An environmentally benign TEMPO-catalyzed efficient alcohol oxidation system with a recyclable hypervalent iodine(III) reagent and its facile preparation

Article abstract of DOI:10.1055/s-0028-1087850

A highly efficient 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO) catalyzed alcohol oxidation system using recyclable 1-chloro-1,2-benziodoxol-3(1H)-one as the terminal oxidant in ethyl acetate, which is an environmentally friend organic solvent, at room temperature has been developed. A variety of alcohols can be oxidized to their corresponding carbonyl compounds in high to excellent yields. Various heteroaromatic rings and C=C bonds are well tolerated under the reaction conditions. 1-Chloro-1,2-benziodoxol-3(1H)-one can be easily recycled after simple solid/liquid-phase separation and the subsequent regeneration sequence. In addition, a safe, very convenient, large-scale, and high-yielding procedure for the preparation of 1-chloro-1,2-benziodoxol-3(1H)-one from 2-iodobenzoic acid has been developed using sodium chlorite as the stoichiometric oxidant in dilute hydrochloric acid at room temperature. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087850

PAPER
1163
An Environmentally Benign TEMPO-Catalyzed Efficient Alcohol Oxidation
System with a Recyclable Hypervalent Iodine(III) Reagent and Its Facile
Preparation
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Qiang Li, Chi Zhang*
The State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. of China
Fax +86(22)23499247; E-mail: zhangchi@nankai.edu.cn
Received 24 September 2008; revised 2 December 2008
iodine reagents are very effective, they require multistep
Abstract: A highly efficient 2,2,6,6-tetramethylpiperidin-1-yloxy
(TEMPO) catalyzed alcohol oxidation system using recyclable 1-
chloro-1,2-benziodoxol-3(1H)-one as the terminal oxidant in ethyl
acetate, which is an environmentally friend organic solvent, at room
synthesis or employ fluorous solvents for the separation of
the products. Recently, Zhdankin and Kirschning devel-
oped new recyclable hypervalent iodine reagents derived
temperature has been developed. A variety of alcohols can be oxi- from inexpensive and readily available 3-iodobenzoic
dized to their corresponding carbonyl compounds in high to excel-
acid, which can be easily recovered by treatment with an-
ionic-exchange resin or by solid/liquid-phase separation.7
lent yields. Various heteroaromatic rings and C=C bonds are well
tolerated under the reaction conditions. 1-Chloro-1,2-benziodoxol-
2-Iodobenzoic acid, similar to 3-iodobenzoic acid, is also
3(1H)-one can be easily recycled after simple solid/liquid-phase
inexpensive and commercially available and it could be
separation and the subsequent regeneration sequence. In addition, a
used in a recycling process. There are many hypervalent
iodine reagents derived from 2-iodobenzoic acid such as
Dess–Martin periodinane (DMP), 2-iodoxybenzoic acid
(IBX), 1-(tert-butylperoxy)-1,2-benziodoxol-3(1H)-one,
1-azido-1,2-benziodoxol-3-(1H)-one, etc. All these hy-
pervalent iodine reagents contain five-membered iodine
heterocycles and have superior thermodynamic stability
and reactivity compared to the corresponding acyclic an-
alogues.8 We have reported two facile preparative meth-
ods for iodobenzene dichloride (PhICl2) and its
application in TEMPO-catalyzed efficient alcohol oxida-
tion reactions.9a However, when alcohols containing an
isolated C=C bond or heteroaromatic rings were tried, the
desired carbonyl compounds could not be obtained with-
out affecting the isolated C=C bond or heteroaromatic
rings. In addition, the reductive product of iodobenzene
dichloride is iodobenzene, which is often removed by col-
umn chromatography. As part of our continuing investiga-
tion on oxidation reactions using hypervalent iodine
reagents,9 we herein introduce a monomeric recyclable
hypervalent iodine(III) reagent, 1-chloro-1,2-benziodox-
ol-3(1H)-one (1, Figure 1), which can oxidize various al-
cohols to the corresponding carbonyl compounds in high
to excellent yields with TEMPO or a structurally less hin-
dered nitroxyl radical 1-Me-AZADO10 (Figure 1) as a cat-
alyst and pyridine as the base. In addition, a facile
preparative method for 1 from 2-iodobenzoic acid has
been developed. Compound 1 was reported over 100
years ago,11 but few practical applications in organic syn-
thesis have been developed despite the fact that 1 was
found to be an effective reagent for the nuclear chlorina-
tion of aromatic hydrocarbons such as durene in acetic
acid.11f
safe, very convenient, large-scale, and high-yielding procedure
for the preparation of 1-chloro-1,2-benziodoxol-3(1H)-one from
2-iodobenzoic acid has been developed using sodium chlorite as
the stoichiometric oxidant in dilute hydrochloric acid at room
temperature.
Key words: alcohol, hypervalent iodine, oxidation, recyclable,
TEMPO
The oxidation of alcohols to carbonyl compounds plays an
important role in organic synthesis and numerous oxi-
dants can accomplish this conversion under diverse reac-
tion conditions.1 Various hypervalent iodine reagents
have been applied in the oxidation of alcohols to their cor-
responding carbonyl compounds due to their ready avail-
ability and easy handling.2 Moreover, a great deal of effort
has been made to develop recyclable hypervalent iodine
reagents to meet the demands for environmentally benign
chemical processes. The first reported examples are the
polymer-supported iodobenzene-based hypervalent io-
dine reagents, such as poly(diacetoxyiodo)styrene and
poly[bis(trifluoroacetoxy)iodo]styrene.3 However, these
polymer-supported reagents require multistep prepara-
tion, they have lower reactivity compared to the corre-
sponding monomeric analogues, and degradation of the
polymer occurs after repeated use. Accordingly, Kita et al.
reported two novel, recyclable, and non-polymeric hyper-
valent iodine reagents based on 1,3,5,7-tetrakis(4-iodo-
phenyl)adamantane and tetrakis(4-iodophenyl)methane
structure.4 Togo and Telvekar reported biphenyl- and ter-
phenyl-based recyclable trivalent iodine reagents.5 An-
other important kind of recyclable non-polymeric
hypervalent iodine reagent involves perfluoro-substituted
alkyl iodides.6 Though these non-polymeric hypervalent
Initially, 1 was found to be able to oxidize decan-1-ol (2a)
to decanal (3a) in 77% yield after one hour with TEMPO
(8 mol%) as a catalyst, 1 (1.5 equiv), and pyridine (1.5
equiv) in chloroform (5 mL) at 50 °C. When the reaction
SYNTHESIS 2009, No. 7, pp 1163–1169
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Advanced online publication: 02.03.2009
DOI: 10.1055/s-0028-1087850; Art ID: F20408SS
© Georg Thieme Verlag Stuttgart · New York

1164
X.-Q. Li, C. Zhang
PAPER
O
Table 1 Organic Solvents Screened for the Oxidation of Decan-1-
ol (2a) at Room Temperaturea
O
I
O
TEMPO (8 mol%)
Cl
O
OH
+
O
Me
Me
8
8
1-chloro-1,2-benziodoxol-3(1H)-one (1)
Py (1.5 equiv)
I
solvent (5 mL), r.t.
Cl
1 (1.5 equiv)
2a (1 mmol)
N
Entry
Solvent
Time (h)
Yieldb (%)
N
O
O
1
2
EtOAc
MeOH
t-BuOH
CHCl3
CH2CH2
acetone
DMF
1.5
12
29
3
85
<5
72
76
51
76
54
49
65
82
TEMPO
1-Me-AZADO
Figure 1 Structures of 1, TEMPO, and 1-Me-AZADO
3
was carried out at room temperature, decanal (3a) was ob-
tained in 76% yield after three hours. Then, various com-
mon organic solvents were screened at room temperature;
the results are summarized in Table 1. Ethyl acetate, a
more environmentally friend organic solvent than chlori-
nated solvents such as dichloromethane and chloroform,12
gave the highest yield of decanal (3a) (85%) within the
shortest reaction time (1.5 h) among all screened solvents.
In the absence of TEMPO, low conversion (27%) of de-
can-1-ol (2a) and, thus, a low yield (8%) of decanal (3a)
were observed. Without pyridine, though the conversion
of decan-1-ol (2a) was 88% after seven hours, the reaction
became complicated and the yield of decanal (3a) was
only 30%. Furthermore, with increased amounts of pyri-
dine under otherwise the same reaction conditions, the
yield of decanal (3a) varied from good to excellent
(Table 2, entries 1–4). When three equivalents of pyridine
were used, decanal (3a) was obtained in quantitative yield
(Table 2, entry 4). If other organic bases were employed
instead of pyridine, both the reaction rate and the yield of
decanal (3a) dramatically decreased (Table 2, entries 5–
8). Consequently, the optimal alcohol oxidation condi-
tions were set with 8 mol% of TEMPO as a catalyst, 1 (1.5
equiv), and pyridine (3.0 equiv), in ethyl acetate (5 mL) at
room temperature (Scheme 1).
4
5
2
6
2
7
2
8
THF
1.5
24
1.5
9
Et2O
10
DME
a Reagents and conditions: decan-1-ol (2a, 1 mmol), TEMPO (8
mol%), 1 (1.5 equiv), Py (1.5 equiv), solvent (5 mL), r.t.
b Isolated yields.
Table 2 Organic Bases Screened for the Oxidation of Decan-1-ol
(2a)a
Entry
Base (equiv)
Py (1.5)
Time (h) Yieldb (%) Conversion (%)
1
2
3
4
5
6
7
8
1.5
1.5
1.5
1.5
85
100
100
100
100
20
Py (2.0)
93
Py (2.5)
96
Py (3.0)
99
DMAP (3.0)
Et3N (1.5)
Et3N (3.0)
NMIc (2.0)
24
15
O
24
24
24
15
18
TEMPO (8 mol%)
O
OH
+
O
Me
Me
none
34
8
8
8
Py (3.0 equiv)
I
EtOAc (5 mL), r.t., 1.5 h
Cl
1 (1.5 equiv)
42
2a (1 mmol)
3a 99%
a Reagents and conditions: decan-1-ol (2a, 1 mmol), TEMPO (8
mol%), 1 (1.5 equiv), base, EtOAc (5 mL), r.t.
b GC yields.
Scheme 1 Optimal reaction conditions for oxidation of decan-1-ol
(2a)
c NMI = N-methylimidazole.
A variety of alcohols 2a–n, including aliphatic primary
and secondary alcohols, benzylic, and allylic alcohols
were tested using this alcohol oxidation system. Like de-
can-1-ol (2a), octan-1-ol (2c), and hexadecan-1-ol (2b)
with shorter or longer carbon chains were readily oxidized
to their corresponding aldehydes 3c and 3b in excellent
yields without overoxidation to the carboxylic acids
(Table 3, entries 1–3). Benzylic and allylic primary alco-
hols 2d–h were also oxidized to their corresponding alde-
hydes 3d–h in excellent yields without oxidizing
heteroaromatic rings or the C=C bond (entries 4–8). Nota-
bly, when undec-10-en-1-ol (2i) having both a primary
hydroxy group and an isolated C=C double bond was test-
ed, undec-10-enal (3i) was obtained in 88% yield together
with trace amounts of 10,11-dichloroundecanal from si-
multaneous chlorination of the C=C bond (entry 9). This
is distinct from the PhICl2/TEMPO/Py system, which
gave 10,11-dichloroundecanal and 10,11-dichlorounde-
can-1-ol as the products. As for secondary alcohols, oc-
Synthesis 2009, No. 7, 1163–1169 © Thieme Stuttgart · New York

PAPER
A TEMPO-Catalyzed Efficient Alcohol Oxidation System
1165
Table 3 Oxidations of Various Alcohols with 1/TEMPO/Pya
tan-2-ol (2j), 1-phenylethanol (2k), and cyclohexanol (2l)
were oxidized to their corresponding ketones 3j–l in ex-
cellent yields after a little longer reaction time than that
for primary alcohols (entries 10–12). However, in the case
of menthol (2m), due to the steric hindrance of the isopro-
pyl group, menthone (3m) could not be obtained after 24
hours at either room temperature or elevated tempera-
tures. When 1-Me-AZADO, a structurally less hindered
nitroxyl radical reported by Iwabuchi et al.,10 was em-
ployed instead of TEMPO, menthone (3m) was produced
in quantitative yield after five hours (entry 13). 1,2-Diphe-
nylethane-1,2-diol (2n) could be oxidized to benzil (3n) in
the quantitative yield without detection of benzaldehyde
from oxidative cleavage of the glycolic C–C bond (entry
14). However, the 1,2-diol was oxidatively cleaved to
give the corresponding aldehydes using the widely em-
ployed iodobenzene diacetate/TEMPO alcohol oxidation
system.13
Entry Alcohol
Time (h) Product
Yieldb (%)
99c
Me
OH
OH
OH
1
1.5
1.5
1.5
3a
3b
3c
8
2a
Me
2
98
14
2b
Me
3
4
92c
6
2c
CH2OH
OH
0.5
4
3d
3e
3f
96c
92c
98c
2d
5
6
O
2e
OH
It was observed that longer reaction times were required
for the oxidation of secondary alcohols than that for pri-
mary alcohols (Table 3, entries 1–3 vs entries 10–12).
This experimental observation implied that a primary al-
cohol might be preferentially oxidized over a secondary
alcohol. This was the case since undecane-1,10-diol (4)
was oxidized to 10-hydroxyundecanal (5) with 1.1 equiv-
alents of 1 in 89% yield after 2.5 hours (Scheme 2).
3
S
2f
CH2OH
Cl
Cl
7
8
6
3g
3h
91
N
2g
OH
0.5
83c
O
TEMPO (8 mol%)
Py (3.0 equiv)
OH
OH
2h
2i
+
O
EtOAc (5 mL), r.t.
2.5 h
Me
OH
Me
O
8
8
I
88d
89
OH
9
1.5
5
3i
3j
8
Cl
1 (1.1 equiv)
4
5 89%
OH
10
Scheme 2 Oxidation of undecane-1,10-diol
2j
OH
The mechanism of this alcohol oxidation system is worth
discussing. The fact that the efficiency of this oxidation
reaction decreased dramatically in the absence of pyridine
suggested that the acid-catalyzed TEMPO dismutation
process to give an oxoammonium salt13 could be ruled
out. Although 10,11-dichloroundecanal was produced
only in 6% yield from the oxidation of undec-10-en-1-ol
(2i) (Table 3, entry 9), the chlorination on the isolated
C=C bond suggested that chlorine atom might be generat-
ed from homolytic cleavage of the I–Cl bond in oxidant
1.9a,14 The fact that the oxoammonium salt could be gen-
erated by the oxidation of TEMPO with chlorine inspired
us to propose that the chlorine atom oxidizes TEMPO to
its oxoammonium salt.15 The proposed mechanism is il-
lustrated in Scheme 3. Initially, homolytic cleavage of the
I–Cl bond yields a chlorine atom and the iodanyl radical
A, which is in equilibrium with the benzoyloxy radical
A¢.14 Then oxoammonium salt B, generated from the oxi-
dation of TEMPO by a chlorine atom,9a,15 oxidizes the al-
cohols to their corresponding carbonyl compounds and is
itself reduced to hydroxylamine C.16 The radical A¢ ac-
complishes the regeneration of TEMPO from hydroxy-
lamine C giving rise to 2-iodobenzoic acid and the
11
12
2.5
5
3k
3l
92
Ph
2k
94c
OH
2l
OH
13e
14f
5
9
3m
3n
97
98
2m
OH
OH
2n
a Unless otherwise noted, the reaction conditions were the same as
shown in Scheme 1.
b Isolated yields.
c GC yields.
d 10,11-Dichloroundecanal was obtained in 6% yield.
e 1-Me-AZADO was used instead of TEMPO as the catalyst.
f 2.2 equivalents of oxidant 1 were used.
Synthesis 2009, No. 7, 1163–1169 © Thieme Stuttgart · New York

1166
X.-Q. Li, C. Zhang
PAPER
catalytic cycle is complete.17 The milder reaction condi- bleach (NaOCl) or sodium chlorite (NaClO2) as the oxi-
tion of 1/TEMPO/Py system (room temperature) than that dant in aqueous hydrochloric acid media.9a Thus, com-
of PhICl2/TEMPO/Py (50 °C) could explain the better pound 1 could be prepared in 94% yield by the oxidation
chemoselectivity when undec-10-en-1-ol (2i) is the sub- of 2-iodobenzoic acid with sodium chlorite19 in aqueous
strate. This was supported by the fact that if undec-10-en- hydrochloric acid media (Scheme 4). Moreover, this
1-ol (2i) was treated with 1/TEMPO/Py at 50 °C under the method could be scaled up to 100 mmol of 2-iodobenzoic
otherwise identical conditions as that at room tempera- acid, giving 26.4 g of compound 1. Compound 1 is very
ture, the ratio of undec-10-enal/10,11-dichloroundecanal stable at room temperature and can be stored at room tem-
was 3.2:1, which is much lower than 14.6:1 obtained at perature without any decomposition for one year. The
room temperature (Table 3, entry 9). This implies that greater stability of 1 than that of iodobenzene dichloride
chlorination occurred to a greater extent when using the 1/ could be explained by better overlap of the lone pair elec-
TEMPO/Py reaction system at high temperature like 50 trons on the iodine atom with the p-orbitals of the benzene
°C. In the iodobenzene diacetate/TEMPO system, 1,2-di- ring.8
ols formed a five-membered ring intermediate after twice
ligand exchange with iodobenzene diacetate and then this
O
Cl
Cl
I
OH
NaClO2
I
OH
intermediate collapsed to give the cleavage products, al-
dehydes. However, in our reaction system, the oxoammo-
nium salt was thought to be the real oxidizing agent,
which could not oxidize 1,2-diols to the glycolic cleavage
product. This observation gives support to the proposed
mechanism. In addition, because the co-product of the 1/
TEMPO/Py system was the pyridine salt of 2-iodobenzoic
acid,18 1 could be easily recycled after simple solid/liquid-
phase separation and the subsequent regeneration step
(86% recovery).
(300 mmol)
filtration
air dry
O
O
O
concd HCl
(200 mL)
H2O
I
Cl
1
(500 mL)
100 mmol
94% yield
Scheme 4 Preparation of 1-chloro-1,2-benziodoxol-3(1H)-one (1)
In summary, a highly efficient TEMPO-catalyzed alcohol
oxidation system using 1-chloro-1,2-benziodoxol-3(1H)-
one (1) as the oxidant has been developed. This system
has several features: (a) the reaction conditions are mild
(room temperature) and the chemical yields vary from
high to excellent; (b) the reaction is performed in ethyl
acetate, which is an environmentally benign organic sol-
vent; (c) the oxidant 1 has high stability and can be recy-
cled via simple manipulation; and (d) various
heteroaromatic rings and C=C bonds are compatible un-
In addition, a facile preparative method of 1 was also de-
veloped. Previously, 1 was prepared by chlorination of 2-
iodobenzoic acid using molecular chlorine in cold chloro-
form or nitromethane via the key intermediate dichloride
of 2-iodobenzoic acid.11 However, the use of molecular
chlorine is tedious and dangerous due to its hazardous na-
ture. We have reported a simple, convenient, and high
yielding preparative method for iodoarene dichloride with
O
O
O
O
I
Cl
+
O
O
I
I
Cl
A'
A
1
O
O
O–
PyH+
OH
Py
I
I
N
O
Cl
O
O
O
O
I
I
A'
A
Cl–
N
N
O
OH
C
B
alcohols
carbonyl compounds
Py⋅HCl
+
Scheme 3 Proposed mechanism
Synthesis 2009, No. 7, 1163–1169 © Thieme Stuttgart · New York

PAPER
A TEMPO-Catalyzed Efficient Alcohol Oxidation System
1167
combined with the Na2CO3 washings from the extraction workup.
Then NaClO2 (15 mmol, 1.7 g) and concd HCl (10 mL) were added
sequentially and the mixture was stirred overnight (10 h). When the
reaction was complete, the mixture was filtered, washed with H2O
and PE and dried (r.t.) to give regenerated 1 (1.83 g, 86% recovery).
The efficiency of the regenerated oxidant 1 did not decrease com-
pared with the freshly prepared 1 both in the reaction rate and yield
when it was used to oxidize decan-1-ol (2a).
der the reaction conditions. These features make this alco-
hol oxidation system potentially useful both in industry
and for the organic synthesis of complex compounds. In
addition, the presented method meets the requirement of
the pharmaceutical industry that asks for oxidation meth-
ods without the use of chlorinated solvents under mild
conditions with good selectivity.20 New investigations of
the synthetic applications of 1 are ongoing in our labora-
tory.
Decanal (3a)9a
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 9.69 (s, 1 H), 2.33–2.37 (m, 2 H),
1.53–1.57 (m, 2 H), 1.19–1.29 (m, 12 H), 0.81 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 202.73, 43.83, 31.77, 29.29,
29.17, 29.09, 22.57, 22.00, 13.99.
Known products were identified by comparison to their literature
1
melting points and H and 13C NMR data. New compounds were
identified by their IR (KBr), 1H and 13C NMR together with elemen-
tary analyses data. Petroleum ether = PE.
Hexadecanal (3b)9a
White solid; mp 32–34 °C (Lit. 35–36 °C).
1-Chloro-1,2-benziodoxol-3(1H)-one (1); Large-Scale Prepara-
tion
1H NMR (400 MHz, CDCl3): d = 9.69 (s, 1 H), 2.33–2.37 (m, 2 H),
1.53–1.57 (m, 2 H), 1.18–1.22 (m, 24 H), 0.81 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 202.84, 43.88, 31.90, 29.64,
29.33, 29.14, 22.66, 22.05, 14.09.
Concd HCl (200 mL) was added dropwise over 2 h to a stirred soln
of 2-iodobenzoic acid (24.8 g, 100 mmol) and NaClO2 (33.8 g, 300
mmol, 80% purity) in H2O (500 mL) at r.t. When the addition of the
concd HCl was completed, stirring was continued overnight (10 h)
at r.t. Light yellow solids gradually precipitated (TLC monitoring).
When the reaction was complete, the light yellow solids were col-
lected by filtration, washed with large amounts of H2O and PE and
then dried by suction at r.t. The color of the solids turned from light
yellow to pale yellow during the filtration workup. The pale yellow
solids were identified to be 1-chloro-1,2-benziodoxol-3-(1H)-one
(1) by comparison of its melting point with that reported in litera-
ture; yield: 26.4 g (94%); mp 172–173 °C (Lit.11c 168–171 °C).
Octanal (3c)9a
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 9.69 (s, 1 H), 2.33–2.36 (m, 2 H),
1.54–1.57 (m, 2 H), 1.21–1.23 (m, 8 H), 0.80 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 202.92, 43.89, 31.59, 29.09,
28.99, 22.56, 22.05, 14.02.
1H NMR (400 MHz, CDCl3): d = 8.17–8.31 (m, 2 H), 8.00 (t,
J = 7.2 Hz, 1 H), 7.80 (t, J = 7.2 Hz, 1 H).
Thiophene-2-carboxaldehyde (3f)21
Colorless oil.
13C NMR (100 MHz, CDCl3): d = 167.11, 136.56, 133.35, 131.80,
128.70, 126.84, 117.07.
1H NMR (400 MHz, CDCl3): d = 9.96 (s, 1 H), 7.77–7.80 (m, 2 H),
7.22–7.24 (m, 1 H).
Oxidation of Alcohols (without Recovery of 1); General Proce-
dure
13C NMR (100 MHz, CDCl3): d = 180.14, 141.15, 133.54, 132.57,
125.55.
1-Chloro-1,2-benziodoxol-3-(1H)-one (1, 1.5 mmol, 423 mg) was
added to a stirred soln of alcohol (1 mmol), TEMPO (0.08 mmol,
12.5 mg), and pyridine (3.0 mmol, 0.26 mL) in EtOAc (5 mL) at r.t.
(TLC monitoring). When the reaction was complete, it was
quenched with sat. Na2S2O3 (10 mL) and then the mixture was ex-
tracted with EtOAc (3 × 30 mL). The combined organic layers were
washed sequentially with 1 M HCl (1 × 15 mL), H2O (1 × 10 mL),
10% Na2CO3 (1 × 15 mL), and brine (1 × 15 mL) and then dried
(anhyd Na2SO4). The organic layer was concentrated in vacuo to af-
ford the crude product. Purification by flash column chromatogra-
phy (PE–EtOAc) afforded the desired carbonyl compounds
(Table 3).
3,5-Dichloropyridine-4-carboxaldehyde (3g)22
Pale yellow solid; mp 76–77 °C (Lit. 75–78 °C).
1H NMR (400 MHz, CDCl3): d = 10.46 (s, 1 H), 8.64 (s, 2 H).
13C NMR (100 MHz, CDCl3): d = 187.22, 149.33, 135.79, 131.61.
Undec-10-enal (3i)23
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 9.76 (t, J = 1.8 Hz, 1 H), 5.75–
5.85 (m, 1 H), 4.92–5.01 (m, 1 H), 2.42 (dt, J = 7.3, 1.8 Hz, 2 H),
2.01–2.06 (m, 2 H), 1.60–1.65 (m, 2 H), 1.30–1.39 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 202.67, 138.98, 114.06, 43.78,
Decanal (3a) with Recovery of Oxidant 1
33.66, 29.19, 29.15, 29.03, 28.92, 28.77, 21.96.
As depicted in Scheme 1, decan-1-ol (2a, 790 mg, 5 mmol) was
treated with 1 (2.12 g, 7.5 mmol) under the standard reaction condi-
tions. When the reaction was complete, most of the EtOAc was re-
moved in vacuo. Then the residue was filtered and the solids were
washed with a little EtOAc and PE to ensure that all the decanal (3a)
were in the filtrate. The filtrate was then diluted with EtOAc (150
mL) and washed with sat. Na2CO3 soln (2 × 15 mL) and the Na2CO3
washings were saved to be used thereafter. After that the EtOAc lay-
er was washed sequentially with 1 M HCl (1 × 25 mL), H2O (1 × 20
mL), and brine (1 × 25 mL). Then the EtOAc layer was dried (an-
hyd Na2SO4) and concentrated in vacuo to afford the crude product,
which was purified by flash column chromatography (PE–EtOAc,
49:1) to give decanal (3a) as a colorless oil; yield: 717 mg (92%).
The solids collected during the previous filtration workup were
10,11-Dichloroundecanal
Colorless oil.
IR (KBr): 2926, 2860, 1728, 1075 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.78 (s, 1 H), 4.01–4.04 (m, 1 H),
3.74–3.78 (m, 1 H), 3.63–3.67 (m, 1 H), 2.43 (t, J = 7.6 Hz, 2 H),
1.94–2.02 (m, 1 H), 1.63–1.72 (m, 3 H), 1.32–1.43 (m, 10 H).
13C NMR (100 MHz, CDCl3,): d = 202.83, 61.18, 48.22, 43.86,
34.98, 29.18, 29.13, 29.06, 28.85, 25.73, 22.01.
Anal. Calcd for C11H20Cl2O: C, 55.24; H, 8.43. Found: C, 54.85; H,
8.78.
Synthesis 2009, No. 7, 1163–1169 © Thieme Stuttgart · New York

1168
X.-Q. Li, C. Zhang
PAPER
(3) (a) Ley, S. V.; Thomas, A. W.; Finch, H. J. Chem. Soc.,
Octan-2-one (3j)9a
Colorless oil.
Perkin Trans. 1 1999, 669. (b) Tohma, H.; Morioka, H.;
Harayama, Y.; Hashizume, M.; Kita, Y. Tetrahedron Lett.
2001, 42, 6899. (c) Togo, H.; Sakuratani, K. Synlett 2002,
1966. (d) Sakuratani, K.; Togo, H. Synthesis 2003, 21.
(e) Shang, Y.; But, T. Y. S.; Togo, H.; Toy, P. H. Synlett
2007, 67. (f) Jang, H.-S.; Chung, W.-J.; Lee, Y.-S.
Tetrahedron Lett. 2007, 48, 3731. (g) Ladziata, U.;
Zhdankin, V. V. Synlett 2007, 527. (h) Karimov, R. R.;
Kazhkenov, Z.-G. M.; Modjewski, M. J.; Peterson, E. M.;
Zhdankin, V. V. J. Org. Chem. 2007, 72, 8149.
1H NMR (400 MHz, CDCl3): d = 2.33–2.37 (m, 2 H), 2.06 (s, 3 H),
1.46–1.51 (m, 2 H), 1.18–1.25 (m, 6 H), 0.82 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 209.24, 43.71, 31.51, 29.74,
28.76, 23.73, 23.41, 13.93.
Acetophenone (3k)9a
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 7.86–7.88 (m, 2 H), 7.46–7.50 (m,
1 H), 7.36–7.39 (m, 2 H), 2.52 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 198.07, 136.96, 133.02, 128.47,
128.20, 26.56.
(4) (a) Tohma, H.; Maruyama, A.; Maeda, A.; Maegawa, T.;
Dohi, T.; Shiro, M.; Morita, T.; Kita, Y. Angew. Chem. Int.
Ed. 2004, 43, 3595. (b) Dohi, T.; Maruyama, A.;
Yoshimura, M.; Morimoto, K.; Tohma, H.; Shiro, M.; Kita,
Y. Chem. Commun. 2005, 2205.
(5) (a) Moroda, A.; Togo, H. Tetrahedron 2006, 62, 12408.
(b) Telvekar, V. N.; Herlekar, O. P. Synth. Commun. 2007,
37, 859.
(6) (a) Rocaboy, C.; Gladysz, J. A. Chem. Eur. J. 2003, 9, 88.
(b) Tesevic, V.; Gladysz, J. A. J. Org. Chem. 2006, 71, 7433.
(7) (a) Yusubov, M. S.; Drygunova, L. A.; Zhdankin, V. V.
Synthesis 2004, 2289. (b) Yusubov, M. S.; Gilmkhanova,
M. P.; Zhdankin, V. V.; Kirschning, A. Synlett 2007, 563.
(c) Kirschning, A.; Yusubov, M. S.; Yusubova, R. Y.; Chi,
K.-W.; Park, J. Y. Beilstein J. Org. Chem. 2007, 3, 19.
(d) Yusubov, M. S.; Funk, T. V.; Chi, K.-W.; Cha, E.-H.;
Kim, G. H.; Kirschning, A.; Zhdankin, V. V. J. Org. Chem.
2008, 73, 295.
(8) Zhdankin, V. V. Curr. Org. Synth. 2005, 2, 121.
(9) (a) Zhao, X.-F.; Zhang, C. Synthesis 2007, 551. (b) Li,
X.-Q.; Zhao, X.-F.; Zhang, C. Synthesis 2008, 2589.
(10) Shibuya, M.; Tomizawa, M.; Suzuki, I.; Iwabuchi, Y. J. Am.
Chem. Soc. 2006, 128, 8412.
Menthone (3m)9a
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.26–2.30 (m, 1 H), 1.82–2.06 (m,
6 H), 1.27–1.30 (m, 2 H), 0.93 (d, J = 6.4 Hz, 3 H), 0.84 (d, J = 7.2
Hz, 3 H), 0.78 (d, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 212.17, 55.69, 50.72, 35.34,
33.78, 27.17, 25.73, 22.16, 21.08, 18.55.
Benzil (3n)9a
Yellow solid; mp 94–96 °C (Lit. 95–96 °C).
1H NMR (400 MHz, CDCl3): d = 7.98 (d, J = 8.0 Hz, 4 H), 7.66–
7.68 (m, 2 H), 7.50–7.54 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 194.51, 134.83, 132.82, 129.78,
128.93.
10-Hydroxyundecanal (5)24
Colorless oil.
(11) For the preparation of 1, see: (a) Meyer, V.; Wachter, W.
Ber. Dtsch. Chem. Ges. 1892, 25, 2632. (b) Willgerodt, C.
J. Prakt. Chem. 1894, 49, 466. (c) Amey, R. L.; Martin, J.
C. J. Org. Chem. 1979, 44, 1779. For the crystal structure of
1, see: (d) Prout, K.; Stevens, N. M.; Coda, A.; Tazzoli, V.;
Shaw, R. A.; Demir, T. Z. Naturforsch., B: Chem. Sci. 1976,
31, 687. (e) Takahashi, M.; Nanba, H.; Kitazawa, T.;
Takeda, M.; Ito, Y. J. Coord. Chem. 1996, 37, 371. For the
chlorination of aromatic hydrocarbons, see: (f) Andrews, L.
J.; Keefer, R. M. J. Am. Chem. Soc. 1959, 81, 4218. For the
application in the mechanism study on the cleavage of toxic
phosphate, see: (g) Moss, R. A.; Zhang, H. J. Am. Chem.
Soc. 1994, 116, 4471.
1H NMR (400 MHz, CDCl3): d = 9.77 (s, 1 H), 3.77–3.81 (m, 1 H),
2.41–2.45 (m, 2 H), 1.59–1.65 (m, 2 H), 1.39–1.45 (m, 3 H), 1.30–
1.33 (m, 10 H), 1.19 (d, J = 6.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 202.81, 67.87, 43.74, 39.18,
29.42, 29.23, 29.14, 28.99, 25.59, 23.34, 21.92.
Acknowledgment
This work was financially supported by The National Natural
Science Foundation of China (No. 20572046 and No. 20872064),
Program for New Century Excellent Talents in University (NCET),
and the 111 Project (B06005). We thank Professor Iwabuchi for e-
mailing us the detailed procedure for the synthesis of 1-Me-
AZADO before the related work was published (ref. 10).
(12) Sheldon, R. A. Green Chem. 2005, 7, 267; or see
http://en.wikipedia.org/wiki/Ethyl_acetate.
(13) De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.;
Piancatelli, G. J. Org. Chem. 1997, 62, 6974.
(14) Iodanyl radical A has been proposed before, generated from
homolytic cleavage of I–X bonds (X = N, O) of analogues of
1, ending up with 2-iodobenzoic acid, see: (a) Zhdankin, V.
V.; Krasutsky, A. P.; Kuehl, C. J.; Simonsen, A. J.;
Woodward, J. K.; Mismash, B.; Bolz, J. T. J. Am. Chem. Soc.
1996, 118, 5192. (b) Ochiai, M.; Ito, T.; Takahashi, H.;
Nakanishi, A.; Toyonari, M.; Sueda, T.; Goto, S.; Shiro, M.
J. Am. Chem. Soc. 1996, 118, 7716. (c) Barluenga, J.;
Campos-Gómez, E.; Rodríguez, D.; González-Bobes, F.;
González, J. M. Angew. Chem. Int. Ed. 2005, 44, 5851.
(15) (a) Hunter, D. H.; Barton, D. H. R.; Motherwell, W. J.
Tetrahedron Lett. 1984, 25, 603. (b) Hunter, D. H.; Racok,
J. S.; Rey, A. W.; Ponce, Y. Z. J. Org. Chem. 1988, 53, 1278.
(16) (a) De Nooy, A. E. J.; Beswmer, A. C.; Van Bekkum, H.
Synthesis 1996, 1153. (b) Adam, W.; Saha-Möller, C. R.;
Ganeshpure, P. A. Chem. Rev. 2001, 101, 3499. (c) Vogler,
T.; Studer, A. Synthesis 2008, 1979.
References
(1) (a) Larock, R. C. Comprehensive Organic Transformations,
2nd ed.; Wiley: New York, 1999. (b) Tojo, G.; Fernández,
M. Oxidation of Alcohols to Aldehydes and Ketones: A
Guide to Current Common Practice; Springer: New York,
2006.
(2) For some reviews on hypervalent iodine reagents, see:
(a) Banks, D. F. Chem. Rev. 1966, 66, 243. (b) Stang, P. J.;
Zhdankin, V. V. Chem. Rev. 1996, 96, 1123. (c) Varvoglis,
A. Hypervalent Iodine in Organic Synthesis; Academic
Press: San Diego, 1997. (d) Stang, P. J.; Zhdankin, V. V.
Chem. Rev. 2002, 102, 2523. (e) Hypervalent Iodine
Chemistry; Wirth, T., Ed.; Springer: Heidelberg, 2003.
(f) Tohma, H.; Kita, Y. Adv. Synth. Catal. 2004, 346, 111.
(g) Wirth, T. Angew. Chem. Int. Ed. 2005, 44, 3656.
(h) Matveeva, E. D.; Proskurnina, M. V.; Zefirov, N. S.
Heteroat. Chem. 2006, 17, 595.
Synthesis 2009, No. 7, 1163–1169 © Thieme Stuttgart · New York

PAPER
A TEMPO-Catalyzed Efficient Alcohol Oxidation System
(19) When bleach was used instead of NaClO2, a mixture
1169
(17) Radical A or A¢ was suggested to be a poor oxidant towards
TEMPO by trapping experiments using TEMPO performed
by Ochiai et al. in their oxidation of the benzylic and allylic
ether by stable hypervalent (tert-butylperoxy)iodanes via
benzylic and allylic radicals in which radical A or A¢ was
employed as a highly efficient hydrogen-abstracting species
(ref. 14b). On the other hand, the oxidation of TEMPO by
chlorine atom is well established (refs. 9a and 15).
Therefore, we proposed that radical A¢ could oxidize
hydroxylamine C to TEMPO via a hydrogen-abstracting
step.
(18) For pyridine used as a nucleophile onto iodine(III) reagents
in the presence of TMSOTf, see: (a) Weiss, R.; Seubert, J.
Angew. Chem. Int. Ed. 1994, 33, 891. (b) Zhdankin, V. V.;
Koposov, A. Y.; Yashin, N. V. Tetrahedron Lett. 2002, 43,
5735. (c) However, the possibility of pyridine being a
nucleophile in the present reaction could be ruled out since
oxidant 1 was recovered more than 90% after stirring the
mixture of 1 and pyridine with or without TEMPO in EtOAc
for much longer time (24 h) than that required for the alcohol
oxidation (0.5 to 9 h). Notably, other organic bases such as
triethylamine and DMAP which could also be used as acid
scavengers destroyed the oxidant 1 which was confirmed by
two control experiments.
containing 1, and other hard to separate byproducts was
obtained. The melting point of obtained products was from
167 °C to 234 °C, very different from that of 1 (Lit.11c 168–
171 °C). Indicated by the melting points, one of the
byproducts may be 1-hydroxy-1,2-benziodoxol-3 (1H)-one
(IBA, Lit.19 mp 231–232 °C). It was reported that IBA could
be generated from hydrolysis of 1 in strong basic media see:
Baker, G. P.; Mann, F. G.; Sheppard, N.; Tetlow, A. J.
J. Chem. Soc. 1965, 3721; Since the pH value of bleach is
13–14, IBA could be generated from 1 at the beginning of
the oxidizing process with bleach as the oxidant.
(20) Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G.
R.; Leazer, J. L. Jr.; Linderman, R. J.; Lorenz, K.; Manley,
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Chem. 2007, 9, 411.
(21) Velusamy, S.; Ahamed, M.; Punniyamurthy, T. Org. Lett.
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(22) Bertini, V.; Lucchesini, F.; Pocci, M.; De Munno, A.
Heterocycles 1995, 41, 675.
(23) Berube, M.; Poirier, D. Org. Lett. 2004, 6, 3127.
(24) Inokuchi, T.; Matsumoto, S.; Torii, S. J. Org. Chem. 1991,
56, 2416.
Synthesis 2009, No. 7, 1163–1169 © Thieme Stuttgart · New York