Environmentally benign oxidation reaction of benzylic and allylic alcohols to carbonyl compounds using Pd/C with sodium borohydride

Article abstract of DOI:10.1055/s-2006-956457

Pd/C catalyst in aqueous alcohol with molecular oxygen, sodium borohydride, and potassium carbonate efficiently oxidized benzylic and allylic alcohols. The use of a reducing reagent, sodium borohydride, for the reactivation of active sites of the Pd surface proved to be remarkable. The utilization of room temperature reaction condition and aqueous alcohol solvent as well as the recyclability of Pd/C makes this manipulation very interesting from an economic and environmental perspective. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-956457

LETTER
95
Environmentally Benign Oxidation Reaction of Benzylic and Allylic Alcohols
to Carbonyl Compounds Using Pd/C with Sodium Borohydride
a
b
a
b
O
G
xidation of Benz
w
ylic and
A
llylic
A
a
n
arbonyl
C
om
g
pounds il An, Minkyung Lim, Kwon-Soo Chun, Hakjune Rhee*
a
Radiopharmaceuticals Laboratory, Korea Institute of Radiological & Medical Sciences, Nowon-Gu, Gongneung-Dong 2154,
Seoul 139-706, Korea
b
Department of Chemistry and Applied Chemistry, Hanyang University, Ansan Sa 1-Dong 1271, Kyunggi-Do 426-791, Korea
Fax +82(31)4073863; E-mail: hrhee@hanyang.ac.kr
Received 19 September 2006
oxidation to the corresponding carbonyl compound using
Pd/C catalyst in the presence of sodium borohydride
under oxygen.
Abstract: Pd/C catalyst in aqueous alcohol with molecular oxygen,
sodium borohydride, and potassium carbonate efficiently oxidized
benzylic and allylic alcohols. The use of a reducing reagent, sodium
borohydride, for the reactivation of active sites of the Pd surface
proved to be remarkable. The utilization of room temperature reac-
tion condition and aqueous alcohol solvent as well as the recyclabil-
ity of Pd/C makes this manipulation very interesting from an
economic and environmental perspective.
To date, it is mostly accepted that the oxidation of primary
alcohol to the corresponding aldehyde follows dehydro-
genation mechanism as shown below in Equation 1.7
Since this oxidation reaction proceeds under an oxygen at-
mosphere, the adsorbed co-product, hydrogen, is oxidized
with molecular oxygen to afford freshly active sites on the
surface of the catalyst.
Key word: palladium, oxidations, alcohols, sodium borohydride,
oxygen
R CH2 OHad
R CH2 Oad
R CH2 Oad
R CH=Oad
+
Hadm
Had
The oxidation of alcohols to aldehydes and ketones is one
of the most important organic manipulations in organic
synthesis. There are versatile methods for such conver-
sion like using metal-based oxidants (chromium reagents,
manganese reagents, ruthenium reagents, etc.), dimethyl
sulfoxide reagents, halogen-based oxidants, Oppenauer
+
1
Equation 1
‘
Over-oxidation’ of the active sites on the surface of the
catalyst due to very high concentration of oxygen has
been commonly known to deactivate the metal catalyst.8
We extraordinarily chose a reducing reagent, sodium
borohydride, which is readily available and relatively sta-
ble in protic solvents, to reactivate the over-oxidized pal-
ladium surface under molecular oxygen. The use of
sodium borohydride posed several considerations includ-
ing its reaction rate and reducing power. It must react with
the over-oxidized palladium surface faster than the reac-
tion product (aldehyde or ketone) would do and its reac-
tivity with respect to time should be checked in the
presence of a protic solvent, especially an aqueous sys-
tem. To verify these factors sodium borohydride was dis-
solved in water and was kept for 24 hours at room
temperature followed by addition of benzaldehyde. Benz-
aldehyde was completely reduced to benzyl alcohol with-
in 20 minutes. To generalize this method we thoroughly
investigated the appropriate reaction conditions, such as
and related oxidants, electrochemical and photochemical
oxidations, and other miscellaneous oxidation methods.2
In addition to these methods, the use of heterogeneous or
immobilized metal catalyst under aerobic condition has
been extensively reported due to the possibility of
recycling the catalyst and the environment friendliness of
3
the system. Several research works related to the aerobic
and catalytic oxidation of alcohols by heterogeneous or
immobilized Pd-catalyst system have been widely devel-
3
a–d,3h–k,4
oped.
Since molecular oxygen is readily available
5
and soluble in common organic solvents, it is ideal to use
as an environmentally benign reoxidant for Pd-catalyst.
However, heterogeneous or immobilized Pd-catalyzed
aerobic oxidations usually require high reaction tempera-
4
tures (> 80 °C). Recently, Sigman and co-workers report-
ed the first example of a Pd-catalyzed aerobic oxidation of
6
alcohols at room temperature. They used homogeneous
Pd(II) catalyst [3 mol% of Pd(OAc) ] with triethylamine
2
the solvent system (H O, aq EtOH, THF, aq THF, DMSO,
as an additive in 15% tetrahydrofuran–toluene solution.
Finding appropriate reaction methods such as lowering
reaction temperature and using readily available hetero-
geneous or immobilized Pd catalyst for aerobic alcohol
oxidation seemed to be very challenging. Here we report
a remarkable method for benzylic and allylic alcohol
2
aq MeCN, etc.), the additive (AcOH, Et N, K CO , etc.),
3
2
3
and the reaction temperature. Optimization of the reaction
conditions for the oxidation of benzyl alcohol and 1-phen-
ylethanol (Scheme 1) as test compounds gave aqueous
ethanol as the best solvent system and potassium carbon-
ate as the most appropriate additive. Furthermore, the use
of Pd/C catalyst with sodium borohydride boosted the
reaction rate as shown in Table 1.
SYNLETT 2007, No. 1, pp 0095–0098
0
4.
0
1.
2
0
0
7
Advanced online publication: 20.12.2006
DOI: 10.1055/s-2006-956457; Art ID: U10706ST
©
Georg Thieme Verlag Stuttgart · New York

9
6
G. An et al.
LETTER
Table 1 The Optimization of Benzyl Alcohol and 1-Phenylethanol Oxidationa
b
Yield (%)c
Entry
Pd/C (equiv)
NaBH (equiv)
K CO (equiv)
Time
24 h
R
4
2
3
1
2
3
4
5
6
7
0.1
–
–
H
71
73
92
87
95
91
87
95
0.1
–
3.0
–
20 h
H
0.1
1.0
0.1
0.1
1.0
1.0
0.1
30 min
1 h
H
0.01
3.0
3.0
–
H
0.025
0.1
20 min
20 min
30 min
20 min
H
Me
Me
Me
0.01
–
8
0.025
3.0
a
Aqueous EtOH (H O–EtOH = 2:1) was used.
Pd/C (10 wt%) was used.
Yields refer to isolated products.
2
b
c
R
O2
R
benzylic or
allylic alcohol
aldehydes
or ketones
+
Pd/C + NaBH4 +
K2CO3
aq alcohol
r.t.
OH
Pd/C, NaBH4
O
K2CO3, aq EtOH
r.t., O2
Scheme 2
R = H, Me
Table 2 The Oxidation of Various Benzylic and Allylic Alcohols
Scheme 1
Entry Starting alcohol
Alcohol
co-solvent)a
Time
Yield
(%)
Entries 5 and 8 in Table 1 reveal that the use of Pd/C
0.025 equiv), sodium borohydride (0.1 equiv), and potas-
b
(
(
sium carbonate (3.0 equiv) at room temperature under an
oxygen atmosphere afforded the best yield for the oxida-
tion. Sodium borohydride (entries 3–8) plays a very sig-
nificant role in this reaction. Furthermore, the results
imply that the reaction of sodium borohydride with the
over-oxidized palladium surface is faster than that of the
reaction product, benzaldehyde or acetophenone. This
clearly illustrates the remarkable ability of sodium boro-
hydride to facilitate the oxidation of benzylic alcohols
with heterogeneous Pd/C catalyst under molecular oxy-
gen. The recyclability of Pd/C catalyst has been also test-
ed with benzyl alcohol. Pd/C was directly filtered from the
reaction mixture, washed with sufficient water and etha-
nol, and was reused for the next cycle. In the first to the
fifth cycles, the reaction product, benzaldehyde was iso-
lated in excellent yields (95%, 93%, 93%, 92%, 92%
yields, respectively). Oxidation reaction in the sixth to the
ninth cycles was monitored by thin layer chromatography,
and the reaction always completed within 20 minutes.
Benzaldehyde was isolated in 93% yield at the tenth trial.
This means that the Pd/C catalyst can be used continuous-
ly for this oxidation reaction.
MeOH
EtOH
i-PrOH
20 min 95
20 min 95
20 min 92
OH
1
MeOH
EtOH
i-PrOH
20 min 92
20 min 94
20 min 95
OH
2
Me
MeOH
EtOH
i-PrOH
30 min 90
30 min 94
20 min 95
OH
3
Me2HC
MeOH
EtOH
i-PrOH
20 min 90
20 min 92
20 min 92
OH
4
MeO
MeOH
EtOH
i-PrOH
2 h
1.5 h
91
93
OH
5
Me2N
30 min 93
MeOH
EtOH
i-PrOH
30 min 91
30 min 91
30 min 90
OH
6
7
F
MeOH
EtOH
i-PrOH
12 h
12 h
12 h
73
30
53
To validate this protocol we applied it to various benzylic
and allyic alcohols in aqueous methanol, ethanol, and iso-
OH
NC
9
propanol solvents (Scheme 2).
Synlett 2007, No. 1, 95–98 © Thieme Stuttgart · New York

LETTER
Oxidation of Benzylic and Allylic Alcohols to Carbonyl Compounds
97
Table 2 The Oxidation of Various Benzylic and Allylic Alcohols
continued)
Table 2 The Oxidation of Various Benzylic and Allylic Alcohols
(continued)
(
Entry Starting alcohol
Alcohol
co-solvent)a
Time
Yield
(%)
Entry Starting alcohol
Alcohol
Time
Yield
(%)
b
(co-solvent)a
b
(
8
MeOH
EtOH
i-PrOH
12 h
12 h
12 h
21
trace
trace
MeOH
EtOH
i-PrOH
3 h
3 h
3 h
87
91
89
OH
OH
OH
20
O2N
MeOH
EtOH
i-PrOH
3 h
3 h
3 h
90
91
93
MeOH
EtOH
i-PrOH
2 h
2 h
2 h
91
88
86
OH
2
1
9
OH
OH
MeOH
EtOH
i-PrOH
1 d
1 d
1 d
87
75
69
MeOH
EtOH
i-PrOH
3 h
3 h
3 h
35
26
NR
0c
22
OH
1
1
CF3
OH
a
Aqueous EtOH (H O–EtOH = 2:1) was used.
2
MeOH
EtOH
i-PrOH
20 min 94
20 min 95
20 min 92
b
c
Yields refer to isolated products.
1
Prolonging the reaction time (> 12 h) showed no improvement in the
yield (TLC monitoring).
OH
MeOH
EtOH
i-PrOH
20 min 92
20 min 93
20 min 95
The progress of the oxidation reaction was monitored via
silica gel thin-layer chromatography. As shown in
Table 2, every aqueous alcoholic co-solvent afforded
good to excellent results. An electron-withdrawing sub-
stituent (entries 7, 8, 10, and 15) on the phenyl group af-
forded poorer reaction yield than the others. Presumably,
benzylic alcohols involving phenyl groups with electron-
withdrawing substituent are less adsorbed on the Pd sur-
face due to the electronic effect. Compared to benzylic al-
cohols, the allylic alcohols needed longer reaction time
1
1
1
2
3
4
OH
MeOH
EtOH
i-PrOH
20 min 93
20 min 93
20 min 95
MeO
OH
MeOH
EtOH
i-PrOH
2 h
2 h
2 h
91
70
70
1
and gave slightly lower yields. H NMR data of all the
products are comparable with the commercially available
compounds.
HO
OH
In conclusion, we have achieved a remarkable method for
the oxidation of various benzylic and allylic alcohols to
the corresponding aldehydes and ketones using Pd/C cat-
alyst in aqueous alcohol with molecular oxygen, sodium
borohydride, and potassium carbonate. The use of a re-
ducing reagent, sodium borohydride, for the reactivation
of the active sites on the Pd surface proved to be remark-
able. We have also investigated the oxidation of primary
alcohol to carboxylic acid using open-air conditions. The
oxidation reaction undergoes smoothly and presumably
this will also be true for the oxidation of alcohols to alde-
hydes. These result will be reported in the due course. The
utilization of room temperature reaction condition and
aqueous alcohol solvent as well as the recyclability of Pd/
C makes this manipulation very interesting from an eco-
nomic and environmental perspective.
MeOH
EtOH
i-PrOH
12 h
12 h
12 h
44
21
20
1
5
O2N
OH
MeOH
EtOH
i-PrOH
30 min 93
30 min 94
30 min 95
1
1
1
1
6
7
8
9
OH
MeOH
EtOH
i-PrOH
20 min 90
20 min 93
20 min 91
OH
MeOH
EtOH
i-PrOH
20 min 90
20 min 93
20 min 93
Acknowledgment
OH
MeOH
EtOH
i-PrOH
1 h
1 h
1 h
91
90
90
This work was initiated by partial support from Hanyang Universi-
ty, Korea, made in the program year of 2004 and partially supported
by Korea Science and Engineering Foundation (KOSEF) and Mini-
stry of Science & Technology (MOST), Korea, through its Nation
Nuclear Technology Program. ML acknowledges the financial
support from the Korean Ministry of Education through the BK21
project for Hanyang University graduate program.
Synlett 2007, No. 1, 95–98 © Thieme Stuttgart · New York

9
8
G. An et al.
LETTER
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9) General Procedure for the Oxidation of Benzylic or
Allylic Alcohols: A catalytic amount of Pd/C (0.025 equiv)
was added to H O (2 volume). NaBH (0.1 equiv) was
(
(
2
2
4
slowly added to this suspension followed by K CO (3.0
2
3
(
equiv). After addition of the starting materials, benzylic or
allylic alcohol (1.0 equiv) was added to the resulting
suspension followed by addition of MeOH, EtOH, or i-PrOH
4
(1 volume) at r.t. The resulting reaction mixture was stirred
vigorously under an oxygen atmosphere (maintained with a
balloon). Alternatively, oxygen gas was bubbled into the
reaction mixture through a long needle with the use of
several balloons. The progress of the oxidation reaction was
monitored by silica gel TLC. The resulting reaction mixture
was neutralized with a dilute HCl solution and the aqueous
layer was extracted with sufficient EtOAc. The organic layer
(
4) (a) Uozumi, Y.; Nakao, R. Angew. Chem. Int. Ed. 2003, 42,
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S. Bull. Chem. Soc. Jpn. 2001, 74, 165. (d) Nishimura, T.;
Kakiuchi, N.; Inoue, M.; Uemura, S. Chem. Commun. 2000,
1
was separated, dried over anhyd MgSO , and concentrated
4
1
245.
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50.
6) Schultz, M. J.; Park, C. C.; Sigman, M. S. Chem. Commun.
002, 3034.
via rotary evaporation. The residue was purified by silica gel
flash column chromatography (EtOAc–n-hexane = 1:3–1:7).
Reactions were typically run on a 2–3-mmol scale.
(
(
2
2
Synlett 2007, No. 1, 95–98 © Thieme Stuttgart · New York

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