactants to various ␤-hydroxy sulfides is observed in short
time periods while the heterogeneous catalyst could be recovered and reused over several cycles without
loosing its activity. Competitive reactions show higher reactivity of aromatic thiols over the aliphatic
counterparts.
Received 21 February 2012
Received in revised form 1 May 2012
Accepted 2 May 2012
Available online 10 May 2012
Keywords:
© 2012 Elsevier B.V. All rights reserved.
Superparamagnetic
Nanocatalysis
Thiolysis
Epoxides
Green chemistry
1. Introduction
make heterogeneous systems more attractive from environmental
point of view [21,22]. In this context, heterogeneous catalysis using
Nucleophilic ring opening of epoxides with thiols is a very fre-
quently used reaction in synthetic organic chemistry and has found
many applications in total synthesis of pharmaceutical [1–3] and
natural [4,5] products, especially in the preparation of leukotrienes
[6]. The reaction leads to the synthesis of ␤-hydroxy sulfides for
which many synthetic procedures involving thiolysis of epoxides is
reported using various methods such as Lewis acid mediation [7–9],
aqueous conditions [10–13], heterogeneous catalysis [14,15], and
non-conventional bases [16,17]. However, in many of the available
methods, the process is performed in a solvent and in the presence
of stoichiometric amounts of a Lewis acid or an additive.
Lewis acid catalysis is of fundamental importance in modern
synthetic organic chemistry due to allowing efficient intercon-
version of various functional groups [18]. However, complete
decomposition of the catalysts and production of environmentally
harmful inorganic salts at workup stage are the drawbacks asso-
ciated with the use of conventional homogeneous Lewis acids. In
contrast, heterogeneous catalysts have been employed extensively
in recent years to boost many synthetic transformations in organic
chemistry [19,20], since they avoid such limitations, require easier
experimental procedures, and involve milder reaction conditions.
In addition, minimal waste disposal and reusability of catalysts
magnetic particles has witnessed a rapid growth in recent years,
due to finding numerous applications in nanocatalysis [23–25],
biotechnology [26], and medicine [27]. Moreover, the magnetic
property of such particles facilitates quantitative recycling of the
catalyst by applying an external magnetic field [28].
Recently, we presented an efficient protocol for rapid room-
temperature protection of alcohols and phenols with HMDS using
superparamagnetic Fe3O4 particles [29]. We then reported the
application of the method in the multi-component Strecker reac-
tion [30]. In these procedures, after completion of the reactions, the
catalyst could be recovered several times using an external mag-
net and efficiently reused in next reactions, while use of no other
additive or co-catalyst was required. In the framework of our stud-
ies on the development of green synthetic procedures [31,32] and
in continuation of our previous experiences on ring opening reac-
tions of epoxides [33,34], we would like here to report an efficient
and novel method for thiolysis of various epoxide rings using cat-
alytic quantities of a magnetically recoverable nanocatalyst while
no other additive or solvent is employed (Scheme 1).
2. Experimental
2.1. General
All reported yields are based on isolated compounds. Melting
points were determined with a Buchi melting point apparatus and
are uncorrected. TLC separations were carried out on silica gel
∗
Corresponding authors. Tel.: +98 21 44580749; fax: +98 21 44580785.
E-mail addresses: mojtahedi@ccerci.ac.ir (M.M. Mojtahedi), abaee@ccerci.ac.ir
(M.S. Abaee).
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2012.05.004

M.M. Mojtahedi et al. / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 68–71
69
Table 1
OH
Fe3O4 catalyzed thiolysis of epoxides 1.
Fe3O4 (10 mol%)
r.t., 10-60 min
R
O
R
+
R'SH
Entry
Epoxide
Thiol
Product
Time (min)
Yield%a
SR'
2a
2b
: R' = C6H5
: R' = 4-ClC6H4
2c: R' = 4-MeC6H4
2d: R' = naphthyl
: R' = C6H5CH2
3
1a
1b
1c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1a
1a
1a
1a
1b
1b
1b
1b
1c
1c
1c
1d
1d
1d
1e
1e
1f
2a
2b
2c
2d
2a
2b
2c
2d
2a
2b
2c
2a
2b
2c
2a
2b
2a
2b
2c
2e
2f
3aa
3ab
3ac
3ad
3ba
3bb
3bc
3bd
3ca
3cb
3cc
3da
3db
3dc
3ea
3eb
3fa
10
10
20
20
15
15
20
20
20
20
20
15
15
20
15
20
15
20
20
60
60
60
98
93
94
96
89
90
75
79
86
90
65
88
87
65
89
85
93
94
81
25
20
<5
: R = PhO
: i-PrO
: n-BuO
1d
: CH2=CHCH2O
1e: Cl
1f: cyclohexene oxide
2e
2f
2g
: R' = 2-furylCH2
: R' = n-octyl
Scheme 1.
plates with UV indicator; visualization was by UV fluorescence or
by staining with iodine vapor. IR spectra were recorded on a FT-IR
Bruker Vector 22 infrared spectrophotometer using KBr disks. NMR
spectra were recorded on FT-NMR Bruker Ultra ShieldTM (500 MHz)
or Bruker AC 80 MHz as CDCl3 solutions with TMS as internal ref-
erence. GC–MS were obtained on a Fisons 8000 Trio instrument
at an ionization potential of 70 eV. XRD analyses were carried out
using a Bruker D8-advance over the 2Â range from 10◦ to 70◦, using
1f
1f
1a
1a
1a
3fb
3fc
3ae
3af
2g
3ag
a
˚
Isolated yields.
Cu radiation (ꢀ = 1.54060 A). Scanning election microphotographs
(SEM) were obtained on a Hitachi S-4160.
Fe3O4 (10 mol%)
r.t., 10 min
3aa
3aa
3ae
3af
(98%) +
(98%) +
(<5%) [>19:1]
(<5%) [>19:1]
1a
2a 2e
+
+
2.2. Materials
The Fe3O4 nanoparticles were prepared according to the known
procedure reported by Stroeve and co-workers [35] using FeCl2
and FeCl3 and analyzed using X-ray powder diffraction and scan-
ning election microscopy experiments. Epoxides 1a–f, thiols 2a–g,
FeCl2, and FeCl3 were purchased from Merck company and were
used as received. TLC and column chromatography experiments
were carried out using silica gel 60 (Merck, less than 0.063 mm) and
ethyl acetate/hexane mixtures (1:4) as the eluent. Solvents were
purchased from Merck company.
Fe3O4 (10 mol%)
r.t., 10 min
1a + 2a + 2f
Fe3O4 (10 mol%)
r.t., 10 min
3aa
3ag
(98%) +
(<5%) [>19:1]
1a
2a 2g
+
+
Fig. 1. Competitive thiolysis of epoxides.
similar conditions, the same epoxide reacted with other aromatic
thiols, including electron withdrawing- and electron releasing sub-
stituted derivatives (entries 2–4) to give more than 85% yields of
3ab–3ad within 10–20 min time periods.
2.3. Typical procedure
A mixture of 3.0 mmol epoxide, 3.0 mmol thiophenol and Fe3O4
(10 mol%) was stirred at room temperature for appropriate length
of time until TLC showed completion of the reaction. The mix-
ture was diluted with diethyl ether. A conventional permanent
magnet was applied externally on to the outside of the reaction
vessel to separate the solid catalyst from the solution. The ethereal
phase was washed with saturated solution of NaHCO3 and filtered
through a short Na2SO4 column. The solvent was removed under
reduced pressure and the product was purified using bulb-to-bulb
distillation or column chromatography over silica gel, if necessary.
The 1H NMR, IR, and GC–MS spectra of the products were obtained
and compared perfectly to those existing in the literature. The recy-
cled catalyst was rinsed with ether, dried in oven (50 ◦C for 2 h), and
reused in next reactions.
To evaluate the selectivity of the present procedure, we decided
at this point to conduct competitive reactions in order to find out
the relative reactivity of thiols for ring opening of epoxides under
the optimized conditions. The results depicted in Fig. 1 show that
treatment of epoxide 1a with an equimolar mixture of thiols 2a and
2e in the presence of the catalyst (10 mol%) leads to predominant
formation of product 3aa, while only trace quantities of the other
possible product (3ae) can be detected leaving 2e almost intact.
Similar results were observed when thiophenol was subjected to
react with benzylic type phenols 2f and 2g. These observations
illustrate that 1a is much more reactive towards aromatic thiols.
The outcome was next applied to the reactions of 1b with the
same thiols to obtain the respective products 3ba–3bd in short
3. Results and discussion
We first subjected 2-(phenoxymethyl)oxirane 1a to react with
thiophenol 2a in the presence of Fe3O4 to find the optimized con-
ditions. Experiment showed that catalytic quantities of the catalyst
(10 mol%) are enough for complete disappearance of the starting
materials in 10 min. Use of lower amounts of Fe3O4 only prolonged
the reaction time or lowered the yield of the reaction. Analysis of
the 1H NMR spectrum of the crude mixture showed the formation
of ␤-hydroxy sulfide 3aa as the sole product of the reaction (Table 1,
entry 1). This indicates that the nucleophilic attack of the thiol
occurs exclusively at the less hindered side of the epoxide. Under
Fig. 2. A typical reaction mixture in the absence or presence of a magnetic field.

70
M.M. Mojtahedi et al. / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 68–71
Table 2
100
80
60
40
20
0
Comparison of the present work with other related procedures for the synthesis of
3fa.
Conditions
Solvent used
Time
Yield%
Reference
Fe3O4
n-Bu3P
–
H2O
Et2O
H2O, CH2Cl2
Et2O
H2O, EtOAc
H2O, Et2O
H2O, Et2O
CH2Cl2
15 min
12 h
30 min
2 h
93a
72b
100b
93a
95a
80a
97a
95a
87a
–
[10]
[7]
[17]
[9]
[11]
[12]
[13]
[8]
Zn(ClO4)2·6H2O
Borax
K2CO3
12 h
␤-Cyclodextrin, 60 ◦
NaOH, MW (150 ◦C)
NaOH (30 ◦C)
LiNTf2
C
15 min
5 min
3 h
20 h
a
Isolated yield.
GC conversion.
b
1
2
3
4
5
6
Fig. 3. Efficient recovery of the catalyst.
OH
R'SH
time periods (entries 5–8). To further illustrate the applicability
of this procedure to other epoxides, we then subjected 1c and
1d to the same conditions to evaluate their reactions with thiols
2a–c. As a result, products 3ca–3cc (entries 9–11) and 3da–3dc
(entries 12–14) were obtained in high yields within comparable
time periods. Epoxide 1e also behaved equally well in reaction
with thiols 2a (entry 15) and 2b (entry 16). For ring opening of
cyclohexene oxide 1f with thiols 2a–c, formation of single prod-
ucts trans-2-(arylthio)cyclohexanols 3fa–3fc was noticed (entries
17–19) within 15–20 min. In all cases, sole formation of single
regioisomeric products was observed indicating the high selec-
tivity of the method. At the end of the reactions, mixtures were
diluted with Et2O and the solid catalyst was then separated from
R
SR'
Fe
O
3O4
Fe3O4
R
O
R
Fig. 5. Proposed mechanism.
the mixtures by applying a magnet on the exterior wall of the reac-
tion tubes. Under the conditions, the same reactions with aliphatic
thiols were much less efficient and gave lower quantities of the
respective products (entries 20–22).
After completion of the reactions, recovery of Fe3O4 from the
reaction mixtures was easily achieved by applying an external per-
manent magnet on the outside wall of the reaction tubes, as shown
in Fig. 2. Therefore, the products were isolated in good purity after
the volatile portions were removed under reduced pressure. Finally,
the recovered catalyst was reused successfully in six subsequent
reactions without significant loss of activity, as illustrated in Fig. 3.
The structure and the identity of the recovered catalyst were
compared with those of fresh Fe3O4 by their XRD patterns. The
results clearly show that the fresh catalyst (Fig. 4a) still maintains
its structure after several recycles (Fig. 4b). In addition, the SEM
micrographs of the catalyst show no much particle size difference
before (Fig. 4c) and after (Fig. 4d) recycling.
Based on the above results, a pathway can be offered for the
reaction (Fig. 5) where Fe3O4 is continuously recovered and reused
throughout the course of the process. This hypothesis is supported
by successful recovery of the catalyst via a simple filtration and
its direct reuse for six times in a row without noticeable loss of
activity. This is also verified by the fact that the catalyst maintains
its structure after recovery, as seen in Fig. 4.
4. Conclusion
In conclusion, we presented a very efficient methodology for
rapid ring opening of epoxides with different thiols at room-
temperature. Use of catalytic amounts of magnetic Fe3O4 in the
presence of no extra additive or solvent, easy recovery of the
Fig. 4. XRD spectrum of fresh catalyst (a). XRD spectrum of recycled catalyst (b).
SEM pattern of fresh catalyst (c). SEM pattern of recycled catalyst (d).

M.M. Mojtahedi et al. / Journal of Molecular Catalysis A: Chemical 361–362 (2012) 68–71
71
catalyst, high region- and chemoselectivity of the protocol, and
environmental safety of the reactions are among the advantages
of the present method. We are currently working on the applica-
tion of this catalyst in other synthetic organic transformations. We
believe that Fe3O4 can also find applications in industrial processes
where the catalyst can be used over several cycles in a continuous
manner while the products are discharged after each cycle and the
reactor is charged with reactants each time. We can reach at a better
conclusion by comparing the performance of the present method
with those of other methodologies available in the literature, as
summarized in Table 2 for product 3fa.
[9] F. Fringuelli, F. Pizzo, S. Tortoioli, L. Vaccaro, Tetrahedron Lett. 44 (2003)
6785–6787.
[10] R.-H. Fan, X.-L. Hou, J. Org. Chem. 68 (2002) 726–730.
[11] M.S. Reddy, B. Srinivas, R. Sridhar, M. Narender, K.R. Rao, J. Mol. Catal. A: Chem.
255 (2006) 180–183.
[12] V. Pironti, S. Colonna, Green Chem. 7 (2005) 43–45.
[13] F. Fringuelli, F. Pizzo, S. Tortoioli, L. Vaccaro, Green Chem. 5 (2003) 436–440.
[14] V. Polshettiwar, M.P. Kaushik, Catal. Commun. 5 (2004) 515–518.
[15] J. Sun, F. Yuan, M. Yang, Y. Pan, C. Zhu, Tetrahedron Lett. 50 (2009) 548–551.
[16] W. Guo, J. Chen, D. Wu, J. Ding, F. Chen, H. Wu, Tetrahedron 65 (2009)
5240–5243.
[17] P. Gao, P.-F. Xu, H. Zhai, Tetrahedron Lett. 49 (2008) 6536–6538.
[18] A. Corma, H. Garcia, Chem. Rev. 103 (2003) 4307–4365.
[19] J.E. Mondloch, E. Bayram, R.G. Finke, J. Mol. Catal. A: Chem. 355 (2012) 1–38.
[20] L. Ronchin, A. Vavasori, L. Toniolo, J. Mol. Catal. A: Chem. 355 (2012) 134–141.
[21] V. Polshettiwar, R.S. Varma, Green Chem. 12 (2010) 743–754.
[22] S.M. Coman, G. Pop, C. Stere, V.I. Parvulescu, J. El Haskouri, D. Beltrán, P. Amorós,
J. Catal. 251 (2007) 388–399.
Acknowledgement
[23] A.-H. Lu, E.L. Salabas, F. Schüth, Angew. Chem. Int. Ed. 46 (2007) 1222–1244.
[24] C.W. Lim, I.S. Lee, Nano Today 5 (2010) 412–434.
[25] V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M. Bouhrara, J.-M. Basset, Chem. Rev.
111 (2011) 3036–3075.
Authors would like to thank Iran National Science Foundation
(INSF-88002468) for financial support of this work.
[26] A.K. Gupta, M. Gupta, Biomaterials 26 (2005) 3995–4021.
[27] M. Mahmoudi, H. Hosseinkhani, M. Hosseinkhani, S. Boutry, A. Simchi, W.S.
Journeay, K. Subramani, S. Laurent, Chem. Rev. 111 (2011) 253–280.
[28] M. Kawamura, K. Sato, Chem. Commun. (2006) 4718–4719.
[29] M.M. Mojtahedi, M.S. Abaee, M. Eghtedari, Appl. Organomet. Chem. 22 (2008)
529–532.
[30] M.M. Mojtahedi, M.S. Abaee, T. Alishiri, Tetrahedron Lett. 50 (2009) 2322–2325.
[31] M.S. Abaee, M.M. Mojtahedi, S. Forghani, N.M. Ghandchi, M. Forouzani, R. Shar-
ifi, B. Chaharnazm, J. Braz. Chem. Soc. 20 (2009) 1895–1900.
[32] M.M. Mojtahedi, M. Javadpour, M.S. Abaee, Ultrason. Sonochem. 15 (2008)
828–832.
References
[1] F. Viola, G. Balliano, P. Milla, L. Cattel, F. Rocco, M. Ceruti, Bioorg. Med. Chem. 8
(2000) 223–232.
[2] A. Conchillo, F. Camps, A. Messeguer, J. Org. Chem. 55 (1990) 1728–1735.
[3] I.A. Dotsenko, M. Curtis, N.M. Samoshina, V.V. Samoshin, Tetrahedron 67 (2011)
7470–7478.
[4] S. Hammarström, B. Samuelsson, D.A. Clark, G. Goto, A. Marfat, C. Mioskowski,
E.J. Corey, Biochem. Biophys. Res. Commun. 92 (1980) 946–953.
[5] J.R. Luly, N. Yi, J. Soderquist, H. Stein, J. Cohen, T.J. Perun, J.J. Plattner, J. Med.
Chem. 30 (1987) 1609–1616.
[6] E.J. Corey, D.A. Clark, A. Marfat, G. Goto, Tetrahedron Lett. 21 (1980) 3143–3146.
[7] Shivani, A.K. Chakraborti, J. Mol. Catal. A: Chem. 263 (2007) 137–142.
[8] J. Cossy, V.R. Bellosta, C. Hamoir, J.-R. Desmurs, Tetrahedron Lett. 43 (2002)
7083–7086.
[33] M.S. Abaee, M.M. Mojtahedi, H. Abbasi, E.R. Fatemi, Synth. Commun. 38 (2008)
282–289.
[34] M.S. Abaee, V. Hamidi, M.M. Mojtahedi, Ultrason. Sonochem. 15 (2008)
823–827.
[35] Y.S. Kang, S. Risbud, J.F. Rabolt, P. Stroeve, Chem. Mater. 8 (1996) 2209–2211.