Ammonium iodide-promoted unprecedented arylsulfonylation of quinone with sodium arylsulfinates

Article abstract of DOI:10.1016/j.tet.2017.10.022

A novel ammonium iodide-promoted arylsulfonylation of quinones with sodium arylsulfinates has been explored. This reaction proceeded smoothly through unique nucleophilic addition reaction and produced the arylsulfonylation products in moderate to good yields. The reactions proceeded efficiently over a broad range of substrates with good regioselectivity and functional group tolerance.

Full text of DOI:10.1016/j.tet.2017.10.022

Accepted Manuscript
Ammonium iodide-promoted unprecedented arylsulfonylation of quinone with sodium
arylsulfinates
Jin-Wei Yuan, Shuai-Nan Liu, Ling-Bo Qu
PII:
S0040-4020(17)31037-2
10.1016/j.tet.2017.10.022
TET 29025
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 14 September 2017
Revised Date: 3 October 2017
Accepted Date: 10 October 2017
Please cite this article as: Yuan J-W, Liu S-N, Qu L-B, Ammonium iodide-promoted unprecedented
arylsulfonylation of quinone with sodium arylsulfinates, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.10.022.
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ACCEPTED MANUSCRIPT
Graphic abstract
Ammonium iodide-promoted unprecedented arylsulfonylation of
quinone with sodium arylsulfinates
Jinwei Yuan,* Shuainan Liu, Lingbo Qu
School of Chemical Engineering and Environment, Henan University of Technology; Academician
Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, PR China
An efficient protocol for the synthesis of quinonyl arylsulfone derivatives has been developed via
ammonium iodide-promoted arylsulfonylation of quinones with sodium arylsulfinates with
moderated to good yields.

ACCEPTED MANUSCRIPT
Ammonium iodide-promoted unprecedented arylsulfonylation of
quinone with sodium arylsulfinates
Jin-Wei Yuan,* Shuai-Nan Liu, Ling-Bo Qu
School of Chemical Engineering and Environment, Henan University of Technology; Academician
Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, PR China
Abstract: A novel ammonium iodide-promoted arylsulfonylation of quinones with sodium
arylsulfinates has been explored. This reaction proceeded smoothly through unique nucleophilic
addition reaction and produced the arylsulfonylation products in moderate to good yields. The
reactions proceeded efficiently over a broad range of substrates with good regioselectivity and
functional group tolerance.
Key words: quinone; sodium arylsulfinate; ammonium iodide-promoted; nucleophilic addition
reaction; arylsulfonylation
1. Introduction
Aryl sulfone skeleton is recognized as a crucial class of scaffold in organic synthesis, medicinal
chemistry, and natural products.[1] The development of facile methods for synthesis of aryl
sulfones has attracted extensive attention.[2] The traditional routes to access sulfones are
oxidation of sulfides and electrophilic sulfonylation of arenes, in which poor functional group
compatibility and necessary strong oxidants or strong acids limit its practical application.[3] In
recent years, transition metal-catalyzed aromatic C-H bond sulfonylation provided a useful tool
for the synthesis of aryl sulfone.[4] However, most of these methods were limited to provide
ortho-C-H sulfonylation with the assistance of a directing group. Direct sulfonylation via C-H
functionalization can provide a shortcut for aryl sulfones under metal or metal-free conditions.[5]
However, direct sulfonylation of an aromatic C-H bond with less reactive sodium arenesulfinates
is rare under metal-free conditions.[6]
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Figure 1. Several FabH inhibitors
As an important cyclic compound, quinone has been found in many natural products,
pharmaceuticals and functional materials.[7] Quinonyl aryl sulfone derivatives can be found to be
useful skeletons in pharmaceutical as an inhibitor of β-Ketoacyl-ACP-synthase III (FabH), which is
a key condensing enzyme in bacterial fatty acid biosynthesis and a part of the dissociated fatty
acid synthase (FAS).[8] 2-Tosylnaphthalene-1,4-diol (A), 2-tosylbenzene-1,4-diol (B) and
2-tosylnaphthalene-1,4-diol (C) were identified as potent FabH inhibitors (Figure 1). Their
biological evaluation showed that the sulfonyl group and naphthalene-1,4-diol were required for
activity against all enzymes.[9] Quinonyl aryl sulfones are generally prepared by oxidation of the
corresponding arylthioquinones.[10] In recent years, alternative approaches have been
developed for the sulfonylation of quinones using aryl sulfonyl halides or aryl sulfonic acids as
sulfonylation reagents through C-H functionalization. In 2016, Wang’s group reported the copper
and triphenylphosphine-promoted sulfenylation of quinones using arylsulfonyl chlorides as a
sulfur source with moderate to good yields (Scheme 1a).[11] Ding and co-workers described a
method to prepare arylsulfonyl-quinones and arylsulfonyl-1,4-diols by Pd-catalyzed direct
C-sulfone formation by C-S coupling of quinones with sulfonyl chloride; and Huang et al
developed an efficient method to sylfonyl quinones and sulfonyl-1,4-diols through Ir-catalyzed
C-S coupling of quinones with sulfonyl chloride (Scheme 1b).[12] In 2004, Yadav’s group disclosed
a method of ionic liquids-promoted addition of arylsulfinic acids to quinones to produce the
corresponding arylsulfonylhydroquinones, and ionic liquid plays the dual role as the solvent and
the catalyst in this reaction (Scheme 1c). [13] Moreover, Bruce et al synthesized a variety of alkyl-
or arylsulfonylhydroquinones by the nucleophilic addition of alkyl- or arylsulfinic acids to
1,4-quinones, and the reaction was conducted using a two phase dichloromethane-water system
in the presence of trifluoroacetic acid.[14]
Despite these significant advances, almost all of these C-H sulfonylation methods often involved
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in transition-metal, acid, or base as a catalyst, and required foul-smelling, toxic, and unstable
sulfur sources as starting materials, which had lower the synthetic efficiency and generality. As a
consequence, it is still an attractive but challenging task to develop a metal-free, environmentally
benign method for the rapid and straightforward construction of C-S bonds. Over the past few
years, iodine-catalyzed systems have been proven to be powerful tools to form C-S bonds;[15]
these systems have been employed in radical and ion reactions. In sharp contrast, iodide catalysts
are less explored over the sulfonylation of quinones. Arylsulfinic acid sodium salts are relative
stable and moisture-insensitive compared to sulfonyl chlorides. They have been widely used as
arylsulfonylation reagents for preparing organosulfonyl compounds.[16] In our continued efforts
on the development of new methods for the sulfonylation of quinones, herein, we report an
effective route for the sulfonylation of quinones through ammonium iodide-promoted
sulfonylation of quinones using sodium sulfinates as the sulfonation reagents (Scheme 1d).
Previous works:
( a )
O
O
O
O
S
R
CuI, PPh3
R
+ Cl
K3PO4, Toluene
120 oC
O
S
O
(b )
O
O
O
R
Pd(OAc)2
O
S
+ Cl
S
or [Cp*IrCl2]2
AgSbF6
O
O
O
R
R
O
NaBH4
OH
( c )
O
O
R [bmim]BF4
O
S
+
HO S
O
OH
O
This work:
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( d )
OH
OH
O
O
R1
R1
R2
NH4I
NaO2S
+
O
S
O
CH3OH, 40oC
R2
Scheme 1 Synthesis of 2-arylsulfonyl benzene-1,4-diols and naphthalene-1,4-diols
2. Results and discussion
We initiated our investigation on the model reaction of p-benzoquinone (1a) with sodium
benzenesulfinate (2a) to optimize the reaction parameters (Table 1). The C2-sulfonylation didn’t
take place in the absence of any catalysts in DMF at room temperature for 1.0 h (Table 1, entry 1).
Inspired by iodide-induced sulfonylation reactions,[15] various additives (4.0 eq.) such as NH4Cl,
NH4I, (NH4)2SO4, KI, I2, and tetra-butylammonium iodide (TBAI) were added for this
transformation to improve the yield (Table 1, entries 2-7), and among them NH4I was found to be
the best, and the target product 3a was afforded in 65% yield (Table 1, entry 3). No desired
transformation was observed employing similar ammonium salt (NH4)2SO4 (Table 1, entry 4),
+
ruling out the function of NH4 in this reaction. Neither the inorganic KI nor the organic
tertra-butylammounium (TBAI) did afford the desired product (Table 1, entries 5 and 7),
suggesting that iodide anion is not the real form for NH4I participated in this conversion. When
using 4.0 equiv of I2 instead of NH4I (Table 1, entry 6), 3a was not also obtained, which indicated
that I2 was not indeed the actual form to promote this conversion. The additive loading was also
investigated, and the result showed that 4.0 eq NH4I was superior to other loading (Table 1,
entries 3, 8-11). It’s necessary to use 4.0 eq NH4I to get satisfactory yield, otherwise the reaction
yield decreased to 30% when the additive loading was decreased to 1.0 eq (Table 1, entry 8). The
solvent also played an important role in the reaction. Solvents such as H2O, CH3CN, dioxane,
CH3OH, DMSO, THF, DCE, and DMF were screened, and CH3OH was clearly found to be superior
to the others (Table 1, entries 3, 12-18), affording 3a in 70% yield (Table 1, entry 15). The ratio of
p-benzoquinone with sodium benzenesulfinate was investigated, and the ratio 1:2 of
p-benzoquinone with sodium benzenesulfinate proved to be the best result, providing 70% yield
of 3a (Supporting information, Table S1, entries 1-4). Subsequently, various reaction
temperatures were also examined, and 40 oC was found to be the best choice (Table 1, entries 15,
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19-21). Finally, the effect of reaction time was also investigated, and good yield could be obtained
in 2.0 h (Table 1, entries 19, 22-25). After surveying a variety of additives, additive loadings,
solvents, the ratio of reactants, reaction temperatures and times, we found that the combination
of the reactant ratio of 1:2 and 4.0 eq NH4I in CH3OH at 40 oC for 2.0 h served as the optimal
conditions for this transformation.
Table 1 Optimization of reaction conditionsa
Entry
1
Additive (eq)
-
Solvent
DMF
Temp (oC)
25
Time (h)
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
Yieldb (%)
trace
40
65
0
2
NH4Cl (4.0)
NH4I (4.0)
(NH4)2SO4
KI (4.0)
DMF
25
3
DMF
25
4
DMF
25
5
DMF
25
0
6
I2 (4.0)
DMF
25
0
7
TBAI (4.0)
NH4I (1.0)
NH4I (2.0)
NH4I (3.0)
NH4I (5.0)
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
DMF
25
0
8
DMF
25
30
32
53
55
0
9
DMF
25
10
11
12
13
14
15
16
17
DMF
25
DMF
25
H2O
25
CH3CN
dioxane
CH3OH
DMSO
THF
25
0
25
30
70
10
10
25
25
25
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18
19
20
21
22
23
24
25
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
NH4I (4.0)
DCE
25
40
50
60
40
40
40
40
1.0
1.0
1.0
1.0
0.5
1.5
2.0
2.5
0
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
80
70
65
70
80
85
85
a
Reaction conditions: p-benzoquinone 1a (0.2 mmol, 21.6 mg), sodium phenylsulfinate 2a (0.4 mmol, 65.6 mg),
additive and solvent (3.0 mL).
b Isolated yield.
With the optimized reaction conditions in hand, we first proceeded to investigate the substrate
scope with respect to sodium sulfinates as shown in Table 2. The sulfonylation showed excellent
functional group tolerance, and sodium arylsulfinates bearing both electron-donating groups and
electron-withdrawing groups could smoothly react with p-benzoquinone 1a to give the desired
products (3a-3l) in good yields (77-90%). To our delight, sodium arylsulfinates with strong
withdrawing electron groups such as –F, –CF3, and –CN were well tolerated in this reaction, and
the corresponding products (3f, 3k and 3l) were obtained in 77-83% yields. It was noteworthy
that halogen substituents such as fluoro, chloro, bromo, and iodo were well tolerated in this kind
of transformation, and the corresponding functionalized products (3f, 3g-3j) could be used as
substrates for further functionalization. In addition, heteroaromatic sulfinate proceeded
smoothly to afford the target product (3m) in good yield (87%). Gratifyingly, the sodium aliphatic
sulfinates could also be used as viable substrates to afford the corresponding sulfones (3n and 3o)
in good yields (84% and 85%). A single crystal of 3d was obtained from trichloromethane. Its
crystal structure (Fig. 1) exhibited that C2 of p-benzoquinone was arylsulfonylated by
NH4I-promoted direct functionalization, and two carbonyl groups of p-benzoquinone were
transformed into two hydroxyl groups. CCDC 1563390 for 3d contains the supplementary
crystallographic data for this paper. The data can be obtained free of charge from the Cambridge
Crystallographic Data Centre.
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Table 2 Substrate scope of sodium sulfinates a,b
OH
OH
OH
OH
O
S
O
S
O
O
S
O
OH
O
OH
OH
3a (85%)
3b (83%)
OH
3c (82%)
OH
O
S
O
O
S
O
S
O
O
OH
O
OH
OH
OH
O
Cl
I
N
F
H
3d (90%)
3e (78%)
OH
3f (83%)
OH
O
S
O
Cl
O
S
O
S
O
OH
O
OH
OH
OH
Br
3g (80%)
3h (79%)
OH
3i (85%)
OH
O
S
O
O
S
O
S
O
OH
O
OH
OH
CF3
CN
3j (88%)
3k (77%)
3l (82%)
OH
OH
OH
O
O
S
O
S
S
N
O
OH
O
O
OH
3o (85%)
OH
3m (87%)
3n (84%)
a
Reaction conditions: p-benzoquinone 1a (0.2 mmol, 21.6 mg), sodium arylsulfinate 2 (0.4 mmol), and NH4I (0.8
mmol, 116 mg) in 3.0 mL CH3OH solvent, 40 oC for 2.0 h.
b Isolated yield.
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Figure 2. Single crystal structure of 3d
After screening various sodium sulfinates, we next sought to expand the scope of different
substituted quinones under the standard reaction conditions (Table 3). The results demonstrated
that p-benzoquinones bearing electron-donating and -withdrawing groups were both well
tolerated in this reaction, and the desired products could be obtained in moderate to good yields
(3p-3t). When 2-methylcyclohexa-2,5-diene-1,4-dione was employed, two isomers were obtained
in a combination yield of 75% (3q : 3q′ = 1 : 1.5). The different substituent position in
p-benzoquinone profoundly affected the reaction yield. When 2,5-disubstituted p-benzoquinones
were employed, the yields of corresponding products were clearly decreased even after an
extended reaction time (3s and 3t), possibly due to the steric interference. To our delight,
naphthalene-1,4-dione could also produce the desired product in a moderate yield (3t).
Unfortunately, 2-substituted naphthalene-1,4-diones such as 2-chloronaphthalene-1,4-dione and
2-methylnaphthalene-1,4-dione failed to give the corresponding products under the current
reaction conditions (3v and 3w), which was presumably attributed to the influence of the steric
hindrance and low reactivity of C3 position.
Table 3 Substrate scope of quinones a,b
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OH
OH
OH
OH
OH
O
S
O
O
S
O
O
S
OH
O
3p (69%)
3q (30%)
3q' (45%)
OH
OH
OH
O
Cl
O
O
S
O
O
S
O
S
O
O
OH
OH
OH
3r (83%)
3s (38%)
3t (43%)
OH
OH
OH
Cl
O
O
O
S
S
S
O
O
O
OH
OH
OH
3u (70%)
3v (0%)
3w (0%)
a
Reaction conditions: quinones 1 (0.2 mmol), sodium phenylsulfinate 2a (0.4 mmol, 65.6 mg), and NH4I (0.8
mmol, 116 mg) in 3.0 mL CH3OH solvent, 40 oC for 2.0 h.
b Isolated yield.
To further explore the utility of this method, the synthesis of bisarylsulfonylated quinone
derivatives was also investigated. Herein, we further examined the reaction of
2,6-dimethylcyclohexa-2,5-diene-1,4-dione (1s) and sodium phenylsulfinate (2a) using
o
NH4I-promoted this transformation. The reaction temperature was increased to 60 C, and the
reaction time was also prolonged to 5.0 h. Interestingly, the result showed that
2,6-dimethyl-3,5-bis(phenylsulfonyl)benzene-1,4-diol was not obtained, and two products were
provided in a combination yield of 66 % (3s : 4s = 1.2 : 1). The structure of 4s was elucidated by
HR MS, IR, and NMR.
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Scheme 2 Synthesis diarylsulfonyl hydroxybenzene derivatives
Reaction conditions: 2,6-dimethylcyclohexa-2,5-diene-1,4-dione 1S (0.2 mmol, 27.2 mg), sodium phenylsulfinate
2a (0.4 mmol, 65.6 mg), and NH4I (0.8 mmol, 116 mg) in 3.0 mL CH3OH solvent, 60 oC for 5.0 h.
To investigate the reaction mechanism, a series of control experiments were conducted (Scheme
3). When hydroquinone was employed, the reaction failed to deliver the desired product 3a
under standard conditions which revealed that the NH4I-promoted sulfonylation of quinones
were not an electrophilic substitution reaction (Scheme 3a). Under the protection of N2, the
target product 3a could be obtained in a good yield, indicating that the oxygen atom of sulfone
group in 3a does not come from O2 (Scheme 3b). Moreover, when a radical inhibitor
2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) was added to the reaction, the yield of the desired
product 3a was decreased slightly, and the formation of 3a was not suppressed, which indicated
that the sulfonylation was not involved in a radical reaction (Scheme 3c). In addition, when
benzenesulfonyl iodine was employed as a sulfonylation source, the reaction didn’t proceed
under the standard conditions. The result suggested that benzenesulfonyl iodine was not a
reactive intermediate (Scheme 3d). Interestingly, when using 2.0 equiv of HI instead of 4.0 equiv
of NH4I, 3a was obtained with 75% yield, which suggested that HI was indeed the actual form to
promote this conversion (Scheme 3e). When phenylsulfinic acid and p-quinone were employed as
reaction materials in the absence of ammonium iodide, we found that the desired product was
given with poor yield (57%) even after long reaction time (4.0 h). When ammonium iodide was
added, the quinones exhibit enhanced reactivity thereby reducing the reaction times and
improving the yields significantly. The use of ammonium iodide for this transformation helps to
avoid the use of corrosive acids as promoters, thereby minimizing the production of acid waste
during workup.
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OH
OH
NH4I, MeOH
40oC, 2.0h
a:
+
O
S
SO2Na
SO2Na
SO2Na
O
OH
OH
O
3a (0%)
OH
NH4I, MeOH
+
O
S
b:
c:
d:
e:
40oC, N2, 2.0h
O
OH
O
O
3a (83%)
OH
NH4I, MeOH
40oC, 2.0h
+
O
S
TEMPO (2.0 equiv)
O
OH
O
O
3a (82%)
OH
NH4I, MeOH
40oC, 2.0h
+
SO2I
O
S
O
OH
3a (0%)
OH
O
O
HI (2.0 equiv)
+
SO2Na
O
S
40oC, 2.0h
MeOH
O
OH
O
3a (75%)
Scheme 3 Control experiments
Although the exact mechanism for this sulfonylation reaction was still unclear at this stage, based
on the above investigations and literature precedents,[13, 17] a plausible mechanism is proposed
and depicted in Scheme 4. Initially, a sulfur centered anion A generated by the resonation of
phenylsulfinate anion, followed by nucleophilic addition to p-benzoquinone 1a. This leads to the
formation of intermediate B. The intermediate C is provided by the resonation of B. Subsequently,
C may undergo a tautomerization to give the intermediate D. Ammonium iodide is decomposed
into a hydroiodic acid and an ammonia. Finally, the intermediate D including an oxygen centered
anion links with a proton to give the desired product 3a.
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O
O
O
O
O
S
O
O
O
S
S O
O
A
B
NH4I
NH3
O
O
S
OH
O
OH
OH
O
S
O
S
O
HI
O
-I-
O
O
3a
D
C
Scheme 4 Proposed reaction mechanism
3. Conclusion
In summary, we have developed an efficient and practical method for the preparation of
2-arylsulfonyl quinone derivatives based on ammonium iodide-promoted reaction of quinone
with sodium arylsulfinates. This reaction initiated via an arylsulfonyl anion generated from a salt
arylsulfinate rather than the arylsulfonyl radical. A plausible reaction mechanism has been given
on the basis of the control experiments.
4. Experimental
4.1 General information
All substrates purchased from J & K Scientific Ltd. were used without further purification. Column
chromatography was performed using 300-400 mesh silica with the indicated solvent system
according to standard techniques. Nuclear magnetic resonance spectra were recorded on Bruker
1
Avance 400 MHz spectrometer. Chemical shifts for H NMR spectra are recorded in parts per
million from tetramethylsilane. Data were reported as follows: chemical shift, multiplicity (s =
singlet, d = doublet, t = triplet, m = multiplet and br = broad), coupling constant in Hz and
integration. Chemical shifts for 13C NMR spectra were recorded in parts per million from
tetramethylsilane. High resolution mass spectra (HR MS) were obtained on Thermo Scientific LTQ
Orbitrap XL instrument using the ESI technique. IR spectra were recorded on Shimadazu IR-408
Fourier transform infrared spectrophotometer using a thin film supported on KBr pellets. Melting
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points were measured on an XT4A microscopic apparatus uncorrected.
4.2 General experimental procedure for the synthesis of arylsulfonylated quinone derivatives (3)
Quinone 1 (0.2 mmol), sodium arylsulfinate 2 (0.4 mmol), and NH4I (0.8mmol, 116 mg) in
methanol (3.0 mL) were added to a 25 mL Schlenk tube. The mixture was heated at 40 oC for 2.0
h (monitored by TLC). After completion of the reaction, the solvent was distilled under vacuum.
10 mL ethyl acetate was added to the residuum, and 20 mL saturated sodium chloride solution
washed two times. The organic phase was dried over anhydrous NaSO4 and concentrated under
vacuum. The crude product was purified by silica gel column chromatography to give the desired
products 3 using ethyl acetate/petroleum ether (1:5 to 1:1) as eluant.
4.2.1. 2-(Phenylsulfonyl)benzene-1,4-diol (3a)
Light yellow solid, mp 197-198 oC [lit13 mp 193 oC]. IR (KBr) ν(cm-1): 3294, 1508, 1462, 1369, 1288,
1223, 1142, 1088. 1H NMR (400 MHz, DMSO) δ: 9.97 (bs, 1H), 9.42 (bs, 1H), 7.89 (dd, JH-H = 7.2 Hz,
JH-H = 1.4 Hz, 2H), 7.66-7.62 (m, 1H), 7.58-7.54 (m, 2H), 7.34 (d, JH-H = 3.0 Hz, 1H), 6.92 (dd, JH-H
=
8.8 Hz, JH-H = 3.0 Hz, 1H), 6.74 (d, JH-H = 8.8 Hz, 1H). 13C NMR (100 MHz, DMSO) δ: 149.9, 148.6,
141.7, 133.5 (CH), 129.2 (CH), 128.2 (CH), 126.4, 123.3 (CH), 118.9 (CH), 116.1 (CH), 114.2 (CH).
HR MS (ESI) m/z: 251.0375 [M + H]+ (calcd for C12H11O4S+ 251.0373).
4.2.2. 2-Tosylbenzene-1,4-diol (3b)
Yellow solid, mp 184-185 oC [lit13 mp 211-212 oC]. IR (KBr) ν(cm-1): 3282, 1593, 1504, 1458, 1365,
1284, 11242, 1138, 1080. 1H NMR (400 MHz, DMSO) δ: 9.91 (bs, 1H), 9.38 (bs, 1H), 7.77 (d, JH-H
=
8.2 Hz, 2H), 7.36-7.32 (m, 3H), 6.90 (dd, JH-H = 8.7 Hz, JH-H = 3.0 Hz, 1H), 6.73 (d, JH-H = 8.7 Hz, 1H),
2.34 (s, 3H). 13C NMR (100 MHz, DMSO) δ: 149.9, 148.6, 144.0, 138.9, 129.7 (CH), 128.3 (CH),
126.8, 123.1 (CH), 118.9 (CH), 114.2 (CH), 21.5 (CH3). HR MS (ESI) m/z: 265.0531 [M + H]+ (calcd
for C13H13IO4S+ 265.0529).
4.2.3. 2-((4-(tert-Butyl)phenyl)sulfonyl)benzene-1,4-diol (3c)
o
Light yellow solid, mp 165-167 C. IR (KBr) ν(cm-1): 3259, 1962, 1597, 1512, 1361, 1281, 1142,
1107. 1H NMR (400 MHz, DMSO) δ: 9.94 (bs, 1H), 9.40 (bs, 1H), 7.84 (d, JH-H = 8.5 Hz, 2H), 7.57 (d,
JH-H = 8.5 Hz, 2H), 7.37-7.36 (m, 1H), 6.93 (dd, JH-H = 8.8 Hz, JH-H = 3.0 Hz, 1H), 6.76 (d, JH-H = 8.8 Hz,
1H), 1.24 (s, 9H). 13C NMR (100 MHz, DMSO) δ: 156.6, 149.9, 148.6, 139.0, 128.2 (CH), 126.8,
126.1 (CH), 123.2 (CH), 119.0 (CH), 114.4 (CH), 35.2, 31.2 (CH3). HR MS (ESI) m/z: 307.0999 [M +
H]+ (calcd for C16H19O4S+ 307.0999).
13

ACCEPTED MANUSCRIPT
4.2.4 2-((4-Methoxyphenyl)sulfonyl)benzene-1,4-diol (3d)
o
o
Light yellow solid, mp 190-191 C [lit18 mp 188-189 C]. IR (KBr) ν(cm-1): 3259, 1593, 1500, 1365,
1273, 1134, 1092. 1H NMR (400 MHz, DMSO) δ: 9.90 (bs, 1H), 9.39 (bs, 1H), 7.85 (d, JH-H = 8.9 Hz,
2H), 7.34 (d, JH-H = 3.0 Hz, 1H), 7.08 (d, JH-H = 8.9 Hz, 2H), 6.91 (dd, JH-H = 8.8 Hz, JH-H = 3.0 Hz, 1H),
6.75 (d, JH-H = 8.8 Hz, 1H), 3.79 (s, 3H). 13C NMR (100 MHz, DMSO) δ: 167.9, 154.6, 153.2, 138.0,
135.4 (CH), 132.0, 127.7 (CH), 123.7 (CH), 119.2 (CH), 118.9 (CH), 60.8 (CH3). HR MS (ESI) m/z:
281.0478 [M + H]+ (calcd for C13H13ClO5S+ 281.0478).
4.2.5. N-(4-((2,5-Dihydroxyphenyl)sulfonyl)phenyl)acetamide (3e)19
Wine red solid, mp 281-282 oC. IR (KBr) ν(cm-1): 3344, 3194, 1678, 1593, 1543, 1504, 1358, 1284,
1261, 1146, 1092. 1H NMR (400 MHz, DMSO) δ: 10.3 (s, 1H), 9.85 (bs, 1H), 9.32 (bs, 1H), 7.81 (d,
JH-H = 8.8 Hz, 2H), 7.73 (d, JH-H = 8.8 Hz, 2H), 7.29 (d, JH-H = 3.0 Hz, 1H), 6.88 (dd, JH-H = 8.8 Hz, JH-H
=
3.0 Hz, 1H), 6.71 (d, JH-H = 8.8 Hz, 1H), 2.07 (s, 3H). 13C NMR (100 MHz, DMSO) δ: 169.5, 149.8,
148.5, 143.8, 135.3, 129.6 (CH), 127.1, 123.0 (CH), 118.9 (CH), 118.6 (CH), 114.2 (CH), 24.5 (CH3).
HR MS (ESI) m/z: 308.0589 [M + H]+ (calcd for C14H14NO5S+ 308.0587).
4.2.6. 2-((4-Fluorophenyl)sulfonyl)benzene-1,4-diol (3f)
White solid, mp 199-200 oC. IR (KBr) ν(cm-1): 3275, 1597, 1504, 1458, 1365, 1277, 1138, 1080. 1H
NMR (400 MHz, DMSO) δ: 10.03 (bs, 1H), 9.42 (bs, 1H), 7.98-7.94 (m, 2H), 7.43-7.38 (m, 2H), 7.32
(d, JH-H = 3.0 Hz, 1H), 6.92 (dd, JH-H = 8.8 Hz, JH-H = 3.0 Hz, 1H), 6.74 (d, JH-H = 8.8 Hz, 1H). 13C NMR
(100 MHz, DMSO) δ: 166.3, 163.8, 138.0 (d, JF-C = 2.7 Hz), 131.5 (d, JF-C = 9.7 Hz) (CH), 126.3, 123.4
(CH), 119.0 (CH), 116.4 (d, JF-C = 22.6 Hz) (CH), 114.1 (CH). 19F NMR (376 MHz, DMSO) δ: -105.7.
HR MS (ESI) m/z: 269.0281 [M + H]+ (calcd for C12H10FO4S+ 269.0278).
4.2.7. 2-((4-Chlorophenyl)sulfonyl)benzene-1,4-diol (3g)
o
o
Light yellow solid, mp 208-209 C [lit20 mp 210-212 C]. IR (KBr) ν(cm-1): 3267, 1504, 1458, 1365,
1296, 1277, 1215, 1142, 1088. 1H NMR (400 MHz, DMSO) δ: 10.05 (bs, 1H), 9.43 (bs, 1H), 7.88 (dd,
JH-H = 6.8 Hz, JH-H = 1.8 Hz, 2H), 7.64 (dd, JH-H = 6.8 Hz, JH-H = 1.8 Hz, 2H), 7.31 (d, JH-H = 3.0 Hz, 1H),
6.93 (dd, JH-H = 8.8 Hz, JH-H = 3.0 Hz, 1H), 6.74 (d, JH-H = 8.8 Hz, 1H). 13C NMR (100 MHz, DMSO) δ:
149.9, 148.6, 140.6, 138.6, 130.2 (CH), 129.4 (CH), 126.0, 123.6 (CH), 119.0 (CH), 114.2 (CH). HR
MS (ESI) m/z: 284.9986 [M + H]+ (calcd for C12H10ClO4S+ 284.9983).
4.2.8. 2-((2-Chlorophenyl)sulfonyl)benzene-1,4-diol (3h)
White solid, mp 212-213 oC. IR (KBr) ν(cm-1): 3294, 1500, 1446, 1346, 1300, 1149, 1126. 1H NMR
14

ACCEPTED MANUSCRIPT
(400 MHz, DMSO) δ: 9.87 (bs, 1H), 9.41 (bs, 1H), 8.22 (dd, JH-H = 7.7 Hz, JH-H = 1.7 Hz, 1H),
7.68-7.59 (m, 2H), 7.56 (dd, JH-H = 7.7 Hz, JH-H = 1.2 Hz, 1H), 7.37 (d, JH-H = 3.0 Hz, 1H), 6.94 (dd,
JH-H = 8.8 Hz, JH-H = 3.0 Hz, 1H), 6.70 (d, JH-H = 8.8 Hz, 1H). 13C NMR (100 MHz, DMSO) δ: 149.6,
148.6, 138.9, 135.2 (CH), 132.4 (CH), 131.8 (CH), 131.2, 127.8 (CH), 125.2, 123.7 (CH), 118.7 (CH),
115.4 (CH). HR MS (ESI) m/z: 284.9979 [M + H]+ (calcd for C12H10ClO4S+ 284.9983).
4.2.9. 2-((4-Bromophenyl)sulfonyl)benzene-1,4-diol (3i)
o
Light yellow solid, mp 216-217 C. IR (KBr) ν(cm-1): 3275, 1570, 1512, 1466, 1365, 1300, 1269,
1215, 1134, 1088. 1H NMR (400 MHz, DMSO) δ: 10.07 (bs, 1H), 9.46 (bs, 1H), 7.83 (d, JH-H = 8.7 Hz,
2H), 7.76 (d, JH-H = 8.7 Hz, 2H), 7.38 (d, JH-H = 3.0 Hz, 1H), 6.97 (dd, JH-H = 8.8 Hz, JH-H = 3.0 Hz, 1H),
6.79 (d, JH-H = 8.8 Hz, 1H). 13C NMR (100 MHz, DMSO) δ: 150.0, 148.7, 141.0, 132.4 (CH), 130.3
(CH), 127.6, 126.0, 123.7 (CH), 119.1 (CH), 116.2 (CH), 114.2 (CH). HR MS (ESI) m/z: 328.9473 [M
+ H]+ (calcd for C12H10BrO4S+ 328.9478).
4.2.10. 2-((4-Iodophenyl)sulfonyl)benzene-1,4-diol (3j)
o
Light yellow solid, mp 215-216 C. IR (KBr) ν(cm-1): 3267, 1562, 1512, 1469, 1373, 1296, 1265,
1215, 1142. 1H NMR (400 MHz, DMSO) δ: 10.03 (bs, 1H), 9.44 (bs, 1H), 7.96 (d, JH-H = 8.5 Hz, 2H),
7.64 (d, JH-H = 8.5 Hz, 2H), 7.33 (d, JH-H = 3.0 Hz, 1H), 6.94 (dd, JH-H = 8.8 Hz, JH-H = 3.0 Hz, 1H), 6.76
(d, JH-H = 8.8 Hz, 1H). 13C NMR (100 MHz, DMSO) δ: 150.0, 148.7, 141.4, 138.2 (CH), 130.0 (CH),
126.0, 123.6 (CH), 119.0 (CH), 114.2 (CH), 102.0. HR MS (ESI) m/z: 376.9334 [M + H]+ (calcd for
C12H10IO4S+ 376.9339).
4.2.11. 2-((4-(Trifluoromethyl)phenyl)sulfonyl)benzene-1,4-diol (3k)
o
White solid, mp 172-173 C. IR (KBr) ν(cm-1): 3417, 3194, 1504, 1462, 1400, 1323, 1273, 1142,
1122, 1061. 1H NMR (400 MHz, DMSO) δ: 10.14 (bs, 1H), 9.50 (bs, 1H), 8.12 (d, JH-H = 8.2 Hz, 2H),
7.94 (d, JH-H = 8.4 Hz, 2H), 7.40 (d, JH-H = 3.0 Hz, 1H), 6.98 (dd, JH-H = 8.8 Hz, JH-H = 3.0 Hz, 1H), 6.79
(d, JH-H = 8.8 Hz, 1H). 13C NMR (100 MHz, DMSO) δ: 149.4 (d, JF-C = 129.8 Hz), 145.6, 133.2 (q, JF-C
=
31.9 Hz), 129.2 (CH), 126.4 (d, JF-C = 3.6 Hz) (CH), 125.5, 124.0 (CH), 123.8 (d, JF-C = 271.3 Hz),
119.1 (CH), 116.1 (CH), 114.2 (CH). 19F NMR (376 MHz, DMSO) δ: -61.8. HR MS (ESI) m/z:
319.0247 [M + H]+ (calcd for C13H10F3O4S+ 319.0246).
4.2.12. 4-((2,5-Dihydroxyphenyl)sulfonyl)benzonitrile (3l)
o
o
Light yellow solid, mp 175-176 C [lit21 mp 182-183 C]. IR (KBr) ν(cm-1): 3252, 1496, 1466, 1392,
1311, 1277, 1233, 1142. 1H NMR (400 MHz, DMSO) δ: 10.17 (bs, 1H), 9.50 (bs, 1H), 8.07-8.02 (m,
15

ACCEPTED MANUSCRIPT
4H), 7.32 (d, JH-H = 2.9 Hz, 1H), 6.95 (dd, JH-H = 8.7 Hz, JH-H = 2.9 Hz, 1H), 6.75 (d, JH-H = 8.7 Hz, 1H).
13C NMR (100 MHz, DMSO) δ: 150.0, 148.8, 145.7, 133.4 (CH), 129.0 (CH), 125.1, 124.1 (CH),
119.0 (CH), 118.1, 115.9, 114.2 (CH). HR MS (ESI) m/z: 276.0323 [M + H]+ (calcd for C13H10NO4S+
276.0325).
4.2.13. 2-(pyridin-2-ylsulfonyl)benzene-1,4-diol (3m)
Yellow solid, mp 154-155 oC. IR (KBr) ν(cm-1): 3444, 3012, 1468, 1431, 1234, 1086, 1024. 1H NMR
(400 MHz, DMSO) δ: 9.87 (bs, 1H), 9.45 (bs, 1H), 8.63 (d, JH-H = 4.4 Hz, 1H), 8.20 (d, JH-H = 7.8 Hz,
1H), 8.12 (m, 1H), 7.67-7.64 (m, 1H), 7.38 (d, JH-H = 3.0 Hz, 1H), 6.97 (dd, JH-H = 8.8 Hz, JH-H = 3.0 Hz,
1H), 6.75 (d, JH-H = 8.8 Hz, 1H). 13C NMR (100 MHz, DMSO) δ: 158.8, 150.3 (CH), 149.9, 148.8,
138.8 (CH), 127.8 (CH), 124.6, 123.6 (CH), 122.9 (CH), 118.7 (CH), 115.2 (CH). HR MS (ESI) m/z:
252.0327 [M + H]+ (calcd for C11H10NO4S+ 252.0325).
4.2.14. 2-(Methylsulfonyl)benzene-1,4-diol (3n)
o
o
Light yellow solid, mp 112-113 C [lit22 mp 121-124 C]. IR (KBr) ν(cm-1): 3346, 3014, 2931, 1518,
1450, 1286, 1196, 1142. 1H NMR (400 MHz, DMSO) δ: 10.05 (bs, 1H), 9.44 (bs, 1H), 7.12 (d, JH-H
=
2.9 Hz, 1H), 6.92 (dd, JH-H = 8.8 Hz, JH-H = 2.9 Hz, 1H), 6.87 (d, JH-H = 8.8 Hz, 1H), 3.20 (s, 3H). 13C
NMR (100 MHz, DMSO) δ: 149.9, 148.4, 126.9, 122.7 (CH), 118.8 (CH), 113.8 (CH), 42.7 (CH3). HR
MS (ESI) m/z: 189.0219 [M + H]+ (calcd for C7H9O4S+ 189.0216).
4.2.15. 2-(Ethylsulfonyl)benzene-1,4-diol (3o)
Light yellow solid, mp 94-95 oC. IR (KBr) ν(cm-1): 3346, 3064, 2987, 1504, 1454, 1340, 1300, 1263,
1223, 1122, 1049. 1H NMR (400 MHz, DMSO) δ: 9.76 (bs, 2H), 7.10 (d, JH-H = 2.9 Hz, 1H), 6.93 (dd,
JH-H = 8.8 Hz, JH-H = 2.9 Hz, 1H), 6.87 (d, JH-H = 8.8 Hz, 1H), 3.34 (q, JH-H = 7.4 Hz, 2H), 1.06 (t, JH-H
=
7.4 Hz, 3H). 13C NMR (100 MHz, DMSO) δ: 149.9, 148.6, 124.3, 122.8 (CH), 118.8 (CH), 114.8 (CH),
47.9 (CH2), 7.4 (CH3). HR MS (ESI) m/z: 203.0375 [M + H]+ (calcd for C8H11O4S+ 203.0373).
4.2.16. 2-(tert-Butyl)-6-(phenylsulfonyl)benzene-1,4-diol (3p)
o
1
Colorless solid, mp 185-186 C. IR (KBr) ν(cm-1): 3467, 3285, 1476, 1445, 1273, 1235, 1195. H
NMR (400 MHz, DMSO) δ: 9.49 (bs, 1H), 8.77 (bs, 1H), 7.94 (d, JH-H = 8.7 Hz, 2H), 7.73-7.69 (m,
1H), 7.67-7.61 (m, 2H), 7.04 (d, JH-H = 3.0 Hz, 1H), 6.96 (d, JH-H = 3.0 Hz, 1H), 1.28 (s, 9H). 13C NMR
(100 MHz, DMSO) δ: 150.7, 146.8, 142.0, 141.6, 134.3 (CH), 130.0 (CH), 127.3 (CH), 126.9, 121.8
(CH), 111.4 (CH), 35.4, 29.7 (CH3). HR MS (ESI) m/z: 307.1002 [M + H]+ (calcd for C16H19O4S+
307.0999).
16

ACCEPTED MANUSCRIPT
4.2.17. 2-Methyl-6-(phenylsulfonyl)benzene-1,4-diol (3q)
Colorless solid, mp 182-183 oC [lit23 mp 177.9-179.8 oC]. IR (KBr) ν(cm-1): 3464, 3286, 1473, 1442,
1
1284, 1223, 1192, 1142, 1122, 1072. H NMR (400 MHz, DMSO) δ: 9.40 (bs, 1H), 8.88 (bs, 1H),
7.89 (d, JH-H = 7.5 Hz, 2H), 7.67-7.64 (m, 1H), 7.60-7.56 (m, 2H), 7.18 (d, JH-H = 2.8 Hz, 1H), 6.85 (d,
JH-H = 2.8 Hz, 1H), 2.06 (s, 3H). 13C NMR (100 MHz, DMSO) δ: 150.3, 146.2, 142.0, 133.6 (CH),
129.8, 129.4 (CH), 128.2, 128.0 (CH), 124.4 (CH), 111.9 (CH), 16.7 (CH3). HR MS (ESI) m/z:
265.0532 [M + H]+ (calcd for C13H13O4S+ 265.0529).
4.2.18. 2-Methyl-5-(phenylsulfonyl)benzene-1,4-diol (3q′)
Colorless solid, mp 173-174 oC [lit23 mp 186.5-187.3 oC]. IR (KBr) ν(cm-1): 3425, 3279, 1523, 1454,
1415, 1369, 1277, 1192,1138,1084. 1H NMR (400 MHz, DMSO) δ: 9.84 (bs, 1H), 9.36 (bs, 1H), 7.88
(d, JH-H = 7.3 Hz, 2H), 7.63-7.60 (m, 1H), 7.57-7.53 (m, 2H), 7.37 (s, 1H), 6.64 (s, 1H), 2.08 (s, 3H).
13C NMR (100 MHz, DMSO) δ: 148.4, 148.1, 142.2, 133.7, 133.3 (CH), 129.2 (CH), 128.0 (CH),
123.6, 119.8 (CH), 113.5 (CH), 16.7 (CH3). HR MS (ESI) m/z: 265.0533 [M + H]+ (calcd for
C13H13O4S+ 265.0529).
4.2.19. 2-Chloro-3-(phenylsulfonyl)benzene-1,4-diol (3r)
Colorless solid, mp 163-165 oC. IR (KBr) ν(cm-1): 3424, 3232, 1459, 1432, 1257. 1H NMR (400 MHz,
DMSO) δ: 10.26 (bs, 2H), 7.89 (d, JH-H = 7.7 Hz, 2H), 7.67-7.63 (m, 1H), 7.61-7.55 (m, 3H), 6.88 (s,
1H). 13C NMR (100 MHz, DMSO) δ: 148.6, 145.9, 141.3, 133.7 (CH), 129.3 (CH), 128.2 (CH), 127.1,
125.7, 118.8 (CH), 115.6 (CH). HR MS (ESI) m/z: 284.9985 [M + H]+ (calcd for C12H10ClO4S+
284.9983).
4.2.20. 3,5-Dimethyl-2-(phenylsulfonyl)benzene-1,4-diol (3s)
o
o
Colorless solid, mp 146-147 C [lit13 mp 146 C]. IR (KBr) ν(cm-1): 3421, 3224, 1616, 1570, 1473,
1
1442, 1346, 1377, 1219, 1126, 1088. H NMR (400 MHz, DMSO) δ: 9.75 (bs, 1H), 8.12 (bs, 1H),
7.84 (d, JH-H = 7.4 Hz, 2H), 7.65 (t, JH-H = 7.3 Hz, 1H), 7.57 (t, JH-H = 7.2 Hz, 2H), 6.60 (s, 1H), 2.39 (s,
3H), 2.15 (s, 3H). 13C NMR (100 MHz, DMSO) δ: 150.6, 146.6, 143.5, 135.3, 133.5 (CH), 129.4 (CH),
126.9 (CH), 125.9, 121.0, 117.3 (CH), 17.7 (CH3), 13.6 (CH3). HR MS (ESI) m/z: 279.0685 [M + H]+
(calcd for C14H15O4S+ 279.0686).
4.2.21. 3,5-Dimethoxy-2-(phenylsulfonyl)benzene-1,4-diol (3t)
Colorless solid, mp 139-140 oC. IR (KBr) ν(cm-1): 3471, 3375, 3278, 2943, 1616, 1577, 1500, 1442,
1373, 1300, 1192, 1153, 1092, 1057. 1H NMR (400 MHz, DMSO) δ: 9.70 (bs, 1H), 7.88 (d, JH-H = 7.3
17

ACCEPTED MANUSCRIPT
Hz, 2H), 7.68-7.65 (m, 1H), 7.61-7.57 (m, 2H), 6.37 (s, 1H), 3.81 (s, 3H), 3.65 (s, 3H). 13C NMR (100
MHz, DMSO) δ: 154.4, 149.2, 143.3, 143.1, 133.8 (CH), 129.5 (CH), 127.1 (CH), 124.8, 109.3, 97.0
(CH), 59.8 (CH3), 56.4 (CH3). HR MS (ESI) m/z: 311.0586 [M + H]+ (calcd for C14H15O6S+ 311.0584).
4.2.22. 2-(Phenylsulfonyl)naphthalene-1,4-diol (3u)
Deep yellow solid, mp 166-167 oC [lit13 mp 178 oC]. IR (KBr) ν(cm-1): 3321, 1577, 1446, 1277, 1126,
1088. 1H NMR (400 MHz, DMSO) δ: 10.21 (bs, 1H), 10.07 (bs, 1H), 8.17 (d, JH-H = 8.3 Hz, 1H), 8.12
(d, JH-H = 8.2 Hz, 1H), 7.95 (d, JH-H = 7.5 Hz, 2H), 7.68-7.56 (m, 5H), 7.28 (s, 1H). 13C NMR (100 MHz,
DMSO) δ: 146.7, 146.0, 142.3, 133.6 (CH), 129.5 (CH), 128.8 (CH), 127.8 (CH), 127.2 (CH), 126.7,
123.6 (CH), 122.8 (CH), 121.2, 104.2 (CH). HR MS (ESI) m/z: 301.0532 [M + H]+ (calcd for
C16H13O4S+ 301.0529).
4.2.23. 4-Hydroxy-2,6-dimethyl-3-(phenylsulfonyl)phenyl benzenesulfonate (4s)
Colorless solid, mp 107-108 oC. IR (KBr) ν(cm-1): 3267, 1608, 1562, 1458, 1369, 1304, 1196, 1122,
1080. 1H NMR (400 MHz, DMSO) δ: 10.84 (bs, 1H), 7.96 (d, JH-H = 7.9 Hz, 2H), 7.88 (t, JH-H = 7.4 Hz,
1H), 7.83 (d, JH-H = 7.6 Hz, 2H), 7.72 (t, JH-H = 7.8 Hz, 2H), 7.66 (d, JH-H = 7.4 Hz, 1H), 7.58 (t, JH-H
=
7.8 Hz, 2H), 6.6 (s, 1H), 2.24 (s, 3H), 2.04 (s, 3H). 13C NMR (100 MHz, DMSO) δ: 155.6, 143.3,
140.2, 139.9, 135.8, 135.6 (CH), 133.9, 133.5 (CH), 130.5 (CH), 129.3 (CH), 128.5 (CH), 127.3 (CH),
123.4, 117.9 (CH), 17.9 (CH3), 14.9 (CH3). HR MS (ESI) m/z: 419.0616 [M + H]+ (calcd for
C20H19O6S2+ 419.0618).
Acknowledgement
This work was supported by the Youth Backbone Teachers of Henan University of Technology (No.
2016003).
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