Recyclable iron/graphite catalyst for c-s cross coupling of thiols with aryl halides under ligand-free conditions

Article abstract of DOI:10.1055/s-0029-1219801

A recyclable iron/graphite (Fe/Cg) catalyst for the efficient C-S cross-coupling of various iodoarenes with aromatic/aliphatic thiols has been developed under ligand-free conditions (26 examples, up to 99% yield). The catalyst can be easily recovered and recycled up to seven cycles without loss of activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1219801

1260
LETTER
Recyclable Iron/Graphite Catalyst for C–S Cross Coupling of Thiols with Aryl
Halides under Ligand-Free Conditions
Catalyst for C–S
C
i
ross
C
j
a
of Thiols
w
y
ith Aryl Halide
s
Kumar Akkilagunta, Vutukuri Prakash Reddy, Kakulapati Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500607, India
Fax +91(40)27160512; E-mail: kakulapatirama@gmail.com
Received 22 January 2010
er, the reaction in the presence of Fe(III)(acac)3 or graph-
Abstract: A recyclable iron/graphite (Fe/Cg) catalyst for the effi-
ite alone gave very low yields of the product (Table 1).
cient C–S cross-coupling of various iodoarenes with aromatic/
The bromo/chloro benzenes were also screened using the
aliphatic thiols has been developed under ligand-free conditions (26
same combination of solvent and base. Of all the iron cat-
alysts employed with various bases, solvents, and aryl
halides, Fe/Cg-catalyzed reaction of iodobenzene with
thiophenol using DMSO–KOH gave the best results
(Figure 1).
examples, up to 99% yield). The catalyst can be easily recovered
and recycled up to seven cycles without loss of activity.
Key words: arylhalides, cross-coupling, recyclable catalyst, iron,
thiols
Table 1 Optimization of Fe/Cg-Ccatalyzed Iodobenzene Reaction
Organosulfur compounds have wide applications in me-
dicinal and material chemistry. Their preparations are a
bit challenging owing to the deactivation of metal by sul-
fur due to its strong co-ordinating properties. Various
Metals viz. Pd,1 Cu,2 Ni,3 Co,4 La,5 etc. are all well ex-
plored for C–S bond formation and the very recent devel-
opment of iron-catalyzed sustainable reactions has drawn
the attention of the scientific community.6 Though C–S
cross-coupling of aryl halides with thiols employing iron
catalysts are reported,7 none of these are recyclable and
apart from this the recent ones using phosphine ligands 8
makes these methods more expensive from the economic
point of view. Considering the above limitations, a recy-
clable protocol employing iron is highly desirable. There-
fore in continuation to our sustainable method
development program9 we present herein our recently in-
novated Fe/Cg10 catalyst for the C–S cross coupling of
various iodoarenes with aromatic/aliphatic thiols under
ligand-free conditions. Metals dispersed on graphite, viz.
M–graphite (M = K, Zn, Sn, Fe, Ti, Pd),11 are reported for
organic transformations, but their tedious preparation pro-
cedures limit their usage as catalysts. However, our iron–
graphite catalyst was prepared via simple easy-to-handle
procedure in which, Fe(III)(acac)3 was dispersed on
graphite simply by stirring in THF solution under nitrogen
atmosphere. The amount of iron was found to be 4.3% on
graphite by ICP-AES analysis.12 The catalytic perfor-
mance of Fe/Cg along with various iron catalysts like Fe/
C, nano Fe3O4, and nano Fe2O3 was screened for the thio-
etherification of iodobenzene and thiophenol as model
reaction, in combination with various bases like Na2CO3,
K2CO3, K3PO4, etc. and solvents toluene, 1,4-dioxane,
DMSO, DMF, etc. for the catalyst, base, and solvent opti-
mization (as summarized in Table 1). The best combina-
tion turned out to be DMSO as solvent and KOH as the
base for the optimum yields obtained (Figure 1). Howev-
with Thiophenola
I
+
SH
S
1a
2a
3a
Entry Fe catalyst Base
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
Temp (°C) Yield (%)
1
2
Fe/Cg
Fe/Cg
Fe/Cg
Fe/Cg
Fe/Cg
Fe/Cg
Fe/Cg
Fe/C
Cs2CO3
125
125
125
125
125
125
125
125
125
125
125
125
125
125
125
125
52
K3PO4
K2CO3
KOt-Bu
Na2CO3
NaOH
KOH
56
3
traces
44
4
5
traces
86
6
7
99
8
KOH
69
9
nanoFe2O3 KOH
nanoFe3O4 KOH
72
10
11
12
13
14
15
16
51
Fe/Cg
KOH
KOH
KOH
KOH
KOH
KOH
toluene
dioxane
DMSO
DMSO
DMSO
DMSO
60
Fe/Cg
24
Fe/Cl3
traces
traces
8
Fe/Cl2
Fe(acac)3
graphite
5
a Reaction conditions: Fe/Cg (7 wt%, 162 mg), iodobenzene (1.2
mmol), thiophenol (1.0 mmol), solvent (1.5 mL), base (2.0 mmol),
under N2 atmosphere for 24 h.
SYNLETT 2010, No. 8, pp 1260–1264
x
x.
x
x.
2
0
1
0
Advanced online publication: 25.03.2010
DOI: 10.1055/s-0029-1219801; Art ID: G01610ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Catalyst for C–S Cross Coupling of Thiols with Aryl Halides
1261
Table 2 Fe/Cg-Catalyzed Coupling of Iodoarenes with Thiolsa
Entry
Iodoarene 1
Thiol 2
Product 3
Yield (%)b
S
I
SH
SH
1
98
67
3a
S
I
2
3
OMe
NO2
MeO
O2N
3b
S
I
I
SH
89
3c
S
SH
SH
SH
SH
SH
4
5
6
7
8
90
71
86
85
82c
3d
S
I
I
Cl
Br
Cl
Br
3e
S
3f
S
I
3g
SPh
I
PhS
3h
I
Ph
Ph
SH
SH
SH
SH
9
10
11
12
97
92
91
95
S
Ph
S
I
3i
4-BrPh
4-BrPh
Ph
I
3j
S
I
N
N
3k
S
I
S
S
3l
O
O
S
SH
I
NH
13
78
NH
N
O
N
O
H
H
3m
Synlett 2010, No. 8, 1260–1264 © Thieme Stuttgart · New York

1262
V. K. Akkilagunta et al.
LETTER
Table 2 Fe/Cg-Catalyzed Coupling of Iodoarenes with Thiolsa (continued)
Entry
14
Iodoarene 1
Thiol 2
Product 3
Yield (%)b
O
O
S
SH
I
NH
72
NH
N
H
O
N
O
H
3n
a Reaction conditions: Fe/Cg (7 wt%, 162 mg), iodoarene (1.2 mmol), thiol (1.0 mmol), DMSO (1.5 mL), KOH (2.0 mmol), 125 °C under
nitrogen atmosphere were stirred for 24 h.
b Isolated yield.
c Conditions: 2 equiv thiophenol.
yields. The reaction of thiophenol with electron-with-
drawing, electron-releasing para-substituted iodoarenes
afforded good yields of coupled partners (entries 2–6,
Table 2). The heteroarenes, iodouracils, and vinyl iodides
successfully cross-coupled in good to excellent yields (en-
tries 9–12) exemplifying the catalyst’s efficiency. We
have further put many aliphatic thiols to test the efficiency
of the catalyst in converting the aryl halides to coupled
products. This was summarized in Table 3 where many al-
iphatic thiols were successfully coupled to afford thioet-
hers in moderate to excellent yields. This reaction might
be proceeding by the activation of aryl halide by iron in
the layers of graphite which further reacts with the mer-
capto nucleophile as proposed by Nagai et al. in the case
of alkylation of phenols.15 Next, we studied recyclability
of the catalyst. The catalyst was easily separated by cen-
trifugation and washed with ethyl acetate followed by ac-
Figure 1
etone, then dried in a hot air oven at 80 °C and employed
Fe/Cg
R1I
R2SH
for the next reaction. It was observed to be recyclable up
to seven cycles without loss of activity (Figure 2). To
check whether any iron has leached into the solution dur-
ing the reaction, the supernatant after the reaction was
subjected to ICP-AES analysis and we found that 0.005%
of iron has leached into the reaction mixture. The XPS16
and IR spectral studies confirmed that Fe(acac)3 on graph-
ite is intact even after the seventh cycle.17 To rule out the
possibility that the reaction was catalyzed by traces of
copper impurities,18 we analyzed iron/graphite carefully
by XPS, EDX, and ICP analysis. The spectral analysis has
shown no signature of copper (934.5 eV binding-energy
curve in XPS was absent).
R1SR2
+
DMSO, KOH
125 °C, 24 h
Scheme 1 Fe/Cg-catalyzed cross-coupling
Thus the optimized reaction conditions for the desired C–
S cross-coupling were found to be 7 wt% (162 mg) 13 of
Fe/Cg, 2.0 equiv of KOH, 125 °C with DMSO (1.5 mL)
as solvent. The yields were higher with DMSO when
compared to other solvents such as DMF, toluene, and di-
oxane. The most probable explanation for the strong de-
pendence of the reaction on the solvent system, especially
DMSO, may be due to the formation of dimsyl ion in the
presence of KOH forming an equilibrium by proton ex-
change with RSH, leading to the formation of RS– thus ac-
celerating the reaction. The formation of dimsyl ion with
KOH and similar type of equilibrium with ROH is already
well established.14 A variety of bases were screened in
which NaOH and KOH provided the product in good to
excellent yields with KOH giving the maximum yield
(Table 1, entries 6 and 7), whereas the yields were moder-
ate with bases like Cs2O3, K3PO4, and KOt-Bu. With the
optimized conditions on hand, we have put a variety of
iodobenzenes to test viz. substituted iodoarenes, iodo-
uracils, vinyl iodides, heteroiodoarenes for thioetherifica-
tion. It can be seen from Table 2 that the reaction of these
iodobenzenes afforded aryl sulfides in excellent to good
Figure 2 Recyclability of Fe/Cg catalyst
Synlett 2010, No. 8, 1260–1264 © Thieme Stuttgart · New York

LETTER
Catalyst for C–S Cross Coupling of Thiols with Aryl Halides
1263
Table 3 Fe/Cg-Catalyzed Coupling of Iodoarenes with Thiolsa
Entry
Iodoarene 1
Thiol 2
Product 3
Yield (%)b
S
I
SH
1
91
84
3o
S
SH
I
I
2
3p
SPh
S
SH
SH
3
4
68
81
6
6
3q
I
I
I
3r
S
5
6
7
8
75
73
92
83
SH
3s
S
6
SH
6
3t
S
I
SH
SH
3u
3v
S
I
S
S
S
S
I
I
9
76
68
SH
3w
3x
3y
3z
C10H21
C16H33
C18H37
10
n-C10H21
n-C16H33
n-C18H37
I
I
11
12
61
58
a Reaction conditions: Fe/Cg (7 wt%, 162 mg), iodoarene (1.2 mmol), thiol (1.0 mmol), DMSO (1.5 mL), KOH (2.0 mmol), 125 °C under
nitrogen atmosphere were stirred for 24 h.
b Isolated yield.
Synlett 2010, No. 8, 1260–1264 © Thieme Stuttgart · New York

1264
V. K. Akkilagunta et al.
LETTER
(4) Wong, Y. C.; Jayanth, T. T.; Cheng, C. H. Org. Lett. 2006,
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ICP-AES and EDX analysis also showed no traces of Cu,
thus ruling out the possibility of traces of copper cata-
lyzing the reaction.
In conclusion we have developed a novel catalytic system
employing heterogeneous iron catalyst, which can be eas-
ily prepared from the readily available raw materials and
can be recycled up to seven cycles without loss of activity
for thioetherification reaction.19
(6) For recent reviews of iron catalysis, see: (a) Bolm, C.;
Legros, J.; Paih, J. L.; Zani, L. Chem. Rev. 2004, 104, 6217.
(b) Enthaler, S.; Junge, K.; Beller, M. Angew. Chem. Int. Ed.
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
(9) (a) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org.
Lett. 2009, 11, 951. (b) Reddy, V. P.; Kumar, A. V.;
Swapna, K.; Rao, K. R. Org. Lett. 2009, 11, 1697.
(c) Reddy, V. P.; Swapna, K.; Kumar, A. V.; Rao, K. R.
J. Org. Chem. 2009, 74, 3189. (d) Kumar, A. V.; Reddy,
V. P.; Sridhar, R.; Srinivas, B.; Rao, K. R. Synlett 2009, 739.
(e) Reddy, V. P.; Swapna, K.; Kumar, A. V.; Rao, K. R.
Synlett 2009, 2783. (f) Reddy, V. P.; Swapna, K.; Kumar,
A. V.; Rao, K. R. Tetrahedron Lett. 2010, 51, 293.
(10) Swapna, K.; Kumar, A. V.; Reddy, V. P.; Rao, K. R. J. Org.
Chem. 2009, 74, 7514.
(11) Savoia, D.; Trombini, C.; Ronchi, A. U. Pure Appl. Chem.
1985, 57, 1887; and the references cited therein.
(12) Procedure for the catalyst preparation, characterization can
be adopted from the experimental section in the Supporting
Information.
(13) Percentage weight with respect to iron (not mol%).
(14) Hunter, D. H.; Cram, D. J. J. Am. Chem. Soc. 1966, 88, 5765.
(15) Nagai, M.; Yoda, T.; Omi, S.; Kodomari, M. J. Catal. 2001,
201, 105.
(16) Surface Analysis by Auger and X-ray Photoelectron
Spectroscopy; Grant, J. T.; Briggs, D., Eds.; IM
Publications: Chichester, 2003.
We are grateful to UGC, New Delhi and CSIR, New Delhi for the
research fellowships to VKA and VPR, respectively.
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Fe/Cg (7 wt%, 162 mg) was added to a 25 mL flask, which
was previously charged with iodoarene (1.2 mmol), thiol
(1 mmol) and KOH (2.0 equiv). Dry DMSO (1.5 mL) was
added while purging the flask with nitrogen. The round-
bottom flask was purged once again and back filled with
nitrogen and heated in an oil bath at 125 °C for a period of
24 h after which the flask was removed from the oil bath and
allowed to come to r.t. Fe/Cg was removed by ultracentri-
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poured into H2O (5 mL), and the aqueous layer was extracted
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