Surfactant-Type Catalyst for Aerobic Oxidative Coupling of Hydrazine with Thiol in Water

Article abstract of DOI:10.1021/acs.joc.9b00451

A series of PEG-functionalized nitrogen ligands were developed to conduct an aerobic oxidative cross-coupling reaction between alkyl- or aryl-hydrazines with thiols in water. This surfactant-type catalyst enables high efficiencies and selectivities, while tolerating a large variety of functional groups. The mother liquor is still catalytically active after five runs.

Full text of DOI:10.1021/acs.joc.9b00451

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Note
Surfactant-Type Catalyst for Aerobic Oxidative
Coupling of Hydrazine with Thiol in Water
Xuanhe Ren, Shanyu Tang, Longjia Li, Jiao Li, Helong Liang,
Ganzhong Li, Guanyu Yang, Heng Li, and Bingxin Yuan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00451 • Publication Date (Web): 04 Jun 2019
Downloaded from http://pubs.acs.org on June 4, 2019
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Surfactant-Type Catalyst for Aerobic Oxidative
Coupling of Hydrazine with Thiol in Water
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Xuanhe Ren,‡ Shanyu Tang,‡ Longjia Li, Jiao Li, Helong Liang, Ganzhong Li, Guanyu Yang,
Heng Li, and Bingxin Yuan*
College of Chemistry and Molecular Engineering, Zhengzhou University, Henan, China 450001
Keywords: Surfactant-type Catalyst • Aerobic Oxidative Coupling • Alkylhydrazine • Water as
Solvent • Catalyst Recycle
O2 as oxidant
R1 NHNH2
HS R2
N
Cu
N
1
:
1
Water as solvent
Catalyst recycle
up to 99% yield
37 examples
N
N
N
R1 S
R2
R1, R2 = alkyl, aryl
Abstract: A series of PEG-functionalized nitrogen ligands were developed to conduct the aerobic
oxidative cross-coupling between alkyl- or aryl-hydrazines with thiols in water. This surfactant-
type catalyst enables high efficiency and selectivity while tolerates a large variety of functional
groups. The mother liquor is still catalytically active after five runs.
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Organosulfides have triggered considerable interest in synthetic chemistry, material chemistry,
food science and pharmaceutical field (Figure 1).1 For instance, saccharin is an artificial
sweetener used in food and drinks with no food energy.2 Penicillin, dapsone and ceftizoxime are
commercialized antibiotics.1h, 1i Butoconazole is a typical antifungal used in gynecology.1i
Omeprazole is used in the treatment of petic ulcer and gastroesophageal reflux.1j Organosulfur
compounds are widely found in nature due to their involvement in DNA cleavage, DNA binding
and protein folding.3
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Representative organosulfur compounds:
H
R
OMe
O
H
O
N
S
O
N
COOH
NH
N
N
S
O
O
H2N
S
O
OH
O
S
O
dapsone
saccharin
penicillin
S
Cl
H
Cl
Cl
H2N
N
SO3
S
N
N
N
S
O
O
N
N
ceftizoxime
omeprazole
butoconazole
Previous Work:
Traditional coupling:
X
HS
S
TM
ligand
X = hal, OTf
Oxidative coupling:
HS
NHNH2
S
Pd, P ligand
O2, toluene
R2
R1
R2
R1
Figure 1. Representative structures and synthesis of organosulfur compounds.
While many efforts have been directed towards the synthesis of organic sulfides,4 transition
metal (mostly palladium) catalyzed cross-coupling reaction of prefunctionalized arenes with
thiols is a powerful tool to construct unsymmetrical C-S bond (Figure 1).5 However, those
methods are limited to narrow substrate scopes, harsh reaction conditions, and inert reaction
atmosphere. Arylhydrazines are known to generate radical species during oxidative degradation,6
thus they have emerged as an environmentally benign arylation agents for cross-coupling
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reactions since the only byproducts are water and nitrogen gas. Recently, Zhao and coworkers
disclosed a Pd(II)-catalyzed oxidative coupling of arylhydrazines with arylthiols in toluene,
affording the unsymmetrical diaryl sulfides in 71-84% yields (Figure 1).7 Later, Hajra et al made
great progress by developing a rose bengal catalyzed aerobic oxidation to synthesize
diarylsulfides in water under 34 W blue LED.8 However, both Zhao’s and Hajra’s protocols are
limited to aryl substrates, consuming 2 equivalents of arylhydrazines against thiols. Therefore,
the development of more efficient and versatile method with higher chemoselectivity and wider
scope is desired.
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3
3
O
O
O
O
O
O
N
N
O
O
3
3
N
N
N
N
L2
L1
3
3
O
O
O
O
O
O
O
3
O
3
N
N
L3
L5
L4
N
N
O
O
O
3
O
3
nitrogen
chelate
PEG
block
N
substrates
N
N
Cu
N
N
N
This Work:
[Cu]
surfactant-type ligand
NHNH2
1
R1
S
R1
HS R2
R2
O2, H2O
R1, R2 = alkyl, aryl
:
1
Figure 2. Designed surfactant-type ligands, and proposed process of the aerobic oxidative
coupling reaction in water.
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Water as solvent is not only a strategy to achieve green synthesis, but also promising to enable
catalyst recycle and simple work-up procedure.9 However, most organic catalysts and reaction
substrates exhibit poor solubility in water. To overcome this obstacle, the traditional solution is
to perform the reaction in the presence of surfactants.10 Novel surfactant systems for catalyst
recovery have been investigated by covalently attaching surfactant scaffolds to the ligands,
addressing the solubility problem of catalysts as well as organic reaction partners.11 We designed
and synthesized a series of PEG-functionalized amphiphilic nitrogen ligands L1-5 (Figure 2).
Such ligands bestow aqueous solubility and surfactant characteristic to their corresponding
transition metal complexes. The probable micellar structures formed in water by self-aggregation
of such surfactant-type ligands are proposed in Figure 2. The hydrophilic PEG tails align to form
the hydrophilic surface of the micelle, while the transition metal coordinates to the N-ligands in
the micellar core. The hydrophobicity of organic substrates forces them to enter and self-enrich
in the micellar core. Hypothetically, the metallomicelles could behave as nanoreactors12 and
facilitate the aerobic oxidative coupling reaction. Herein, we developed surfactant-type catalyst
for environmentally friendly and highly chemoselective aerobic oxidative coupling of alkyl- and
arylhydrazines with thiols in water, avoiding the employment of excess hydrazines.
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Table 1. Optimization of the Reaction Conditions. a
S
NHNH2
HS
catalyst, ligand
+
Cs2CO3, O2, H2O
100 oC, 12h
OCH3
OCH3
1a
2a
3a
Entry
Catalyst
CuCl
Ligand Yield (%) b
1
2
3
L1
L1
L1
84
70
75
CoCl2
Mn(CH3COO)2•2H2O
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FeCl3
CuBr
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
--
60
65
6
CuI
85
7
CuCl2•2H2O
Cu(NO3)2•3H2O
Cu(CH3COO)2•H2O
Cu(OTf)2
85
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8
99 (73 c)
70
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70
Cu(NO3)2•3H2O
Cu(NO3)2•3H2O
Cu(NO3)2•3H2O
Cu(NO3)2•3H2O
Cu(NO3)2•3H2O
--
57
40
56
60
50
--
37
[a] 1a (0.2 mmol), 2a (0.2 mmol), catalyst (5 mol%), ligand (5 mol%), Cs2CO3 (1.0 equiv.), 1 atm O2, H2O (2
mL), 100 oC, 12 h. [b] Isolated yields. [c] Cu(NO3)2•3H2O (3 mol%), L1 (3 mol%).
To test our hypothesis, a model reaction was performed between phenylhydrazine 1a (1
equiv.) and 4-methoxybenzenethiol 2a (1 equiv.) with CuCl as catalyst, L1 as ligand, and
Cs2CO3 as base under 1 atm O2 in water (Table 1). Various transition metal salts (Cu, Co, Mn,
Fe) were screened (Entry 1-4), and CuCl turned out to be the most active. Subsequently, a series
of Cu(I) and Cu(II) species were tested (Entry 5-10). Cu(NO3)2•3H2O was found to be the
optimal catalyst and give the desired diarylsulfide 3a in quantitative yield (Entry 8). Comparing
to the result of L1, other PEG-modified amphiphilic nitrogen ligands L2-5 resulted in much
lower yields (Entry 11-14). The control experiments were conducted in the absence of
Cu(NO3)2•3H2O or L1. The target product was formed in much lower yields (Entry 15, 16),
indicating the necessity of catalyst and ligand. Furthermore, we tried to bring down the catalyst
loading to 3 mol%, however, the product yield decreased to 73% (Entry 8).
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Table 2. Screening other reaction parameters. a
5
6
7
8
S
NHNH2
HS
L1
Cu(NO3)2 3H2O,
+
base, atmosphere,
H2O, time, 100 oC,
OCH3
OCH3
1a
2a
3a
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Entry
Base
Time (h) H2O (mL) Atmosphere Yield (%) b
1
2
Na2CO3
K2CO3
NaOH
--
12
12
12
12
12
10
8
2
2
O2
O2
O2
O2
O2
O2
O2
O2
O2
N2
Air
70
61
52
53
72 c
86
82
50
48
20
74
3
2
4
2
5
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
2
6
2
7
2
8
12
12
12
12
1
9
0.5
2
10
11
2
[a] 1a (0.2 mmol), 2a (0.2 mmol), Cu(NO3)2•3H2O (5 mol%), L1 (5 mol%), base (1.0 equiv.), 1 atm
atmosphere, H2O (x mL), 100 oC, y h. [b] Isolated yields. [c] 80 oC.
Further optimizations revealed that this reaction proceeded more efficiently in the presence of
Cs2CO3 as base (Table 2, Entry 1-4). Interestingly, the ion effect of base plays an important role
on the reaction (Entry 1-2). Other reaction parameters including reaction temperature, reaction
hour, and solvent volume were tested to get the optimal reaction conditions (Entry 4-9). Control
experiments were conducted under nitrogen (Entry 10) and air (Entry 11), stating the necessity of
molecular oxygen as the oxidant for this oxidative coupling reaction.
Table 3. Substrate scope of hydrazines.a, b
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HS
S
L1
Cu(NO3)2 3H2O,
R
R
NHNH2
+
OCH3 Cs2CO3, O2, H2O
100 oC, 12 h
OCH3
2a
3
1
6
S
S
S
7
8
9
OCH3
OCH3
OCH3
OCH3
c
3a
3c
: 99%
: 92%
S
3b
: 92%
S
S
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OCH3 H3CO
OCH3
3d
3e
: 73%
S
: 69%
S
3f
: 90%
S
Cl
F
OCH3
OCH3
Cl
Br
OCH3
OCH3
3i
3h
: 90%
S
3g
: 79%
: 90%
S
Cl
Cl
S
OCH3
OCH3
3j
3k
3l
: 90%
S
: 89%
S
: 85%
S
Br
OCH3 NC
OCH3 O2N
OCH3
OCH3
c
3m
3n
: 90%
: 95%
3o
: 41%
S
NO2
NO2
S
S
OCH3
O2N
OCH3
c
3p
3r
: 68%
S
: 75%
S
3q
: 65%
N
S
OCH3
OCH3
OCH3
c
3t
3u
: 85%
: 90%
3s
: 94%
[a] 1 (R-NHNH2•HCl, 0.2 mmol), 2a (0.2 mmol), Cu(NO3)2•3H2O (5 mol%), L1 (5 mol%), Cs2CO3 (2 equiv.),
1 atm O2, H2O (2 mL), 100 oC, 12 h. [b] Isolated yields. [c] 1 (R-NHNH2), Cs2CO3 (1 equiv.)
With the optimal condition in hand, we proceed to examine the substrate scopes of hydrazines
to react with 4-methoxybenzenethiol 2a (Table 3). One extra equivalent of base was added to
quench the acid when RNHNH2•HCl was adopted as substrate. Fortunately, a large variety of
aryl- and alkylhydrazines were well tolerated. Arylhydrazines bearing electron-donating groups,
such as methyl (at para-, meta- or ortho-position), dimethyl and methoxy groups, led to the
formation of products 3b-f in good to excellent yields. Compared to 3b and 3c, the relatively
lower yield of product 3d might be caused by the steric effect of methyl group at ortho-position
on the benzene ring. Halogen (F, Cl, Br) substituted arylhydrazines furnished the corresponding
diarylsulfides successfully (3g-m), providing potential synthetic applications via conventional
coupling reaction. Arylhydrazines with strong electron-withdrawing substituents, such as nitrile
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and nitro, furnished products smoothly (3n-q). 2-Naphthylhydrazine and 2-pyridinylhydrazine as
substrates could also give products (3r, 3s) in excellent yields. To be noticed, alkylhydrazines
were well tolerated and gave the corresponding organosulfides (3t, 3u) in excellent yields.
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Table 4. Substrate scope of thiols. a, b
NHNH2
S
L1
Cu(NO3)2 3H2O,
R
+
R
S
SH
Cs2CO3, O2, H2O
100 oC, 12 h
1a
2
4
S
S
Ph
S
Ph
Ph
Ph
Ph
NH2
c
d
d
4d
: 99%
S
4a
4b
4c
: 95%
: 97%
: 97%
Br
S
S
Ph
S
Ph
Ph
N
e
NO2
Cl
c
4f
4g
: 70%
: 60%
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4e
4h
: 99%
: 85%
S
N
S
N
S
S
Ph
Ph
Ph
Ph
S
N
N
Ph
e
e
e
e
4i
4j
4k
4l
: 76%
: 95%
O
: 95%
: 75%
S
Ph
S
S
Ph
S
N
Ph
e
4n
4o
4p
: 70%
: 58%
: 50%
4m
: 81%
[a] 1a (0.2 mmol), 2 (0.2 mmol), Cu(NO3)2•3H2O (5 mol%), L1 (5 mol%), Cs2CO3 (1 equiv.), H2O (2 mL), 1
atm O2, 100 oC, 12 h. [b] Isolated yields. [c] 24 h. [d] 36 h. [e] No base.
Further insight into the aerobic oxidative coupling reaction of hydrazines with thiols was
obtained by examining the substrate scope of thiols (Table 4). Nearly all phenylthiols bearing
electron-donating and electron-withdrawing groups, except for nitro-substituted phenylthiol (2g),
afforded the target products in 70-99% yields. Interestingly, heteroaromatic thiols were
successfully converted in good to excellent yields (4h-m) in the absence of base. Benzyl thiol
and alkyl thiols were also tolerated (4n-p).
S
NHNH2
HS
L1
Cu(NO3)2 3H2O,
+
OCH3 Cs2CO3, O2, H2O
100 oC, 12 h
2a
OCH3
3a
1 g, 95%
1a
Scheme 1. Gram-scale synthesis.
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The scalability of our protocol was evaluated by performing the reaction on a 5 mmol scale
(Scheme 1). The target product 3a was formed in 95% yield, showing good potential in practical
synthesis. Since the use of water as solvent offers the opportunity to recycle the catalyst, we
performed mother liquor circulation experiments on the model reaction of 1a with 2a (Figure S1,
see supporting information). As product 3a is a liquid, it was obtained by simple extraction of the
aqueous phase with hexane. Fresh batch of substrates was added to the recovered mother liquor
for next run. The aqueous phase is still catalytically active after five runs with minor decrease in
reactivity or product yield.
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To probe the reaction mechanism, we added a typical radical scavenger, 2,2,6,6-
(tetramethylpiperidin-1-yl)oxyl (TEMPO), to the oxidative coupling reaction between hydrazine
1a and thiol 2a under the standard reaction conditions (Scheme 2, reaction A). The reaction was
sufficiently suppressed by TEMPO, indicating radical intermediates might be involved in the
catalytic cycle. We utilized 1,2-bis(4-methoxyphenyl)disulfane instead of 4-
methoxybenzenethiol 2a to react with phenylhydrazine 1a (Scheme 2, reaction B). The desired
product was obtained in 72% yield. Furthermore, the reaction of 1a with DMPO in the absence
of 2a was carried out, and the products were analyzed via HRMS. The corresponding adduct of
DMPO with the phenyl radical generated from 1a was detected (Scheme 2, reaction C). When 2a
was treated with TEMPO in the absence of 1a, adduct of TEMPO with the thiyl radical from 2a
was observed as well (Scheme 2, reaction D). Conclusively, the reaction possibly proceeds via a
radical pathway.
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2 eq TEMPO
Cu(NO3)2 3H2O,
S
OCH3
NHNH2
L1
A)
B)
+
Cs2CO3, O2, H2O
100 oC, 12 h
OCH3
HS
3a
: 30%
S
1a
2a
S
NHNH2
L1
Cu(NO3)2 3H2O,
+
Cs2CO3, O2, H2O
100 oC, 12 h
OCH3
H3CO
2
1a
3a
: 72%
0.2 mmol
0.1 mmol
1 eq DMPO
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NHNH2
L1
N
Cu(NO3)2 3H2O,
C)
O
Cs2CO3, O2, H2O
100 oC, 12 h
1a
HRMS detected
1 eq TEMPO
D) HS
L1
Cu(NO3)2 3H2O,
N
S
O
Cs2CO3, O2, H2O
100 oC, 12 h
OCH3
OCH3
2a
HRMS detected
Scheme 2. Mechanistic studies by experiments.
A possible mechanism for this Cu-catalyzed aerobic oxidative cross-coupling reaction
between phenylhydrazine and thiol was proposed in Scheme 3. In cycle I, ligand exchange of the
Cu(II) precursor by phenylhydrazine leads to the formation of copperdiaziridine intermediate A.
Protonolysis of A releases the organocopper intermediate B and a copperdiaziridine complex C,
which the latter collapses to release nitrogen gas and water in the presence of O2 while
regenerate the Cu(II). On the other hand, phenylcopper specie B affords the corresponding phenyl
radical and Cu(I) specie with the aid of Cu(II). In cycle II, the reaction of Cu(II) complex with thiol
generate thiyl copper intermediate D, then transformed into the corresponding thiyl radical and
Cu(I). Heterocoupling of thiyl radical and phenyl radical furnishes the desired product, while
Cu(II) could be regenerated by the oxidation of Cu(I). Meanwhile, the disulfide is produced by the
homocoupling of thiyl radicals, then reacts with phenyl radical to give the desired product and
regenerate the thiyl radical.
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HX
Ph NHNH2
4
R
SH
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N
N
N
N
HX
Cu(II)
Cu(II)X2
Ph
N
NH
A
Cycle I
Cycle II
Cu(II), HX
9
N
N
X
D
O2
Cu
O2, HX
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R
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N
N
Cu(II)
HN NH
N2, H2O
C
N
N
X
N
N
(I)
Cu
Cu
X
Ph
Cu(II)
B
Cu(II)
Ph
S
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Ph
S
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S
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2
S
S
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Ph
Ph
S
R
R
R
R
S
Scheme 3. Proposed Reaction Mechanism.
In summary, we have established an efficient and benign surfactant-type catalyst for aerobic
oxidative coupling of hydrazines with thiols. Organosulfides can be obtained in good to excellent
yields by using O2 as the sole oxidant and water as solvent. This new Cu-surfactant catalysis
leads to highly effecient and chemoselective cross-coupling reaction thus no excess amount of
one substrate is required. A large range of substituents are bearable, including halogens (Cl, Br).
More importantly, alkylhydrazines are able to afford the desired products in excellent yields.
Gram-scale reaction were successfully performed, providing an valuable tool for synthetic
chemistry as well as industrial manufacturing. The mother liquor could be recycle for five run
with minor loss in reactivity and product yield.
EXPERIMENTAL SECTION
General Information. All materials and catalysts were purchased from general merchant and
used in the original state unless otherwise stated. 1H NMR and 13C NMR spectra were recorded
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at a Bruker Avance III HD spectrometer (Bremen, Germany) at 600 MHz (400 MHz) for 1H
NMR and 150 MHz (100 MHz) for 13C NMR with CDCl3 or d6-DMSO as the solvent and TMS
as the internal standard. High resolution mass spectra (HRMS) were measured with an Agilent
1290-6540 Q-TOF (Santa Clara, USA). (Santa Clara, USA). Low resolution mass spectra
(LRMS) were recorded at an electron ionization (EI) conditions by using a Shimadzu GCMS-
QP2010 Plus mass spectrometer (Kyoto, Japan). The melting points of the products were
determined by an X-4 micro-melting point apparatus (Beijing, China).
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General procedure for PEG-functionalized ligands: A 25 mL Schlenk tube was charged with
triethylene glycol monomethyl ether (3 mmol, 5.0 equiv), NaH (3.6 mmol, 6.0 equiv) and DMF
(3 mL). The resulting mixture was stirred at room temperature for 10 minutes until no bubbles
appeared. Then, 2,9-dibromo-1,10-phenanthroline (0.6 mmol, 1.0 equiv) was added. The reaction
mixture was heated at 110 oC for 4 h. Once finished, the reaction mixture was cooled to room
temperature then extracted with dichloromethane (3 × 50 mL). The organic phase was collected
and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated by
rotovap, and the residue was purified via column chromatography to afford products L1-L5.
General procedure for synthesis of organosulfide: A 25 mL Schlenk tube was charged with
hydrazine (21.7 mg, 0.2 mmol), thiol (28.0 mg, 0.2 mmol), Cu(NO3)2•3H2O (2.4 mg, 0.01
mmol), L1 (4.8 mg, 0.01 mmol), Cs2CO3 (65.2 mg, 0.2 mmol), H2O (2 mL), 1 atm O2, and then
the resulting mixture was stirred at 100 oC. After 12 h, the reaction mixture was extracted with
dichloromethane (3 × 50 mL), and then dried over anhydrous sodium sulfate and filtered. After
evaporation of the solvent under vacuum, the residue was purified via column chromatography to
afford products 3a-3u, 4a-4p.
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Procedure for mother liquor circulation: To a reactor (50 mL) was added phenylhydrazine
(65.1 mg, 0.6 mmol), 4-methoxythiophenol (84.1 mg, 0.6 mmol), Cu(NO3)2•3H2O (7.2 mg, 0.03
mmol), L1 (14.4 mg, 0.03 mmol), Cs2CO3 (195.5 mg, 0.6 mmol), H2O (6 mL).The reactor was
charged with O2 1 atm three times. Subsequently, the reactor was stirred at 100 oC for 12 h. After
cooling to room temperature, the reaction mixture was extracted with hexane. The organic phase
was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo.
The crude material was purified by column chromatography (hexane : DCM = 2 : 1 as eluent) to
afford the desired product. The aqueous phase was reused directly in the next run by adding a
fresh batch of 4-methoxythiophenol (84.1 mg, 0.6 mmol) and phenylhydrazine (65.1 mg, 0.6
mmol). The aqueous phase was used for 5 runs, with the yields varying as follow: 99%, 95%,
92%, 90%, 88%.
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Procedure for gram scale synthesis: A 250 mL Schlenk flask was charged with
phenylhydrazine (540.7 mg, 5 mmol), 4-methoxythiophenol (701.0 mg, 5 mmol),
Cu(NO3)2•3H2O (60.0 mg, 0.25 mmol), L1 (120.0 mg, 0.25 mmol), Cs2CO3 (1629.1 mg, 5
mmol), H2O (50 mL). Subsequently, the reactor was stirred under at 100 oC for 12 h. After
cooling to room temperature, the reaction mixture was extracted with hexane. The organic phase
was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated on
rotovap. The crude material was purified by column chromatography (hexane : DCM = 2 : 1 as
eluent) to afford the desired product in 95% yield.
4,7-Bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-1,10-phenanthroline (L1). Orange oil (284.9
mg, 94% yield) (methyl alcohol as eluent). 1H NMR (400 MHz, CDCl3) δ = 8.99 (d, J = 5.2 Hz,
2H), 8.20 (s, 2H), 6.99 (d, J = 5.3 Hz, 2H), 4.44-4.37 (m, 4H), 4.07-4.01 (m, 4H), 3.85-3.80 (m,
4H), 3.74-3.65 (m, 8H), 3.57-3.52 (m, 4H), 3.37 (s, 6H). 13C NMR (100 MHz, CDCl3) δ = 161.4,
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151.1, 146.9, 120.9, 119.1, 103.5, 71.9, 71.1, 70.7, 70.6, 69.4, 68.1, 59.1. HRMS (ESI): m/z
calcd for C26H37N2O8 [M+H]+, 505.2544; found, 505.2548.
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3,8-Bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-1,10-phenanthroline (L2). Yellow oil (248.5
mg, 82% yield) (ethyl acetate : methyl alcohol = 10 : 1 as eluent). 1H NMR (400 MHz, CDCl3) δ
= 8.90 (d, J = 2.9 Hz, 2H), 7.68 (s, 2H), 7.51 (d, J = 2.9 Hz, 2H), 4.33-4.28 (m, 4H), 3.99-3.93
(m, 4H), 3.81-3.75 (m, 4H), 3.73-3.64 (m, 8H), 3.57-3.50 (m, 4H), 3.37 (s, 6H). 13C NMR (100
MHz, CDCl3) δ = 153.6, 142.9, 140.5, 127.9, 126.7, 115.2, 71.9, 70.9, 70.6, 70.6, 69.6, 67.9,
59.0. HRMS (ESI): m/z calcd for C26H37N2O8 [M+H]+, 505.2544; found, 505.2548.
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2,9-Bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-1,10-phenanthroline (L3). Cololess oil
(272.7 mg, 90% yield) (ethyl acetate as eluent). 1H NMR (400 MHz, CDCl3) δ = 8.04 (d, J = 8.7
Hz, 2H), 7.56 (s, 2H), 7.09 (d, J = 8.7 Hz, 2H), 4.89-4.82 (m, 4H), 4.03-3.97 (m, 4H), 3.81-3.74
(m, 4H), 3.71-3.60 (m, 8H), 3.54-3.48 (m, 4H), 3.34 (s, 6H). 13C NMR (100 MHz, CDCl3) δ =
162.1, 142.9, 139.0, 125.2, 123.4, 113.6, 71.9, 70.6, 70.6, 70.5, 69.9, 65.1, 59.0. HRMS (ESI):
m/z calcd for C26H37N2O8 [M+H]+, 505.2544; found, 505.2543.
4,4'-Bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bipyridine (L4). Yellow oil (284.9 mg,
89% yield) (ethyl acetate as eluent). 1H NMR (400 MHz, CDCl3) δ = 8.45 (d, J = 5.7 Hz, 2H),
7.98 (d, J = 2.4 Hz, 2H), 6.90-6.82 (m, 2H), 4.31-4.25 (m, 4H), 3.92-3.86 (m, 4H), 3.76-3.62 (m,
12H), 3.56-3.49 (m, 4H), 3.36 (s, 6H). 13C NMR (100 MHz, CDCl3) δ = 165.9, 157.8, 150.1,
111.5, 106.6, 71.9, 70.9, 70.7, 70.6, 69.4, 67.5, 59.1. HRMS (ESI): m/z calcd for C24H37N2O8
[M+H]+, 481.2544; found, 481.2549.
6,6'-Bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bipyridine (L5). Yellow oil (284.9 mg,
89% yield) (ethyl acetate as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.98-7.92 (m, 2H), 7.71-
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7.61 (m, 2H), 6.82-6.74 (m, 2H), 4.61 (t, J = 3.8 Hz, 4H), 3.96-3.88 (m, 4H), 3.79-3.63 (m,
12H), 3.57-3.52 (m, 4H), 3.37 (s, 6H). 13C NMR (100 MHz, CDCl3) δ = 162.9, 153.2, 139.3,
113.7, 111.3, 71.9, 70.7, 70.7, 70.6, 69.8, 64.9, 59.1. HRMS (ESI): m/z calcd for C24H37N2O8
[M+H]+, 481.2544; found, 481.2549.
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1-Methoxy-4-(phenylthio)-Benzene (3a)7 Yellow oil. (42.7 mg, 99% yield) (hexane : DCM =
2 : 1 as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.43-7.40 (m, 2H), 7.24-7.11 (m, 5H), 6.91-6.87
(m, 2H), 3.82 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 159.9, 138.6, 135.4, 129.0, 128.2, 125.8,
124.3, 115.0, 55.4. LRMS (EI) m/z calcd for C13H12OS [M]+, 216; found, 216.
Methoxy-4-[(4-methylphenyl) thio]-benzene (3b)7 Yellow solid. (44.3 mg, 92% yield)
(hexane : DCM = 2 : 1 as eluent) 45-46 oC. 1H NMR (400 MHz, CDCl3) δ = 7.29 (d, J = 8.9 Hz,
2H), 7.06 (d, J = 8.2 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.9 Hz, 2H), 3.73 (s, 3H),
2.23 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 159.5, 136.1, 134.4, 134.4, 129.8, 129.4, 125.6,
114.9, 55.4, 21.0. LRMS (EI) m/z calcd for C14H14OS [M]+, 230; found, 230.
1-[(4-Methoxyphenyl) thio]-3-methyl-Benzene (3c)7 Yellow oil. (42.3 mg, 92% yield)
(hexane : DCM = 2 : 1 as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.36-7.30 (m, 2H), 7.05 (t, J
= 7.7 Hz, 1H), 6.94 (s, 1H), 6.88 (d, J = 7.6 Hz, 2H), 6.85-6.78 (m, 2H), 3.75 (s, 3H), 2.20 (s,
3H). 13C NMR (100 MHz, CDCl3) δ = 159.7, 138.8, 138.2, 135.2, 128.9, 128.8, 126.8, 125.4,
124.5, 114.9, 55.4, 21.4. LRMS (EI) m/z calcd for C14H14OS [M]+, 230; found, 230.
1-[(4-Methoxyphenyl) thio]-2-methyl-Benzene (3d)7 Yellow oil. (33.5 mg, 73% yield)
(hexane : DCM = 2 : 1 as eluent). 1H NMR (600 MHz, CDCl3) δ = 7.24 (d, J = 8.8 Hz, 2H), 7.09
(d, J = 7.4 Hz, 1H), 7.03-6.95 (m, 2H), 6.90 (d, J = 7.6 Hz, 1H), 6.80 (d, J = 8.7 Hz, 2H), 3.73 (s,
3H), 2.30 (s, 3H). 13C NMR (150 MHz, CDCl3) δ = 159.6, 137.1, 137.1, 134.1, 130.2, 129.1,
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126.5, 126.2, 124.5, 115.1, 55.4, 20.3. LRMS (EI) m/z calcd for C14H14OS [M]+, 230; found,
230.
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4-[(4-Methoxyphenyl) thio]-1,2-dimethyl-Benzene (3e)7 Yellow oil. (33.2 mg, 69% yield)
(hexane : DCM = 2 : 1 as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.31-7.25 (m, 2H), 6.99-6.87
(m, 3H), 6.81-6.76 (m, 2H), 3.73 (s, 3H), 2.13 (s, 3H), 2.12 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ = 159.4, 137.5, 135.0, 134.4, 134.2, 130.7, 130.3, 127.1, 125.8, 114.8, 55.4, 19.8, 19.4. LRMS
(EI) m/z calcd for C15H16OS [M]+, 244; found, 244.
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1,1'-Thiobis[4-methoxybenzene] (3f)13 Yellow oil. (44.3 mg, 90% yield) (hexane : DCM = 2 :
1 as eluent). 1H NMR (600 MHz, CDCl3) δ = 7.21 (d, J = 7.6 Hz, 4H), 6.76 (d, J = 7.6 Hz, 4H),
3.82 (s, 6H). 13C NMR (150 MHz, CDCl3) δ = 159.0, 132.7, 127.5, 114.8, 55.4. LRMS (EI) m/z
calcd for C14H14O2S [M]+, 246; found, 246.
1-Fluoro-4-[(4-methoxyphenyl) thio]-Benzene (3g)13 Yellow oil. (42.1 mg, 90% yield)
(hexane : DCM = 2 : 1 as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.29 (d, J = 8.8 Hz, 2H),
7.15-7.09 (m, 2H), 6.88 (t, J = 8.7 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H). 13C NMR (100
MHz, CDCl3) δ = 162.8, 160.4, 159.7, 134.6, 133.2, 133.1, 131.1, 131.0, 125.2, 116.2, 116.0,
115.0, 55.4. LRMS (EI) m/z calcd for C13H11FOS [M]+, 234; found, 234.
4-[(4-Methoxyphenyl) thio]-1-methyl-2-chloro-Benzene (3h).Yellow oil. (41.7 mg, 79%
yield) (hexane : DCM = 2 : 1 as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.35-7.30 (m, 2H),
7.07-6.97 (m, 2H), 6.92-6.97 (m, 1H), 6.85-6.80 (m, 2H), 3.75 (s, 3H), 2.23 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ = 156.0, 137.3, 135.4, 134.9, 133.7, 131.2, 128.5, 126.7, 123.9, 115.1, 55.4,
19.6. HRMS (ESI) m/z calcd for C14H14ClOS [M+H]+, 265.0448; found, 265.0437.
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1-Chloro-4-[(4-methoxyphenyl) thio]-Benzene (3i)7 Yellow solid. (45.0 mg, 90% yield)
(hexane : DCM = 2 : 1 as eluent). 54-56 oC. 1H NMR (400 MHz, CDCl3) δ = 7.35-7.31 (m, 2H),
7.14-7.09 (m, 2H), 7.03-6.96 (m, 2H), 6.85-6.80 (m, 2H), 3.75 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ = 160.1, 137.4, 135.5, 131.6, 129.3, 129.0, 123.8, 115.2, 55.4. LRMS (EI) m/z calcd
for C13H11ClOS [M]+, 250; found, 250.
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1-Chloro-3-[(4-methoxyphenyl) thio]-Benzene (3j)14 Yellow solid. (45.0 mg, 90% yield)
(hexane : DCM = 2 : 1 as eluent). 50-53 oC. 1H NMR (400 MHz, CDCl3) δ = 7.39-7.33 (m, 2H),
7.06 (t, J = 7.7 Hz, 1H), 7.02-6.97 (m, 2H), 6.94-6.90 (m, 1H), 6.87-6.82 (m, 2H), 3.76 (s, 3H).
13C NMR (100 MHz, CDCl3) δ = 160.3, 141.4, 136.2, 134.8, 129.9, 127.0, 125.6, 125.4, 122.6,
115.3, 55.4. LRMS (EI) m/z calcd for C13H11ClOS [M]+, 250; found, 250.
1-Chloro-2-[(4-methoxyphenyl) thio]-Benzene (3k)13 Yellow oil. (44.5 mg, 89% yield)
(hexane : DCM = 2 : 1 as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.42-7.37 (m, 2H), 7.28-7.24
(m, 1H), 6.99-6.95 (m, 2H), 6.92-6.86 (m, 2H), 6.66-6.61 (m, 1H), 3.77 (s, 3H). 13C NMR (100
MHz, CDCl3) δ = 160.6, 138.8, 137.0, 131.0, 129.5, 127.5, 127.1, 126.0, 121.6, 115.4, 55.4.
LRMS (EI) m/z calcd for C13H11ClOS [M]+, 250; found, 250.
1-Bromo-4-[(4-methoxyphenyl) thio]-Benzene (3l)7 Yellow solid. (49.9 mg, 85% yield)
(hexane : DCM = 2 : 1 as eluent). 54-57 oC. 1H NMR (400 MHz, CDCl3) δ = 7.33 (d, J = 8.8 Hz,
2H), 7.26 (d, J = 8.6 Hz, 2H), 6.92 (d, J = 8.6 Hz, 2H), 6.83 (d, J = 8.8 Hz, 2H), 3.75 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ = 160.1, 138.2, 135.7, 131.9, 129.4, 123.5, 119.4, 115.2, 55.4. LRMS
(EI) m/z calcd for C13H11BrOS [M]+, 294; found, 294.
1-Bromo-3-[(4-methoxyphenyl) thio]-Benzene (3m)15 Yellow solid. (52.7 mg, 90% yield)
(hexane : DCM = 2 : 1 as eluent). 48-51 oC. 1H NMR (400 MHz, CDCl3) δ = 7.39-7.32 (m, 2H),
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7.18-7.12 (m, 2H), 7.02-6.93 (m, 2H), 6.87-6.81 (m, 2H), 3.75 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ = 160.3, 141.6, 136.2, 130.2, 129.9, 128.5, 126.0, 123.0, 122.7, 115.3, 55.4. LRMS
(EI) m/z calcd for C13H11BrOS [M]+, 294; found, 294.
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4-[(4-Methoxyphenyl) thio]-Benzonitrile (3n)16 White solid. (45.8 mg, 95% yield) (hexane :
DCM = 2 : 1 as eluent). 94-95 oC. 1H NMR (400 MHz, CDCl3) δ = 7.42-7.33 (m, 4H), 6.99 (d, J
= 8.7 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 161.0,
147.4, 137.2, 132.3, 126.0, 120.3, 119.0, 115.6, 108.0, 55.5. LRMS (EI) m/z calcd for
C14H11NOS [M]+, 241; found, 241.
1-Methoxy-4-[(4-nitrophenyl) thio]-Benzene (3o)7 Yellow solid. (19.7 mg, 41% yield)
(hexane : DCM = 2 : 1 as eluent). 59-60 oC. 1H NMR (400 MHz, CDCl3) δ = 7.96 (d, J = 8.9 Hz,
2H), 7.41 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 8.9 Hz, 2H), 6.92 (d, J = 8.7 Hz, 2H), 3.79 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ = 161.1, 150.1, 145.0, 137.2, 125.6, 124.0, 120.2, 115.7, 55.5. LRMS
(EI) m/z calcd for C13H11NO3S [M]+, 261; found, 261.
1-[(4-Methoxyphenyl) thio]-2-nitro-Benzene (3p)17 Yellow solid. (35.5 mg, 68% yield)
(hexane : DCM = 2 : 1 as eluent). 91-93 oC. 1H NMR (400 MHz, CDCl3) δ = 8.16 (d, J = 8.2 Hz,
1H), 7.43 (d, J = 8.7 Hz, 2H), 7.30-7.22 (m, 1H), 7.15-7.06 (m, 1H), 6.93 (d, J = 8.7 Hz, 2H),
6.76 (d, J = 8.2 Hz, 1H), 3.80 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 161.2, 144.6, 140.8,
137.8, 133.4, 127.9, 125.8, 124.7, 121.2, 115.7, 55.5. LRMS (EI) m/z calcd for C13H11NO3S
[M]+, 261; found, 261.
1-[(4-Methoxyphenyl) thio]-2, 4-dinitro-Benzene (3q)18 Yellow solid. (39.8 mg, 65% yield)
(hexane : DCM = 2 : 1 as eluent). 108-110 oC. 1H NMR (400 MHz, CDCl3) δ = 9.03 (d, J = 2.3
Hz, 1H), 8.09-8.00 (m, 1H), 7.43 (d, J = 8.6 Hz, 2H), 6.99 (d, J = 8.6 Hz, 2H), 6.92 (d, J = 9.1
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Hz, 1H), 3.83 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 161.9, 149.6, 144.1, 143.6, 137.6, 128.7,
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126.8, 121.5, 119.2, 116.3, 55.6. LRMS (EI) m/z calcd for C13H10N2O5S [M]+, 306; found, 306.
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2-[(4-Methoxyphenyl) thio]-Naphthalene (3r)7 White solid. (39.6 mg, 75% yield) (hexane :
DCM = 2 : 1 as eluent). 65-66 oC. 1H NMR (400 MHz, CDCl3) δ = 7.70-7.55 (m, 3H), 7.52 (d, J
= 1.3 Hz, 1H), 7.41-7.28 (m, 4H), 7.24-7.18 (m , 1H), 6.84 (d, J = 8.8 Hz, 2H), 3.75 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ = 159.9, 135.9, 135.3, 133.8, 131.7, 128.6, 127.7, 127.2, 126.7,
126.5, 126.4, 125.7, 124.4, 115.1, 55.4. LRMS (EI) m/z calcd for C17H14OS [M]+, 266; found,
266.
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2-[(4-methoxyphenyl) thio]-Pyridine (3s)13 Colorless solid. (40.8 mg, 94% yield) (hexane :
DCM = 2 : 1 as eluent). 45-46 oC. 1H NMR (400 MHz, CDCl3) δ = 8.36-8.29 (m, 1H), 7.49-7.43
(m, 2H), 7.39-7.30 (m, 1H), 6.94-6.83 (m, 3H), 6.71 (d, J = 8.1 Hz, 1H), 3.78 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ = 162.8, 160.7, 149.3, 137.3, 136.7, 121.0, 120.4, 119.5, 115.3, 55.4.
LRMS (EI) m/z calcd for C12H11NOS [M]+, 217; found, 217.
1-[(1, 1-Dimethylethyl) thio]-4-methoxy-Benzene (3t)16 Colorless oil. (35.3 mg, 90% yield)
(hexane : DCM = 2 : 1 as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.40-7.34 (m, 2H), 6.81-6.76
(m, 2H), 3.75 (s, 3H), 1.19 (s, 9H). 13C NMR (100 MHz, CDCl3) δ = 160.3, 138.9, 123.6, 114.0,
55.3, 45.5, 30.8. LRMS (EI) m/z calcd for C11H16OS [M]+, 196; found, 196.
1-Methoxy-4-[(1-methylethyl) thio]-Benzene (3u)19 Colorless oil. (30.9 mg, 85% yield)
(hexane : DCM = 2 : 1 as eluent). 1H NMR (600 MHz, CDCl3) δ = 7.32 (d, J = 8.6 Hz, 2H), 6.78
(d, J = 8.6 Hz, 2H), 3.73 (s, 3H), 3.18-3.03 (m, 1H), 1.17 (d, J = 6.7 Hz, 6H). 13C NMR (150 MHz,
CDCl3) δ = 158.4, 134.6, 124.4, 113.3, 54.3, 38.5, 22.1. LRMS (EI) m/z calcd for C10H14OS [M]+,
182; found, 182.
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1-Methyl-4-(phenylthio)-Benzene (4a)20 Colorless oil. (38.8 mg, 97% yield) (hexane as
eluent). 1H NMR (400 MHz, CDCl3) δ = 7.37 (d, J = 8.1 Hz, 2H), 7.34-7.30 (m, 4H), 7.27-7.22
(m, 1H), 7.20 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H). 13C NMR (100MHz, CDCl3) δ = 137.7, 137.2,
132.4, 131.3, 130.2, 129.8, 129.1, 126.5, 21.2. LRMS (EI) m/z calcd for C13H12S [M]+, 200;
found, 200.
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1-Methyl-3-(phenylthio)-Benzene (4b)21 Colorless oil. (38.8 mg, 97% yield) (hexane as
eluent). 1H NMR (400 MHz, CDCl3) δ = 7.35-7.26 (m, 4H), 7.25 -7.12 (m, 4H), 7.06 (d, J = 7.4
Hz, 1H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 139.1, 136.1, 135.2, 131.9, 130.8, 129.2,
129.1, 128.4, 128.1, 126.9, 21.3. LRMS (EI) m/z calcd for C13H12S [M]+, 200; found, 200.
1-Methyl-2-(phenylthio)-Benzene (4c)22 Colorless oil. (38.0 mg, 95% yield) (hexane as
eluent). 1H NMR (400 MHz, CDCl3) δ = 7.23-7.05 (m, 9H), 2.30 (s, 3H). 13C NMR (100MHz,
CDCl3) δ = 140.0, 136.2, 133.8, 133.0, 130.6, 129.7, 129.2, 127.9, 126.8, 126.4, 20.6. LRMS
(EI) m/z calcd for C13H12S [M]+, 200; found, 200.
4-(Phenylthio)-Benzenamine (4d)23 Colorless oil. (39.6 mg, 99% yield) (hexane : DCM = 2 :
1 as eluent). 1H NMR (400 MHz, DMSO) δ = 7.27-7.20 (m, 2H), 7.20-7.14 (m, 2H), 7.13-7.05
(m, 1H), 7.02-6.97 (m, 2H), 6.62 (d, J = 8.6 Hz, 2H), 5.53 (s, 2H). 13C NMR (100 MHz, DMSO)
δ = 150.1, 140.2, 136.5, 129.0, 125.9, 125.0, 114.8, 114.5. LRMS (EI) m/z calcd for C11H9NS
[M]+, 201; found, 201.
1-Chloro-4-(phenylthio)-Benzene (4e)20 Colorless oil. (43.6 mg, 99% yield) (hexane as
eluent). 1H NMR (400 MHz, CDCl3) δ = 7.29-7.22 (m, 4H), 7.22-7.15 (m, 5H). 13C NMR
(100MHz, CDCl3) δ = 135.1, 134.7, 133.0, 132.0, 131.3, 129.4, 129.4, 127.5. LRMS (EI) m/z
calcd for C12H9ClS [M]+, 220; found, 220.
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1-Bromo-2-(phenylthio)-Benzene (4f)21 Colorless oil. (37.1 mg, 70% yield) (hexane as
eluent). 1H NMR (400 MHz, CDCl3) δ = 7.51-7.45 (m, 1H), 7.41-7.28 (m, 5H), 7.10-7.03 (m,
1H), 6.96-6.90 (m, 1H), 6.85-6.81 (m, 1H). 13C NMR (100 MHz, CDCl3) δ = 138.8, 133.6,
133.0, 132.7, 129.8, 129.7, 128.5, 127.8, 127.3, 123.0. LRMS (EI) m/z calcd for C12H9BrS [M]+,
265; found, 265.
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1-Nitro-4-(phenylthio)-Benzene (4g)7 Brown oil. (27.7 mg, 60% yield) (hexane : DCM = 2 :
1 as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.99 (d, J = 9.0 Hz, 2H), 7.51-7.44 (m, 2H), 7.41-
7.36 (m, 3H), 7.10 (d, J = 9.0 Hz, 2H).13C NMR (100 MHz, CDCl3) δ = 148.6, 145.4, 134.8,
130.4, 130.1, 129.7, 126.7, 124.1. LRMS (EI) m/z calcd for C12H9NO2S [M]+, 231; found, 231.
4-(Phenylthio)-Pyridine (4h)20 Brown oil. (31.8 mg, 85% yield) (hexane : EtOAc = 10 : 1 as
eluent). 1H NMR (400 MHz, CDCl3) δ = 8.27 (d, J = 5.7 Hz, 2H), 7.51-7.43 (m, 2H), 7.43-7.34
(m, 3H), 6.87 (d, J = 6.2 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ = 150.7, 149.2, 135.3, 130.0,
129.8, 129.3, 120.8. LRMS (EI) m/z calcd for C11H9NS [M]+, 187; found, 187.
2-(Phenylthio)-Pyridine (4i)21 Brown oil. (34.0 mg, 95% yield) (hexane : EtOAc = 10 : 1 as
eluent). 1H NMR (400 MHz, CDCl3) δ = 8.41-8.30 (m, 1H), 7.57-7.47 (m, 2H), 7.42-7.32 (m,
4H), 6.97-6.88 (m, 1H), 6.81 (d, J = 8.1 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ = 161.6, 149.4,
136.9, 135.0, 130.9, 129.7, 129.2, 121.4, 119.9. LRMS (EI) m/z calcd for C11H9NS [M]+, 187;
found, 187.
2-(Phenylthio)-Pyrimidine (4j)22 Brown oil. (33.1 mg, 95% yield) (hexane : EtOAc = 2 : 1 as
eluent). 1H NMR (600 MHz, CDCl3) δ = 8.42 (d, J = 4.1 Hz, 2H), 7.57 (d, J = 2.2 Hz, 2H), 7.37
(s, 3H), 6.90 (s, 1H). 13C NMR (100 MHz, CDCl3) δ = 172.9, 157.6, 135.3, 129.4, 129.4, 129.3,
117.1. LRMS (EI) m/z calcd for C10H8N2S [M]+, 188; found, 188.
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2-(Phenylthio)-Thiophene (4k)20 Colorless oil. (28.8 mg,75% yield) (hexane as eluent). 1H
NMR (600 MHz, CDCl3) δ = 7.40 (d, J = 5.3 Hz, 1H), 7.24-7.15 (m, 3H), 7.14-7.05 (m, 3H),
7.03-6.98 (m, 1H). 13C NMR (150 MHz, CDCl3) δ = 138.7, 136.1, 131.3, 129.0, 127.9, 127.8,
127.2, 126.1. LRMS (EI) m/z calcd for C10H8S2 [M]+, 192; found, 192.
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2-(Phenylthio)-Benzothiazole (4l)24 Yellow oil. (36.9 mg, 76% yield) (hexane as eluent). 1H
NMR (600 MHz, CDCl3) δ = 7.81 (d, J = 8.1 Hz, 1H), 7.66 (d, J = 7.2 Hz, 2H), 7.57 (d, J = 7.9
Hz, 1H), 7.49-7.36 (m, 3H), 7.33 (t, J = 7.6 Hz, 1H), 7.22-7.16 (m, 1H). 13C NMR (150 MHz,
CDCl3) δ = 169.7, 153.9, 135.6, 135.4, 130.5, 130.0, 130.0, 126.2, 124.4, 122.0, 120.8. LRMS
(EI) m/z calcd for C13H9NS2 [M]+, 243; found, 243.
2-(Phenylthio)-Benzoxazole (4m)24 Yellow oil. (36.7 mg, 81% yield) (hexane as eluent). 1H
NMR (400 MHz, CDCl3) δ = 7.67-7.60 (m, 2H), 7.56-7.50 (m, 1H), 7.42-7.32 (m, 4H), 7.20-
7.16 (m, 2H). 13C NMR (100MHz, CDCl3) δ = 163.4, 151.9, 142.0, 134.5, 130.3, 130.0, 127.1,
124.4, 124.3, 119.1, 110.1. LRMS (EI) m/z calcd for C13H9NOS [M]+, 227; found, 227.
[(Phenylmethyl) thio]-Benzene (4n)20 White solid. (23.2 mg, 58% yield) (hexane : DCM = 2 :
1 as eluent). 35-38 oC. 1H NMR (600 MHz, CDCl3) δ = 7.30-7.02 (m, 10H), 4.04 (s, 2H). 13C
NMR (150 MHz, CDCl3) δ = 137.5, 136.4, 129.9, 128.8, 128.5, 127.2, 126.4, 39.1. LRMS (EI)
m/z calcd for C13H12S [M]+, 265; found, 265.
(Cyclohexylthio)-Benzene (4o)20 Colorless oil. (19.0 mg, 50% yield) (hexane : DCM = 2 : 1
as eluent). 1H NMR (400 MHz, CDCl3) δ = 7.35-7.29 (m, 2H), 7.22-7.19 (m, 2H), 7.16-7.11 (m,
1H), 3.06-2.99 (m, 1H), 1.96-1.86 (m, 2H), 1.74-1.66 (m, 2H), 1.57-1.51 (m, 1H), 1.31-1.16 (m,
5H). 13C NMR (100 MHz, CDCl3) δ = 135.2, 131.9, 128.8, 126.6, 46.6, 33.4, 26.1, 25.8. LRMS
(EI) m/z calcd for C12H16S [M]+, 192; found, 192.
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(Hexylthio)-Benzene (4p)25 Colorless oil. (27.2 mg, 70% yield) (hexane as eluent). 1H NMR
(600 MHz, CDCl3) δ = 7.27-7.12 (m, 4H), 7.05 (t, J = 7.0 Hz, 1H), 2.81 (t, J = 7.3 Hz, 2H),
1.63-1.48 (m, 2H), 1.36-1.15 (m, 6H), 0.79 (t, J = 6.3 Hz, 3H). 13C NMR (150MHz, CDCl3) δ =
137.2, 128.9, 128.8, 125.6, 33.6, 31.4, 29.2, 28.6, 22.6, 14.1. LRMS (EI) m/z calcd for C12H8S
[M]+, 194; found, 194.
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ASSOCIATED CONTENT
Supporting Information. The following files are available free of charge.
Copies of 1H NMR and 13C NMR spectra for all compounds (PDF).
AUTHOR INFORMATION
Corresponding Author
*Bingxin Yuan (E-mail: bxyuan@zzu.edu.cn).
Author Contributions
All authors have given approval to the final version of the manuscript. ‡These authors
contributed equally.
Notes
The authors declare no conflict of interest.
ACKNOWLEDGMENT
The authors thank the National Natural Science Foundation of China (No. 21801229) for the
funding support.
REFERENCES
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