8650
J . Org. Chem. 2001, 66, 8650-8653
systems as concerns the oxidant. However, they have
Selective Aer obic Oxid a tion of Alcoh ols
other disadvantages. The copper-based method is largely
ineffective for simple (nonallylic or nonbenzylic) aliphatic
especially secondary alcohols. In addition, relatively high
catalytic loads, usually at least 10 mol % each of TEMPO
and cupric ion are needed. The ruthenium-based system
overcomes the disadvantage of the lack of reactivity for
simple aliphatic alcohols, but it requires an expensive
noble metal and preferably an intrinsically oxidatively
unstable triphenylphosphine ligand, which has to be
present in order to obtain appreciable catalyst activity.
The enzyme-based method affords only low to modest
conversions after long reaction times, and the rate of
these enzymatically catalyzed oxidation reactions cannot
be increased by significantly increasing the temperature
because of the thermal lability of the enzymes.
w ith a Com bin a tion of a P olyoxom eta la te
a n d Nitr oxyl Ra d ica l a s Ca ta lysts
Revital Ben-Daniel,† Paul Alsters,‡ and
Ronny Neumann*,†
Department of Organic Chemistry, Weizmann Institute of
Science, Israel, 76100, and DSM Research, Koestraat 1,
6160 MD Geleen, The Netherlands
Ronny.Neumann@weizmann.ac.il
Received J une 11, 2001
In tr od u ction
The discovery of new environmentally friendly methods
for selective catalytic oxidation of alcohol substrates to
aldehyde and ketones is an important goal in the
development of modern methods for chemical synthesis.1
In this context, of special significance is the use of
intrinsically non-waste-producing oxidants such as mo-
lecular oxygen from air and hydrogen peroxide. It has
been shown in the past that stable nitroxyl radicals such
as 2,2,6,6-tetramethylpiperidine-1-oxy (TEMPO) is able
to mediate the oxidation of primary alcohols to aldehydes
with a variety of terminal oxidants.2 Especially common
is the use of hypochlorite,3 but the use of electrocatalytic
conditions,4 peracetic acid together with a catalytic
amount of bromide,5 m-chloroperbenzoic acid,6 bromite,7
persulfate,8 and hydrogen peroxide together with hydro-
gen bromide and methylrhenium trioxide as catalyst have
also been reported.9 The use of these nitroxyl reaction
systems has one or more disadvantages including a high
price of oxidant, formation of considerable amounts of
organic waste, and the use of halide (chloride and/or
bromide)-containing oxidants which in turn form nonde-
sirable halide-containing wastes. To obviate these dis-
advantages, molecular oxygen can also as be used as
terminal oxidant in the presence of cupric ion catalysts,10
a ruthenium catalyst, RuCl2(PPh3)3,11 or enzymes with
or without metal complexes.12 These methods have the
advantage of being intrinsically waste-free synthetic
Resu lts a n d Discu ssion
In this present communication we describe the highly
selective and active aerobic oxidation of alcohols in the
combined presence of a nitroxyl radical, TEMPO, and a
polyoxometalate, H5PV2Mo10O40, as cocatalysts. This
specific polyoxometalate has been shown to have catalytic
activity in a myriad of applications13 with, however, only
limited reactivity for alcohol oxidation.14 Typically, reac-
tions were carried out in solution by mixing the alcohol
substrate with catalytic amounts of H5PV2Mo10O40
×
34H2O, and TEMPO, in acetone under 2 atm O2 in a 25
mL glass pressure tube. The results, Table 1, showed
high conversion of the alcohol substrate. In all cases,
ketones or aldehydes were the only detected reaction
products in the oxidation of secondary and primary
alcohols, respectively. Clearly the method is universal for
the oxidation of benzylic, allylic, secondary, and primary
alcohols to their respective carbonyl compounds without
over-oxidation. The rates of oxidation of the representa-
tive benzylic, allylic, secondary, and primary alcohols
were studied in order to distinguish between the reactiv-
ity of the different alcohol types using benzyl alcohol, cis-
2-hexen-1-ol, 2-octanol, and 1-octanol as substrates.
Oxidation of benzyl alcohol and cis-2-hexen-1-ol (1 M
alcohol (ROH), 0.01 M H5PV2Mo10O40, 0.03 M TEMPO, 2
atm O2) proceeded already at 25 °C with rates of
-d[ROH]/dt ) 8.5 × 10-4 M/min and 6.3 × 10-4 M/min,
respectively. For 2-octanol and 1-octanol, similar (slightly
higher) rates were observed only at 100 °C, -d[ROH]/dt
) 2.8 × 10-3 M/min and 2.1 × 10-3 M/min, respectively.
Clearly, the rates of oxidation of alcohols are benzylic ∼
allylic > secondary ∼ primary. This reactivity profile,
especially the observation that the rate of oxidation of
2-octanol is similar to that of 1-octanol, is typical of such
† Weizmann Institute of Science.
‡ DSM Research.
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A
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10.1021/jo0105843 CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/16/2001