Efficient copper(I)-catalyzed C-S cross-coupling of thiols with aryl halides in an aqueous two-phase system

Article abstract of DOI:10.1080/17415993.2010.547197

A mild and convenient C-S bond formation reaction catalyzed by CuI/L-proline in an aqueous two-phase system was achieved, providing a simple method for the synthesis of aryl sulfides in good yields.

Full text of DOI:10.1080/17415993.2010.547197

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Efficient copper(I)-catalyzed C–S cross-
coupling of thiols with aryl halides in
an aqueous two-phase system
Xin-Yan Zhang a , Xiao-Yan Zhang b & Sheng-Rong Guo b
a Lishui Vocational and Technical College, Lishui, 323000, People's
Republic of China
b Department of Chem, Lishui University, Lishui, 323000, People's
Republic of China
Available online: 28 Jan 2011
To cite this article: Xin-Yan Zhang, Xiao-Yan Zhang & Sheng-Rong Guo (2011): Efficient copper(I)-
catalyzed C–S cross-coupling of thiols with aryl halides in an aqueous two-phase system, Journal of
Sulfur Chemistry, 32:1, 23-35
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Journal of Sulfur Chemistry
Vol. 32, No. 1, February 2011, 23–35
Efficient copper(I)-catalyzed C–S cross-coupling of thiols with
aryl halides in an aqueous two-phase system
Xin-Yan Zhanga, Xiao-Yan Zhangb and Sheng-Rong Guob*
aLishui Vocational and Technical College, Lishui 323000, People’s Republic of China; bDepartment of
Chem, Lishui University, Lishui 323000, People’s Republic of China
(Received 29 August 2010; final version received 8 December 2010)
A mild and convenient C–S bond formation reaction catalyzed by CuI/L-proline in an aqueous two-phase
system was achieved, providing a simple method for the synthesis of aryl sulfides in good yields.
Keywords: C–S cross-coupling reactions; CuI; thiols; aryl halides; aqueous two-phase system
1. Introduction
C(aryl)–S bonds are present in a large number of molecules that are of interest as pharmaceuticals
and as useful polymeric materials. For this reason, the development of efficient S-arylation meth-
ods is a subject of interest in organic chemistry (1–3). Transition metal-catalyzed or -mediated
arylation of thiols is a direct and powerful method to form these products. Although palladium-
catalyzed C–S bond formation has achieved some good results (4–7), the use of copper catalysts
for this transformation is still attractive from an industrial perspective (8–10). Traditional copper-
mediated couplings between thiols and aryl halides have required the use of copper salts in greater
than stoichiometric amounts, polar solvents such as HMPA, and high temperatures around 200 ◦C
(11). Recently, along with the development of the research on mild copper-catalyzed aromatic
carbon–heteroatom bond formations, copper-catalyzed C–S bond formation has received atten-
tion and this approach is still attractive owing to the advantages of copper over other metals, such
as its price and minor toxicity than Pd and Ni (12, 13).
The use of water as a solvent for organic reactions has been extensive in recent years (14–18)
since water is cheap, nontoxic, safe, and environmentally benign relative to organic solvents.
Recently, Rout et al. (19) described a procedure for C–S bond formation by using a combination
*Corresponding author. Email: guosr9609@163.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2010.547197
http://www.informaworld.com

24 X.-Y. Zhang et al.
of CuI and tetrabutyl ammonium bromide (TBAB) in water, but the reaction time is too long.
Considering the lack of effective methods to synthesize aryl thioethers and their considerable
interest, our group developed a new efficient protocol for the CuI-catalyzed S-arylation of aryl
thiols with aryl bromides and chlorides in an aqueous two-phase system (ATPS).
ATPSs were mainly composed of two-incompatible polymers (e.g. dextran/poly ethylene gly-
col/water) or an organic solvent and a salt (e.g. ethanol/phosphate/water), and it was widely used in
biochemistry (20). Our recent results on C–C bond formation in anATPS encouraged us to extend
the system for C–S bond formation (21, 22); thus, in continuation of our work on coupling reac-
tions, herein, we report a general, efficient protocol for copper-catalyzed C–S coupling in anATPS.
2. Results and discussion
Our experiments were first conducted by coupling 4-methoxyl thiophenol with bromobenzene
catalyzed by 5 mol% of copper (I) iodide and 10 mol% of L-proline, which was proved to be an
effective catalyst system in many researches in various solvents (23–25). As indicated in Table 1,
in pure water, only 62% conversion was obtained after 6 h (Table 1, Entries 2 and 4). Addition of
PTC (e.g. TBAB) led to a gradual increase in the conversion rate (Table 1, Entries 1 and 3). In
anhydrous ethanol, only 78% conversion was achieved after 6 h (Table 1, Entries 5–8); we also
scanned other traditional solvents; polar solvents were better than less polar solvents (Table 1,
Entries 9–12). We then scanned the various ATPS solvents. We selected three kinds of typical
ATPS as reaction solvents to find out the best one for the cross-coupling reaction; to our surprise,
the cross-coupling reaction (Table 1, Entry 16) proceeded to give 98% yield catalyzed with CuI/l-
proline in EtOH/K3PO4/water (add the inorganic salt to the mixture of 6 ml of water and 4 ml
Table 1. The effects of different solvents in the coupling of 4-methoxyl thiophenol
with bromobenzene catalyzed by CuI/l-proline.a
Entry
Solvent
Water
Water
Water
Water
EtOH
EtOH
EtOH
EtOH
DMF
DMSO
1,4-dioxane
Toluene
EtOH/water
EtOH/water
EtOH/water
EtOH/water
EtOH/water
Acetone/water
Acetone/water
PEG2000/water
PEG2000/water
EtOH/water
EtOH/water
Inorganic salts
Catalyst
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
K2CO3
K2CO3
K3PO4
K3PO4
K2CO3
K2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K2CO3
K2CO3
K3PO4
K3PO4
K2HPO4
K2CO3
K3PO4
K2CO3
K3PO4
K3PO4
K3PO4
CuI (add PTC)
CuI/l-proline
CuI (add PTC)
CuI/l-proline
CuI (or CuO)
CuI/l-proline
CuI (or Cu(OAc)2)
CuI/l-proline
CuI/l-proline
CuI/l-proline
CuI/ L-proline
CuI/l-proline
CuI
CuI/l-proline
CuI (or CuO)
CuI/l-proline
CuI/l-proline
CuI/l-proline
CuI/l-proline
CuI/l-proline
CuI/l-proline
Cu(OAc)2)/l-proline
CuO/l-proline
45 (52)
52
57 (59)
62
73 (62)
74
71 (66)
78
82
80
73
69
83
93
88 (72)
98
91
82
85
86
89
78
82
Notes: aReaction conditions: 4-methoxyl thiophenol (5.5 mmol), bromobenzene (5 mmol), 5 mol%
of CuI, 10 mol% of L-proline, 12 mmol base, in 10 ml of solvent at 80 ◦C for 6 h in air atmosphere.
bIsolated yield (average of two runs).

Journal of Sulfur Chemistry 25
of EtOH, then the mixture solution separates into two phases clearly) in an ATPS refluxed for
6 h, the acetone/K3PO4 system (add the inorganic salt to the mixture of 6 ml of water and 4 ml of
acetone, then the mixture solution separates into two phases clearly) proceeded to give 85% yield
(Table 1, Entries 18 and 19), and the PEG2000/K2HPO4 system gave 89% yield (add the inorganic
salt to the mixture of 6 ml of water and 4 g of PEG2000, then the mixture solution separates into
two phases clearly; Table 1, Entries 20 and 21), while there was no reaction in the acid ATPS
such as acetone/(NH4)2SO4 or PEG2000/(NH4)2SO4 system and a mediate yield was obtained in
the ATPS catalyzed only by the CuI without an amino acid. Lastly, using the Cu(II) salts such as
Cu(OAc)2 and CuO as catalysts to promote the coupling reaction, the corresponding diaryl sulfide
was obtained in 62–82% yield (Table 1, Entries 5, 7, 15, 22, and 23). From all those experimental
data in Table 1, we consider that the ATPS with the catalyst system CuI/l-proline is better than
pure water, ethanol, DMF and other traditional solvents for the cross-coupling reaction and that the
optimal condition for the cross-coupling reaction is the EtOH/K3PO4 ATPS as a solvent catalyzed
by CuI/l-proline (Scheme 1).
Scheme 1. Optimization of the reaction conditions.
To explore the scope of the present reaction and expand the scope of our solvent system, we
examined different aryl halides (Table 2). All the aryl halides reacted with thiophenol to give the
Table 2. Cross-coupling of thiophenol with aryl halides in the EtOH/K3PO4/water ATPS.a
Entry
1
Halides
Aryl sulfides
Time (h)
6
Yield (%)b
98
2
3
4
5
97
95
4
5
8
8
84
83
6
6
85
(Continued)

26 X.-Y. Zhang et al.
Table 2. Continued.
Entry
7
Halides
Aryl sulfides
Time (h)
5
Yield (%)b
95
8
6
96
9
10
11
6
7
6
97
95
92
12
13
14
4
5
6
97
98
94
Notes: aReaction conditions: thiophenol (5.5 mmol), halides (5 mmol), 5 mol% of CuI, 10 mol% of l-proline, 12 mmol of
K3PO4, 6 ml of water, and 4 mL of EtOH refluxed at 80 ◦C for 6 h. bIsolated yield (average of two runs).
corresponding aryl sulfides in good yields for 4–8 h in the presence of 5 mol% of CuI and 10 mol%
of l-proline using the EtOH/K3PO4/water ATPS as the reaction solvent (Table 2, Entries 1–14)
(Scheme 2).
Scheme 2. C–S Coupling of various halides with thiophenol.
By using the same protocol, we were also able to couple aryl halides with various substituted
thiophenols, and the results are summarized in Table 3. The substituted arylthiols were success-
fully coupled with the all aryl bromides and chlorides, and no significant electronic effects were

Journal of Sulfur Chemistry 27
Table 3. Cross-coupling of thiophenol with aryl halides in the EtOH/K3PO4/water ATPS.a
Entry
Halides
Thiols
Aryl sulfides
Yield (%)b/time (h)
1
96/3
2
3
91/4
93/4
4
5
91/5
96/4
95/5
94/5
92/6
94/4
92/4
6
7
8
9
10
11
94/5
(Continued)

28 X.-Y. Zhang et al.
Table 3. Continued.
Entry
Halides
Thiols
Aryl sulfides
Yield (%)b/time (h)
12
82/8
13
14
15
84/8
97/2
96/4
16
17
18
19
93/4
85/6
96/8
89/8
20
21
86/8
96/6
(Continued)

Journal of Sulfur Chemistry 29
Table 3. Continued.
Entry
Halides
Thiols
Aryl sulfides
Yield (%)b/time (h)
22
87/6
81/9
23
24
85/12
Notes: aReaction conditions: thiophenol (5.5 mmol), halides (5 mmol), 5 mol% of CuI, 10 mol% of l-proline, 12 mmol of K3PO4, 6 ml of
water and 4 ml of EtOH refluxed at 80 ◦C for 6 h in air atmosphere.
bIsolated yield (average of two runs).
Scheme 3. Reaction of thiols with chloro- and bromobenzene.
observed for para-substituted arylthiols when K3PO4 was used as a base in the aqueous two-phase
media; ortho-substituted arylthiols typically gave a lower yield in the reaction (Entries 12, 20, 22,
23, and 24) (Scheme 3).
3. Conclusions
In summary, we have reported a practical, environmentally more friendly procedure for the copper-
catalyzed S-arylation of thiols with aryl halides in the ATPS that proceeds to give good yields.
The protocol is of potentially practical utility because of the low cost and the availability of aryl
chlorides and the advantages associated with the use of water, but the reaction mechanism is not
clear, maybe the specific interface action was the direct factor.
4. Experimental section
Materials and methods: all thiols (≥98%) were purchased from SHOU&FU Chemical company
(www.shoufu.com); halides (99%) and CuI (99.99%) were purchased fromAldrich. NMR spectra
(300 MHz for 1H and 75 MHz for 13C) were recorded with a Advance-300 Bruker spectrometer
by using CDCl3 as the solvent and Me4Si as the internal standard. Flash column chromatography

30 X.-Y. Zhang et al.
was performed on silica gel (230–400 mesh) with ethyl acetate and hexane as eluents. Melting
points were determined by using a Büchi B-540 melting point apparatus and are uncorrected.
4.1. General procedure for the C–S cross-coupling reaction
Thiophenol (5.5 mmol), halides (5 mmol), 5 mol% of CuI, 10 mol% of l-proline, and 12 mmol
of K3PO4were added to in about 10 ml of the solvent (6 ml of water and 4 ml of EtOH) in air
atmosphere, refluxed at 80 ◦C for the appropriate time, and monitored by TLC. Then the contents
were cooled to room temperature and filtered, and H2O (3 ml) and Et2O (5 ml) were added. The
aqueous layer was extracted using Et2O (10 mL × 4). The combined organic layers were washed
with saturated brine and dried over Na2SO4. The solvent was removed in vacuo, and the residue
was further purified by column chromatography on silica (eluent: EtOAc/petroleum ether = 1:15)
to afford the desired product.
4.2. Data
4.2.1. Diphenyl sulfide (Table 2, Entry 1, 3a)
Colorless liquid (26) 1H NMR (300 MHz, CDCl3): δ 7.15 (m, 2H), 7.19 (m, 4H), 7.25 (m, 4H);
13C NMR (75 MHz, CDCl3): δ 135.7, 130.9, 129.1, 126.9.
4.2.2. 3-Nitrophenyl phenyl sulfide (Table 2, Entry 2, 3b) (27)
M.p.: 40–41 ◦C (Lit. 42 ◦C), 1H NMR (CDCl3): δ 7.16 (m, 3H), 7.38 (m, 3H), 7.67 (m, 1H), 7.85
(m, 1H), 8.12 (m, 1H); 13C NMR (CDCl3): δ 147.0, 139.6, 135.2, 134.9, 131.2, 130.1, 129.1 (2C),
127.8, 123.5, 122.4.
4.2.3. 2-Phenylsulfanylpyridine (Table 2, Entry 3, 3c)
Colorless liquid (28). IR (neat): 3050, 1573, 1446, 1417, 1121, 752 cm−1. GC-MS: (EI, m/z):
189 [M+2]+; 1H NMR (300 MHz, CDCl3): δ 6.86 (d, J = 7.5 Hz, 1H), 6.96 (ddd, J = 1.1, 4.8,
7.4 Hz, 1H), 7.40 (m, 4 H), 7.58 (m, 2H), 8.39 (br d, J = 4.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3): δ 119.8, 121.3, 129.0, 129.6, 131.1, 134.9, 136.6, 149.5, 161.5.
4.2.4. 3-Chloro-2-phenylsulfanylpyridine (Table 2, Entry 4, 3d)
1
Light yellow oil (29). IR (KBr): 3053, 1560, 1477, 1387, 1151, 1026, 749 cm−1. H NMR
(300 MHz, CDCl3): δ 6.93 (dd, J = 4.5, 7.5 Hz, 1H), 7.44 (m, 3H), 7.59 (m, 3H), 8.22 (d,
J = 4.5 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 120.6, 123.2, 129.0, 129.1, 135.4, 136.2, 138.8,
147.3, 157.4.
4.2.5. 2-(Phenylthio)thiophene (Table 2, Entry 5, 3e)
Colorless oil (26). 1H NMR (CDCl3, 300 MHz) δ: 7.52 (dd, J = 4.1, 2H), 7.32 (m, 6H), 7.12 (m,
1H); 13C NMR (75 MHz, CDCl3): δ 124.3, 125.9, 127.0, 127.9, 128.9, 131.2, 135.9, 138.6; Anal
Calcd. for: C, 62.46; H, 4.19; S, 33.35. Found: C, 62.41; H, 4.15; S, 32.35.

Journal of Sulfur Chemistry 31
4.2.6. 3-(Phenylthio)thiophene (Table 2, Entry 6, 3f)
Colorless oil (26). 1H NMR (CDCl3, 300 MHz) δ: 7.62 (q, J = 6.8 Hz, 1H), 7.30 (m, 2H), 7.24
(m, 3H), 6.93 (d, J = 5.6 Hz, 1H), 6.76 (d, J = 4.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ
134.5, 129.4, 129.0, 127.6, 127.4, 125.6, 125.2, 124.6;Anal calcd for: C, 62.46; H, 4.19; S, 33.35.
Found : C, 62.41; H, 4.15; S, 32.35.
4.2.7. 4-(Phenylthio)benzonitrile (Table 2, Entry 7, 3g)
White solid (28), m.p.: 52–53 ◦C. GC-MS: (EI, m/z): 211 (M+); 1H NMR (300 MHz, CDCl3): δ
7.72 (dd, J = 8.7, 3.0 Hz, 2H), 7.54 (m, 2H), 7.51–7.50 (m, 3H), 7.24 (dd, J = 8.7, 3.0 Hz, 2H);
13C NMR (75 MHz, CDCl3): δ 145.8, 134.7, 132.5, 131.0, 130.1, 129.6, 127.5, 119.0, 108.9.
4.2.8. 4-Methylphenyl phenyl sulfide (Table 2, Entry 8, 3h)
1
A clear oil (28). H NMR (300 MHz, CDCl3): δ 2.25 (s, 3H), 7.02 (d, J = 7.9, 2H), 7.19 (m,
7H); 13C NMR (75 MHz, CDCl3): δ 137.5, 137.1, 132.2, 131.2, 130.0, 129.7, 129.0, 126.4, 21.1.
4.2.9. 4,4-Dimethyl-6-(phenylthio)thiochromane (Table 2, Entry 8, 3i)
Yellow crystals, m.p.: 81–83 ◦C. 1H NMR (CDCl3, 300 MHz): δ 1.45 (s, 6H) , 2.03 (m, 2H), 3.12
(m, 2H), 7.22 (d, J = 6.4 Hz, 1H), 7.38 (m, 2H), 7.49 (m, 2H), 7.62 (m, 3H); 13C NMR (75 MHz,
CDCl3): δ 142.3, 141.2, 137.2, 131.1, 128.8, 127.3, 127.0, 126.8, 125.3, 124.9.
4.2.10. 4-(Phenylthio)benzaldehyde (Table 2, Entry 10, 3j)
Yellow crystals (30), m.p.: 51–54 ◦C. IR (KBr): ν 2750, 1652, 1535, 785 cm−1. 1H NMR (CDCl3,
300 MHz) δ: 7.25 (d, J = 4.6 Hz, 2H), 7.44 (m, 3H), 7.52 (m, 2H), 7.71 (q, J = 8.6 Hz, J =
4.6 Hz, 2H), 9.91 (s, 1H); 13C NMR (75 MHz, CDCl3): 127.33, 129.15, 129.82, 130.13, 131.44,
133.82, 134.34, 147.19, 191.11.
4.2.11. 4-Benzotrifluoride(phenyl)sulfane (Table 2, Entry 11, 3k)
A clear oil (28). 1H NMR (300 MHz, CDCl3): δ 7.24–7.48 (m, 9H); 13C NMR (75 MHz, CDCl3,)
δ: 143.0, 133.6, 132.7, 129.9, 129.7, 128.7, 128.4, 126.1, 125.9.
4.2.12. 1-(4-(Phenylthio)phenyl)ethanone (Table 2, Entry 12, 3l)
1
White solid (29), m.p.: 62–63.6 ◦C. H NMR (300 MHz, CDCl3): δ 2.53 (s, 3H), 7.19 (d, J =
8.4 Hz, 2H), 7.39 (m, 3H), 7.49 (m, 2H), 7.80 (d, J = 8.4 Hz, 2H,); 13C NMR (75 MHz, CDCl3):
δ 197.2, 145.0, 134.7, 134.0, 132.3, 129.8, 129.1, 128.9, 127.7, 26.6.
4.2.13. (4-nitrophenyl)(phenyl)sulfane (Table 2, Entry 13, 3m)
1
Yellow solid (28), m.p.: 56–57 ◦C. H NMR (300 MHz, CDCl3): δ 7.28 (dd, J = 9.2, 2.3 Hz,
2H), 7.54 (m, 3H), 7.58 (d, J = 2.8 Hz, 2H), 8.13 (dd, J = 9.2, 2.3 Hz, 2H); 13C NMR (75 MHz,
CDCl3): δ 148.7, 145.5, 134.9, 130.5, 130.2, 129.9, 126.8, 124.2.

32 X.-Y. Zhang et al.
4.2.14. 4-Methoxyphenyl phenyl sulfide (Table 3, Entry 1, 4a)
Colorless liquid (28). 1H NMR (CDCl3): δ 3.62 (s, 3H), 6.71 (d, J = 8.8 Hz, 2H), 6.98 (m, 3H),
7.04 (m, 2H), 7.23 (d, J = 8.8 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 159.7, 138.5, 135.3 (2C),
128.8 (2C), 128.1 (2C), 125.7, 124.2, 114.9 (2C), 55.3.
4.2.15. 4-Methylphenyl phenyl sulfide (Table 3, Entry 2, 4b)
A clear oil (31). 1H NMR (300 MHz, CDCl3) δ 2.25 (s, 3H), 7.02 (d, J = 7.9, 2H), 7.14 (m, 7H);
13C NMR (75 MHz, CDCl3) δ 137.5, 137.1, 132.2, 131.2, 130.0, 129.7, 129.0, 126.4, 21.1.
4.2.16. 3-Methylphenyl phenyl sulfide (Table 3, Entry 3, 4c)
Colorless liquid (32). 1H NMR (300 MHz, CDCl3): δ 2.18 (s, 3H), 6.92 (m, 1H), 7.08 (m, 4H),
7.16 (m, 2H), 7.21 (m, 2H); 13C NMR (75 MHz, CDCl3): δ 138.9, 136.0, 135.1, 131.7, 130.6
(2C), 129.0 (2C), 128.9, 128.2, 127.9, 126.7, 21.2.
4.2.17. (4-Isopropylphenyl)(phenyl)sulfane (Table 3, Entry 4, 4d)
1
Colorless liquid (33). H NMR (300 MHz, CDCl3): δ 1.28 (d, J = 6.2 Hz, 6H), 2.76–3.03 (m,
1H), 7.11–7.44 (m, 9H); 13C NMR (75 MHz, CDCl3): δ 148.3, 136.8, 131.9, 131.7, 130.0, 129.0,
128.1, 127.3, 127.1, 126.4, 33.7, 23.8.
4.2.18. (4-Fluorophenyl)(phenyl)sulfide (Table 3, Entry 5, 4e)
Colorless liquid (34). 1H NMR (300 MHz, CDCl3): δ 7.05 (m, 2H), 7.21 (m, 1H), 7.26 (m, 4H),
7.40 (m, 2H); 13C NMR (75 MHz, CDCl3): δ 116.3 , 116.5, 126.7, 129.2 (2C), 129.9 (2C), 130.2,
134.0, 134.1, 136.6, 161.1, 163.6.
4.2.19. (4-Chlorophenyl)(phenyl)sulfane (Table 3, Entry 6, 4f)
1
Colorless liquid (35). H NMR (CDCl3, 300 MHz): δ 7.16 (d, J = 8.5 Hz, 2H), 7.22–7.40 (m,
7H); 13C NMR (75 MHz, CDCl3): 135.4, 134.7, 132.1, 132.0, 131.4, 129.3, 127.5.
4.2.20. (4-Bromophenyl)(phenyl)sulfane (Table 3, Entry 7, 4g)
1
Colorless liquid (36). H NMR (CDCl3, 300 MHz): δ 7.20–7.38 (m, 9H); 13C NMR (75 MHz,
CDCl3) δ:135.0, 134.6, 132.9, 131.9, 131.2, 129.2, 127.4.
4.2.21. (Naphthalen-6-yl)(phenyl)sulfane (Table 3, Entry 8, 4h)
Colorless liquid (22). 1H NMR (CDCl3, 300 MHz) δ: 7.05–7.58 (m, 8H), 7.62–7.96 (m, 4H); 13
C
NMR (75 MHz, CDCl3): δ 135.8, 133.7, 132.9, 132.2, 130.8, 129.8, 129.1, 128.8, 128.7, 127.6,
127.3, 127.0, 126.5, 126.1.

Journal of Sulfur Chemistry 33
4.2.22. 2-p-Tolylsulfanylpyridine (Table 3, Entry 9, 4i)
1
Colorless liquid (29). IR (neat): 3042, 2920, 1571, 1448, 1417, 1123, 758 cm−1; H NMR
(300 MHz, CDCl3): δ 2.41 (s, 3H), 6.80 (d, J = 7.4 Hz, 1H), 6.92 (ddd, J = 0.9, 4.8, 7.4 Hz, 1H),
7.20 (d, J = 7.8 Hz, 2H), 7.38 (m, 1H), 7.47 (d, J = 7.8 Hz, 2H), 8.36 (br d, J = 4.8 Hz, 1H);
13C NMR (75 MHz, CDCl3): d = 21.3, 119.5, 120.9, 127.2, 130.4, 135.2, 136.6, 139.4, 149.4,
162.1.
4.2.23. 2-(4-Bromophenylsulfanyl)pyridine (Table 3, Entry 10, 4j)
White solid (29), m.p.: 78–81 ◦C. IR (KBr): 3045, 1571, 1416, 1123, 1009, 758 cm−1. 1H NMR
(300 MHz, CDCl3): δ 6.94 (d, J = 8.0 Hz, 1H), 6.99 (ddd, J = 0.8, 4.8, 7.4 Hz, 1H), 7.38–7.47
(m, 3H), 7.53 (d, J = 8.8 Hz, 2H), 8.38 (br d, J = 4.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ
120.2, 121.6, 123.3, 130.2, 132.7, 136.1, 136.7, 149.6, 160.1. ESI MS: m/z = 266 (M + H).
4.2.24. 2-(4-Chlorophenylsulfanyl)pyridine (Table 3, Entry 11, 4k)
Light yellow liquid (29). IR (KBr): 3044, 1551, 1443, 1083, 816, 743 cm−1. 1H NMR (300 MHz,
CDCl3): δ 6.93 (d, J = 8.0 Hz, 1H), 6.98 (ddd, J = 0.9, 4.8, 7.4 Hz, 1H), 7.37 (d, J = 8.3 Hz,
2H), 7.45 (m, 1H), 7.49 (d, J = 8.3 Hz, 2H), 8.37 (br d, J = 4.8 Hz, 1H); 13C NMR (75 MHz,
CDCl3): δ 120.2, 121.6, 129.8, 135.3, 136.0, 136.7, 149.7, 160.4.
4.2.25. 2-(2-Methoxyphenylsulfanyl)pyridine (Table 3, Entry 12, 4l)
Colorless liquid (29). IR (KBr): 2836, 1574, 1477, 1274, 1122, 755 cm−1. 1H NMR (300 MHz,
CDCl3): δ 3.81 (s, 3H), 6.80 (d, J = 8.0 Hz, 1H), 6.88–7.03 (m, 3H), 7.33–7.45 (m, 2H), 7.55
(m, 1H), 8.36 (br d, J = 5.1 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 55.8, 111.5, 119.5, 120.7,
121.3, 131.2, 136.4, 136.4, 136.9, 149.3, 159.6, 160.7.
4.2.26. 2-(Naphthalen-2-ylsulfanyl)pyridine (Table 3, Entry 13, 4m)
1
Light yellow oil (29). IR (KBr): 2922, 1570, 1447, 1414, 1121, 752 cm−1. H NMR ( MHz,
CDCl3): δ 6.89 (d, J = 7.8 Hz, 1H), 6.96 (ddd, J = 0.9, 4.8, 7.5 Hz, 1H), 7.40 (m, 1H), 7.50
(m, 2H), 7.8 (d, J = 8.4 Hz, 1H), 7.77–7.88 (m, 3H), 8.11 (s, 1H), 8.40 (d, J = 4.8 Hz, 1H);
13C NMR ( MHz, CDCl3): δ 119.9, 121.4, 126.6, 127.0, 127.8, 129.2, 133.8, 134.6, 134.5, 136.7,
149.5, 161.4.
4.2.27. (3-Nitrophenyl)(p-tolyl)sulfane (Table 3, Entry 14, 4n)
White solid (30), m.p.: 108–110 ◦C. 1H NMR (300 MHz, CDCl3): δ 8.39 (t, 1H), 8.17–8.20 (dd,
J = 8.2, 1.1 Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H), 7.44–7.54 (m, 3H), 7.31 (m, 2H), 2.36 (s, 3H);
13C NMR (75 MHz, CDCl3): δ 148.8, 137.7, 136.9, 130.8, 129.3, 127.5, 127.2, 126.7, 122.9,
122.2, 23.1.
4.2.28. (4-Bromophenyl)(3-nitrophenyl)sulfane (Table 3, Entry 15, 4o)
Whitesolid(27), m.p.:132–134 ◦C. 1HNMR(300 MHz, CDCl3):δ 8.15(t, 1H), 8.07(dd, J = 8.2,
1.2 Hz, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.71–7.79 (m, 2H), 7.45–7.54 (m, 3H), 2.36 (s, 3H); 13
C
NMR (75 MHz, CDCl3): δ 148.5, 138.9, 135.8, 133.6, 132.3, 132.1, 128.0, 127.9, 122.0, 121.8.

34 X.-Y. Zhang et al.
4.2.29. (4-Chlorophenyl)(3-nitrophenyl)sulfane (Table 3, Entry 16, 4p)
White solid(31), m.p.: 115–117 ◦C. 1H NMR (300 MHz, CDCl3): δ 8.13(t, 1H), 8.03 (dd, J = 8.2,
1.2 Hz, 1H), 7.80–7.74 (m, 3H), 7.51 (t, 1H), 7.30–7.36 (m, 2H); 13C NMR (75 MHz, CDCl3): δ
148.4, 139.9, 134.8, 133.8, 132.9, 130.7, 130.5, 129.9, 123.0, 122.6.
4.2.30. 4-(p-Tolylthio)benzaldehyde (Table 3, Entry 17, 4q)
Yellow solid (30), m.p.: 53–53 ◦C. IR (KBr): ν 2780, 1602, 1565, 785, 767 cm−1. H NMR
1
(CDCl3, MHz): δ 2.36 (s, 3H), 7.20 (m, 4H), 7.43 (dd, J = 8.0, 1.9 Hz, 2H), 7.70 (dd, J = 8.2 Hz,
J = 1.7 Hz, 2H), 9.81 (s, 1H); 13C NMR (75 MHz, CDCl3): δ 21.3, 126.6, 128.5, 129.4, 129.8,
130.1, 130.6, 134.8, 139.7, 148.2, 191.1.
4.2.31. 4-(4-Fluorophenylthio)benzaldehyde (Table 3, Entry 18, 4r)
1
Yellow crystals (30), m.p.: 63–65 ◦C. IR (KBr): ν 2716, 1685, 1550 ,785 760 cm−1. H NMR
(CDCl3, 300 MHz): δ 7.18 (m, 4H), 7.22 (m, 2H), 7.32 (dt, J= 6.7 Hz, J = 1.8 Hz, 2H), 9.90
(s, 1H); 13C NMR (75 MHz, CDCl3): 116.9, 117.2, 126.7, 130.1, 133.8, 136.8, 136.9, 147.3,
161.8, 165.1, 191.0.
4.2.32. 4-(3-(Trifluoromethyl)phenylthio)benzaldehyde (Table 3, Entry 19, 4s)
Light yellow oil (30). 1H NMR(CDCl3, 300 MHz): δ 7.37 (dd, J= 8.8 Hz, J = 1.6 Hz, 2H), 7.56
(m, 1H), 7.66 (m, 2H), 7.77 (m, 3H), 9.94 (s, 1H); 13C NMR (MHz, CDCl3): 125.50, 128.53,
129.44, 129.90, 130.18, 130.48, 130.91, 133.89, 134.46, 136.53, 144.87, 191.17.
4.2.33. 4-(2-Chloro-6-methylphenylthio)benzaldehyde (Table 3, Entry 20, 4t)
1
White crystals (30), m.p.: 42–44 ◦C. H NMR (CDCl3, 300 MHz): δ 2.28 (s, 3H), 7.11 (dd,
J = 6.8, 2.4 Hz, 2H), 7.34 (m, 2H), 7.45 (d, J = 2.1 Hz, 1H), 7.80 (dd, J = 8.3, 2.6 Hz, 2H),
9.87 (s, 1H); 13C NMR (75 MHz, CDCl3): 20.1, 127.1, 129.7, 132.1, 132.1, 132.3, 133.9, 134.8,
140.3, 145.5, 190.9.
4.2.34. 4-(3-Fluoro-4-methoxyphenylthio)benzaldehyde (Table 3, Entry 21, 4u)
White solid (30), m.p.: 74–76 ◦C. 1H NMR (CDCl3, 300 MHz): δ 3.93 (s, 3H), 7.02 (t, J = 8.4 Hz,
1H), 7.17 (dd, J = 7.0, 2.6 Hz, 1H), 7.42 (m, 3H), 7.72 (dd, J = 6.9, 3.2 Hz, 2H), 9.90 (s, 1H);
13C NMR (75 MHz, CDCl3): 56.32, 114.24, 122.68, 126.51, 130.15, 131.67, 133.72, 147.60,
149.19, 150.84, 154.66, 191.09.
4.2.35. 4-(2,5-Difluorophenylthio)benzaldehyde (Table 3, Entry 22, 4v)
White solid (30), m.p.: 50–52 ◦C. 1H NMR (CDCl3, MHz): δ 7.19 (m, 3H), 7.34 (dd, J = 8.2,
3.2 Hz, 1H), 7.80 (dd, J = 6.7, 2.4 Hz, 2H), 9.95 (s, 1H); 13C NMR (75 MHz, CDCl3): 117.20,
117.53, 117.92, 128.47, 130.32, 134.67, 143.28, 156.98, 160.25, 190.99.

Journal of Sulfur Chemistry 35
4.2.36. 4-(2,4-Dimethoxyphenylthio)benzaldehyde (Table 3, Entry 23, 4w)
White solid (30), m.p.: 124–126 ◦C. 1H NMR (CDCl3, 300 MHz): δ 3.79 (s, 3H), 3.87 (s, 3H),
6.62 (m, 2H), 7.11 (dd, J = 6.8, 4.8 Hz, 2H), 7.53 (m, 1H), 7.74 (m, 2H), 9.87 (s, 1H); 13C NMR
(75 MHz, CDCl3): 55.56, 56.01, 99.58, 105.81, 125.49, 129.92, 133.15, 136.66, 148.37, 160.39,
161.28, 191.22.
4.2.37. 4-(2-Isopropylphenylthio)benzaldehyde (Table 3, Entry 24, 4x)
Yellow oil (30). 1H NMR (CDCl3, 300 MHz): δ 1.18 (s, 3H), 1.20 (s, 3H), 3.58 (q, J = 1.8 Hz,
1H), 7.12 (d, J = 8.3 Hz, 2H), 7.27 (m, 1H), 7.45 (d, J = 4.2 Hz, 2H), 7.52 (d, J = 8.3 Hz,
1H), 7.71 (d, J = 8.3 Hz, 2H), 9.89 (s, 1H); 13C NMR (75 MHz, CDCl3): 23.74, 31.02, 126.52,
126.74, 127.14, 130.11, 130.48, 130.57, 133.37, 136.73, 148.38, 152.75, 191.20.
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