Aerobic Cross-Dehydrogenative Coupling Reactions for Selective Mono- And Dithiolation of Phenols

Article abstract of DOI:10.1021/acs.joc.1c00898

A highly efficient strategy for the direct thiolation of phenols under transition metal-free and solvent-free conditions has been developed. These reactions are operationally simple with employing air (molecular oxygen) as an ideal oxidant and can selectively provide mono- and dithiolation products in good to excellent yields under basic conditions. The reaction tolerates a broad range of aryl thiols and arenes and is especially applicable for large-scale synthesis.

Full text of DOI:10.1021/acs.joc.1c00898

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Article
Aerobic Cross-Dehydrogenative Coupling Reactions for Selective
Mono- and Dithiolation of Phenols
Dong-Yang Han, Xiao-Peng Liu, Ruo-Pu Li, and Da-Zhen Xu*
Cite This: J. Org. Chem. 2021, 86, 10166−10176
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ABSTRACT: A highly efficient strategy for the direct thiolation of phenols
under transition metal-free and solvent-free conditions has been developed.
These reactions are operationally simple with employing air (molecular
oxygen) as an ideal oxidant and can selectively provide mono- and
dithiolation products in good to excellent yields under basic conditions.
The reaction tolerates a broad range of aryl thiols and arenes and is especially
applicable for large-scale synthesis.
Scheme 1. CDC for C(sp2)−S Bond Formation
INTRODUCTION
■
The construction of C−S bonds is of great importance in
organic synthesis because sulfur moieties are widely found in
commercially available drugs, natural products, and funda-
mental materials.1 As a consequence, chemists have paid much
attention to develop effective methods for their formation. In
this context, transition metals catalyzed the cross-coupling of
aryl halides, thiols, or disulfides and have been developed as
one of the most reliable methods for the construction of C−S
bonds.2 The direct cross-dehydrogenative coupling (CDC)
between C−H and S−H is a more attractive strategy for C−S
bond formation than the traditional methods as it offers
shorter synthetic routes with wide availability of starting
materials and atom economical and environmentally benign
protocols (Scheme 1).3 In the past decade, a number of CDC
methodologies have been established for C(sp2)−S bond
formation under transition-metal-catalyzed or metal-free
conditions (Scheme 1a).4,5 However, the overwhelming
majority of selective mono- and dithiolation of arene reactions
with high ortho selectivity that have been reported so far
require directing groups (DGs) in the presence of transition-
metal catalysts (Scheme 1b).6 In addition, these trans-
formations are usually performed in toxic organic solvents
and require using stoichiometric amounts of chemical oxidants.
Therefore, the invention of more safe and efficient protocols
for selective mono- and dithiolation of arenes from readily
accessible substrates remains a challenging issue.
and environmental friendliness.8 What is more, it is so difficult
to achieve high chemoselectivity for C−H functionalization
without transition-metal catalysts. Therefore, performing such
transformations under transition-metal-free and solvent-free
conditions and employing air as the oxidant is a dream
Performing direct oxidative C−H functionalization under
simple and green reaction conditions to achieve high
chemoselectivity is always a longstanding goal for organic
chemists.7 From the point of view of sustainable and green
chemistry, solvents occupy a strategic place. The reaction
performed in green solvents or under solvent-free conditions is
greatly desired. On the other hand, in contrast to the
traditional chemical oxidants, molecular oxygen, especially
air, is considered to be an ideal oxidant due to its abundance
Received: April 19, 2021
Published: July 12, 2021
https://doi.org/10.1021/acs.joc.1c00898
J. Org. Chem. 2021, 86, 10166−10176
© 2021 American Chemical Society
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a
Table 1. Optimization of the Reaction Conditions
b
entry
catalyst
base (equiv)
K2CO3 (1)
time (h)
yield (%)
1
2
FeCl3·6H2O
FeCl3·6H2O
1
3
85
3
4
5
6
7
8
9
10
11
12
13
K2CO3 (1)
Na2CO3 (1)
Cs2CO3 (1)
K3PO4 (1)
KOH (1)
NaOH (1)
tBuOK (1)
tBuOLi (1)
DBU (1)
3
3
3
3
3
3
1.5
3
3
71
41
90
43
70
62
93
87
c
tBuOK (0.5)
tBuOK (0.1)
2
2
77, 95
38, 71
c
a
b
c
Reaction conditions: 1a (0.6 mmol, 1.0 equiv), 2a (1.8 mmol, 3.0 equiv), under open air. Yields of isolated products. 1a (5 mmol, 1.0 equiv), 2a
(7.5 mmol, 1.5 equiv), tBuOK (2.5 mmol, 0.5 equiv).
reaction. Here, within our program on sustainable oxidation for
C−C and C−heteroatom bond formation,9 we disclose an
unprecedented base-air oxidation system for direct selective
thiolation of arenes. This work has made notable achievements
that include (1) a free hydroxyl group as a DG to control
regioselectivity, (2) controlled temperature for selective mono-
and dithiolation, (3) air (molecular oxygen) as the terminal
oxidant, (4) performing under transition-metal-free and
solvent-free conditions, and (5) readily available for large-
scale synthesis.
With the optimized reaction conditions in hand (Table 1,
entry 9), we first investigated the substrate scope of 2-
naphthols 1 with a large variety of aryl thiols 2 for the
monothiolation reaction (Scheme 2). Overall, the direct
thiolation reaction possesses good functional group tolerance
on the aromatic ring of thiols, including electron-withdrawing
and electron-donating groups at the para, meta, and ortho
a
Scheme 2. Reaction Scope of Aryl Thiols
RESULTS AND DISCUSSION
■
The thiolation between 2-naphthol (1a) and 4-chlorobenze-
nethiol (2a) was selected as model reaction for screening
various parameters with air as the oxidant (Table 1). Initial
attempts employing FeCl3·6H2O as the catalyst and K2CO3 as
the base under solvent-free conditions at 80 °C afforded
monothiolation product 3a in 85% yield (entry 1). However,
FeCl3·6H2O could not catalyze this process without any base
(entry 2). To our surprise, product 3a could be obtained in
71% yield in the absence of iron salt under base conditions
(entry 3). Although the iron salts could give a higher yield of
3a in a short time (entry 1 vs 3), we chose to optimize the
reaction conditions under base conditions without any
transition-metal catalysts. Next, a series of inorganic bases
such as Na2CO3, Cs2CO3, K3PO4, KOH, NaOH, tBuOK, and
tBuOLi were evaluated (entries 4−10). They all could drive
this reaction, and tBuOK delivered desired product 3a in a
good yield up to 93% (entry 9). An organic base named 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) was also investigated,
but it failed to promote this reaction (entry 11). It was found
that an excellent yield of 95% was obtained when the reaction
was performed in gram-scale synthesis with 0.5 equiv of tBuOK
(entry 12). Even when the amount of the base was decreased
to 0.1 equiv, the reaction still proceeded smoothly to provide
3a in 71% yield (entry 13). These results indicate that the
present methodology is easily applicable for large-scale
synthesis.
a
Reaction conditions: 1a (0.6 mmol, 1.0 equiv), 2 (1.8 mmol, 3.0
equiv), and tBuOK (1.0 equiv), under open air. Yields of isolated
products. DMSO (0.6 mL) was used. At 150 °C. At 120 °C.
a
b
c
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a
Scheme 3. Selective Synthesis of Mono- and Dithiolated Phenols
a
Reaction conditions: 4 (0.6 mmol, 1.0 equiv), 2 (1.8 mmol, 3.0 equiv), and tBuOK (1.0 equiv), under open air. Yields of isolated products.
a
Scheme 4. Reaction Scope of Arenes
a
Reaction conditions: 1 (0.6 mmol, 1.0 equiv), 2 (1.8 mmol, 3.0 equiv), and tBuOK (1.0 equiv), under open air. Yields of isolated products. aKOH
b
c
was used instead of tBuOK, performed in DMSO (1 mL). At 120 °C. At 150 °C.
positions. They all successfully furnished the thiolation
products (3a−h) in good to excellent yields. There is no
obvious steric effect of the ortho position. Remarkably, aryl
thiol with disubstituent also smoothly delivered the desired
products (3i and 3j). Naphthalene-2-thiol with an extended π-
framework was also reactive (3k). Additionally, heterocyclic
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thiols, even a strong coordinating pyridine thiol, were well
tolerated to afford the thiolated products (3l and 3m) in high
yields. The naphthol derivatives were compatible and gave the
corresponding products (3n and 3o) in good yields as well.
Notably, benzeneselenol could also be coupled with 2-
naphthol under the optimized conditions and successfully
converted into the desired selenenyl product (3p) with a
satisfactory yield. It is worth highlighting that the present
catalytic system was compatible with various functional groups
such as halogens (fluoro, chloro, and bromo), hydroxyl, and
cyano, which could be easily further functionalized. However,
2-methoxynaphthalene did not yield the desired product (3q).
The reason may be that the radical intermediate could be not
generated under the present conditions.
Scheme 5. Gram-Scale Synthesis and Synthetic
Manipulations
a
Due to the strong electronic directing effects of the hydroxyl
group, the functionalization of phenols often yields a mixture
of ortho- and para-substituted products. Next, 1-naphthol was
selected as the model substrate to invest the conditions for
selective synthesis of substituted phenols. It was found that
monothiolation product 5a could be obtained in 85% yield
under the standard conditions. When the temperature was
raised to 120 °C, it exclusively afforded dithiolation product 6a
in 88% yield (see Table S2 in the Supporting Information).
Next, we evaluated the utility of this method for selective
synthesis of mono- and dithiolated phenols. Scheme 3 shows
that the reaction between 1-naphthol with a variety of aryl
thiols all proceeded smoothly and selectively delivered the
corresponding mono- (5a−f) and dithiolation products (6a−f)
in good to excellent yields under 80 or 120 °C. O-cresol as
another kind of phenol was also investigated. The mono- and
dithiolation products 5g and 6g were obtained in 83 and 88%
yield, respectively. The dithiolation products could be also
prepared in a two-step protocol by introducing two different
aryl thiol groups (6h). The abovementioned results indicate
that base-promoted aerobic CDC reaction for selective
synthesis of mono- and dithiolated phenols has been
successfully established.
a
Conditions: (i) oxone (0.6 equiv) and ethanol, 60 °C, 2h, 86% yield.
(ii) Oxone (1.5 equiv) and ethanol/H2O (1:1), 60 °C, 3h, 92% yield.
(iii) CH3I (1.5 equiv), K2CO3 (2.0 equiv), and DMF, r.t., 98% yield.
(iv) Tf2O (1.5 equiv), pyridine (2.0 equiv), and DCM, 0 °C to r.t.,
98% yield.
To gain an understanding of the reaction mechanism, some
control experiments were carried out (Scheme 6). First, we
performed the homocoupling of 1a and 2a under the standard
conditions(Scheme 6a,b). Only 2a afforded corresponding
coupling product 13. Next, treatment of 1a with homocoupling
Scheme 6. Control Experiments
Subsequently, various arenes were tested for the mono-
thiolation under the optimized conditions (Scheme 4). The
results are very encouraging. Different kinds of arenes
including phenols, naphthylamines, and indoles worked well
with this method. A variety of phenols showed high reactivity
to afford the corresponding products (5h−j), including
polyaromatic 1-hydroxypyrene (5j). However, naphthylamines
showed less reactivity and afforded the desired product in
moderate yields (7a−c). Indoles even containing a very strong
electron-withdrawing nitro group were all well tolerated and
provided the corresponding thiolation products (8a−c) in
good to excellent yields.
To demonstrate the practicality of this unique thiolation
reaction, we also conducted the gram-scale synthesis of 5i and
8a (Scheme 5a). The results are very encouraging. When we
decreased the base loading and substrate ratio to 0.5 equiv and
1:1.5, respectively, all the thiolation products could be isolated
in higher yields. Then, several derivatization experiments were
carried out. Compound 3a could be oxidized by treatment with
oxone in different solvents, affording corresponding sulfoxide
(9) and sulfone (10) in 86 and 92% yield, respectively.
Alternatively, the hydroxyl group of 3a could be easily
transformed to the methoxy group (11). Furthermore,
trifluoromethanesulfonate (12) could be obtained in a near
quantitative yield from 3a.
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Scheme 7. Proposed Reaction Mechanism
product 13 delivered thiolation product 3a in 94% yield
(Scheme 6c). The abovementioned results indicate that
intermediate 13 may be involved in the reaction. When the
reaction was performed under N2, the coupling of 1a with 2a
did not proceed, which implies the importance of air
(molecular oxygen; Scheme 6d). Moreover, the reaction was
completely inhibited in the presence of TEMPO (2,2,6,6-
tetramethyl-1-piperidinyloxy; Scheme 6e) or DPE (1,1-
diphenylethylene; Scheme 6f), thus indicating that a radical
process may be involved. The isolation of product 14 suggests
that intermediate A (see Scheme 7) may be generated in the
reaction.
On the basis of the preliminary experimental results, a
tentative mechanism is depicted in Scheme 7. Initially, aryl
thiol 2 undergoes homocoupling reaction to form intermediate
13, which could be transformed to radical A under basic
conditions (Scheme 7a). Subsequently, A abstracts a hydrogen
atom from phenol to form 2 and the radicals B, C, and D.
Next, A couples with C to furnish the desired monothiolation
product, which could be further oxidized to give radical F.
Then, G of resonance F easily couples with radical A to afford
the dithiolation product through intermediate H. Naphthyl-
amines and indoles undergo a similar transformation.
EXPERIMENTAL SECTION
■
General Information. All reagents including the starting materials
(arenes and thiols) are commercially available (purchased from
Sigma-Aldrich, TCI, and Alfa Aesar) and were used without further
purification. The melting points were determined with an X-4
1
apparatus and are uncorrected. H NMR and 13C NMR spectra were
recorded on a Bruker AV-400 spectrometer with DMSO-d6 as the
solvent. The chemical shifts are reported relative to tetramethyl silane
(TMS) as the internal standard. The H NMR data are reported as
1
the chemical shift in parts per million, multiplicity (s, singlet; d,
doublet; t, triplet; and m, multiplet), coupling constant in hertz, and
number of protons. High-resolution mass spectrometry (HRMS)
spectra were obtained on an IonSpec Fourier-transform ion cyclotron
resonance mass spectrometer with electrospray ionization (ESI)
resource.
General Procedure for the Preparation of Compounds 3, 5,
7, and 8. In a 10 mL reaction vial, equipped with a magnetic stirring
bar, arenes (0.6 mmol), aromatic thiols (1.8 mmol), and t-BuOK (0.6
mmol, 67.3 mg) were added. Then, the vial was placed in a preheated
metal block at 80 °C in the presence of ambient air. The formation of
the monothiolation products was monitored by TLC. After
completion of the reaction, the mixture was cooled to 50 °C and
diluted with ethyl acetate (5.0 mL) and then quenched with cold
water (15 mL) and extracted with ethyl acetate (2 × 20 mL). After
drying with anhydrous Na2SO4, the organic layer was concentrated
under reduced pressure, and the residue was purified by column
chromatography on silica gel (200−300 mesh) using petroleum/ethyl
acetate (20/1−10/1) as eluent to afford the desired monothiolation
products.
CONCLUSIONS
■
1-((4-Chlorophenyl)thio)naphthalen-2-ol (3a).4c The title com-
pound was isolated by column chromatography (eluent: petroleum
ether) as a white solid in 93% yield (160.0 mg). mp 180−181 °C. 1H
NMR (400 MHz, DMSO-d6): δ 10.39 (s, 1H, OH), 8.17 (d, 1H,
ArH, J = 8.8 Hz), 7.98 (d, 1H, ArH, J = 8.8 Hz), 7.89 (d, 1H, ArH, J =
8 Hz), 7.50 (t, 1H, ArH, J = 7.8 Hz), 7.38−7.33 (m, 2H, ArH), 7.25
(d, 2H, ArH, J = 8.4 Hz), 6.94 (d, 2H, ArH, J = 8.4 Hz). 13C{1H}
NMR (100 MHz, DMSO-d6): δ 158.9, 137.3, 136.1, 132.8, 129.8,
129.3, 129.0, 128.2, 127.7, 124.2, 123.8, 118.9, 107.4.
In summary, we have developed selective CDC reaction for the
synthesis of mono- and dithiolation arenes under basic
conditions without using any transition-metal catalysts and
solvents. Environmentally friendly air (molecular oxygen) was
employed as an ideal oxidant. This method is featured with
simple and green reaction conditions, broad substrate scope,
and good functional group tolerance, providing a practical
protocol for synthetic chemistry and industrial manufacturing.
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1-(4-Bromo-phenylsulfanyl)-naphthalen-2-ol (3b).10 The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a pale yellow solid in 95% yield (188.8 mg).
1-(2,4-Dichloro-phenylsulfanyl)-naphthalen-2-ol (3i). The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a pale yellow liquid in 85% yield (163.8 mg).
1H NMR (400 MHz, DMSO-d6): δ 10.62 (s, 1H, OH), 8.05 (t, 2H,
ArH, J = 9.2 Hz), 7.92 (d, 1H, ArH, J = 8.0 Hz), 7.66 (d, 1H, ArH, J =
2.4 Hz), 7.53−7.49 (m, 1H, ArH), 7.40−7.36 (m, 2H, ArH), 7.13
(dd, 1H, ArH, J = 8.8 Hz), 6.27 (d, 1H, ArH, J = 8.4 Hz). 13C{1H}
NMR (100 MHz, DMSO-d6): δ 159.4, 136.4, 136.0, 133.5, 130.7,
129.9, 129.3, 129.2, 128.5, 128.2, 127.2, 124.0, 123.9, 119.0, 105.5.
HRMS (ESI) m/z: calcd for C16H11Cl2OS ([M + H]+), 320.9902;
found, 320.9904.
1
mp 118−119 °C. H NMR (400 MHz, DMSO-d6): δ 10.41 (s, 1H,
OH), 8.18 (d, 1H, ArH, J = 8.4 Hz), 7.98 (d, 1H, ArH, J = 9.0 Hz),
7.89 (d, 1H, ArH, J = 8.0 Hz), 7.52−7.48 (m, 1H, ArH), 7.39−7.34
(m, 4H, ArH), 6.90 (d, 2H, ArH, J = 8.6 Hz). 13C{1H} NMR (100
MHz, DMSO-d6): δ 158.9, 138.0, 136.1, 132.9, 132.2, 129.1, 129.0,
128.3, 128.1, 124.3, 123.8, 119.0, 118.0, 107.4.
1-(4-Fluoro-phenylsulfanyl)-naphthalen-2-ol (3c).11 The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a white solid in 96% yield (155.5 mg). mp
116−118 °C. 1H NMR (400 MHz, DMSO-d6): δ 10.33 (s, 1H, OH),
8.24 (d, 1H, ArH, J = 8.0 Hz), 7.97 (d, 1H, ArH, J = 8.0 Hz), 7.88 (d,
1H, ArH, J = 8.0 Hz), 7.52−7.49 (m, 1H, ArH), 7.37−7.34 (m, 2H,
ArH), 7.08−7.00 (m, 4H, ArH). 13C{1H} NMR (100 MHz, DMSO-
d6): δ 160.6 (d, JCF = 240.4 Hz), 158.8, 136.2, 133.6, 132.7, 129.0,
128.5, 128.1, 124.4, 123.7, 119.0, 116.6, 116.3, 108.6. 19F NMR (376
MHz, CDCl3): δ −116.2.
1-((2,4-Difluorophenyl)thio)naphthalen-2-ol (3j). The title com-
pound was isolated by column chromatography (eluent: petroleum
1
ether) as a yellow sticky liquid in 93% yield (160.9 mg). H NMR
(400 MHz, DMSO-d6): δ 10.56 (s, 1H, OH), 8.25 (d, 1H, ArH, J =
8.4 Hz), 8.01 (d, 1H, ArH, J = 9.2 Hz), 7.90 (d, 1H, ArH, J = 8.0 Hz),
7.56−7.51 (m, 1H, ArH), 7.41−7.30 (m, 3H, ArH), 6.91−6.86 (m,
1H, ArH), 6.62−6.56 (m, 1H, ArH). 13C{1H} NMR (100 MHz,
DMSO-d6): δ 159.3, 136.2, 133.0, 129.1, 128.3, 124.1, 123.8, 120.9,
120.7, 119.0, 112.7, 112.5, 105.9, 105.0, 104.7, 104.5. 19F NMR (376
MHz, CDCl3): δ −107.5, −111.8. HRMS (ESI) m/z: calcd for
C16H11F2OS ([M + H]+), 289.0493; found, 289.0494.
1-p-Tolylsulfanyl-naphthalen-2-ol (3d).4c The title compound
was isolated by column chromatography (eluent: petroleum ether) as
a pale yellow solid in 83% yield (132.7 mg). mp 76−78 °C. 1H NMR
(400 MHz, DMSO-d6): δ 10.24 (s, 1H, OH), 8.23 (d, 1H, ArH, J =
8.0 Hz), 7.93 (d, 1H, ArH, J = 8.0 Hz), 7.85 (d, 1H, ArH, J = 8.0 Hz),
7.47 (t, 1H, ArH, J = 8.0 Hz), 7.37−7.31 (m, 2H, ArH), 6.98 (d, 2H,
ArH, J = 8.0 Hz), 6.88 (d, 2H, ArH, J = 8.0 Hz), 2.17 (s, 3H, CH).
13C{1H} NMR (100 MHz, DMSO-d6): δ 158.8, 136.3, 134.7, 134.6,
132.4, 130.5, 130.3, 129.1, 129.0, 128.6, 128.0, 126.6, 124.6, 123.7,
119.0, 108.7, 20.9.
1-(Naphthalen-2-ylsulfanyl)-naphthalen-2-ol (3k).4c The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a white solid in 94% yield (170.6 mg). mp
1
87−88 °C. H NMR (400 MHz, DMSO-d6): δ 10.45 (s, 1H, OH),
8.31 (d, 1H, ArH, J = 8.8 Hz), 8.02 (d, 1H, ArH, J = 8.8 Hz), 7.90 (d,
1H, ArH, J = 8.0 Hz), 7.79−7.73 (m, 2H, ArH), 7.62−7.60 (m, 1H,
ArH), 7.50−7.33 (m, 6H, ArH), 7.20 (dd, 1H, ArH, J1 = 2.0 Hz, J2 =
8.8 Hz). 13C{1H} NMR (100 MHz, DMSO-d6): δ 159.1, 136.4, 136.0,
133.8, 132.8, 131.3, 129.2, 129.1, 128.9, 128.1, 128.0, 127.0, 125.7,
125.2, 124.6, 123.8, 123.6, 119.1, 108.0.
1-((4-Nitrophenyl)thio)naphthalen-2-ol (3e).11 The title com-
pound was isolated by column chromatography (eluent: petroleum
ether: ethyl acetate = 8:1) as a yellow solid in 83% yield (148.1 mg).
1
mp 125−127 °C. H NMR (400 MHz, DMSO-d6): δ 10.67 (s, 1H,
1-(Pyridin-4-ylsulfanyl)-naphthalen-2-ol (3l). The title compound
was isolated by column chromatography (eluent: petroleum ether) as
a yellow liquid in 90% yield (136.8 mg). 1H NMR (400 MHz,
DMSO-d6): δ 10.60 (s, 1H, OH), 8.25 (dd, 2H, ArH, J1 = 1.4 Hz, J2 =
4.8 Hz), 8.10 (d, 1H, ArH, J = 8.0 Hz), 8.03 (d, 1H, ArH, J = 8.0 Hz),
7.92 (d, 1H, ArH, J = 8.0 Hz), 7.53−7.49 (m, 1H, ArH), 7.40−7.36
(m, 2H, ArH), 6.86 (dd, 2H, ArH, J1 = 1.6 Hz, J2 = 4.6 Hz). 13C{1H}
NMR (100 MHz, DMSO-d6): δ 159.2, 149.7, 149.5, 136.0, 133.4,
129.2, 129.1, 128.5, 124.0, 120.3, 119.0, 104.9. HRMS (ESI) m/z:
calcd for C15H12NOS ([M + H]+), 254.0634; found, 254.0647.
1-(Benzothiazol-2-ylsulfanyl)-naphthalen-2-ol (3m).4c The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a gray solid in 92% yield (170.8 mg). mp
156−158 °C. 1H NMR (400 MHz, DMSO-d6): δ 10.99 (s, 1H, OH),
8.24 (d, 1H, ArH, J = 8.4 Hz), 8.09 (d, 1H, ArH, J = 8.4 Hz), 7.94 (d,
1H, ArH, J = 8.0 Hz), 7.83−7.77 (m, 2H, ArH), 7.56 (t, 1H, ArH, J =
7.6 Hz), 7.41 (d, 3H, ArH, J = 7.6 Hz), 7.26 (t, 1H, ArH, J = 7.2 Hz).
13C{1H} NMR (100 MHz, DMSO-d6): δ 105.7, 118.6, 120.9, 121.5,
OH), 8.12 (d, 1H, ArH, J = 8.4 Hz), 8.06 (d, 3H, ArH, J = 8.8 Hz),
7.93 (d, 1H, ArH, J = 8.0 Hz), 7.52 (t, 1H, ArH, J = 7.5 Hz), 7.45−
7.34 (m, 2H, ArH), 7.12 (d, 2H, ArH, J = 8.8 Hz). 13C{1H} NMR
(100 MHz, DMSO-d6): δ 159.2, 148.7, 144.8, 135.9, 133.5, 129.2,
129.1, 128.5, 125.8, 124.5, 124.0, 123.9, 119.0, 105.6.
1-(3-Chloro-phenylsulfanyl)-naphthalen-2-ol (3f). The title com-
pound was isolated by column chromatography (eluent: petroleum
ether) as a white solid in 94% yield (161.8 mg). mp 115−117 °C. 1H
NMR (400 MHz, DMSO-d6): δ 10.47 (s, 1H, OH), 8.20 (d, 1H,
ArH, J = 8.0 Hz), 8.00 (d, 1H, ArH, J = 12.0 Hz), 7.89 (d, 1H, ArH, J
= 8.0 Hz), 7.50 (t, 1H, ArH, J = 8.0 Hz), 7.40−7.34 (m, 2H, ArH),
7.20 (t, 1H, ArH, J = 8.0 Hz), 7.11 (d, 1H, ArH, J = 8.0 Hz), 6.94 (d,
2H, ArH, J = 12.0 Hz). 13C{1H} NMR (100 MHz, DMSO-d6): δ
159.1, 140.9, 136.2, 134.1, 133.1, 131.0, 129.1, 128.3, 125.2, 125.1,
124.7, 124.2, 123.9, 119.0, 107.0. HRMS (ESI) m/z: calcd for
C16H11ClNaOS ([M + Na]+), 309.0111; found, 309.0109.
1-(3-Fluoro-phenylsulfanyl)-naphthalen-2-ol (3g).10 The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a yellow sticky liquid in 96% yield (155.7 mg).
1H NMR (400 MHz, DMSO-d6): δ 10.52 (s, 1H, OH), 8.22 (d, 1H,
ArH, J = 8.4 Hz), 8.03 (d, 1H, ArH, J = 9.2 Hz), 7.92 (d, 1H, ArH, J =
8.0 Hz), 7.55−7.50 (m, 1H, ArH), 7.43−7.36 (m, 2H, ArH), 7.28−
7.22 (m, 1H, ArH), 6.93−6.89 (m, 1H, ArH), 6.84−6.82 (m, 1H,
ArH), 6.74−6.71 (m, 1H, ArH). 13C{1H} NMR (100 MHz, DMSO-
d6): δ 162.9 (d, JCF = 243.8 Hz), 159.1, 141.1, 136.2, 133.1, 129.1,
128.3, 124.3, 123.8, 122.0, 119.0, 112.6, 112.2, 107.0. 19F NMR (376
MHz, CDCl3): δ −111.4.
123.2, 123.6, 123.9, 126.1, 128.3, 128.6, 128.7, 133.9, 134.7, 135.4,
153.8, 159.1, 170.4.
6-Bromo-1-(4-chloro-phenylsulfanyl)-naphthalen-2-ol (3n).12
The title compound was isolated by column chromatography (eluent:
petroleum ether) as a white solid in 97% yield (212.8 mg). mp 198−
201 °C. 1H NMR (400 MHz, DMSO-d6): δ 10.63 (s, 1H, OH), 8.17
(d, 1H, ArH, J = 2.0 Hz), 8.10 (d, 1H, ArH, J = 8.8 Hz), 7.98 (d, 1H,
ArH, J = 8.8 Hz), 7.62 (dd, 1H, ArH, J1 = 2.0 Hz, J2 = 9.0 Hz), 7.39
(d, 1H, ArH, J = 8.8 Hz), 7.26 (d, 2H, ArH, J = 8.4 Hz), 6.94 (d, 2H,
ArH, J = 8.4 Hz). 13C{1H} NMR (100 MHz, DMSO-d6): δ 164.1,
141.7, 139.7, 136.8, 135.8, 135.5, 135.1, 134.7, 134.6, 134.3, 134.1,
132.6, 131.5, 125.0, 121.5, 112.7.
1-(2-Chloro-phenylsulfanyl)-naphthalen-2-ol (3h).10 The title
compound was isolated by column chromatography (eluent:
1
petroleum ether) as a yellow liquid in 93% yield (160.0 mg). H
5-(4-Chloro-phenylsulfanyl)-6-hydroxy-naphthalene-2-carboni-
trile (3o). The title compound was isolated by column chromatog-
raphy (eluent: petroleum ether) as a white solid in 88% yield (164.6
NMR (400 MHz, DMSO-d6): δ 10.55 (s, 1H, OH), 8.12 (d, 1H,
ArH, J = 8.0 Hz), 8.01 (d, 1H, ArH, J = 8.0 Hz), 7.89 (d, 1H, ArH, J =
8.0 Hz), 7.50−7.41 (m, 3H, ArH), 7.35 (t, 1H, ArH, J = 8.0 Hz),
7.07−7.03 (m, 1H, ArH), 7.01−6.97 (m, 1H, ArH), 6.33−6.31 (m,
1H, ArH). 13C{1H} NMR (100 MHz, DMSO-d6): δ 159.4, 137.3,
136.2, 133.2, 130.1, 129.9, 129.2, 129.1, 128.3, 127.9, 126.2, 126.1
124.1, 123.9, 119.1, 106.1.
1
mg). mp 157−159 °C. H NMR (400 MHz, DMSO-d6): δ 11.13 (s,
1H, OH), 8.54 (d, 1H, ArH, J = 1.4 Hz), 8.30 (d, 1H, ArH, J = 8.8
Hz), 8.13 (d, 1H, ArH, J = 9.2 Hz), 7.78 (dd, 1H, ArH, J1 = 1.6 Hz, J2
= 8.8 Hz), 7.50 (d, 1H, ArH, J = 9.2 Hz), 7.27 (d, 2H, ArH, J = 8.4
Hz), 6.96 (d, 2H, ArH, J = 8.8 Hz). 13C{1H} NMR (100 MHz,
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DMSO-d6): δ 161.2, 137.7, 136.1, 134.8, 133.1, 129.7, 129.0, 128.3,
127.6, 127.4, 125.2, 120.3, 119.2, 107.9, 105.5. HRMS (ESI) m/z:
calcd for C17H11ClNOS ([M + H]+), 312.0244; found, 312.0248.
1-Phenylselanyl-naphthalen-2-ol (3p).13 The title compound was
isolated by column chromatography (eluent: petroleum ether) as a
HRMS (ESI) m/z: calcd for C16H11Cl2OS ([M + H]+), 320.9902;
found, 320.9902.
4-(4-Chloro-phenylsulfanyl)-2-methyl-phenol (5g). The title
compound was isolated by column chromatography (eluent:
1
petroleum ether) as a colorless liquid in 83% yield (124.8 mg). H
1
white solid in 80% yield (143.6 mg). mp 78−79 °C. H NMR (400
NMR (400 MHz, DMSO-d6): δ 9.87 (s, 1H, OH), 7.32 (d, 2H, ArH,
J = 8.4 Hz), 7.25 (s, 1H, ArH), 7.18 (dd, 1H, ArH, J1 = 2.4 Hz, J2 =
8.4 Hz), 7.05 (d, 2H, ArH, J = 8.4 Hz), 6.87 (d, 1H, ArH, J = 8.4 Hz),
2.12 (s, 3H, CH). 13C{1H} NMR (100 MHz, DMSO-d6): δ 157.3,
138.8, 137.5, 134.1, 130.4, 129.5, 128.7, 126.4, 119.6, 116.4, 16.3.
HRMS (ESI) m/z: calcd for C13H10ClOS ([M − H]‑), 249.0146;
found, 249.0144.
MHz, DMSO-d6): δ 10.25 (s, 1H, OH), 8.25 (d, 1H, ArH, J = 8.4
Hz), 7.94 (d, 1H, ArH, J = 8.8 Hz), 7.85 (d, 1H, ArH, J = 8.0 Hz),
7.48−7.44 (m, 1H, ArH), 7.37−7.31 (m, 2H, ArH), 7.17−7.08 (m,
5H, ArH). 13C{1H} NMR (100 MHz, DMSO-d6): δ 157.7, 136.1,
132.8, 132.0, 129.2, 128.6, 128.5, 127.5, 126.4, 125.6, 123.1, 118.1,
107.5.
2-(4-Chloro-phenylsulfanyl)-naphthalen-1-ol (5a).14 The title
compound was isolated by column chromatography (eluent:
2-(4-Chloro-phenylsulfanyl)-4-methyl-phenol (5h).14 The title
compound was isolated by column chromatography (eluent:
1
1
petroleum ether) as a colorless liquid in 85% yield (146.2 mg). H
petroleum ether) as a colorless liquid in 85% yield (127.8 mg). H
NMR (400 MHz, DMSO-d6): δ 10.02 (s, 1H, OH), 8.27 (d, 1H,
ArH, J = 8.0 Hz), 7.89 (d, 1H, ArH, J = 7.6 Hz), 7.61−7.54 (m, 2H,
ArH), 7.46 (d, 1H, ArH, J = 8.4 Hz), 7.39 (d, 1H, ArH, J = 8.4 Hz),
7.35 d, 2H, ArH, J = 8.8 Hz), 7.11 (d, 2H, ArH, J = 8.8 Hz). 13C{1H}
NMR (100 MHz, DMSO-d6): δ 154.5, 136.2, 134.8, 131.9, 130.3,
129.0, 128.8, 127.6, 127.4, 125.7, 125.1, 122.6, 120.3, 110.3.
NMR (400 MHz, DMSO-d6): δ 9.77 (s, 1H, OH), 7.35 (d, 2H, ArH,
J = 8.4 Hz), 7.11 (d, 2H, ArH, J = 8.8 Hz), 7.06 (d, 2H, ArH, J = 7.6
Hz), 6.86 (d, 1H, ArH, J = 7.6 Hz), 2.17 (s, 3H, CH). 13C{1H} NMR
(100 MHz, DMSO-d6): δ 155.1, 135.7, 134.7, 131.0, 130.3, 129.4,
128.9, 128.6, 117.0, 115.9, 19.8.
6-(4-Chloro-phenylsulfanyl)-benzo[1,3]dioxol-5-ol (5i). The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a white solid in 88% yield (148.2 mg). mp
2-(4-Bromo-phenylsulfanyl)-naphthalen-1-ol (5b). The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a white solid in 87% yield (172.9 mg). mp
1
109−111 °C. H NMR (400 MHz, DMSO-d6): δ 9.75 (s, 1H, OH),
1
72−74 °C. H NMR (400 MHz, DMSO-d6): δ 10.05 (s, 1H, OH),
7.31 (d, 2H, ArH, J = 8.8 Hz), 7.03 (d, 2H, ArH, J = 8.4 Hz), 6.90 (s,
1H, ArH), 6.61 (s, 1H, ArH), 6.00 (s, 2H, CH). 13C{1H} NMR (100
MHz, DMSO-d6): δ 154.7, 150.2, 140.9, 137.8, 130.1, 129.3, 128.2,
114.8, 106.3, 102.0, 98.6. HRMS (ESI) m/z: calcd for C13H9ClO3S
(M+), 279.9961; found, 279.9962.
8.30 (d, 1H, ArH, J = 7.6 Hz), 7.93−7.91 (m, 1H, ArH), 7.63−7.56
(m, 2H, ArH), 7.51−7.48 (m, 3H, ArH), 7.42 (d, 1H, ArH, J = 8.4
Hz), 7.07 (d, 2H, ArH, J = 8.4 Hz). 13C{1H} NMR (100 MHz,
DMSO-d6): δ 155.1, 137.4, 135.3, 132.5, 132.4, 129.5, 128.1, 127.9,
126.2, 125.6, 123.1, 120.8, 119.0, 110.5. HRMS (ESI) m/z: calcd for
C16H12BrOS ([M + H]+), 330.9787; found, 330.9793.
2-(4-Chloro-phenylsulfanyl)-pyren-1-ol (5j). The title compound
was isolated by column chromatography (eluent: petroleum ether) as
a yellow liquid in 67% yield (145.1 mg). 1H NMR (400 MHz,
DMSO-d6): δ 10.41 (s, 1H, OH), 8.43 (d, 1H, ArH, J = 9.2 Hz), 8.26
(s, 1H, ArH), 8.22−8.15 (m, 3H, ArH), 8.06−7.95 (m, 3H, ArH),
7.39 (d, 2H, ArH, J = 8.8 Hz), 7.21 (d, 2H, ArH, J = 8.8 Hz). 13C{1H}
NMR (100 MHz, DMSO-d6): δ 152.0, 135.9, 131.8, 131.6, 131.4,
131.1, 130.4, 130.0, 129.7, 127.4, 127.3, 127.2, 126.1, 125.5, 125.3,
125.2, 124.8, 122.1, 120.0, 117.9. HRMS (ESI) m/z: calcd for
C22H14ClOS ([M + H]+), 361.0448; found, 361.0451.
2-p-Tolylsulfanyl-naphthalen-1-ol (5c).14 The title compound
was isolated by column chromatography (eluent: petroleum ether) as
a pink solid in 90% yield (143.9 mg). mp 180−181 °C. 1H NMR (400
MHz, DMSO-d6): δ 9.85 (s, 1H, OH), 8.25−8.22 (m, 1H, ArH),
7.86−7.84 (m, 1H, ArH), 7.56−7.51 (m, 2H, ArH), 7.41 (d, 1H,
ArH, J = 8.8 Hz), 7.30 (d, 1H, ArH, J = 8.4 Hz), 7.13−7.08 (m, 4H,
ArH), 2.25 (s, 3H, CH). 13C{1H} NMR (100 MHz, DMSO-d6): δ
153.9, 136.2, 134.8, 133.3, 131.6, 130.3, 129.1, 128.1, 127.5, 126.1,
125.5, 122.9, 120.6, 112.9, 20.98.
2-((4-Chlorophenyl)thio)phenol (5k).15 The title compound was
isolated by column chromatography (eluent: petroleum ether) as a
colorless liquid in 51% yield (72.4 mg). 1H NMR (400 MHz,
chloroform-d): δ 7.51 (dd, 1H, ArH, J1 = 7.7, J2 = 1.6 Hz), 7.41−7.35
(m, 1H, ArH), 7.23−7.17 (m, 2H, ArH), 7.07 (dd, 1H, ArH, J1 = 8.2,
J2 = 1.1 Hz), 7.02−6.98 (m, 2H, ArH), 6.98−6.93 (m, 1H, ArH), 6.43
(s, 1H, OH). 13C{1H} NMR (100 MHz, CDCl3): δ 157.18, 136.83,
134.45, 132.57, 132.15, 129.32, 128.12, 121.46, 115.93, 115.75.
General Procedure for the Preparation of Compounds 6a−
g. In a 10 mL reaction vial, equipped with a magnetic stirring bar,
arenes (0.6 mmol), aromatic thiols (1.8 mmol), and t-BuOK (0.6
mmol, 67.3 mg) were added. Then, the vial was placed in a preheated
metal block at 120 °C in the presence of ambient air. The formation
of the dithiolation products was monitored by TLC. After completion
of the reaction, the mixture was cooled to 50 °C and diluted with
ethyl acetate (5.0 mL) and then quenched with cold water (15 mL)
and extracted with ethyl acetate (2 × 20 mL). After drying with
anhydrous Na2SO4, the organic layer was concentrated under reduced
pressure, and the residue was purified by column chromatography on
silica gel (200−300 mesh) using petroleum/ethyl acetate (20/1−10/
1) as the eluent to afford desired dithiolation products.
2-(4-Fluoro-phenylsulfanyl)-naphthalen-1-ol (5d).14 The title
compound was isolated by column chromatography (eluent:
1
petroleum ether) as a colorless liquid in 90% yield (145.9 mg). H
NMR (400 MHz, DMSO-d6): δ 9.95 (s, 1H, OH), 8.27−8.25 (m, 1H,
ArH), 7.88−7.86 (m, 1H, ArH), 7.58−7.53 (m, 2H, ArH), 7.44 (d,
1H, ArH, J = 8.8 Hz), 7.35 (d, 1H, ArH, J = 8.4 Hz), 7.25−7.21 (m,
2H, ArH), 7.19−7.14 (m, 2H, ArH). 13C{1H} NMR (100 MHz,
DMSO-d6): δ 162.6, 160.1, 154.2, 135.0, 132.6, 132.5, 131.8, 130.9,
130.8, 128.1, 127.7, 126.2, 125.5, 123.0, 120.7, 116.8, 116.6, 112.4. 19F
NMR (376 MHz, CDCl3): δ −111.4.
2-(2-Chloro-phenylsulfanyl)-naphthalen-1-ol (5e). The title
compound was isolated by column chromatography (eluent:
1
petroleum ether) as a colorless liquid in 91% yield (156.6 mg). H
NMR (400 MHz, DMSO-d6): δ 10.12 (s, 1H, OH), 8.31 (d, 1H,
ArH, J = 8.0 Hz), 7.92 (d, 1H, ArH, J = 7.6 Hz), 7.64−7.55 (m, 2H,
ArH), 7.51−7.49 (m, 2H, ArH), 7.39 (d, 1H, ArH, J = 8.4 Hz), 7.18−
7.13 (m, 2H, ArH), 6.60−6.57 (m, 1H, ArH). 13C{1H} NMR (100
MHz, DMSO-d6): δ 156.0, 137.0, 135.6, 132.9, 130.5, 130.0, 128.2,
128.2, 128.1, 127.2, 127.0, 126.3, 125.7, 123.2, 121.1, 108.8. HRMS
(ESI) m/z: calcd for C16H12ClOS ([M + H]+), 287.0292; found,
287.0293.
2,4-Bis-(4-chloro-phenylsulfanyl)-naphthalen-1-ol (6a).16 The
title compound was isolated by column chromatography (eluent:
petroleum ether) as a white solid in 88% yield (226.7 mg). mp 141−
142 °C. 1H NMR (400 MHz, DMSO-d6): δ 10.70 (s, 1H, OH), 8.40
(d, 1H, ArH, J = 8.4 Hz), 8.18 (d, 1H, ArH, J = 7.2 Hz), 7.77 (s, 1H,
ArH), 7.64 (d, 2H, ArH, J = 3.2 Hz), 7.37 (d, 2H, ArH, J = 8.0 Hz),
7.28 (d, 2H, ArH, J = 8.0 Hz), 7.18 (d, 2H, ArH, J = 8.0 Hz), 7.03 (d,
2H, ArH, J = 8.0 Hz). 13C{1H} NMR (100 MHz, DMSO-d6): δ
157.2, 141.3, 137.1, 136.0, 135.3, 131.2, 130.8, 129.8, 129.7, 129.6,
129.3, 128.8, 127.0, 126.8, 125.8, 124.2, 119.4, 111.7.
2-(2,4-Dichloro-phenylsulfanyl)-naphthalen-1-ol (5f). The title
compound was isolated by column chromatography (eluent:
1
petroleum ether) as a colorless liquid in 88% yield (169.6 mg). H
NMR (400 MHz, DMSO-d6): δ 10.19 (s, 1H, OH), 8.31 (d, 1H,
ArH, J = 8.0 Hz), 7.92 (d, 1H, ArH, J = 7.2 Hz), 7.67−7.56 (m, 3H,
ArH), 7.51 (d, 1H, ArH, J = 8.8 Hz), 7.40 (d, 1H, ArH, J = 8.4 Hz),
7.26−7.23 (m, 1H, ArH), 6.57 (d, 1H, ArH, J = 8.8 Hz). 13C{1H}
NMR (100 MHz, DMSO-d6): δ 156.1, 136.5, 135.8, 132.8, 131.1,
130.5, 129.4, 128.4, 128.2, 128.2, 126.3, 125.7, 123.3, 121.2, 108.3.
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2,4-Bis-(4-bromo-phenylsulfanyl)-naphthalen-1-ol (6b). The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a yellow solid in 92% yield (286.1 mg). mp
161−164 °C. 1H NMR (400 MHz, DMSO-d6): δ 10.72 (s, 1H, OH),
8.39−8.37 (m, 1H, ArH), 8.18−8.15 (m, 1H, ArH), 7.76 (s, 1H,
ArH), 7.67−7.63 (m, 2H, ArH), 7.49 (d, 2H, ArH, J = 8.8 Hz), 7.41
(d, 2H, ArH, J = 8.4 Hz), 7.09 (d, 2H, ArH, J = 8.8 Hz), 6.95 (d, 2H,
ArH, J = 8.8 Hz). 13C{1H} NMR (100 MHz, DMSO-d6): δ 157.3,
141.5, 137.7, 136.7, 135.4, 132.5, 129.9, 129.4, 129.0, 127.1, 126.7,
125.8, 124.2, 119.4, 119.1, 119.0, 111.4. HRMS (ESI) m/z: calcd for
C22H13Br2OS2 ([M − H]‑), 514.8780; found, 514.8783.
172.1 mg), 4-methylbenzenethiol (1.8 mmol, 223.6 mg), and t-BuOK
(0.6 mmol, 67.3 mg) were added. Then, the vial was placed in a
preheated metal block at 80 °C in the presence of ambient air. The
formation of the dithiolation product was monitored by TLC. After
completion of the reaction, the mixture was cooled to 50 °C and
diluted with ethyl acetate (5.0 mL) and then quenched with cold
water (15 mL) and extracted with ethyl acetate (2 × 20 mL). After
drying with anhydrous Na2SO4, the organic layer was concentrated
under reduced pressure, and the residue was purified by column
chromatography on silica gel (200−300 mesh) using petroleum/ethyl
acetate (20/1−10/1) as the eluent to afford desired dithiolation
1
2,4-Bis-p-tolylsulfanyl-naphthalen-1-ol (6c). The title compound
was isolated by column chromatography (eluent: petroleum ether) as
product 6h as a colorless liquid in 86% yield (211.1 mg). H NMR
(400 MHz, DMSO-d6): δ 10.52 (s, 1H, OH), 8.40−8.31 (m, 1H,
ArH), 8.27−8.16 (m, 1H, ArH), 7.66−7.59 (m, 3H, ArH), 7.40−7.30
(m, 2H, ArH), 7.16 (d, 2H, ArH, J = 8.6 Hz), 7.08−6.95 (m, 4H,
ArH), 2.21 (s, 3H, CH). 13C{1H} NMR (100 MHz, DMSO-d6): δ
155.8, 139.1, 135.5, 135.4, 134.5, 133.1, 130.7, 129.9, 129.4, 129.1,
128.5, 127.9, 126.4, 126.1, 125.3, 123.5, 120.8, 111.3, 20.4. HRMS
(ESI) m/z: calcd for C23H17ClOS2 (M+), 408.0409; found, 408.0401.
1-(4-Chloro-phenylsulfanyl)-naphthalen-2-ylamine (7a).4c The
title compound was isolated by column chromatography (eluent:
petroleum ether) as a brown liquid in 55% yield (94.3 mg). 1H NMR
(400 MHz, DMSO-d6): δ 7.98 (d, 1H, ArH, J = 8.4 Hz), 7.79 (d, 1H,
ArH, J = 8.8 Hz), 7.73 (d, 1H, ArH, J = 8.0 Hz), 7.41−7.36 (m, 1H,
ArH), 7.26 (d, 2H, ArH, J = 8.4 Hz), 7.20−7.17 (m, 2H, ArH), 6.95
(d, 2H, ArH, J = 8.6 Hz), 6.07 (s, 2H, NH). 13C{1H} NMR (100
MHz, DMSO-d6): δ 151.0, 136.6, 132.3, 129.9, 129.4, 129.0, 128.1,
127.7, 123.1, 122.0, 118.7, 100.4.
1
a white solid in 83% yield (193.5 mg). mp 102−104 °C. H NMR
(400 MHz, DMSO-d6): δ 10.40 (s, 1H, OH), 8.34−8.30 (m, 1H,
ArH), 8.19−8.16 (m, 1H, ArH), 7.62−7.57 (m, 2H, ArH), 7.54 (s,
1H, ArH), 7.13 (s, 4H, ArH), 7.03 (d, 2H, ArH, J = 8.4 Hz), 6.95 (d,
2H, ArH, J = 8.0 Hz), 2.26 (s, 3H, CH), 2.20 (s, 3H, CH). 13C{1H}
NMR (100 MHz, DMSO-d6): δ 155.2, 139.0, 136.7, 135.9, 134.6,
133.8, 132.4, 130.5, 130.4, 129.7, 128.6, 128.2, 126.8, 126.6, 125.8,
123.8, 120.8, 114.0, 21.0, 20.9. HRMS (ESI) m/z: calcd for
C24H21OS2 ([M + H]+), 389.1028; found, 389.1024.
2,4-Bis-(4-fluoro-phenylsulfanyl)-naphthalen-1-ol (6d). The title
compound was isolated by column chromatography (eluent:
petroleum ether) as a white solid in 81% yield (192.7 mg). mp
108−109 °C. 1H NMR (400 MHz, DMSO-d6): δ 10.54 (s, 1H, OH),
8.36−8.33 (m, 1H, ArH), 8.20−8.18 (m, 1H, ArH), 7.66−7.55 (m,
3H, ArH), 7.30−7.26 (m, 2H, ArH), 7.21−7.16 (m, 2H, ArH), 7.12−
7.07 (m, 4H, ArH). 13C{1H} NMR (100 MHz, DMSO-d6): δ 161.6
(d, JCF = 242.6 Hz), 161.2 (d, JCF = 242.1 Hz), 155.6, 139.1, 134.6,
132.7, 131.6, 130.3, 128.9, 126.9, 126.6, 125.6, 123.9, 120.8, 117.0,
116.8, 113.7. 19F NMR (376 MHz, CDCl3): δ −115.2, −116.6.
HRMS (ESI) m/z: calcd for C22H14F2OS2 (M+), 396.0454; found,
396.0452.
1-p-Tolylsulfanyl-naphthalen-2-ylamine (7b).4c The title com-
pound was isolated by column chromatography (eluent: petroleum
ether) as a yellow liquid in 47% yield (74.8 mg). 1H NMR (400 MHz,
DMSO-d6): δ 8.05 (d, 1H, ArH, J = 8.4 Hz), 7.79 (d, 1H, ArH, J = 8.8
Hz), 7.74 (d, 1H, ArH, J = 8.0 Hz), 7.40 (t, 1H, ArH, J = 7.2 Hz),
7.21−7.17 (m, 2H, ArH), 7.03 (d, 2H, ArH, J = 7.6 Hz), 6.89 (d, 2H,
ArH, J = 7.2 Hz), 6.01 (s, 2H, NH), 2.21 (s, 3H, CH). 13C{1H} NMR
(100 MHz, DMSO-d6): δ 150.7, 134.8, 133.8, 131.9, 130.1, 128.9,
127.9, 127.7, 126.4, 123.4, 121.9, 118.6, 20.9.
2,4-Bis-(2-chloro-phenylsulfanyl)-naphthalen-1-ol (6e). The title
compound was isolated by column chromatography (eluent:
1
petroleum ether) as a colorless liquid in 90% yield (231.9 mg). H
NMR (400 MHz, DMSO-d6): δ 10.88 (s, 1H, OH), 8.44−8.41 (m,
1H, ArH), 8.13−8.11 (m, 1H, ArH), 7.77 (s, 1H, ArH), 7.70−7.66
(m, 2H, ArH), 7.52−7.47 (m, 2H, ArH), 7.23−7.17 (m, 2H, ArH),
7.14−7.06 (m, 2H, ArH), 6.76−6.73 (m, 1H, ArH), 6.47 (dd, 1H,
ArH, J1 = 1.6 Hz, J2 = 7.6 Hz). 13C{1H} NMR (100 MHz, DMSO-
d6): δ 158.6, 142.6, 137.3, 136.2, 135.9, 130.9, 130.2, 130.0, 129.8,
128.4, 128.3, 127.8, 127.5, 127.4, 127.2, 126.9, 125.7, 124.4, 117.8,
109.8. HRMS (ESI) m/z: calcd for C22H14Cl2OS2 (M+), 427.9863;
found, 427.9843.
2-(4-Chloro-phenylsulfanyl)-naphthalen-1-ylamine (7c).17 The
title compound was isolated by column chromatography (eluent:
petroleum ether) as a brown liquid in 43% yield (73.7 mg). 1H NMR
(400 MHz, DMSO-d6): δ 7.80 (d, 1H, ArH, J = 7.8 Hz), 7.55−7.51
(m, 2H, ArH), 7.49−7.44 (m, 1H, ArH), 7.38 (d, 1H, ArH, J = 8.4
Hz), 7.33−7.29 (m, 2H, ArH), 7.15 (d, 1H, ArH, J = 8.4 Hz), 7.05−
7.01 (m, 2H, ArH), 6.21 (s, 2H, NH). 13C{1H} NMR (100 MHz,
DMSO-d6): δ 148.0, 136.8, 135.4, 134.0, 130.2, 129.4, 128.5, 128.4,
128.1, 127.7, 125.3, 123.7, 123.0, 116.8, 104.4. HRMS (ESI) m/z:
calcd for C16H13ClNS ([M + H]+), 286.0452; found, 286.0465.
3-((4-Chlorophenyl)thio)-1H-indole (8a).18 The title compound
was isolated by column chromatography (eluent: petroleum ether/
ethyl acetate = 4:1) as a white solid in 84% yield (130.9 mg). mp
116−118 °C. 1H NMR (400 MHz, DMSO-d6): δ 11.75 (s, 1H, NH),
7.79 (d, 1H, CH, J = 2.4 Hz), 7.50 (d, 1H, ArH, J = 8.0 Hz), 7.38 (d,
1H, ArH, J = 8.0 Hz), 7.26 (d, 2H, ArH, J = 8.6 Hz), 7.20 (t, 1H,
ArH, J = 6.0 Hz), 7.08 (t, 1H, ArH, J = 7.0 Hz), 7.01 (d, 2H, ArH, J =
8.8 Hz). 13C{1H} NMR (100 MHz, DMSO-d6): δ 138.9, 137.2, 133.1,
129.7, 129.2, 128.8, 127.3, 122.7, 120.7, 118.6, 112.9, 99.1.
2,4-Bis-(2,4-dichloro-phenylsulfanyl)-naphthalen-1-ol (6f). The
title compound was isolated by column chromatography (eluent:
1
petroleum ether) as a colorless liquid in 91% yield (272.1 mg). H
NMR (400 MHz, DMSO-d6): δ 11.01 (s, 1H, OH), 8.46−8.44 (m,
1H, ArH), 8.11−8.09 (m, 1H, ArH), 7.83 (s, 1H, ArH), 7.73−7.63
(m, 4H, ArH), 7.27 (dd, 1H, ArH, J1 = 2.0 Hz, J2 = 8.8 Hz), 7.14 (dd,
1H, ArH, J1 = 2.0 Hz, J2 = 8.8 Hz), 6.73 (d, 1H, ArH, J = 8.4 Hz),
6.55 (d, 1H, ArH, J = 8.8 Hz). 13C{1H} NMR (100 MHz, DMSO-d6):
δ 159.0, 142.8, 136.7, 135.9, 135.8, 131.5, 130.9, 130.8, 130.7, 130.0,
129.5, 129.4, 128.7, 128.5, 128.4, 127.2, 127.0, 125.6, 124.5, 117.4,
109.2. HRMS (ESI) m/z: calcd for C22H12Cl4OS2 (M+), 495.9084;
found, 495.9075.
5-Chloro-3-(4-chloro-phenylsulfanyl)-1H-indole (8b).5c The title
compound was isolated by column chromatography (eluent:
petroleum ether/ethyl acetate = 4:1) as a white solid in 85% yield
2,4-Bis((4-chlorophenyl)thio)-6-methylphenol (6g). The title
compound was isolated by column chromatography (eluent:
1
(150.0 mg). mp 132−134 °C. H NMR (400 MHz, DMSO-d6): δ
1
petroleum ether) as a colorless liquid in 88% yield (207.7 mg). H
11.97 (s, 1H, NH), 7.90 (d, 1H, ArH, J = 2.8 Hz), 7.52 (d, 1H, ArH, J
= 8.6 Hz), 7.33 (d, 1H, ArH, J = 1.8 Hz), 7.29 (d, 2H, ArH, J = 8.6
Hz), 7.21 (dd, 1H, ArH, J1 = 2.0 Hz, J2 = 8.6 Hz), 7.01 (d, 2H, ArH, J
= 8.6 Hz). 13C{1H} NMR (100 MHz, DMSO-d6): δ 137.8, 135.3,
134.5, 129.7, 129.6, 128.9, 127.0, 125.1, 122.4, 117.1, 114.2, 98.6.
3-(4-Chloro-phenylsulfanyl)-5-nitro-1H-indole (8c). The title
compound was isolated by column chromatography (eluent:
petroleum ether/ethyl acetate = 4:1) as a yellow solid in 95% yield
NMR (400 MHz, DMSO-d6): δ 9.53 (s, 1H, OH), 7.40−7.37 (m, 2H,
ArH), 7.36−7.32 (m, 2H, ArH), 7.30 (dd, 1H, ArH, J1 = 0.8 Hz, J2 =
2.3 Hz), 7.22−7.18 (m, 2H, ArH), 7.14−7.06 (m, 3H, ArH), 2.22 (s,
3H, CH). 13C{1H} NMR (100 MHz, DMSO-d6): δ 155.9, 137.1,
136.9, 136.5, 134.6, 131.9, 131.4, 131.2, 129.9, 129.7, 129.6, 128.0,
122.5, 121.6, 17.1. HRMS (ESI) m/z: calcd for C19H15Cl2OS2 ([M +
H]+), 392.9936; found, 392.9939.
1
Procedure for the Preparation of Compound 6h. In a 10 mL
reaction vial, equipped with a magnetic stirring bar, 4a (0.6 mmol,
(173.7 mg). mp 191−193 °C. H NMR (400 MHz, DMSO-d6): δ
12.47 (s, 1H, NH), 8.25 (d, 1H, ArH, J = 2.2 Hz), 8.14 (s, 1H, ArH),
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Article
8.10 (dd, 1H, ArH, J1 = 2.2 Hz, J2 = 9.0 Hz), 7.71 (d, 1H, ArH, J = 9.0
Hz), 7.30 (d, 2H, ArH, J = 8.6 Hz), 7.01 (d, 2H, ArH, J = 8.0 Hz).
13C{1H} NMR (100 MHz, DMSO-d6): δ 141.6, 140.0, 137.2, 136.8,
300 mesh) using petroleum/ethyl acetate (10/1) as the eluent to
afford pure product 12 as wax in 98% yield (205.2 mg). H NMR
1
(400 MHz, DMSO-d6): δ 8.44−8.34 (m, 2H, ArH), 8.24−8.16 (m,
1H, ArH), 7.81−7.69 (m, 3H, ArH), 7.37−7.29 (m, 2H, ArH), 7.12−
7.03 (m, 2H, ArH). 13C{1H} NMR (100 MHz, DMSO): δ 150.0,
134.5, 134.4, 133.4, 131.6, 129.8, 129.8, 129.6, 129.2, 128.3, 126.4,
122.4, 120.3, 117.0. 19F NMR (376 MHz, CDCl3): δ −73.5 (d, J =
11.3 Hz). HRMS (ESI) m/z: calcd for C17H11ClF3O3S2 ([M + H]+),
418.9785; found, 418.9790.
129.9, 129.0, 127.9, 127.3, 117.7, 114.7, 113.3, 102.1. HRMS (ESI)
m/z: calcd for C14H9ClN2O2S (M+), 304.0073; found, 304.0073.
Product Transformation Processes for Compounds 9−12. 1-
((4-Chlorophenyl)sulfinyl)naphthalen-2-ol (9). In a 25 mL reaction
flask, equipped with a magnetic stirring bar, 3a (1.0 mmol, 286.8 mg)
and oxone (0.6 mmol, 368.9 mg) were added to ethanol (5.0 mL).
After the resulting mixture was stirred at 60 °C (oil bath) for 2 h, the
mixture was cooled to room temperature and water (5 mL) was
added. Then, the mixture was extracted with ethyl acetate (2 × 20
mL). After drying with anhydrous Na2SO4, the organic layer was
concentrated under reduced pressure, and the residue was purified by
column chromatography on silica gel (200−300 mesh) using
petroleum/ethyl acetate (20/1) as the eluent to afford pure product
9 as a white solid (260.4 mg, 86% yield). mp 191−193 °C. 1H NMR
(400 MHz, DMSO-d6): δ 11.25 (s, 1H, OH), 8.38 (d, 1H, ArH, J =
8.5 Hz), 7.99 (d, 1H, ArH, J = 9.0 Hz), 7.86 (d, 1H, ArH, J = 7.9 Hz),
7.65−7.54 (m, 4H, ArH), 7.41 (t, 1H, ArH, J = 7.7 Hz), 7.33 (t, 1H,
ArH, J = 7.5 Hz), 7.26 (d, 1H, ArH, J = 9.0 Hz). 13C{1H} NMR (100
MHz, DMSO): δ 157.1, 144.6, 135.2, 135.1, 129.7, 129.4, 128.9,
128.0, 126.4, 124.2, 122.4, 118.9, 118.3, 99.9. HRMS (ESI) m/z:
calcd for C16H12ClO2S ([M + H]+), 303.0241; found, 303.0239.
1-((4-Chlorophenyl)sulfonyl)naphthalen-2-ol (10).19 In a 25 mL
reaction flask, equipped with a magnetic stirring bar, 3a (1.0 mmol,
286.8 mg) and oxone (1.5 mmol, 922.1 mg) were added to mixed
solvent of ethanol and water (1:1, 5.0 mL). After the resulting mixture
was stirred at 60 °C (oil bath) for 3 h, the mixture was cooled to room
temperature and water (5 mL) was added. Then, the mixture was
extracted with ethyl acetate (2 × 20 mL). After drying with anhydrous
Na2SO4, the organic layer was concentrated under reduced pressure,
and the residue was purified by column chromatography on silica gel
(200−300 mesh) using petroleum/ethyl acetate (20/1) as the eluent
to afford pure product 10 as a white solid (293.3 mg, 92% yield). mp
119−121 °C. 1H NMR (400 MHz, DMSO-d6): δ 11.35 (s, 1H, OH),
9.06 (d, 1H, ArH, J = 8.8 Hz), 8.13 (d, 1H, ArH, J = 9.0 Hz), 8.01−
7.89 (m, 3H, ArH), 7.69−7.61 (m, 3H, ArH), 7.45 (t, 1H, ArH, J =
7.6 Hz), 7.20 (d, 1H, ArH, J = 9.0 Hz).13C{1H} NMR (100 MHz,
DMSO-d6): δ 157.9, 142.5, 138.4, 137.7, 130.7, 129.6, 129.5, 129.2,
129.1, 128.4, 126.4, 124.3, 122.8, 119.4, 115.5.
Procedure for the Control Experiment [Scheme 6b, 1,2-
Bis(4-chlorophenyl)disulfane (13)].5c In a 10 mL reaction flask,
equipped with a magnetic stirring bar, 4-chlorobenzenethiol (1.8
mmol, 260.3 mg) and t-BuOK (0.6 mmol, 67.3 mg) were added.
Then, the vial was placed in a preheated metal block and stirred at 80
°C in the presence of ambient air. After the reaction had reached
completion (monitored by TLC), cold water (15 mL) was added.
The mixture was extracted with ethyl acetate (2 × 20 mL). After
drying with anhydrous Na2SO4, the organic layer was concentrated
under reduced pressure, and the residue was purified by column
chromatography on silica gel (200−300 mesh) using petroleum/ethyl
acetate (20/1−10/1) as the eluent to afford pure 1,2-bis(4-
chlorophenyl)disulfane 13 in 98% yield (253.3 mg) as a light yellow
1
solid. mp 69−71 °C. H NMR (400 MHz, DMSO-d6): δ 7.61−7.46
(m, 8H, ArH). 13C{1H} NMR (100 MHz, DMSO-d6): δ 134.5, 132.5,
129.4, 129.1.
Procedure for the Control Experiment [Scheme 6f, (4-
Chlorophenyl)(2,2-diphenylethyl)sulfane (14)].21 In a 10 mL
reaction flask, equipped with a magnetic stirring bar, 2-naphthol (0.6
mmol, 86.5 mg), 4-chlorobenzenethiol (1.8 mmol, 260.3 mg), 1,1-
diphenylethylene (1.2 mmol, 216.2 mg), and t-BuOK (0.6 mmol, 67.3
mg) were added. Then, the vial was placed in a preheated metal block
at 80 °C in the presence of ambient air. After completion of the
reaction (monitored by TLC), cold water (15 mL) was added. After
drying with anhydrous Na2SO4, the mixture was extracted with ethyl
acetate (2 × 20 mL). The organic layer was concentrated under
reduced pressure, and the residue was purified by column
chromatography on silica gel (200−300 mesh) using petroleum/
ethyl acetate (20/1−9/1) as the eluent to provide 13 and 14 in 85%
(219.7 mg) yield and 7% (40.9 mg, yield based on 4-
chlorobenzenethiol) yield, respectively. 1H NMR (400 MHz,
DMSO-d6): δ 7.39−7.33 (m, 7H, ArH), 7.32−7.23 (m, 5H, ArH),
7.19 (t, 2H, ArH, J = 7.1 Hz), 4.18 (t, 1H, CH, J = 8.0 Hz), 3.73 (d,
2H, CH, J = 8.0 Hz). 13C{1H} NMR (100 MHz, DMSO-d6): δ 143.3,
135.5, 130.2, 129.7, 128.9, 128.4, 127.7, 126.5, 49.8, 37.4.
(4-Chlorophenyl)(2-methoxynaphthalen-1-yl)sulfane (11).20 In a
5 mL reaction flask, equipped with a magnetic stirring bar, 3a (0.5
mmol, 143.4 mg) and K2CO3 (1.0 mmol, 138.2 mg) were added to
dry DMF (2.0 mL) under argon. Then, CH3I (46.7 μL, 0.75 mmol)
was added dropwise with a syringe. After stirring at room temperature
for 3 h, the mixture was quenched with water (5 mL) and extracted
with ethyl acetate (2 × 20 mL). After drying with anhydrous Na2SO4,
the organic layer was concentrated under reduced pressure, and the
residue was purified by column chromatography on silica gel (200−
300 mesh) using petroleum/ethyl acetate (10/1) as the eluent to
afford pure product 11 as a white solid (147.4 mg, 98%). mp 112−
113 °C. 1H NMR (400 MHz, DMSO-d6): δ 8.26 (d, 1H, ArH, J = 8.5
Hz), 8.19 (d, 1H, ArH, J = 9.1 Hz), 7.98 (d, 1H, ArH, J = 8.3 Hz),
7.63 (d, 1H, ArH, J = 9.1 Hz), 7.59−7.51 (m, 1H, ArH), 7.48−7.39
(m, 1H, ArH), 7.29−7.20 (m, 2H, ArH), 6.98−6.89 (m, 2H, ArH),
3.94 (s, 3H, CH). 13C{1H} NMR (101 MHz, DMSO-d6): δ 159.7,
137.2, 135.7, 133.2, 129.8, 129.6, 129.3, 129.1, 128.5, 127.8, 124.6,
124.5, 114.5, 110.9, 57.1.
1-((4-Chlorophenyl)thio)naphthalen-2-yl Trifluoromethanesul-
fonate (12). In a 5 mL reaction flask, equipped with a magnetic
stirring bar, 3a (0.5 mmol, 143.4 mg) and pyridine (80.7 μL, 1 mmol)
were added to dry CH2Cl2 (1.0 mL) under argon at 0 °C. Then,
trifluoromethanesulfonic anhydride (125 μL, 0.75 mmol) was added
dropwise to the mixture at 0 °C. After complete addition, the mixture
was warmed to room temperature and stirred for 2 h. The mixture
was then quenched with water (5 mL) and extracted with ethyl
acetate (2 × 20 mL). After drying with anhydrous Na2SO4, the
organic layer was concentrated under reduced pressure, and the
residue was purified by column chromatography on silica gel (200−
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00898.
1
Optimization details, control experiments, and H, 13C,
and 19F NMR spectra of all products (PDF)
AUTHOR INFORMATION
■
Corresponding Author
Da-Zhen Xu − National Engineering Research Center of
Pesticide (Tianjin), State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China; orcid.org/0000-
0001-5076-7558; Email: xudazhen@nankai.edu.cn;
Fax: +86 22 2350 5948
Authors
Dong-Yang Han − National Engineering Research Center of
Pesticide (Tianjin), State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
10174
https://doi.org/10.1021/acs.joc.1c00898
J. Org. Chem. 2021, 86, 10166−10176

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pubs.acs.org/joc
Article
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Xiao-Peng Liu − National Engineering Research Center of
Pesticide (Tianjin), State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
Ruo-Pu Li − National Engineering Research Center of
Pesticide (Tianjin), State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00898
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by National Training
Programs of Innovation and Entrepreneurship for Under-
graduates (nos. 201910055087, 202010055079, and
202110055069). We also thank the Chemistry College of
Nankai University for its support.
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