Aerobic oxidation of alcohols to carbonyl compounds mediated by poly(ethylene glycol)-supported TEMPO radicals

Article abstract of DOI:10.1016/j.tet.2005.07.107

Two poly(ethylene glycol)-supported TEMPO (PEG-TEMPO) has been successfully applied as soluble, recyclable catalysts in the chemoselective oxidation of primary and benzylic alcohols with molecular oxygen in the presence of Co(NO₃)₂ and Mn(NO₃)₂ as co-catalysts (Minisci's conditions). Under those conditions, secondary alcohols are also oxidized to ketones, although usually in lower yields. The insertion of a spacer between the PEG moiety and TEMPO has beneficial effects on both the activity and ease of recovery of the supported catalyst.

Full text of DOI:10.1016/j.tet.2005.07.107

Tetrahedron 61 (2005) 12058–12064
Aerobic oxidation of alcohols to carbonyl compounds mediated by
poly(ethylene glycol)-supported TEMPO radicals
Maurizio Benaglia,a Alessandra Puglisi,a Orsolya Holczknecht,b Silvio Quicib
and Gianluca Pozzib,
*
a
`
Dipartimento di Chimica Organica e Industriale, Universita degli Studi di Milano, Via Golgi 19, I-20133 Milano, Italy
bCNR, Istituto di Scienze e Tecnologie Molecolari, via Golgi 19, 20133 Milano, Italy
Received 14 June 2005; revised 15 July 2005; accepted 15 July 2005
Available online 17 October 2005
Abstract—Two poly(ethylene glycol)-supported TEMPO (PEG-TEMPO) has been successfully applied as soluble, recyclable catalysts in
the chemoselective oxidation of primary and benzylic alcohols with molecular oxygen in the presence of Co(NO3)2 and Mn(NO3)2 as
co-catalysts (Minisci’s conditions). Under those conditions, secondary alcohols are also oxidized to ketones, although usually in lower yields.
The insertion of a spacer between the PEG moiety and TEMPO has beneficial effects on both the activity and ease of recovery of the
supported catalyst.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
process.12 A more versatile and efficient catalytic procedure
in which buffered bleach acts as the terminal oxidant was
introduced in 1987 by Montanari and co-workers.13 The
oxidation reaction proceeds under mild conditions and both
primary and secondary alcohols are converted to carbonyl
compounds in high yields, even in large scale operations. In
addition, the oxidation of primary alcohols can be driven to
give carboxylic acids by adding a phase-transfer catalyst to
the biphasic aqueous/organic system.14 Many other organic
and inorganic terminal oxidants (e.g., [bis(acetoxy)iodo]-
benzene (BAIB),15 trichloroisocyanuric acid (TCCA),16
oxone,17 or iodine18) have been subsequently introduced
with the aim of further expanding the already wide
applicability of Montanari’s procedure.
Catalytic oxidation using the stable nitroxyl radical 2,2,6,6-
tetramethylpiperidine-1-oxyl (TEMPO) in combination
with safe and easy to handle primary oxidants has become
one of the most promising procedures to convert primary
and secondary alcohols into the corresponding carbonyl
compounds.1–4 Indeed, efficient traditional methods for this
functional group transformation involve the use of
stoichiometric amounts of either inorganic oxidants (e.g.,
chromium (VI) salts) or organic oxidants (e.g., activated
DMSO).5–7 These methods hardly satisfy the current demand
for non-polluting chemical processes of high atom efficiency,
thus rendering new selective procedures, which do not
generate large amounts of by-products highly desirable.8,9
A different approach, pioneered by Semmelhack and
co-workers,19 consists of the use of oxygen as the primary
oxidant in conjunction with a TEMPO/metal catalyst
combination. The use of oxygen would be preferred over
that of the above-mentioned oxidants from both an
economic and an environmental standpoint and Semmel-
hack actually demonstrated the aerobic oxidation of allylic
and benzylic alcohols to aldehydes by TEMPO/CuCl in
DMF. Unfortunately, this method is ineffective with
aliphatic and alicyclic alcohols and its applicability is
therefore, limited.† Better results were obtained by Sheldon
Several organic and inorganic oxidants react with TEMPO
generating the corresponding oxoammonium salt. The latter
is a much stronger oxidant than the nitroxyl radical and
cleanly reacts with alcohols to give aldehydes or ketones.10
Based on this, several catalytic systems in which the
oxoammonium salt is (re)generated in situ from sub-
stoichiometric amounts of TEMPO have been developed.
Early examples of TEMPO-mediated reactions included
the oxidation of secondary alcohols to ketones with
m-chloroperbenzoic acid,11 and the oxidation of primary,
secondary and benzylic alcohols in an electrochemical
† According to Semmelhack, an oxoammonium salt generated by oxidation
of TEMPO by Cu(II) is the actual oxidant, but, as pointed out by Sheldon,
the lack of reactivity of aliphatic alcohols is not consistent with this
hypothesis. For an exhaustive discussion and more plausible reaction
mechanisms see Ref. 4.
Keywords: Alcohols; Aldehydes; Ketones; Oxidation; Soluble polymers.
*
Corresponding author. Tel.: C39 2 50 31 41 63; fax: C39 2 50 31 41 59;
e-mail: gianluca.pozzi@istm.cnr.it
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.107

M. Benaglia et al. / Tetrahedron 61 (2005) 12058–12064
12059
and co-workers who achieved the aerobic oxidation of a
broad range of alcohols using a combination of RuCl2-
(PPh3)3 and TEMPO in chlorobenzene, toluene or even in
the absence of a solvent.8,20,21 Besides requiring an
expensive transition-metal complex, the method operates
at a relatively high temperature (100 8C) and, in the case of
secondary alcohols, high oxygen pressure (up to 10 bar).
These drawbacks are partly avoided by using a combination
of TEMPO and the polyoxometalate H5[PV2Mo10O4].22
More recently, the aerobic oxidation of alcohols under
fluorous biphasic conditions and atmospheric pressure in the
presence of TEMPO and synthetically demanding fluorous
Cu(I) complexes has been independently described by two
groups.23,24 A mixture of CuBr2, 2,2,0-bipyridine and
t-BuOK was shown to catalyze the aerobic oxidation of
primary and benzylic alcohols in the presence of TEMPO in
CH3CN/H2O 1:1 as a solvent under mild conditions.25,26
Another uncomplicated and cheap catalytic system com-
prised of TEMPO in combination with tiny amounts of
Mn(NO3)2 and Co(NO3)2 in CH3COOH was reported by
Minisci and co-workers.27,28 This combination is particu-
larly effective for the oxidation of primary and benzylic
alcohols, but good results are also obtained with less
reactive secondary alcohols. In order to avoid the use of
metal salts, Hu and co-workers developed two aerobic
processes in which TEMPO is used in combination with
Br2/NaNO2 or 1,3-dibromo-5,50-dimethylidantoin/NaNO2
TEMPO, respectively.29,30 Teflon-lined apparatus, oper-
ating pressures up to 9 bar and relatively high amounts
of TEMPO and co-catalysts (up to 10 mol% in the
case of the oxidation of secondary alcohols in the
presence of 1,3-dibromo-5,50-dimethylidantoin/NaNO2)
were required.
and co-workers who attached 4-oxo-2,2,6,6-tetramethyl-
piperidine-1-oxyl to a commercially available aminopropyl-
functionalized silica and an aminopropyl-functionalized
porous glass. These catalysts were employed in combination
with bleach under Montanari’s conditions affording high
yields and selectivities. Ten subsequent reaction runs were
demonstrated, although partial degradation of the supported
TEMPO catalysts was observed.38,40 Silica matrices doped
with TEMPO prepared under mild conditions by the sol–gel
approach were also found to be selective and recyclable
heterogeneous catalysts for the oxidation of alcohols with
bleach.41,42 A polymer immobilized nitroxyl radical derived
from a commercially available oligomeric 2,2,6,6-tetra-
methylpiperidine (Chimassorb 994) was developed by
Sheldon and co-workers.43 Analogously to TEMPO, this
catalyst allowed the smooth conversion of benzylic, primary
and secondary alcohols to carbonyl compounds with bleach
as the terminal oxidant. In addition, when using methyl-tert-
butylether or no solvent, the catalyst proved to be
heterogeneous and could be recycled.44 Very recently,
Toy and co-workers have shown that TEMPO attached to a
swellable resin and polystyrene-supported diacetoxyiodo-
sobenzene can be used simultaneously for the selective
oxidation of a variety of alcohols.45 The polymeric oxidant
in excess and the supported TEMPO catalyst can be
recovered by simple filtration and reused.
As a result of the increasing interest in recoverable soluble
reagents and catalysts,46 in the last few years immobiliz-
ation of TEMPO onto soluble polymers has started to
emerge as an alternative to the above-mentioned hetero-
geneous supports. Soluble polymer-supported TEMPO
radicals have been prepared by ring-opening methatesis of
norbornene derivatives.47 Preliminary tests revealed that the
activity of these catalysts was consistently lower than that of
TEMPO in the oxidation of alcohols under Montanari’s
conditions. Promising results have been obtained in the
oxidation of alcohols with various primary oxidants
(including bleach) catalyzed by a TEMPO derivative
tethered onto a modified commercially available poly-
(ethylene glycol) (PEG) monomethyl ether of molecular
weight of about 5000 Da.48 The catalyst was easily
recovered by selective precipitation from Et2O and its
recyclability was studied using the oxidation of 1-octanol
with the mild oxidant BAIB as a model reaction. The results
of independent studies on the catalytic performance and
recyclability of a series of PEG-supported TEMPO
derivatives in the oxidation of alcohols under Montanari’s
conditions has been also disclosed.49,50 Even more recently,
it has been shown that recoverable soluble TEMPO catalysts
can be designed without recourse to polymeric supports.
Fluorous TEMPO derivatives have been used as selective
catalysts for the oxidation of alcohols under mild,
homogeneous conditions.51 The peculiar solubility proper-
ties ensured by the presence of highly fluorinated domains
allowed the easy recovery of some of these catalysts by
liquid–liquid or solid-phase extraction of the reaction
mixture. Gao and co-workers reported the synthesis of a
TEMPO radical attached to an imidazolium cation and
investigated its catalytic activity for the oxidation of
alcohols with bleach in a biphasic system ionic liquid/
water. The catalytic activity of this system was similar to
Recovery and recycling of TEMPO by immobilization on
either inorganic or organic supports has been actively
investigated. Indeed, whichever oxidant is used, separation
of the products from TEMPO could require lengthy workup
procedures, especially when reactions are run on large scale.
Moreover, TEMPO is quite expensive, so it is desirable to
be able to separate the catalyst after the oxidation reaction
and to reuse it. Electrochemical processes were readily
adapted to meet these goals and several examples of
graphite felt electrodes and glassy carbon electrodes coated
with TEMPO and related radicals have been used for the
electrochemical oxidation of alcohols.31,32 In 1985,
Miyazawa and Endo reported the synthesis of soluble and
insoluble polystyrene-type polymers featuring TEMPO
residues, which were used as catalysts for the oxidation of
benzyl alcohol to benzaldehyde with K3Fe(CN)6 or CuCl2/
Cu(OH)2 as the terminal oxidants.33,34 While no mention of
recovery and recycling of these catalysts was provided, the
same group later reported that 4-hydroxy-2,2,6,6-tetra-
methylpiperidine-1-oxyl (4-OH-TEMPO) immobilized
onto silica or ferrite (previously functionalized by the
reaction of their surface hydroxyl groups with 4-trimethoxy-
silyl-1,2,5,6-tetrahydrophthalic anhydride) could be
recycled up to 45 times in the benzyl alcohol oxidation
promoted by CuCl2/Cu(OH)2.35 Silica-supported TEMPO
radicals and their use in alcohol oxidations were
subsequently reported by several groups. Both silica gel
and ordered mesoporous silica (e.g., MCM-41) were
used,36–39 the best results being obtained by Bolm

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M. Benaglia et al. / Tetrahedron 61 (2005) 12058–12064
that observed with TEMPO and the ionic liquid phase
containing the catalyst was recycled up to three times.52
2. Results and discussion
Poly(ethylene glycol)s (PEGs) of Mw greater than 2000 Da
are readily functionalized, inexpensive polymers that
exhibit excellent solubility in many organic solvents,
including CH2Cl2 and CH3COOH. PEG precipitation as a
semicrystalline solid can be then induced by dilution of the
solution with an incompatible solvent, such as Et2O. This
behavior and the ease of functionalization make PEG a
popular soluble polymeric support for homogeneous
catalysts.55 Indeed, the choice of proper solvent combi-
nations makes it possible to run a reaction under
homogeneous catalysis conditions (where the PEG-sup-
ported catalyst is expected to perform at its best) and then to
recover the catalyst by precipitation/filtration as if it were
bound to an insoluble matrix.
Despite the obvious advantages of using of oxygen as
terminal oxidant, examples of aerobic oxidation of alcohols
in the presence of recoverable and recyclable nitroxyl
radicals are limited. A few solid polymer-supported
TEMPO derivatives have been tested as catalysts for the
aerobic oxidation of benzylic alcohols under Semmelhack’s
conditions (CuCl/DMF).39,44 A tetranitroxyl radical poorly
soluble in most organic solvents, developed by Ciba
chemists, gave good results in the aerobic oxidation of a
wider range of substrates under slightly modified Minisci’s
conditions and was recycled for four times.53 Analogously,
a new polymer-supported TEMPO prepared by reaction
between 4-OH-TEMPO and a carboxylic acid function-
alized fiber was used as an heterogeneous catalyst under
Minisci’s conditions showing high activity and selectivity
for the oxidation of primary alcohols to aldehydes.54
In a recent communication, we described the synthesis of
the PEG-supported nitroxyl radical 1 (PEG-TEMPO 1,
Fig. 1) in which a TEMPO moiety is connected to the
polymeric backbone (MwZ5000)‡ by a benzylic ether linker
(Scheme 1).48 As shown by Ferreira et al., the same TEMPO
residue can be attached directly to the PEG chain terminus
via an ether linkage.49 A slight modification of their original
method (Scheme 2) allowed us to prepare PEG-TEMPO 2 in
80% yield from 4-OH-TEMPO and the known PEG
mesylate derivative 3.56
We here show that PEG-supported TEMPO derivatives can
be conveniently employed as homogeneous, recoverable
and recyclable catalysts for the aerobic oxidation of
alcohols under Minisci’s conditions, combining the advant-
ages typical of heterogenized TEMPO with those of the
soluble parent compound.
Both PEG-supported TEMPO derivatives were found to be
completely soluble in CH3COOH, the solvent of choice for
the oxidation of alcohols under the conditions developed by
Minisci, which are the most convenient among those
Scheme 2. Synthesis of PEG-TEMPO 2.
Figure 1. PEG-supported TEMPO radicals.
Scheme 1. Synthesis of PEG-TEMPO 1.
‡ Commercially available PEGs possess very narrow polydispersity
indices. Mw of the PEG used actually ranges from 4500 to 5500 Da.

M. Benaglia et al. / Tetrahedron 61 (2005) 12058–12064
Table 2. Aerobic oxidation of 4-bromobenzyl alcohol
12061
proposed for the aerobic oxidation of alcohols catalyzed by
TEMPO.27,28 Thus, the oxidation of the model compound
4-bromobenzyl alcohol was studied using a combination of
Mn(NO3)2$H2O (2 mol%), Co(NO3)2$H2O (2 mol%) and
PEG-TEMPO (1 or 2) in acetic acid (Scheme 3). We were
pleased to observe that using 5 mol% of either 1 or 2,
4-bromobenzaldehyde was formed quantitatively at room
temperature under atmospheric pressure of oxygen in less
than 3 h (Table 1, entries 1 and 2). It should be noted that
under similar conditions, but in the presence of TEMPO, the
aerobic oxidation of para-substituted benzyl alcohols
proceeds much slower, requiring up to 6 h and 10 mol%
of nitroxyl radical to go to completion.27 When the amount
of PEG-TEMPO was reduced to 2 mol%, the oxidation still
went to completion smoothly in 4 h in the case of 1, whereas
only 92% conversion was attained using the linker-less
radical 2 (entries 3 and 4). The higher activity of 1 was
further evidenced by experiments carried out using 1 mol%
of PEG-TEMPO (entries 5 and 6).
Run
PEG-TEMPO
Conversion (%) Selectivity (%)
1
2
3
4
5
6
1
2
3
4
5
6
1
O99
O99
O99
91
O99
O99
O99
O99
O99
O99
O99
O99
O99
O99
O99
O99
83
74
2
O99
98
96
92
84
80
Recycling of PEG-TEMPO radicals. TZ25 8C; O2Z1 atm; PEG-TEM-
POZ5 mol%; Mn(NO3)2Z2 mol%; Co(NO3)2Z2 mol%; reaction timeZ
3 h; conversion and selectivity determined by GC (see Section 4 for
details).
Recovery and recycling of PEG-TEMPO 2 was also
demonstrated, but in that case direct precipitation of the
radical was not viable. Indeed, a slurry formed upon
addition of ice-cold Et2O to the reaction solution and a
sensible loss of 2 was observed after filtration. A procedure
similar to that employed for the recovery of the above-
mentioned tetranitroxyl radical, proved to be more effective.
Acetic acid was first evaporated, followed by addition of
ice-cold Et2O to dissolve the reaction product leaving the
insoluble PEG-TEMPO 2 as a solid residue. Six subsequent
runs using 4-bromobenzyl alcohol as a substrate were thus
carried out, with results very close to those obtained in the
case of PEG-TEMPO 1.
Attempts to recover and recycle the two PEG-TEMPO
radicals also gave good results (Table 2). The post-reaction
work-up was particularly straightforward in the case of 1,
which was precipitated out from the acetic acid solution by
adding ice-cold Et2O. The radical was recovered by
filtration, dried under vacuum and re-used without any
further treatment. Fresh Mn(NO3)2$H2O and Co(NO3)2$
H2O were added to each successive run. No decrease in the
rate and in the selectivity of oxidation was observed in the
first three runs. However, the activity of the catalytic
system progressively decreased in the fourth and fifth
run and conversion of 4-bromobenzyl alcohol to 4-bromo-
benzaldehyde was as low as 74% after a reaction time of 3 h
in the sixth run. These results compare well with those
reported in the case of a soluble tetranitroxyl radical, which
has been used as catalyst in the oxidation of benzyl alcohol
with a ratio substrate/radicalZ41 (corresponding to a
concentrationZ10 mol% of nitroxyl radical) and recycled
for four times affording benzaldehyde in 95% yield in the
fourth run.53
The aerobic oxidation of a variety of alcohols catalyzed by
PEG-TEMPO radicals under Minisci’s conditions was next
examined (Table 3). Benzylic alcohols were readily
oxidized with high conversion and high selectivity to the
corresponding aldehydes both in the presence of PEG-
TEMPO 1 and PEG-TEMPO 2 (catalyst loadingZ5 mol%,
entries 1–3). Analogously to what was observed with
TEMPO,27 the oxidation of primary alcohol was best
performed at 40 8C in the presence of either 5 or 10 mol% of
PEG-TEMPO 1 depending on the substrate (entries 4, 7 and
9). Besides aldehydes, small amounts of carboxylic acids
(!5% of the starting alcohol) were detected. The difficult
conversion of unreactive aliphatic primary alcohols using
oxygen as terminal oxidant proceeded more slowly in the
presence of PEG-TEMPO 2. For instance, with a catalyst
loading of 5 mol% conversion of 1-octanol attained 65% in
4 h (entry 5) against 97% attained in the reaction catalyzed
by PEG-TEMPO 1 (entry 4). The reaction did not go to
completion even in the presence of 10 mol% of PEG-
Scheme 3. Aerobic oxidation of alcohols under Minisci’s conditions
catalyzed by PEG-TEMPO.
Table 1. Aerobic oxidation of 4-bromobenzyl alcohol to aldehyde, catalyzed by PEG-TEMPO radicals in combination with Mn(II) and Co(II) nitratesa
Entry
Radical
Mol%
Time (h)
Conversion (%)
Selectivity (%)
1
2
3
4
1
2
1
2
5
5
2
2
1
1
10
3
3
4
4
5
5
6
O99
O99
O99
92
90
72
O99
O99
O99
O99
O99
O99
O99
5
1
6
2
TEMPO
7b
O99
a TZ25 8C; O2Z1 atm; Mn(NO3)2Z2 mol%; Co(NO3)2Z2 mol%; conversion and selectivity determined by GC (see Section 4 for details).
b Literature data (Ref. 27). SubstrateZ4-methylbenzyl alcohol. TZ20 8C.

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M. Benaglia et al. / Tetrahedron 61 (2005) 12058–12064
Table 3. Aerobic oxidation of alcohols to carbonyl compounds, catalyzed by PEG-TEMPO radicals in combination with Mn(II) and Co(II) nitratesa
Entry
PEG-TEMPO
Alcohol
T (8C)
Time (h)
Conversion (%)
Selectivity (%)
1
2
3
1
2
1
Benzyl alcohol
Benzyl alcohol
4-Nitrobenzyl
alcohol
25
25
25
3
3
3
O99
O99
O99
O99
O99
O99
4
5
6
7
8
9
10
11
12
13
14
15
1
1-Octanol
1-Octanol
1-Octanol
1-Undecanol
1-Undecanol
Cinnamyl alcohol
1-Phenylethanol
Cyclooctanol
Cyclooctanol
2-Octanol
40
40
40
40
40
40
25
40
40
40
40
40
4
4
4
4
4
6
5
4
97
65
75
O99
78
O99
96
O99
68
51
95
94
94
96
2
2b
1
2b
1b
1
96
O99
O99
O99
O99
O99
O99
O99
1b
2b
1b
2b
1b
4
24
24
24
2-Octanol
2-Undecanol
43
52
a O2Z1 atm; PEG-TEMPOZ5 mol%; Mn(NO3)2Z2 mol%; Co(NO3)2Z2 mol%; conversion and selectivity determined by GC (see Section 4 for details).
b PEG-TEMPOZ10 mol%.
TEMPO 2 (entry 6). Secondary alcohols were also oxidized
to ketones (entries 10–15) at 40 8C, reaction rates depending
on the steric hindrance of the substrate as found in the case
of other primary oxidants.48 Thus, in the presence of PEG-
TEMPO 1, 1-phenylethanol and cyclooctanol were readily
oxidized in high yield to acetophenone and cyclooctanone,
respectively, (entries 10 and 11), whereas conversion of
2-octanol and 2-undecanol slightly exceeded 50% after 24 h
(entries 13 and 15). The lower activity of PEG-TEMPO 2
with respect to PEG-TEMPO 1 was demonstrated again in
the oxidation of 2-octanol and cyclooctanol (entries 12
and14). Seen as a whole, these results clearly show that the
insertion of a spacer separating the PEG chain from the
TEMPO moiety has a beneficial effect on the catalytic
activity of these supported systems. The presence of a
spacer possibly prevents that partial hindrance of the active
site within the polymeric structure as a result of coiling of
the PEG polymeric backbone, which was suggested to be
the cause of the reduced catalytic activity of certain linker-
less PEG-TEMPO.49
as previously described.48,56 GC analyses were performed
on an Agilent 6850 instrument (column: HP-1 100%
dimethylpolysiloxane 30 m!320 mm!0.25 mm). Car-
rierZHe (constant flow, 2.2 mL/min); modeZsplit (split
ratioZ80:1); injector TZ250 8C; detector (FID) tZ280 8C.
The products of the oxidation reactions were determined by
comparison with the commercially available carbonyl
compounds and carboxylic acids.
4.2. PEG-TEMPO 2
To a suspension of 60% NaH in mineral oil (25 mg,
0.63 mmol) in dry DMF (4 mL) was added 4-hydroxy-
TEMPO (108 mg, 0.63 mmol) and the resulting slurry was
stirred at room temperature for 1 h under nitrogen. A
solution of PEG-mesylate 3 (800 mg, 0.16 mmol),
previously dried under vacuum at 100 8C for 1 h, in dry
DMF (4 mL) was then added and the mixture was stirred for
70 h at 70 8C. After cooling to room temperature, the
suspension was filtered and the filtrate evaporated to dryness
under reduced pressure. The residue was taken up in CH2Cl2
(2 mL) and added to Et2O (70 mL). The precipitate was
collected by filtration, washed with Et2O (3!30 mL) and
dried under vacuum. PEG-TEMPO 1 (650 mg, 80%) was
obtained as a pale orange solid (physical data in agreement
with those reported in the literature).50
3. Conclusions
Two poly(ethylene glycol)-supported TEMPO (PEG-
TEMPO) prepared from readily available precursors proved
to be efficient catalysts in the chemoselective oxidation of
alcohols with molecular oxygen under mild conditions.
Catalytic activities and selectivities of these soluble
TEMPO derivatives are similar to those exhibited by the
parent compound, and even higher in the case of PEG-
TEMPO 1. In addition, both PEG-TEMPO offer the
advantages of simplified workup procedure and easy
recycling, which are usually associated with the use of
heterogenized TEMPO.
4.3. General procedure for the aerobic oxidation of
alcohols
Reactions were carried out in a jacketed 20 mL Schlenk
tube thermostated by circulating water (Haake F3 Cryostat)
and fitted with a stirring bar. The reactor was charged with
(a) a freshly prepared solution of alcohol (1 mmol) and
n-decane (71.1 mg, 0.5 mmol, internal standard for GC) in
acetic acid (1 mL); (b) a freshly prepared solution of
Mn(NO3)2$H2O (5.0 mg, 0.02 mmol) and Co(NO3)2$H2O
(5.8 mg, 0.02 mmol) in acetic acid (1 mL). The combined
solutions were stirred 5 min, then PEG-TEMPO
(0.05–0.1 mmol) was added. The Schlenk tube was attached
to a gas burette filled with oxygen and the solution was
stirred for the time indicated in Tables 1–3. A 20 mL sample
of the solution was diluted with 0.2 mL ice-cold Et2O.
4. Experimental
4.1. General
Solvents were purified by standard methods and dried if
necessary. Commercially available reagents were used as
received. PEG-TEMPO 1 and PEG mesylate 3 was prepared

M. Benaglia et al. / Tetrahedron 61 (2005) 12058–12064
12063
13. Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem.
1987, 52, 2559–2562.
The precipitated catalyst was eliminated by filtration on
PTFE septum and the liquid layer was analyzed by GC.
14. Anelli, P. L.; Banfi, S.; Montanari, F.; Quici, S. J. Org. Chem.
1989, 54, 2970–2972.
4.4. Oxidation of 4-bromobenzyl alcohol: catalyst
recycling
15. De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.;
Piancatelli, G. J. Org. Chem. 1997, 62, 6974–6977.
16. De Luca, L.; Giacomelli, G.; Porcheddu, A. Org. Lett. 2001, 3,
3041–3043.
The jacketed reactor thermostated at 25 8C was charged
with (a) a freshly prepared solution of 4-bromobenzyl
alcohol (374.1 mg, 2 mmol) and n-decane (142.2 mg,
1 mmol, internal standard for GC) in acetic acid (2 mL);
(b) a freshly prepared solution of Mn(NO3)2$H2O (10.0 mg,
0.04 mmol) and Co(NO3)2$H2O (11.6 mg, 0.04 mmol) in
acetic acid (1 mL). The combined solutions were stirred
5 min, then PEG-TEMPO 1 (550 mg, 0.1 mmol) was added
and the solution was stirred for 3 h under an atmosphere of
molecular oxygen. Ice-cold Et2O (10 mL) was added and
the precipitated PEG-TEMPO 1 was filtered on a sintered
glass funnel and washed with cold Et2O (3!3 mL). The
combined organic phase was analyzed by GC, whereas the
recovered PEG-TEMPO 1 was dried under vacuum and
used for the subsequent run. When PEG-TEMPO 2
(510 mg, 0.1 mmol) was used, acetic acid was evaporated
under reduced pressure prior to the addition of Et2O. Results
are reported in Table 2.
17. Bolm, C.; Magnus, A. S.; Hildebrand, J. P. Org. Lett. 2000, 2,
1173–1175.
18. Miller, R. A.; Hoerrner, R. S. Org. Lett. 2003, 5, 285–287.
´
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