Anionic WS-TEMPO-mediatory electrooxidation of alcohols in water: halide-free oxidation directed towards a totally closed system

Article abstract of DOI:10.1016/j.tetlet.2007.10.088

Electrooxidation of alcohols in water with water-soluble N-oxyl derivatives bearing a sulfonic acid group (anionic WS-TEMPOs) as a mediator proceeded to afford the corresponding ketones and aldehydes in moderate to good yields. The aqueous solution containing WS-TEMPOs could be readily recovered and reused for the electrooxidation of alcohols, thereby providing a totally closed system.

Full text of DOI:10.1016/j.tetlet.2007.10.088

Available online at www.sciencedirect.com
Tetrahedron Letters 48 (2007) 8994–8997
Anionic WS-TEMPO-mediatory electrooxidation of alcohols
in water: halide-free oxidation directed towards
a totally closed system
Koichi Mitsudo, Hiroki Kumagai, Fumiko Takabatake, Jun Kubota and Hideo Tanaka*
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University,
3
-1-1 Tsushima-Naka, Okayama 700-8530, Japan
Received 19 September 2007; revised 15 October 2007; accepted 18 October 2007
Available online 22 October 2007
Abstract—Electrooxidation of alcohols in water with water-soluble N-oxyl derivatives bearing a sulfonic acid group (anionic WS-
TEMPOs) as a mediator proceeded to afford the corresponding ketones and aldehydes in moderate to good yields. The aqueous
solution containing WS-TEMPOs could be readily recovered and reused for the electrooxidation of alcohols, thereby providing
a totally closed system.
ꢀ
2007 Elsevier Ltd. All rights reserved.
Water has received considerable attention as one of the
most desirable reaction media, because it is cheap, safe,
and environment-friendly. From the environmental
ucts could be easily isolated by an extractive workup.
Because 1 that was dissolved in water remained in the
aqueous phase after the extraction, the recovered aque-
ous phase could be reused for electrooxidation (Fig. 1).
Though various primary and secondary alcohols could
be oxidised by the cationic WS-TEMPO mediatory sys-
tem, the addition of NaBr was indispensable for the
reaction, probably because 1 could not be oxidised
directly at the anode owing to the repulsion between
the anode and the cationic TEMPO. Since the addition
of NaBr occasionally causes undesired bromination of
the substrates, an oxidation system without NaBr is
preferable. We can reasonably expect that WS-TEMPO
bearing a sulfonic acid group as an anionic hydrophilic
1
point of view, we developed an interest in the electrooxi-
2
dative transformation system in water, which provides
a totally closed system. For instance, we have developed
electrooxidation systems for alcohols in aqueous media
3
dispersed with N-oxyl-immobilised silica gel or polymer
4
particles. Both the dispersed phase and dispersion med-
ia could easily be recovered and reused. Recently, we
developed an electrooxidation system in aqueous NaBr
using a water-soluble N-oxyl derivative (cationic WS-
TEMPO 1) bearing an ammonium group as a cationic
5
hydrophilic moiety. In the system, the oxidised prod-
OH
Organic Solvent
R
R'
Evaporation
O
Ultrasound
Irradiation
Org. phase
Extraction (Product)
R
R'
Aq.phase
WS-TEMPO
Aq. phase
WS-TEMPO
Alcohol
WS-TEMPO
Electrolysis
Figure 1. A totally closed system using WS-TEMPO for the electrooxidation of alcohols in water.
Keywords: Electrooxidation; Alcohol; Water-soluble mediator; N-Oxyl; TEMPO; Water.
*
Corresponding author. Tel.: +81 86 251 8072; fax: +81 86 251 8079; e-mail: tanaka95@cc.okayama-u.ac.jp
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.088

K. Mitsudo et al. / Tetrahedron Letters 48 (2007) 8994–8997
8995
a
moiety (anionic WS-TEMPO) should be brought into
Table 2. Electrooxidation of 3a with a variety of electrolytes
direct contact with an anode, and the oxidation using
anionic WS-TEMPO as a mediator should proceed
smoothly without the addition of NaBr. In this study,
we report an electrooxidation system for alcohols using
anionic WS-TEMPO 2 as a mediator. (see Schemes 1
and 2).
2
a or 2b (10 mol %)
OH
O
electrolyte (0.1 M)
H O, room temp.
2
undivided cell, (Pt)-(Pt)
6
,7
Cl
Cl
30 mA, 2.5 F/mol
3a
4a
b
Entry
Mediator
Electrolyte
Conv. (%)
Yield (%)
We first conducted the WS-TEMPO 2a/2b-mediatory
electrooxidation of benzylic alcohol 3a in distilled water,
and found that the reaction proceeded without NaBr as
expected (Table 1). When 2.5 F/mol of electricity was
passed through an aqueous solution of 3a, the oxidation
reaction proceeded to afford the corresponding ketone
1
2
3
4
5
6
7
8
9
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
—
—
LiClO
LiClO
NaClO4
NaClO
63
63
62
72
53
64
51
87
69
94
58
57
61
68
51
63
45
83
58
90
4
4
4
4a without the addition of NaBr (entries 1 and 2). With
4.5 F/mol of electricity, 3a was entirely consumed and
4a was obtained in 92% (using 2a, entry 5) and 95%
Et
4
Et
4
Et
4
Et
4
NOTs
NOTs
NClO
NClO
4
4
1
0
(
using 2b, entry 6) yields, respectively.
a
In the presence of 2, benzylic alcohol 3a (1.0 mmol) was oxidised
electrochemically in aq 0.1 M supporting electrolyte solution at room
temperature (30 mA, 2.5 F/mol).
With regard to the abovementioned syntheses, the cur-
rent efficiency of the electrooxidation method was unsat-
isfactory. To enhance the efficiency of the reaction,
further optimisation of the anionic WS-TEMPO-media-
tory electrooxidation system was carried out. During the
course of this study, we found that the efficiency of the
b
Isolated yield.
2b was used as a mediator, the yield of 4a drastically
changed due to the addition of the electrolyte. Several
types of electrolytes were employed for the electrooxida-
tion of 3a. LiClO and NaClO were not effective for the
2
-mediatory electrooxidation was highly influenced by
the supporting electrolyte (Table 2). In particular, when
4
4
reaction. By the addition of LiClO or NaClO , the yield
4
4
of 4a slightly increased to 68% and 63%, respectively
entries 4 and 6). Quaternary ammonium salts were
found to be suitable for the oxidation. By using
(
Et
N
H
N
Et
Et NOTs, 4a was obtained in 83% yield (entry 8), and
the optimum yield of 4a (90%) was obtained when
Et
4
O
N
O
Br
1
employing Et NClO (entry 10).
4
4
Scheme 1. Cationic WS-TEMPO 1.
Recently, we found that the formation of a nanoemul-
sion complex of TEMPO and amphiphilic alcohols
enhances the reactivity of the electrooxidation of
H
N
H
N
8
-
-O3S
alcohols in water. We assumed that a similar phenom-
O S
3
enon would occur in the anionic WS-TEMPO-media-
tory electrooxidation of alcohols, that is, the anionic
WS-TEMPO might form an anionic oil-in-water emul-
sion including benzylic alcohol, and the attractive force
between the sulfonate ion and the positive charge of
anode would facilitate direct electron transfer from the
N-oxyl moiety to the anode (Fig. 2). The high reactivity
of WS-TEMPO 2b was probably caused by the high
stability of the nanoemulsion formed by 2b, which has
a long hydrophobic alkyl chain.
H+
O
H+
O
N
N
O
O
2b
2
a
Scheme 2. Anionic WS-TEMPOs 2a and 2b.
Table 1. WS-TEMPO-mediatory electrooxidation of benzylic alcohol
a
3a
OH
O
2
a or 2b (10 mol %)
H O, room temp.
undivided cell, (Pt)-(Pt)
2
Similar to 1, 2a and 2b were found to remain intact in
the aqueous solution after the extractive workup pro-
cess, and the aqueous phase containing 2a or 2b could
be reused. The recycle use of the aqueous phase contain-
ing 2b is shown in Figure 3. After the first run, the elec-
trooxidation of 3a using the recovered aqueous solution
of 2b was carried out to afford 4a in 95% yield. The same
process was repeated for a total of five times. The yield
of 3a varied in the range of 80–95%; these results showed
that the aqueous solution of 2b could be reused.
Cl
Cl
3
0 mA
3
a
4a
b
Entry Mediator Electricity (F/mol) Conv. (%) Yield (%)
1
2
3
4
5
6
2a
2b
2a
2b
2a
2b
2.5
2.5
3.5
3.5
4.5
4.5
63
63
100
100
100
100
58
57
77
86
92
95
a
In the presence of 2 (10 mol %), 3 (1.0 mmol) was oxidised electro-
chemically in distilled water at room temperature (30 mA).
Isolated yield.
Finally, the 2b-mediatory electrooxidation of several
b
9
alcohols was carried out in water (Table 3). The

8996
K. Mitsudo et al. / Tetrahedron Letters 48 (2007) 8994–8997
SO3-
100
9
0
0
-O3S
SO3-
SO3-
8
N
O
70
-O3S
6
0
0
+
+
+
+
+
+
anionic
5
emulsion
-O3S
-
SO3
40
30
SO3-
2
0
0
0
1
direct
electrooxidation
1
2
3
4
5
run
+
+
+
+
+
+
e-
SO3-
4 4
Figure 3. Recycle use of the Et NClO solution containing 2b.
-O3S
SO3-
SO3-
SO3-
N
O
-
3
O S
of 3a, the reaction of benzylic alcohols, which do not have
an electron-withdrawing group, proceeded smoothly in
water, without the addition of an electrolyte. Several
primary and secondary benzylic alcohols bearing elec-
tron-donating groups were electrooxidised under similar
conditions, and the corresponding carbonyl compounds
were obtained in good to high yields (entries 2–4). It is
noteworthy that the oxidation of (4-methoxyphenyl)-1-
ethanol, which was partially brominated by electrooxida-
tion using NaBr, was not accompanied by side-reactions,
anode
anionic
emulsion
-O3S
SO3-
Figure 2. Plausible mechanism of oxidation of anionic WS-TEMPO at
anode.
electrooxidation of 1-phenyl-1-propanol (3b) in water
gave 4b in 81% yield (entry 1). In contrast to the reaction
a
Table 3. 2b-Mediatory electrooxidation of several alcohols
OH
2b (10 mol %)
O
H O, room temp.
undivided cell,( Pt)-(Pt)
2
Ar
R
Ar
R
3
30 mA, 2.5F/mol
4
b
Entry
1
Alcohol
OH
Product
Yield (%)
O
81
3b
4b
OH
O
c
2
91
MeO
3c
MeO
4c
OH
O
3
4
5
88
87
63
t-Bu
3d
OH
t-Bu
4d
O
H
MeO
3e
MeO
4e
OH
OH
O
3
f
4f
O
6
22
3
g
4g
a
b
c
2
In the presence of 2b (10 mol %), 3 (1.0 mmol) was oxidised electrochemically in H O at room temperature (30 mA, 2.5 F/mol).
Isolated yield.
2a can also be utilized (92% yield).

K. Mitsudo et al. / Tetrahedron Letters 48 (2007) 8994–8997
8997
and the desired ketone 4c was obtained as the
sole product (91% yield, entry 2). The electrooxidation
of solid benzylic alcohol 3g hardly proceeded, and the
desired ketone 4g was obtained only in 22% yield (entry
5. Kubota, J.; Shimizu, Y.; Mitsudo, K.; Tanaka, H. Tetra-
hedron Lett. 2005, 46, 8975.
6
. WS-TEMPO 2a was prepared according to the literature
procedure, see: Akutsu, H.; Yamada, J.; Nakatsuji, S.
Chem. Lett. 2003, 32, 1118.
5
); this was probably due to the difficulty in the formation
7
. WS-TEMPO 2b was prepared as follows: To a solution of
of the emulsion complex of WS-TEMPO including
the benzylic alcohol.
4
1
-(6-bromohexanoylamino)-2,2,6,6-tetramethylpiperidine-
-oxyl (1000 mg, 2.9 mmol) in EtOH (18 mL) was added
2 3 2
dropwise a solution of Na SO (378 mg, 3.0 mmol) in H O
In summary, the 2a- or 2b-mediatory electrooxidation of
benzylic alcohols was found to proceed smoothly with-
out the addition of NaBr, and the corresponding
carbonyl compounds were obtained selectively. The
aqueous phase recovered after the oxidation reaction
contained 2, and could be reused for the next electrooxi-
dation reaction. The further study of the anionic WS-
TEMPO-mediatory electrooxidation is in progress in
our laboratory.
(6 mL) and stirred at 70 ꢁC for 3 h. After cooling to room
temperature, the mixture was concentrated under reduced
pressure. The residue was purified by column chromato-
graphy on silica gel (CH
2 2
Cl /MeOH 5:1) to afford 6-(2,2,6,
6
-tetramethyl-piperidin-1-oxyl-4-ylamino)-6-oxohexane-1-
1
sulfonic acid 2b (529 mg, 52%). H NMR (200 MHz,
CD OD) d 1.17 (d, J = 3.2 Hz, 12H), 1.25–1.77 (m, 10H),
.16 (t, J = 7.7 Hz, 2H), 2.80 (t, J = 7.7 Hz, 2H), 4.00–4.10
3
2
13
(
m, 1H); C NMR (150 MHz, CDCl ) d 20.3, 25.6, 26.6,
3
2
2
9.1, 32.5, 36.8, 41.9, 45.8, 52.3, 60.3, 175.1; IR (KBr) 3449,
À1
978, 1648, 1221, 1042 cm
.
Anal. Calcd for
C H N O S: C, 51.55; H, 8.36; N, 8.02. Found: C,
Acknowledgements
15 29
2
5
5
1.50; H, 7.86; N, 8.45.
This research was supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. We
thank the SC-NMR Laboratory of Okayama University
H
N
Na SO (1.1 equiv)
2 3
Br
O
N
0 oC, 3 h
7
O
1
13
for H and C NMR analysis.
References and notes
. For reviews, see: (a) Li, C.-J. Chem. Rev. 1993, 93, 2023; (b)
H
N
HO S
3
O
N
O
2
b
1
5
2%
Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media;
John Wiley & Sons, Inc.: New York, 1997; (c) Grieco, P. A.
Organic Synthesis in Water; Blackie Academic & Profes-
sional: London, 1998.
8. Yoshida, T.; Kuroboshi, M.; Oshitani, J.; Goto, K.;
Tanaka, H. Synlett 2007, 2691.
2
. For the electrooxidation of alcohols in homogeneous
aqueous media, see: (a) Shono, T.; Matsumura, Y.;
Hayashi, J.; Mizoguchi, M. Tetrahedron Lett. 1979, 20,
9. The typical procedure of the electrooxidation is as follows:
In a beaker-type undivided cell was placed a mixture of
1-(4-methoxyphenyl)ethanol 3c (152 mg, 1.0 mmol) and 2b
1
65; (b) Moyer, B. A.; Thompson, M. S.; Meyer, T. J. J.
(35 mg, 0.10 mmol) in H O (8 mL). Two platinum elec-
2
2
Am. Chem. Soc. 1980, 102, 2310.
trodes were immersed in the mixture (1.5 · 1.0 cm ), and
the entire apparatus was sonicated for 10 min. Sub-
sequently, constant current electrolysis was carried out at
room temperature with vigorous stirring until 2.5 F/mol of
electricity was passed. After the electrolysis, the mixture
was extracted with EtOAc (4 · 15 mL). The combined
3
4
. (a) Tanaka, H.; Kawakami, Y.; Goto, K.; Kuroboshi, M.
Tetrahedron Lett. 2001, 42, 445; (b) Tanaka, H.; Chou, J.;
Mine, M.; Kuroboshi, M. Bull. Chem. Soc. Jpn. 2004, 77,
1
745.
. (a) Tanaka, H.; Kubota, J.; Itogawa, S.; Ido, T.; Kuro-
boshi, M.; Shimamura, K.; Uchida, T. Synlett 2003, 951;
2 4
organic phase was dried over Na SO and concentrated
(
b) Tanaka, H.; Kubota, J.; Miyahara, S.; Kuroboshi, M.
under reduced pressure. The residue was purified by column
chromatography on silica gel (hexane/EtOAc 5:1) to afford
1-(4-methoxyphenyl)ethanone 4c (137 mg, 91%).
Bull. Chem. Soc. Jpn. 2005, 78, 1677; (c) Kubota, J.; Ido, T.;
Kuroboshi, M.; Tanaka, H.; Uchida, T.; Shimamura, K.
Tetrahedron 2006, 62, 4769.