Phenyliodine(III) Bis(trifluoroacetate) (PIFA)-Mediated Synthesis of Aryl Sulfides in Water

Article abstract of DOI:10.1021/acs.joc.8b00435

An environmentally benign method for the synthesis of aryl sulfides in water under mild conditions has been realized, in which arenes are coupled with equal stoichiometry of allyl sulfides. This arylthiolation is enabled by the presence of the Lipshutz su

Full text of DOI:10.1021/acs.joc.8b00435

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Phenyliodine(III) Bis(trifluoroacetate) (PIFA)-
Mediated Synthesis of Aryl Sulfides in Water
Qingyuan Feng, Dengfeng Chen, Mei Hong, Fei Wang, and Shenlin Huang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00435 • Publication Date (Web): 17 Apr 2018
Downloaded from http://pubs.acs.org on April 17, 2018
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The Journal of Organic Chemistry
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Phenyliodine(III) Bis(trifluoroacetate) (PIFA)-Mediated Synthe-
sis of Aryl Sulfides in Water
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Qingyuan Feng,† Dengfeng Chen,† Mei Hong,† Fei Wang,†,‡ Shenlin Huang*,†,‡
†Jiangsu Provincial Key Lab for the Chemistry and Utilization of AgroꢀForest Biomass, College of Chemical Engineering,
Nanjing Forestry University, Nanjing, 210037, P. R. China
‡Jiangsu Key Lab of BiomassꢀBased Green Fuels and Chemicals, Jiangsu CoꢀInnovation Center of Efficient Processing and
Utilization of Forest Resources, Nanjing Forestry University, Nanjing, 210037, P. R. China
Supporting Information Placeholder
ABSTRACT: An environmentally benign method for the synthesis of aryl sulfides in water under mild conditions has been realꢀ
ized, in which arenes are coupled with equal stoichiometry of allyl sulfides. This arylthiolation is enabled by the presence of the
Lipshutz surfactant, TPGSꢀ750ꢀM, using water as the recyclable reaction medium.
Aryl sulfides are key constituents of pharmaceuticals,1 ligands,2 and organic materials3 and are useful intermediates4 in modern
organic chemistry. Accordingly, a wide variety of approaches to aryl sulfides have been developed. One of the most common
methods involves the transition metalꢀcatalyzed coupling of aryl halides or pseudohalides with thiols or other sulfur based partners,5
which typically require prefunctionalized arenes (e.g. aryl halides). The direct C–H arythiolation of arenes mediated by transition
metals6 offers improved reaction efficiency; however, these reactions often require expensive and sometimes toxic transition metꢀ
als, raising issues of metal contamination especially in the pharmaceutical industry. More recently, direct C–H arylthiolation for the
synthesis of aryl sulfides under metalꢀfree conditions7 has emerged. Various electrophilic sulfur reagents and precursors including
thiols,8 disulfides,9 sulfonyl chlorides,10 sulfonyl hydrazines,11 Nꢀ(thio)succinicmides,12 sodium sulfonates,13 and others14 have been
employed. While these represent powerful transformations, the vast majority of current synthetic approaches suffer from limitations
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including: the use of bad odor, airꢀsensitive thiol substrates, strongly basic media, inert atmosphere, excess oxidants, high reaction
temperature, and toxic organic solvents. Therefore, the development of new sustainable protocols for the synthesis of aryl sulfides
in green solvents, such as water,15 under mild conditions is still highly desirable for sustainable organic synthesis.
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Scheme 1. PIFA-Mediated Direct C–H arylthiolation
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The arylthiolation of arenes with benzyl phenyl sulfide in the presence of phenyliodine(III) bis(trifluoroacetate) (PIFA) was first
reported by Kita et al.16 in 1996 and involved a oneꢀpot twoꢀstep procedure at ꢀ78 °C (Scheme 1A). Given PIFA, which belongs to
one of the most important classes of hypervalent iodine(III) reagents,17 is easy accessible and low toxic, this transformation is poꢀ
tentially useful. However, only one substrate, oꢀdimethoxybenzene was reported using halogenated solvent CH2Cl2, which is enviꢀ
ronmentally egregious.18 In addition, the E Factor19 from Kita’s procedure is very high. As our continuing efforts exploring organoꢀ
sulfur chemistry in water,20 we report herein an environmentally benign method for the synthesis of aryl sulfides via C–H functionꢀ
alization of electronꢀrich arenes in water (Scheme 1B). This new method offers some advantages, including a benign reaction solꢀ
vent, a 1:1 ratio of the two coupling partners, catalytic use of ZnCl2 under micellar conditions,21 and recyclable reaction medium
and catalyst.
Our optimization studies focused on the reaction between mꢀdimethoxybenzene and commercially available allyl phenyl sulfide
(Table 1). To our delight, the desired arylthiolation product 1 was obtained in 70% yield after a 24 h reaction that employed 10 mol%
ZnCl2 as the catalyst, 1 equiv PIFA as the oxidant, and 2 wt% TPGSꢀ750ꢀM/H2O as the solvent (Table 1, entry 1). In order to shed
light on the role of each reagent, several control experiments were subsequently conducted. Reaction efficiency was dramatically
affected upon removing ZnCl2 from the reaction (Table 1, entry 2), which suggested that the reactivity of PIFA might be further
enhanced by Lewis acid ZnCl2.22 Attempts to replace ZnCl2 with other Lewis acids, such as LiCl and BF3•Et2O, resulted in a much
lower yield (Table 1, entries 3 and 4). Inferior reaction performance was also observed when a variety of alternative solvents such
as toluene, THF, MeCN, CH2Cl2, toluene/water, CH2Cl2/water, or pure water were used (Table 1, entries 5
TPGSꢀ750ꢀM, developed by Lipshutz,23 might be playing a significant role in the micellar catalysis.
–11). This confirmed that
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Table 1. Optimization of the Reaction Conditions
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entry
1
variation from the standard condition
none
yieldb
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without ZnCl2
LiCl instead of ZnCl2
BF3•Et2O instead of ZnCl2
in toluene
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in THF
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in MeCN
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in CH2Cl2
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in toluene/water
in CH2Cl2/water
in H2O
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aConditions: mꢀdimethoxybenzene (0.24 mmol), allyl phenyl sulfide (0.24 mmol), ZnCl2 (0.024 mmol), PIFA (0.24 mmol), solvent (0.6
M) at 60 °C for 24 h. bYields were determined by HPLC analysis with 1ꢀnitro naphthalene as an internal standard.
Using the standard conditions described in Table 1, we next explored the scope of this transformation. With respect to ally sulꢀ
fides, diverse ally aryl sulfides served as effective crossꢀcoupling partners with mꢀdimethoxybenzene or 1,3,5ꢀtrimethoxybenzene
(Scheme 2). Product 1 was isolated in 67% yield. Arylthiolation products were obtained in moderate to excellent yields (45%–98%)
with allyl sulfides containing electronꢀdonating (2–6) and electronꢀwithdrawing (7–14) functional groups. It is worth highlighting
that versatile bromo, chloro, and fluoro substituents were well tolerated, which could be potentially further functionalized. While
electronic effects had no significant influence on the process (3, 5, and 14), steric effects resulted in noticeable differences in reacꢀ
tivity (5 vs 6, and 8 vs 9). Naphthylꢀsubstituted substrates were also competent in the reaction conditions, delivering desired sulfides
(15 and 16) in good yields.
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Scheme 2. Scope of ally sulfides
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10 mol% ZnCl2
1 equiv PIFA
OMe
OMe
SAr
ArS
+
2 wt% TPGS-750-M/H2O
60 °C, 24 h
MeO
R1
MeO
R1 = H, OMe
OMe
OMe
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9
OMe
S
OMe
S
OMe
OMe
3, 70%
OMe
S
S
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MeO
MeO
MeO
MeO
OMe
Br
1, 67%
2, 52%
4, 56%
Br
OMe
OMe
OMe
S
S
S
S
MeO
OMe
Cl
MeO
OMe
8, 79%
MeO
OMe
MeO
5, 87%
6, 66%
7, 52%
F
F
OMe
Br
OMe
OMe
OMe
S
S
S
S
MeO
OMe
CF3
MeO
OMe MeO
OMe MeO
12, 58%
9, 45%
OMe
10, 55%
11, 61%
NO2
OMe
OMe
OMe
S
S
S
S
MeO
OMe MeO
OMe
14, 98%
MeO
MeO
OMe
16, 66%
13, 50%
15, 50%
We next evaluated the scope with regards to the arene coupling partner (Scheme 3). Various electronꢀrich arenes were successfulꢀ
ly coupled to allyl phenyl sulfide. Alkoxybenzenes proceeded well under the standard conditions, giving the corresponding prodꢀ
ucts in high yields (17 and 18). Phenols also underwent smooth C–H arylthiolation, albeit in lower yields (19 and 20). In addition,
extended aromatics were successfully applied (21–26). Finally, this coupling reaction is compatible with free hydroxyl (19, 20, 22
and 24), amine (25 and 27), and amide (26) groups. With respect to limitatioins, this method is unsuccessful with arenes like simple
phenol, anisole, and toluene, or arenes with electronꢀwithdrawing groups.
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Scheme 3. Scope of arenes
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To further demonstrate the sustainability of this micelleꢀenabled coupling, we performed recycling of the aqueous medium conꢀ
taining the surfactant TPGSꢀ750ꢀM and ZnCl2 catalyst (Scheme 4). Once an arylthiolation was complete, the reaction solution was
extracted with a minimum volume of ethyl acetate, providing the desired coupling product. To the remaining aqueous mixture, was
then introduced 1,3,5ꢀtrimethoxybenzene (1 equiv), allyl phenyl sulfide (1 equiv), and PIFA (1 equiv), leading to another arylthiolaꢀ
tion. As shown in scheme 4, the arylthiolation proceeded efficiently without significant loss of yields and with a low E factor for
each recycle. The E factor can be reduced dramatically compared to Kita’s reaction conditions (Scheme 1a).
Scheme 4. Recycle Studies
Lastly, a hypothetical mechanism for the arylthiolation is outlined in Scheme 5a. We propose that the first step is the formation
of radical cation intermediate A, via a single electron transfer (SET) process.8d Subsequent nucleophilic attack of radical cation B
by the sulfide would give rise to the sulfonium salt B. Following deallylation7b would liberate the desired aryl sulfide product 1.
Importantly, it has been shown that PIFA is an excellent SET oxidant.17, 24 Moreover, the addition of radical scavenger TEMPO
prevented formation of sulfide 1, suggesting that radical intermediates might be involved in the transformation.
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Scheme 5. Proposed Reaction mechanism
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In summary, we have demonstrated an environmentally benign method for the synthesis of diaryl sulfides under micellar condiꢀ
tions. The C–H arylthiolation process was enabled by the presence of the Lipshutz surfactant, TPGSꢀ750ꢀM. Most notably, this
reaction proceeded in an aqueous reaction medium that avoids organic solvent and allows for the recycling of the water, surfactant,
and the catalyst.
ASSOCIATED CONTENT
EXPERIMENTAL SECTION
General Experimental.
General Information: All glassware was oven dried and all solvents were distilled prior to use, unless otherwise noted. Unless
otherwise noted, all reactions were performed under an atmosphere of argon. Optimization and substrate screens were performed in
2ꢀmL and 4ꢀmL vials. All reagents were used as received from commercial suppliers unless otherwise indicated. TPGSꢀ750ꢀM was
prepared according to the literature.23d The 2 wt% TPGSꢀ750ꢀM/H2O solution was prepared by dissolving TPGSꢀ750ꢀM in water.
Allyl phenyl sulfide were prepared according to the procedures reported in the literature 25. Thinꢀlayer chromatography (TLC) was
carried out on Merck silica gel plates (60Fꢀ254) and compounds were visualized using UV light absorbance and/or Vanillin reagent,
and High Performance Liquid Chromatography (HPLC) with UV detection at 254 nm. For HPLC yields, UV response factors relaꢀ
tive to an internal standard (1ꢀNitronaphthalene). Flash column chromatography was performed using silica gel 60 (230ꢀ400 mesh).
1
High resolution mass spectra were acquired by Agilent 6500 QTOFMS (ESI). All H NMR, 13C NMR spectra were recorded on
Bruker DRXꢀ600 or AMXꢀ400 instruments. Chemical shifts were given in parts per million (ppm, δ), referenced to the solvent peak
1
of CDCl3, defined at δ = 7.26 (1H NMR), defined at δ = 77.16 (13C NMR). Coupling constants were quoted in Hz (J). H NMR
Spectroscopy splitting patterns were designated as singlet (s), doublet (d), triplet (t), quartet (q). Splitting patterns that could not be
interpreted or easily visualized were designated as multiplet (m) or broad (br).
General Procedure for the Preparation of aryl sulfides: An ovenꢀdried 4 mL vial was charged with ZnCl2 (0.024 mmol, 10
mol%), arene (0.24 mmol, 1 eq), 2 wt% TPGSꢀ750ꢀM/H2O (0.4 mL, 0.6 M) and allyl sulfide (0.24 mmol, 1 eq) sequentially. The
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mixture was stirred for about 1 min until a homogeneous solution appeared. PIFA (0.24 mmol, 1 eq) was added and the solution
was heated at 60 °C for 24 hours. After the completion monitored by TLC, the reaction was cooled to RT and extracted by EtOAc
(3×0.4 mL), the organic phases was dried over anhydrous Na2SO4 and concentrated in vacuo. The crude was purified by flash colꢀ
umn chromatography (petroleum ether /EtOAc = 50/1 to petroleum ether /EtOAc = 20/1) to afford desired aryl sulfides.
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(2,4-Dimethoxyphenyl)(phenyl)sulfane (1).26 The product was obtained as a colorless oil (39.5 mg, 0.161 mmol, 67% yield). 1H
NMR (600 MHz, CDCl3) δ 7.34 (d, J = 8.4 Hz, 1H), 7.22 (m, 2H), 7.12 (m, 3H), 6.53 (d, J = 2.5 Hz, 1H), 6.50 (dd, J = 8.4, 2.5 Hz,
1H), 3.84 (s, 3H), 3.81 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 162.0, 160.5, 137.9, 136.9, 128.9, 127.9, 125.6, 112.3, 105.5, 99.4,
56.1, 55.6.
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(2,4-Dimethoxyphenyl)(4-methoxyphenyl)sulfane (2).9d The product was obtained as a colorless oil (34.5 mg, 0.125 mmol, 52%
yield). 1H NMR (400 MHz, CDCl3) δ 7.29 – 7.24 (m, 2H), 7.07 (d, J = 8.5 Hz, 1H), 6.86 – 6.80 (m, 2H), 6.48 (d, J = 2.5 Hz, 1H),
6.42 (dd, J = 8.5, 2.5 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H), 3.79 (s, 3H).
(4-Methoxyphenyl)(2,4,6-trimethoxyphenyl)sulfane (3).7c The product was obtained as a white solid (51.4 mg, 0.168 mmol, 70%
1
yield). H NMR (400 MHz, CDCl3) δ 7.09 – 7.04 (m, 2H), 6.76 – 6.71 (m, 2H), 6.19 (s, 2H), 3.85 (s, 3H), 3.81 (s, 6H), 3.74 (s,
3H).
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(2,4-Dimethoxyphenyl)(p-tolyl)sulfane (4).9d The product was obtained as a colorless oil (35.0 mg, 0.134 mmol, 56% yield). H
NMR (400 MHz, CDCl3): δ 7.24 (d, J = 8.4 Hz, 1H), 7.12 – 7.08 (m, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.51 (d, J = 2.5 Hz, 1H), 6.47
(dd, J = 8.4, 2.5 Hz, 1H), 3.821 (s, 3H), 3.818 (s, 3H) 2.30 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.5, 159.9, 135.9, 135.6,
133.5, 129.8, 129.2, 113.8, 105.4, 99.4, 56.1, 55.6, 21.1
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p-Tolyl(2,4,6-trimethoxyphenyl)sulfane (5).26 The product was obtained as a white solid (60.6mg, 0.209 mmol, 87% yield). H
NMR (400 MHz, CDCl3) δ 6.99 – 6.93 (m, 4H), 6.21 (s, 2H), 3.87 (s, 3H), 3.81 (s, 6H), 2.25 (s, 3H).
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m-Tolyl(2,4,6-trimethoxyphenyl)sulfane (6). The product was obtained as a white solid (46.0 mg, 0.158 mmol, 66% yield). H
NMR (400 MHz, CDCl3) δ7.03 (t, J = 7.7 Hz, 1H), 6.88 (s, 1H), 6.84 (d, J = 7.5 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H), 6.22 (s, 2H),
3.88 (s, 3H), 3.81 (s, 6H), 2.24 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 163.0, 162.7, 138.6, 138.3, 128.5, 126.5, 125.5, 122.8, 91.4,
56.5, 55.6, 21.5. HRMSꢀESI (m/z) [M+H]+ calculated for C16H19O3S 291.1049, found 291.1056. HRMSꢀESI (m/z) [M+K]+ calcuꢀ
lated for C16H18KO3S 329.0608, found 329.0609.
(4-Bromophenyl)(2,4-dimethoxyphenyl)sulfane (7).27 The product was obtained as a colorless oil (40.4 mg, 0.125 mmol, 52%
yield). 1H NMR (400 MHz, CDCl3) δ 7.37 (dd, J = 8.1, 0.5 Hz, 1H), 7.34 – 7.28 (m, 2H), 6.99 – 6.94 (m, 2H), 6.55 – 6.48 (m, 2H),
3.84 (s, 3H), 3.80 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 162.4, 160.7, 137.6, 137.4, 131.8, 129.0, 119.0, 111.4, 105.6, 99.6, 56.1,
55.7.
(3-Bromophenyl)(2,4,6-trimethoxyphenyl)sulfane (8). The product was obtained as a white solid (67.3 mg, 0.190 mmol, 79%
yield). 1H NMR (400 MHz, CDCl3) δ 7.15 (ddd, J = 7.7, 1.8, 1.2 Hz, 1H), 7.09 (t, J = 1.7 Hz, 1H), 7.01 (t, J = 7.8 Hz, 1H), 6.98 –
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6.93 (m, 1H), 6.22 (s, 2H), 3.88 (s, 3H), 3.81 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 163.4, 162.6, 159.6, 156.7, 141.5, 129.9,
128.1, 127.5, 124.3, 122.8, 91.8, 91.5, 56.4, 55.7, 55.6. HRMSꢀESI (m/z) [M+K]+ calculated for C15H15BrKO3S 392.9557, found
392.9570.
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(2-Bromophenyl)(2,4,6-trimethoxyphenyl)sulfane (9).26 The product was obtained as a white solid (38.2 mg, 0.108 mmol, 45%
yield). 1H NMR (400 MHz, CDCl3) δ 7.46 (dd, J = 7.9, 1.3 Hz, 1H), 7.06 – 6.99 (m, 1H), 6.92 – 6.85 (m, 1H), 6.51 (dd, J = 8.0, 1.5
Hz, 1H), 6.23 (s, 2H), 3.88 (s, 3H), 3.80 (s, 6H).
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(4-Chlorophenyl)(2,4,6-trimethoxyphenyl)sulfane (10).26 The product was obtained as a white solid (40.9 mg, 0.132 mmol, 55%
yield). 1H NMR (400 MHz, CDCl3) δ 7.13 – 7.09 (m, 2H), 6.97 – 6.92 (m, 2H), 6.21 (s, 2H), 3.87 (s, 3H), 3.81 (s, 6H).
(4-Fluorophenyl)(2,4,6-trimethoxyphenyl)sulfane (11).26 The product was obtained as a white solid (43.1 mg, 0.146 mmol, 61%
yield). 1H NMR (400 MHz, CDCl3) δ 7.06 – 6.99 (m, 2H), 6.89 – 6.83 (m, 2H), 6.20 (s, 2H), 3.86 (s, 3H), 3.81 (s, 6H).
(2,4-Dimethoxyphenyl)(4-fluorophenyl)sulfane (12). The product was obtained as a colorless oil (36.8 mg, 0.139 mmol, 58%
yield). 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 8.6 Hz, 1H), 7.19 – 7.13 (m, 2H), 6.98 – 6.90 (m, 2H), 6.53 – 6.46 (m, 2H), 3.82
(s, 3H), 3.81 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 161.9, 161.6 (d, J = 245.3 Hz), 160.1, 135.96, 132.5 (d, J = 3.1 Hz), 130.7 (d,
J = 7.9 Hz), 116.0 (d, J = 22.0 Hz), 113.4, 105.6, 99.5, 56.1, 55.6. HRMSꢀESI (m/z) [M+H]+ calculated for C14H14FO2S 265.0693,
found 265.0681.
(4-(Trifluoromethyl)phenyl)(2,4,6-trimethoxyphenyl)sulfane (13). The product was obtained as a colorless oil (41.3 mg, 0.120
mmol, 50% yield). 1H NMR (600 MHz, CDCl3) δ 7.38 (d, J = 8.3 Hz, 1H), 7.06 (d, J = 8.3 Hz, 1H), 6.23 (s, 1H), 3.89 (s, 3H), 3.81
(s, 6H). 13C NMR (150 MHz, CDCl3) δ 163.6, 162.7, 144.4, 126.4 (q, J = 32.4 Hz), 125.4 (q, J = 7.5 Hz), 125.2, 124.6 (q, J = 271.5
Hz), 91.8, 91.4, 56.4, 55.6. HRMSꢀESI (m/z) [M+H]+ calculated for C16H16F3O3S 345.0767, found 345.0769. HRMSꢀESI (m/z)
[M+K]+ calculated for C16H15F3KO3S 383.0326, found 383.0323.
(4-Nitrophenyl)(2,4,6-trimethoxyphenyl)sulfane (14).26 The product was obtained as a yellow solid (75.5 mg, 0.235 mmol, 98%
yield). 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.9 Hz, 2H), 7.05 (d, J = 8.9 Hz, 2H), 6.24 (s, 2H), 3.90 (s, 3H), 3.81 (s, 6H).
(2,4-Dimethoxyphenyl)(naphthalen-2-yl)sulfane (15). The product was obtained as a colorless oil (35.5 mg, 0.120 mmol, 50%
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yield). H NMR (600 MHz, CDCl3) δ7.76 (d, J = 7.9 Hz, 1H), 7.69 (d, J = 8.6 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 1.1
Hz, 1H), 7.45 – 7.36 (m, 3H), 7.28 (dd, J = 8.6, 1.8 Hz, 1H), 6.56 (d, J = 2.5 Hz, 1H), 6.52 (dd, J = 8.5, 2.5 Hz, 1H), 3.85 (s, 3H),
3.81 (s, 3H). 13C NMR (100 MHz, CDCl3) δ162.0, 160.5, 136.8, 135.4, 134.0, 131.8, 128.4, 127.8, 127.2, 126.5, 126.5, 125.9,
125.5, 112.4, 105.6, 99.5, 56.1, 55.7. HRMSꢀESI (m/z) [M+K]+ calculated for C18H16KO2S 335.0503, found 335.0500.
Naphthalen-2-yl(2,4,6-trimethoxyphenyl)sulfane (16).26 The product was obtained as a white solid (51.7 mg, 0.158 mmol, 66%
yield). 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.8 Hz, 1H), 7.62 (dd, J = 13.8, 8.4 Hz, 2H), 7.42 – 7.30 (m, 3H), 7.21 (dd, J =
8.6, 1.9 Hz, 1H), 6.25 (s, 2H), 3.90 (s, 3H), 3.81 (s, 6H).
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Phenyl(2,4,6-trimethoxyphenyl)sulfane (17).26 The product was obtained as a white solid (62.3 mg, 0.226 mmol, 94% yield). 1H
NMR (600 MHz, CDCl3): δ 7.15 (m, 2H), 7.03 (m, 3H), 6.22 (s, 2H), 3.87 (s, 3H), 3.81 (s, 6H).
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Phenyl(2,3,4-trimethoxy-6-methylphenyl)sulfane (18). The product was obtained as a white solid (55.7 mg, 0.192 mmol, 80%
yield). 1H NMR (600 MHz, CDCl3) δ 7.18 (t, J = 7.8 Hz, 2H), 7.06 (t, J = 7.4 Hz, 1H), 7.00 (d, J = 7.4 Hz, 2H), 6.67 (s, 1H), 3.90
(s, 3H), 3.87 (s, 3H), 3.78 (s, 3H), 2.37 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 156.0, 154.6, 141.1, 139.8, 139.0, 128.9, 126.0,
124.8, 116.8, 109.6, 61.6, 61.1, 56.1, 21.5. HRMSꢀESI (m/z) [M+H]+ calculated for C16H19O3S 291.1049, found 291.1054. HRMSꢀ
ESI (m/z) [M+K]+ calculated for C16H18KO3S 329.0608, found 329.0618.
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3,5-Dimethoxy-2-(phenylthio)phenol (19).28 The product was obtained as a colorless oil (25.8 mg, 0.098 mmol, 41% yield). H
NMR (600 MHz, CDCl3): δ 7.21 (t, J = 7.7 Hz, 2H), 7.12 (t, J = 7.3 Hz, 1H), 7.06 (d, J = 7.4 Hz, 2H), 6.92 (s, 1H), 6.30 (d, J = 2.6
Hz, 1H), 6.14 (d, J = 2.5 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 3H).
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3,5-Dimethyl-4-(phenylthio)phenol (20).13b The product was obtained as an orange oil (14.4 mg, 0.062 mmol, 26% yield). H
NMR (400 MHz, CDCl3): δ 7.17 (t, J = 7.7 Hz, 2H), 7.05 (t, J = 7.3 Hz, 1H), 6.91 (d, J = 7.5 Hz, 2H), 6.69 (s, 2H), 2.38 (s, 6H).
(4-Methoxynaphthalen-1-yl)(phenyl)sulfane (21).24b The product was obtained as a white solid (42.1 mg, 0.158 mmol, 66%
yield). 1H NMR (600 MHz, CDCl3) δ 8.35 – 8.30 (m, 2H), 7.80 (d, J = 8.0 Hz, 1H), 7.55 – 7.47 (m, 2H), 7.15 (t, J = 7.7 Hz, 2H),
7.08 – 7.01 (m, 3H), 6.84 (d, J = 8.0 Hz, 1H), 4.05 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 157.3, 139.2, 135.9, 135.4, 129.0, 127.8,
126.8, 126.8, 126.1, 125.9, 125.2, 122.7, 120.3, 104.2, 55.8.
1-(Phenylthio)naphthalen-2-ol (22).13b The product was obtained as a white solid (21.2 mg, 0.084 mmol, 35% yield). H NMR
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(600 MHz, CDCl3) δ 8.24 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.9 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.53 – 7.48 (m, 1H), 7.41 – 7.37
(m, 1H), 7.36 (d, J = 8.9 Hz, 1H), 7.22 – 7.16 (m, 3H), 7.11 (m, 1H), 7.07 – 7.02 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 157.1,
135.6, 135.5, 133.0, 129.6, 129.3, 128.7, 128.1, 126.5, 126.0, 124.8, 124.0, 117.0, 108.2.
(2-Methoxynaphthalen-1-yl)(phenyl)sulfane (23).13b The product was obtained as a colorless oil (22.4 mg, 0.084 mmol, 35%
yield). 1H NMR (400 MHz, CDCl3): δ 8.46 (d, J = 8.6 Hz, 1H), 7.98 (d, J = 9.1 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.50 (t, J = 7.6
Hz, 1H), 7.39 (t, J = 8.3 Hz, 2H), 7.13 (t, J = 7.6 Hz, 2H), 7.07 – 6.97 (m, 3H), 3.97 (s, 3H).
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1-(Phenylthio)naphthalene-2,7-diol (24).13b The product was obtained as a white solid (25.7 mg, 0.096 mmol, 40% yield). H
NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 2.5 Hz, 1H), 7.21 – 7.09 (m, 6H), 7.01
(dd, J = 7.3, 1.8 Hz, 2H), 6.97 (dd, J = 8.7, 2.5 Hz, 1H).
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1-(Phenylthio)naphthalen-2-amine (25).11b The product was obtained as a brown solid (41.0 mg, 0.163 mmol, 68% yield). H
NMR (600 MHz, CDCl3): δ 8.28 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 7.7 Hz, 1H),
7.30 – 7.26 (m, 1H), 7.16 (t, J = 7.7 Hz, 2H), 7.09 – 7.05 (m, 2H), 7.03 (d, J = 8.4 Hz, 2H), 4.73 (br, 2H).
N-(1-(phenylthio) naphthalen-2-yl)methacrylamide (26). The product was obtained as a brown oil (33.7 mg, 0.106 mmol, 44%
yield). 1H NMR (600 MHz, CDCl3) δ 9.33 (s, 1H), 8.85 (d, J = 9.0 Hz, 1H), 8.44 (d, J = 8.5 Hz, 1H), 8.01 (d, J = 9.1 Hz, 1H), 7.86
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(d, J = 8.1 Hz, 1H), 7.52 (t, J = 7.7 Hz, 1H), 7.45 (t, J = 7.4 Hz, 1H), 7.18 (t, J = 7.4 Hz, 2H), 7.11 (t, J = 7.3 Hz, 1H), 7.00 (d, J =
7.8 Hz, 2H), 5.75 (s, 1H), 5.43 (s, 1H), 2.01 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 166.4, 140.8, 140.6, 135.5, 135.5, 131.8, 131.3,
129.5, 128.6, 128.0, 126.4, 126.1, 125.9, 125.3, 121.1, 119.7, 113.8, 18.6. HRMSꢀESI (m/z) [M+H]+ calculated for C20H18NOS
320.1104, found 320.1101. HRMSꢀESI (m/z) [M+K]+ calculated for C20H17KNOS 358.0662, found 358.0664.
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2,6-Dimethyl-4-(phenylthio)aniline (27).29 The product was obtained as a brown oil (29.7 mg, 0.130 mmol, 54% yield). 1H NMR
(400 MHz, CDCl3): δ 7.20 (t, J = 7.6 Hz, 2H), 7.16 – 7.07 (m, 5H), 3.74 (s, 2H), 2.17 (s, 6H).
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Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
Further experimental details and copies of 1H and 13C NMR Spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: shuang@njfu.edu.cn.
ACKNOWLEDGMENT
Financial support provided by the Natural Science Foundation of China (21502094), the Natural Science Key Project of the Jiangsu Higher
Education Institutions (17KJA220003), and the Natural Science Foundation of Jiangsu Province (BK20140969) is warmly acknowledged.
We are also grateful for support by the Topꢀnotch Academic Programs Project of Jiangsu Higher Education Institutions (TAPP), the Prioriꢀ
ty Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and advanced analysis and testing center of Nanjing
Forestry University.
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