TEMPO-tert-butyl nitrite: An efficient catalytic system for aerobic oxidation of alcohols

Article abstract of DOI:10.1002/adsc.200800501

A metal-free catalytic system consisting of 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) and tert-butyl nitrite has been developed to activate molecular oxygen for the aerobic oxidation of alcohols. A variety of active and non-active alcohols were oxidized to their corresponding carbonyl compounds in high selectivity and yields.

Full text of DOI:10.1002/adsc.200800501

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DOI: 10.1002/adsc.200800501
TEMPO-tert-Butyl Nitrite: An Efficient Catalytic System for
Aerobic Oxidation of Alcohols
Xijun He,a Zhenlu Shen,a,* Weimin Mo,a Nan Sun,a Baoxiang Hu,a
and Xinquan Hua,b,*
a
College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, Peopleꢀs
Republic of China
Fax : (+86)-571-8832-0103; e-mail: xinquan@zjut.edu.cn or zhenlushen@zjut.edu.cn
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese
b
Academy of Sciences, Lanzhou 730000, Peopleꢀs Republic of China
Received: August 11, 2008; Revised: October 14, 2008; Published online: December 19, 2008
Abstract: A metal-free catalytic system consisting
of 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO)
and tert-butyl nitrite has been developed to activate
molecular oxygen for the aerobic oxidation of alco-
hols. A variety of active and non-active alcohols
were oxidized to their corresponding carbonyl com-
pounds in high selectivity and yields.
Therefore, it is desirable to develop of an efficient
and selective catalyst system for the aerobic oxidation
of a broad range of alcohols. Although the catalytic
system TEMPO/NaNO2/HCl was recently developed
for selective aerobic oxidation of a variety of primary
and secondary alcohols under mild conditions,[7] its
application to substrates containing acid-sensitive
functional groups might be limited because a high
loading of HCl (10–16 mol%) was used. Very recent-
ly, we have reported an efficient aerobic oxidation of
various active alcohols with high turnover number
(TON) under almost neat condition with TEMPO/
tert-butyl nitrite (TBN)/aqueous HBr as the catalytic
system.[8] In this system, the organic nitrite, TBN,
served as an efficient NO equivalent to activate mo-
Keywords: alcohols; tert-butyl nitrite; molecular
oxygen; oxidation; TEMPO; 2,2,6,6-tetramethylpi-
peridine N-oxyl (TEMPO)
Selective oxidation of alcohols is an important reac- lecular oxygen and enabled the aerobic oxidation at
tion in organic chemistry.[1,2] Among the stoichiomet- very high-volume efficiency.
ric oxidants, molecular oxygen is a preferred terminal
Generally, the TEMPO cation, which was initially
oxidant from both economical and environmental per- formed via oxidation of TEMPO, acts as the active
spectives. We have previously developed a three-com- oxidant in the TEMPO-catalyzed oxidation of alco-
ponent catalyst system, consisting of 2,2,6,6-tetrame- hols. According to the literature, the electrode poten-
thylpiperidine N-oxyl (TEMPO), Br2 and NaNO2, to tial (E0) of TEMPO cation/TEMPO is 0.75 V,[2h] while
activate molecular oxygen for the selective aerobic E0 of N2O4/NO is 1.03 V.[9] Based on this information,
oxidation of alcohols to their corresponding carbonyl we reckoned that NO2 can oxidize TEMPO into the
compounds.[3] The method hinges upon a key finding TEMPO cation to initialize the oxidation (Scheme 1).
that the inorganic salt, NaNO2, could serve as an NO Under high temperatures TBN can release NO or
equivalent to activate molecular oxygen under acidic NO2 because of its thermal instability. NO can be
conditiona. This concept has been extended and ap- quickly oxidized into NO2 by molecular oxygen. Con-
plied for a broad array of substrates with good selec- sequently, NO2 oxidizes TEMPO into the TEMPO
tivities.[4] However, most of these methods require a cation, which can fulfil the oxidation of an alcohol
Br source as the co-catalyst to bridge the two catalytic substrate to its corresponding carbonyl compound.
cycles between TEMPO cation/TEMPOH and NO/ Upon completion of the alcohol oxidation, the
NO2. As a result, those substrates bearing an olefin TEMPO cation turns into its reduced state,
moiety are not favored due to side reactions of HBr TEMPOH, which on further reaction with NO2 forms
or Br2 with the carbon-carbon double bonds.[5] More- the TEMPO cation, and thus completes a catalytic
over, the aerobic oxidation of aliphatic primary alco- cycle. Therefore, a potential double-component cata-
hols remains a challenge because their propensity lytic system, TEMPO/NO2, could be established to
toward being overoxidized into acids and/or ortho furnish the aerobic oxidation using TBN as the NO
esters under these conditions.[6]
equivalent.
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89

Xijun He et al.
Table 1. Aerobic oxidation of benzyl alcohols.[a]
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Entry Substrate
Product
Catalyst Time Yield
[mol%] [h] [%][b]
AHCTUNGTRENNUNG
1
2
3
0.5:4
0.5:4
0.5:4
2
4
3
96
95
96
4
0.5:4
5
94
5
6
0.5:4
0.5:4
4
2
95
96
Scheme 1. A proposed overall mechanism of the TEMPO-
TBN catalytic system for the aerobic oxidation of alcohols.
7
8
0.5:4
0.5:4
2
3
95
96
Herein, we report a TEMPO/TBN double-compo-
nent catalyst system for the highly selective aerobic
oxidation of various alcohols, including benzyl alco-
hols, as well as primary and secondary aliphatic alco-
hols [Eq. (1)].
9
0.5:4
1:4
20
3
97
94
93
10
11
1:4
2
12[c]
13[c]
0.5:4
0.5:4
0.5:4
3
3
4
95
93
96
Our initial experiment of aerobic oxidation of
benzyl alcohol to benzaldehyde was carried out with
2 mol% of TEMPO, 8 mol% of TBN in 1,2-dichloro-
ethane at 808C under 0.2 MPa of oxygen. It was
found that benzyl alcohol was smoothly converted
into benzaldehyde in full conversion with a little ben-
zoic acid.[10] This preliminary result showed that the
Br-free catalytic system for aerobic oxidation of alco-
hols designed in Scheme 1 was feasible. After optimi-
zation of reaction temperature, oxygen pressure and
molar ratio of both catalytic components, this reaction
could be completed with 0.5 mol% of TEMPO and
4 mol% of TBN under 0.2 MPa of oxygen at 808C in
14
[a]
All reactions were carried out with 10 mmol of substrate
in 10 mL of ClCH2CH2Cl. Catalyst=TEMPO/TBN in
the specified molar ratio, O2 (0.2 MPa), 808C, 100% con-
versions for all substrates according to GC analysis.
Isolated yield.
[b]
[c]
AcOH (1 mL) was added.
2 h. The end point of reaction time could be deter- isolated yields (entries 1–9). The reaction time dis-
mined simply by observation of the vessel pressure played a correlation with the substituent effects. Even
through a barometer. Several solvents, such as t- the highly electron-deficient p-nitrobenzyl alcohol can
BuOH, toluene, PhCl, PhCF3, AcOH, CH3CN and be smoothly oxidized after an extended reaction time
H2O were also tested under the same reaction condi- (entry 9, Table 1).
tions, the conversions of benzyl alcohol were only 1.0,
For electron-rich alcohol substrates, such as 2-fur-
2.0, 2.2, 2.2, 42.3, 60.6 and 4.5%, respectively.[11] The furylmethanol and 2-thiophene-methanol, this catalyst
dramatic difference of conversions of benzyl alcohol system can provide clean aldehyde products (en-
might be relevant to real electrode potentials of tries 10 and 11, Table 1) without affecting the aromat-
redox pairs in these solvents.
ic ring, while some brominated aldehyde by-product
To explore the substrate scopes, we applied this was observed[3,4a,8] in the previous Br-containing cata-
newly developed method to a variety of alcohols. The lytic system for this type of alcohol. As usual, for the
results of benzylic alcohols and their heteroaromatic oxidation of pyridine-methanols, one equivalent of
analogs are summarized in Table 1. As can be seen AcOH was needed to control the pH during the oxi-
from Table 1, all tested benzylic alcohols were fully dation (entries 12 and 13, Table 1). Notably, 4-methyl-
converted into their corresponding aldehydes in high thiobenzyl alcohol, which bears two labile function
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TEMPO-tert-Butyl Nitrite: An Efficient Catalytic System
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groups, could be selectively converted into 4-methyl- zoin in 12 h (entry 6, Table 2). Compared with benzyl-
thiobenzaldehyde without any detectable sulfur oxida- ic alcohols, aliphatic alcohols are less active substrates
tion. This result demonstrates that thioethers can tol- for oxidation. Indeed, secondary aliphatic alcohols
erate the aerobic oxidation under the TEMPO/TBN could be oxidized into ketones by increasing the load-
catalytic system (entry 14, Table 1).
ing of TEMPO (entries 7–9, Table 2). To our delight,
With these results in hand, we examined the aero- high selectivities were achieved in the oxidation of
bic oxidation of various alcohols including secondary primary alcohols. For example, with 1-octanol as the
benzylic, primary, secondary aliphatic alcohols, and substrate, only a trace amount of 1-octyl octanoate
also cinnamyl alcohol. The results summarized in was observed (entry 10, Table 2). A high isolated
Table 2 demonstrate the effectiveness of this bromine- yield of phenylacetaldehyde was also obtained under
free catalytic system for the preparation of various al- similar conditions (entry 11, Table 2). Unfortunately,
dehydes and ketones. All substituted a-phenyletha- the oxidation of cinnamyl alcohol, a typical allylic-
nols could be smoothly converted into their corre- type alcohol substrate, did not provide the expected
sponding acetophenones in high yields (entries 1–5, result. Only a 13.6% conversion was observed, al-
Table 2). For 1,2-diphenylethane-1,2-diol, which is though the selectivity was as good as usual (entry 12,
prone to forming benzaldehyde because of the easy Table 2). A slight improvement was observed with the
carbon-carbon bond cleavage in some other oxidation addition more TEMPO in the catalytic system. Ac-
systems,[4b] it could be also smoothly oxidized to ben- cording to our proposed mechanism in Scheme 1, we
postulate that the alcohol oxidation step was a slow
transformation. TEMPO cation was decomposed to
Table 2. Aerobic oxidation of benzylic secondary, primary
form of 2,2,6,6-tetramethylpiperidine (TEMPH),
which discontinued the catalytic cycle, rather than the
normal TEMPOH.
and secondary aliphatic alcohols.[a]
Entry Substrate
Product
Catalyst Time Yield
In conclusion, we have successfully developed a
new metal-free catalytic system, with TBN as the NO
equivalent to activate molecular oxygen, and which
was applied in the aerobic oxidation of a broad range
of alcohol substrates, including benzylic alcohols, het-
eroaromatic analogues, substituted a-phenylethanols,
primary and secondary aliphatic alcohols, to their cor-
responding aldehydes and ketones. This novel catalyt-
ic system not only provides an efficient method to
prepare various aldehydes and ketones from alcohols
but may also inspire other uses of organic NO equiva-
lents in the oxidation chemistry.
[mol%] [h]
[%][b]
1
2
3
0.5:4
0.5:4
0.5:4
3
3
2
96
97
97[c]
4
5
6
0.5:4
0.5:4
0.5:4
2
98
96
95
4
12
Experimental Section
7
8
2-Octanol
1-Octanol
2-Octanone
1-Octanal
2:4
4:4
7
95
93
Typical Procedure for Aerobic Oxidation of Benzyl
Alcohol to Benzaldehyde
10
To a Teflon-lines 316 L stainless steel autoclave (300 mL)
with magnetic stirring bar, were added 10 mL of 1,2-di-
chloroethane, which contained 7.8 mg of TEMPO
(0.05 mmol, 0.5 mol%), 46 mL of TBN (41 mg, 0.4 mmol,
4 mol%) and 1.08 g of benzyl alcohol (10 mmol). Then the
autoclave was closed and charged with oxygen to 0.2 MPa.
The autoclave was placed in an oil bath, which was preheat-
ed to 808C. Two hours later, the barometer dropped to
0.18 MPa and indicated that the reaction was finished. The
autoclave was taken out from the oil bath, cooled to room
temperature and carefully depressurized. The sample was di-
luted with 1,2-dichloroethane and the conversion and selec-
tivity were detected by GC without any purification. GC re-
sults showed the reaction to be complete, the liquid in the
autoclave was transferred into a separation funnel, washed
with aqueous Na2S2O3 solution (10 mLꢂ3), the organic layer
was dried over anhydrous Na2SO4, concentrated to dryness
9
4:4
12
95
10
11
2:4
2:4
6
3
94[d]
90
12
2:4
12
13.6[e]
[a]
All reactions were carried out with 10 mmol of substrate
in 10 mL of ClCH2CH2Cl. Catalyst=TEMPO/TBN in
the specified molar ratio, O2 (0.2 MPa), 808C. 100% con-
versions by GC analysis unless otherwise specified.
Isolated yield.
99% conversion.
1% of 1-octyl 1-octanate was observed.
GC conversion with a >99% selectivity.
[b]
[c]
[d]
[e]
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Xijun He et al.
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to yield the product as a liquid; yield: 1.02 g (96%).
1H NMR confirmed that it was the desired benzaldehyde.
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This work was financially supported by the National Natural
Science Foundation of China (NSFC, 20772111) and the Nat-
ural Science Foundation of Zhejiang Province (Y406419).
The authors thank Dr. Hanmin Huang, Dr. Tony Y. Zhang
and Dr. Wenjun Tang for their helpful discussions.
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