A nitric acid-assisted carbon-catalyzed oxidation system with nitroxide radical cocatalysts as an efficient and green protocol for selective aerobic oxidation of alcohols

Article abstract of DOI:10.1002/adsc.201000366

The incorporation of nitroxide radicals into a nitric acid-assisted carbon-catalyzed oxidation system (NACOS) afforded a highly efficient, widely applicable, non-metallic approach for the selective aerobic oxidations of alcohols. Without any solvent, this novel protocol has the ability to oxidize various primary alcohols to their corresponding aldehydes with selectvities as high as 99% at full conversions, with only 0.1 mol% of nitroxide radicals and <4.5 wt% of activated carbon under mild conditions (temperatures as low as 50°C and atmospheric pressure). The performances of several stable nitroxide radicals have been compared. The effects of nitric acid concentration, activated carbon loading, and temperature have been studied for the oxidation of benzyl alcohol. The enhanced NACOS represents a greener and more efficient fundamental chemical process, due to its use of molecular oxygen as an oxidant, and its solvent-free nature.

Full text of DOI:10.1002/adsc.201000366

FULL PAPERS
DOI: 10.1002/adsc.201000366
A Nitric Acid-Assisted Carbon-Catalyzed Oxidation System with
Nitroxide Radical Cocatalysts as an Efficient and Green Protocol
for Selective Aerobic Oxidation of Alcohols
a
a
a
a
Yongbo Kuang, Hodaka Rokubuichi, Yuta Nabae, Teruaki Hayakawa,
a,
and Masa-aki Kakimoto *
Department of Organic and Polymeric Materials, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8552, Japan
a
Fax : (+81)-3-5734-2875; phone: (+81)-3-5734-2433; e-mail: mkakimot@o.cc.titech.ac.jp
Received: May 9, 2010; Published online: September 22, 2010
Abstract: The incorporation of nitroxide radicals The performances of several stable nitroxide radicals
into a nitric acid-assisted carbon-catalyzed oxidation have been compared. The effects of nitric acid con-
system (NACOS) afforded a highly efficient, widely centration, activated carbon loading, and tempera-
applicable, non-metallic approach for the selective ture have been studied for the oxidation of benzyl al-
aerobic oxidations of alcohols. Without any solvent, cohol. The enhanced NACOS represents a greener
this novel protocol has the ability to oxidize various and more efficient fundamental chemical process,
primary alcohols to their corresponding aldehydes due to its use of molecular oxygen as an oxidant, and
with selectvities as high as 99% at full conversions, its solvent-free nature.
with only 0.1 mol% of nitroxide radicals and <4.5
wt% of activated carbon under mild conditions (tem- Keywords: aerobic oxidation; alcohols; carbon; nitric
peratures as low as 508C and atmospheric pressure). acid; nitroxide radicals
Introduction
of non-metallic oxidation systems, largely ignoring
their inherent advantages.
Selective oxidation of organic compounds, as high-
We are particularly interested in the potential of
lighted by the Technology Vision 2020 report, is one carbon-based materials in activating oxygen for the
[
1]
of the major challenges facing the chemical industry.
selective oxidation of organic compounds. Very re-
The selective transformation of alcohols to aldehydes cently, we revealed a novel nitric acid-assisted carbon-
[
6]
and ketones, in particular, is among the most impor- catalyzed oxidation system, called NACOS. NACOS
[
2]
tant synthetic operations in organic chemistry. Nu- offers a new non-metallic route for oxygen activation
merous methods have been reported and widely used and works well with many different carbon materials,
for this purpose utilizing various organic and inorgan- such as nanoshell carbon, activated carbon and
ic oxidants, for example DMSO and Cr(VI)-based re- carbon black. However, the current scope of NACOS
[2b,3]
gents.
However, those conventional oxidants are is relatively narrow (i.e., limited to benzylic alcohols),
generally employed in greater than one equivalent and the selectivity to aldehyde for primary alcohol ox-
quantities, with large amounts of toxic waste being idation is somewhat dependent on the structural fea-
produced. From the viewpoints of atom economy, tures of the carbon catalyst and the substrate concen-
cost efficiency and green chemistry, atmospheric tration. It also suffers from a high loading of nitric
oxygen is obviously superior to other reagents, and acid, although this is almost completely recovered
[
4]
thus represents the quintessential oxidant. Never- after the reaction. Therefore, we were considering
theless, to harness its power has never been an easy how to further develop the potential of NACOS. In
job, except for the processes of combustion or explo- our mechanistic investigation of NACOS, we showed
sion. In the past decades, most efforts have been di- that the intermediate from nitric acid acts as the pri-
rected to the development of heterogeneous and ho- mary oxidant and then is recovered by oxygen. We
mogeneous transition metal-based catalysts, summar- argue that the limitations of NACOS come from the
[
5]
ized in many recent review papers. In contrast, kinetically low reactivity and deficient selectivity of
much less attention has been paid to the development that intermediate toward the conversion of the hy-
droxy group to the carbonyl group. To deal with those
Adv. Synth. Catal. 2010, 352, 2635 – 2642
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2635

Yongbo Kuang et al.
FULL PAPERS
issues, we postulated that the insertion of an appropri-
ate cocatalyst into the existing catalytic cycles might
help. The cocatalyst should be able to create a more
kinetically favored reaction cycle and possess higher
selectivity for oxidation of the hydroxy group. Fortu-
nately, we found such a target, namely nitroxide radi-
cal.
Nitroxide radicals have been long known as effi-
cient catalysts for the selective oxidation of alcohols
[
(
e.g.,
2,2,6,6-tetramethylpiperidine
1-oxyl
[7]
TEMPO)]. In the presence of oxidants, the nitro-
xide radical is oxidized to the oxoammonium ion,
which then acts as the primary oxidant for alcohols
with itself being reduced to a hydroxylamine. During
the process of the catalytic cycle, oxoammonium cat-
ions can be continuously provided by the re-oxidation
of hydroxylamines. Various stoichiometric oxidants
Scheme 1. Nitroxide radical-enhanced NACOS.
[
8]
have been traditionally employed, i.e., NaClO,
[
9]
[10]
PhI
chloroper
few reports on the use of oxygen as the oxidant in the run, as shown in Table 1. On comparing run 1 and 2,
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc) ,
N-chlorosuccinimide,
and
m- ed three comparative reactions in the absence of any
2
[
11]
ACHTUNGTRENNUNGo xybenzoic acid. In addition, there are a alcohol to check the remains of nitric acid after each
[
12]
presence of transition metal-based catalysts. Nota- where the same amounts of activated carbon (AC)
bly, Huꢁs group has recently reported a series of were added while different atmospheres were applied
metal-free aerobic alcohol oxidation protocols (the (N vs. O ), one can see that nitric acid was consumed
2
2
[
13]
[14]
TEMPO/Br /NaNO system,
and its variations).
under N , and could be recovered in the presence of
2
2
2
Those methods provided great advances in the field O . Furthermore, the decomposed product NO was
2
2
of non-metallic aerobic oxidation. However, they re- observed above the mixture as a brown gas under N2.
quire an expensive teflon-lined autoclave to achieve In the absence of AC (run 3), even under heating,
high operating pressures, a Br source which inevitably nitric acid remained intact. These findings provide
results in Br-substituted by-products, and often chlor- further support to our proposed mechanism of
[
6]
ine-containing solvents (CH Cl or ClCH CH Cl). Al- NACOS, and more importantly suggest the feasibili-
2
2
2
2
though in their latest report, the use of the Br source ty of inserting a nitroxide radical-based catalytic cycle
was eliminated, the employment of organic nitrite will into NACOS.
introduce small organic molecule contaminants into
Six nitroxide radicals were chosen to be evaluated,
[
14c]
the final products.
In contrast, our nitroxide radi- including TEMPO, three TEMPO derivatives, 2-aza-
cal-enhanced NACOS protocol (Scheme 1), described
ACHTUNGTRENNUNGa damantane N-oxyl (AZADO) and 1-Me-AZADO.
herein, involves no halogen-containing reagents, intro- Trial oxidations were conducted with benzyl alcohol
duces no additional organic contaminants, and deliv- as the substrate without any solvent and the loadings
ers the desired yields and selectivity for a wide range of cocatalysts were initially set at 0.1 mol%
of alcohols under solvent-free or minimum solvent- (Figure 1). Under identical conditions, the perfor-
use conditions, depending on the substrates.
mance of TEMPO was much better than its three de-
rivatives, especially the one with a bulky electron-
withdrawing group. AZADO and 1-Me-AZADO
were reported to have higher catalytic efficiency than
Results and Discussion
[
15]
TEMPO due to less steric hindrance.
However,
To ensure the success of incorporating nitroxide radi- they have not yet been employed in aerobic alcohol
cals, there is one prerequisite that the activation of oxidations. As expected, the two displayed enhanced
nitric acid on carbon must be demonstrated to be in- activities than TEMPO under our conditions, namely,
dependent of the alcohol substrates. Thus we conduct- TEMPO took more than double the time (10 h) to
Table 1. Dissociation of HNO on AC in 1,4-dioxane under N and O atmosphere.
3
2
2
Run
AC [mg]
1,4-dioxane [mL]
67% HNO [mmol]
Atm.
Temp. [8C]
Time [h]
HNO remaining [%]
3
3
1
2
3
100
100
0
5
5
5
5
5
5
N2
O2
N2
90
90
90
4
4
4
57%
98%
99%
2636
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2635 – 2642

A Nitric Acid-Assisted Carbon-Catalyzed Oxidation System with Nitroxide Radical Cocatalysts
Scheme 2. The autoxidation of benzaldeyde.
concentration. Thus it can be easily inferred that the
reaction between the oxoammonium ion and benzyl
alcohol is quite fast and is not the rate-determining
step.
We then evaluated the effect of HNO concentra-
3
tion. As mentioned above, one of the objectives of
this work is to reduce the use of HNO , but not at the
3
sacrifice of reaction rate. In Figure 2 (top), the results
Figure 1. Aerobic oxidation of benzyl alcohol with various
nitroxide radicals as cocatalysts. General conditions: benzyl
alcohol (40 mmol), nitroxide radical (0.04 mmol, 0.1 mol%),
activated carbon (100 mg), 67% HNO (0.8 mmol, 2 mol%),
3
9
08C, O (atm).
2
achieve full conversion compared with 1-Me-
AZADO (4 h).
To our delight, in all these reactions, the selectivity
to aldehyde remained in the range of 95% to ca.
9
9%. As is well known, it is very difficult to maintain
good aldehyde selectivity while the concentration be-
comes high, especially under solvent-free conditions.
The main reason for this is the autoxidation of ben-
zaldehyde (Scheme 2). According to the notion of
green chemistry, the use of organic solvents should be
[
16]
avoided as much as possible.
In particular, there
have been many attempts at the solvent-free aerobic
[
17]
oxidation of benzyl alcohol.
We also carried out
6]
[
such reactions with NACOS. However, none of
those methods match the current approach in terms
of aldehyde selectivity at high substrate conversion.
Notably, with the addition of active nitroxide radicals,
Figure 2. The effect of HNO concentration. General condi-
3
tions: benzyl alcohol (40 mmol), TEMPO (0.1 mol%), O2
roughly linear reaction curves were obtained, indicat- (1 atm), 908C. (top) 200 mg of AC were added in each run.
ing that the reaction rate is independent of substrate (bottom) No AC.
Adv. Synth. Catal. 2010, 352, 2635 – 2642
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2637

Yongbo Kuang et al.
FULL PAPERS
from two comparative reactions with different
amounts of HNO (2 mol% and 4 mol%) are shown.
3
It seems that in the presence of a fixed amount of
AC, doubling the amount of HNO3 results in an
almost doubled reaction rate. It is conceivable that
the presence of AC is superfluous, if HNO3 has
enough oxidative power to promote the redox of ni-
troxide radicals. Thus we carried out reactions with
varying loadings of HNO in the absence of AC. The
3
results are shown in Figure 2 (bottom). Very slow re-
action rates were observed. Even after about 20 h of
reaction, the conversion was still below 10%. In fact,
HNO is able to oxidize TEMPO at a fast rate, evi-
3
denced by the color change of the reaction mixture.
HNO was charged into the reactor after TEMPO.
3
Upon its addition, the light red color (due to
TEMPO) quickly became deeper (TEMPO being oxi-
dized to the oxoammonium cation), and soon the mix-
ture turned colorless (the cation being reduced to hy-
droxylamine TEMPOH). The mixture then remained
colorless for a long time. Therefore, the rate-deter-
mining step in this case is likely to be the reoxidation
of TEMPOH to TEMPO (Scheme 3).
Figure 3. The effect of AC loading. General conditions:
benzyl alcohol (40 mmol), TEMPO (0.1 mol%), HNO3
(
2 mol%), O (1 atm), 908C. (top) The plot of conversion as
2
a function of time. (bottom) The plot of conversion as a
function of AC loading for a given time.
Scheme 3.
rate was maintained throughout the reaction. This im-
After demonstrating the necessity of AC, the fol- plies that all the catalytic steps, from the activation of
lowing issue to be dealt with is how its loading HNO on carbon, to the oxidation of alcohol by the
3
amounts affect the reaction rate. A series of reactions TEMPO cation, do not require high temperatures to
were conducted under the same conditions with the be promoted and this can bring great benefits for the
AC loading ranging from zero to 300 mg. Figure 3 oxidations of thermally instable alcohols. Further-
(
top) shows the results of conversions against reaction more, a linear dependence of reaction rate on temper-
time, while in Figure 3 (bottom) the conversions are ature is found by plotting the conversions against
plotted as a function of AC loadings at a given time. temperature for a given time [Figure 4 (bottom)].
Generally the reaction rates increase with increasing
Since TEMPO is used in a homogeneous manner
AC loading, but not in a linear relationship. As shown and is unlike carbon catalysts that can be simply re-
in Figure 3 (bottom), the sharpest increase was only covered by filtration, it is better to use as small an
obtained when the AC loading was no larger than amount as possible from the economic point of view.
10 mg. After this the slope becomes gentler with the We managed to reduce the use of TEMPO to
increasing AC loading. 0.1 mol% from 1 mol%. However, it is interesting to
In Figure 4, reactions carried out at temperatures see how increased use affects the reaction rate. In the
ranging from 508C to 1108C are compared. At elevat- presence of AC, a much faster reaction rate (although
ed temperature, reactions proceeded very fast. For in- not doubled) was observed with a doubled amount of
stance, at 1108C, full conversion could be achieved TEMPO (Figure 5, open squares and open triangles).
within 2 h (TOF=500). To our surprise, even at tem- While in the absence of AC, no significant increase
peratures as low as 508C, after 15 h, the desired re- was obtained and the reaction rates were very low
sults were obtained and a roughly constant reaction (Figure 5, solid squares and solid triangles). Notably,
2638
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2635 – 2642

A Nitric Acid-Assisted Carbon-Catalyzed Oxidation System with Nitroxide Radical Cocatalysts
when the temperature was decreased to 508C, the oxi-
dation proceeded with an extremely slow rate without
the carbon catalyst (Figure 5, solid circles).
To study the scope of the modified NACOS system,
we applied it to various primary and secondary alco-
hols. Although AZADO and 1-Me-AZADO show
better performance, considering their current high
prices, the cheaper and more widely available
TEMPO was mainly used in our scope investigations.
To shorten the reaction time, 0.2 mol% of TEMPO
and 4 mol% of HNO against alcohols were chosen as
3
the general conditions. We first applied the same sol-
vent-free reaction conditions as benzyl alcohol to
other three benzylic alcohols (4-methoxybenzyl alco-
hol, 3-nitrobenzyl alcohol, and 3-phenoxybenzyl alco-
hol), in consideration of their liquid states at room
temperature. The reactions went smoothly for all the
three substrates, and as expected, electron-withdraw-
ing substituents resulted in longer reaction times
(
Table 2, entries 1–3). The substrates in entries 4–6
have melting points which are higher than room tem-
perature but lower than that for the reaction. It seems
that they can also be oxidized under solvent-free con-
ditions. However, due to the relatively low tempera-
ture, the substrate flow was observed to freeze on the
condenser, causing undesired sample loss. To solve
this problem, a small amount of 1,4-dioxane (1 mL,
less than one quarter of the volume of the substrate)
was added to the reaction mixture. 0.2 mol% of
TEMPO was enough for full conversion of 4-methox-
ybenzyl alcohol as well as 4-chlorobenzyl alcohol, but
was insufficient for 4-nitrobenzyl alcohol. The strong
Figure 4. The effect of temperature. General conditions:
benzyl alcohol (40 mmol), TEMPO (0.2 mol%), HNO3
(
4 mol%), O (1 atm), AC (200 mg), 908C. (top) The plot of
2
conversion as a function of time. (bottom) The plot of con-
version as a function of temperature for a given time.
electron-withdrawing group NO at the para-position
2
makes this substrate much more inactive towards oxi-
dation, therefore the amount of TEMPO was dou-
bled, after which ideal results were obtained (entry 6).
So from the reactivity for benzylic alcohols it can be
concluded that electron-withdrawing substituents gen-
erally lead to lower activities than electron-donating
ones, and for substrates with same substituents, para-
positioned ones are less active than meta-positioned
ones. This system also works well with secondary ben-
zylic alcohols, for example, in entry 7, the oxidation of
dl-1-phenylethyl alcohol gave perfect results within
4
h under solvent-free conditions.
The previous NACOS protocol is limited to benzyl-
[
6]
ic alcohols, but with the incorporation of nitroxide
radicals, the scope can be expanded to aliphatic alco-
hols, even under solvent-free conditions. Generally,
aliphatic alcohols are less active than benzylic alco-
hols towards oxidation. We found that higher loadings
of TEMPO are necessary to obtain high conversions
for these substrates (Table 3). Among all the tested
aliphatic alcohols, 2-adamantanol showed the highest
reactivity (entry 6). 1 mol% of TEMPO was adequate
Figure 5. Comparison of reactions carried out with and with-
out AC at different TEMPO concentrations. General condi-
tions: benzyl alcohol (40 mmol), HNO3 (4 mol%), O2
(
1 atm). The quantities in mol% represent the amounts of
TEMPO used in each run. Open symbols (C): 200 mg of AC to achieve ideal results. Due to its very high melting
added. Solid symbols (NC): no carbon added.
point, the oxidation of 2-adamantanol cannot be car-
Adv. Synth. Catal. 2010, 352, 2635 – 2642
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2639

Yongbo Kuang et al.
FULL PAPERS
Table 2. Selective aerobic oxidation of benzylic alcohols.
[a]
[b]
[b]
Entry
1
Substrate
Product
Time [h]
3
Conversion [%]
100
Selectivity [%]
98
2
3
7
96
100
5
4
7
4
4
95
100
98
c)
4
99
95
99
c)
5
99
[
c,d]
6
7
100
100
100
[
a]
General conditions: substrate (40 mmol), TEMPO (0.08 mmol, 0.2 mol%), activated carbon (200 mg), 67% HNO3
1.6 mmol, 4 mol%), 908C.
Determined by GC-MS, based on area normalization.
Additional 1 mL of 1,4-dioxane, 958C.
TEMPO (0.4 mol%).
(
[
[
[
b]
c]
d]
Table 3. Selective aerobic oxidation of aliphatic alcohols.
[a]
[b]
[b]
Entry
Substrate
Product
Time [h]
Conversion [%]
Selectivity [%]
[
d]
1
2
1-decanol
1-dodecanol
decanal
dodecanal
14
14
96
97
90[
d]
93
[d]
3
5
89
71
4
5
16
16
90
87
100
100
[
c]
6
7
8
3
99
32
27
100
100
100
13
13
[
a]
General conditions: substrate (20 mmol), TEMPO (1 mmol, 5 mol%), AC (100 mg), 67% HNO (1.6 mmol, 8 mol%),
3
5
08C.
[
[
[
b]
c]
d]
Determined by GC-MS, based on area normalization.
Substrate (5 mmol), 1,4-dioxane (5 mL), TEMPO (1 mol%), HNO (10 mol%), AC (100 mg).
The corresponding acids were the main by-products.
3
ried out without a solvent. Thus 1,4-dioxane was used served that even with increased use of TEMPO, good
as the solvent and the reaction was conducted at a results could not be obtained when we conducted the
high concentration of 1 mol/L. Notably, the use of reactions at 908C. Through GC-MS analysis, we de-
1,4-dioxane can also bring greater ease in the separa- tected that TEMPO was mostly converted to 2,2,6,6-
tion of products thanks to its high solubility in water. tetramethylpiperidine and 2,2,6,6-tetramethyl-1-nitro-
For the oxidation of other aliphatic alcohols, we ob- sopiperidine after the reaction, which can be ex-
2640
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2635 – 2642

A Nitric Acid-Assisted Carbon-Catalyzed Oxidation System with Nitroxide Radical Cocatalysts
substrate scopes including cyclic alcohols, however,
high operation pressures are required. The Mn/Co/
TEMPO system reported by Cecchetto et al. can be
[18]
also applied to inactive alcohols like cyclohexanol.
Although it requires relatively high TEMPO loading
10 mol%), it can be done with very mild conditions,
(
i.e., room temperature and atmospheric pressure, thus
it is quite suitable for thermally instable alcohols.
Scheme 4. The consumption of TEMPO.
Conclusions
[
12c]
plained by the reactions shown in Scheme 4.
Therefore the reaction temperature was lowered to We have succeeded in establishing a powerful oxida-
08C in order to solve the thermal-instability issue. tion system based on NACOS through the incorpora-
5
To our delight, our method then worked well with tion of nitroxide radicals. The enhanced nitroxide rad-
varied primary and secondary aliphatic alcohols (en- ical-NACOS delivers great benefits, including mini-
tries 1–5). Interestingly, for primary alcohols, high se- mized or even no use of solvents, largely reduced use
lectivities to aldehydes were maintained at the sacri- of nitric acid, improved reactivity and selectivity, and
fice of reaction rate. Generally, aliphatic aldehydes expanded substrate accessibility. In our last report, we
are much less stable than benzylic aldehydes and demonstrated the feasibility of using carbon-based
have a larger tendency to undergo autoxidation to catalysts to replace transition-metals in aerobic oxida-
form acids, especially at high concentration and high tions. Here we show further that carbon-based sys-
temperature. Thus a lower temperature is favored for tems can have comparable performances with those
the production of aldehydes by aerobic oxidation, al- based on transition-metals. Moreover, it embodies the
though this is at the expense of reaction rate. As for concept of green chemistry.
the cyclic alcohols, high conversions seemed to be
We believe that carbon-based catalysts can find
very difficult to obtain (entries 7 and 8). Initially, we more applications in organic synthesis and other relat-
ascribed the failures to the quick decomposition of ed fields. Particularly, the idea of inserting an appro-
TEMPO under these particular environments. How- priate mediator into the catalytic cycles of NACOS
ever, most of the TEMPO was found to remain intact may inspire other researches and lead to more discov-
after reaction through careful examination. Thus we eries of new green and efficient oxidation systems for
speculate that the main reason is probably the solvent many other functional groups.
effect. As there was no other solvent, the substrate
itself served as the solvent, and over the course of the
reaction, the mixture composition changed due to the Experimental Section
formation of ketone products, resulting in the unfa-
vored change of the chemical environment for the ox- General
idation reaction.
All alcohol substrates, nitroxide radicals and activated
carbon (AC) (NORIT SX Plus) were obtained from com-
It would be interesting to compare TEMPO-based
aerobic alcohol oxidation systems, in terms of activity,
mercial suppliers and were used as received. Oxidation reac-
regardless whether metal is used. However, there is
tions were carried out using a SIBATA Chemist Plaza
no general standard for evaluation. In practice, both CP100 multi-reactor equipped with 130ꢂ200 mm sized test
properties of substrates and features of available pro- tubes as reaction vessels and separate magnetic stirrers.
tocols should be taken into consideration. For syn- Samples were analyzed with a SHIMAZDU GCMS-QP2010
Plus, using a Restek Rxi-1 ms column. Quantitative analysis
was based on area normalization.
thetic chemists, methods that do not require high op-
erating pressures are favored since most laboratories
are not equipped with autoclaves. In particular, for
the oxidation of benzylic alcohols, the system report-
ed herein is obviously superior to other methods with
respect to TOF of TEMPO and ease of operation. For
the oxidation of aliphatic alcohols, all reported meth-
ods require at least 1 mol% of TEMPO (mostly 5–
Typical Procedure for the Oxidation of Liquid
Alcohol Substrates (Benzyl Alcohol)
2
4
00 mg of AC, 6.3 mg (0.04 mmol) of TEMPO, and
.228 mL (40 mmol) of benzyl alcohol were charged sequen-
tially into a test tube. After the mixture had been sonicated
for 20 s, 0.1075 mL (1.6 mmol) of 67% HNO3 was added
dropwise under stirring. The tube was then sealed and evac-
uated using an aspirator, followed by the attachment of an
1
0 mol%). Our system requires 5 mol% of TEMPO
and works well with long-chain aliphatic alcohols, but
has difficulties with cyclic ones. The TEMPO/Br /
2
[
13]
NaNO system reported by Liu et al., and the Ru/ oxygen balloon. The reaction mixture was heated to 908C,
2
[
12b]
TEMPO system by Dijksman et al.,
have large using an aluminum block, for 5 h. Samples were taken at ap-
Adv. Synth. Catal. 2010, 352, 2635 – 2642
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2641

Yongbo Kuang et al.
FULL PAPERS
propriate intervals through a silicon septum using a hypo-
dermic needle and were filtered through a 45 nm syringe
filter prior to GC-MS analysis.
f) T. Matsumoto, M. Ueno, N. Wang, S. Kobayashi,
Chem. Asian J. 2008, 3, 196–214.
[6] Y. Kuang, N. M. Islam, Y. Nabae, T. Hayakawa, M.-a.
Kakimoto, Angew. Chem. 2010, 122, 446–450; Angew.
Chem. Int. Ed. 2010, 49, 436–440.
[7] a) A. E. J. deNooy, A. C. Besemer, H. van Bekkum,
Synthesis 1996, 1153–1174; b) W. Adam, C. R. Saha-
Moller, P. A. Ganeshpure, Chem. Rev. 2001, 101, 3499–
3548; c) T. Vogler, A. Studer, Synthesis 2008, 1979–
1993.
The oxidation procedure for alcohols with high melting
points was similar to that described above, except that the
substrates were charged in solid form (melted upon heating)
and a small amount of 1,4-dioxane (less than one quarter of
the substrate volume) was added at the beginning. In the ox-
idation of solid substrates (2-adamantanol), 1,4-dioxane was
À1
used as solvent and the concentration was 1 mmolmL .
[
8] a) P. L. Anelli, C. Biffi, F. Montanari, S. Quici, J. Org.
Chem. 1987, 52, 2559–2562; b) P. L. Anelli, S. Banfi, F.
Montanari, S. Quici, J. Org. Chem. 1989, 54, 2970–
Determination of HNO Recovery
3
The resultant mixture was collected by filtration using a
2
972.
45 mm syringe filter. In a beaker, 1 mL of the filtrate was di-
[
9] A. De Mico, R. Margarita, L. Parlanti, A. Vescovi, G.
Piancatelli, J. Org. Chem. 1997, 62, 6974–6977.
10] J. Einhorn, C. Einhorn, F. Ratajczak, J. L. Pierre, J.
Org. Chem. 1996, 61, 7452–7454.
11] S. D. Rychnovsky, R. Vaidyanathan, J. Org. Chem.
1999, 64, 310–312.
12] a) M. F. Semmelhack, C. R. Schmid, D. A. Cortes, C. S.
Chou, J. Am. Chem. Soc. 1984, 106, 3374–3376; b) A.
Dijksman, I. Arends, R. A. Sheldon, Chem. Commun.
luted to 40 mL with deionized water. The solution was
stirred for several minutes and then filtered to remove in-
soluble substances. A pH meter was used to determine the
pH value of the solution. Based on the pH value, the recov-
[
[
[
ery of HNO after the reaction was calculated.
3
Acknowledgements
1
999, 1591–1592; c) A. Dijksman, A. Marino-Gonza-
lez, A. M. I. Payeras, I. Arends, R. A. Sheldon, J. Am.
Chem. Soc. 2001, 123, 6826–6833.
13] R. H. Liu, X. M. Liang, C. Y. Dong, X. Q. Hu, J. Am.
Chem. Soc. 2004, 126, 4112–4113.
14] a) R. H. Liu, C. Y. Dong, X. M. Liang, X. J. Wang,
X. Q. Hu, J. Org. Chem. 2005, 70, 729–731; b) Y. Xie,
W. M. Mo, D. Xu, Z. L. Shen, N. Sun, B. X. Hu, X. Q.
Hu, J. Org. Chem. 2007, 72, 4288–4291; c) X. J. He,
Z. L. Shen, W. M. Mo, N. Sun, B. X. Hu, X. Q. Hu,
Adv. Synth. Catal. 2009, 351, 89–92.
We are grateful to New Energy and Industrial Technology
Development Organization (NEDO) in Japan for providing
financial support, and to Stephen Lyth for useful discussions.
[
[
References
[1] Vision 2020 Catalysis Report, www.ccrhq.org/
vision2020/catalysis.
[
2] a) R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxida-
tions of Organic Compounds, Academic Press, New
York, 1981; b) G. Tojo, M. Fernandez, Oxidations of
Alcohols to Aldehydes and Ketones, Springer, New
York, 2006.
[15] M. Shibuya, M. Tomizawa, I. Suzuki, Y. Iwabuchi, J.
Am. Chem. Soc. 2006, 128, 8412–8413.
[16] a) P. T. Anastas, M. M. Kirchhoff, Acc. Chem. Res.
2002, 35, 686–694; b) S. F. Liu, J. L. Xiao, J. Mol. Catal.
A: Chem. 2007, 270, 1–43.
[
[
[
3] R. C. Larock, Comprehensive Organic Transformations:
A Guide to Functional Group Preparations, 2nd edn.,
Wiley-VCH, New York, 1999.
4] a) D. Lenoir, Angew. Chem. 2006, 118, 3280–3284;
Angew. Chem. Int. Ed. 2006, 45, 3206–3210; b) S. S.
Stahl, Science 2005, 309, 1824–1826.
[17] a) V. R. Choudhary, P. A. Chaudhari, V. S. Narkhede,
Catal. Commun. 2003, 4, 171–175; b) V. R. Choudhary,
A. Dhar, P. Jana, R. Jha, B. S. Uphade, Green Chem.
2005, 7, 768–770; c) K. Ohkubo, K. Suga, S. Fukuzumi,
Chem. Commun. 2006, 2018–2020; d) O. F. Ozturk, B.
Zumreoglu-Karan, S. Karabulut, Catal. Commun. 2008,
9, 1644–1648; e) D. I. Enache, J. K. Edwards, P.
Landon, B. Solsona-Espriu, A. F. Carley, A. A. Herz-
ing, M. Watanabe, C. J. Kiely, D. W. Knight, G. J.
Hutchings, Science 2006, 311, 362–365.
5] a) T. Mallat, A. Baiker, Chem. Rev. 2004, 104, 3037–
3
6
058; b) B. Z. Zhan, A. Thompson, Tetrahedron 2004,
0, 2917–2935; c) T. Punniyamurthy, S. Velusamy, J.
Iqbal, Chem. Rev. 2005, 105, 2329–2363; d) M. J.
Schultz, M. S. Sigman, Tetrahedron 2006, 62, 8227–
[18] A. Cecchetto, F. Fontana, F. Minisci, F. Recupero, Tet-
8
241; e) A. Arcadi, Chem. Rev. 2008, 108, 3266–3325;
rahedron Lett. 2001, 42, 6651–6653.
2642
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2635 – 2642