Mild oxidation of alcohols using soluble polymer-supported TEMPO in combination with oxone: Effect of a basic matrix of TEMPO derivatives

Article abstract of DOI:10.3987/COM-10-12027

The highly efficient and mild oxidation of alcohols using new soluble polymer-supported TEMPO derivatives in combination with Oxone is disclosed. Two types of the PEG-supported TEMPO derivative were easily synthesized by a simple esterification or Click Chemistry. The oxidation of primary alcohols with the precatalysts, TBAB, and Oxone in CH₂Cl₂ or BTF proceeded to afford the corresponding oxidized products. As a result of the reactions using several TEMPO derivatives including the nonpolymer-supported and insoluble polymer-supported compounds under the same reaction conditions, the synthesized PEG-supported TEMPO bearing a succinate spacer between the PEG and TEMPO parts was chosen as the best due to its high reactivity and product selectivity. This reaction was also applicable for the oxidation of secondary alcohols. In this system, the isolation of the products was achieved by simple filtration. The PEG-supported TEMPO bearing a succinate spacer was easily recovered and reused at least 10 times without a purification process. The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-10-12027

HETEROCYCLES, Vol. 81, No. 11, 2010
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HETEROCYCLES, Vol. 81, No. 11, 2010, pp. 2539 - 2553. © The Japan Institute of Heterocyclic Chemistry
Received, 23rd July, 2010, Accepted, 3rd September, 2010, Published online, 6th September, 2010
DOI: 10.3987/COM-10-12027
MILD
OXIDATION
OF
ALCOHOLS
USING
SOLUBLE
POLYMER-SUPPORTED TEMPO IN COMBINATION WITH OXONE:
EFFECT OF A BASIC MATRIX OF TEMPO DERIVATIVES
Kazutsugu Matsumoto,* Toshiaki Iwata, Masahiro Suenaga, Masayuki
Okudomi, Masaki Nogawa, Mariko Nakano, Ai Sugahara, Yuta Bannai, and
Kenji Baba
Department of Chemistry, Meisei University, 2-1-1 Hodokubo, Hino, Tokyo
191-8506, Japan
Abstract – The highly efficient and mild oxidation of alcohols using new soluble
polymer-supported TEMPO derivatives in combination with Oxone is disclosed.
Two types of the PEG-supported TEMPO derivative were easily synthesized by a
simple esterification or Click Chemistry. The oxidation of primary alcohols with
the precatalysts, TBAB, and Oxone in CH2Cl2 or BTF proceeded to afford the
corresponding oxidized products. As a result of the reactions using several
TEMPO derivatives including the nonpolymer-supported and insoluble
polymer-supported compounds under the same reaction conditions, the
synthesized PEG-supported TEMPO bearing a succinate spacer between the PEG
and TEMPO parts was chosen as the best due to its high reactivity and product
selectivity. This reaction was also applicable for the oxidation of secondary
alcohols. In this system, the isolation of the products was achieved by simple
filtration. The PEG-supported TEMPO bearing a succinate spacer was easily
recovered and reused at least 10 times without a purification process.
INTRODUCTION
The development of safe and mild oxidation procedures is still an attractive research field, and many
oxidizing reagents have been utilized for the transformation of alcohols to carbonyl compounds. In
particular, the reaction using a metal-free catalyst, such as 2,2,6,6-tertamethylpiperidinyl-1-oxyl
(TEMPO), is preferable for an environment-friendly system. On the other hand, the use of polymer-bound
catalysts has emerged because the recoverable and recyclable reagents allow us to realize a sustainable

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HETEROCYCLES, Vol. 81, No. 11, 2010
synthesis. In this context, several polymer-bound TEMPO species have also been reported.1 Recently,
poly(ethylene glycol) (PEG) has been recognized as an inexpensive and convenient soluble polymer,2-5
and the oxidations of alcohols using a PEG-supported TEMPO have also been developed under
homogeneous conditions.6-10 In almost all cases, the reactions were tested in combination with aqueous
bleach, which is a strong terminal oxidant, and the troublesome extraction procedure must also be
examined. We now disclose a mild and environment-friendly oxidation process of alcohols using a new
PEG-supported TEMPO in combination with Oxone (2KHSO5·KHSO4·K2SO4) as a co-oxidant, and the
easy isolation of the products was accomplished by simple filtration. We also investigated the effect of a
basic matrix of TEMPO derivatives.
RESULTS AND DISCUSSION
1
The purity of PEG-supported compounds can be determined by a H NMR analysis, and the integrated
intensities of the protons of a TEMPO part can be compared to that of the PEG-methylenes as the
reference. The simplest PEG-supported TEMPO (1, Scheme 1), which has no spacer between the PEG
and TEMPO, is commercially available from Aldrich. The average MW of the basic PEG of the
1
commercial 1 was estimated to be 3400 by an ESI-TOFMS analysis, but a H NMR analysis of the
commercial 1 indicated that the purity was estimated to be ca.50%. Moreover, in many previous cases,
the structure of the spacer between the PEG and the functionalized part should be important for the
reactivity, selectivity, etc.2-5 We then decided to prepare a new and highly pure PEG-supported TEMPO
bearing a spacer by a simple procedure.
O N
O
O
N O
PEG3400
1
Scheme 1
For the easy and effective preparation of the PEG-supported TEMPO, we tried to combine PEG with
TEMPO as ester bonds through a succinate spacer (Scheme 2). The reaction of 4-hydroxy TEMPO, the
free radical 2, and succinic anhydride with DMAP in CH2Cl2 proceeded at room temperature to give the
corresponding monocarboxylic acid 3 in an excellent yield. The sequential coupling of 3 with
PEG4600-OH (4, av MW 4600) using DMAP and DCC in CH2Cl2 at room temperature afforded the
PEG-supported TEMPO 5. The purity was estimated to be over 95% by a 1H NMR analysis. Compound 5
was easily precipitated by dilution with Et2O, and was treated as a solid.

HETEROCYCLES, Vol. 81, No. 11, 2010
2541
O
N
HO
OH
O
N
O
N
O
N
PEG4600 (4)
DMAP, DCC
CH2Cl2, rt
O
O
O
, DMAP
O
O
O
CH2Cl2, rt
99%
O
O
O
O
O
98%
OH
OH
O
O
O
2
3
5
Scheme 2
The production of 5 was confirmed by an ESI-TOFMS analysis. Figure 1a shows a part of the mass
spectrum obtained for PEG4600-OH (4). Because the spectrum shows the characteristic PEG series of ions
with a m/z 22 spacing, the most abundant ion was estimated to be 2301 Da and the molecular mass of 4
was determined to be ca. 4556 Da ([HO(CH2CH2O)103H·2Na]2+; z = +2). On the other hand, the mass
spectrum series of compound 5 was shifted to a higher m/z range (Figure 1b). The estimated m/z of 5 is
then 2555 Da as the most abundant ion, and the molecular mass was found to be ca. 5064 Da. This result
is almost consistent with the calculated mass (5061 Da) from C13H21NO5(CH2CH2O)103C13H21NO4.
(a)
2301
2301
600
400
200
0
Intensity
1800
3200
m/z
(b)
800
600
400
200
2555
Intensity
0
1800
3200
m/z
Figure 1. The ESI-TOFMS spectra of PEG and the PEG-supported compound. (a) the original
PEG4600-OH (4), and (b) the PEG4600-supported TEMPO 5.

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HETEROCYCLES, Vol. 81, No. 11, 2010
On the other hand, a tetra(ethylene glycol)(TEG)-supported TEMPO 7 bearing a shorter chain was also
synthesized by the coupling of 3 with TEG-OH (6) using the same procedure mentioned above (Scheme
3). Compound 7 was purified by column chromatography on silica gel, because compound 7 was liquid.
O
N
O
N
O
4H
HO
6
DMAP, DCC
O
O
O
O
3
O
O
CH2Cl2, rt
O
4
O
84%
7
Scheme 3
We also synthesized an alternative PEG-supported TEMPO 11 with Click Chemistry as the key step
(Scheme 4).11 The mesylate 8 derived from 4 was treated with sodium azide to afford the modified
PEG-N3 9. On the other hand, the 4-propargylated TEMPO 10 was prepared using propargyl bromide by
the same already reported method.12 After some trials, compound 10 was smoothly ligated with 9 using a
catalytic amount of CuSO4 and sodium ascorbate in CH2Cl2-H2O at room temperature to give the
PEG-supported TEMPO 11 bearing a triazol ring as the linker, although the purity (ca. 70%) was lower
than that of compound 7.
MsCl, Et3N
CH2Cl2, rt
56%
NaN3
DMF, 95 °C
98%
4
2
N3
N3
MsO
OMs
8
9
O
N
HC CCH Br
NaH,
2
DMF, rt
64%
O
10
N
N
CuSO4, Na ascorbate
CH2Cl2-H2O (1 : 1), rt
O N
O
N
N
+
9
10
O
N O
N
N
11
Scheme 4

HETEROCYCLES, Vol. 81, No. 11, 2010
2543
For the oxidation of alcohols with the PEG derivatives, we decided to use Oxone, which was well-known
as an environmentally safe and nontoxic reagent, as the most suitable co-oxidant, and we noticed that the
use of Oxone allowed us to proceed with easy handling and a controllable addition.13,14 In our case, the
PEG-supported precatalysts were soluble in some organic solvents, while Oxone was not. These
compounds could then be separated by simple filtration.
Initially, the oxidation of 1-octanol (12a) as a representative aliphatic primary alcohol by the PEG
supported TEMPO 5 bearing an ester linker was investigated under various reaction conditions (Scheme
5). In the preliminary experiments, we focused on the reaction conversion, which was determined by GC.
The experimental procedure was quite simple, and a typical example is as follows. To a solution of 5
(0.01 eq) in CH2Cl2 were added Oxone (2.2 eq), tetrabutyl ammonium bromide (TBAB, 0.04 eq), and 12a
(100 mg, 0.77 mmol; substrate conc., 0.15 M), and then the mixture was stirred at room temperature.
Because compound 5 contained two TEMPO parts per molecule, the solution substantially included 2
mol% of TEMPO. As expected, the PEG-supported TEMPO 5 proved to be an effective preoxidant, and
the conversion reached 100% after a 24 h-reaction. During the reaction, the halide ion significantly
affected the efficiency of the catalysis, and the reaction with TBAF (fluoride) and TBAI (iodide) hardly
proceeded. The addition of even TBAC (chloride), which indicated an effective halide source coupling
with TEMPO,13 decreased the conversion to 51%. We also investigated the influence of the solvent. Many
solvents including 1,4-dioxane, THF, DMF, and ethyl acetate scarcely provided the oxidized products,
while the reaction in toluene, which was effective for the oxidation of alcohols with TEMPO,13 gave a
low conversion (34%). On the other hand, the alcohol 12a was also effectively oxidized in CHCl3 and
benzotrifluoride (CF3C6H5, BTF), and the conversions were 98% and 100%, respectively. BTF is a
relatively low toxic compound, and has recently been used as an alternative solvent to CH2Cl2 in organic
reactions.15,16 Because BTF has a lower volatility as compared to CH2Cl2, we easily maintained the
reaction conditions in BTF. We then decided to mainly use BTF mainly in the following experiment.
5 (2 mol%)
TBAB (0.04 eq)
Oxone (2.2 eq)
O
O
+
OH
H
OH
CH2Cl2 or BTF, rt
12a
14a
13a
Scheme 5

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HETEROCYCLES, Vol. 81, No. 11, 2010
Table 1. Oxidation of 12a with TEMPO derivativesa
TEMPO derivative
(10 mol%)
TBAB (0.04 eq)
Oxone (2.2 eq)
O
O
+
OH
H
OH
BTF, 9 h, rt
12a
14a
13a
Ratio of
13a/14ab
Entry
TEMPO derivative
Conv. (%)
1
2
3
4
5
6
7
PEG-TEMPO 5c
TEMPO
100
81
84/16
92/8
PEG-TEMPO 11d
PEG-TEMPO 1e
TEG-TEMPO 7
Polystyrene-TEMPOf
Silica gel-TEMPOg
100
99
23/77
24/76
92/8
64
69
88/12
37
100/0
aUnless otherwise noted, the reaction was performed using 12a (sub. conc. 0.15 M) with TEMPO
derivatives (10 mol%), TBAB (0.04 eq), and Oxone (2.2 eq) at rt.
bDetermined by GC analysis with CP-Cyclodextrin-B-236-M19 (Chrompack).
cThe loading capacity was estimated at ca. 0.39 mmol TEMPO /g (>95% purity).
dThe loading capacity was estimated at ca. 0.28 mmol TEMPO /g (70% purity).
eThe loading capacity was estimated at ca. 0.27 mmol TEMPO /g (50% purity).
fThe loading capacity was ca. 1.1 mmol TEMPO/g.
gThe loading capacity was ca. 0.7 mmol TEMPO/g.
Table 1 shows the oxidations of 12a with some TEMPO derivatives including the PEG-supported
compounds 5 and 11 under the optimum conditions. The oxidation of 12a with 5 (0.05 eq, 10 mol% of
TEMPO) in BTF completely proceeded for 9 h to afford the corresponding oxidized compounds (entry 1).
During the reaction process, we achieved the easy separation of the products due to the use of PEG as the
basic matrix of TEMPO without any extraction procedures. When the reaction was finished, a simple
filtration removed Oxone from the reaction mixture. After evaporation, the residue was poured into Et2O
to precipitate the mixture of the PEG-supported 5 and TBAB, which was collected by filtration. Finally,
the products were obtained after evaporation. The products of the reaction with 5 included both octanal
(13a) and octanoic acid (14a, the ratio of 13a/14a was 84/16), but the aldehyde 13a as the major product
was easily isolated by column chromatography in a good isolated yield (83%). The oxidation of 13a to
14a was caused by Oxone,17,18 because TEMPO without Oxone did not catalyze the oxidation of 13a
under the same reaction conditions. Practically, the oxidation of 13a with Oxone (2.2 eq) in BTF at room
temperature proceeded to afford the carboxylic acid 14a, and the conversion of the 24-h reaction was up
to 100%. Unfortunately, reducing the amount of Oxone did not improve the selectivity, but required a

HETEROCYCLES, Vol. 81, No. 11, 2010
2545
longer reaction time for completely consuming the starting alcohol. On the other hand, the original
TEMPO had a lower activity in this system, and the conversion for the 9-h reaction was 81%, while the
ratio of 13a/14a was slightly up to 92/8 (entry 2). The alternative PEG-supported compound 11 bearing a
triazol spacer also had a higher catalytic activity. The oxidation of 12a with 11 also finished within 9 h,
but the main product was the carboxylic acid 14a (entry 3). Interestingly, the commercially available
PEG-TEMPO 1 gave the almost same result of that of 11 (entry 4). In these cases, lowering the reaction
time did not significantly improve the selectivity. It is noteworthy that the reaction using TEG-TEMPO 7,
which has the same spacer as that of the compound 5 and a shorter ethylene glycol chain, gave the
aldehyde 13a as the major product, but the conversion was quite low (64%). These results indicated that
the oxidation of 12a could be accelerated by the presence of the PEG part of the catalyst in this reaction
system, and the structure of the spacer between the PEG and TEMPO parts could also affect the oxidation
activity of 13a with Oxone. We also examined the reaction of 12a using insoluble polystyrene and silica
gel-supported TEMPO derivatives, which were purchased from Aldrich (entries 6 and 7, respectively). As
expected, the reactivities were lower than those of the PEG-TEMPO derivatives, and the conversions with
polystyrene-TEMPO and silica gel-TEMPO sfter 9 hours were 69 and 37%, respectively. Finally, we
decided to use compound 5 in the following studies, because we needed the lowest amount of the
precatalyst 5 in the reaction due to the highest purity, and the ratio of the products was easy to control
when using 5.
Table 2. Oxidation of primary alcohols with PEG-supported TEMPO 5a
O
O
5, TBAB, Oxone
+
R
OH
organic solvent, rt
R
OH
R
H
12
14
13
Yield of the
major product
(%)
Ratio of
13/14b
Entry
R
Solvent
Time (h)
1
2
3d
4d
5d
b
Ph
BTF
3
9
98/2c
76/24
0/100
0/100
0/100
70
62
98
85
91
c PhCH2CH2
CH2Cl2
a
C7H15
Ph
BTF + DMF (addition after 3h)
BTF + DMF (addition after 3h)
11
8
b
c PhCH2CH2 BTF + DMF (addition after 3h)
6
aUnless otherwise noted, the reaction was performed using 12 (sub. conc. 0.15 M) with 5 (10 mol%),
TBAB (0.04 eq), and Oxone (2.2 eq) at rt.
bDetermined by GC analysis with CP-Cyclodextrin-B-236-M19 (Chrompack).
cDetermined after the methyl esterification of 14b with trimethylsilyldiazomethane.
dAfter the substrate was completely consumed in BTF, the same volume of DMF as the initial BTF was
added to the mixture.

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HETEROCYCLES, Vol. 81, No. 11, 2010
We next tried to examine the oxidation of other primary alcohols using the PEG-supported 5 (Table 2). In
the case of benzyl alcohol (12b) (entry 1), the oxidation in BTF was finished in only 3 h with an excellent
selectivity to afford benzaldehyde (13a) as almost the sole product (13b/14b = 98/2). On the other hand,
the reaction of 3-phenyl-1-propanol (12c) in BTF for 10 h gave 3-phenypropanoic acid (14c) as the major
product (13c/14c = 33/67). In this case, changing the solvent to CH2Cl2 inverted the 13c/14c ratio, and the
reaction of 12c in CH2Cl2 for 9 h gave the 3-phenylpropanal (13c) in 62% isolated yield (13c/14c = 76/24;
entry 2). In the case of 12a, a longer reaction time in BTF gave the carboxylic acid 14a as the major
product, but the time taken to thoroughly react the aldehyde 13a needed 24 h. In a previous paper, DMF
was used as an effective solvent for the oxidation of aldehydes to carboxylic acids.18 In order to accelerate
the further oxidation of 12a to 13a, we then examined the addition of DMF to the reaction mixture after
12a was completely consumed (after 9h; entry 3). As expected, the oxidation of 13a was smoothly
finished within only another 2 h, and the compound 14a was produced in 98% yield. This procedure was
also applicable for the efficient production of other carboxylic acids, and the reactions of 12b and 12c
also gave benzoic acid (14b) and 14c in good yields, respectively (entries 4 and 5). In these cases, the
carboxylic acids containing no significant impurities were obtained without any purification steps.
Table 3. Oxidation of secondary alcohols with PEG-supported TEMPO 5.a
OH
O
5, TBAB, Oxone
R1 R2
R1 R2
BTF, rt
15
16
Entry
R1
R1
Time (h)
Yield (%)
1
2
3
4
5
6
7
a
b
c
d
e
f
Me(CH2)5
Me(CH2)7
PhCH2CH2
BnOCH2CH2
Ph
Me
Me
Me
Me
Me
24
24
24
24
7
82
80
75
76
98
91b
98
–(CH2)5–
–(CH2)7–
7
g
5
aAll of the reactions were performed using 15 (sub. conc. 0.15 M) with 5 (10 mol%), TBAB (0.04 eq),
and Oxone (2.2 eq) in BTF at rt.
bDetermined by GC with dodecane as the internal standard.
We next applied our oxidation protocol to various secondary alcohols 15, and these results are
summarized in Table 3. As expected, in all cases, the PEG-supported TEMPO 5 efficiently catalyzed the

HETEROCYCLES, Vol. 81, No. 11, 2010
2547
oxidations of 15a-g, and the conversions reached 100%. Although the reactivity of the aliphatic
secondary alcohols was lower than that of the primary alcohols, the 24-h reactions of 2-octanol (15a,
entry 1), 2-decanol (15b, entry 2), 4-phenyl-2-butanol (15c, entry 3), and 4-benzyloxy-2-butanol (15d,
entry 4) gave the corresponding ketones, 2-octanone (16a), 2-decanone (16b), 4-phenyl-2-butanone (16c),
and 4-benzyloxy-2-butanone (16d) in good yields, respectively. On the other hand, the oxidation of an
aromatic alcohol, 1-phenylethanol (15e, entry 5), and cyclic alcohols, cyclohexanol (15f, entry 6) and
cyclooctanol (15g, entry 7), smoothly proceeded in a manner similar to the primary alcohols to afford
acetophenone (16e), cyclohexanone (16f), and cyclooctanone (16g), respectively.
Table 4. Recycling of 5 for the Oxidation of 15ba
OH
O
5, TBAB, Oxone
BTF, 24 h, rt
Me(CH2)7
Me
15b
Me(CH2)7
Me
16b
Run
Conv. (%)
1
2
100
100
96
93
98
98
70
85
69
69
3
4
5
6
7
8
9
10
aAll of the reactions were carried out using 15b (sub. conc. 0.15 M) with 5 (10 mol%), TBAB (0.04 eq),
and Oxone (2.2 eq) in BTF for 24 h at rt.
As mentioned above, the recovery of the PEG-supported TEMPO 5 was quite simple, and the reusability
of the precatalyst 5 was examined for the oxidation of 15b (Table 4). In almost cases, the precatalyst was
recovered in ca. 90% yield based on the weight of the starting 5. The recovered and dried solid 5 included
a small amount of TBAB, however, the contained TBAB could be removed by washing the solution of
the solid in CH2Cl2 with 2 M HCl. However, for those listed in Table 4, we directly reused the recovered
5 again for the next run without any further purification in order to produce a simple procedure. It is
noteworthy that the conversions of the reactions from the first run to sixth run remained almost constant
(>93%). The conversions gradually decreased from the seventh run, because the impurities in the

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HETEROCYCLES, Vol. 81, No. 11, 2010
recovered 5 steadily increased. However, we observed the moderate activity (conv. 69%) in the recovered
precatalyst even after ten uses.
CONCLUSION
In summary, we have easily prepared new soluble polymer bound TEMPO derivatives and used it for the
oxidation of primary and secondary alcohols in combination with Oxone as the co-oxidant in BTF at
room temperature. We also investigated the effect of a basic matrix of TEMPO derivatives, and we found
that the PEG-supported TEMPO derivative bearing a succinate spacer gave the best result. Our mild and
environment-friendly oxidation system has the advantages not only for the facile separation of products,
but also for an easy recovery and convenient recycling.
EXPERIMENTAL
4.1. General
1H (300 MHz) and 13C (75 MHz) NMR spectra were measured on a JEOL JNM AL-300 with
tetramethylsilane (TMS) as the internal standard. ESI-TOF mass spectra were measured in MeOH-H2O
solution including AcONa with a JEOL JMS-T100. GLC data were obtained on GL Sciences GC 353B
and sic 480II data station (System Instruments Inc.) using CP-Cyclodextrin-B-236-M19 (Chrompack;
0.25 mm x 50 m; carrier gas, He; head pressure, 2.4 kg/cm2). E. Merck Kieselgel 60 F254 Art.5715 was
used for analytical TLC. Preparative TLC was performed on E. Merck Kieselgel 60 F254 Art.5744.
Column chromatography was performed with Silica Gel 60N (63-210 mm, Kanto Chemical Co. Inc.). All
other chemicals were also obtained from commercial sources. Polymer-bound reagents were purchased
from Aldrich Chem Co. [PEG supported-TEMPO with an ether linker (No. 678325), TEMPO
polymer-bound (No. 566098), TEMPO on silica gel (No. 709859)].
4.2. Preparation of PEG-supported TEMPO 5.
Under an argon atmosphere, to a solution of 4-hydroxy TEMPO, the free radical (2, 500 mg, 2.90 mmol)
in CH2Cl2 (5.5 mL) were added solutions of DMAP (1.06 g, 8.71 mmol) in CH2Cl2 (7 mL) and succinic
anhydride (872 mg, 8.71 mmol) in CH2Cl2 (39 mL) at 0 °C. After stirring overnight at room temperature,
the mixture was washed with 2 M HCl, and the products were extracted from the water layer with CH2Cl2
(x3). The combined organic layer was dried over Na2SO4. After evaporation under reduced pressure, the
residue was purified by flash column chromatography on silica gel (hexane/AcOEt = 1/1) to give the
1
compound 3 as an orange crystal (779 mg, 99%); H NMR (500 MHz, CDCl3) ! = 1.29 (s, 6H), 1.38 (s,
6H), 1.94 (dd, J1=J2=12.5 Hz, 2H), 2.30 (dd, J1=4.0 Hz, J2=13.5 Hz, 2H), 2.42-2.48 (m, 2H), 2.63–2.69
(m, 2H), 4.95–5.04 (m, 2H); 13C NMR (125 MHz, CDCl3) ! = 20.9, 27.9, 30.5, 31.2, 41.7, 64.7, 65.0,

HETEROCYCLES, Vol. 81, No. 11, 2010
2549
173.6, 179.4.
Under an argon atmosphere, to a solution of PEG4600-OH (4, 2.00 g, 0.435 mmol) in CH2Cl2 (20 mL) were
added a solution of 3 (391 mg, 1.44 mmol) in CH2Cl2 (5 mL), DMAP (266 mg, 2.18 mmol), and a
solution of DCC (283 mg, 1.31 mmol) in CH2Cl2 (25 mL) at 0 °C. After stirring overnight at room
temperature, the mixture was filtrated through a Celite pad. After the filtrate was washed with 2 M HCl,
the organic layer was dried over Na2SO4. After evaporation in vacuo, the residue was poured into Et2O to
precipitate the PEG-supported TEMPO 5 as a white solid in 98% yield (2.18 g; purity, ca. 96%); 1H NMR
(500 MHz, CDCl3 with phenylhydrazine) ! 1.21 (s, 12H), 1.24 (s, 12H), 1.56-1.72 (m, 4H), 1.88-1.97 (m,
4H), 2.57-2.66 (m, 8H), 3.44-3.80 (m, PEG-methylenes), 4.25 (t, J = 5.0 Hz, 4H), 5.04-5.11 (m, 2H); 13C
NMR (125 MHz, CDCl3 with phenylhydrazine) ! 22.9, 28.2, 28.6, 40.8, 43.0, 63.1, 66.3, 68.3, 69.5, 69.8
(PEG-methylenes), 70.0, 171.0, 171.6; ESI-TOF MS m/z 2555 Da (2553.5 Da calcd for
[C13H21NO5(CH2CH2O)103C13H21NO4!2Na]2+). The purity of 5 was determined by a 1H NMR analysis. The
integrated intensities of protons of a TEMPO part were compared with that of the PEG-methylenes as the
reference.
4.3. Preparation of TEG-supported TEMPO 7.
Under an argon atmosphere, to a solution of 3 (706 mg, 2.59 mmol) in CH2Cl2 (10 mL) were added a
solution of TEG-OH (6, 62.9 mg, 0.324 mmol) in CH2Cl2 (5 mL), DMAP (949 mg, 7.77 mmol), and a
solution of DCC (3.20 g, 15.5 mmol) in CH2Cl2 (10 mL) at 0 °C. After stirring overnight at room
temperature, the mixture was filtrated through a Celite pad. After evaporation under reduced pressure, the
residue was purified by flash column chromatography on silica gel (hexane/AcOEt = 5/1 to 1/1, to
1
AcOET) to give the compound 7 as an orange liquid (192 mg, 84%); H NMR (500 MHz, CDCl3 with
phenylhydrazine) ! 1.21 (s, 12H), 1.24 (s, 12H), 1.62 (dd, J1 = J2 = 11.5 Hz, 4H), 1.87-1.97 (m, 4H),
2.56-2.62 (m, 4H), 2.62-2.68 (m, 4H), 3.60-3.68 (m, 8H), 3.71 (t, J = 4.5 Hz, 4H), 4.26 (t, J = 4.5 Hz, 4H),
5.02-5.10 (m, 2H); 13C NMR (125 MHz, CDCl3 with phenylhydrazine) ! 21.1, 28.9, 29.2, 41.8, 43.2, 63.8,
65.5, 69.0, 70.5, 70.6, 171.7, 172.2; ESI-TOF MS m/z 725.3825 (725.3831 calcd for C34H58N2O13Na+).
4.4. Preparation of PEG-supported TEMPO 11.
Under an argon atmosphere, methanesulfonyl chloride (0.35 mL, 4.51 mmol) and triethylamine (1.50 mL,
10.8 mmol) were added to a solution of 4 (3.00 g, 0.60 mmol) in CH2Cl2 (13 mL), and the solution was
stirred overnight at room temperature. After evaporation in vacuo, the residue was poured into Et2O to
precipitate a white solid. After the solid was washed with 2-propanol, evaporation and precipitation gave
the mesylate 8 as a white solid in 99% yield (3.03 g); 1H NMR (500 MHz, CDCl3) ! 3.09 (s, 3H) 3.38 (s,

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3H), 3.46-3.82 (m, PEG-methylenes), 4.39 (t, J = 4.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) ! 37.6, 58.9,
68.9, 69.2, 70.4 (PEG), 70.5, 70.6, 71.8.
Under an argon atmosphere, sodium azide (256 mg, 3.94 mmol) were added to a solution of 8 (4.00 g,
0.788 mmol) in toluene (10.5 mL), and the solution was stirred overnight at 95 °C. The mixture was
evaporated in vacuo, and the residue was filtrated through a Celite pad. After evaporation, the residue was
1
poured into Et2O to precipitate the compound 9 as a white solid in 95% yield (3.75 g); H NMR (500
13
MHz, CDCl3) ! 3.38 (s, 3H), 3.40 (t, J = 5.0 Hz, 2H), 3.46-3.82 (m, PEG-methylenes); C NMR (125
MHz, CDCl3) 50.5, 58.9, 69.9, 70.4 (PEG), 70.55, 70.62, 71.8.
Under an argon atmosphere, to NaH (558 mg, 12.8 mmol) were added a solution of 2 (2.00 g, 11.6 mmol)
in DMF (8 mL) at 0 °C. After stirring 1 h, propargyl bromide (1.89 ml, 15.9 mmol) was added to the
mixture. After stirring for 20 h at room temperature, the mixture was quenched with water, and the
products were extracted with AcOEt (x3). The combined organic layer was washed with brine (x2), and
dried over Na2SO4. After evaporation under reduced pressure, the residue was purified by flash column
chromatography on silica gel (hexane/AcOEt = 10/1) to give the compound 10 as an orange crystal (1.56
1
g, 64%); H NMR (500 MHz, CDCl3) ! = 1.19 (s, 6H), 1.25 (s, 6H), 1.51 (dd, J1=J2=11.5 Hz, 2H),
1.91-2.07 (m, 2H), 2.43 (dd, J1=J2=2.5 Hz, 1H), 3.85 (dddd, J1=J2=4.0 Hz, J3=J4=11.5 Hz, 1H), 4.17 (d, J
= 2.5 Hz, 2H);13C NMR (125 MHz, CDCl3) ! = 20.7, 31.8, 44.1, 55.2, 59.8, 69.5, 74.1, 80.0.
Under an argon atmosphere, to a solution of 9 (1.00 g, 0.290 mmol) in CH2Cl2 (1.5 mL) were added
CuSO4·5H2O (7.3 mg, 29.2 mmol), sodium ascorbate (17.4 mg, 87.8 mmol), 10 (146 mg, 0.695 mmol),
and water (1.5 mL). After stirring overnight at room temperature, 2 M HCl was added to the mixture, and
the products were extracted with CH2Cl2 (x4). The combined organic layer was dried over Na2SO4. After
evaporation in vacuo, the residue was poured into Et2O to precipitate the PEG-supported TEMPO 11 as
an orange solid in 97% yield (1.10 g; purity, ca. 70%); 1H NMR (500 MHz, CDCl3 with phenylhydrazine)
! 1.35 (s, 12H), 1.48 (s, 12H), 1.78-2.00 (m, 4H), 2.07-2.20 (m, 4H), 3.50 (t, J = 5.0 Hz, 4H), 3.45-3.75
(m, PEG-methylenes), 3.78 (t, J = 5.0 Hz, 4H), 3.87 (t, J = 5.0 Hz, 8H), 4.55 (t, J = 5.0 Hz, 4H), 4.65 (s,
4H), 7.36 (s, 2H); 13C NMR (125 MHz, CDCl3 with phenylhydrazine) ! 21.1, 30.8, 43.9, 50.2, 61.8, 69.5,
70.5 (PEG-methylenes), 123.7, 145.3, 151.2; ESI-TOF MS m/z 2536 Da (2523 Da calcd for
1
[C12H20N4O2(CH2CH2O)103 C12H20N4O2!2Na]2+). The purity of 11 was determined by a H NMR analysis.
The integrated intensities of protons of a TEMPO part were compared with that of the PEG-methylenes as
the reference.

HETEROCYCLES, Vol. 81, No. 11, 2010
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4.5. Typical procedure for the oxidation of 2-decanol (15b) using 5 with Oxone.
Under an argon atmosphere, to a solution of 5 (648 mg, 0.126 mmol) in BTF (10 mL) were added Oxone
(3.41 g, 5.54 mmol), TBAB (28.1 mg, 0.101 mmol), and a solution of 15b (398 mg, 2.52 mmol) in BTF
(10 mL). After stirring for 24 h at room temperature, the mixture was filtrated through a cotton plug.
After evaporation in vacuo, the residue was poured into Et2O to precipitate 5 (617 mg, 95%). After
evaporation in vacuo, the residue was purified by flash column chromatography on silica gel
(hexane/AcOEt = 20/1) to give 16b as a colorless oil (314 mg, 80%).
The reactions of the other substrates were carried out by the same procedure. The results were shown in
the text.
4.6. Several data of the GC conditions.
Oxidation of 1-octanol (12a): injection, 160 °C; detection, 160 °C; oven, 140 °C; retention time, 5.0
(1-octanal (13a)), 6.4 (12a), and 15.1 (octanoic acid (14a)) min.
Oxidation of benzyl alcohol (12b): injection, 160 °C; detection, 160 °C; oven, 140 °C; retention time,
5.4 (benzaldehyde (13b)), 6.3 (12b), and 6.8 (methyl benzoate) min.
Oxidation of 3-phenyl-1-propanol (12c): injection, 200 °C; detection, 200 °C; oven, 180 °C; retention
time, 5.4 (3-phenylpropanal (13c)), 6.5 (12c), and 11.8 (3-phenylpropanoic acid (14c)) min.
Oxidation of cyclohexanol (15f): injection, 160 °C; detection, 160 °C; oven, 140 °C; retention time, 4.7
(cyclohexanone (16f)) and 6.6 (dodecane as a internal standard) min.
ACKNOWLEDGEMENTS
This work was partially supported by a Grant-in-Aid for Scientific Research (No. 21550051) from the
Ministry of Education, Culture, Sports, Science and Technology, Japan. We thank Material Science
Research Center (Meisei university) for NMR analysis.
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