Oxidation of alcohols with nitroxyl radical resins under two-phase conditions

Article abstract of DOI:10.1055/s-2005-922775

The oxidation of alcohols to carbonyl compounds such as aldehydes and ketones was studied using potassium hexacyanoferrate(III) mediated by nitroxyl radical polystyrene resins as catalyst under organic-aqueous two-phase conditions. Primary alcohols are readily oxidized to the corresponding aldehydes in excellent yield with no overoxidation to carboxylic acids. Secondary alcohols are converted to the corresponding ketones with a much lower efficiency. Oxidative cyclization of 1,4- and 1,5-diols to γ- and δ-lactones, respectively, proceeded nicely. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-922775

LETTER
69
Oxidation of Alcohols with Nitroxyl Radical Resins under Two-Phase
Conditions
a
b
b
O
Y
xidation of Alco
o
w
ith Nit
s
roxyl
R
ad
h
ical Resins itomo Kashiwagi,* Hiroshi Ikezoe, Tetsuya Ono
a
School of Pharmaceutical Sciences, Ohu University, 31-1 Misumido, Tomita-machi, Koriyama, Fukushima 963-8611, Japan
Fax +81(24)9329138; E-mail: y-kashiwagi@pha.ohu-u.ac.jp
b
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan
Received 13 October 2005
Abstract: The oxidation of alcohols to carbonyl compounds such
as aldehydes and ketones was studied using potassium hexacyano-
ferrate(III) mediated by nitroxyl radical polystyrene resins as cata-
lyst under organic–aqueous two-phase conditions. Primary alcohols
are readily oxidized to the corresponding aldehydes in excellent
yield with no overoxidation to carboxylic acids. Secondary alcohols
are converted to the corresponding ketones with a much lower effi-
ciency. Oxidative cyclization of 1,4- and 1,5-diols to g- and d-lac-
tones, respectively, proceeded nicely.
K3[Fe(CN)6]
O
N
N
OH
R
O
R'
O
O
Key words: nitroxyl radical resin, potassium hexacyanofer-
TEMPO PS resin
R
rate(III), alcohol, oxidation, two-phase conditions
K4[Fe(CN)6]
OH
R'
O
N
O
1
Oxoammonium ions are known as nonmetallic oxidizing
reagents of alcohols to the corresponding carbonyl com-
pounds under mild reaction conditions, and are avail-
able easily from the corresponding nitroxyl radicals by
2
–4
aq phase (0.1 M KOH)
org. phase (toluene)
Figure 1 Oxidation of alcohols with K Fe(CN) mediated by
3
6
one-electron oxidation. On the other hand, polymeric TEMPO PS resin under organic–aqueous two-phase solution system.
5
reagents have attracted much interest in organic synthe-
sis, because they can be used in high excess and are re-
ever, almost all of reactions require the same amount of
moved by filtration, the products can be easily analyzed
organic solvent as water. The use of water instead of
and further transformation in solution. Recently, Rade-
organic solvents is strongly desired from the viewpoint of
mann and co-workers have reported on the generation of
environmental safety and economical cost. For this rea-
oxoammonium halides as oxidizing reactive species on a
son, we tried to use a small amount of organic solvent,
solid support such as polystyrene and on the use of this re-
which may be kept in the polystyrene (PS) resin by hydro-
phobic interaction, as an organic layer of two-phase
reaction.
6
agent in the oxidation of alcohols. TEMPO polystyrene
(
TEMPO PS) may also be used to catalyzed the oxidation
of alcohols with oxone in the presence of a phase-transfer
7
Preparative, oxidation of alcohols with nitroxyl radical
resins under two-phase conditions was described as fol-
lows. TEMPO PS resin (TEMPO loading: 2.0 mmol/g,
agent such as tetrabutylammonium bromide. Further-
more, a related study that uses TEMPO PS together with
polystyrene-supported diacetoxyiodosobenzene to selec-
tively oxidize alcohols to aldehydes and ketones was re-
3
00 mg) was added to the toluene solution (4 mL) contain-
8
–11
ing alcohol (4 mmol), 2,6-lutidine (4 mmol) and tetralin as
internal standard (0.5 mmol). This TEMPO PS resin
dispersed suspension was stirred for one hour at room
temperature and then separated. The swelled resin was
washed three times with water and then added to 10 mL of
ported.
However, these reagents were used in high
excess to substrate. Herein we report on the first efficient
oxidation of alcohols to carbonyl compounds using potas-
sium hexacyanoferrate(III) [K Fe(CN) ] mediated by
3
6
TEMPO PS as catalyst under polymer-supported organic–
aqueous two-phase conditions (Figure 1).
0
.1 M aqueous KOH solution containing 3.29 g (10
mmol) of K Fe(CN) . The reaction mixture was stirred at
3
6
Several oxidation reactions of alcohols in organic–aque-
ous two-phase solution have been reported using regener-
room temperature. During oxidation reaction, aliquots of
reaction mixture were occasionally analyzed by HLPC
1
2–15
ating oxidants such as positive halogen sources
high-valency metal salts
and
which were mediated by the
oxidation of nitroxyl radical to oxoammonium ion. How-
18
and GC. At the end of the reaction, the swelled resin was
1
6,17
separated, washed three times with water, extracted three
times with toluene and filtered in vacuo. This extracted
solution was dried with magnesium sulfate and evaporat-
ed. The residue was distilled or isolated by column
chromatography. The products were identified by the
SYNLETT 2006, No. 1, pp 0069–0072
0
5.
0
1.
2
0
0
6
Advanced online publication: 16.12.2005
DOI: 10.1055/s-2005-922775; Art ID: U28805ST
1
13
usual spectral data (mass, IR, H NMR and C NMR).
©
Georg Thieme Verlag Stuttgart · New York

7
0
Y. Kashiwagi et al.
LETTER
The results of oxidation of a variety of primary and sec- conditions primary alcohol was converted quantitatively
ondary alcohols are shown in Table 1. The primary alco- into aldehyde after three hours whereas virtually no
hols (entries 1–6) such as 1-octanol, nerol, benzyl alcohol, ketone (<0.1%) could be detected by GC.
4
-methoxybenzyl alcohol, 4-nitrobenzyl alcohol and cin-
namyl alcohol were oxidized to the corresponding alde-
hydes. Under standard reaction conditions aliphatic and
benzylic primary alcohols are oxidized within 0.5–10
hours. In the case of benzylic alcohols, electron-donating
groups slow down the reaction (entry 4) whereas electron-
withdrawing groups accelerate it (entry 5). Allyl alcohols
CHO
OH
TEMPO PS resin
+
(98%)
+
2,6-lutidine
K3Fe(CN)6
KOH
OH
O
r.t., 3 h
(
<0.1%)
(
entries 2 and 6) are also oxidized to the corresponding
Scheme 1 Oxidation of 1-octanol in the presence of 2-octanol.
aldehydes in adequate yields.
On the other hand, the secondary alcohols (entries 7–10)
such as 2-octanol, cyclohexanol, 1-phenylethanol, and 1-
hydroxyindan are converted to the corresponding ketones
with much lower efficiency under the same conditions.
This observation suggested a possible chemoselective ox-
idation of primary alcohols in the presence of secondary
alcohols. The results from the oxidation of 1:1 mixture of
The results of oxidation of various diols are shown in
Table 2. Oxidative cyclization of 1,4- and 1,5-diols to g-
and d-lactones, respectively, proceeded nicely (entries 1
and 2). cis-Cyclohexane-1,2-dimethanol is also converted
into cyclization product (entry 5). However, 1,n-diols (n >
5
) gave non-cyclization products such as 1,n-dialdehyde
or n-hydroxyalkanal, predominantly (entries 3 and 6). 1,4-
Benzenedimethanol as the benzylic primary-primary diol
is oxidized to the corresponding dialdehyde with excellent
1
-octanol and 2-octanol are shown in Scheme 1 and
Figure 2. Indeed, the present oxidation system proved to
be exceptionally chemoselective: under standard reaction
Table 1 Oxidation of Primary and Secondary Alcohols
Entry
1
Substrate
Product
Time (h)
3
Yield (%)a
98
CHO
OH
CHO
OH
OH
2
2.5
98
CHO
3
4
2
7
97
96
CHO
OH
OH
MeO
O2N
MeO
O2N
CHO
CHO
5
0.5
98
OH
OH
6
7
3
88
24
10
O
OH
O
8
9
6
4
3
36
65
58
OH
O
O
OH
1
0
a
Yields were determined by calibrated quantitative GC or HPLC analysis using as internal standard.
Synlett 2006, No. 1, 69–72 © Thieme Stuttgart · New York

LETTER
Oxidation of Alcohols with Nitroxyl Radical Resins
71
1
0
0
0
.0
.8
.6
.4
A possible reaction mechanism is as follows (Figure 3).
The nitroxyl radical catalyst on resin was first oxidized by
Fe(III) to give oxoammonium ion on organic–aqueous in-
terface, and subsequently alcohol was oxidized by the
oxoammonium ion in the organic phase of resin to give
the corresponding carbonyl compound, in which an ad-
duct made up of the alcohol and the oxoammonium ion is
attacked by a Lewis base to form the second intermediate
0.2
1
9
leading to the products, hydroxylamine and a protic acid
+
II
–
such as H K [Fe (CN) ] which was neutralized by KOH
3
6
0
1
2
3
4
to give potassium ferrocyanide. Either the hydroxylamine
is oxidized to the nitroxyl radical by Fe(III) or the reaction
Reaction time (h)
Figure 2 Oxidation of a mixture of 1-octanol and 2-octanol (1:1) by of the hydroxylamine and the oxoammonium ion produc-
TEMPO PS resin together with K Fe(CN) . 1-Octanol: {; 1-octan-
3
6
es the nitroxyl radical. In either case, the nitroxyl radical
is re-oxidized chemically by Fe(III) to complete a catalyt-
ic cycle.
one: z; 2-octanol: ꢀ; 2-octanone: „.
In conclusion, we have demonstrated the first efficient ox-
yield (entry 4). In case of intermolecular competition be-
tween primary and secondary alcohols, oxidation of 1,10-
undecanediol gave 82% isolated yield of 10-hydroxyun-
decanal with 6% ketoaldehyde, the amount of isomeric
keto alcohol remaining less than 0.1% (entry 6). Even in
the case of doubly activated secondary alcohols the meth-
ods ensures oxidation of primary alcohols with a very
high chemoselectivity (entry 7).
idation of alcohols using K Fe(CN) mediated by TEMPO
3
6
polystyrene resin under an organic–aqueous two-phase
solution system. This method is promising in organic
synthesis from an environmental, practical and safety
viewpoint. This present work has the advantage of not
separating the product and TEMPO from a reaction
solution. Primary alcohols are readily oxidized with no
Table 2 Oxidation of Various Diols
Entry
1
Substrate
Product
Time (h)
3.5
Yield (%)a
97
OH
HO
O
O
O
2
3
4
HO
HO
OH
OH
3
4
5
98
93
95
O
OHC
3
3
CHO
CHO
OH
HO
OHC
O
OH
OH
5
6
3
3
96
O
OHC
OHC
3
3
OH
O
82b
6
HO
3
+
OH
OH
OH
CHO
7
1
8c
0
7
+
4
OH
O
CHO
a
Yields were determined by calibrated quantitative GC or HPLC analysis using as internal standard.
Ketoalcohol could not be detected.
b
c
1
% Ketoalcohol and 5% starting diol could be detected.
Synlett 2006, No. 1, 69–72 © Thieme Stuttgart · New York

7
2
Y. Kashiwagi et al.
LETTER
(
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R
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H
N
N
N
OH
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(
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OH
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(
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org. phase (toluene)
Figure 3 Schematic diagram of organic–aqueous two-phase oxida-
tion of alcohols with K Fe(CN) mediated by TEMPO PS resin.
3
6
7
35. (e) Kuroboshi, M.; Yoshihara, H.; Cortona, M. N.;
overoxidation to carboxylic acids. Furthermore, this
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(
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Acknowledgment
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4
3
This work was supported in part by Grants-in-Aid (No. 15590035)
from Japan Society for the Promotion of Science. The Takeda
Science Foundation, the Casio Science Promotion Foundation and
the Shiseido Grants for Scientific Research are also acknowledged
for financial support.
2
2
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Synlett 2006, No. 1, 69–72 © Thieme Stuttgart · New York