Triflylation of 1,4-Benzoquinones with sodium trifluoromethanesulfinate

Article abstract of DOI:10.1016/j.jfluchem.2019.109410

The iodine-promoted triflylation of 1,4-benzoquinones with cheap and easily available sodium trifluoromethanesulfinate is achieved under mild conditions. A series of aryl triflones were obtained in moderate to good yields. The method could also be extended to triflylation of 1,4-benzoquinone monoamines and perfluoroalkanesulfonylation with sodium perfluoroalkanesulfinates.

Full text of DOI:10.1016/j.jfluchem.2019.109410

Journal Pre-proof
Triflylation of 1,4-Benzoquinones with Sodium Trifluoromethanesulfinate
Sheng-Li Yue, Min Jiang, Hui Li, Jin-Tao Liu
PII:
S0022-1139(19)30298-2
DOI:
https://doi.org/10.1016/j.jfluchem.2019.109410
FLUOR 109410
Reference:
To appear in:
Journal of Fluorine Chemistry
Received Date:
Revised Date:
Accepted Date:
21 August 2019
31 October 2019
1 November 2019
Please cite this article as: Yue S-Li, Jiang M, Li H, Liu J-Tao, Triflylation of 1,4-Benzoquinones
with Sodium Trifluoromethanesulfinate, Journal of Fluorine Chemistry (2019),
doi: https://doi.org/10.1016/j.jfluchem.2019.109410
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Triflylation
of
1,4-Benzoquinones
with
Sodium
Trifluoromethanesulfinate
Sheng-Li Yuea, Min Jiangb, Hui Li a,* lihui@shnu.edu.cn, Jin-Tao Liub,*
jtliu@sioc.ac.cn
aShanghai Engineering Research Center of Green Energy Chemical Engineering, College of Chemistry and Materials
Science, Shanghai Normal University, 100 Guilin Road, Shanghai 200234, China
bKey Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Road, Shanghai 200032, China
*Corresponding author.
Graphic Abstract
The iodine-promoted triflylation of 1,4-benzoquinones with cheap and easily available sodium
trifluoromethanesulfinate is achieved under mild conditions. A series of aryl triflones were obtained
in moderate to good yields. The method could also be extended to triflylation of 1,4-benzoquinone
monoamines and perfluoroalkanesulfonylation with sodium perfluoroalkanesulfinates.
Highlights
 Triflylation of 1,4-benzoquinones with cheap and easily available sodium
trifluoromethanesulfinate was investigated.
 A series of aryl triflones were separated in moderate to good yields.
1

 Perfluoroalkanesulfonylation could also work well in the presence of sodium
perfluoroalkanesulfinates as reagent.
Abstract
The iodine-promoted triflylation of 1,4-benzoquinones with cheap and easily available
sodium trifluoromethanesulfinate is achieved under mild conditions. A series of aryl
triflones were obtained in moderate to good yields. The method could also be extended
to triflylation of 1,4-benzoquinone monoamines and perfluoroalkanesulfonylation
with sodium perfluoroalkanesulfinates.
Keywords:
Triflylation,
perfluoroalkanesulfonylation,
iodine,
sodium
trifluoromethanesulfinate, benzoquinone
1. Introduction
Sulfones represent an important subclass of organic compounds and are found in a
variety of biologically active molecules [1]. Recently, aryl sulfones have attracted
considerable attention in the area of synthetic organic chemistry owing to their
important role as key structural units of many biologically active compounds [2]. For
example, quinonyl sulfone derivatives, such as 2-tosylbenzene-1,4-diol (I) and 2-
tosylnaphthalene-1,4-diols (II and III), are useful compounds in the field of
pharmaceutical as potent inhibitor of -Ketoacyl-ACP-synthase III (FabH) (Figure 1)
[3]. Generally, sulfones could be prepared by oxidation of the corresponding sulfides
in the presence of strong oxidants [4]. Recently, several examples about direct
sulfonylation of benzoquinone were also reported under metal or metal free conditions
[5].
2

Figure 1. Potent FabH inhibitors
On the other hand, the introduction of fluorine atom or fluoroalkyl groups may
modulate physical and electronic properties of a molecule [6]. Because of their high
hydrophobicities, metabolic activities and bioavailabilities, fluorinated compounds
have recently attracted more and more attention in medicinal and life sciences [7].
Among various fluorinated functional groups, trifluoromethanesulfonyl (CF3SO2)
plays an important role in organofluorine chemistry due to its strong electron-
withdrawing effect and high lipophilicity [8]. Over the past decade, various efficient
approaches toward the synthesis of aryl(heteroaryl) triflones has been developed [9].
However, works on the triflylation of benzoquinone are rarely reported [10]. It is known
that sodium trifluoromethanesulfinate (CF3SO2Na) is a cheap and easily available
commercial chemical, and has been used as effective trifluoromethylating and
trifluoromethylthiolating reagents [11]. In 2016, Huang and co-workers reported an
iodine-mediated direct C-H triflylation of styrenes with CF3SO2Na [12]. Recently, the
trifluoromethylthiolation-based bifunctionalization of indoles with CF3SO2Na was
developed in our lab [13]. In our continuous study on the application of CF3SO2Na, it
was found that the triflylation of benzoquinones could be achieved with
CF3SO2Na/iodine system to give the corresponding trifluoromethanesulfonyl 1,4-
benzenediols. The results are reported in this paper.
2. Results and Discussion
We embarked on our investigation with the reaction of 1,4-benzoquinone (1a) with
sodium trifluoromethanesulfinate. Gratefully, when 0.5 equivalent of iodine was used
in N,N-dimethylformide (DMF) at 40 oC, triflylation product 2a was obtained in 32%
yield (Table, entry 1). Further investigation showed that increasing the amount of
CF3SO2Na or iodine was in favor of the formation of triflylation product. Screening the
ratio of reactants indicated that 90% yield of 2a could be achieved with a ratio of
1a/CF3SO2Na/iodine = 1:1.2:1.2 (entries 2-5). Iodine is essential for the reaction, and
no reaction was detected in the absence of iodine (entry 6). Other iodine reagents, such
3

as NH4I, NIS and PhI(OAc)2 were also tested. NIS and PhI(OAc)2 afforded low yield
of 2a, and NH4I could not promote the reaction (entries 7-9). Further investigation of
o
reaction temperature showed that better result was obtained at 40 C (entries 10-12).
Except DMF, other solvents were also examined. It was found that tetrahydrofuran
(THF), 1,4-dioxane, dimethylsulfoxide (DMSO) and 1,2-dichloroethane (DCE) could
not give better result although THF and DMSO also afforded 2a in good yields (entries
13-16). After survey a variety of the ratio of reactants, additives, reaction temperature
and solvents, the optimal conditions for the formation of 2a were set to 1.0 equiv of 1a,
1.2 equiv of CF3SO2Na and 1.2 equiv of iodine in DMF at 40 oC.
Table 1. Condition optimization for the triflylation of 1a with CF3SO2Na
entry[a] [I]
solvent
temp. (oC)
1a/CF3SO2Na/[I]
yield (2a, %)[b]
1
I2
1/1/0.5
1/1/1
DMF
DMF
40
40
32
70
75
90
90
NR
13
44
trace
80
80
82
71
20
80
2
I2
1/1.5/1
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
THF
40
40
40
3
I2
1/1.2/1.2
1/1.5/1.2
1/1.2/0
4
I2
5
I2
6
-
40
40
1/1.2/1.2
1/1.2/1.2
7
NIS
40
40
8
PhI(OAc)2
9
NH4I
I2
1/1.2/1.2
1/1.2/1.2
10
11
12
13
14
15
50
30
1/1.2/1.2
1/1.2/1.2
1/1.2/1.2
1/1.2/1.2
1/1.2/1.2
I2
I2
rt
40
I2
40
40
I2
1,4-Dioxane
DMSO
I2
4

1/1.2/1.2
40
16
I2
DCE
8
b
a Reaction conditions: 1a (0.5 mmol), CF3SO2Na (1.0-1.5 equiv), [I] (1.0-1.2 equiv), solvent (2.0 mL), 24 h.
Determined by 19F NMR using PhCF3 as internal standard.
With the optimized reaction conditions in hand, we next studied the scope of
benzoquinone for this triflylation reaction. As shown in Scheme 1, a range of 2-
substituted p-benzoquinones 1 containing both electron-withdrawing and electron-
donating groups could react with CF3SO2Na to give the corresponding triflylation
products 2 in moderate to good yields. The substrates bearing methyl, t-butyl, methoxy
or ethoxy substituent gave the expected products in 60-79% yields. The reaction of
bromo-substituted benzoquinone also occurred to give product 2f and 2f′ in 42% overall
yield. It is worth mentioning that both 2,6-substituted 1,4-benzenediols 2 and 2,5-
substituted 1,4-benzenediols 2' were obtained in the
Scheme 1. Perfluoroalkanesulfonylation of 1 with RfSO2Naa
5

a Reaction conditions: 1 (0.5 mmol), RfSO2Na (0.6 mmol), I2 (0.6 mmol), DMF (2 mL), 40 oC, 24 h, isolated yields.
b Reaction conditions: 1 (0.5 mmol), RfSO2Na (0.75 mmol), I2 (0.6 mmol), DMF (2 mL), 60 oC, 24 h, isolated yields.
above reactions. Comparison of their NMR spectra showed that 2,6-substituted 1,4-
benzenediols 2 were major products in most reactions [5d], with an exception of the
reaction of 2-ethyloxy 1,4-benzoquinone 1d, in which 2,5-substituted 1,4-benzenediol
2d' was formed as major product. Under standard conditions, naphthalene-1,4-dione
could also react with CF3SO2Na to give triflylation product 2g in 48% yield.
Furthermore, the method could be extended to perfluoroalkanesulfonylation. In the
presence of RfSO2Na, such as ClCF2CF2SO2Na, n-C4F9SO2Na and n-C6F13SO2Na,
perfluoroalkanesulfonylation reaction of 1a occurred readily under similar conditions,
6

giving the corresponding perfluoroalkanesulfonylation products 2h-2j in moderate
yields.
We also tried the reactions of 2,6-dimethyl p-benzoquinone (1k) and 2-
methylnaphthalene-1,4-dione (1l), unfortunately, no reaction occurred with full
recovery of starting materials under similar conditions.
To further explore the scope of this method, 1,4-benzoquinone monoamines were
synthesized using procedures reported in literature [14], and their reactions with
RfSO2Na were studied. The results are shown in Scheme 2. The reactions of N- (4-
methylphenylsulfonyl)-1,4-benzoquinone monoamine (3a) and N-phenyl-1,4-
benzoquinone monoamine (3b) with CF3SO2Na took place readily to give the expected
triflylation products 4a and 4b in 76% and 41% yield, respectively. NOE experiment
showed that the sulfonyl group was introduced into the ortho-position of hydroxyl
group (see supporting information). In addition, perfluoroalkanesulfonylation of 3a was
also achieved with ClCF2CF2SO2Na, n-C4F9SO2Na or n-C6F13SO2Na.
Scheme 2. Perfluoroalkanesulfonylation of benzoquinone monoamine with RfSO2Na
a Reaction conditions: 1 (0.5 mmol), RfSO2Na (0.6 mmol), I2 (0.6 mmol), DMF (1 mL), 40 oC, 24 h, isolated yields.
On the basis of above experimental results and related literature [12], a possible
reaction mechanism is proposed as shown in Scheme 3. Iodonium ion intermediate A
7

-
might be formed first, which is attacked by CF3SO2 anion to afford intermediate B.
Subsequent deiodination and aromatization give the final product 2a.
Scheme 3. Proposed reaction mechanism
3. Conclusion
In conclusion, we have demonstrated a novel triflylation of 1,4-benzoquinones with
cheap and easily available sodium trifluoromethanesulfinate. Promoted by iodine, the
triflylation reaction occurred readily under transition-metal-free and mild conditions,
providing a practical method for the synthesis of a series of aryl triflones. Furthermore,
this protocol could be extended to perfluoroalkanesulfonylation with sodium
perfluoroalkanesulfinates.
4. Experimental
4.1. General
Unless otherwise mentioned, solvents and reagents were purchased from commercial
sources and used as received. Solvents were freshly distilled by standard procedure
prior to use. Melting points were measured on a RY-I apparatus and uncorrected. 1H
NMR spectra were recorded in CDCl3 on a Bruker AM 400 spectrometer (400 MHz)
with TMS as internal standard. 19F NMR spectra were taken on a Bruker AM 400 (376
13
MHz) spectrometer with CFCl3 as external standard. C NMR spectra were recorded
8

in CDCl3 on a Varian AM-400 spectrometer (100 MHz) with TMS as internal standard.
For compounds 2h-2j and 4c-4e, the peaks for fluorine-possessing carbon atoms in
perfluoroalkyl groups are difficult to find out in their 13C NMR spectra because of their
multiplicity. High Resolution Mass Spectra (HRMS) were recorded on an IonSpec FT-
ICR mass spectrometer with ESI resource.
4.2. General procedure for the triflylation:
To a solution of 1a (0.5 mmol) and iodine (0.6 mmol, 1.2 equiv) in DMF (2.0 mL) was
added CF3SO2Na (0.6 mmol, 1.2 equiv). The mixture was stirred at 40 ℃for 24 h. After
the reaction was completed (monitored by TLC), saturated sodium thiosulfate solution
was added under stirring until the mixture became colorless. The resulting mixture was
extracted with EtOAc for three times (3 x 6.0 mL). The combined organic solution was
washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel (EA:PE = 1:5) to give
product 2a.
4.2.1. 2-(Trifluoromethanesulfonyl)benzene-1,4-diol (2a)
White solid (104 mg, 86%), m.p. 77-79 ℃. IR (neat, cm-1): ν 3402, 2959, 2925, 1497,
1352, 1207, 1116, 1048, 915. 1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H, OH), 9.74
(s, 1H, OH), 7.21 (dd, J = 8.9, 2.9 Hz, 1H), 7.16 (d, J = 2.8 Hz, 1H), 7.03 (d, J = 8.9
Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ 152.70 (s), 150.35 (s), 127.84 (s), 120.20
(q, J = 325 Hz), 120.07 (s), 116.14 (s), 115.43 (s). 19F NMR (376 MHz, DMSO-d6) δ -
77.31 (s). ESI-MS (m/z, %): 260.0 (20) [M+NH4]+. HRMS (ESI) Calcd. for
C7H9F3NO4S [M+NH4]+ requires 260.0199, found 260.0198.
4.2.2. The mixture of 2-methyl-6-(trifluoromethanesulfonyl)benzene-1,4-diol (2b)
and 2-methyl-5-(trifluoromethanesulfonyl)benzene-1,4-diol (2b')
Light yellow solid (101 mg, 79%). The ratio of 2b/2b' was determined as 4.5:1.0 by
19F NMR analysis. IR (neat, cm-1): ν 3438, 2926, 2855, 1715, 1475, 1204, 1098, 1012,
877, 630. 1H NMR (400 MHz, CDCl3) 2b: δ 8.28 (s, 1H, OH), 7.14 (d, J = 2.5 Hz, 1H),
9

6.98 (d, J = 2.4 Hz, 1H), 4.98 (s, 1H, OH), 2.26 (s, 3H); 2b': δ 8.03 (s, 1H, OH), 7.04
13
(s, 1H), 6.94 (s, 1H), 5.06 (s, 1H, OH), 2.31 (s, 3H). C NMR (100 MHz, CDCl3) δ
152.94 (s), 151.53 (s), 148.52 (s), 148.08 (s), 140.36 (s), 131.36 (s), 129.15 (s), 121.43
(s), 120.20 (q, J = 325 Hz), 114.28 (s), 112.72 (s), 111.58 (s), 109.13 (s), 16.88 (s),
19
16.14 (s). F NMR (376 MHz, CDCl3) 2b: δ -79.14 (s); 2b': δ -79.29 (s). ESI-MS
(m/z, %): 257.0 (10) [M+H]+. HRMS (ESI) Calcd. for C8H8F3O4S [M+H]+ requires
257.0012, found 257.0010.
4.2.3. The mixture of 2-tert-butyl-6-(trifluoromethanesulfonyl)benzene-1,4-diol
(2c) and 2-tert-butyl-5-(trifluoromethanesulfonyl)benzene-1,4-diol (2c')
Light yellow solid (114 mg, 77%). The ratio of 2c/2c' was determined as 10:1 by 19F
NMR analysis. IR (neat, cm-1): ν 3410, 2960, 2925, 1613, 1473, 1446, 1207, 1126, 1084,
863, 790. 1H NMR (400 MHz, CDCl3) 2c: δ 8.61 (s, 1H, OH), 7.25 (d, J = 3.0 Hz, 1H),
7.01 (d, J = 2.9 Hz, 1H), 5.02 (s, 1H, OH), 1.40 (s, 9H); 2c': δ 7.98 (s, 1H, OH), 7.06
13
(s, 1H), 6.96 (s, 1H), 5.21 (s, 1H, OH), 1.41 (s, 9H). C NMR (100 MHz, CDCl3) δ
152.94 (s), 152.52 (s), 151.80 (s), 148.52 (s), 148.29 (s), 142.48 (s), 126.29 (s), 124.71
(s), 119.87 (q, J = 325 Hz), 118.72 (s), 115.37 (s), 112.84 (s), 112.25 (s), 35.89 (s),
19
35.74 (s), 29.09 (s), 28.84 (s). F NMR (376 MHz, CDCl3) 2c: δ -79.25 (s); 2c': δ -
79.20 (s). ESI-MS (m/z, %): 299.1 (15) [M+H]+. HRMS (ESI) Calcd. for C11H14F3O4S
[M+H]+ requires 299.0481, found 299.0480.
4.2.4. The mixture of 2-ethoxy-6-(trifluoromethanesulfonyl)benzene-1,4-diol (2d)
and 2-ethoxy-5-(trifluoromethanesulfonyl)benzene-1,4-diol (2d')
19
Gray solid (81 mg, 60%). The ratio of 2d/2d' was determined as 1:2.3 by F NMR
analysis. IR (neat, cm-1): ν 3405, 2924, 2854, 1715, 1621, 1463, 1361, 1260, 1210, 1046,
846, 799. 1H NMR (400 MHz, DMSO-d6) 2d: δ 10.01 (s, 1H, OH), 9.73 (s, 1H, OH),
6.90 (d, J = 2.7 Hz, 1H), 6.72 (d, J = 2.7 Hz, 1H), 4.09 (q, J = 6.9 Hz, 2H), 1.38 (t, J =
6.8 Hz, 3H); 2d': δ 10.94 (s, 1H, OH), 9.34 (s, 1H, OH), 7.10 (s, 1H), 6.61 (s, 1H), 4.09
(q, J = 6.9 Hz, 2H), 1.33 (t, J = 6.8 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) δ 161.58
(s), 159.90 (s), 155.23 (s), 154.37 (s), 147.63 (s), 145.02 (s), 125.16 (q, J = 325 Hz),
10

124.95 (q, J = 325 Hz), 120.68 (s), 120.49 (s), 115.19 (s), 110.52 (s), 109.25 (s), 106.97
(s), 70.10 (s), 69.56 (s), 19.51 (s). 19F NMR (376 MHz, DMSO-d6) 2d: δ -77.14 (s); 2d':
δ -78.07 (s). ESI-MS (m/z, %): 308.8 (100) [M+Na]+. HRMS (ESI) Calcd. for
C9H9F3NaO5S [M+Na]+ requires 309.0015, found 309.0018.
4.2.5. The mixture of 2-methoxy-6-(trifluoromethanesulfonyl)benzene-1,4-diol (2e)
and 2-methoxy-5-(trifluoromethanesulfonyl)benzene-1,4-diol (2e')
Gray solid (81 mg, 60%). The ratio of 2e/2e' was determined as 3:2 by 19F NMR
analysis. IR (neat, cm-1): ν 3426, 2954, 2924, 2853, 1631, 1508, 1443, 1247, 1221, 1122,
1049, 871, 841. 1H NMR (400 MHz, DMSO-d6) 2e: δ 10.28 (s, 1H, OH), 9.82 (s, 1H,
OH), 6.98 (s, 1H), 6.79 (s, 1H), 3.91 (s, 3H); 2e': δ 11.06 (s, 1H, OH), 9.46 (s, 1H, OH),
7.14 (s, 1H), 6.68 (s, 1H), 3.91 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 157.54 (s),
155.21 (s), 150.46 (s), 150.43 (s), 142.81 (s), 140.23 (s), 120.39 (q, J = 325 Hz), 120.18
(q, J = 325 Hz), 115.87 (s), 115.71 (s), 109.70 (s), 105.78 (s), 104.67 (s), 101.70 (s),
56.93(s), 56.41(s); 19F NMR (376 MHz, DMSO-d6) 2e: δ -76.16 (s); 2e': δ -78.08 (s).
ESI-MS (m/z, %): 290 (100) [M+NH4]+. HRMS (ESI) Calcd. for C8H11F3NO5S
[M+NH4]+ requires 289.9961, found 289.9961.
4.2.6. The mixture of 2-bromo-6-(trifluoromethanesulfonyl)benzene-1,4-diol (2f)
and 2-bromo-5-(trifluoromethanesulfonyl)benzene-1,4-diol (2f')
Light yellow solid (67 mg, 42%). The ratio of 2f/2f' was determined as 4.5:1.0 by 19F
NMR analysis. IR (neat, cm-1): ν 3421, 2925, 2855, 1477, 1435, 1209, 1117, 1064, 940,
793. 1H NMR (400 MHz, DMSO-d6) 2f: δ 10.59 (s, 1H, OH), 10.19 (s, 1H, OH) 7.49
(d, J = 2.5 Hz, 1H), 7.21 (d, J = 2.5 Hz, 1H); 2f': δ 11.28 (s, 1H, OH), 10.53 (s, 1H,
13
OH), 7.30 (s, 1H), 7.27 (s, 1H). C NMR (100 MHz, DMSO-d6) δ 152.34 (s), 151.55
(s), 148.15 (s), 147.71 (s), 129.67 (s), 122.79 (s), 122.47 (s), 120.64 (s), 120.01 (q, J =
325 Hz), 116.81 (s), 116.75 (s), 115.67 (s), 115.16 (s). 19F NMR (376 MHz, DMSO-d6)
2f: δ -76.22 (s); 2f': δ -77.23 (s). ESI-MS (m/z, %): 321.9 (10) [M+H]+. HRMS (ESI)
Calcd. for C7H5BrF3O4S [M+H]+ requires 321.8960, found 321.8961.
11

4.2.7. 2-(Trifluoromethanesulfonyl)naphthalene-1,4-diol (2g)
Orange solid (70 mg, 48%). m.p. 137-139 ℃. IR (neat, cm-1): ν 3511, 3393, 2922, 2853,
1
1622, 1603, 1454, 1344, 1214, 1197, 1072, 862, 766. H NMR (400 MHz, CDCl3) δ
9.21 (s, 1H, OH), 8.43 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.80 (tt, J = 5.7,
2.9 Hz, 1H), 7.72 – 7.67 (m, 1H), 6.87 (s, 1H), 5.54 (s, 1H, OH). 13C NMR (100 MHz,
CDCl3) δ 153.64 (s), 145.31 (s), 131.27 (s), 130.75 (s), 127.92 (s), 125.74 (s), 124.50
19
(s), 122.37 (s), 120.05 (q, J = 325 Hz), 103.55 (s), 103.27 (s). F NMR (376 MHz,
CDCl3) δ -79.02 (s). ESI-MS (m/z, %): 293.0 (100) [M+H]+. HRMS (ESI) Calcd. for
C11H8F3O4S [M+H]+ requires 293.0012, found 293.0012.
4.2.8. 2-(2-Chloro-1,1,2,2-tetrafluoroethanesulfonyl)benzene-1,4-diol (2h)
White solid (91 mg, 58%). m.p. 66-69 ℃. IR (neat, cm-1): ν 3410, 2958, 2924, 2854,
1
1747, 1715, 1681, 1541, 1457, 1260, 1093, 1022, 798. 668. H NMR (400 MHz,
DMSO-d6) δ 10.85 (s, 1H, OH), 9.68 (s, 1H, OH), 7.19 (dd, J = 8.9 Hz, 3.0 Hz, 1H),
7.14 (d, J = 2.8 Hz, 1H), 7.01 (d, J = 8.9 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ
19
152.91 (s), 150.23 (s), 127.85 (s), 120.02 (s), 116.86 (s), 116.37 (s). F NMR (376
MHz, DMSO-d6) δ -66.19 – -66.25 (m, 2F), -110.24 (t, J = 2.2 Hz, 2F). ESI-MS
(m/z, %): 307.9 (40) [M]+. HRMS (ESI) Calcd. for or C8H5ClF4O4S [M]+ requires
307.9460, found 307.9459.
4.2.9. 2-(Perfluorobutanesulfonyl)benzene-1,4-diol (2i)
White solid (140 mg, 71%). m.p. 69-71 ℃. IR (neat, cm-1): ν 3415, 2925, 2855, 1715,
1
1496, 1351, 1237, 1158, 1114, 1053, 1024, 915, 786. H NMR (400 MHz, DMSO-d6)
δ 10.96 (s, 1H, OH), 9.76 (s, 1H, OH), 7.26 (dd, J = 8.9, 3.0 Hz, 1H), 7.19 (d, J = 2.8
Hz, 1H), 7.07 (d, J= 8.9 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ 153.10 (s), 150.30
(s), 128.14 (s), 120.10 (s), 116.38 (s), 116.32 (s). 19F NMR (376 MHz, DMSO-d6) δ -
80.42 (s, 3F), -111.83 (t, J = 12.3 Hz, 2F), -121.43 (s, 2F), -125.67 (s, 2F). ESI-MS
(m/z, %): 392.0 (100) [M]+. HRMS (ESI) Calcd. for or C10H5F9O4S [M]+ requires
391.9692, found 391.9691.
12

4.2.10. 2-(Perfluorohexanesulfonyl)benzene-1,4-diol (2j)
White solid (160 mg, 65%). m.p. 78-80 ℃. IR (neat, cm-1): ν 3403, 2925, 1496, 1442,
1
1354, 1235, 1206, 1149, 1020, 916, 885. H NMR (400 MHz, DMSO-d6) δ 10.90 (s,
1H, OH), 9.69 (s, 1H, OH), 7.20 (dd, J = 8.9, 3.0 Hz, 1H), 7.13 (d, J = 3.0 Hz, 1H),
13
7.01 (d, J = 8.9 Hz, 1H). C NMR (100 MHz, DMSO-d6) δ 153.10 (s), 150.29 (s),
128.14 (s), 120.09 (s), 116.37 (s), 116.30 (s). 19F NMR (376 MHz, DMSO-d6) δ -80.38
(t, J = 9.8 Hz, 3F), -111.62 (t, J = 13.7 Hz, 2F), -120.45 (s, 2F), -121.63 (s, 2F), -122.66
(s, 2F), -125.90 (dd, J = 13.7, 8.4 Hz, 2F). ESI-MS (m/z, %): 510.0 (5) [M+NH4]+.
HRMS (ESI) Calcd. for C12H9F13NO4S [M+NH4]+ requires 510.0039, found 510.0036.
4.2.11.
N-{4-Hydroxy-3-(trifluoromethanesulfonyl)phenyl}-p-
methylbenzenesulfonamide (4a)
White solid (150 mg, 76%). m.p. 151-154 ℃. IR (neat, cm-1): ν 3420, 3270, 2925, 2854,
1507, 1355, 1159, 1120, 1090, 1053, 935, 812. 1H NMR (400 MHz, DMSO-d6) δ 11.71
(s, 1H, OH), 10.17 (s, 1H, NH), 7.54 (d, J = 8.3 Hz, 2H), 7.46 (dd, J = 8.9, 2.7 Hz, 1H),
7.42 (d, J= 2.7 Hz, 1H), 7.34 (d, J = 8.1 Hz, 2H), 7.07 (d, J = 8.9 Hz, 1H), 2.33 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 157.21 (s), 144.00 (s), 136.20 (s), 134.05 (s), 130.13
(s), 130.00 (s), 127.19 (s), 125.02 (s), 120.02 (q, J = 325 Hz), 119.88 (s), 115.79 (s),
21.39 (s). 19F NMR (376 MHz, DMSO-d6) δ -77.35 (s). ESI-MS (m/z, %): 396.0 (30)
[M+H]+. HRMS (ESI) Calcd. for C14H13F3NO5S2 [M+H]+ requires 396.0182, found
396.0179.
4.2.12. N-{4-Hydroxy-3-(trifluoromethanesulfonyl)phenyl}-benzeneamine (4b)
Light green solid (65 mg, 41%). m.p. 62-65 ℃. IR (neat, cm-1): ν 3416, 2924, 2854,
1
1715, 1600, 1489, 1455, 1352, 1257, 1206, 1119, 800, 720. H NMR (400 MHz,
DMSO-d6) δ 11.15 (s, 1H, OH), 8.24 (s, 1H, NH), 7.55-7.44 (m, 2H), 7.24 (t, J = 7.8
Hz, 2H), 7.12 (t, J = 8.4 Hz, 1H), 6.96 (d, J = 8.2 Hz, 2H), 6.83 (d, J = 7.3 Hz, 1H). 13C
NMR (100 MHz, DMSO-d6) δ 153.58 (s), 144.00 (s), 136.56 (s), 130.10 (s), 129.82 (s),
19
120.32 (s), 120.24 (q, J = 325 Hz), 119.97 (s), 119.35 (s), 116.17 (s), 115.83 (s). F
NMR (376 MHz, DMSO-d6) δ -77.25 (s). ESI-MS (m/z, %): 318.1 (100) [M+H]+.
13

HRMS (ESI) Calcd. for C13H11F3NO3S [M+H]+ requires 318.0406, found 318.0403.
4.2.13. N-{4-Hydroxy-3-(2-chloro-1,1,2,2-tetrafluoroethanesulfonyl)phenyl}-p -
methylbenzenesulfonamide (4c)
White solid (135 mg, 58%). m.p. 118-120 ℃. IR (neat, cm-1): ν 3419, 3268, 2925, 2854,
1598, 1488, 1351, 1238, 1127, 1034, 937, 870, 813, 720. 1H NMR (400 MHz, DMSO-
d6) δ 11.65 (s, 1H, OH), 10.14 (s, 1H, NH), 7.53 (d, J = 8.0 Hz, 2H), 7.47 (dd, J = 8.9,
2.2 Hz, 1H), 7.34-7.30 (m, 3H), 7.06 (d, J = 8.9 Hz, 1H), 2.33 (s, 3H). 13C NMR (100
MHz, DMSO-d6) δ 157.47 (s), 143.93 (s), 136.16 (s), 134.30 (s), 130.10 (s), 129.80 (s),
127.19 (s), 125.54 (s), 119.81 (s), 117.13 (s), 21.37 (s) 19F NMR (376 MHz, DMSO-d6)
δ -66.45 (s, 2F), -110.46 (s, 2F). ESI-MS (m/z, %): 484.0 (70) [M+Na]+. HRMS (ESI)
Calcd. for C15H12ClF4NNaO5S2 [M+Na]+ requires 483.9674, found 483.9671.
4.2.14.
N-{4-Hydroxy-3-(perfluorobutanesulfonyl)phenyl}-p
-
methylbenzenesulfonamide (4d)
White solid (142 mg, 52%). m.p. 128-131 ℃. IR (neat, cm-1): ν 3275, 2924, 2853, 1715,
1
1599, 1489, 1455, 1351, 1206, 1161, 1026, 870, 811. H NMR (400 MHz, DMSO-d6)
δ 11.70 (s, 1H, OH), 10.15 (s, 1H, NH), 7.52 (d, J = 8.2 Hz, 2H), 7.47 (dd, J = 9.0, 2.6
Hz, 1H), 7.37 (d, J = 2.5 Hz, 1H), 7.31 (d, J = 8.1 Hz, 2H), 7.07 (d, J = 8.9 Hz, 1H),
2.31 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 157.63 (s), 143.90 (s), 136.16 (s),
134.54 (s), 130.03 (s), 129.89 (s), 127.19 (s), 125.49 (s), 119.92 (s), 116.64 (s), 21.25
(s). 19F NMR (376 MHz, DMSO-d6) δ, -80.38 (t, J = 9.3 Hz, 3F), -111.89 (t, J = 12.9
Hz, 2F), -121.52 (s, 2F), -125.63~-125.70 (m, 2F). ESI-MS (m/z, %): 568.0 (75)
[M+Na]+. HRMS (ESI) Calcd. for C17H12F9NNaO5S2 [M+Na]+ requires 567.9905,
found 567.9901.
4.2.15.
N-{4-Hydroxy-3-(perfluorobutanesulfonyl)phenyl}-p
-
methylbenzenesulfonamide (4e)
White solid (181 mg, 56%). m.p. 144-146 ℃. IR (neat, cm-1): ν 3296, 2923, 2853, 1715,
1541, 1489, 1361, 1290, 1203, 1141, 1108, 953, 833, 810. 1H NMR (400 MHz, DMSO-
14

d6) δ 11.71 (s, 1H, OH), 10.17 (s, 1H, NH), 7.54 (d, J = 8.1 Hz, 2H), 7.49 (dd, J = 8.9,
2.9 Hz, 1H), 7.39 (d, J= 2.5 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.9 Hz, 1H),
2.32 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 157.62 (s), 143.84 (s), 136.19 (s),
134.50 (s), 130.00 (s), 129.89 (s), 127.19 (s), 125.47 (s), 119.91 (s), 116.65 (s), 21.16
19
(s). F NMR (376 MHz, DMSO-d6) δ -80.42 (t, J = 9.6 Hz, 3F), -111.73 (t, J = 13.7
Hz, 2F), -120.58 (s, 2F), -121.70 (s, 2F), -122.69 (s, 2F), -125.93 (s, 2F). ESI-MS
(m/z, %): 646.0 (30) [M+H]+. HRMS (ESI) Calcd. for C19H13F13NO5S2 [M+H]+
requires 646.0022, found 646.0014.
Conflict of interest
The authors declared that they have no conflicts of interest to this work.
We declare that we do not have any commercial or associative interest that represents a
conflict of interest in connection with the work submitted.
Acknowledgements
Financial support from the National Natural Science Foundation of China (No.
21572257) is gratefully acknowledged.
References:
[1] (a) T. Otzen, E.G. Wempe, B. Kunz, R. Bartels, G. Lehwark-Yvetot, W. Hansel,
K.-J. Schaper, J.K. Seydel, J. Med. Chem. 47 (2004) 240. (b) W.-M. Xu, F.-F. Han,
M. He, D.-Y. Hu, J. He, S. Yang, B.-A. Song, J. Agric. Food Chem. 60 (2012) 1036.
(c) Y. Harrak, G. Casula, J. Basset, G. Rosell, S. Plescia, D. Raffa, M.G. Cusimano,
R. Pouplana, M.D. Pujol, J. Med. Chem. 53 (2010) 6560. (d) R.L. Lopez de
Compadre, R.A. Pearlstein, A.J. Hopfinger, J.K. Seyde, J. Med. Chem. 30 (1987)
900. (e) Z.Y. Sun, E. Botros, A.D. Su, Y. Kim, E. Wang, N.Z. Baturay, C.H. Kwon,
J. Med. Chem. 43 (2000) 4160. (f) M. Teall, P. Oakley, T. Harrison, D. Shaw, E.
Kay, J. Elliott, U. Gerhard, J.L. Castro, M. Shearman, R.G. Ball, N.N. Tsou, Biorg.
Med. Chem. Lett. 15 (2005) 2685. (g) D.C. Meadows, T. Sanchez, N. Neamati, T.W.
North, J. Gervay-Hague, Biorg. Med. Chem. 15 (2007) 1127.
[2] (a) R.A. Hartz, A.G. Arvanitis, C. Arnold, J.P. Rescinito, K.L. Hung, G. Zheng, H.
Wong, Bioorg. Med. Chem. Lett. 16 (2006) 934. (b) S. Sulzer-Mosse, A. Alexakis,
15

J. Mareda, G. Bollot, G. Bernardinelli, Y. Filinchuk, Chem. Eur. J. 15 (2009) 3204.
(c) J. Colomb, G. Becker, S. Fieux, J. Med. Chem. 57 (2014) 3884. (d) M. Artico,
R. Silvestri, S. Massa, A.G. Loi, S. Corrias, G. Piras, P.L. Colla, J. Med. Chem. 39
(1996) 522.
[3] (a) J.Z. Lu, P.J. Lee, N.C. Waters, Comb. Chem. High Throughput Screening. 8
(2005) 15. (b) M.M. Alhamadsheh, W.N. Water, S. Sachdeva, P. Lee, K.A.
Reynolds, Bioorg. Med. Chem. Lett. 18 (2008) 6402.
[4] (a) M. Lutz, M. Wenzler, I. Likhotvorik, Synthesis 50 (2018) 2231. (b) K. Suzuki,
J. Jeong, K. Yamaguchi, N. Mizuno, New J. Chem. 40 (2016) 1014. (c) G.W. Gokel,
H.M. Gerdes, D.M. Dishong, J. Org. Chem. 45 (1980) 3634. (d) L. Xu, J. Cheng,
M.L. Trudell, J. Org. Chem. 68 (2003) 5388. (e) S. Yamazaki, Bull. Chem. Soc.
Jpn. 69 (1996) 2955. (f) K. Sato, M. Hyodo, M. Aoki, X.-Q. Zheng, R. Noyori,
Tetrahedron 57 (2001) 2469.
[5] (a) B.Y. Ge, D.W. Wang, W.F. Dong, P. Ma, Y.L. Li, Y.Q. Ding, Tetrahedron Lett.
55 (2014) 5443. (b) L. Wang, Y.B. Xie, Q.L. Yang, M.G. Liu, K.B. Zheng, Y. Hu,
N.-Y. Huang, J. Iran Chem. Soc. 13 (2016) 1797. (c) J.S. Yadav, B.V.S. Reddy, T.
Swamy, N. Ramireddy, Synthesis 2004 (2004) 1849. (d) J.W. Yuan, S.N. Liu, L.B.
Qu, Tetrahedron 73 (2017) 6763.
[6] (a) K. Müller, C. Faeh, F. Diederich, Science 317 (2007) 1881. (b) S. Purser, P.R.
Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 37 (2008) 320. (c) A.J.
Cresswell, S.G. Davies, P.M. Roberts, J.E. Thomson, Chem. Rev. 115 (2015) 566.
(d) J. Charpentier, N. Früh, A. Togni, Chem. Rev. 115 (2015) 650. (e) X. Liu, C. Xu,
M. Wang, Q. Liu, Chem. Rev. 115 (2015) 683. (f) X.-H. Xu, K. Matsuzaki, N.
Shibata, Chem. Rev. 115 (2015) 731. (g) C. Ni, M. Hu, J. Hu, Chem. Rev. 115 (2015)
765. (h) Y. Zhou, J. Wang, Z. Gu, S. Wang, W. Zhu, J.L. Acena, V.A. Soloshonok,
K. Izawa, H. Liu, Chem. Rev. 116 (2016) 422.
[7] (a) J. Wang, M. Sanchez-Rosello, J.L. Acena, C. Pozo, A.E. Sorochinsky, S. Fustero,
V.A. Soloshonok, H. Liu, Chem. Rev. 114 (2014) 2432. (b) E.P. Gillis, K.J. Eastman,
M.D. Hill, D.J. Donnelly, N.A. Meanwell, J. Med. Chem. 58 (2015) 8315. (c) S.-L.
Zhang, C. Xiao, H.-X. Wan, Dalton Trans. 47 (2018) 4779. (d) L.M. Yagupolskii,
Aromatic and Heterocyclic Compounds with Fluorine-containing Substituents (in
Russian), Naukova Dumka, Kiev (1988).
16

[8] (a) F. Terrier, E. Magnier, E. Kizilian, C. Wakselman, E. Buncel, J. Am. Chem. Soc.
127 (2005) 5563. (b) V.M. Bzhezovsky, N.N. Ilchenko, E.G. Kapustin, M.B. Chura,
L.M. Yagupolskii, L. Gorb, J. Leszczynski, Struct. Chem. 15 (2004), 527. (c) P.
Ondachi, A. Castro, C.W. Luetje, M.I. Damaj, S.W. Mascarella, H.A. Navarro, F.I.
Carroll, J. Med. Chem. 55 (2012) 6512. (d) J. Chen, H. Zhou, A. Aguilar, L. Liu, L.
Bai, D. McEachern, C.-Y. Yang, J.L. Meagher, J.A. Stuckey, S. Wang, J. Med. Chem.
55 (2012) 8502.
[9] (a) K. Zhang, X.-H. Xu, F.-L. Qing, J. Org. Chem. 80 (2015) 7658. (b) Q. Wang, Z.
Qi, F. Xie, X. Li, Adv. Synth. Catal. 357 (2015) 355. (c) B. Alcaide, P. Almendros,
I. Fernández, C. LázaroMilla, Chem. Commun. 51 (2015) 3395. (d) K. Matsuzaki,
K. Okuyama, E. Tokunaga, N. Saito, M. Shiro, N. Shibata, Org. Lett. 17 (2015)
3038. (e) L.M. Yagupolskii, N.V. Kondratenko, V.P. Sambur, Synthesis 1975
(1975) 721.
[10] R.M. Scribner, J. Org. Chem. 31 (1966) 3671.
[11] (a) Z. Guan, H. Wang, Y. Huang, Y. Wang, S. Wang, A. Lei, Org. Lett. 21 (2019)
4619. (b) L. Zhang, G. Zhang, P. Wang, Y. Li, A. Lei, Org. Lett. 20 (2018) 7396.
(c) X. Zhao, A. Wei, B. Yang, T. Li, Q. Li, D. Qiu, K. Lu, J. Org. Chem. 82 (2017)
9175.
[12] L.-N. Hua, H. Li, F.-L. Qing, Y. Huang, X.-H. Xu, Org. Biomol. Chem. 14 (2016)
8443.
[13] (a) D.-W. Sun, X. Jiang, M. Jiang, Y. Lin, J.-T. Liu, Eur. J. Org. Chem. (2017) 3505.
(b) D.-W. Sun, X. Jiang, M. Jiang, Y. Lin, J.-T. Liu, Eur. J. Org. Chem. (2018) 2078.
[14] H. Chen, S. Zhao, S. Cheng, X. Dai, X. Xu, W. Yuan, X. Zhang, J. Heterocyclic
Chem. 56 (2019) 1672.
17