In situ formation of NOx and Br anion for aerobic oxidation of benzylic alcohols without transition metal

Article abstract of DOI:10.1055/s-0029-1219202

The reaction of KBrO₃ and NH₂OHHCl in situ generates NO_x and Br anion, which combine with 2,2,6,6-tetramethylpiperidine-N- oxide (TEMPO) to construct a NO-activating dioxygen, Br-assisted, TEMPO-catalyzed aerobic oxidation

Full text of DOI:10.1055/s-0029-1219202

LETTER
437
In situ Formation of NO and Br Anion for Aerobic Oxidation of Benzylic
x
Alcohols without Transition Metal
a
a
a
a
b
a
I
G
n
situFormationo
u
f
N
O
and
B
a
r
A
nion nyu Yang,* Wei Wang, Weimin Zhu, Cunbin An, Xinqin Gao, Maoping Song*
x
a
Department of Chemistry, Zhengzhou University, 75 Daxue Road, Zhengzhou 450052, P. R. of China
Fax +86(371)67763927; E-mail: yangguanyu@zzu.edu.cn; E-mail: mpsong9350@zzu.edu.cn
b
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, P. R. of China
Received 20 October 2009
alcohols could be converted to their corresponding alde-
hydes or ketones in high yields. However, organic TBN
and DBDMH are unstable, and the handling of them, as
Abstract: The reaction of KBrO and NH OH·HCl in situ generates
3
2
NO and Br anion, which combine with 2,2,6,6-tetramethylpiperi-
x
dine-N-oxide (TEMPO) to construct a NO-activating dioxygen, Br-
assisted, TEMPO-catalyzed aerobic oxidation of alcohols. Cata- well as hazardous Br , requires precaution procedures that
2
lyzed by KBrO/NH OH·HCl/TEMPO, various benzylic alcohols are difficult to handle in industrial-scale applications.
2
can be oxidized quantitatively to their corresponding carbonyl com-
pounds under mild conditions. The easy handling and simple prod-
uct separation make the process an attractive candidate for the
oxidation of alcohols.
It is known that the reaction of KBrO and the nitrogen-
3
containing compounds can produce nitrogen oxides, bro-
11
mide anion, and oxybromo species. This implies that the
reaction of KBrO and NH OH·HCl could occur as depict-
3
2
Key words: oxidation, alcohols, catalyst, bromate, hydroxylammo-
nium, 2,2,6,6-tetramethylpiperidine-N-oxide
ed in Equation 1.
So by using KBrO and NH OH·HCl together in the
3
2
TEMPO-catalyzed aerobic oxidation of alcohols, NO,
The oxidation of alcohols to the corresponding aldehydes NO , and Br anion could be generated in situ and then
and/or ketones is of fundamental importance in synthetic serve as cocatalysts. Herein, we report an aerobic alcohol
2
1
research and industrial manufacturing. Use of molecular oxidation under mild conditions, using KBrO ,
3
oxygen as the terminal oxidant is of economic and envi- NH
ronmental benefits in the oxidation of organic com-
pounds. Various investigations showed that 2,2,6,6-
tetramethylpiperidine-N-oxide (TEMPO), as a small mol-
ecule organocatalyst, could efficiently and selectively cat-
alyze the aerobic oxidation of alcohols in combination
with some transition-metal cocatalyst such as Cu–
Mn mixed oxide, NaNO /FeCl , Mn(NO ) /Co(NO ) or
Mn(NO ) /Cu(NO ) , Cu complexes, and RuCl (PPh )
Recently, an interesting transition-metal-free catalytic
system encompassing Br , NaNO , and TEMPO was re-
ported for the aerobic oxidation of alcohols. The catalytic
mechanism involves three tandem reaction cycles: 1) a re-
dox cycle of NO and NO responsible for activating the
molecular oxygen, 2) a redox cycle of TEMPO and its
oxoammonium cation resulting in the oxidation of alco-
hols to the corresponding carbonyl compounds, and 3) the
redox cycle of Br and HBr bridging between the above
two cycles. This system was further improved by using
,3-dibromo-5,5-dimethylhydantoin (DBDMH) as a bro-
mine source instead of Br , and tert-butyl nitrite (TBN)
OH·HCl, and TEMPO as catalytic system.
2
The aerobic oxidation of alcohols was performed using
benzyl alcohol as the model substrate in dichloromethane
under dioxygen (0.30 MPa) at room temperature
12
(
Table 1). The initial test (entry 1) gave an encouraging
result that a complete conversion of benzyl alcohol to ben-
zaldehyde was realized by using 10 mol% of TEMPO, 10
mol% of NH OH·HCl, and 5 mol% of KBrO as catalysts,
and no noticeable overoxidation to benzoic acid was de-
tected. And this clearly showed that the KBrO3/
2
3
4
2
3
3 2
3 2
2
3
5
6
7
3
2
3 2
2
3 3.
2
2
NH OH·HCl/TEMPO system exhibited good catalytic
2
8
performance. In sharp contrast, the reaction occurred
barely in the absence of any component of the catalyst un-
der the same conditions (entries 2–4). In addition, using
2
KBrO alone gave the conversion of 1.9% (entry 5),
3
meaning that benzyl alcohol was oxidized less effectively
by KBrO . And it was noteworthy that when the atmo-
3
2
sphere over the mixture was replaced with O three times
2
in the case of using the three catalytic components togeth-
er, the conversion was only 2.6% (entry 6). The possible
1
9
2
cause could be that the gaseous NO and NO , the real ac-
2
1
0
as an efficient NO equivalent instead of NaNO , respec-
tively. Catalyzed by TEMPO/NaNO /Br , TEMPO/
NaNO /DBDMH, or TEMPO/TBN/HBr, a wide range of
2
tive components of the catalytic system, were missing
during the atmosphere replacement, and, as a result, the
oxidation did not work well. These preliminary results
2
2
2
3 NO + 3 NO2 + 4 Br– + 6 Cl– +6 H+ + 4 K+ + 9 H O..
2
4
KBrO3 + 6 NH2OH⋅HCl
Equation 1
SYNLETT 2010, No. 3, pp 0437–0440
1
2.
0
2.
2
0
1
0
Advanced online publication: 15.01.2010
DOI: 10.1055/s-0029-1219202; Art ID: W16609ST
©
Georg Thieme Verlag Stuttgart · New York

4
38
G. Yang et al.
LETTER
suggested that the reaction of KBrO and NH OH·HCl Table 1 Aerobic Oxidation of Benzyl Alcohol Catalyzed by
3
2
could occur easily to in situ generate NO, NO , and Br an- KBrO
/NH
OH·HCl/TEMPO at Room Temperaturea
2
3
2
ion, as expected, and all of them with TEMPO constructed
the tandem triple catalytic cycles, which promoted the
aerobic oxidation.
Entry
TEMPO
mol%)
NH OH·HCl
KBrO3
(mol%)
Conv.
(%)
2
b
(
mol(%)
10
10
0
1
10
0
5
5
5
0
5
5
5
5
5
5
5
5
5
5
5
5
5
3
1
0.5
100
1.2
Further investigations on this novel three-component cat-
alytic system for the benzyl alcohol oxidation are shown
in Table 1. As can be seen, the decrease in the loading
amounts of each component led to the rate decrease of ox-
idation to different degrees, but the low dosage of TEM-
PO still had a significant catalytic activity. Decreasing the
load amount of TEMPO to 0.1 mol% in the presence of 10
2
3
4
5
6c
7
8
9
10
10
0
0.5
10
0
0
1.9
mol% NH OH·HCl and 5 mol% KBrO , oxidation pro-
2
3
10
5
10
10
10
10
10
10
10
10
5
2.6
ceeded in only 34.5% conversion in the course of 3 hours
entry 12), although benzyl alcohol was completely oxi-
100
100
100
98.3
63.8
34.5
100
58.9
33.8
20.7
1.5
(
dized to benzaldehyde (entry 13) by prolonging the time
to 24 hours under the same conditions.
3
1
The conversion reached as high as 98.3% under the same
conditions in the presence of 0.5 mol% of TEMPO (entry 10
0). Hence, 0.5 mol% was chosen as the loading amount
of TEMPO in the further optimization tests. It was obvi-
0.5
0.3
0.1
0.1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
1
1
2
ous that the loading amount of NH OH·HCl and KBrO3
12
had a greater influence on the rate than that of TEMPO;
1
3d
5
0
8.9% product conversion was realized in the presence of
.5 mol% TEMPO, 5 mol% NH OH·HCl, and 5 mol%
2
14
KBrO (entry 14), but a lower conversion (20.4%) was ob-
3
1
5
3
tained in the presence of 3 mol% KBrO and 10 mol%
3
NH OH·HCl (entry 18). Further decreasing the loading
2
16
1
amounts of both NH OH·HCl and KBrO to 0.5 mol%
2
3
1
1
7
8
0.5
10
10
10
failed to give good yields of the oxidation product (entries
8
–10
1
7 and 20). As documented before,
a cascade of redox
20.4
33.4
6.3
tricycle reactions is involved in such transition-metal-free
oxidation systems. We suggested that the TEMPO redox 19
should proceed faster than the redoxes of NO and Br an-
x
2
0
ion, and therefore, the loading amounts of NH OH·HCl
2
a
and KBrO should be more than the amount of TEMPO in
The oxidations were carried out using 2 mL benzyl alcohol (19.33
3
mmol) and 10 mL CH Cl under £0.3 MPa O for 3 h in all cases.
order to keep the three reaction cycles proceeding.
2
2
2
b
The conversions and the selectivities were based on GC with area
normalization; the selectivities of benzaldehyde were 100% in all
The system was employed further in catalyzing the aero-
bic oxidation for various alcohols. The oxidations of all case.
c
The atmosphere over the mixture was replaced with O for three
alcohols were analyzed by GC-MS analysis, and, to our
expectation, the corresponding carbonyl compounds were
the sole organic products. Each oxidation test was deter-
mined with GC measurement. If the oxidation of the alco-
hol substrate was not completed, the reaction was
repeated again by prolonging the reaction time until no al-
cohol could be detected by GC analysis. Due to the water-
solubility of TEMPO and other inorganic residues, isola-
tions of the corresponding carbonyl compounds were per-
formed easily by merely washing the reaction mixture
with water several times. The isolated carbonyl com-
2
times before stirring began.
d
For 24 h.
fect was observed in the oxidations of p-methylbenzyl al-
cohol, p-methoxybenzyl alcohol, and p-chlorobenzyl
alcohol. For p-nitrobenzyl alcohol, due to the presence of
an electron-withdrawing nitro group, the oxidation need-
ed 24 hours to realize 97.5% conversion at 50 °C. Howev-
er, with a higher TEMPO loading (1 mol%) at a higher
temperature (80 °C), the complete oxidation could also be
achieved in a shorter time of six hours. Furthermore, no
matter where the methyl is located, all methylbenzyl alco-
hols could be oxidized to the corresponding aldehydes un-
der the same conditions. On the other hand, cinnamyl
alcohol, 2-phenethanol, and cyclohexanol were oxidized
in isolated yields of 95%, 93%, and 77%, respectively, un-
der slightly different reaction conditions.
1
pounds were characterized by H NMR spectroscopy (see
Supporting Information). The isolated yields and some
1
3
GC yields were presented in Table 2. As can be seen, by
increasing the temperature from room temperature to
5
0 °C with the optimized amounts of the catalysts (0.5
mol% of TEMPO, 10 mol% of NH OH·HCl, and 5 mol%
2
of KBrO ), oxidation of benzyl alcohol was accomplished
3
in the shorter course of two hours. Similar temperature ef-
Synlett 2010, No. 3, 437–440 © Thieme Stuttgart · New York

LETTER
In situ Formation of NO and Br Anion
439
x
a
Table 2 Oxidation of Different Alcohols Catalyzed by KBrO /NH OH·HCl/TEMPO
3
2
Alcohol
TEMPO (mol%)
.5
Temp (°C) Time (h) Products
Yield (%)b
OH
0
50
2
CHO
97c
OH
0.5
.5
25
80
8
6
95.9
96
c
0
CHO
OH
0.5
0.5
25
50
12
12
85.7
99
c
MeO
Cl
CHO
MeO
Cl
OH
0.5
0.5
25
50
24
12
89.6
CHO
c
93
OH
0.5
1.0
50
80
24
6
97.5
97
O2N
CHO
c
O2N
OH
OH
0.5
80
80
6
6
93c
CHO
CHO
98c
0
0
.5
.5
25
80
18
12
CHO
40.5
c
OH
1.0
95
OH
0.5
1
25
80
24
6
O
98.2
93
c
0
5
.5
25
25
24
24
64.0
77
c
OH
O
a
The reactions were carried out under 0.3 MPa of dioxygen in 10 mL of CH Cl ; the used amounts of solid substrates were 1.0 g and liquid
2
2
were 2 mL; 5.0 mol% of KBrO and 10.0 mol% of NH OH·HCl were used in all case.
3
2
b
c
GC yields.
Isolated yields.
In summary, a transition-metal-free, efficient catalytic tion of China (No. 20872133), and Opening Research Foundation of
State Key Laboratory of Fine Chemicals, Dalian University of
Technology.
system consisting of KBrO , NH OH·HCl, and TEMPO
was developed that was able to perform the aerobic oxida-
tions of various alcohols to their corresponding carbonyl
3
2
compounds under mild conditions. During the catalytic References and Notes
process, the reaction of KBrO and NH OH·HCl could in
3
2
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situ generate NO and Br anion. The redox cycle of NOx
x
played an important role in activating molecular oxygen
for this Br-assisted, TEMPO-catalyzed aerobic oxidation.
The easy handling and simple separation make the process
an attractive method for the oxidation of alcohols.
2
004, 2203. (f) Lenoir, D. Angew. Chem. Int. Ed. 2006, 45,
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Acknowledgment
This work was supported financially by China Postdoctoral Science
Foundation (No. 20070410251), National Natural Science Founda-
Synlett 2010, No. 3, 437–440 © Thieme Stuttgart · New York

4
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LETTER
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(12) General Typical Procedure for the Oxidation
The reaction was carried out in a 70 mL autoclave, and the
general procedure is described typically with benzyl alcohol
as follows: To a reactor were added benzyl alcohol (2 mL,
19.3 mmol), NH OH·HCl (174.8 mg, 10 mol%), KBrO
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2
3
7
087. (m) Herrerías, C. I.; Zhang, T. Y.; Li, C.-J.
(161.2 mg, 5 mol%), TEMPO (15.1 mg, 0.5 mol%), and
CH Cl (10 mL). The closed autoclave was charged with O
2
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2
2
(
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to 0.3 MPa and warmed to 80 °C under stirring. The pressure
of O was kept under 0.4 MPa for 2 h. After cooled to r.t., 20
2
mL CH Cl were added to the autoclave. Then the solution
2
2
was analyzed by gas chromatography, which was conducted
using an Agilent Technologies 6890N Network GC System
with a flame ionization detector and a DB-1 capillary
column (30 m × 0.535 mm × 3.0 mm).
2
007, 16, 210.
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(
(
(
2
(13) General Isolation Procedure for the Oxidation Product
After GC showed the reaction to be complete, the reaction
mixture was diluted with CH Cl and transferred into a
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2
2
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separation funnel. The CH Cl solution was washed with 15
2 2
mL of a sat. solution of Na CO , followed by brine. The
2
3
organic layer was dried over anhyd Na SO , and the solvent
2
4
(
was evaporated to yield the product without further
purification.
Synlett 2010, No. 3, 437–440 © Thieme Stuttgart · New York

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