Highly practical sodium(i)/azobenzene catalyst system for aerobic oxidation of benzylic alcohols

Article abstract of DOI:10.1039/c5ra15286k

An economic, environmental and practical aerobic oxidation of benzylic alcohols and hetero aryl alcohols to the corresponding carbonyl compounds with good substrate scope is disclosed for the first time. Good to excellent yields were obtained by employing economic and commercially available sodium bromide and a catalytic amount of azobenzene under metal-free and ligand-free conditions. Moreover, aldehydes and acids, the oxidation products of benzylic 1° alcohols, could be obtained using sodium bromide and sodium hydroxide as the co-catalyst respectively in high yields.

Full text of DOI:10.1039/c5ra15286k

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Highly Practical Sodium (Ⅰ)/ Azobenzene Catalyst System for
Aerobic Oxidation of Benzylic Alcohols
Chengkou Liu,a,† Zheng Fang,a,† Zhao Yang,b Qingwen Li,a Shiyu Guo,a and Kai Guoa,c,*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
An economic, environmental and practical aerobic oxidation of benzylic alcohols and hetero aryl alcohols to the
corresponding carbonyl compounds with good substrate scope is disclosed firstly. Good to excellent yields were obtained
by employing economic and commercial available sodium bromide and catalyst amount of azobenzene under metal-free
and ligand-free conditions. Moreover, aldehydes and acids, the oxidation products of benzylic 1o alcohols, could be
obtained using sodium bromide and sodium hydroxide as the co-catalyst respectively in high yields.
www.rsc.org/
Consequently, the development of green, economical and
practical oxidation process is still a big challenge.
Introduction
Azo compounds have been used as the oxidant of alcohols for
From both economic and environmental viewpoints, the
selective oxidation of benzylic alcohols to the corresponding
carbonyl compounds is one of the most challenging
transformations. Many traditional and novel methods have
been developed with the efforts of many researchers over the
past few decades. Manganese1-4 and chromium oxides5-7 may
be still the most used oxidants in the oxidation of alcohols,
such as KMnO4, MnO2 and PCC. Unfortunately, stoichiometric
heavy metal waste was produced at the same time, which
limits these reagents into the small-scale. Besides, iodine
decades.29 And, researchers were devoted to finding efficient
catalysts and co-catalysts because of the low-reactivity and
high cost of azo compounds. Many oxidation systems have
been developed, such as azo compounds together with
Grignard reagent30 or AZADO (2-Azaadamantane-N-oxyl).31
And, many metal compounds were proved to be efficient
catalyst for the oxidation of alcohols by azo compounds, such
as Cu,32-34 Mg,35 Ni35 and Zn35. Moreover, copper was used
mostly. Lately, the azo compounds were often used as the
ligands of the copper to catalyse the oxidation reaction.
reagent,8-10 such as Dess-Martin reagent, and activated-DMSO
reagent,11,
such as Swern reagent were built, and the
12
oxidation products of alcohols were obtained smoothly.
However, either economics (The iodine reagents were usually
costly) or the difficulty of the operation (Low temperature
should be kept when Swern reagent was used), limits the use
of these reagents. Besides these reagents, DDQ (2, 3-dichloro-
5, 6-dicyano-1, 4-benzoquinone),13-16 TEMPO (2, 2, 6, 6-
tetramethylpiperidinooxy)17-19 and NaClO20-22 were also used
as the oxidant of benzylic alcohols. Unfortunately, some
drawbacks were existent, such as high cost, using complex
ligands and danger. In summary, dioxygen should be the most
practical oxidant. In recent years, many oxidation systems of
dioxygen have been developed. The most common systems
were dioxygen together with noble metals (e.g, Pd, Pt, Au,
Ru)23-26 or complex and commercially unavailable ligands.27, 28
Results and discussion
Within the context, we desired to develop a novel oxidation
system using catalytic amount of azo compounds together
with dioxygen without any heavy metal or complex co-catalyst.
The 4-Nitrobenzyl alcohol was chosen as the model substrate
for our initial study. The detailed results were summarized in
Table 1.
Firstly, the reaction did not occur when azo compounds were
used alone, which indicated that these azo compounds
showed lower reactivity (Table 1, entries 1-6). To our delight,
the expected oxidation product was obtained when NaBr, the
inexpensive and readily available reagent, was added (Table1,
entry 8). However, the reaction did not proceed when DIAD
was used. The instability of DIAD may be the main reason
(Table1, entry 7). Fortunately, the decrease of the equivalent
of the catalyst azobenzene did not cause the obvious drop of
the yield (Table1, entry 9). Further solvent screening indicated
that 1, 4-Dioxane was the best one among N, N-
dimethylformamide, Dimethyl sulfoxide, Acetonitrile and
Toluene (Table1, entries 9-13). An obvious lower yield was
obtained when polar solvent was used, which indicated
possible critical complex was unstable in these polar solvent.
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Table 1 optimization of the reaction conditiona
involved. Moreover, further investigation of the equivalent of
NaBr showed the amount of the co-catalyst influenced the
reaction process obviously (Table SI). It might be the reason
why Na2CO3 gave a higher yield compared with NaHCO3. No
product was detected when the reaction was conducted under
Ar atmosphere, which suggested dioxygen was the actual
oxidant (Table 1, entries 9, 24).
OH
O
conditions
O2N
1a
O2N
2a
Entry
Catalyst
(mol%)
Co-
T
Solvent
T(h)
Yield
(%)b
We set out to explore the methodology with respect to the
substitution of the aryl ring and aliphatic alcohols (Table 2) .In
general, the oxidation reaction is affected by steric hindrance
and electronic factors moderately.18, 36And, aliphatic alcohols
often show lower reactivity. One set of alcohols oxidation was
performed following the optimized procedure above. It was
observed that both electron-rich and electron-deficient
benzylic alcohols could be oxidized smoothly in moderate to
good yields (Table 2, entries 1- 10). Nevertheless, electron-
withdrawing groups attached to the phenyl rings of substrate
showed lower reactivity obviously (Table 2, entries 1-3). As,
more reaction time should be needed to reach the full
conversion. To our delight, the efficiency of this reaction was
not affected obviously by substituents at different positions of
the aryl ring and steric hindrance (Table 2, entries 1- 3, 9, 10).
Moreover, there was no obvious effect observed between 1o
benzylic alcohols and 2o benzylic alcohols and hetero aryl
alcohols were oxidized to afford the corresponding products in
good yields (Table 2, entries 1-13). Unfortunately, almost no
desired product was obtained when aliphatic alcohols were
texted (Table 2, entries 14, 15).
catalyst
(℃)
1
2
3
4
DIAD（200）
DIAD（200）
DIAD（200）
Azobenzene
(200)
-
-
-
-
80
80
80
80
DMSO
Toluene
Dioxane
DMSO
24
24
24
24
trace
trace
trace
trace
5
6
Azobenzene
(200)
-
-
80
80
Toluene
Dioxane
24
24
trace
trace
Azobenzene
(200)
7
8
DIAD（200）
Azobenzene
(200)
NaBr
NaBr
80
80
Dioxane
Dioxane
24
24
trace
90
9
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
NaBr
NaBr
NaBr
NaBr
80
80
80
80
Dioxane
DMF
48
48
48
48
88
5
10
11
12
DMSO
8
Acetonit
rile
8
13
14
15
16
17
18
19
20
21
22
23
24c
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
Azobenzene(5)
NaBr
NaBr
80
65
50
80
80
80
80
80
80
80
80
80
Toluene
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
48
48
48
48
48
48
48
48
48
48
48
48
42
78
NaBr
22
TBAB
KBr
trace
trace
trace
35
NH4Cl
NaCl
Table 2 NaBr/azobenzene-promoted oxidation of alcoholsa
NaHCO3
Na2CO3
NaOH
Na2SO4
NaBr
trace
64
OH
R2
O
2
azobenzene
NaBr/O2
--
R1
R1
R2
1
82
/
Entry
Substrates
R1
T
Product
No
Yield
(%)b
R2
(h)
areaction conditions: 1a (1mmol), catalyst, co-catalyst (2mmol), solvent (3 mL), T (℃),
under O2 (O2 balloon), DIAD: diisopropyl azodicarboxylate
byield: isolated yield.
cunder N2
1
2
o-NO2Ph
H
H
48
48
48
24
24
24
24
24
24
24
24
24
36
48
48
2b
2c
2a
2d
2e
2f
86
85
.
m-NO2Ph
p-NO2Ph
p-OMePh
p-ClPh
.
3
H
88
4
H
94
5
H
96
When the temperature was decreased to 65
℃, a little drop of
6
p-ClPh
CH3
H
96
the yield was obtained even though the reaction time was
extended (Table1, entry 14). Even worse, the yield was
dropped to 22 % when the temperature was decreased to 50
7
p-BrPh
2g
2h
2i
94
8
p-BrPh
CH3
Ph
H
95
9
Ph
92
℃, which indicated that temperature affected this oxidation
10
11
12
13
14
15
2,6-dichloro-Ph
2-Furan
2j
93
H
2k
2l
92
reaction obviously (Table 1, entries 9, 14, 15). In addition,
further co-catalyst screened showed that this catalytic process
was promoted by the Na+ rather than Br- or K+ (Table 1, entries
9, 16, 17). And, different Na+ source have different catalytic
activity (Table1, entries 9, 19-23). NaBr was the best choice. It
was possible that the catalytic performance of different Na-
based co-catalysts was influenced by pKb. And, neutral co-
catalysts showed higher catalytic activity. So, relatively good
yields were obtained when NaBr, Na2SO4 and NaCl were
2-Thiophene
3-Pyridine
Hexyl alcohol
Cyclohexanol
H
93
H
2m
2n
2o
89
trace
trace
areaction conditions: 1 (1mmol), azobenzene (0.05 mmol), NaBr (2 mmol), 1,4-
Dioxane (3 mL), 80℃, under O2 (O2 balloon). byield: isolated yield.
2 | J. Name., 2012, 00, 1-3
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O
2
OH
R2
was observed in the absence of azobenzene, which would be
discussed detailed in another paper later.
azobenzene
NaBr/O2
R1
R1
R2
Br
1
Following this new protocol, a wide range of acids were
obtained from the oxidation of 1o alcohols in excellent yields
(scheme 2). The 1o benzylic alcohols could be oxidized to acid
efficiently. Fortunately, the effect of different electronic
properties (electron-donating or electron-withdrawing) of the
substituents could be ignored. Moreover, the desired products
could be got when hetero aryl 1o alcohols were investigated,
which indicated that the Na+/azobenzene oxidation system
was very practical.
Cl
O
O
O
O
(2p, 96%, 24h)
(2q, 94%, 24h)
(2r, 94%, 24h)
(2s, 93%, 24h)
I
OH
O
Cl
O
O
O
(2t, 92%, 24h)
(2u, 95%, 24h)
(2v, 92%, 24h)
(2w, 95%, 24h)
Br
O
O
O
O
F3C
F
OH
O
azobenzene
NaOH/O2
(2x, 94%, 24h)
(2y, 92%, 24h)
(2z, 94%, 36h)
(2aa, 90%, 48h)
R3
H
R3
OH
O
O
O
O
1
3
O
(2ae, 90%, 24h)
O
F
O
O
O
O
(2ab, 96%, 24h)
(2ac, 95%, 24h)
(2ad, 94%, 36h)
OH
OH
OH
OH
O
O
S
O2N
Cl
Br
3a,94%,24h
O
3b,92%,24h
3c,94%,24h
3d,95%,24h
O
O
N
(2af, 92%, 24h)
(2ah, 96%, 24h)
(2ag, 90%, 36h)
(2ai,92%,24h)
O
OH
O
OH
O
O
S
OH
OH
Scheme 1 library synthesis of aldehydes and ketones
The standard reaction conditions: 1 (1 mmol), azobenzene (0.05 mmol), NaBr (2
N
3e,93%,24h
Scheme 2 library synthesis of acids
The standard reaction conditions: 1 (1 mmol), azobenzene (0.05 mmol), NaOH (2
3f,88%,24h
3g,86%,24h
3h,90%,24h
mmol), 1, 4-Dioxane (3 mL), 80
isolated products.
℃, under O2 (O2 balloon). Yields shown were the
The experimental results above showed that this oxidation
system was applicable to all kinds of 1o benzylic alcohols, 2o
benzylic alcohols and hetero aryl alcohols. The limitation of
steric hindrance and electronic nature could be ignored. A
library of aldehydes and ketones were synthesized from
various alcohols in good yields (scheme 1).
mmol), 1, 4-Dioxane (3 mL), 80
isolated products.
℃, under O2 (O2 balloon). Yields shown were the
Conclusions
As we all know, the dismutation reaction could occur under
the strong alkaline condition when the aldehyde did not
involve any ɑ-H.37-39 And, the corresponding alcohol and acid
were got. In table 1, when NaOH was chosen as the co-
catalyst, the oxidation of alcohol and the cannizzaro reaction
occurred smoothly. And, the acids were obtained in good
yields as the final product. To our knowledge, a special base
(sodium pyrazolide) could promote the oxidation of 1o benzylic
alcohol to the corresponding acid successfully. Afterwards,
NaH was found to be a useful replacer in this oxidation
system.40 Similarly, NaOH here may be used as the promoter
just like the NaH before. In other words, we guessed the
transformation could occur normally without any azobenzene.
In summary, a practical and economical oxidation system of
Na+/azobenzene/O2 was built firstly, although some oxidation
systems
of
Cu/azo
compounds
(CuCl.Phen.DEAD-
H2.K2CO3/CuCl.dpPhen.DBAD.Cs2CO342) were reported before.
A series of benzylic alcohols and hetero aryl alcohols could be
oxidized to the corresponding carbonyl compounds smoothly.
Moreover, the products of 1o alcohols could be controlled by
the different co-catalyst. And, the aldehydes and acids were
obtained accordingly. Although the exact mechanism was
uncertain, it was easy to believe that the Na+ here played a
similar role as Cu42 above.
Finally, we found that lei and his co-workers41 reported on Acknowledgements
aerobic oxidation of benzylic alcohols into the corresponding
The research has been supported by National Key Basic
acids under NaOH/air/THF conditions in 2013. Nevertheless,
the oxidation system of azobenzene/NaOH/O2 was still
meaningful. As, higher yields of heterocyclic alcohols were
obtained compared with oxidation system without
azobenzene. Especially, 2, 5-furandicarboxylic acid was
obtained in excellent isolated yield from oxidation of 5-
Research Program of China (973 Program) 2012CB725204; the
National High Technology Research and Development Program
of China (863 Program) 2014AA022101; the National Natural
Science Foundation of China (Grant No.U1463201 and
81302632); the National Science and Technology Major
Projects for "Major New Drugs Innovation and Development"
(2013ZX09103001-004).
hydroxymethylfurfural
under
azobenzene/sodium
methanolate/O2. However, an obvious decrease of the yield
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