Copper-catalyzed direct preparation of diaryl sulfides from aryl iodides using potassium thiocyanate as a sulfur transfer reagent

Article abstract of DOI:10.1016/j.tetlet.2011.06.107

A method for direct preparation of diaryl sulfides from aryl iodides using potassium thiocyanate as a sulfur-transfer agent is reported. A catalyst system comprising of a simple copper salt, tetrabutylammonium bromide as a phase-transfer agent and water as the solvent is used. Microwave heating at 200 °C for 60 min allows for the conversion of a range of aryl iodides to the corresponding diaryl sulfides.

Full text of DOI:10.1016/j.tetlet.2011.06.107

Tetrahedron Letters 52 (2011) 4587–4589
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Copper-catalyzed direct preparation of diaryl sulfides from aryl iodides
using potassium thiocyanate as a sulfur transfer reagent
⇑
Christopher B. Kelly, Christopher (Xiang) Lee, Nicholas E. Leadbeater
Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269-3060, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A method for direct preparation of diaryl sulfides from aryl iodides using potassium thiocyanate as a sul-
fur-transfer agent is reported. A catalyst system comprising of a simple copper salt, tetrabutylammonium
bromide as a phase-transfer agent and water as the solvent is used. Microwave heating at 200 °C for
60 min allows for the conversion of a range of aryl iodides to the corresponding diaryl sulfides.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 4 May 2011
Revised 21 June 2011
Accepted 28 June 2011
Available online 2 July 2011
Keywords:
Copper
Diaryl sulfides
Aryl halides
Potassium thiocyanate
Water
Transition metal catalyzed carbon-heteroatom bond-forming
reactions have proven to be very versatile in the preparation of a
range of key compounds.1,2 A review of the literature shows that,
compared to C–O and C–N bond-forming reactions, couplings
involving sulfur are far less prevalent.3 This is due, at least in part,
to the fact that sulfur compounds can often poison transition-
metal complexes through irreversible ligation. Indeed, immobilized
thiols are often used as post-reaction scavengers for a number of
transition metal-mediated reactions. This being said, there are a
number of routes to diaryl and aryl–alkyl thiols4 involving the
use of copper,5 palladium,6 or nickel complexes.7 The majority of
these routes involve coupling of a thiol with an aryl halide in an
Ullmann-like reaction. Here we report a methodology for the prep-
aration of symmetrical diaryl sulfides from aryl iodides using KSCN
as the source of the sulfur bridging atom, copper(I) oxide as the
catalyst, and water as the solvent.
In our laboratory we have become interested in developing
methods for performing metal-mediated carbon-heteroatom bond
forming reactions using a range of nucleophilic coupling partners.
These include K4Fe(CN)6 and Cu2Fe(CN)6 for cyanation,8,9 water for
formation of phenols10 and phenoxides and alkoxides for the syn-
thesis of aryl ethers.9 Most recently, our attention has turned to the
reaction chemistry of thiocyanates with aryl halides. Aryl thiocya-
nates are versatile starting materials for a range of sulfur-contain-
ing compounds, particularly heterocycles. Suzuki and Abe reported
a methodology for conversion of aryl iodides to the corresponding
thiocyanates using the cuprate complex K[Cu(SCN)2], prepared in-
situ from CuSCN and KSCN.14 The reaction is performed in DMF and
requires stoichiometric quantities of the cuprate complex.
Our starting point was to screen reaction conditions that built
upon our work with other nucleophilic coupling partners. To this
end, we decided to focus attention on the use of water as a solvent,
tetrabutylammonium bromide (TBAB) as phase-transfer agent,
and simple copper salts as the catalyst in conjunction with KSCN
as the thiocyanate source. Using a scientific microwave unit as a
convenient heating tool, 4-iodotoluene as a test substrate, and
performing the reaction at 170 °C in a sealed vessel employing a
stoichiometric quantity of CuI and 2 equiv KSCN we observed a
25% conversion to the corresponding thiocyanate after 20 min.
We also observed a small quantity of di-p-tolyl sulfide (1) formed
as a byproduct (Scheme 1). Further assessment of copper salts and
reaction conditions showed us that the formation of the diaryl sul-
fide was more favorable than that of the corresponding aryl thiocy-
anate, especially when using Cu2O. This interested us in light of the
very recent report by Zhou and co-workers who have shown that
when using CuCl2 as a catalyst, 1,10-phenanthroline as ligand, tet-
rabutylammonium fluoride (TBAF) as additive and cesium carbon-
ate as base, it is possible to perform copper-catalyzed C–S bond
formation between aryl halides and potassium thiocyanate leading
to diaryl sulfides.11 Reactions were performed at 130 °C for 48 h.
Our attention therefore turned to developing a more expedient
and simple route to symmetrical diaryl sulfides.
Using 4-iodotoluene as the substrate and employing a stoichi-
ometric quantity of copper(I) oxide and 2 equiv KSCN, we were
able to generate 1 in 88% conversion (Table 1, entry 1). Interesting,
⇑
Corresponding author. Tel.: +1 860 617 3518; fax: +1 860 486 2981.
E-mail address: nicholas.leadbeater@uconn.edu (N.E. Leadbeater).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.06.107

4588
C. B. Kelly et al. / Tetrahedron Letters 52 (2011) 4587–4589
S
Table 2
SCN
+
I
MW, 170 oC, 30 min
Cu2O, TBAB, H2
Copper-catalyzed preparation of diaryl sulfides from aryl halidesa
+
KSCN
O
S
I
1
MW
+
KSCN
Cu2O, TBAB, H2
O
Scheme 1.
R
R
R
Entry
Aryl halide
Yield (%)b
Zhou and coworkers reported that copper(I) oxide was an ineffec-
tive catalyst for diaryl sulfide formation but under our conditions it
performs better than all other copper salts screened. The reaction
required heating to 200 °C for 1 h using water as the solvent and
1 equiv TBAB as the phase-transfer agent. Increasing the quantity
of KSCN to 2.5 equiv while keeping all other conditions the same
led to a quantitative conversion to 1 (Table 1, entry 2). Our next
objective was to reduce the quantity of Cu2O required, turning
the process from stoichiometric to catalytic in copper. We found
that we could reduce the loading to 30 mol % without a deleterious
effect on product conversion (Table 1, entry 3). At catalyst loadings
below 30 mol %, a significant drop in conversion was observed
(Table 1, entries 4 and 5). We were also able to reduce the quantity
of TBAB required to 30 mol % (Table 1, entry 6). Interestingly, addi-
tion of a base (Cs2CO3) which was deemed essential by Zhou and
co-workers in their methodology,11 led to competitive formation
of 4-methylphenol in our case (Table 1, entry 7). Attempts to per-
form the reaction using either aqueous acetonitrile or polar aprotic
organic solvents were either less successful or else yielded no
product (Table 1, entries 8–10), showing that water was the opti-
mal solvent. Therefore, our optimized conditions were: Cu2O
(30 mol %) as catalyst, KSCN (2.5 equiv), 30 mol % TBAB as phase-
transfer agent, water as solvent, heating at 200 °C for 60 min. As
was the case with our methodologies for cyanation of aryl halides,
we found here that, while we observed high conversions to 1, the
method used to isolate the product was critical to obtaining good
yields. Our optimized work-up used ethyl acetate as solvent in
an aqueous-organic extraction, this leading to a 75% yield of 1
(Table 1, entry 11).
1
2
75 (48)c
65
I
OMe
I
CF3
3
4
5
60
63
61
I
F
I
COMe
I
I
6
60
7
8
58
56
I
I
I
9
trace
40d
36
N
10
11
Br
OMe
Br
a
Reactions were performed on the 1 mmol scale using 30 mol % Cu2O as catalyst,
2.5 equiv KSCN as sulfur source, 30 mol % TBAB as phase-transfer agent and 1 mL
water as solvent. Reaction mixture was heated to 200 °C for 60 min.
Determined using 1H NMR spectroscopy by comparison with an internal
b
With optimized conditions in hand, we next screened a repre-
sentative range of aryl halide substrates.12,13 The results are shown
in Table 2. The aryl iodides screened could be converted to the
corresponding diaryl sulfides in good yields (Table 2, entries 1–8).
standard.
c
Isolated yield.
Product conversion.
d
An exception was 3-iodopyridine where only a trace of the desired
product was formed (Table 2, entry 9). Extending the methodology
to aryl bromides was not as successful as with the corresponding
aryl iodides (Table 2, entries 10 and 11).
Table 1
Optimization of conditions for the direct conversion of 4-iodotoluene to di-p-tolyl
sulfide, 1
S
I
MW
+
KSCN
In conclusion, we present here a methodology for a direct and
rapid preparation of diaryl sulfides from aryl iodides using potas-
sium thiocyanate as the source of sulfur. The work complements
the very recent report by Zhou and co-workers,11 advantages of
our approach being substantially shorter times (1 h rather than
48 h), no need for added base or ligand and the use of a sub-
stoichiometric quantity of TBAB as opposed to its more aggressive
fluoride analog. Our catalyst system comprises a simple copper salt
and heating at 200 °C for 60 min allows for the conversion of a
range of aryl iodides to the corresponding dialkyl sulfides.
Cu2O, TBAB, H2
O
1
Entry Reaction conditionsa,b
Conv
(%)c
1
2
3
4
5
6
7
1 equiv Cu2O, 2 equiv KSCN, 1 equiv TBAB, water
1 equiv Cu2O, 2.5 equiv KSCN, 1 equiv TBAB, water
30 mol % Cu2O, 2.5 equiv KSCN, 1 equiv TBAB, water
20 mol % Cu2O, 2.5 equiv KSCN, 1 equiv TBAB, water
10 mol % Cu2O, 2.5 equiv KSCN, 1 equiv TBAB, water
30 mol % Cu2O, 2.5 equiv KSCN, 30 mol % TBAB, water
30 mol % Cu2O, 2.5 equiv KSCN, 30 mol % TBAB, 1 equiv
Cs2CO3, water
88
100
100
63
55
100
0
8
9
30 mol % Cu2O, 2.5 equiv KSCN, 30 mol % TBAB, 9:1
acetontrile/water
33
0
Acknowledgments
30 mol % Cu2O, 2.5 equiv KSCN, 30 mol % TBAB,
acetonitrile
This work was funded by the National Science Foundation
(CAREER award CHE-0847262). The authors thank CEM Corp. for
microwave equipment support. Michael Mercadante is thanked
for assistance.
10
11
30 mol % Cu2O, 2.5 equiv KSCN, 30 mol % TBAB, NMPd
30 mol % Cu2O, 2.5 equiv KSCN, 30 mol % TBAB, water
0
75e
a
Conditions: reactions performed on the 1 mmol scale using 1 mL solvent.
Reaction mixture heated to target temperature and held for 60 min.
b
For clarity, changes in reaction conditions from entry 1 are noted in bold.
References and notes
c
Determined using 1H NMR spectroscopy.
d
N-methyl-2-pyrrolidone.
Product yield.
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3054; (b) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003, 42, 5400; (c)
e

C. B. Kelly et al. / Tetrahedron Letters 52 (2011) 4587–4589
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tetrabutylammonium bromide (97 mg, 0.3 mmol), and water (1 mL). The
mixture was stirred for 1 min before sealing the tube with a septum and
placing the reaction mixture into the microwave cavity (CEM Discover). An
initial microwave power of 150 W was used, the temperature being ramped
from rt to 200 °C where it was held for 60 min (caution: The water is heated
well above its boiling point so all necessary precautions should be taken when
performing such experiments. Vessels designed to withhold elevated pressures
must be used. The microwave apparatus used here incorporates a protective
metal cage around the microwave vessel in case of explosion. After completion
of an experiment, the vessel must be allowed to cool to a temperature below
the boiling point of the solvent before removal from the microwave cavity and
opening to the atmosphere.). The reaction mixture was stirred continuously
throughout. The reaction was run in triplicate. After allowing the three
identical reaction mixtures to cool to rt, the vessels were opened and their
contents poured into a separatory funnel and the tubes washed three times
with ethyl acetate (approximately 3 mL each time) followed by two washes
with water (5 mL each time). All washings were added to the separatory funnel
along with an additional 20 mL of ethyl acetate. Typically an emulsion was
formed after shaking; therefore brine (approximately 5 mL) was added to aid
separation. The aqueous layer was extracted twice more with ethyl acetate
(approximately 30 mL each time). The organic washings were combined,
washed with deionized water (approximately 20 mL), collected, dried over
MgSO4, and then the ethyl acetate removed in vacuo. Purification was
accomplished by column chromatography (100% hexanes) affording the
product as a white solid (152 mg, 48%).1H NMR (CDCl3): d/ppm 7.22 (4H, d),
7.08 (4H, d), 2.37 (6H, s). 13C NMR (CDCl3): d/ppm 137.11, 132.97, 131.32,
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