Green, transition-metal-free aerobic oxidation of alcohols using a highly durable supported organocatalyst

Article abstract of DOI:10.1002/anie.200701918

(Chemical Equation Presented) Up-tempo catalysis: The nitroxyl radical 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) supported on the mesoporous material SBA-15 provides a highly stable and reusable catalyst (1) for the aerobic oxidation of primary, secondary, and highly hindered alcohols. The catalyst can be recovered and reused in at least another 14 reaction cycles.

Full text of DOI:10.1002/anie.200701918

Communications
DOI: 10.1002/anie.200701918
Aerobic Oxidations
Green, Transition-Metal-Free Aerobic Oxidation of Alcohols Using a
Highly Durable Supported Organocatalyst**
Babak Karimi,* Abbass Biglari, James H. Clark, and Vitaly Budarin
Dedicated to Süd-Chemie on the occasion of its 150th anniversary
Selective oxidation of alcohols to carbonyl compounds is one
of the most important and challenging transformations in the
synthesis of fine chemicals and intermediates.[1] Traditionally,
the oxidation of alcohols has been achieved with stoichio-
metric inorganic oxidants, notably CrVI-based reagents.[2]
Unfortunately, these oxidants are not only relatively expen-
sive but they also produce large quantities of noxious heavy-
metal waste. Consequently, the use of molecular oxygen as the
terminal oxidant in the transition-metal-catalyzed oxidation
of alcohols has received great attention in recent years to
achieve both economic and environmental benefits.[3,4] Of
particular interest in this field is the use of the stable nitroxyl
radical 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in
combination with a co-oxidant as an alternative to metal-
based oxidants.[5] Additionally, it was shown that TEMPO-
catalyzed oxidations can be performed on a large industrial
scale using household bleach under non-aerobic conditions.[6]
Only a few groups have reported catalytic systems
involving TEMPO in combination with transition metals
such as Ru[7] and Cu[8,9] as alternative catalysts for the
oxidation of alcohols using molecular oxygen or air under
mild reaction conditions. However, many of these methods
are inefficient with aliphatic[8] and secondary alcohols,[9] and
their applicability are therefore limited. Furthermore, some
of them require an expensive transition-metal complex and/or
operate at relatively high temperatures (1008C).[7] Although,
some of these drawbacks can be partly avoided by using a
combination of TEMPO with a catalytic amount of MnII-
CoII,[10] the recyclability of the catalysts and product isolation
are still key important issues. TEMPO is a rather expensive
chemical reagent, and therefore its efficient recycling is highly
desirable, especially when the reactions are run on a large
scale. Therefore, several research groups have addressed the
problem of recyclability of TEMPO by designing various
types of supported TEMPO.[11,12] These catalysts were then
employed in combination with O2 and transition-metal
salts,[8–10] or other types of stoichiometric oxidizing agents in
the oxidation of alcohols.[5] However, while these catalytic
systems afford high product yields and selectivities, in most
cases partial degradation of the supported TEMPO catalysts
was observed. It is also worth mentioning that these protocols
still use non-recoverable, hazardous or expensive transition
metals. Recently, Toy and co-workers have developed an
attractive multipolymer reaction system for the aerobic
oxidation of alcohols and to recover both TEMPO and the
catalytic CuII complex at the same time.[13] However, this
method is only effective for the aerobic oxidation of highly
active primary benzylic alcohols after prolonged heating
(18 h) in CH3CN-H2O solvent mixtures.
It seems that while chemists have paid much attention to
designing new improved protocols based on TEMPO/tran-
sition-metal/O2 systems, they have largely ignored the advan-
tages inherent in a metal-free catalytic system. If such
oxidations could be performed in a transition-metal-free
catalytic system using air as terminal oxidant, the processes
would be significantly safer, cheaper, and greener than many
of the processes in use today. Recently, Hu and co-workers
presented a novel metal-free TEMPO-catalyzed aerobic
oxidation of alcohols.[14] While this method provided an
interesting achievement in the field of aerobic oxidation of
alcohols, it required expensive teflon-lined apparatus, high
loadings of TEMPO which is not recoverable (homogeneous,
up to 10 mol%), high operating pressures (up to 9 bar),
relatively high temperatures (up to 808C), and an environ-
mentally undesirable chlorinated solvent (CH2Cl2). Thus,
from the standpoint of practical, environmental, and eco-
nomic concerns, it is still highly desirable to develop cleaner,
milder, cheaper, and recyclable TEMPO catalytic systems for
the aerobic oxidation of alcohols, especially for large-scale
operations.
[*] Prof. Dr. B. Karimi, A. Biglari
Department of Chemistry
While several types of supported aminoxyl radicals have
already been reported,[11,12] to the best of our knowledge,
none of them have been studied in the transition-metal-free
aerobic oxidation of alcohols. We report herein for the first
time the use of a novel and extremely stable version of
supported TEMPO for the effective aerobic oxidation of
alcohols, with both activated and non-activated hydroxy
groups, in the absence of any transition-metal-containing co-
catalyst. It has been well documented that ordered mesopo-
rous materials (such as MCM-41[15] and SBA-15[16]) with
relatively uniform pore diameters (2–30 nm), large void
volumes, and high surface areas can serve as more well-
Institute for Advanced Studies in Basic Sciences (IASBS)
PO Box 45195-1159, Gava Zang, Zanjan (Iran)
Fax: (+98)241-424-9023
E-mail: karimi@iasbs.ac.ir
Homepage: http://www.iasbs.ac.ir/faculty/chemistry/karimi/
Prof. J. H. Clark, Dr. V. Budarin
Clean Technology Centre, University of York
York YO10 5DD (UK)
[**] This work was supported by the IPM and IASBS Research Councils.
The authors thank the referees for their valuable comments.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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defined support materials, in comparison to amorphous solids,
onto which organic groups can be anchored.[17] These nano-
structured materials are also superior to organic polymers,
because the application of the latter is significantly restricted
as a result of their high price and easy thermal and chemical
damage of the organic backbone.[18] Here, we chose to employ
the mesoporous silica SBA-15 as a support for nitroxyl
radicals not only because it has larger and more accessible
channels but also as it displays higher thermal and hydro-
thermal stability than MCM-41.[16]
SBA-15 was obtained by treating pluronic P123
[EO20PO70EO20 (EO = ethylene oxide, PO = propylene
oxide), Mav = 5800 gmolÀ1; Aldrich] and (EtO)4Si under
acidic conditions following the reported procedure.[20] The
resulting SBA-15 was then functionalized with aminopropyl
spacers followed by reductive amination with 1-hydroxy-4-
oxo-2,2,6,6-tetramethylpiperidine to afford the corresponding
immobilized TEMPO 1 according to known procedures with
~
&
Figure 1. Benzyl alcohol conversion ( ) and selectivity ( ) for benzal-
dehyde formation as a function of reaction time (508C, atmospheric
pressure of O2 (1 atm)).
In contrast to homogeneous TEMPO procedures that are
equally applicable to the conversion of a variety of alcohols in
different reaction media,[5] heterogeneous TEMPO catalysis
often fails to show similar versatility. This is unfortunate as
the low product volumes of the fine chemical industries and
the new combinatorial applications of solid-phase synthesis
do indeed require such a high degree of versatility. Here
catalyst 1 shows excellent reactivity for the selective oxidation
of various types of secondary and highly hindered alcohols, a
feature not observed with the previous heterogeneous
TEMPO/transition-metal/O2 protocols (Table 1, entries 11–
15, 19, 20).[13]
Generally, many of the reported transition-metal-based
systems are unable to catalyze the aerobic oxidation of
alcohols that contain heteroatoms, because of the strong
coordination of these alcohols to a metal center which results
in deactivation of the catalyst. However, catalyst 1 also shows
excellent tolerance for a broad range of bifunctional alcohols
and is notably not deactivated by nitrogen- and sulfur-
containing substrates (Table 1, entries 8, 9).
slight modifications.[11b,19] Catalyst 1 was characterized by
simultaneous thermal analysis (STA), diffuse reflectance
Fourier transform (DRIFT) IR spectroscopy, surface analysis,
and transmission electron microscopy (TEM).[19]
The SBA-15-supported TEMPO catalyst 1 was initially
investigated for the oxidation of benzyl alcohol as shown in
Scheme 1, in the absence of any transition-metal co-catalyst
Scheme 1. General protocol for the aerobic oxidation of alcohols using
catalyst 1.
The most important issues that must be resolved for
heterogeneous catalysts are the lifetimes of the catalyst and
the possibility that the active component (i.e. TEMPO) can
leach from the solid into solution, thereby leading to gradual
deactivation of the catalyst. The heterogeneous nature of the
catalyst was confirmed in a filtration experiment, in which the
reaction mixture was filtered after 30 min (60% conversion).
No catalytic activity was observed in the filtrate during 5 h
after filtration. To show that no deactivation occurred in the
aerobic oxidation of benzyl alcohol to give benzaldehyde
(Table 1, entry 1), the recovered catalyst was successively
used in a second run. When the reaction time was set to 1.5 h,
which proved to be sufficient for conversion of benzyl alcohol,
comparably excellent yields of benzaldehyde were obtained
in 14 subsequent runs using the same catalyst to give a total
turnover number (TON) of over 1000.[19]
(1 mol% 1, 10 mol% NaNO2, 8 mol% nBu4NBr, CH3CO2H
as solvent, O2 (1 atm), 508C). Under these conditions, catalyst
1 was highly active for the transformation, and the selectivity
to benzaldehyde was 99.8% or greater at 100% conversion,
with the only by-product being benzyl acetate (less than
0.2%). Interestingly, note that while the initial selectivity of 1
for benzaldehyde was approximately 93% owing to the fast
formation of benzyl acetate (after 10 min), smooth hydrolysis
of benzyl acetate by the by-product water followed by
oxidation of the resulting benzyl alcohol led to an increase
of the final selectivity to benzaldehyde (Figure 1).
Supported reagent 1 (1–1.5 mol%) is also a highly
efficient and selective heterogeneous catalyst for the aerobic
oxidation of a wide range of primary, secondary, and even
sterically hindered alcohols under similar reaction conditions
(Table 1). Air can also be conveniently used instead of pure
oxygen without affecting the efficiency of the reaction.
Although, the use of air requires slightly longer reaction
times, it does not affect the final product selectivities
(Table 1).
To the best of our knowledge, these recovery results are
far superior compared to those reported in the case of
recyclable nitroxyl radicals under aerobic oxidation condi-
tions. This reusability also demonstrates the high stability of
our new heterogeneous system. Although no significant
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Table 1: Aerobic oxidation of alcohols using 1.
change in the activity of the catalyst
was observed, we performed several
studies (surface analysis, DRIFT-IR
spectroscopy measurements, kinetic
measurement of NH3, simultaneous
thermal and TEM analysis) on cat-
alyst 1 after the 14th reaction cycle
to determine any change in the
catalyst structure at a molecular
level. Surface analysis showed that
there is no significant change in the
surface area (from 517 to
516 m2 gÀ1) and a slight decrease in
the total pore volume from 0.68 to
0.65 cm3 gÀ1. Note also that the N2
adsorption/desorption analysis of
the recovered catalyst showed very
similar isotherms to those of the
fresh catalyst 1, with relatively
sharp adsorption and desorption of
type IVin the P/P0 range 0.5–0.8,
which is characteristic of highly
ordered mesoporous materials (Fig-
ures 1S vs 4S in the Supporting
Information).
Entry
R1
R2
t [h]
Productyield [%] [a,b,c]
O2
air
O2
air
1
2
3
4
5
6
7
8
9
Ph
H
H
H
H
H
H
H
H
H
H
Me
Et3
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
3
2.5
3
3
100 (99.8)
100 (99.8)
99 (99.1)
99.7 (99.4)
100 (99.5)
99.8 (99.6)
100 (98.8)
98.1 (97.1)
92 (99.2)
100 (99.1)
100 (99.1)
94.5 (97.4)
100 (99.4)
100 (99.2)
99.4 (98.9)
100 (99)
–
2,6-Cl2C6H4
2-MeC6H4
3-BrC6H4
4-MeOC6H4
3-ClC6H4
4-NO2C6H4
4-MeSC6H4
3-pyridyl
2-furyl
3
2.5
2.5
3
–
–
3
4.5
100 (99.8)
–
10
11
12
1.5
2.5
4.5
98 (99.0)
97.6 (99)
94.2 (98)
100 (99)
Ph
Ph
100 (99.2)
13
3
4.5
100 (99.8)
100 (99.8)
14
15
16
17
18
Ph
4-BrC6H4
PhCH2CH2CH2
CH3(CH2)4CH2
CH3(CH2)4CH2
Ph
Ph
H
H
Me
4.5
4.5
2
2.5
3
6
8
3
3
4
100 (99.3)
100 (99.1)
99 (95.0)
100 (99.8)
100 (99.8)
99 (94.6)
98 (79)[e]
88 (98.0)
100 (76.2)[d]
93 (98.0)
19
20
9.5
–
96 (97.0)
–
10
11
100 (99.6)
99 (99.8)
Interestingly, BJH calculations
also show a narrow mesoporous
diameter of 7.9 nm for 1 prior to
and after the 14th reaction cycle, a
value which is in good agreement
with the mesoporous diameter esti-
mated from the TEM images (Fig-
ure 2a,b vs 2c,d). These observa-
tions are remarkable and suggest
that most of the nanometer-scale
void space and the channels of the
parent SBA-15 remain intact during
the catalysis and recycling process-
es.
[a] GC yield based on internal standard method unless otherwise stated. [b] Numbers in parentheses
refer to selectivity for formation of carbonyl compound. [c] Conditions: Method A: primary and
secondary benzylic alcohols (10 mmol), nBu4NBr (8 mol%), NaNO2 (10 mol%), and catalyst 1 (ꢀ1
mol%) in CH3CO2H (3 mL) at50 8C; Method B: aliphatic and hindered alcohols (10 mmol), nBu4NBr
(14 mol%), NaNO2 (20 mol%), and catalyst 1 (ꢀ1.5 mol%) in CH3CO2H (10 mL) at60 8C.
[d] Approximately 10% of the corresponding acid was formed. [e] Approximately 11.5% of the
corresponding acid was formed.
Further evidence for lack of
degradation of the anchored
organic nitroxyl group in our proto-
col was obtained by FTIR analysis
of the catalyst prior to and after the
14th oxidation run (Figure 6S in the
Supporting
Information).
The
absorption bands in the 2850–
2980 cmÀ1 region (asymmetric and
symmetric vibrations of alkyl
groups in the catalyst) and the
broad signals overlapping in the
1070–1220 cmÀ1 region (Si-O-Si
symmetric stretching)[20] clearly
show that neither the anchored
organic groups nor the silica poly-
meric backbone of SBA-15 are sig-
nificantly affected by prolonged use
in the reaction system. Kinetic com-
parison of simultaneous thermal
Figure 2. a) BJH average pore diameter of catalyst 1 prior to the oxidation. b) TEM image of catalyst 1
prior to the oxidation. c) BJH average pore diameter of catalyst 1 after the 14th reaction cycle. d) TEM
image of catalyst 1 after the 14th reaction cycle. Scale bars: 100 nm.
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[4] For some related examples of transition-metal-catalyzed aerobic
decomposition also shows nearly the same profile for weight
loss after the 14th use as for the fresh catalyst (Figure 7S in the
Supporting Information). There is only a slight change in the
amount of NH3 created during thermal analysis from 0.66 to
0.60 ( ꢀ 9% decrease) from the surface of SBA-15 after the
14th use (Figure 7SD vs 7SB in the Supporting Information).
These results clearly show that the catalyst is very durable and
no significant restructuring of the catalyst takes place on
multiple uses.
In conclusion, we have shown that SBA-15 can be used to
support the nitroxyl radical TEMPO to give an extremely
stable and reusable catalyst for the aerobic oxidation of
alcohols (including primary, secondary, and highly hindered
ones) in the absence of any transition-metal-containing co-
catalyst. TEM, DRIFT IR, kinetic measurement of NH3, and
simultaneous thermal analyses of the catalyst prior to and
after the 14th reaction cycle clearly show that neither the
anchored organic group nor the nanometer-scale voids and
channels of the parent SBA-15 are significantly affected by
prolonged use in the reaction system. To the best of our
knowledge, this method is the first example of transition-
metal-free aerobic oxidation of a wide range of alcohols using
a nanostructured supported organocatalyst under normal
pressure of air. The general achievements in this study have
established a pathway for the development of new transition-
metal-free catalytic protocols in the aerobic oxidation of
alcohols.
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Experimental Section
Oxidation of primary and secondary benzylic alcohols (Method A): A
mixture of alcohol (10 mmol), nBu4NBr (0.26 g, ꢀ 8 mol%), NaNO2
(0.070 g, 10 mol%), and catalyst 1 (0.303 g, ꢀ 1 mol%) in CH3CO2H
(3 mL) was prepared in a two-necked flask at 508C. The flask was
then filled with pure oxygen or air (balloon-filled), and the resulting
mixture was stirred at 508C under an oxygen/air atmosphere (for the
time indicated in Table 1. The progress of the reaction was monitored
by GLC using the internal standard addition method. After com-
pletion of the reaction, the reaction mixture was filtered off and the
catalyst was rinsed with Et2O (3 ” 25 mL). The excess of solvent was
removed from the filtrate under reduced pressure to give the
corresponding carbonyl compounds (Table 1). In most cases, the
purity of the products was analyzed by GC to be greater than 99%
without any chromatographic purification.
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Received: May 2, 2007
Published online: July 26, 2007
Keywords: alcohols · mesoporous materials · oxidation ·
.
supported catalysts · sustainable chemistry
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