Catalyst-Free Sulfonylation of 2-Methoxyphenols: Facile One-Pot Synthesis of (Arylsulfonyl)catechols in Aqueous Media

Article abstract of DOI:10.1002/ejoc.201701038

A new water-assisted carbon–sulfur bond-formation strategy is described for direct access to highly valuable (arylsulfonyl)catechols. This scalable transformation is remarkable, as a tandem dearomatization/sulfonylation and hydroxylation process enabled t

Full text of DOI:10.1002/ejoc.201701038

DOI: 10.1002/ejoc.201701038
Full Paper
Direct Sulfonylation
Catalyst-Free Sulfonylation of 2-Methoxyphenols: Facile One-
Pot Synthesis of (Arylsulfonyl)catechols in Aqueous Media
Neha Taneja[a] and Rama Krishna Peddinti*[a]
Abstract: A new water-assisted carbon–sulfur bond-formation The sulfonylation operates under very mild conditions, shows a
strategy is described for direct access to highly valuable (aryl- broad substrate scope, gives high conversions, and can be car-
sulfonyl)catechols. This scalable transformation is remarkable, ried out on a gram scale. Thus, this method represents a green,
as a tandem dearomatization/sulfonylation and hydroxylation efficient method for carbon–sulfur bond formation. The aryl
process enabled the title compounds to be formed in one pot sulfones were also further transformed into molecules that are
under catalyst-free conditions. Mechanistic studies revealed important for drug discovery.
that water plays a key role in the synthesis of the catechols.
Introduction
sulfonate esters with organometallic compounds, the sulf-
onylation of arenes, and palladium- and copper-catalysed oxid-
ative coupling reactions of arenesulfonyl chlorides with aryl-
boronic acids.[6] However, new advances in this research area
are also being made, including the generation of a sulfone func-
tionality through metal-mediated or metal-free reactions of so-
dium sulfinates, or through the direct catalytic introduction of
SO2.[7] Willis[8a] and Shavnaya[8b] introduced the bench-stable
reagents DABSO {DABCO (1,4-diazabicyclo[2.2.2]octane) + SO2}
and K2S2O5 as surrogates for SO2 gas for the introduction of
sulfone groups (Scheme 1). The Mhaske group explored aryne
chemistry[9] to access diaryl sulfone derivatives. Soon after this,
Organosulfone chemistry[1] has undergone a renaissance in re-
cent decades, as sulfonyl-derived functional groups such as sulf-
ones and sulfonamides are found in a wide range of pharma-
ceutically active molecules[2] and agrochemicals[3] (Figure 1).
Moreover, sulfones have attracted considerable interest as ver-
satile synthetic intermediates[4] for useful organic transforma-
tions, including enantioselective catalysis.[5] This has provided
impetus to research directed towards the development of prac-
tical, efficient, and convenient methods for the formation of
carbon–sulfur bonds.
unprecedented methods for carbon–sulfur bond formation
[10]
were developed, using K2S2O8
and thiosulfonates[11] as
highly effective sulfonating agents. However, these protocols
have one or more innate drawbacks, such as harsh conditions,
a narrow substrate scope, or a reliance on sodium sulfinates,
which have a limited availability.
The catechol structural motif is found in every area of the
chemical industry.[12] These structures are ordinarily accessed
by orthoformylation of phenols followed by a Dakin reaction.[13]
Another method involves transition-metal-catalysed C–H
hydroxylation[14] and oxidative dehydrogenation of cyclohex-
anones to give phenols.[15] However, multistep procedures in-
volving the installation and removal of functional groups, and
the requirements of strong oxidants and transition-metal cata-
lysts limits the applicability of these processes. The high de-
mand for catechols in the chemical industry[16] has promoted
the development of convenient routes to access these com-
pounds.
Figure 1. Drugs with diaryl sulfone and catechol skeletons.
Traditionally, the synthesis of diaryl sulfones takes place
through the oxidation of sulfides and sulfoxides, the reaction of
The dihydroxy-substituted aryl sulfone[17] motif is found as a
substructure of many biologically active molecules of pharma-
ceutical relevance. For example, sulfone-derived catechols form
the integral part of COMT inhibitors.[18] These molecules are
anti-Parkinson's agents, and were previously prepared by a
multistep process involving sulfonylation of dimethoxybenzene
[a] Department of Chemistry, Indian Institute of Technology, Roorkee,
Roorkee 247667, Uttarakhand, India
E-mail: rkpedfcy@iitr.ac.in
ramakpeddinti@gmail.com
www.iitr.ac.in/~CY/rkpedfcy
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201701038.
Eur. J. Org. Chem. 2017, 5306–5314
5306
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Scheme 1. Literature reports (a–c) and present protocol (d). TBAB = tetrabutylammonium bromide.
derivatives followed by conversion of the methoxy group to a Results and Discussion
hydroxy moiety under harsh acidic conditions (Scheme 1c). In
the past two years, sulfonyl hydrazides[19] have been explored
We began our studies by choosing 4-bromoguaiacol (1b) and
benzenesulfonyl hydrazide (3) as model substrates for a sulf-
onylation reaction run at 70 °C in air in the absence of a cata-
lyst. At the outset, 4-bromoguaiacol was dearomatized in the
presence of PhI(OAc)2 (1.2 equiv.) in methanol. Then, benzene-
sulfonyl hydrazide was added, and the mixture was stirred at
70 °C. Disappointingly, no new spot was observed on TLC
as stable, solid, noncorrosive, readily accessible, odour-free
sulfonylating reagents. The compatibility of sulfonyl hydrazides
with water has made them new green reagents for sulfonyl-
ation. Water stimulates these transformations, and adds a pow-
erful dimension to the environmentally friendly synthesis of
sulfones.[20]
As part of our quest for environmentally friendly chemistry, (Table 1, Entry 1). With the aim of facilitating the reaction, water
in this paper we disclose a one-pot, catalyst-free, water-medi- (1 mL) was added to the reaction mixture after the dearomati-
ated, highly convenient approach for carbon–sulfur bond for- zation, and the mixture was stirred at 70 °C. To our delight,
mation to synthesize dihydroxy-substituted diaryl sulfones sulfonated product 8b was obtained in 40 % yield (Table 1, En-
starting from stable, inexpensive, and easily accessible sulfonyl try 2). To evaluate the effect of the solvent on the reaction,
hydrazides and guaiacol derivatives. The reaction proceeds the methanol was evaporated from the reaction mixture under
through sulfonylation of masked o-benzoquinones generated reduced pressure after the dearomatization of guaiacol 1b, and
in situ; these valuable synthetic intermediates[21] are obtained the residue was diluted with acetonitrile/water (2:1). Benzene-
by the dearomatization of phenols.[22] The compounds ob- sulfonyl hydrazide was then added, and the mixture was stirred
tained are precursors for potent COMT inhibitors, important at 70 °C for 2 h to give 8b in 55 % yield, along with unexpected
therapeutic agents for the treatment of Parkinson's disease.
product 7b in 30 % yield (Table 1, Entry 3). To achieve optimum
Eur. J. Org. Chem. 2017, 5306–5314
www.eurjoc.org
5307 © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 1. Optimization of the reaction conditions.[a]
Entry
3 [equiv.]
Catalyst
Solvent
Yield [%][b]
7b
8b
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
1
–
–
–
–
–
–
–
–
–
–
–
–
–
I2
MeOH
n.d.
n.d.
30
58
65
63
55
n.d.
n.d.
65
60
70
85
82
n.r.
n.r.
85
n.d.
40
55
25
15
MeOH/H2O (2:1)
MeCN/H2O (2:1)
MeCN/H2O (1:1)
MeCN/H2O (1:2)
THF/H2O (1:2)
DMF/H2O (1:2)
toluene/H2O (1:2)
CH2Cl2/H2O (1:2)
H2O
MeCN/H2O (1:2)
MeCN/H2O (1:2)
MeCN/H2O (1:2)
MeCN/H2O (1:2)
MeCN/H2O (1:2)
MeCN/H2O (1:2)
MeCN/H2O (1:2)
MeCN/H2O (1:2)
15
n.d.
n.d.
n.d.
15
20
15
9[c]
10
11
12
13
14
15
16
17[d]
18[e]
1
1.2
0.7
0.5
0.5
0.5
0.5
0.5
0.5
15
n.d.
n.r.
n.r.
10
I2 + H2O2
I2 + TBHP[f]
–
–
60
n.d.
[a] Reaction conditions: 1b (0.5 mmol), PhI(OAc)2 (0.6 mmol), 3 (0.25 mmol), solvent (3 mL), stirred at 70 °C under air for 2 h. [b] Pure and isolated yields;
n.d. = not determined; n.r. = no reaction. [c] Reaction carried out in a sealed tube. [d] Reaction was carried out at room temperature for 24 h. [e] Reaction
was carried out at 100 °C. [f] TBHP = tert-butyl hydroperoxide.
sulfonylation conditions, the amount of water in the solvent tion. Using the optimized sulfonylation procedure, several ar-
system was increased (Table 1, Entries 4 and 5); with aceto- enesulfonyl hydrazides 3–5 bearing substituents with varying
nitrile/water (1:2), dihydroxy derivative 7b was obtained in 65 % electronic properties were tested in the reaction with 4-halo-2-
yield, along with a 15 % yield of 8b (Table 1, Entry 5). The signif- methoxyphenols 1a–1c. The corresponding dihydroxyaryl sulf-
icant rise in the yield of 7b as a result of increasing the quantity ones 7a–7c, 9a–9c, and 11a–11c were obtained in good to
of water shows the crucial role of water in this sulfonylation high yields of 50–80 %, along with 8a–8c, 10a–10c, and 12a–
reaction. The protocol was also tested using different solvents 12c as minor products in 0–30 % yield. The reaction of 4-halo-
and catalysts, and by varying the temperature and the amount substituted methoxyphenols with 4-bromobenzenesulfonyl
of substrate.
hydrazide (6) resulted in the selective formation of the corre-
sponding catechols 13a–13c (Scheme 2).
Screening of other solvents such as methanol, THF, DMF, tol-
uene, CH2Cl2, and H2O revealed acetonitrile to be the most ef-
Various functional groups, as in 4-methyl-2-methoxyphenol
fective solvent for this transformation (Table 1, Entries 6–10). (1d) and 4-hydroxy-3-methoxyacetophenone (1e), were well
We then optimized the reaction with different concentrations tolerated under the optimized conditions, and the sulfonylated
of 3, and we observed that increasing the amount of 3 resulted products were formed in good yields. It is noteworthy that
in a slight decrease in the yield of 7b (Table 1, Entry 11). De- methyl-substituted guaiacol 1d underwent sulfonylation to give
creasing the amount of 3 from 1 to 0.5 equiv. resulted in an catechol-substituted phenyl sulfones 7d, 9d, 11d, and 13d se-
increase in the efficiency of the reaction, and the corresponding lectively in 60–80 % yield. In contrast, acetovanillone (1e) gave
catechol 7b was obtained in a maximum yield of 85 % (Table 1, the corresponding (arylsulfonyl)guaiacol derivatives 8e, 10e,
Entries 12 and 13). The use of a catalyst failed to improve the 12e, and 14e exclusively in 55–66 % yield (Scheme 3).
yield (Table 1, Entries 14–16). On the other hand, lowering the
temperature from 70 °C caused a substantial drop in the reac-
tion rate and an increase in the reaction time (Table 1, Entry 17).
At higher temperature, nonspecific decomposition was ob-
served in the reaction (Entry 18).
Encouraged by this green and sustainable protocol for the
synthesis of (arylsulfonyl)catechols, a gram-scale reaction was
carried out. The efficacy of the process was demonstrated by
carrying out a reaction between 4-iodoguaiacol (1c; 1.85 g,
7.4 mmol) and benzenesulfonyl hydrazide (3; 1 g) to give sulf-
Easily accessible 4-substituted guaiacols and sulfonyl hydraz- one 7c in 62 % yield, along with a 24 % yield of (arylsulf-
ides were used to study the general scope of this transforma- onyl)guaiacol 8c (Scheme 4).
Eur. J. Org. Chem. 2017, 5306–5314
www.eurjoc.org
5308
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Scheme 2. Sulfonylation of 4-halo-2-methoxyphenols 1a–1c. Reaction conditions: methoxyphenol 1 (0.5 mmol), PhI(OAc)2 (0.6 mmol), methanol (5 mL), room
temp.; then arenesulfonyl hydrazide 3–6 (0.25 mmol), acetonitrile/water (1:2), 70 °C. Yields of pure and isolated products.
Scheme 3. Sulfonylation of 2-methoxyphenols 1d and 1e. Reaction conditions: methoxyphenol 1d or 1e (0.5 mmol), PhI(OAc)2 (1.1 equiv.), methanol (5 mL);
then arenesulfonyl hydrazide 3–6 (0.25 mmol), acetonitrile/water (1:2), 70 °C. Yields of isolated products.
We next turned our attention to the reaction mechanism. At and 4 using 2 equiv. of the radical inhibitor TEMPO [(2,2,6,6-
first, to test our working hypothesis based on the intermediacy tetramethylpiperidin-1-yl)oxyl; Scheme 5]. This reaction gave
of a sulfinyl anion in water,[20] we carried out the reaction of 1d product 9d in 65 % yield, which is consistent with the proposed
Eur. J. Org. Chem. 2017, 5306–5314
www.eurjoc.org
5309
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Scheme 4. Gram-scale reaction.
Figure 2. ORTEP plot for compound 7a.
ionic intermediate. Subsequently, to elucidate the origin of the
second hydroxy group in the catechol products, an isotopic la-
belling experiment was carried out (Scheme 5). When we car-
ried out the above reaction in H218O, the 18O-labelled product
9d′ was detected by HRMS analysis (see the Supporting Infor-
mation). This isotopic labelling experiment showed that the
oxygen atom of the second hydroxy group in the catechol
product originates from water.
form species C, and subsequent rearomatization yields the (aryl-
sulfonyl)guaiacol derivative as the minor product. Species C de-
velops a positive charge on the oxygen atom, which facilitates
nucleophilic attack by water on the neighbouring carbon atom.
A series of steps resulting in rearomatization leads to the (aryl-
sulfonyl)catechol derivative as the major product of the sulf-
onylation reaction.
Having established the scope of the reaction with various
hydrazides and 2-methoxyphenols, we further demonstrated
the potential of the dihydroxyaryl sulfone products (Scheme 7).
We envisioned that the two free OH groups could undergo
acetalization to give ketals 15 and 16, analogues of COMT in-
hibitors, and new precursors for cannabinoid-1 receptor inverse
agonists for the treatment of obesity.[24]
Scheme 5. Mechanistic considerations.
The relative positions of the various substituent groups were
confirmed with the help of single-crystal X-ray[23] diffraction
studies on dihydroxy sulfone derivative 7a (Figure 2).
The proposed mechanism for the sulfonylation reaction is
shown in Scheme 6. Intially, the sulfonyl hydrazide is trans-
formed into intermediate A which, in the presence of water,
resonates with species B. The sulfur-centred anion attacks the
3-position of MOB (i.e., 6,6-dialkoxycyclohexa-2,4-dienone) to
Scheme 7. Synthetic transformation of (arylsulfonyl)catechol. (i) (COCl)2
(8 equiv.), 4,4′-dimethoxybenzophenone (1.5 equiv.), 60 °C, 30 min; (ii) temp.
raised to 160 °C, (arylsulfonyl)catechol (1 equiv.), 40 min.
Scheme 6. Proposed reaction mechanism.
Eur. J. Org. Chem. 2017, 5306–5314
www.eurjoc.org
5310
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
7.44 (m, 3 H), 6.88 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3
[D6]DMSO): δ = 150.4, 143.7, 140.9, 132.8, 128.6, 128.2, 127.9, 123.6,
118.2, 117.4 ppm. HRMS (ESI-TOF): calcd. for C12H9ClO4S [M + Na]+
306.9802; found 306.9806.
+
Conclusions
By using sulfonyl hydrazides in water, we have developed a
direct, one-pot, water-assisted sulfonylation of guaiacol deriva-
tives for the direct synthesis of (arylsulfone)catechols in good
to high yields without using any catalyst. The yields of the prod-
ucts should be treated as overall yields of three steps, i.e.,
dearomatization, sulfonylation, and demethoxy-hydroxylation.
The process is short and operationally simple, and has a broad
substrate scope. Furthermore, the diaryl sulfone products may
be converted into biologically valuable compounds used for
drug discovery.
4-Chloro-2-methoxy-5-(phenylsulfonyl)phenol (8a): Brown solid
(11 mg, 15 %). M.p. 144–145 °C. 1H NMR (400 MHz, CDCl3
+
[D6]DMSO): δ = 10.59 (br. s, 1 H), 10.12 (br. s, 1 H), 7.84–7.77 (m, 2
H), 7.71–7.67 (m, 1 H), 7.64 (s, 1 H), 7.62–7.58 (m, 2 H), 6.87 (s, 1 H),
3.38 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3 + [D6]DMSO): δ = 151.6,
144.7, 140.7, 129.3, 129.1, 127.8, 127.5, 127.0, 118.2, 117.1, 59.8 ppm.
HRMS (ESI-TOF): calcd. for C13H11ClO4S [M + Na]+ 320.9958; found
320.9958.
4-Bromo-5-(phenylsulfonyl)benzene-1,2-diol (7b): Brown solid
(68 mg, 82 %). M.p. 110–111 °C. 1H NMR (400 MHz, CDCl3
+
[D6]DMSO): δ = 9.25 (br. s, 1 H), 8.95 (br. s, 1 H), 7.76–7.74 (m, 3 H),
7.45–7.41 (m, 1 H), 7.36–7.32 (m, 2 H), 6.95 (s, 1 H) ppm. 13C NMR
(100 MHz, CDCl3 + [D6]DMSO): δ = 150.3, 144.2, 132.8, 128.7, 128.5,
128.2, 128.0, 121.6, 118.1, 110.7 ppm. HRMS (ESI-TOF): calcd. for
C13H11BrO4S [M + Na]+ 364.9453; found 364.9456.
Experimental Section
General Remarks: Unless otherwise noted, chemicals were pur-
chased at the highest purity grade available, and were used without
further purification. Thin-layer chromatography was carried out on
Merck precoated 0.25 mm silica gel plates (60F-254), using UV light
for visualization. Silica gel (100–200 mesh) was used for column
chromatography. NMR spectra were recorded with
(400 MHz) instrument in CDCl3 and [D6]DMSO, using tetramethyl-
silane (TMS) as an internal standard. Chemical shifts (δ) are reported
as parts per million (ppm) on the δ scale downfield from TMS. H
4-Bromo-2-methoxy-5-(phenylsulfonyl)phenol (8b): Brown solid
(13 mg, 17 %). M.p. 94–95 °C. 1H NMR (400 MHz, CDCl3 + [D6]DMSO):
δ = 7.95–7.92 (m, 3 H), 7.60–7.56 (m, 1 H), 7.51–7.47 (m, 2 H), 7.05
(s, 1 H), 3.92 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3 + [D6]DMSO):
δ = 150.5, 144.9, 140.4, 133.1, 132.3, 128.7, 128.4, 117.4, 117.1, 111.4,
56.6 ppm. HRMS (ESI-TOF): calcd. for C12H9BrO4S [M + Na]+
350.9297; found 350.9290.
a JEOL
1
NMR spectra were referenced to CDCl3 (δ =7.26 ppm), and 13C NMR
spectra were referenced to CDCl3 (δ =77.0 ppm, the middle peak).
Coupling constants are expressed in Hz. The following abbrevia-
tions are used to explain the multiplicities: s = singlet, d = doublet,
dd = doublet of doublets, t = triplet, q = quartet, m = multiplet.
Melting points were recorded with an Opti Melt automated melting
point system. High-resolution mass spectra (HRMS) were recorded
with a Bruker micrOTOF™-Q II mass spectrometer (ESI-MS).
4-Iodo-5-(phenylsulfonyl)benzene-1,2-diol (7c): Brown solid
(47 mg, 50 %). M.p. 109–110 °C. 1H NMR (400 MHz, CDCl3
+
[D6]DMSO): δ = 8.88 (br. s, 1 H), 7.86 (s, 1 H), 7.82–7.75 (m, 2 H),
7.49–7.45 (m, 1 H), 7.41–7.37 (m, 2 H), 7.34 (s, 1 H) ppm. 13C NMR
(100 MHz, CDCl3 + [D6]DMSO): δ = 150.4, 144.2, 140.5, 132.7, 129.4,
127.8, 121.7, 117.9, 110.4, 90.9 ppm. HRMS (ESI-TOF): calcd. for
C12H9IO4S [M + Na]+ 398.9158; found 398.9157.
General Procedure for the Synthesis of Diaryl Sulfones 7–14:
Guaiacol derivative 1 (0.5 mmol) was dissolved in dry MeOH (2 mL),
and solid PhI(OAc)2 (0.6 mmol) was added at room temperature.
The mixture was stirred for 5 min. After complete conversion of the
guaiacol derivative into its MOB 2, the MeOH was removed under
reduced pressure. The residue was dissolved in acetonitrile/water
(1:2; 3 mL), and sulfonyl hydrazide 3–6 (0.25 mmol) was added. The
reaction mixture was stirred at 70 °C. When TLC showed that the
reaction was complete, the mixture was extracted with EtOAc (3 ×
5 mL). The combined organic extracts were washed with brine
(10 mL), dried with anhydrous sodium sulfate, and filtered. The sol-
vent was removed under reduced pressure, and the residue was
purified by flash column chromatography (hexanes/EtOAc, 3:1).
4-Iodo-2-methoxy-5-(phenylsulfonyl)phenol (8c): Brown solid
(30 mg, 30 %). M.p. 105–106 °C. 1H NMR (400 MHz, CDCl3
+
[D6]DMSO): δ = 7.98 (s, 1 H), 7.95–7.93 (m, 2 H), 7.58–7.55 (m, 1 H),
7.50–7.46 (m, 2 H), 7.35 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3 +
[D6]DMSO): δ = 151.4, 146.6, 139.9, 132.9, 128.8, 128.6, 128.3, 126.0,
124.4, 117.9, 80.5, 56.1 ppm. HRMS (ESI-TOF): calcd. for C13H11IO4S
[M + Na]+ 412.9314; found 412.9310.
4-Methyl-5-(phenylsulfonyl)benzene-1,2-diol (7d): Colourless
solid (42 mg, 70 %). M.p. 118–119 °C. 1H NMR (400 MHz, CDCl3
+
[D6]DMSO): δ = 8.19 (br. s, 1 H), 7.97 (br. s, 1 H), 7.78 (d, J = 4.0 Hz,
2 H), 7.73 (s, 1 H), 7.52–7.48 (m, 1 H), 7.45–7.42 (m, 2 H), 6.66 (s, 1
H), 2.12 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3 + [D6]DMSO): δ =
149.6, 142.5, 142.2, 132.5, 130.8, 128.8, 127.2, 119.0, 116.8, 19.4 ppm.
HRMS (ESI-TOF): calcd. for C13H12O4S [M + Na]+ 287.0348; found
287.0348.
General Procedure for the Synthesis of 15 and 16: 4,4′-Di-
methoxybenzophenone (1.5 equiv.) and oxalyl chloride (8 equiv.)
were stirred at 60 °C for 30 min. After this time, the temperature
was raised to 110 °C to remove the excess oxalyl chloride, and then
the corresponding 2-methyl-4,5-dihydroxyphenyl sulfone derivative
(1 equiv.) was added to the mixture. The resulting dark-red solution
was stirred at 160 °C for 40 min. After this time, the mixture was
cooled, and EtOAc was added to the viscous mixture. The solution
was washed with satd. aq. NaCl, and dried with MgSO4, and the
solvent was evaporated under reduced pressure. The crude product
was purified by column chromatography (hexanes/EtOAc, 10:1 or
20:1).
1-[4-Hydroxy-5-methoxy-2-(phenylsulfonyl)phenyl]ethanone
(8e): Viscous colourless liquid (48 mg, 62 %). 1H NMR (400 MHz,
CDCl3 + [D6]DMSO): δ = 7.82–7.80 (m, 2 H), 7.46–7.39 (m, 4 H), 6.65
(s, 1 H), 3.83 (s, 3 H), 2.54 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3 +
[D6]DMSO): δ = 202.4, 150.9, 147.3, 141.9, 132.7, 128.7, 128.5, 128.1,
127.3, 116.3, 108.7, 56.1, 31.6 ppm. HRMS (ESI-TOF): calcd. for
C15H14O5S [M + Na]+ 329.0454; found 329.0454.
4-Chloro-5-tosylbenzene-1,2-diol (9a): Brown solid (45 mg, 60 %).
M.p. 105–106 °C. 1H NMR (400 MHz, CDCl3 + [D6]DMSO): δ = 8.99
4-Chloro-5-(phenylsulfonyl)benzene-1,2-diol (7a): Brown solid (br. s, 1 H), 8.79 (br. s, 1 H), 7.72 (s, 1 H), 7.68 (d, J = 8.4 Hz, 2 H),
(42 mg, 60 %). M.p. 173–174 °C. 1H NMR (400 MHz, CDCl3
[D6]DMSO): δ = 7.88 (d, J = 7.6 Hz, 2 H), 7.57–7.53 (m, 1 H), 7.48–
+
7.18 (d, J = 8.0 Hz, 2 H), 6.79 (s, 1 H), 2.32 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3 + [D6]DMSO): δ = 150.5, 143.5, 137.7, 129.1, 128.2,
Eur. J. Org. Chem. 2017, 5306–5314
www.eurjoc.org
5311
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
127.8, 123.2, 118.2, 117.2, 21.5 ppm. HRMS (ESI-TOF): calcd. for 4-Bromo-5-(4-nitrophenylsulfonyl)benzene-1,2-diol (11b): Col-
C13H11ClO4S [M + Na]+ 320.9958; found 320.9958.
ourless solid (70 mg, 75 %). M.p. 94–95 °C. 1H NMR (400 MHz, CDCl3
+ [D6]DMSO): δ = 8.89 (br. s, 1 H), 8.70 (br. s, 1 H), 7.82 (s, 1 H), 7.71
(d, J = 10.4 Hz, 2 H), 7.55 (d, J = 6.8 Hz, 2 H), 7.06 (s, 1 H) ppm. 13C
NMR (100 MHz, CDCl3 + [D6]DMSO): δ = 151.4, 149.7, 146.4, 144.7,
129.0, 127.5, 123.6, 121.7, 118.2, 110.4 ppm. HRMS (ESI-TOF): calcd.
for C12H8BrNO6S [M + Na]+ 395.9147; found 395.913.
4-Chloro-2-methoxy-5-tosylphenol (10a): Brown solid (16 mg,
1
20 %). M.p. 99–100 °C. H NMR (400 MHz, CDCl3 + [D6]DMSO): δ =
8.94 (br. s, 1 H), 7.68–7.65 (m, 3 H), 7.16 (d, J = 8.0 Hz, 2 H), 6.76 (s,
1 H), 3.76 (s, 3 H), 2.29 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3
+
[D6]DMSO): δ = 150.4, 143.7, 143.5, 137.8, 129.1, 129.0, 127.8, 127.7,
118.1, 117.2, 56.1, 21.2 ppm. HRMS (ESI-TOF): calcd. for C14H13ClO4S
[M + Na]+ 335.0115; found 335.0114.
4-Bromo-2-methoxy-5-(4-nitrophenylsulfonyl)phenol (12b): Yel-
1
low solid (34 mg, 20 %). M.p. 87–88 °C. H NMR (400 MHz, CDCl3 +
[D6]DMSO): δ = 8.33 (d, J = 9.2 Hz, 2 H), 8.12 (d, J = 9.2 Hz, 2 H),
7.97 (s, 1 H), 7.08 (s, 1 H), 3.96 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3 + [D6]DMSO): δ = 151.4, 150.2, 146.0, 145.2, 130.5, 129.6,
127.7, 123.9, 117.5, 111.6, 56.6 ppm.
4-Bromo-5-tosylbenzene-1,2-diol (9b): Brown solid (51 mg, 60 %).
M.p. 210–211 °C. H NMR (500 MHz, CDCl3 + [D6]DMSO): δ = 9.18–
1
8.96 (br. s, 2 H), 7.82 (s, 1 H), 7.72 (d, J = 8.0 Hz, 2 H), 7.22 (d, J =
7.5 Hz, 2 H), 7.03 (s, 1 H), 2.35 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3 + [D6]DMSO): δ = 150.4, 144.3, 140.5, 132.6, 128.8, 128.4, 4-Iodo-5-(4-nitrophenylsulfonyl)benzene-1,2-diol (11c): Colour-
127.8, 121.6, 118.0, 110.4, 29.4 ppm. HRMS (ESI-TOF): calcd. for less viscous liquid (71 mg, 68 %). 1H NMR (400 MHz, CDCl3 +
C
13H11BrO4S [M + Na]+ 364.9453; found 364.9494.
[D6]DMSO): δ = 9.02 (br. s, 1 H), 8.24 (d, J = 7.2 Hz, 2 H), 8.01 (d, J =
5.6 Hz, 2 H), 7.82 (s, 1 H), 7.04 (s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3 + [D6]DMSO): δ = 50.9, 150.0, 146.5, 144.4, 129.4, 128.3, 123.8,
121.8, 118.3, 111.1 ppm. HRMS (ESI-TOF): calcd. for C12H8INO6S [M
+ Na]+ 443.9009; found 443.9008.
4-Bromo-2-methoxy-5-tosylphenol (10b): Brown solid (26 mg,
28 %). 1H NMR (400 MHz, CDCl3 + [D6]DMSO): δ = 7.93 (s, 1 H), 7.81
(d, J = 8.4 Hz, 2 H), 7.27 (d, J = 8.4 Hz, 2 H), 7.04 (s, 1 H), 3.92 (s, 3
H), 2.40 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3 + [D6]DMSO): δ =
150.4, 144.8, 144.1, 137.3, 132.5, 129.3, 128.5, 117.3, 117.0, 111.3, 4-Iodo-2-methoxy-5-(4-nitrophenylsulfonyl)phenol (12c): Col-
56.6, 21.6 ppm. HRMS (ESI-TOF): calcd. for C14H13BrO4S [M + Na]+ ourless solid (17 mg, 15 %). M.p. 85–86 °C. 1H NMR (400 MHz, CDCl3
394.9349; found 394.9349.
+ [D6]DMSO): δ = 8.32 (d, J = 8.4 Hz, 2 H), 8.12 (d, J = 8.8 Hz, 2 H),
8.01 (s, 1 H), 7.37 (s, 1 H), 3.94 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3 + [D6]DMSO): δ = 150.9, 150.1, 146.1, 145.6, 133.5, 129.8,
124.2, 124.0, 117.8, 81.7, 56.7 ppm. HRMS (ESI-TOF): calcd. for
4-Iodo-5-tosylbenzene-1,2-diol (9c): Brown solid (58 mg, 60 %).
M.p. 156–157 °C. 1H NMR (400 MHz, CDCl3 + [D6]DMSO): δ = 8.64
(br. s, 1 H), 7.89 (s, 1 H), 7.74 (d, J = 8.0 Hz, 2 H), 7.38 (s, 1 H), 7.21
(d, J = 7.6 Hz, 2 H), 2.32 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3 +
C
13H10INO6S [M + Na]+ 457.9165; found 457.9165.
[D6]DMSO): δ = 149.9, 144.9, 143.5, 137.3, 132.9, 129.1, 128.7, 128.3, 4-Methyl-5-(4-nitrophenylsulfonyl)benzene-1,2-diol (11d): Yel-
1
127.0, 118.3, 80.6, 21.5 ppm. HRMS (ESI-TOF): calcd. for C13H11IO4S
low solid (55 mg, 72 %). M.p. 111–112 °C. H NMR (400 MHz, CDCl3
+ [D6]DMSO): δ = 8.29 (d, J = 8.0 Hz, 2 H), 7.98 (d, J = 9.2 Hz, 2 H),
7.74 (s, 1 H), 6.71 (s, 1 H), 2.25 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3 + [D6]DMSO): δ = 150.6, 149.5, 147.8, 143.0, 128.2, 128.1,
123.90, 123.92, 119.3, 116.9, 19.4 ppm. HRMS (ESI-TOF): calcd. for
C13H11NO6S [M + Na]+ 332.0199; found 332.021.
[M + Na]+ 412.9314; found 412.9314.
4-Iodo-2-methoxy-5-tosylphenol (10c): Brown viscous liquid
1
(20 mg, 20 %). H NMR (400 MHz, CDCl3 + [D6]DMSO): δ = 8.37 (br.
s, 1 H), 7.92 (s, 1 H), 7.74 (d, J = 8.0 Hz, 2 H), 7.27 (s, 1 H), 7.21 (d,
J = 8.0 Hz, 2 H), 3.82 (s, 3 H), 2.35 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3 + [D6]DMSO): δ = 151.1, 146.1, 144.0, 136.5, 134.1, 129.2, 1-[4-Hydroxy-5-methoxy-2-(4-nitrophenylsulfonyl)phenyl]-
128.4, 124.2, 117.6, 80.3, 56.1, 21.4 ppm. HRMS (ESI-TOF): calcd. for
C
ethanone (12e): Viscous colourless liquid (58 mg, 66 %). 1H NMR
(400 MHz, CDCl3 + [D6]DMSO): δ = 8.32 (d, J = 9.2 Hz, 2 H), 8.09 (d,
J = 9.2 Hz, 2 H), 7.65 (s, 1 H), 6.79 (s, 1 H), 3.97 (s, 3 H), 2.64 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3 + [D6]DMSO): δ = 202.0, 150.5,
150.1, 147.7, 146.7, 135.6, 129.2, 129.1, 124.1, 116.4, 108.5, 56.7,
31.6 ppm. HRMS (ESI-TOF): calcd. for C15H13NO7S [M + Na]+
374.0304; found 374.0298.
14H13IO4S [M + Na]+ 426.9471; found 426.9450.
4-Methyl-5-tosylbenzene-1,2-diol (9d): Colourless solid (56 mg,
80 %). M.p. 137–138 °C. 1H NMR (400 MHz, CDCl3 + [D6]DMSO): δ =
7.92 (s, 1 H), 7.71 (d, J = 6.4 Hz, 2 H), 7.28 (d, J = 8.0 Hz, 2 H), 6.72
(s, 1 H), 2.40 (s, 3 H), 2.28 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3 +
[D6]DMSO): δ = 149.3, 143.1, 142.4, 138.9, 130.0, 129.1, 128.6, 126.9,
118.8, 116.5, 21.2, 19.0 ppm. HRMS (ESI-TOF): calcd. for C14H14O4S
[M + Na]+ 301.0505; found 301.0506.
4-(4-Bromophenylsulfonyl)-5-chlorobenzene-1,2-diol (13a):
Brown solid (63 mg, 70 %). M.p. 131–132 °C. 1H NMR (400 MHz,
CDCl3 + [D6]DMSO): δ = 8.17 (br. s, 1 H), 7.95 (s, 1 H), 7.77 (d, J =
12.0 Hz, 2 H), 7.61 (d, J = 8.8 Hz, 2 H), 7.45 (s, 1 H) ppm. 13C NMR
(100 MHz, CDCl3 + [D6]DMSO): δ = 149.8, 144.7, 139.3, 131.9, 130.0,
128.7, 128.1, 128.0, 118.4 ppm. HRMS (ESI-TOF): calcd. for
C12H8ClBrO4S [M + Na]+ 384.8907; found 384.8907.
1-(4-Hydroxy-5-methoxy-2-tosylphenyl)ethanone (10e): Colour-
1
less solid (52 mg, 65 %). M.p. 106–107. H NMR (400 MHz, CDCl3 +
[D6]DMSO): δ = 7.77 (d, J = 8.4 Hz, 2 H), 7.50 (s, 1 H), 7.27 (d, J =
8.4 Hz, 2 H), 6.67 (s, 1 H), 3.91 (s, 3 H), 2.64 (s, 3 H), 2.37 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3 + [D6]DMSO): δ = 201.4, 150.7,
147.1, 143.2, 138.6, 133.8, 129.3, 128.9, 126.9, 115.8, 108.5, 55.5, 31.2, 4-(4-Bromophenylsulfonyl)-5-bromobenzene-1,2-diol (13b):
20.8 ppm. HRMS (ESI-TOF): calcd. for C16H16O5S [M + Na]+ 343.0610;
found 343.0612.
Brown solid (76 mg, 75 %). M.p. 112–113 °C. 1H NMR (400 MHz,
CDCl3 + [D6]DMSO): δ = 9.09 (br. s, 1 H), 8.84 (br. s, 1 H), 7.79 (s, 1
H), 7.71 (d, J = 10.4 Hz, 2 H), 7.53 (d, J = 8.4 Hz, 2 H), 7.03 (s, 1 H)
ppm. 13C NMR (100 MHz, CDCl3 + [D6]DMSO): δ = 150.4, 144.3,
139.8, 131.8, 129.6, 129.4, 128.0, 121.7, 118.1, 110.8 ppm. HRMS (ESI-
TOF): calcd. for C12H8Br2O4S [M + Na]+ 428.8402; found 428.8391.
4-Chloro-5-(4-nitrophenylsulfonyl)benzene-1,2-diol (11a): Yel-
low viscous liquid (50 mg, 60 %). 1H NMR (400 MHz CDCl3 +
[D6]DMSO): δ = 9.15 (br. s, 1 H), 8.17 (d, J = 11.2 Hz, 2 H), 7.93 (d,
J = 8.8 Hz, 2 H), 7.66 (s, 1 H), 6.75 (s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3 + [D6]DMSO): δ = 151.5, 149.9, 146.6, 144.0, 128.9, 126.1, 4-(4-Bromophenylsulfonyl)-5-iodobenzene-1,2-diol (13c): Brown
123.7, 123.5, 118.4, 117.5 ppm. HRMS (ESI-TOF): calcd. for
solid (62 mg, 55 %). M.p. 130–131 °C. 1H NMR (400 MHz, CDCl3
[D6]DMSO): δ = 9.00–8.79 (br. s, 2 H), 7.85 (s, 1 H), 7.69 (d, J = 6.8 Hz,
+
C12H8ClNO6S [M + Na]+ 351.9653; found 351.9653.
Eur. J. Org. Chem. 2017, 5306–5314
www.eurjoc.org
5312
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
2 H), 7.53 (d, J = 8.8 Hz, 2 H), 7.36 (s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3 + [D6]DMSO): δ = 150.4, 145.2, 139.4, 132.1, 131.7, 129.7,
128.8, 127.7, 118.5, 80.6 ppm. HRMS (ESI-TOF): calcd. for C12H8IBrO4S
[M + Na]+ 476.8263; found 476.8263.
Expert Opin. Pharmacother. 2002, 3, 1313; d) Y. I. Zhu, M. J. Stiller, J. Am.
Acad. Dermatol. 2001, 45, 420.
[3]
[4]
a) W.-M. Xu, F.-F. Han, M. He, D.-Y. Hu, J. He, S. Yang, B.-A. Song, J. Agric.
Food Chem. 2012, 60, 1036; b) P. Boger, J. Pestic. Sci. 2003, 28, 324.
a) H. Yang, R. G. Carter, L. N. Zakharov, J. Am. Chem. Soc. 2008, 130, 9238;
b) P. J. Crowley, J. Fawcett, B. M. Kariuki, A. C. Moralee, J. M. Percy, V.
Salafia, Org. Lett. 2002, 4, 4125; c) N. S. Simpkins, Sulfones in Organic
Synthesis, Pergamon Press, Oxford, 1993.
a) J. Choi, P. Martín-Gago, G. C. Fu, J. Am. Chem. Soc. 2014, 136, 12161;
b) B. K. Peters, T. Zhou, J. Rujirawanich, A. Cadu, T. Singh, W. Rabten, S.
Kerdphon, P. J. Andersson, J. Am. Chem. Soc. 2014, 136, 16557; c) K. M.-
H. Lim, T. Hayashi, J. Am. Chem. Soc. 2015, 137, 3201.
a) H. Chen, H. Xie, S. Chen, L. Yang, G.-J. Deng, Org. Lett. 2014, 16, 50; b)
S. C. Cullen, S. Shekhar, N. K. Nere, J. Org. Chem. 2013, 78, 12194; c) S.
Liang, R.-Y. Zhang, L.-Y. Xi, S.-Y. Chen, X.-Q. Yu, J. Org. Chem. 2013, 78,
11874; d) X. Zhou, J. Luo, J. Liu, S. Peng, G.-J. Deng, Org. Lett. 2011, 13,
1432; e) K. M. Maloney, J. T. Kuethe, K. Linn, Org. Lett. 2011, 13, 102; f)
K. Bahrami, M. M. Khodaei, M. S. Arabi, J. Org. Chem. 2010, 75, 6208.
a) S. Liang, G. Manolikakes, Adv. Synth. Catal. 2016, 358, 2371; b) A.
Meyer, V. W.-H. Lau, B. König, B. V. Lotsch, Eur. J. Org. Chem. 2017, 2179;
c) L. Sumunnee, C. Buathongjan, C. Pimpasri, S. Yotphan, Eur. J. Org.
Chem. 2017, 1025.
4-(4-Bromophenylsuphonyl)-5-methylbenzene-1,2-diol (13d):
Colourless solid (53 mg, 62 %). 1H NMR (400 MHz, CDCl3 +
[D6]DMSO): δ = 8.34 (d, J = 10.0 Hz, 2 H), 7.64 (s, 1 H), 7.61 (d, J =
8.8 Hz, 2 H), 7.53 (d, J = 8.4 Hz, 2 H), 6.63 (s, 1 H), 2.18 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3 + [D6]DMSO): δ = 149.7, 142.6, 141.1,
131.9, 130.5, 128.6, 127.9, 127.3, 119.1, 116.7, 19.0 ppm. HRMS (ESI-
TOF): calcd. for C13H11BrO4S [M + Na]+ 364.9453; found 364.9451.
[5]
[6]
1-[2-(4-Bromophenylsulfonyl)-4-hydroxy-5-methoxyphenyl]-
ethanone (14e): Viscous yellow liquid (53 mg, 55 %). 1H NMR
(400 MHz, CDCl3 + [D6]DMSO): δ = 9.11 (s, 1 H), 7.65 (d, J = 8.8 Hz,
2 H), 7.51 (d, J = 8.4 Hz, 2 H), 7.45 (s, 1 H), 6.66 (s, 1 H), 3.81 (s, 3
H), 2.51 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3 + [D6]DMSO): δ =
206.7, 151.1, 147.5, 140.8, 134.1, 131.7, 129.0, 128.9, 127.6, 116.3,
108.9, 55.7, 30.5 ppm. HRMS (ESI-TOF): calcd. for C15H13BrO5S [M +
Na]+ 406.9559; found 406.9614.
[7]
[8]
a) E. J. Emmett, B. R. Hayter, M. C. Willis, Angew. Chem. Int. Ed. 2013, 52,
12679; Angew. Chem. 2013, 125, 12911; b) A. Shavnya, K. D. Hesp, V.
Mascitti, A. C. Smith, Angew. Chem. Int. Ed. 2015, 54, 13571; Angew. Chem.
2015, 127, 13775.
V. G. Pandya, S. B. Mhaske, Org. Lett. 2014, 16, 3836.
Y. Yang, Z. Chen, Y. Rao, Chem. Commun. 2014, 50, 1503.
2,2-Bis(4-methoxyphenyl)-5-methyl-6-tosylbenzo[1,3]dioxole
(15): Colourless liquid (260 mg, 70 %). 1H NMR (400 MHz, CDCl3):
δ = 7.76–7.73 (m, 3 H), 7.47 (d, J = 8.8 Hz, 4 H), 7.26 (d, J = 8.0 Hz,
2 H), 6.91 (d, J = 8.8 Hz, 4 H), 6.69 (s, 1 H), 3.78 (s, 6 H), 2.38 (s, 3
H), 2.36 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 160.5, 151.4,
143.8, 138.8, 133.9, 131.9, 131.7, 129.7, 128.0, 127.6, 119.2, 113.7,
112.3, 109.6, 55.4, 21.6, 20.1 ppm. HRMS (ESI-TOF): calcd. for
C28H24O6S [M + Na]+ 525.1342; found 525.1362.
[9]
[10]
[11]
[12]
P. K. Shyam, H.-Y. Jang, J. Org. Chem. 2017, 82, 1761.
a) J. H. P. Tyman, Synthetic and Natural Phenols, Elsevier, New York, 1996;
b) W. Li, D. Xie, J. W. Frost, J. Am. Chem. Soc. 2005, 127, 2874.
a) T. V. Hansen, L. Skattebøl, Tetrahedron Lett. 2005, 46, 3357; b) B. Saikia,
P. Borahb, N. B. Chandra, Green Chem. 2015, 17, 4533.
[13]
[14]
2,2-Bis(4-methoxyphenyl)-5-methyl-6-(4-nitrophenyl-
sulfonyl)benzo[1,3]dioxole (16): White solid (224 mg, 65 %). M.p.
a) C. Yuan, Y. Liang, Y. Hernandez, A. Berriochoa, K. N. Houk, D. Siegel,
Nature 2013, 499, 192; b) J. Gallardo-Donaire, R. Martin, J. Am. Chem.
Soc. 2013, 135, 9350; c) F. Yang, K. Rauch, K. Kettelhoit, L. Ackermann,
Angew. Chem. Int. Ed. 2014, 53, 11285; Angew. Chem. 2014, 126, 11467;
d) G. Shan, X. Yang, L. Ma, Y. Rao, Angew. Chem. Int. Ed. 2012, 51, 13070;
Angew. Chem. 2012, 124, 13247; e) J. Serrano-Plana, I. Garcia-Bosch, R.
Miyake, M. Costas, A. Company, Angew. Chem. Int. Ed. 2014, 53, 9608;
Angew. Chem. 2014, 126, 9762; f) Y. Yan, P. Feng, Q.-Z. Zheng, Y.-F. Liang,
J.-F. Lu, Y. Cui, N. Jiao, Angew. Chem. Int. Ed. 2013, 52, 5827; Angew. Chem.
2013, 125, 5939; g) Y.-F. Liang, X. Wang, Y. Yuan, Y. Liang, X. Li, N. Jiao,
ACS Catal. 2015, 5, 6148; h) C. Huang, N. Ghavtadze, B. Chattopadhyaya,
V. Gevorgyan, J. Am. Chem. Soc. 2011, 133, 17630.
Y.-F. Liang, X. Li, X. Wang, M. Zou, C. Tang, Y. Liang, S. Song, N. Jiao, J.
Am. Chem. Soc. 2016, 138, 12271.
See ref.[12b]
a) D. Nematollahi, R. Rahchamani, Tetrahedron Lett. 2002, 43, 147; b) D.
Nematollahi, D. Habibi, A. Alizadeh, Phosphorus Sulfur Silicon Relat. Elem.
2006, 181, 1391; c) H. Beiginejad, D. Nematollahi, F. Varmaghani, M. Ba-
yat, H. Salehzadeh, J. Electrochem. Soc. 2013, 160, G3001.
1
206–207 °C. H NMR (400 MHz, CDCl3): δ = 8.31 (d, J = 6.8 Hz, 2 H),
8.01 (d, J = 9.2 Hz, 2 H), 7.73 (s, 1 H), 7.45 (d, J = 6.8 Hz, 4 H), 6.89
(d, J = 8.8 Hz, 4 H), 6.72 (s, 1 H), 3.81 (s, 6 H), 2.34 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 160.4, 152.1, 150.0, 147.5, 146.2, 134.4,
131.2, 129.6, 128.6, 127.8, 124.3, 119.6, 113.6, 112.4, 109.7, 55.4,
19.9 ppm. HRMS (ESI-TOF): calcd. for C28H24O6S [M + Na]+ 556.1036;
found 556.1037.
Acknowledgments
[15]
We sincerely thank the Science and Engineering Research Board
(SERB), New Delhi for financial support, and the Department of
Science and Technology (DST), FIST program for the HRMS facil-
ity. N. T. thanks the Ministry of Human Resource Development
(MHRD) for a research fellowship.
[16]
[17]
[18]
[19]
a) R. Paulini, C. Lerner, F. Diederich, R. Jakob-Roetne, G. Zürcher, E. Bor-
roni, Helv. Chim. Acta 2006, 89, 1856; b) F. Diederich, R. Jakob-Roetne, C.
Lerner, R. Paulini, US 20050137162 A1, 2005.
a) P.-Y. Ji, M.-Z. Zhang, J.-W. Xu, Y.-F. Liu, C.-C. Guo, J. Org. Chem. 2016,
81, 5181; b) X. Zhao, T. Li, L. Zhanga, K. Lu, Org. Biomol. Chem. 2016, 14,
1131; c) G. Rong, J. Mao, H. Yan, Y. Zheng, G. Zhang, J. Org. Chem. 2015,
80, 4697; d) F.-L. Yang, S.-K. Tian, Tetrahedron Lett. 2017, 58, 457.
a) Y. Yang, L. Tang, S. Zhang, X. Guo, Z. Zha, Z. Wang, Green Chem. 2014,
16, 4106; b) L. Bin, L. Yagin, Y. Linqian, W. Xiaoyu, W. Wanguo, Tetrahedron
2017, 73, 2760.
a) C.-C. Liao, R. K. Peddinti, Acc. Chem. Res. 2002, 35, 856; b) S. K. R.
Parumala, R. K. Peddinti, Org. Lett. 2013, 15, 3546; c) L. Kürti, P. Herczegh,
J. Visy, M. Simonyi, S. Antus, A. Pelter, J. Chem. Soc. Perkin Trans. 1 1999,
379; d) M. Uyanik, N. Sasakura, M. Mizuno, K. Ishihara, ACS Catal. 2017,
7, 872; e) S. Quideau, L. Pouysegu, A.-V. Avellan, D. K. Whelligan, M. A.
Looney, Tetrahedron Lett. 2001, 42, 7393; f) L. Ttoian-Gautier, J. D. Winte,
P. Gerbaux, C. Moucheron, J. Org. Chem. 2013, 78, 11096.
Keywords: Sulfur · Sulfones · Synthetic methods · Water
chemistry · Sulfonylation
[1] a) Q. A. Acton (Ed.), Sulfones – Advances in Research and Application,
Scholarly Editions, Atlanta, 2013; b) D. Zheng, R. Mao, Z. Li, J. Wu, Org.
Chem. Front. 2016, 3, 359; c) R. Mao, Z. Yuan, R. Zhang, Y. Ding, X. Fan,
J. Wu, Org. Chem. Front. 2016, 3, 1498; d) D. Zheng, M. Chen, L. Yao, J.
Wu, Org. Chem. Front. 2016, 3, 985; e) A. S. Deeming, C. J. Russell, M. C.
Willis, Angew. Chem. Int. Ed. 2016, 55, 747; Angew. Chem. 2016, 128, 757;
f) N.-W. Liu, S. Liang, G. Manolikakes, Synthesis 2016, 48, 1939.
[2] a) Y. Harrak, G. Casula, J. Basset, G. Rosell, S. Plescia, D. Raffa, M. G. Cusi-
mano, R. Pouplana, M. D. Pujol, J. Med. Chem. 2010, 53, 6560; b) E. C. A.
Brot, D. K. J. Keefe, B. P. Haney, N. Metcalfe, G. J. Palmer, P. K. Isbester
(CeNeRx BioPharma Inc.), US 2008009542 A1, 2008; c) P. F. Schellhammer,
[20]
[21]
Eur. J. Org. Chem. 2017, 5306–5314
www.eurjoc.org
5313
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[22]
[24] L. Alig, J. Alsenz, M. Andjelkovic, S. Bendels, A. Bénardeau, B. Konrad, A.
Bourson, P. David-Pierson, W. Guba, S. Hildbrand, D. Kube, T. Lübbers,
A. V. Mayweg, R. Narquizian, W. Neidhart, M. Nettekoven, J.-M. Plancher,
C. Rocha, M.-R. Evans, S. Röver, G. Schneider, S. Taylor, P. Waldmeier, J.
Med. Chem. 2008, 51, 2115.
a) S. P. Roche, J. A. Porco Jr., Angew. Chem. Int. Ed. 2011, 50, 4068; Angew.
Chem. 2011, 123, 4154; b) Q. Ding, Y. Ye, R. Fan, Synthesis 2013, 45, 1; c)
L. Pouysegu, D. Deffieux, S. Quideau, Tetrahedron 2010, 66, 2235; d) N.
Taneja, R. K. Peddinti, Tetrahedron Lett. 2016, 57, 3958.
[23] CCDC 1552158 (for 7a) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre.
Received: July 25, 2017
Eur. J. Org. Chem. 2017, 5306–5314
www.eurjoc.org
5314
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim