Electrochemical oxidation of aminophenols in the presence of benzenesulfinate

Article abstract of DOI:10.1016/j.tet.2012.11.005

The anodic oxidation of aminophenols and their amino-protected derivatives was investigated by using cyclic voltammetry and preparative electrolysis methods. The results showed that like the catechols the amino-protected aminophenol could also undergo Michael addition, and that the benzenesulfonate group was regioselectively introduced at the meta-position of the amino group. In contrast, the expected products were not formed from the oxidation of unprotected aminophenols. Finally, a reaction mechanism is proposed.

Full text of DOI:10.1016/j.tet.2012.11.005

Tetrahedron 69 (2013) 658e663
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Electrochemical oxidation of aminophenols in the presence
of benzenesulfinate
,
a
Huan-Lan Xiao a, Cheng-Wen Yang a, Ni-Tao Zhang a, Cheng-Chu Zeng a , Li-Ming Hu ,
*
Hong-Yu Tian b, R. Daniel Little c
a College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China
b School of Food Chemistry, Beijing Technology and Business University, Beijing 100048, China
c Department of Chemistry & Biochemistry, University of California Santa Barbara, Santa Barbara, CA 93106, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 July 2012
Received in revised form 10 October 2012
Accepted 2 November 2012
Available online 8 November 2012
The anodic oxidation of aminophenols and their amino-protected derivatives was investigated by using
cyclic voltammetry and preparative electrolysis methods. The results showed that like the catechols the
amino-protected aminophenol could also undergo Michael addition, and that the benzenesulfonate
group was regioselectively introduced at the meta-position of the amino group. In contrast, the expected
products were not formed from the oxidation of unprotected aminophenols. Finally, a reaction mecha-
nism is proposed.
Keywords:
Electrochemical synthesis
Aminophenol
Ó 2012 Elsevier Ltd. All rights reserved.
S-Nucleophiles
Michael addition
1. Introduction
synthesis of coumestan using an anodic oxidation of catechols.
Later, Nematollahi6 studied the mechanism by cyclic voltammetry
Oxidative dearomatization of ortho- and para-substituted phe-
nols produces cyclohexadienones, substances that have been widely
used in the synthesis of natural products and other materials.1
Frequently, various oxidizing systems based on heavy metals2 and
organic oxidants3 have been utilized in their construction. Chemo-
and regioselective oxidative dearomatization using less toxic organic
oxidants, such as hypervalent iodine reagents (including PhI(OAc)2
and PhI(OTf)2) have received attention recently; these processes
occur under mild conditions.4 Forexample, para-substituted phenols
are oxidatively dearomatized using PhI(OAc)2 as the oxidant, com-
bining an amine-catalyzed enantioselective desymmetrizing
Michael addition, to form highly functionalized polycyclic mole-
cules.4d In addition, ortho-substituted phenols were oxidatively
dearomatized to produce chiral o-benquinol, which was further used
in the synthesis of the natural product called biscarvacrol.4e The
underlying mechanisms for each of these examples involve the in
situ formation of cyclohexadienones and a sequent Michael reaction.
Electrochemical oxidation, using the electron as a reagent,
provides an alternative approach for the oxidative dearomatization
of electron-rich catechols, that frequently follows environmentally
benign practices. Tabakovic5 first reported the electrochemical
and synthesized a variety of polyhydroxylated aromatics. In recent
years, our interest in the potential HIV integrase inhibitory activity
of polyhydroxylated aromatics has led us to investigate the anodic
oxidation of catechols in the presence of S-,7 C-mononucleophiles8
and C,N-dinucleophiles,9 leading to the electrochemical synthesis
of substituted catechols and fused indole derivatives containing
free hydroxyl groups.
Considering that electron rich benzene derivatives, including
the o-aminophenols and p-aminophenols, could possibly form
iminocyclohexadienone structures (i.e., analogues of cyclo-
hexadienone)10 upon oxidative dearomatization, we reasoned that
they may undergo Michael addition in a manner analogous to the
chemistry observed for catechols. To explore such a hypothesis, we
report herein the in situ anodic oxidation of amino-(un)protected
aminophenol (1aed and 2a,b) in the presence of benzenesulfinate
as nucleophiles (Fig. 1). The results indicate that similar reactions
do occur for the amino-protected aminophenols.
2. Results and discussion
2.1. Cyclic voltammetric studies
The electrochemical behaviour of aminophenols (1a,b and 2a)
and their corresponding amino-protected derivatives (1c,d and 2b)
* Corresponding author. Fax: þ86 10 67392001; e-mail address: zengcc@bjut.edu.cn
(C.-C. Zeng).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.005

H.-L. Xiao et al. / Tetrahedron 69 (2013) 658e663
659
hydroxylation or dimerization reactions are too slow to be observed
on the time scale of the cyclic voltammetry experiment.5e9 The
amino-protected aminophenols 1c and 1d also exhibited reversible
electrochemical behaviour. Compared with p-aminophenols 1a and
1b, the potentials of amino-protected p-aminophenols 1c and 1d
shift positively, with the oxidation peak potential and reduction
peak potential at 0.57 V and 0.13 V for 1c and at 0.56 V and 0.11 V for
1d, respectively, due to the inductive effect of the tosyl group.
Next, o-aminophenols 2a and 2b were investigated in the
absence of benzenesulfinate; the results indicate that CVs of all
o-aminophenol derivatives, including o-aminophenol (2a) and
amino-protected o-aminophenols 2b exhibit an irreversible redox
couple, a behaviour that is quite different from that of the p-ami-
nophenols. As shown in Fig. 2 and Table 1, upon scanning anodi-
cally, 2a exhibits two irreversible oxidation waves at þ0.36 V and
þ0.99 V versus Ag/AgCl (KCl 3 M). Similarly, the irreversible
oxidation wave of 2b is ‘centered’ at about 0.55 versus Ag/AgCl (KCl
3 M). These results clearly demonstrate that, the in situ generated
intermediate from o-aminophenols 2a or 2b are not stable under
the reaction conditions and undergo chemical reaction(s) even on
the time scale of CV, regardless of whether the amino group is
protected or not.
Fig. 1. Structures of starting aminophenols 1aed and 2a,b.
in the absence and presence of benzenesulfinate was firstly ex-
amined by cyclic voltammetry (CV) carried out at room tempera-
ture in a mixed solution of acetonitrile and water containing 0.2 M
acetate buffer (pH 7.0) as the supporting electrolyte. For compari-
son, catechol was also investigated. The CV results are summarized
in Table 1 and typical CVs are shown in Fig. 2.
Table 1
Oxidation and reduction potentials of aminophenols and catechola
In addition, for comparison, the CV of catechol was also
investigated. Similar to previous reports,5e7 it gives a reversible
oxidation peak at 0.48 V versus Ag/AgCl and a reduction peak at
0.04 V versus Ag/AgCl.
Entry
Compounds
Ep (ox)
Ep (red)
1
2
3
4
5
6
7
1a
1b
1c
1d
2a
2b
Catechol
0.25
0.22
0.57
0.56
0.36, 0.99
0.55
0.48
0.02
ꢀ0.01
0.13
0.11
d
Finally, the electrochemical oxidation of amino-protected ami-
nophenol in the presence of benzenesulfinate was investigated. As
shown in Fig. 3 using 1c as an example, when 1 equiv amount of
benzenesulfinate 3a was added to the solution of 1c, the voltam-
mogram of the mixture exhibits two anodic peaks A1 (þ0.55 V vs
Ag/AgCl) and A2 (þ1.02 V vs Ag/AgCl), whereas the cathodic peak
shift to 0.10 V versus Ag/AgCl and its cathodic current decreases
dramatically (curve c, Fig. 3). Curve b in Fig. 3 is the CV of benze-
nesulfinate 3a, where one irreversible anodic wave at 0.84 V is
observed. The behaviour that the cathodic current decreases in-
dicates a chemical reaction occurs between the electrochemically
generated iminocyclohexadienone intermediate and benzene-
sulfinate, and therefore Michael addition products may be formed
upon anodic oxidation of a mixture of amino-protected amino-
phenol and benzenesulfinate when the electrolyzed potential was
controlled at the anodic potential of amino-protected aminophenol
d
0.04
a
Concentration of substrates: 1 mM; electrolyte: 0.2 M acetate buffer solution/
acetonitrile (3:1 (v/v), pH 7); working electrode: glassy carbon; reference electrode:
Ag/AgCl (3 M); scan rate: 100 mV/s.
Fig. 2. Cyclic voltammograms of 2 mM of o-aminophenol (2a), N-(2-hydroxyphenyl)-
4-methylbenzenesulfonamide (2b), p-aminophenol (1a), N-(4-hydroxyphenyl)-4-
methylbenzenesulfonamide (1c) and catechol at a glassy carbon working electrode,
platinum wire counter and Ag/AgCl reference electrodes, in a mixed solution of acetate
buffer (0.2 M, pH 7) and acetonitrile (v/v¼3:1), scan rate: 100 mV/s.
As shown in Fig. 2, the CV of 1a exhibits a reversible oxidation
wave at 0.25 V versus Ag/AgCl (KCl 3 M) when scanning anodically,
and a reduction peak at 0.02 V during the reverse scan. In the case
of 1b, a similar reversible CV was observed; the oxidation and re-
duction peaks were located at 0.22 V and ꢀ0.01 V versus Ag/AgCl.
Moreover, the ratio of the current amplitudes for the oxidation and
reduction processes, Iopx/Ipred, was equal to unity indicating that the
in situ formed iminocyclohexadienone intermediates are stable
under pH 7 acetate buffer, and that the side-reactions, such as
Fig. 3. Cyclic voltammograms of N-(4-hydroxyphenyl)-4-methylbenzenesulfonamide
(1c), 2 mM of sodium benzenesulfinate (3a) and a mixture of 2 mM of 1c and 2 mM
of 3a, at a glassy carbon working electrode, platinum wire counter and Ag/AgCl (3.0 M)
reference electrodes, in a mixed solution of acetate buffer (0.2 M, pH 7) and acetonitrile
(v/v¼3:1), scan rate: 100 mV/s.

660
H.-L. Xiao et al. / Tetrahedron 69 (2013) 658e663
(0.55 V vs Ag/AgCl for 1c), where, undesired oxidation of benze-
nesulfinate will not take place due to their significantly higher
anodic potentials (0.84 V vs 0.55 V).
R1
SO2Na
R1
OH
OH
3
In a word, the electrochemical behaviour of the p-amino-
phenols, including their derivatives where the amino group is
protected, display a reactivity pattern that is similar to catechol,
whereas, o-aminophenols are quite different and their in situ
generated intermediate(s) are less stable than those derived from
catechol.
S
NHTs
NHTs
CPE at 0.4 V vs Ag wire
Acetate buffer/CH3CN
O
O
2b
4e-f
4e: R1 = H ( 51%)
4f: R1 = CH3 ( 56%)
Scheme 2. Anodic oxidation of 2b in the presence of sodium benzenesulfonate 3.
2.2. Electrochemical oxidation of the aminophenols in the
presence of sodium benzenesulfonate
hexadienones and nucleophiles would proceed when the imino-
cyclohexadienone was generated from p-aminophenols (1a and 1b)
and o-aminophenol (2a) wherein the amino group is not protected.
Therefore, 1a, 1b and 2a were subjected to oxidation under
the conditions used for the oxidation of 1c; it was observed that
the initial current, which was more than 50 mA, soon decreased to
less than 5 mA. With the passing of current, polymer formed on
the anode surface. After the consumption of starting aminophenols,
none of the expected products, 4gei, were detected by TLC
(Scheme 3).
After carrying out CV analysis of aminophenols, we then turned
our attention to the preparative electrolysis. The amino-protected
p-aminophenols were firstly subjected to anodic oxidation in the
presence of nucleophiles; thus, a solution of an equivalent of N-(4-
hydroxyphenyl)-4-methylbenzenesulfonamide (1c) and sodium
benzenesulfinate (3a) was electrolyzed at a controlled potential of
0.4 V versus Ag wire (w0.6 V vs Ag/AgCl) (Scheme 1). Due to the
It is noteworthy that structurally, compounds 4 are 1,4-Michael
addition products. Note that the benzenesulfinate group is
positioned at meta to the amino group. In principle, two possible
products may be formed from the Michael addition of iminocyclo-
hexadienone due to its asymmetrical structure. Take the reaction of
2b and 3b as an example, the in situ formed iminocyclohexadienone
may undergo Michael addition to form 4f and 4f0. However, the
result indicates the exclusive formation of 4f (Scheme 4). This was
demonstrated from the 1H NMR spectrum of reaction product. As
shown in Fig. 4, the doublet at 6.88 ppm with coupling constant of
8.4 Hz and the double doublet at 7.47 ppm with coupling constant of
8.4 Hz and 2.4 Hz, comprises an AB system, and the doublet at
6.88 ppm is assigned to the proton signal next to the phenolic
hydroxy group of aminophenol unit due to its high field shift. The
doublet at 7.64 ppm with coupling constant of 2.4 Hz, is ascribed to
be the signal of aromatic proton next to amino group of amino-
phenol unit; it is spin coupled by the proton at 7.47 ppm (4J).
Therefore, the structure of the product is assignedas 4f. In contrast, if
the structure of the product was 4f0, the signal of the proton next to
the phenolic hydroxy should be doublet situated at high field with
a small coupling constant, about 2.4 Hz. The regioselective Michael
addition is consistent with a previous literature report.11
From the mechanistic viewpoint, the formation of compounds 4
can be proposed to arise via an EC mechanism on the basis of the
above CV analysis and preparative electrolysis results, as well as
related reported results.6e9 As shown in Scheme 5, the anodic
oxidation of aminophenols 1 and 2 in aqueous medium leads to the
formation of the corresponding iminocyclohexadienone 5 or 6.10
The active intermediate diffuses to the bulk solution and reacts as
Michael acceptor with benzenesulfinate to convert to products
after aromatization. Since the products have a higher oxidation
potential than the starting materials and display low solubility in
the supporting electrolyte solution, products 4 precipitate and are
formed exclusively.
Scheme 1. Anodic oxidation of 1c and 1d in the presence of sodium benzenesulfonate 3.
low solubility of 1c, acetonitrile was added as a co-solvent. Ac-
cordingly, a mixed solvent of acetate buffer solution and acetoni-
trile (3:1 ratio of acetate buffer to acetonitrile, pH 7) was used as
supporting electrolyte. As the electrolysis proceeded, the colour of
the anolyte became darker and eventually changed to brown.
Precipitation occurred. Meanwhile the current decreased from an
initial value of 30 mA to less than 2 mA. After filtration, a white
powder was obtained in a 55% yield and was identified to be N-[4-
hydroxy-5-(phenylsulfonyl)phenyl]benzenesulfonamide (4a). The
reaction was also carried out using constant current technique;
however, a complex mixture was generated when the electrolysis
was performed at 10 mA or 20 mA of current. Therefore, the con-
trolled potential technique is preferable for the present case.
Next, the controlled potential electrolysis of 1c was performed in
the presence of 3b, leading to the formation of adduct 4b in a 53%
yield (Scheme 1). Similarly, a reaction also took place for alkyl-
substituted p-aminophenol and better yields were obtained in the
case of N-(4-hydroxy-2-methylphenyl)-4-methylbenzenesulfona
mide (1d). For example, 66% of 4c and 72% of 4d were generated
when 3a and 3b (respectively) were used as a nucleophile to trap
the in situ formed iminocyclohexadienone from 1d.
To determine the limitation and scope of the anodic oxidation of
aminophenols in the presence of sodium benzenesulfonate, we
then investigated the anodic oxidation of amino-protected o-ami-
nophenol. As shown in Scheme 2, the anodic oxidation of 2b in the
presence of 3 gave 4e and 4f in 51% and 56% yields, respectively.
The above results indicate that the iminocyclohexadienones,
generated in situ from the oxidative dearomatization of amino-
phenols 1c, 1d and 2b, systems whose amino groups are protected
by a benzenesulfonyl group, do undergo Michael addition with the
benzenesulfonate. Based upon these observations, we were in-
terested in determining how the reaction between iminocyclo-
3. Conclusion
In summary, in order to determine whether the aminophenols
undergo reactions similar to catechols, the electrochemical
oxidation of aminophenols was studied. It was found that the CVs
of p-aminophenols 1a and 1b, and their amino-protected
derivatives (1c and 1d) exhibited similar CVs and gave reversible
electrochemical oxidation and reduction waves in the absence of
benzenesulfinate, whereas that of o-aminophenols (2a) and its

H.-L. Xiao et al. / Tetrahedron 69 (2013) 658e663
661
Scheme 3. Anodic oxidation of 1a, 1b or 2a in the presence of sodium benzenesulfonate.
Scheme 4. The two possible reaction pathways.
software, using a conventional three-electrode cell. The working
electrode was a glassy carbon disk electrode (ca. ɸ¼3 mm). The
auxiliary and reference electrodes in these studies were Pt and
saturated Ag/AgCl, respectively. Glassy carbon was polished with
a polishing cloth before each measurement. All electrodes for CV
experiments were from CH Instruments, Inc. USA. Acetate buffer
was prepared from NaOAc and HOAc, and the pH was monitored
using a digital pH meter. The scan rate was 50 mV/s. The concen-
tration of 1, 2 and 3 was 2 mmol Lꢀ1, while that of the supporting
electrolyte was 0.2 mol Lꢀ1
.
For controlled potential coulometry (CPC), an ‘H’-type cell, ca-
pacity 100 mL, was equipped with a medium glass frit as a mem-
brane. The anode compartment contained an assembly of six
graphite rods as the anode, whose upper rims were wrapped by
a copper wire, and a polished silver wire as the quasi-reference
electrode, immersed in electrolyte solution in a glass cylinder
with a fine glass frit at its end. A platinum plate (2 cm2) served as
the counter electrode is immersed in the cathode compartment.
The applied potential throughout CPC was 0.6 V versus Ag wire and
controlled by the 273A Potentiostat/Galvanostat. During electroly-
sis, a magnetic stirrer stirred the mixture.
Fig. 4. Partial 1H NMR spectrum of compound 4b.
amino-protected derivatives shown only an irreversible oxidation
wave. These results indicate that under the reaction conditions, the
iminocyclohexadienone intermediates from p-aminophenols are
more stable than those obtained from o-aminophenols. Upon
preparative scale of electrolysis, polymerization was observed in
the cases of the aminophenols themselves. In contrast, Michael
addition products were isolated in moderate yields from amino-
protected aminophenol derivatives. Based on these results, an EC
mechanism was proposed for the formation of compounds 4.
All melting points were measured with a XT4A Electrothermal
melting point apparatus and are uncorrected. IR spectra were
recorded as KBr pellets. 1H and 13C NMR spectra were recorded with
a AV 400M Bruker spectrometer (400 MHz 1H frequency, 100 MHz
13C frequency). Chemical shifts are given as
d values (internal
standard: TMS). The MS spectra (ESI) were recorded on a Bruker
esquire 6000 mass spectrometer. HR-MS (TOF-EI) were recorded on
a GCT CA 127 Micronass UK mass spectrometer.
4-Amino-3-methylphenol 1b and sodium 4-methylbenzenesu-
lfinate 3b were reagent-grade from Alfa Aesar China (Tianjin Co.,
Ltd.), whereas N-(hydroxyphenyl)benzenesulfonamide 1c, 1d and
2b were prepared according to known procedure.12 Other chem-
icals and solvents were from Beijing Chemicals Co. and used
without further purification. Doubly distilled de-ionized water was
used for preparation of aqueous acetate buffer. All experiments
were performed at room temperature and ambient pressure.
4. Experimental section
4.1. Instruments and reagents
Cyclic voltammograms were measured by using a 273A Poten-
tiostat/Galvanostat equipped with electrochemical analysis

662
H.-L. Xiao et al. / Tetrahedron 69 (2013) 658e663
Scheme 5. Proposed mechanism for the conversion of amino-protected aminophenols 1c, 1d and 2b to 4aef.
4.2. General procedure for the synthesis of compounds 4aef
9.45 (br, 1H, NH), 10.77 (br, 1H, OH); 13C NMR (100 MHz, DMSO-d6):
18.5, 21.48, 119.5, 124.3,126.5, 127.4, 128.0, 128.5, 129.3, 130.1, 133.7,
d
To the anode compartment, which is kept in water at room
temperature, was added 60 mL of 0.2 M sodium acetate buffer
(pH¼7) and 30 mL of acetonitrile. Meanwhile, 20 mL of a mixed
solution of sodium acetate buffer and acetonitrile (v/v¼3:1) was
added to the cathode compartment. The electrolyte was pre-
electrolyzed at 0.6 V versus Ag wire to remove impurity till the
current decreased to less than 2 mA. Subsequently, 2 mmol of N-
(hydroxyphenyl)benzenesulfonamide 1c, 1d or 2b and 2 mmol of
sodium benzenesulfinate 3 were added to the cell and electrolysis
was continued. The electrolysis was terminated when the starting
N-(hydroxyphenyl)benzenesulfonamide was consumed as de-
termined by TLC. After electrolysis, the anolyte was neutralized
using acetic acid. The formed precipitate was filtered, washed by
water several times and dried under vacuum to give the desired
compounds 4aef in white powder.
137.4, 141.7, 143.7, 145.1, 154.6; FT-IR (KBr): n 3338, 3256, 1606, 1508,
1450, 1159 cmꢀ1; ESI-MS: m/z 418 [MþH]þ, 834.7 [2MþH]þ; HREI-
MS: m/z calcd for C20H19NO5S2 [M]þ 417.0705, found 417.0710.
4.2.4. N-[4-Hydroxy-2-methyl-5-(4-methylphenylsulfonyl)phenyl]-
4-methylbenzenesulfonamide (4d). Yield 72%; mp: 200e201 ꢁC
(dec); 1H NMR (400 MHz, DMSO-d6):
d 2.02 (s, 3H, CH3), 2.38 (s, 3H,
CH3), 2.42 (s, 3H, CH3), 6.63 (s, 1H, AreH), 7.25 (s, 1H, AreH), 7.38 (d,
2H, J¼8.8 Hz, AreH), 7.41 (d, 2H, J¼9.2 Hz, AreH), 7.52 (d, 2H,
J¼8.0 Hz, AreH), 7.57 (d, 2H, J¼8.0 Hz, AreH), 9.41 (br, 1H, NH),
10.73 (br, 1H, OH); 13C NMR (100 MHz, DMSO-d6):
d 18.5, 21.5, 119.5,
124.5, 126.2, 127.4, 128.1, 128.5, 129.7, 130.1, 137.4, 138.9, 143.6, 144.1,
144.9, 154.9; FT-IR (KBr): n ;
3367, 3275, 1612, 1597, 1383, 1181 cmꢀ1
ESI-MS: m/z 431.9 [MþH]þ, 862.8 [2MþH]þ; HREI-MS: m/z calcd for
C21H21NO5S2 [M]þ 431.0861, found 431.0868.
4.2.1. N-[4-Hydroxy-3-(phenylsulfonyl)phenyl]-4-methylbenzenesulf
4.2.5. N-[2-Hydroxy-5-(phenylsulfonyl)phenyl]-4-methylbenzenesulf
onamide (4a). Yield 55%; mp: 184e185 ꢁC (dec); 1H NMR (400 MHz,
onamide (4e). Yield 51%; mp: 105e106 ꢁC (dec); 1H NMR (400 MHz,
DMSO-d6):
d
2.36 (s, 3H, CH3), 6.78 (d, 1H, J¼8.8 Hz, AreH), 7.20 (dd,
DMSO-d6):
d
2.34 (s, 3H, CH3), 6.89 (d, 1H, J¼8.4 Hz, AreH), 7.29 (d,
1H, J¼8.8, 2.4 Hz, AreH), 7.36 (d, 2H, J¼8.0 Hz, AreH), 7.55e7.59 (m,
5H, AreH), 7.66 (t, 1H, J¼7.6 Hz, AreH), 7.72 (d, 2H, J¼7.2 Hz, AreH),
10.01 (br,1H, NH),10.70 (br,1H, OH); 13C NMR (100 MHz, DMSO-d6):
2H, J¼8.0 Hz, AreH), 7.51 (dd, 2H, J¼8.4, 2.4 Hz, AreH), 7.56e7.78 (m,
8H, AreH), 9.64 (br, 1H, NH), 10.98 (br, 1H, OH); 13C NMR (100 MHz,
DMSO-d6): d 21.4, 116.5, 122.6, 125.9, 126.1, 127.2, 127.2, 130.0, 130.1,
d
21.4,118.7,122.8,126.6,127.3,128.3,129.3,130.0,130.1,130.5,133.8,
131.1, 133.7, 137.4, 142.4, 143.7, 154.7; FT-IR (KBr): n 3557, 3485, 3237,
136.5,141.4,144.3, 153.5; FT-IR (KBr):
n
3390, 3254,1596,1504,1466,
1587, 1508, 1461 cmꢀ1; ESI-MS: m/z 401.8 [MꢀH]ꢀ, 425.7 [MþNa]þ;
1163 cmꢀ1; ESI-MS: m/z 403.9 [MþH]þ, 806.8 [2MþH]þ; HREI-MS:
HREI-MS:m/zcalcd forC19H17NO5S2 [M]þ 403.0548, found403.0552.
m/z calcd for C19H17NO5S2 [M]þ 403.0548, found 403.0550.
4.2.6. N-[2-Hydroxy-5-(4-methylphenylsulfonyl)phenyl]-4-methyl-
4.2.2. N-[4-Hydroxy-3-(4-methylphenylsulfonyl)phenyl]-4-methylben
benzenesulfonamide (4f). Yield 56%; mp: 200e201 ꢁC (dec); 1H NMR
(400 MHz, DMSO-d6): d 2.34 (s, 3H, CH3), 2.37 (s, 3H, CH3), 6.88 (d,
zenesulfonamide (4b). Yield 53%; mp: 185e186 ꢁC (dec); 1H NMR
(400 MHz, DMSO-d6):
d
2.37 (s, 6H, CH3), 6.70 (d,1H, J¼8.8 Hz, AreH),
1H, J¼8.4 Hz, AreH), 7.29 (d, 2H, J¼8.0 Hz, AreH), 7.40 (d, 2H,
J¼8.0 Hz, AreH), 7.47 (dd, 2H, J¼8.4, 2.4 Hz, AreH), 7.59 (d, 2H,
J¼8.4 Hz, AreH), 7.64 (d, 2H, J¼8.4 Hz, AreH), 7.64 (d, 1H, J¼2.4 Hz,
AreH), 10.29 (br, 2H, OH and NH); 13C NMR (100 MHz, DMSO-d6):
7.14 (d, 2H, J¼8.0, 2.4 Hz, AreH), 7.36 (d, 4H, J¼8.0 Hz, AreH), 7.51 (d,
1H, J¼8.4 Hz, AreH), 7.55 (d, 2H, J¼8.4 Hz, AreH), 7.60 (d, 2H,
J¼8.0 Hz, AreH), 10.10 (br, 2H, OH and NH); 13C NMR (100 MHz,
DMSO-d6):
d
21.4, 21.4, 118.8, 122.9, 126.8, 127.3, 128.2, 128.7, 129.7,
d 21.4, 21.4, 116.4, 122.4, 125.8, 127.2, 127.3, 130.0, 130.5, 131.5, 137.4,
130.0,130.4,136.6,138.6,143.7,144.2,154.1; FT-IR (KBr):
n
3387, 3254,
139.6,143.7,144.2,154.6; FT-IR (KBr): n 3360, 3269,1595,1507,1446,
1597, 1505, 1395, 1399, 1161, 1145 cmꢀ1; ESI-MS: m/z 415.8 [MꢀH]ꢀ;
1399 cmꢀ1; ESI-MS: m/z 415.8 [MꢀH]ꢀ, 439.9 [MþNa]þ; HREI-MS:
HREI-MS: m/z calcd for C20H19NO5S2 [M]þ 417.0705, found 417.0709.
m/z calcd for C20H19NO5S2 [M]þ 417.0705, found 417.0710.
4.2.3. N-[4-Hydroxy-2-methyl-5-(phenylsulfonyl)phenyl]-4-methylbe
Acknowledgements
nzenesulfonamide (4c). Yield 66%; mp: 243e245 ꢁC (dec); 1H NMR
(400 MHz, DMSO-d6):
d
2.03 (s, 3H, CH3), 2.41 (s, 3H, CH3), 6.65 (s,1H,
This work was supported by grants from the National Basic
Research Program of China (No. 2009CB930200), The National Key
Technology R&D Program (2011BAD23B01), Beijing Natural Science
AreH), 7.28 (s, 1H, AreH), 7.40 (d, 2H, J¼8.0 Hz, AreH), 7.54 (d, 2H,
J¼8.0Hz, AreH), 7.58(t, 2H, J¼7.6 Hz, AreH), 7.65e7.70(m, 3H, AreH),

H.-L. Xiao et al. / Tetrahedron 69 (2013) 658e663
663
queu, K.; Sotiropoulos, J. M.; Quideau, S. Angew. Chem., Int. Ed. 2008, 47,
3552e3555.
Foundation (No. 7112008) and Beijing City Education Committee
(KM201010005009). We also thank Mrs. Jinchao Wei in Institute of
Chemistry, CAS, for the HREI-MS measurement.
5. (a) Grujie, Z.; Tabakovic, I.; Trkovnik, M. Tetrahedron Lett. 1976, 52, 4823e4824;
(b) Tabakovic, I.; Grujie, Z.; Bejtovic, Z. J. Heterocycl. Chem. 1983, 20, 635e638.
6. (a) Golabi, S. M.; Nematollahi, D. J. Electroanal. Chem. 1997, 420, 127e134; (b)
Nematollahi, D.; Rahchamani, R. Tetrahedron Lett. 2001, 43, 147e150; (c)
Nematollahi, D.; Golabi, S. M. J. Electroanal. Chem. 1996, 405, 133e140; (d)
Shahrokhian, S.; Hamzehloei, A. Electrochem. Commun. 2003, 706e710; (e)
Nematollahi, D.; Habibi, D.; Rahmati, M.; Rafiee, M. J. Org. Chem. 2004, 69,
2637e2640; (f) Fakhari, A. R.; Nematollahi, D.; Shamsipur, M.; Makarem, S.;
Davarani, S. S. H.; Alizadeh, A.; Khavasi, H. R. Tetrahedron 2007, 63, 3894e3898.
7. (a) Zeng, C.-C.; Ping, D.-W.; Zhang, S.-C.; Zhong, R.-G.; Becker, J. Y. J. Electroanal.
Chem. 2008, 622, 90e96;(b)Zeng, C.-C.;Liu,C.-F.;Zeng, J.;Zhong,R.-G. J. Electroanal.
Chem. 2007, 608, 85e90; (c) Zeng, C.-C.; Liu, F.-J.; Ping, D.-W.; Hu, L.-M.; Cai, Y.-L.;
Zhong, R.-G. Tetrahedron 2009, 65, 4505e4512; (d) Zeng, C.-C.; Liu, F.-J.; Ping, D.-W.;
Cai, Y.-L.; Zhong, R.-G.; Becker, J. Y. J. Electroanal. Chem. 2009, 625, 131e137.
8. (a) Gao, X.-G.; Yang, C.-W.; Zhang, Z.-Z.; Zeng, C.-C.; Song, X.-Q.; Hu, L.-M.;
Zhong, R.-G.; She, Y.-B. Tetrahedron 2010, 66, 9880e9887.
9. (a) Zeng, C.-C.; Ping, D.-W.; Xu, Y.-S.; Hu, L.-M.; Zhong, R.-G. Eur. J. Org. Chem.
2009, 5832e5840; (b) Zeng, C.-C.; Liu, F.-J.; Ping, D.-W.; Hu, L.-M.; Cai, Y.-L.;
Zhong, R.-G. J. Org. Chem. 2009, 74, 6386e6389; (c) Bai, Y.-X.; Ping, D.-W.; Little,
R. D.; Tian, H.-Y.; Hu, L.-M.; Zeng, C.-C. Tetrahedron 2011, 67, 9334e9341; (d)
Zeng, C.-C.; Ping, D.-W.; Hu, L.-M.; Song, X.-Q.; Zhong, R.-G. Org. Biomol. Chem.
2010, 8, 2465e2472.
10. (a) Jensen, K. L.; Franke, P. T.; Nielsen, L. T.; Daasbjerg, K.; Jørgensen, K. A. Angew.
Chem., Int. Ed. 2010, 49, 129e133; (b) Engler, T. A.; Chai, W.; Latessa, K. O. J. Org.
Chem. 1996, 61, 9297e9308; (c) Engler, T. A.; Wanner, J. J. Org. Chem. 2000, 65,
2444e2457.
References and notes
1. For reviews on the utilization of cyclohexadienone ketals and quinols, see: (a)
ꢀ
Quideau, S.; Pouysegu, L.; Deffieux, D. Synlett 2008, 467e495; (b) Magdziak, D.;
Meek, S. J.; Pettus, T. R. R. Chem. Rev. 2004, 104, 1383e1429.
2. (a) Gong, J.-X.; Lin, G.; Sun, W.-B.; Li, C.-C.; Yang, Z. J. Am. Chem. Soc. 2010, 132,
16745e16746; (b) Green, J. C.; Pettus, T. R. R. J. Am. Chem. Soc. 2011, 133,
1603e1608; (c) Bubb, W. A.; Sternhell, S. Tetrahedron Lett. 1970, 51, 4499e4502;
(d) Hewitt, D. G. J. Chem. Soc. C 1971, 2967e2973; (e) Coutts, I. G. C.; Allcock, R.
W.; Scheeren, H. W. Tetrahedron Lett. 2000, 41, 9105e9107; (f) krohn, K.;
Beckmann, K.; Aust, H. J.; Draeger, S.; Schulz, B.; Busemann, S.; Bingmann, G.
Liebigs. Ann/Recl. 1997, 2531e2534; (g) Imamoto, T.; Sugiura, Y. J. Phys. Org.
Chem. 1989, 2, 93e102; (h) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima,
T.; Kamiya, Y. J. Am. Chem. Soc. 1989, 111, 4392e4398; (i) Clark, D. A.; Riccardis,
F. D.; Nicolaou, K. C. Tetrahedron 1994, 50, 11391e11426.
3. (a) Arzeno, H.; Barton, D. H. R.; Berge-Lurion, R. M.; Lusinchi, X.; Pinto, B. M. J.
Chem. Soc., Perkin Trans. 1 1984, 2069e2076; (b) Barton, D. H. R.; Berge-Lurion,
R. M.; Lusinchi, X.; Pinto, B. M. J. Chem. Soc., Perkin Trans. 1 1984, 2077e2080.
4. (a) Gu, Q.; Rong, Z.-Q.; Zheng, C.; You, S.-L. J. Am. Chem. Soc. 2010, 132,
4056e4057; (b) Nicolaou, K. C.; Li, A.; Edmonds, D. J.; Tria, G. S.; Ellery, S. P. J.
Am. Chem. Soc. 2009, 131, 16905e16918; (c) Matsuura, B. S.; Condie, A. G.; Buff,
R. C.; Karahalis, G. J.; Stephenson, C. R. J. Org. Lett. 2011, 13, 6320e6323; (d) Vo,
N. T.; Pace, R. D. M.; O’Hara, F.; Gaunt, M. J. J. Am. Chem. Soc. 2008, 130,
11. Adams, R.; Whitaker, L. J. Am. Chem. Soc. 1956, 78, 658e660.
12. Kurita, K.; Keisuke. Chem. Ind. (London) 1974, 8, 345e346.
ꢀ
404e405; (e) Pouysegu, L.; Chassaing, S.; Dejugnac, D.; Lamidey, A. M.; Mi-