Sodium hypochlorite pentahydrate (NaOCl·5H2O) crystals as an extraa?ordinary oxidant for primary and secondary alcohols

Article abstract of DOI:10.1055/s-0033-1340483

Sodium hypochlorite pentahydrate crystals containing less free sodium hydroxide and sodium chloride have been developed as an improved oxidant. Primary and secondary alcohols have been oxidized to the corresponding aldehydes and ketones with ?NaOCl·5H₂O in the presence of TEMPO/Bu₄NHSO₄. This new oxidation method does not require pH adjustment and is applicable to sterically hindered secondary alcohols. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340483

5
96▌
LETTER
letter
Sodium Hypochlorite Pentahydrate (NaOCl·5H O) Crystals as an Extra-
2
ordinary Oxidant for Primary and Secondary Alcohols
NaOCl·5H
2
O Crystals as Oxidant for Alcoho
a
ls
a
b
c
c
d
Tomohide Okada, Tomotake Asawa, Yukihiro Sugiyama, Masayuki Kirihara, Toshiaki Iwai, Yoshikazu Kimura*
a
R&D Department of Chemicals, Nippon Light Metal Company, Ltd., Kambara, Shimizu-ku, Shizuoka 421-3203, Japan
b
Market Development Department, Nippon Light Metal Company, Ltd., Higashi-shinagawa, Shinagawa-ku, Tokyo 140-8628, Japan
c
Department of Materials and Life Science, Shizuoka Institute of Science and Technology, 2200-2 Toyosawa, Fukuroi, Shizuoka 437-8555,
Japan
d
Research and Development Department, Iharanikkei Chemical Industry Co. Ltd., Kambara, Shimizu-ku, Shizuoka 421-3203, Japan
Fax +81(54)3855821; E-mail: kimura.yoshikazu@iharanikkei.co.jp
Received: 30.10.2013; Accepted after revision: 25.11.2013
2
has been developed by Iwabuchi et al. Such catalysts
proved to be highly efficient for the oxidation of alcohols,
especially sterically hindered secondary alcohols. How-
ever, the synthesis of those catalysts (AZADO and related
Abstract: Sodium hypochlorite pentahydrate crystals containing
less free sodium hydroxide and sodium chloride have been devel-
oped as an improved oxidant. Primary and secondary alcohols have
been oxidized to the corresponding aldehydes and ketones with
NaOCl·5H O in the presence of TEMPO/Bu NHSO . This new ox- compounds) involves multiple steps, and aqueous sodium
2
4
4
idation method does not require pH adjustment and is applicable to hypochlorite must be adjusted to pH 8–9 with aqueous so-
sterically hindered secondary alcohols.
dium hydrogen carbonate in order for the oxidation reac-
Key words: sodium hypochlorite pentahydrate, TEMPO, 1-Me- tions to proceed efficiently. The oxidation process using
AZADO
aqueous NaOCl has inherently poor volume efficiency be-
cause the concentration of commercial aqueous NaOCl
solution is only about 10%. Further dilution arising from
Although various methodologies for the oxidation of pri- the pH adjustment may render the solution unsuitable for
mary and secondary alcohols to the corresponding alde- large-scale synthesis.
hydes and ketones have been reported, more
environmentally benign and economical oxidation pro-
We have recently developed a new manufacturing process
for sodium hypochlorite pentahydrate (NaOCl·5H O)
2
cesses are still required. Oxidation with aqueous sodium
crystals (Figure 1), which have several advantages over
hypochlorite (NaOCl) catalyzed by the 2,2,6,6-tetrameth-
commercial 13% aqueous sodium hypochlorite (pH 13):
ylpiperidinium oxy radical (TEMPO) seems to be one
(
1) the available chlorine content is about 42%, (2) the pH
of the best methods meeting the above requirements.
TEMPO-catalyzed oxidation of primary alcohols to the
aldehydes has been reported to proceed in high yields, but
poor results have been obtained with secondary alcohols.1
This has been attributed to the four methyl groups of
TEMPO preventing bulky substrate from forming the key
intermediate (Scheme 1).2
upon dissolution is around 11, since the solution contains
less than 0.08 wt% hydroxide ions, (3) the crystals are
much more stable than aqueous sodium hypochlorite at
below ambient temperature.3
1-Me-AZADO
TEMPO
vs
N
O
N
O
OH
R2
R1
Scheme 1 Key step for the oxidation of alcohols
NaOCl oxidation of alcohols catalyzed by less hindered 2-
azaadamantane N-oxyls (AZADO and related products)
Figure 1 NaOCl·5H O crystals
2
SYNLETT 2014, 25, 0596–0598
Advanced online publication: 08.01.2014
In this communication, a novel oxidation method for alco-
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
hols employing the NaOCl·5H O crystals and that is cat-
2
DOI: 10.1055/s-0033-1340483; Art ID: ST-2013-U1017-L
Georg Thieme Verlag Stuttgart · New York
alyzed by TEMPO or 1-Me-AZADO is described. Our
©

LETTER
NaOCl·5H O Crystals as Oxidant for Alcohols
597
2
newly developed process has some favorable characteris- ment (Table 1, entry 7). Various kinds of solvents were
tics; (1) pH adjustment is not required, (2) primary alco- examined, but dichloromethane proved to be the best. In-
hols are selectively oxidized to the corresponding stead of TEMPO, the use of 1-Me-AZADO to catalyze the
aldehydes, (3) secondary alcohols, even when sterically oxidation of 1 with NaOCl·5H O crystals was also exam-
2
hindered, can be oxidized to afford the corresponding ke- ined. The reaction was very fast even without pH adjust-
tones in high yields.
ment, affording 2 in quantitative yield (Table 1, entry 13),
but the use of aqueous NaOCl instead of NaOCl·5H O
crystals gave poor results (Table 1, entry 14). In the ab-
sence of nitroxyl radicals, the oxidation reaction of 1 with
2
Treatment of 2-octanol (1) with 1.2 equivalents of
NaOCl·5H O crystals in dichloromethane in the presence
2
of 0.01 equivalents of TEMPO and 0.05 equivalents of
tetrabutylammonium hydrogen sulfate (Bu NHSO ) at 5
NaOCl·5H O crystals proceeded slowly (Table 1, entry
2
4
4
1
).
°
C for one hour gave a 97% yield of 2-octanone (2, Table
1
, entry 3). Several reaction conditions were examined, as Next, we examined the oxidation of some other alcohols
shown in Table 1.
with NaOCl·5H O crystals in the presence of Bu NHSO
2
4
4
and TEMPO or 1-Me-AZADO. The results are shown in
Table 2. 2-Octanol, 3-octanol, 1-octanol, and benzyl
Bu NHSO proved to be a much better phase-transfer cat-
4
4
4
alyst than Bu NBr or Bu NCl. However, an addition of
4
4
alcohol gave the corresponding ketones and aldehydes in
high yields in the presence of 0.01 equivalents of
TEMPO. L-Menthol and 2,6-dimethyl-4-heptanol (as ex-
amples of sterically hindered secondary alcohols) were
oxidized to the corresponding ketones in 96% and 88%
yields, respectively, in the presence of TEMPO, after op-
0
.05 equivalents of NaHSO and a small amount of water
4
into the reaction conditions of Table 1, entry 5 gave an
9% yield of 2 (Table 1, entry 6). Bu NHSO seems to
8
4
4
have both roles of a neutralization of liberated NaOH in
NaOCl·5H O and a phase-transfer catalyst. A control ex-
2
periment using commercial aqueous NaOCl solution
timization of the amount of NaOCl·5H O crystals and the
2
(
about 13wt%, 2.2 M) was performed in a similar fashion.
reaction temperature.
A mixture of 1, TEMPO, Bu NHSO , and aqueous NaOCl
4
4
gave 2 in only 2% yield after two hours without pH adjust-
Table 1 Oxidation of 2-Octanol to 2-Octanone with NaOCla
O
OH
NaOCl (1.2 equiv)
4
catalyst (0.01 equiv)
4
Bu4NX (0.05 equiv)
2
1
5
Solvent
CH Cl
°C
Entry
Catalyst
X
NaOCl
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
–
HSO4
HSO4
HSO4
Br
NaOCl·5H O
24
27
1
78
9
2
2
2
2
2
2
2
2
2
2
CH Cl
–
aq NaOCl
2
CH Cl
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
NaOCl·5H O
97
14
10
89c
2
2
2
CH Cl
NaOCl·5H O
2
2
2
CH Cl
Cl
NaOCl·5H O
2
2
2
CH Cl
Cl
NaOCl·5H O
2
2
2
CH Cl
HSO4
–
aq NaOCl
2
2
CH Cl
NaOCl·5H O
2
0.1
55
97
53
78d
100
14
2
2
PhCF3
HSO4
HSO4
HSO4
HSO4
HSO4
HSO4
NaOCl·5H O
2
2
1
1
1
1
0
1
2
3
4
1
EtOAc
MeCN
AcOH
CH Cl
NaOCl·5H O
2
2
NaOCl·5H O
2
2
NaOCl·5H O
2
2
1-Me-AZADO
1-Me-AZADO
NaOCl·5H O
1
2
2
2
1
CH Cl
aq NaOCl
1
2
2
a
(10 mmol), NaOCl (12 mmol), TEMPO or 1-Me-AZADO (0.1 mmol), phase-transfer catalyst (0.5 mmol), solvent (30 mL) without pH ad-
justment.
b
GC yield using an internal standard.
c
addition of NaHSO ·H O (0.5 mmol) and H O (0.2 mL).
4
2
2
d
At r.t.
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 596–598

5
98
T. Okada et al.
LETTER
Table 2 Examples for Oxidation of Alcohols with NaOCl·5H Oa
the presence of TEMPO is yet unknown, but it may relate
to a different intermediate.
2
O
OH
NaOCl⋅5H O
2
In conclusion, the ready availability, high volume effi-
TEMPO (0.01 equiv)
Bu4NHSO4 (0.05 equiv)
CH2Cl2
R1
R2
R1
R2
ciency, and high activity of NaOCl·5H O for the oxida-
2
tion of alcohols should make this a very attractive
oxidation method for laboratory and industrial use.
Substrate
NaOCl·5H O CH Cl Temp Time Yield
2 2 2
b
(
equiv)
(mL) (°C)
(h)
(%)
References and Notes
OH
1
1
.2
.2
30
10
5
5
1
0.5
97
(95)
(
1) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org.
Chem. 1987, 52, 2559.
4
(
2) (a) Shibuya, M.; Tomizawa, M.; Suzuki, I.; Iwabuchi, Y.
J. Am. Chem. Soc. 2006, 128, 8412. (b) Iwabuchi, Y.
J. Synth. Org. Chem. Jpn. 2008, 66, 1076.
3) Asawa, T.; Tuneizumi, T.; Iwasaki, Y. JP 4211130, 2008.
4) Typical Experiment for the Oxidation of 2-Octanol (1)
OH
1
1.2
.2
30
10
5
5
1
0.5
97
(96)
3
(
(
5
OH
OH
1.1
30
30
5
5
1
1
91
99
NaOCl·5H O crystals (2.0 g, 12.2 mmol) were added in one
2
portion to a mixture of Bu NHSO (0.17 g, 0.50 mmol),
4
4
TEMPO (21 mg, 0.13 mmol), and 1 (1.30 g, 10.0 mmol) in
1
.1
CH Cl (10 mL) at 5 °C. After 15 min, GC monitoring
2
2
showed that 1 had been consumed. The reaction was stopped
after 0.5 h by quenching with aq sat. Na SO solution (20
OH
1
1
1
.6
.6
.4
10
8
30
15
15
r.t.
2
2.25
0.5
96
(92)
98
2
3
c
mL). The organic layer was separated, and the aqueous layer
was extracted with CH Cl (30 mL). The combined organic
d
2
2
layers were washed with H O (30 mL), dried over Na SO ,
2
2
4
and concentrated to give 2 as colorless oil (1.27 g, crude
OH
1.4
10
10
30
r.t.
15
r.t.
7
6
0.5
77
88
95
yield of 99.2%, GC analysis showed the product to be 96.8%
pure). A 0.42 g portion of the crude 2 was purified by bulb-
to-bulb distillation (6 kPa, 120–130 °C) to afford pure 2
(0.40 g, 95%). GC–MS analysis gave identical results to
those of an authentic sample.
1
1
.8
.4
d
a
Substrate (10 mmol), TEMPO (0.1 mmol), Bu NHSO (0.5 mmol),
CH Cl (10 mL or 30 mL) without pH adjustment.
GC yield using an internal standard. Parentheses are referred to the
4
4
2
2
b
(
5) Oxidation of L-Menthol
isolated yield.
NaOCl·5H O (658.0 mg, 4 mmol) was added in one portion
2
c
Substrate (2.5 mmol), TEMPO (0.022 mmol), Bu NHSO (0.131
mmol), CH Cl (8 mL) without pH adjustment.
-Me-AZADO was used instead of TEMPO.
4
4
to a mixture of Bu NHSO (44.5 mg, 0.131 mmol), TEMPO
4
4
2
2
(3.4 mg, 0.022 mmol), and L-menthol (391.5 mg, 2.5 mmol)
in CH Cl (8 mL) at 15 °C. The mixture was stirred at 15 °C
d
1
2
2
for 2.25 h, and then the reaction was quenched by treatment
with sat. aq Na SO solution (5 mL). The aqueous layer was
2
3
The stereochemistry of L-menthone was confirmed as that
with retention of the configuration by measurement of its
optical rotation. 1-Me-AZADO was shown to be a supe-
extracted with CH Cl (3 × 10 mL). The combined organic
2
2
layers were washed with sat. brine, dried over anhydrous
Na SO , and concentrated to give L-menthone as a colorless
5
2
4
rior catalyst for the oxidations of L-menthol and 2,6-di-
oil (475.7 mg), which was purified by column
chromatography on silica gel to give pure L-menthone
methyl-4-heptanol with NaOCl·5H O crystals, affording
2
2
5
6
(
355.3 mg, 92%). [α] –28.1 (c 0.0156, EtOH) {lit. [α]D
D
high yields of the ketones in very short reaction times. Al-
though TEMPO proved to be inferior to 1-Me-AZADO as
a catalyst, considering the ready availability of TEMPO,
it may still be more practical for a large-scale synthesis.
The precise reason why some sterically hindered second-
1
–
3
1
28.6}. H NMR (400 MHz, CDCl ): δ = 2.35 (ddd, J = 13.1,
.6, 2.3 Hz, 1 H), 2.18–1.80 (m, 6 H), 1.43–1.29 (m, 2 H),
.01 (d, J = 6.4 Hz, 3 H), 0.91 (d, J = 6.8 Hz, 3 H), 0.85 (d,
3
J = 6.8 Hz, 3 H). See ref. 7.
(6) Timshina, A. V. Russian J. Org. Chem. 2008, 44, 1043.
(7) Iwabuchi, Y.; Hayashi, M. WO 2012008228, 2012.
ary alcohols can be oxidized with NaOCl·5H O crystals in
2
Synlett 2014, 25, 596–598
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