One-pot synthesis of symmetrical and unsymmetrical aryl sulfides by Pd-catalyzed couplings of aryl halides and thioacetates

Article abstract of DOI:10.1021/jo2007253

Aryl sulfides were obtained from the coupling reaction of S-aryl (or S-alkyl) thioacetates and aryl bromides in the presence of palladium catalyst. This reaction method enables the one-pot synthesis of symmetrical and unsymmetrical diaryl sulfides by employing potassium thioacetate with aryl iodides and aryl bromides.

Full text of DOI:10.1021/jo2007253

FEATURED ARTICLE
pubs.acs.org/joc
One-Pot Synthesis of Symmetrical and Unsymmetrical Aryl Sulfides
by Pd-Catalyzed Couplings of Aryl Halides and Thioacetates
Namjin Park, Kyungho Park, Mihee Jang, and Sunwoo Lee*
Department of Chemistry, Institute of Basic Science, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju 500-757,
Republic of Korea
S Supporting Information
b
ABSTRACT: Aryl sulfides were obtained from the coupling
reaction of S-aryl (or S-alkyl) thioacetates and aryl bromides in
the presence of palladium catalyst. This reaction method enables
the one-pot synthesis of symmetrical and unsymmetrical diaryl
sulfides by employing potassium thioacetate with aryl iodides and
aryl bromides.
’ INTRODUCTION
Here, we report a simple, mild, functional group-tolerant
system for the synthesis of the symmetrical and unsymmetrical
aryl sulfides from potassium thioacetate (1a) with aryl halides
under thermal conditions. Considering the cost, potassium
thioacetate is an excellent sulfur surrogate.16
Palladium-catalyzed carbonꢀcarbon and carbonꢀheteroatom
bond formations are practical methods and have been widely
employed in organic synthesis.1 Among carbonꢀheteroatom
bond formations, carbonꢀnitrogen bond formations have been
extensively studied and developed for practical applications since
Buchwald and Hartwig independently developed the coupling
of aryl halides and amines.2 The analogous reactions form-
ing carbonꢀoxygen3 and carbonꢀsulfur4 bonds have also been
studied over the past decade. Aryl sulfides are important synthetic
intermediates often found in biologically and pharmaceutically
active compounds.5
Since Migita first reported the coupling reaction of aryl halides
with thiols in the presence of Pd(PPh3)4 as the catalyst and
NaOtBu as a base in polar solvent,6 palladium-,4 nickel-,7 copper-,8
cobalt-,9 indium-,10 and iron-based11 catalytic systems have been
studied for this purpose. In the case of the palladium catalytic
system, the development of an efficient ligand has been the main
research subject because ligands have played a key role in this
transformation.12 Among them, the Josiphos CyPF-tBu ligand
showed high turnover numbers and broad scope in this coupling
reaction.4cꢀf
Asa sourceofsulfurinthe CꢀSbondformation, the thiol group
has been most often employed in the coupling reaction of aryl
halides in the presence of transition-metal catalysts. However, the
direct use of thiols has intrinsic drawbacks due to their foul smell,
which could lead to a severe environmental problem and, thus,
place a ceiling on any large scale process. In addition, they are
prone to undergo oxidative homocoupling to produce disulfides as
byproducts. To solve these drawbacks, disulfides have been
employed,13 but these require a stoichiometric amount of reduc-
tant. Recently, thiourea14 and potassium thiocyanate15 have been
reported as a sulfur source in the CꢀS bond formation. However,
the former is limited to the aryl alkyl sulfide, and the latter requires
high temperature and long reaction time and, moreover, is limited
to aryl iodides. Therefore, the development of a foul-smell-free
method having a broad scope of aryl halides is needed.
’ RESULTS AND DISCUSSION
To reach our goal, first, we attempted to find the reaction
condition of the direct coupling reaction of thioacetate and aryl
halides. The protected thiols such as thiosilate,4c thiocyanate,17
and indium thiolate18 have been reported in the direct coupling
reaction with aryl halides. Lai reported the coupling reaction of
potassium thioacetate and aryl bromides to produce S-aryl thioa-
cetates under microwave conditions.19 However, there is no
example of the direct coupling reaction of acetyl-protected thiol.20
As a model reaction, phenyl thioacetate was chosen in the coupling
reaction of 4-bromotoluene. The screening for optimized condi-
tion was conducted with respect to the ligand, palladium source,
base, and solvent. The results were summarized in Table 1.
First, we screened a variety of ligands in the presence of strong
base such as NaOtBu which has been most frequently employed
in the CꢀS bond formation reactions. As expected, monodentate
phosphine showed very low yields (entries 1 and 2), and
chelating phosphine ligands afforded the desired product in
excellent yields (entries 3 and 4). It has been reported that
monodentate phosphine showed lower activity than bidentate
one in the palladium-catalyzed coupling reaction of thiol and
aryl halides.21 1,10-Bis(diphenylphosphino)ferrocene (dppf) was
chosen as the ligand after cost consideration.22 Evaluation of
palladium sources revealed that Pd(dba)2 is superior to all other
choices. To expand functional group tolerance of this Pd(dba)2/
dppf catalytic system, we next examined weak bases in this model
coupling reaction. Among the bases screened, K3PO4 showed
better yields than other weak bases such as Na2CO3, K2CO3,
Received: April 6, 2011
Published: May 06, 2011
r
2011 American Chemical Society
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|

The Journal of Organic Chemistry
FEATURED ARTICLE
Table 1. Optimization of the Direct CꢀS Coupling of
S-Phenyl Thioacetate and 4-Bromotoluenea
Table 2. Role of Ketone in the Direct CꢀS Coupling of
S-Phenyl Thioacetate and 4-Bromotoluenea
entry
Pd
Pd(dba)2
ligand
base
convb (%) yieldb (%)
entry
ketone
acetone
amount
convb (%)
yieldb (%)
BiphPtBu2 NaOtBu
BiphPCy2 NaOtBu
Xantphose NaOtBu
5
2
0
0
c
1
1
2c
3
4
5
6
7
0.3 mL
0.3 mL
0.1 mL
1.0 mL
0.3 mL
0.3 mL
3.0 mmol
100
3
97
0
d
2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(OAc)2
acetone
3
98
100
100
72
60
72
52
56
48
10
0
95
97
94
65
52
68
45
34
42
7
acetone
62
56
97
94
89
88
4
dppf
dppf
NaOtBu
NaOtBu
NaOtBu
NaOtBu
K3PO4
Na2CO3
K2CO3
Cs2CO3
Et3N
acetone
100
100
95
5
methyl ethyl ketone
cyclohexanone
benzophenone
6
Pd(CH3CN)2Cl2 dppf
7
Pd(acac)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
dppf
dppf
dppf
dppf
dppf
dppf
dppf
dppf
dppf
dppf
97
8
a Reaction conditions: S-phenyl thioacetate (0.3 mmol), 4-bromo-
toulene (0.3 mmol), Pd(dba)2 (0.015 mmol), 1,10-bis(diphenyl-
phosphino)ferrocene (0.021 mmol), K3PO4 (0.36 mmol), toluene
(0.6 mL), at 110 °C for 6 h in a screw cap vial. b Determined by GC
analysis with an internal standard of naphthalene. In the absence of
ligand.
9
10
11
12
c
13f Pd(dba)2
14g Pd(dba)2
15h Pd(dba)2
16i Pd(dba)2
K3PO4
K3PO4
KOH
0
0
0
0
0
thioacetate, we then proceeded to test the scope and limitations
of a variety of thioacetates and aryl bromides. The results are
summarized in Table 3. Aryl bromides bearing an electron-
donating group such as methyl and methoxy, afforded the
corresponding diaryl sulfides in good yields (entries 1ꢀ3).
Sterically hindered substrates such as 2-bromobiphenyl produced
the desired product in 72% yield (entry 4). 4-Bromobenzaldehyde
and 2-bromopyridine showed 62% and 82% yields, respectively
(entries 5 and 6). S-4-Methoxyphenyl thioacetate (1c) reacted
with 2-bromoanisole to produce the corresponding diaryl sulfide
in 67% yield. When S-alkyl thioacetates were employed, all
thioacetates were coupled with aryl bromides to form alkyl aryl
sulfides in high yields. In particular, cynano-substituted thioace-
tates (1f) afforded the coupled products in 81% yield (entry 13),
and the benzyl- and tert-butyl-substituted thioacetates showed
good yields (entries 14 and 15).
Wefound that4-iodoanisole reacted with potassium thioacetate
(1a) to produce only S-4-methoxylphenyl thioacetate at 70 °C,
even in the presence of bromobenzene, as shown in Scheme 1.19,26
This result suggests that this methodology can be applied for
the one-pot synthesis of unsymmetrical diaryl sulfide by varying
only the reaction temperature. The reactions were carried out in
the presence of equal amounts of aryl iodide, aryl bromide, and
potassium thioacetate at 70 °C for 3 h and stirred at 110 °C for 6 h.
Results are shown in Table 4.
We found that the electronic property of different substituents
on the aryl rings did not affect this coupling reaction very much, and
aryl halides bearing both electron-withdrawing groups and elec-
tron-donating groups worked well. In the case of 1-methoxy-
2-(phenylthio)benzene (5a and 5k) and 1-methoxy-3-(pheny-
lthio)benzene (5b and 5j), they could be obtained from both
iodobenzene andbromobenzene. Aryl halides bearingether, amine,
ketone, and ester groups afforded the corresponding products in
good yields. In addition, heteroaryl sulfides were obtained with
satisfactory yields (5gꢀi,oꢀr).
K3PO4
100
97
a Reaction conditions: S-phenyl thioacetate (0.3 mmol), 4-bromotou-
lene(0.3mmol), palladium(0.015mmol), ligand(0.021mmol), base(0.36
mmol), toluene (0.6 mL) at 110 °C for 6 h in a screw cap vial. b Determined
by GC analysis with an internal standard of naphthalene. c 2-(Di-tert-
butylphosphino)biphenyl. d 2-(Dicyclohexylphosphino)biphenyl. e 4,5-Bis-
(diphenylphosphino)-9,9-dimethylxanthene. f Addition of H2O (0.3 mL).
g Addition of MeOH (0.3 mL). h Addition of i-PrOH (0.3 mL). i Addition of
acetone (0.3 mL).
Cs2CO3, and Et3N, even though its yield was not higher than
NaOtBu (entries 8ꢀ12). When the reactions were carried out in
the presence of H2O or MeOH cosolvents, no desired product
was found (entries 13 and 14). And the reaction condition of i-
PrOH and KOH, which showed good reactivity in the coupling
reaction of thiol and aryl idodide,23 did not produce the coupled
product even though it showed 10% conversion yield of 4-bro-
motoluene (entry 15). Surprisingly, when acetone was added to
toluene, the reaction was dramatically improved to give the
desired coupling product in quantitative yield (entry 16).24
To investigate the role of acetone, a variety of ketones were
employed as a cosolvent. The results are summarized in Table 2.
When the reaction was carried out with acetone cosolvent in the
absence of ligand, no desired product was found (entry 2). This
result means that acetone does not work as an activated ligand.
When the the amount of acetone was decreased to 0.1 mL, the
yield of product decreased (entry 3). However, when the amount
of acetone was increased to 1.0 mL, the yield of product did not
decrease (entry 4). We obtained similar results in the presence of
other ketones such as methyl ethyl ketone, cylcohexanone, and
benzophenone instead of acetone (entries 5ꢀ7). Although the
role of ketone is not clear so far, it can be suggested that it is likely
to accelerate the deprotection of S-phenyl thioacetate.25
Having successfully demonstrated the viability of the Pd(dba)2/
dppf-catalyzed direct coupling of aryl bromides with phenyl
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FEATURED ARTICLE
Table 3. CꢀS Bond Formation of Thioacetates and Aryl
Table 4. Synthesis of Unsymmetrical Diaryl Sulfidesa
Bromidesa
a Reaction conditions: potassium thioacetate 1a (2.0 mmol), aryl
bromide 2 (2.0 mmol), aryl iodide 4 (2.0 mmol), Pd(dba)2 (0.2 mmol),
1,10-bis(diphenylphosphino)ferrocene (0.28 mmol), K3PO4 (2.4 mmol),
toluene (2.0 mL), acetone (1.0 mL) at 70 °C for 3 h, and subsequently at
110 °C for 6 h under nitrogen atmosphere. Reaction time was not
optimized.
a Reaction conditions: thioacetate 1(3.0 mmol), arylbromide2(3.0 mmol),
Pd(dba)2 (0.15 mmol), 1,10-bis(diphenylphosphino)ferrocene (0.21
mmol), K3PO4 (3.6 mmol), toluene (3. 0 mL), acetone (1.5 mL) at 110
°C for 6 h under nitrogen atmosphere; reaction time was not optimized.
Table 5. Synthesis of Symmetrical Diaryl Sulfides.a
Scheme 1. Competition Reaction of 4-Iodoanisole and Bro-
mobenzene with Potassium Thioacetate27
Next, we expanded this reaction condition to the synthesis
of the symmetric diaryl sulfide from one-pot reaction of aryl
bromides and potassium thioacetate (1a). When 2 equiv of aryl
bromides and 1 equiv of 1a were reacted under our optimized
conditions, the desired diaryl sulfides were formed. The results
are summarized in Table 5.
Bromobenzene produced the diphenyl sulfide (6a) in 97%
yield. Aryl bromides bearing methyl, methoxy, and phenyl at the
ortho position, which are sterically demanding substrates, afforded
the corresponding diaryl sulfide in good yield (6b, 6c, and 6d).
4-Bromoanisole and 1-bromonaphthalene showed 90% and 96%
yields, respectively (6e and 6f). However, aryl bromides bearing an
a Reaction conditions: potassium thioacetate 1a (2.0 mmol), aryl
bromide 2 (4.0 mmol), Pd(dba)2 (0.2 mmol), 1,10-bis(diphenylphos-
phino)ferrocene (0.28 mmol), K3PO4 (2.4 mmol), toluene (2.0 mL),
acetone (1.0 mL) at at 110 °C for 6 h. Reaction time was not optimized.
electron-withdrawing group and heteroaromatic bromide showed
slightly lower yields (6g and 6h).
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FEATURED ARTICLE
’ CONCLUSION
128.9, 128.2, 125.7, 124.3, 115.0, 55.3; HRMS (ESI) [M]þ calcd for
C13H12OS 216.0609, found 216.0607.
In summary, the directed CꢀS bond formation from thioacetate
has been discovered and successfully applied to the coupling of aryl
bromides and a variety of thioacetates. In addition, this reaction
condition was applied to the synthesis of symmetric and unsymetric
diaryl sulfide by use of potassium thioacetate as a sulfur source. This
method provided tolerance to functional groups and foul-smell-free
environmental conditions.
2-(Phenylthio)biphenyl (3bd)32 (Table 3, Entry 4). S-Phenyl thioa-
cetate (1b) (456 mg, 3.00 mmol) was coupled with 2-bromobiphenyl
(2d) (699 mg, 3.00 mmol) to give 566 mg (2.16 mmol, 72%) of 3bd as a
1
colorless oil after chromatography: H NMR (300 MHz, CDCl3) δ
7.41ꢀ7.30 (m, 5), 7.28ꢀ7.17(m, 9H); 13C NMR (75.5 MHz, CDCl3) δ
143.0, 140.6, 135.6, 135.0, 131.8, 131.2, 130.5, 129.3, 129.1, 128.0, 127.9,
127.4, 127.1, 126.7; MS (EI) m/z = 262 (Mþ, 100), 229 (14), 184 (28),
152 (14).
4-(Phenylthio)benzaldehyde (3be)9 (Table 3, Entry 5). S-Phenyl
thioacetate (1b) (456 mg, 1.00 mmol) was coupled with 4-bromoben-
zaldehyde (2e) (555 mg, 3.00 mmol) to give 398 mg (1.86 mmol, 62%)
’ EXPERIMENTAL SECTION
Thioacetate 1b and 1h were commercially available, and 1c,28 1d,29
1
1f,30 and 1g31 were prepared by known procedures.
of 3be as a yellow oil after chromatography: H NMR (300 MHz,
CDCl3) δ 9.91 (S, 1H), 7.72 (dd, J = 8.7, 1.8 Hz, 2H), 7.55ꢀ7.51 (m,
2H), 7.44ꢀ7.41 (m, 3H), 7.24 (dd, J = 8.7, 1.8 Hz, 2H); 13C NMR (75.5
MHz, CDCl3) δ 191.2, 147.3, 134.4, 133.7, 131.3, 130.1, 129.8, 129.2,
127.2; HRMS (ESI) [M]þ calcd for C13H10OS 214.0452, found
214.0459.
S-2-Ethylhexyl Ethanethioate (1e). Potassium thioacetate (1a)
(1.14 g, 10.0 mmol) and 2-ethylhexyl bromide (1.15 g, 6.0 mmol) were
placed in a small round-bottomed flask. Toluene (10.0 mL) and acetone
(5.0 mL) were then added together. The reaction mixture was stirred for
3 h at 110 °C under nitrogen atmosphere. After completion, the reaction
mixture cooled to room temperature. The reaction mixture was poured
into 10 mL of saturated aqueous ammonium chloride and extracted with
Et2O (3 ꢁ 15 mL). The combined ether extracts were washed with brine
(40 mL), dried over MgSO4, and passed through Celite. The product
solvent was removed under vacuum, and the resulting crude product was
purified by flash chromatography on silica gel. The compound 1e was
obtained with 1.102 g (5.86 mmol, 98%) as a colorless oil: 1H NMR (300
MHz, CDCl3) δ 2.91 (dd, J = 6.0, 1.8 Hz, 2H), 2.34 (s, 3H), 1.37ꢀ1.28
(m, 9H), 0.91ꢀ0.86 (m, 6H); 13C NMR (75.5 MHz, CDCl3) δ 195.8,
39.2, 32.9, 32.4, 30.6, 28.7, 25.6, 22.8, 14.0, 10.8; HRMS (ESI) [M]þ
calcd for C10H20OS 188.3362, found 188.3362.
General Procedure for the CꢀS Bond Formation of Thio-
acetates and Aryl Bromides. Pd(dba)2 (86.2 mg, 0.15 mmol), 1,10-
bis(diphenylphosphino)ferrocene (116.4 mg, 0.21 mmol), aryl bro-
mides (3.00 mmol), thioacetates (3.00 mmol), and K3PO4 (764 mg,
3.60 mmol) were placed in a small round-bottomed flask. Toluene
(3.0 mL) and acetone (1.5 mL) were then added together. The reaction
mixture was stirred for 6 h at 110 °C under nitrogen atmosphere and
then cooled to room temperature. The reaction mixture was poured into
10 mL of saturated aqueous ammonium chloride and extracted with
Et2O (3 ꢁ 15 mL). The combined ether extracts were washed with brine
(40 mL), dried over MgSO4, and passed through Celite. The solvent was
removed under vacuum, and the resulting crude product was purified by
flash chromatography on silica gel. The product was eluted with ethyl
acetate in hexane.
2-(Phenylthio)pyridine (3bf)33 (Table 3, Entry 6). S-Phenyl thioace-
tate (1b) (456 mg, 3.00 mmol) was coupled with 2-bromopyridine (2f)
(474 mg, 3.00 mmol) to give 460 mg (2.46 mmol, 82%) of 3bf as a
colorless oil after chromatography: 1H NMR (300 MHz, CDCl3) δ 8.42
(dd, J = 4.8, 2.0 Hz, 1H), 7.65ꢀ7.58 (m, 2H), 7.48ꢀ7.40 (m, 4H),
7.01ꢀ6.97 (m, 1H), 6.88 (d, J = 8.0 Hz, 1H); 13C NMR (75.5 MHz,
CDCl3) δ 161.5, 149.5, 136.7, 134.9, 131.0, 129.6, 129.0, 121.3, 119.8;
HRMS (ESI) [M]þ calcd for C11H9NS 187.0456, found 187.0456.
1-Methoxy-2-[(4-methoxyphenyl)thio]benzene (3ch)33 (Table 3,
Entry 7). S-4-Methoxyphenyl thioacetate (1c) (547 mg, 3.00 mmol)
was coupled with 2-bromoanisole (2h) (561 mg, 3.00 mmol) to give 494
mg (2.01 mmol, 67%) of 3ch as a colorless oil after chromatography: 1H
NMR (300 MHz, CDCl3) δ 7.42 (dt, J = 8.7, 3.3 Hz, 2H), 7.14ꢀ7.06 (m,
1H), 6.89 (dt, J = 8.7, 3.0 Hz, 2H), 6.82 (d, J = 8.1 Hz, 1H), 6.78 (d, J =
4.2 Hz, 2H), 3.87 (s, 3H), 3.78 (s, 3H); 13C NMR (75.5 MHz, CDCl3)
δ 159.8, 155.5, 135.9, 127.9, 127.2, 136.5, 122.6, 121.0, 114.9, 110.2,
55.7, 55.2; HRMS (ESI) [M]þ calcd for C14H14O2S 246.0715, found
246.0717.
n-Hexyl Phenyl Sulfide (3di)34 (Table 3, Entry 8). S-Hexyl thioacetate
(1d) (480 mg, 3.00 mmol) was coupled with bromobenzene (2i) (471
mg, 3.00 mmol) to give 530 mg (2.73 mmol, 91%) of 3di as a colorless
oil after chromatography: 1H NMR (300 MHz, CDCl3) δ 7.29 (d, J = 7.2
Hz, 2H), 7.22 (t, J = 7.5 Hz, 2H), 7.10 (t, J = 7.1 Hz, 1H), 2.87 (t, J = 7.4
Hz, 2H), 1.62 (p, J = 7.7 Hz, 2H), 1.39 (p, J = 6.9 Hz, 2H), 1.29ꢀ1.23
(m, 4H), 0.87 (t, J = 6.9 Hz, 3H); 13C NMR (75.5 MHz, CDCl3) δ
137.5, 129.1, 129.1, 125.9, 33.9, 31.8, 29.5, 28.9, 22.9, 14.4; MS (EI) m/z =
194 (Mþ, 75), 123 (30), 110 (100), 77 (9), 65 (9), 43 (9).
4-Tolyl Phenyl Sulfide (3ba)11c (Table 3, Entry 1). S-Phenyl thioace-
tate (1b) (456 mg, 3.00 mmol) was coupled with 4-bromotoluene (2a)
(513 mg, 3.00 mmol) to give 552 mg (2.76 mmol, 92%) of 3ba as a pale
yellow oil after chromatography: 1H NMR (300 MHz, CDCl3) δ
7.38ꢀ7.19 (m, 9H), 2.41 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ
137.5, 137.1, 132.2, 131.3, 130.0, 129.8, 129.0, 126.4, 21.1; HRMS (ESI)
[M]þ calcd for C13H12S 200.0660, found 200.0662.
Hexyl p-Tolyl Sulfide (3da)10b (Table 3, Entry 9). S-Hexyl thioacetate
(1d) (480 mg, 3.00 mmol) was coupled with 4-bromotoluene (2a) (513
mg, 3.00 mmol) to give 487 mg (2.34 mmol, 78%) of 3da as a colorless
oil after chromatography: 1H NMR (300 MHz, CDCl3) δ 7.34 (d, J = 8.1
Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 2.96 (t, J = 7.4 Hz, 2H), 2.4 (s, 3H),
1.72 (p, J = 7.4 Hz, 2H), 1.51 (p, J = 7.5 Hz, 2H), 1.40ꢀ1.37 (m, 4H),
0.99 (t, J = 6.9, 3H); 13C NMR (75.5 MHz, CDCl3) δ 136.0, 133.6,
131.4, 130.0, 129.9, 34.7, 31.7, 29.6, 28.8, 22.9, 21.3, 14.4; MS (EI) m/z =
208 (Mþ, 100), 137 (36), 124 (100), 91 (36), 77 (9).
2-Tolyl Phenyl Sulfide (3bb)4a (Table 3, Entry 2). S-Phenyl thioacetate
(1b) (456 mg, 3.00 mmol) was coupled with 2-bromotoluene (2b) (513
mg, 3.00 mmol) to give 546 mg (2.73 mmol, 91%) of 3bb as a colorless
1
oil after chromatography: H NMR (300 MHz, CDCl3) δ 7.31ꢀ7.10
(m, 9H), 2.37 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ 140.0, 136.1,
133.7, 133.0, 130.6, 129.6, 128.1, 127.9, 126.7, 126.3, 20.6; HRMS (ESI)
[M]þ calcd for C13H12S 200.0660, found 200.0662.
Hexyl 4-Methoxyphenyl Sulfide (3dc)35 (Table 3, Entry 10). S-Hexyl
thioacetate (1d) (480 mg, 3.00 mmol) was coupled with 4-bromoanisole
(2c) (561 mg, 3.00 mmol) to give 551 mg (2.46 mmol, 82%) of 3dc
1-Methoxy-4-(phenylthio)benzene (3bc)8e (Table3, Entry 3). S-Phenyl
thioacetate (1b) (456 mg, 3.00 mmol) was coupled with 4-bromoanisole
(2c) (561 mg, 3.00 mmol) to give 494 mg (2.28 mmol, 76%) of 3bc as a
colorless oil after chromatography: 1H NMR (300 MHz, CDCl3) δ 7.41
(dd, J = 8.7, 2.1 Hz, 2H), 7.25ꢀ7.09 (m, 5H), 6.89 (dd, J = 8.7, 2.1 Hz,
2H), 3.81 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ 159.8, 138.6, 135.3,
1
as a colorless oil after chromatography: H NMR (300 MHz, CDCl3)
δ 7.33 (d, J = 8.4 Hz, 2H), 6.83 (d, J = 9.0 Hz, 2H), 3.78 (s, 3H), 2.80
(t, J = 7.4 Hz, 2H), 1.57 (p, J = 7.5 Hz, 2H), 1.38 (p, J = 7.5 Hz, 2H),
1.28ꢀ1.25 (m, 4H), 0.87 (t, J = 6.6 Hz, 3H); 13C NMR (75.5 MHz,
CDCl3) δ 158.7, 132.9, 127.0, 114.5, 55.3, 35.8, 31.4, 29.3, 28.4, 22.6, 14.1;
MS (EI) m/z = 224 (Mþ, 100), 153 (18),140 (90), 125 (20), 109 (10).
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FEATURED ARTICLE
2-Ethylhexyl Phenyl Sulfide (3ei) (Table 3, Entry 11). S-2-Ethylhexyl
thioacetate (1e) (564 mg, 3.00 mmol) was coupled with bromobenzene
(2i) (471 mg, 3.00 mmol) to give 579 mg (2.61 mmol, 87%) of 3ei as a
colorless oil after chromatography: 1H NMR (300 MHz, CDCl3) δ 7.20
(d, J = 7.2 Hz, 2H), 7.12 (t, J = 7.7 Hz, 2H), 7.00 (t, J = 7.2, 1H), 2.78 (d,
J = 6.3 Hz, 2H), 1.47 (m, 1H), 1.40ꢀ1.22 (m, 4H), 1.18ꢀ1.12 (m, 4H),
0.81ꢀ0.70 (m, 6H); 13C NMR (75.5 MHz, CDCl3) δ 137.7, 128.7, 125.4,
38.9, 37.9, 32.4, 28.7, 25.6, 23.0, 14.1, 10.7; MS(EI) m/z = 222 (Mþ, 90),
123 (45), 110 (100), 77 (9), 71 (15), 57 (20), 41 (18). Anal. Calcd for
C14H22S: C, 75.61; H, 9.97; S, 14.42. Found: C, 75.59; H, 9.74; S, 14.08.
2-Ethylhexyl p-Tolyl Sulfide (3ea)36 (Table 3, Entry 12). S-2-Ethylhexyl
thioacetate e (1e) (564 mg, 3.00 mmol) was coupled with 4-bromoto-
luene (2a) (513 mg, 3.00 mmol) to give 524 mg (2.22 mmol, 74%) of 3ea
as a colorless oil after chromatography: 1H NMR (300 MHz, CDCl3) δ
7.23 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 7.8 Hz, 2H), 2.85 (d, J = 6.0 Hz, 2H),
2.28 (s, 3H), 1.54 (m, 1H), 1.47ꢀ1.34 (m, 4H), 1.31ꢀ1.22 (m, 4H),
0.90ꢀ0.83 (m,6H); 13C NMR (75.5 MHz, CDCl3) δ 135.8, 134.3, 129.9,
129.1, 39.3, 39.1, 32.7, 29.1, 25.9, 23.3, 21.3, 14.4, 11.1; MS (EI) m/z =
236 (Mþ, 85), 137 (35), 124 (100), 91 (20), 71 (9).
111.2, 56.2; HRMS (ESI) [M]þ calcd for C13H12OS 216.0609, found
216.0610.
1-Methoxy-3-(phenylthio)benzene (5b)39. Potassium thioacetate
(1a) (228 mg, 2.00 mmol) was coupled with iodobenzene (408 mg,
2.00 mmol) and 3-bromoanisole (374 mg, 2.00 mmol) to give 355 mg
1
(1.64 mmol, 82%) of 5b as a colorless oil after chromatography: H
NMR (300 MHz, CDCl3) δ 7.38ꢀ7.22 (m, 5H), 7.19 (d, J = 7.8 Hz,
1H), 6.90 (d, J = 6.9 Hz, 1H), 6.86 (m, 1H), 6.77 (ddd, J = 8.4, 2.1, 0.9
Hz, 1H), 3.75 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ 160.1, 137.2,
135.3, 131.4, 129.9, 129.2, 127.2, 123.0, 115.9, 112.8, 55.3; HRMS (ESI)
[M þ Li]þ calcd for C13H12OSLi 223.0769, found 223.0767.
N,N-Dimethyl-4-(phenylthio)benzenamine (5c)9. Potassium thioa-
cetate (1a) (228 mg, 2.00 mmol) was coupled with iodobenzene (408
mg, 2.00 mmol) and 4-bromo-N,N-dimethylaniline (400 mg, 2.00
mmol) to give 358 mg (1.56 mmol, 78%) of 5c as a white solid after
chromatography: mp 69ꢀ70 °C; 1H NMR (300 MHz, CDCl3) δ 7.39
(dd, J = 8.7, 2.1 Hz 2H), 7.22- 7.17 (m, 2H), 7.12ꢀ7.05 (m, 3H), 6.71 (d,
J = 8.7 Hz, 2H), 2.99 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ 150.4,
140.1, 136.0, 128.7, 127.6, 127.0, 125.0, 113.1, 40.4; HRMS (ESI) [M]þ
calcd for C14H15NS 229.0925, found 229.0924.
4-(Phenylthio)butanenitrile (3fi)37 (Table 3, Entry 13). S-3-Cyano-
propyl thioacetate (1f) (429 mg, 3.00 mmol) was coupled with
bromobenzene (2i) (471 mg, 3.00 mmol) to give 432 mg (2.43 mmol,
1-Naphthyl Phenyl Sulfide (5d)8e. Potassium thioacetate (1a) (228
mg, 2.00 mmol) was coupled with iodobenzene (408 mg, 2.00 mmol)
and 1-bromonaphthalene (414 mg, 2.00 mmol) to give 449 mg (1.90
mmol, 95%) of 5d as a colorless oil after chromatography: 1H NMR (300
MHz, CDCl3) δ 8.39ꢀ8.36 (m, 1H), 7.84 (t, J = 9.3 Hz, 2H), 7.65 (dd,
J = 7.2, 1.2 Hz, 1H), 7.51ꢀ7.45 (m, 2H), 7.39 (dd, J = 8.1, 7.2 Hz, 1H),
7.22ꢀ6.88 (m, 5H); 13C NMR (75.5 MHz, CDCl3) δ 136.9, 134.2,
133.5, 132.5, 131.2, 129.2, 129.0, 128.9, 128.5, 126.9, 126.4, 126.1, 125.8,
125.6; HRMS (ESI) [M þ H]þ calcd for C16H12S 237.0660, found
237.0661.
1
81%) of 3fi as a pale yellow oil after chromatography: H NMR (300
MHz, CDCl3) δ 7.37ꢀ7.21 (m, 5H), 3.02 (t, J = 6.8 Hz, 2H), 2.49 (t, J =
7.2 Hz, 2H), 1.94 (p, J = 7.1 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ
134.6, 129.9, 129.0, 126.6, 118.9, 32.4, 24.7, 15.8; MS (EI) m/z = 177
(Mþ, 100), 123 (80), 110 (40), 77 (10), 65 (10).
Benzyl Phenyl Sulfide (3gi)34 (Table 3, Entry 14). S-Benzyl thioace-
tate (1g) (498 mg, 3.00 mmol) was coupled with bromobenzene (2i)
(471 mg, 3.00 mmol) to give 588 mg (2.94 mmol, 98%) of 3gi as a white
solid after chromatography: mp 41ꢀ42 °C; 1H NMR (300 MHz,
CDCl3) δ 7.50ꢀ7.30 (m, 10H), 4.27 (s, 2H); 13C (75.5 MHz, CDCl3)
δ 137.9, 136.9, 130.1, 129.3, 128.9, 127.6, 126.7, 39.4; MS (EI) m/z =
200 (Mþ, 70), 109 (9), 91 (100), 65 (15), 51 (5), 39 (5).
4-Phenylsulfanylacetophenone (5e)11c. Potassium thioacetate (1a)
(228 mg, 2.00 mmol) was coupled with iodobenzene (408 mg, 2.00
mmol) and 4-bromoacetophenone (398 mg, 2.00 mmol) to give 384 mg
(1.68 mmol, 84%) of 5e as a yellow solid after chromatography: mp
63ꢀ64 °C; 1H NMR (300 MHz, CDCl3) δ 7.82 (dt, J = 8.7, 2.1 Hz, 2H),
7.50 (m, 2H), 7.42ꢀ7.38 (m, 3H), 7.21 (dt, J = 8.7, 21. Hz, 2H), 2.55 (s,
3H); 13C NMR (75.5 MHz, CDCl3) δ 197.1, 144.9, 134.5, 133.8, 132.1,
129.7, 128.9, 128.8, 127.5, 26.4; HRMS (ESI) [M]þ calcd for C14H12OS
228.0609, found 228.0609.
4-Methoxyphenyl 2-Methyl-2-propyl Sulfide (3hc)38 (Table 3, Entry
15). S-tert-Butyl thioacetate (1h) (396, 3.00 mmol) was coupled with
4-bromoanisole (2c) (561 mg, 3.00 mmol) to give 512 mg (2.61 mmol,
1
87%) of 3hc as a colorless oil after chromatography: H NMR (300
MHz, CDCl3) δ 7.43 (m, 2H), 6.84 (m, 2H), 3.79 (s, 3H), 1.25 (s, 9H);
13C NMR (75.5 MHz, CDCl3) δ 160.1, 138.8, 123.5, 113.9, 55.1, 45.3,
30.7; MS (EI) m/z = 196 (Mþ, 11), 140 (100).
4-Phenylsulfanylbenzoic Acid Methyl Ester (5f)11c. Potassium thioa-
cetate (1a) (228 mg, 2.00 mmol) was coupled with iodobenzene (408
mg, 2.00 mmol) and methyl 4-bromobenzoate (430 mg, 2.00 mmol) to
give 425 mg (1.74 mmol, 87%) of 5f as a colorless oil after chromatog-
raphy: 1H NMR (300 MHz, CDCl3) δ 7.89 (d, J = 8.7 Hz, 2H),
7.50ꢀ7.47 (m, 2H), 7.40ꢀ7.37 (m, 3H), 7.20 (d, J = 8.7 Hz, 2H), 3.89
(s, 3H); 13C NMR (75.5 MHz, CDCl3) δ 166.7, 144.3, 133.7, 132.4,
130.1, 129.6, 128.6, 127.6, 125.8, 52.1; HRMS (ESI) [M]þ calcd for
C14H12O2S 244.0558, found 244.0556.
General Procedure for the Synthesis of Unsymmetrical
Diaryl Sulfides. Pd(dba)2 (115 mg, 0.20 mmol), 1,10-bis(diphenyl-
phosphino)ferrocene (155 mg, 0.28 mmol), aryl iodides (2.00 mmol),
aryl bromides (2.00 mmol), potassium thioacetates (228 mg, 2.00 mmol),
and K3PO4 (509 mg, 2.40 mmol) were placed in a small round-bottomed
flask. Toluene (2.0 mL) and acetone (1.0 mL) were then added together.
The reaction mixture was stirred for 3 h at 70 °C under nitrogen
atmosphere. The reaction temperature was increased to 110 °C, and
the mixture was stirred for 6 h under nitrogen atmosphere. After
completion, the reaction mixture was cooled to room temperature. The
reaction mixture was poured into 10 mL of saturated aqueous ammonium
chloride and extracted with Et2O (3 ꢁ 15 mL). The combined ether
extracts were washed with brine (40 mL), dried over MgSO4, and passed
through Celite. The solvent was removed under vacuum, and the resulting
crude product was purified by flash chromatography on silica gel. The
product was eluted with ethyl acetate in hexane.
5-(Phenylthio)pyrimidine (5g)40. Potassium thioacetate (1a) (228
mg, 2.00 mmol) was coupled with iodobenzene (408 mg, 2.00 mmol)
and 5-bromopyrimidine (318 mg, 2.00 mmol) to give 320 mg (1.70
mmol, 85%) of 5g as a colorless oil after chromatography: 1H NMR (300
MHz, CDCl3) δ 9.03 (s, 1H), 8.59 (s, 2H), 7.46ꢀ7.37 (m, 5H); 13C
NMR (75.5 MHz, CDCl3) δ 157.0, 156.3, 133.5, 132.7, 131.7, 129.9,
128.8; MS (EI) m/z = 188 (Mþ, 100), 160 (13), 134 (20), 77 (8), 5 (8).
3-(Phenylthio)pyridine (5h)39. Potassium thioacetate (1a) (228 mg,
2.00 mmol) was coupled with iodobenzene (408 mg, 2.00 mmol) and
3-bromopyridine (316 mg, 2.00 mmol) to give 266 mg (1.42 mmol,
71%) of 5h as a colorless oil after chromatography: 1H NMR (300 MHz,
CDCl3) δ 8.56 (dd, J = 2.4, 0.6 Hz, 1H), 8.45 (dd, J = 4.2, 1.5 Hz, 1H),
7.58 (dt, J = 8.1, 1.5 Hz, 1H), 7.39ꢀ7.27 (m, 5H), 7.20 (ddd, J = 7.2, 4.8,
0.6 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ 150.9, 147.7, 137.8, 133.8,
133.5, 131.6, 129.4, 127.8, 123.8; MS (EI) m/z = 187 (Mþ, 100), 160
(5), 115 (5), 77 (5), 5 (11), 39 (5).
1-Methoxy-2-(phenylthio)benzene (5a)9. Potassium thioacetate
(1a) (228 mg, 2.00 mmol) was coupled with iodobenzene (408 mg,
2.00 mmol) and 2-bromoanisole (374 mg, 2.00 mmol) to give 423 mg
1
(1.96 mmol, 98%) of 5a as a colorless oil after chromatography: H
NMR (300 MHz, CDCl3) δ 7.43ꢀ7.27 (m, 6H), 7.16 (dd, J = 7.5, 1.5
Hz, 1H), 6.97ꢀ6.90 (m, 2H), 3.92 (s, 3H); 13C NMR (75.5 MHz,
CDCl3) δ 157.6, 134.9, 132.0, 131.7, 129.4, 128.7, 127.3, 124.4, 121.6,
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2-(Phenylthio)thiazole (5i)41. Potassium thioacetate (1a) (228 mg,
2.00 mmol) was coupled with iodobenzene (408 mg, 2.00 mmol) and
2-bromothiazole (328 mg, 2.00 mmol) to give 275 mg (1.42 mmol,
71%) of 5i as a colorless oil after chromatography: 1H NMR (300 MHz,
CDCl3) δ 7.70 (d, J = 3.3 Hz, 1H), 7.63ꢀ7.60 (m, 2H), 7.40 (t, J =
4.2 Hz, 3H), 7.21 (d, J = 3.6 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ
165.8, 143.4, 133.6, 131.8, 129.7, 129.4, 120.3; MS (EI) m/z = 193 (Mþ,
45), 192(100), 109 (4), 77 (4), 58 (9).
1-Methoxy-3-(phenylthio)benzene (5j = 5b). Potassium thioacetate
(1a) (228 mg, 2.00 mmol) was coupled with bromobenzene (314 mg,
2.00 mmol) and 3-iodoanisole (468 mg, 2.00 mmol) to give 401 mg
(1.86 mmol, 93%) of 5j as a colorless oil after chromatography.
1-Methoxy-2-(phenylthio)benzene (5k = 5a). Potassium thioacetate
(1a) (228 mg, 2.00 mmol) was coupled with bromobenzene (408 mg,
2.00 mmol) and 2-iodoanisole (468 mg, 2.00 mmol) to give 410 mg
(1.90 mmol, 95%) of 5k as a colorless oil after chromatography.
4-Acetylphenyl Naphthyl Sulfide (5l)42. Potassium thioacetate (1a)
(228 mg, 2.00 mmol) was coupled with 1-bromonaphthalene (414 mg,
2.00 mmol) and 4-iodoacetophenone (492 mg, 2.00 mmol) to give 529
mg (1.90 mmol, 95%) of 5l as a colorless oil after chromatography: 1H
NMR (300 MHz, CDCl3) δ 8.33 (d, J = 8.7 Hz, 1H), 8.04ꢀ7.90 (m,
3H), 7.78 (d, J = 8.7 Hz, 2H), 7.59ꢀ7.53 (m, 3H), 7.10 (d, J = 8.7 Hz,
2H), 2.54 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ 197.4, 145.7, 135.4,
134.7, 134.5, 134.3, 131.1, 129.1, 129.0, 128.2, 127.8, 127.0, 126.4, 126.2,
126.0, 26.7; MS (EI) m/z = 278 (Mþ, 100), 263 (86), 234 (43), 202
(14), 115 (14).
3-[(4-Methoxyphenyl)thio]pyridine (5q)33. Potassium thioacetate
(1a) (228 mg, 2.00 mmol) was coupled with 3-bromopyridine (316 mg,
2.00 mmol) and 4-iodoanisole (468 mg, 2.00 mmol) to give 382 mg
1
(1.76 mmol, 88%) of 5q as a colorless oil after chromatography: H
NMR (300 MHz, CDCl3) δ 8.44 (d, J = 3.3 Hz, 1H), 8.35 (dd, J = 4.8,
1.8 Hz, 1H), 7.43ꢀ7.40 (m, 3H), 7.10 (ddd, J = 8.1, 4.8, 0.9 Hz, 1H),
6.90 (d, J = 9.0 Hz, 2H), 3.79 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ
160.5, 149.1, 147.0, 136.3, 135.9, 135.6, 123.9, 122.8, 115.5, 55.6; MS
(EI) m/z = 217 (Mþ, 100), 202 (39), 173 (22).
5-(4-Methoxyphenylthio)pyrimidine (5r). Potassium thioacetate
(1a) (228 mg, 2.00 mmol) was coupled with 5-bromopyrimidine (318
mg, 2.00 mmol) and 4-iodoanisole (468 mg, 2.00 mmol) to give 354 mg
1
(1.62 mmol, 81%) of 5r as a colorless oil after chromatography: H
NMR (300 MHz, CDCl3) δ 8.93 (s, 1H), 8.43 (s, 2H), 7.42 (d, J = 9.0
Hz, 2H), 6.90 (d, J = 8.7 Hz, 2H), 3.79 (s, 3H); 13C NMR (75.5 MHz,
CDCl3) δ 161.0, 155.7, 155.3, 136.3, 135.6, 120.6, 115.8, 55.7; MS (EI)
m/z = 218 (Mþ, 100), 203 (30), 176 (10), 121 (10). Anal. Calcd for
C11H10N2OS: C, 60.53; H, 4.62; N, 12.83; S, 14.69. Found: C, 60.80; H,
4.41; N, 12.75; S, 14.94.
General Procedure for the Synthesis of Symmetric Diaryl
Sulfides. Pd(dba)2 (115 mg, 0.20 mmol), 1,10-bis(diphenylpho-
sphino)ferrocene (155 mg, 0.28 mmol), aryl bromides (4.00 mmol),
potassium thioacetate (228 mg, 2.00 mmol), and K3PO4 (509 mg, 2.40
mmol) were placed in a small round-bottomed flask. Toluene (2.0 mL) and
acetone (1.0 mL) were then added in one portion. The reaction mixture was
stirred for 6 h at 110 °C under nitrogen atmosphere and then cooled to room
temperature. The reaction mixture was poured into 10 mL of saturated
aqueous ammonium chloride and extracted with Et2O (3 ꢁ 15 mL). The
combined ether extracts were washed with brine (40 mL), dried over
MgSO4, and passed through Celite. The solvent was removed under vacuum,
and the resulting crude product was purified by flash chromatography on
silica gel. The product was eluted with ethyl acetate in hexane.
1-(4-(4-Methoxyphenylthio)phenyl)ethanone (5m)43. Potassium
thioacetate (1a) (228 mg, 2.00 mmol) was coupled with 4-bromoanisole
(374 mg, 2.00 mmol) and 4-iodoacetophenone (492 mg, 2.00 mmol) to
give 424 mg (1.64 mmol, 82%) of 5m as a colorless oil after chromatog-
raphy: 1H NMR (300 MHz, CDCl3) δ 7.80 (d, J = 8.7 Hz, 2H), 7.49 (d,
J = 8.7 Hz, 2H), 7.12 (d, J = 8.7 Hz, 2H), 6.98 (d, J = 8.7 Hz, 2H), 3.87 (s,
3H), 2.55 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ 196.9, 160.5, 146.7,
136.7, 133.7, 128.7, 125.6, 121.2, 115.2, 55.3, 26.3; MS (EI) m/z = 258
(Mþ, 100), 243 (83), 215 (12), 200 (12), 184 (10), 171 (12), 139 (12).
1-[4-(o-Tolylthio)phenyl]ethanone (5n)44. Potassium thioacetate
(1a) (228 mg, 2.00 mmol) was coupled with 2-bromotoluene (342
mg, 2.00 mmol) and 4-iodoacetophenone (492 mg, 2.00 mmol) to give
344 mg (1.42 mmol, 71%) of 5n as a colorless oil after chromatography:
1H NMR (300 MHz, CDCl3) δ 7.83 (dt, J = 8.7, 2.1 Hz, 2H), 7.55 (d, J =
7.2 Hz, 1H), 7.39ꢀ7.37 (m, 2H), 7.30ꢀ7.26 (m, 1H), 7.12 (dt, J = 8.7,
2.1 Hz, 2H), 2.57 (s, 3H), 2.41 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ
197.0, 144.9, 142.1, 135.8, 133.9, 131.0, 130.2, 129.7, 128.8, 127.1, 126.2,
26.4, 20.6; MS (EI) m/z = 242 (Mþ, 81), 227 (100), 184 (37), 165 (7).
1-[4-(Pyridin-3-ylthio)phenyl]ethanone (5o). Potassium thioacetate
(1a) (228 mg, 2.00 mmol) was coupled with 3-bromopyridine (316 mg,
2.00 mmol) and 4-iodoacetophenone (492 mg, 2.00 mmol) to give 339 mg
(1.48 mmol, 74%) of 5o as a colorless oil after chromatography: 1H NMR
(300MHz, CDCl3) δ8.51ꢀ8.49 (m, 1H), 7.97 (d, J= 8.7 Hz, 2H), 7.62 (d,
J = 8.7 Hz, 2H), 7.56 (dd, J = 8.1, 1.8 Hz, 1H), 7.18ꢀ7.10 (m, 2H), 2.63 (s,
3H); 13C NMR (75.5 MHz, CDCl3) δ 197.5, 158.9, 150.3, 139.0, 137.3,
136.7, 133.0, 129.4, 123.8, 121.4, 26.9; HRMS (ESI) [M]þ calcd for
C13H11NOS 229.0561, found 229.0562. Anal. Calcd. for C13H11NOS: C,
68.09; H, 4.84; N, 6.11; S: 13.98. Found: C, 68.08; H, 4.71; N, 6.14; S, 13.82.
1-[4-(Pyrimidin-5-ylthio)phenyl]ethanone (5p). Potassium thioace-
tate (1a) (228 mg, 2.00 mmol) was coupled with 5-bromopyrimidine
(318 mg, 2.00 mmol) and 4-iodoacetophenone (492 mg, 2.00 mmol) to
give 309 mg (1.34 mmol, 67%) of 5p as colorless oil after chromatog-
raphy: 1H NMR (300 MHz, CDCl3) δ 9.16 (s, 1H), 8.75 (s, 2H), 7.90
(d, J = 8.7 Hz, 2H), 7.34 (d, J = 8.7 Hz, 2H), 2.59 (s, 3H); 13C NMR
(75.5 MHz, CDCl3) δ 197.1, 159.8, 157.9, 140.4, 136.2, 130.7, 129.8,
129.6, 26.8; MS (EI) m/z = 230(Mþ, 60), 215 (100), 160 (9), 133 (10),
89 (9). Anal. Calcd for C12H10N2OS: C, 62.59; H, 4.38; N, 12.16; S,
13.92. Found: C, 62.71; H, 4.41; N, 12.15; S, 13.94.
Diphenyl Sulfide (6a)4a. Potassium thioacetate (1a) (228 mg, 2.00
mmol) was coupled with bromobenzene (628 mg, 4.00 mmol) to give
361 mg (1.94 mmol, 97%) of 6a as a colorless oil after chromatography:
1H NMR (300 MHz, CDCl3) δ 7.32 (m, J = 8 Hz, 4H), 7.30 (m, J = 8 Hz,
4H), 7.25 (m, J = 8 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ 135.8,
131.0, 129.2, 127.0; HRMS (ESI) [M]þ calcd for C12H10S 186.0503,
found 186.0505.
2,20-Ditolyl Sulfide (6b)45. Potassium thioacetate (1a) (228 mg, 2.00
mmol) was coupled with 2-bromotoluene (684 mg, 4.00 mmol) to give
412 mg (1.92 mmol, 96%) of 6b as a white liquid after chromatography:
1H NMR (300 MHz, CDCl3) δ 7.24ꢀ7.03 (m, 8H), 2.37 (s, 6H); 13
C
NMR (75.5 MHz, CDCl3) δ 139.2, 134.6, 131.4, 130.8, 127.4, 127.0,
20.7; MS (EI) m/z = 214 (Mþ, 100), 199 (14), 184 (13), 165 (12), 122
(29).
2,20-Dimethoxyphenyl Sulfide (6c)15. Potassium thioacetate (1a)
(228 mg, 2.00 mmol) was coupled with 2-bromoanisole (748 mg,
4.00 mmol) to give 453 mg (1.84 mmol, 92%) of 6c as a white liquid
after chromatography: 1H NMR (300 MHz, CDCl3) δ 7.29 (dt, J = 8.4,
1.8 Hz, 2H), 7.12 (dd, J = 7.5, 1.5 Hz, 2H), 6.94 (t, J = 7.5 Hz, 4H), 3.90
(s, 6H); 13C NMR (75.5 MHz, CDCl3) δ 158.1. 132.2, 128.7, 122.9,
121.5, 111.1, 56.1; MS (EI) m/z = 246 (Mþ, 100), 231 (8), 216 (17),
200 (33), 187 (10), 171 (10).
2,20-Biphenyl Sulfide (6d). Potassium thioacetate (1a) (228 mg, 2.00
mmol) was coupled with 2-bromobiphenyl (932 mg, 4.00 mmol) to
give 636 mg (1.88 mmol, 94%) of 6d as a white liquid after chromatog-
raphy: 1H NMR (300 MHz, CDCl3) δ 7.43ꢀ7.39 (m, 6H), 7.37ꢀ7.34
(m, 8H), 7.33ꢀ7.30 (m, 4H); 13C NMR (75.5 MHz, CDCl3) δ 143.9,
141.0, 135.2, 132.7, 130.9, 129.6, 128.3, 128.1, 127.6, 127.3; MS (EI) m/
z = 338 (Mþ, 100), 184 (26), 152 (14). Anal. Calcd for C24H18S: C,
85.17; H, 5.36; S, 9.47. Found: C, 85.22; H, 5.16; S, 9.51.
4,40 -Dimethoxyphenyl Sulfide (6e)33. Potassium thioacetate (1a)
(228 mg, 2.00 mmol) was coupled with 4-bromoanisole (748 mg, 4.00
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FEATURED ARTICLE
mmol) to give 443 mg (1.8 mmol, 90%) of 6e as a yellow liquid after
chromatography: 1H NMR (300 MHz, CDCl3) δ 7.27 (dt, J = 9.0, 2.4
Hz, 4H), 6.83 (dt, J = 9.0, 2.4 Hz, 4H), 3.78 (s, 6H); 13C NMR (75.5
MHz, CDCl3) δ 159.0, 132.7, 127.4, 114.7, 55.3; HRMS (ESI) [M]þ
calcd for C14H14O2S 246.0715, found 246.0711.
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1,10-Dinaphthyl Sulfide (6f)15. Potassium thioacetate (1a) (228 mg,
2.00 mmol) was coupled with 1-bromonaphthalene (828 mg, 4.00
mmol) to give 550 mg (1.92 mmol, 96%) of 6f as a white liquid after
1
chromatography: H NMR (300 MHz, CDCl3) δ 8.41 (t, J = 3.3 Hz,
2H), 7.78 (t, J = 6 Hz, 2H), 7.67 (d, J = 8.1 Hz, 2H), 7.44 (d, J = 9.6 Hz,
4H), 7.28ꢀ7.17 (m, 4H); 13C NMR (75.5 MHz, CDCl3) δ 134.5, 133.0,
132.8, 130.3, 129.0, 128.4, 127.2, 126.8, 126.3, 125.5; MS (EI) m/z = 286
(Mþ, 100), 271 (7), 252 (27), 142 (9), 126 (9), 115 (11).
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4,40-Diacetylphenyl Sulfide (6g)15. Potassium thioacetate (1a) (228
mg, 2.00 mmol) was coupled with 4-bromoacetophenone (796 mg, 4.00
mmol) to give 351 mg (1.3 mmol, 65%) of 6g as a colorless oil after
chromatography: 1H NMR (300 MHz, CDCl3) δ 7.93 (d, J = 8.7 Hz,
4H), 7.43 (d, J = 8.4 Hz, 4H), 2.62 (s, 6H); 13C NMR (75.5 MHz,
CDCl3) δ 197.3, 141.3, 136.2, 130.9, 126.5, 26.9; MS (EI) m/z = 270
(Mþ, 64), 255 (100), 184 (18), 43 (14).
3,30-Dipyridine Sulfide (6h)15. Potassium thioacetate (1a) (228 mg,
2.00 mmol) was coupled with 3-bromopyridine (632 mg, 4.00 mmol) to
give 241 mg (1.28 mmol, 64%) of a colorless oil as after chromatogra-
phy: 1H NMR (300 MHz, CDCl3) δ 8.61 (s, 2H), 8.53 (d, J = 3.9 Hz,
2H), 7.65 (d, J = 7.8 Hz, 2H), 7.26 (t, J = 4.8 Hz, 2H); 13C NMR (75.5
MHz, CDCl3) δ 151.9, 148.9, 138.9, 132.1, 124.4; MS (EI) m/z = 188
(Mþ, 100), 161 (14), 78 (13), 51 (14), 39 (12).
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S
Supporting Information.
Spectra of obtained com-
b
pounds. This material is available free of charge via the Internet at
http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: sunwoo@chonnam.ac.kr.
(13) (a) Zhang, S.; Qian, P.; Zhang, M.; Hu, M.; Cheng, J. J. Org. Chem.
2010, 75, 6732–6735. (b) Kumar, S.; Engman, L. J. Org. Chem. 2006,
71, 5400–5403. (c) Taniguchi, N. J. Org. Chem. 2004, 69, 6904–6906.
(14) Firouzabadi, H.; Iranpoor, N.; Gholinejad, M. Adv. Synth. Catal.
2010, 352, 119–124.
’ ACKNOWLEDGMENT
This work was supported by National Research Foundation
of Korea Grant funded by the Korean Government (2009-
0072357)
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