LETTER
2041
A Novel and Efficient Oxidation of Benzyl Alcohols to Benzaldehydes with
DMSO Catalyzed by Acids
O
C
xidation of Ben
h
zyl
A
lcohols
u
to Benzalde
n
hydes bao Li,* Yanli Xu, Ming Lu, Zhuxuan Zhao, Lanjun Liu, Zheyuan Zhao, Yi Cui, Pengwu Zheng, Xioujie Ji,
Guangjie Gao
Department of Chemistry, School of Science, School of Electronic and Information Engineering, Tianjin University 300072, China
Fax +86(22)27403475; E-mail: lichunbaosyn@sohu.com
Received 14 October 2002
trobenzaldehyde at elevated temperature with acetonitrile
as solvent (with 45% yield). It has been reported that
DMSO with HBr oxidize the methylene between two car-
Abstract: Oxidation of benzyl alcohols to the corresponding alde-
hydes was achieved by an acid catalyzed DMSO oxidation. When
the oxidation was catalyzed by HBr, no side products were detected.
In most cases, the yields were excellent. The oxidation rate depends
6
bonyl groups into a third carbonyl group. It is believed
on both the nature and the position of the substituents on the aromat- that bromine, generated in situ from the oxidation of HBr
ic rings. A tentative mechanism is proposed for the oxidation.
by DMSO, is the oxidant. But this mechanism is probably
not valid here because the hydroxy group of menthol was
not oxidized by DMSO with HBr and 1-phenyl-1-pen-
tanol was oxidized into a mixture of pentanophenone and
Key words: oxidation, DMSO, HBr, benzyl alcohols, benzalde-
hydes
1
-phenyl-1-pentene by DMSO with HBr. Since it is well-
documented that bromine oxidizes secondary alcohols
faster than it oxidize primary alcohols.1 The oxidation of
benzyl alcohols to benzaldehydes with air in refluxing
DMSO was reported to take place via radical mechanism
Oxidation of alcohols to ketones or aldehydes is one of the
,7
1
most useful transformations in organic chemistry. Acti-
2
3
vated DMSO methods such as the Swern oxidation are
often used for this purpose. The disadvantages of the
Swern oxidation are the required anhydrous conditions
and the low temperatures needed to avoid Pummerer re-
arrangement. Even under these conditions the formation
of side products from Pummerer rearrangement is more
8
by Traynelis et al. We carried out the HBr-catalyzed ox-
idation under a nitrogen atmosphere and found that air has
not affected the acid-catalyzed oxidation at all. Based on
these facts, we tentatively put forward the following
mechanism (Scheme 1).
3
than 50% in some cases. In addition, the oxalyl chloride
used in the Swern oxidation is moisture sensitive, irri-
tating and toxic. It is therefore desirable to simplify the
reaction conditions.
H+
DMSO
+
H
-
ArCH O S+
Ar CH2
Ar-CHO
Ar-CH OH
2
-
H O
2
We theorized that benzyl cation formed under acidic con-
ditions would react with DMSO to form a benzyloxydi-
methylsulfonium salt. Elimination of a benzylic proton
Scheme 1
and dimethylsulfide would then result in benzaldehyde.4 The above facts as well as the reaction rates in Table 1
agreed well with the mechanism proposed above. As
shown in Table 1, electron donating groups such as -OH
and -OR on aromatic ring lead to higher reaction rates (en-
tries 2, 6, 7). Electron withdrawing groups such as -NO2
or -X reduce the reaction rates substantially (entries 10–
To the best of our knowledge, this kind of oxidation is not
known although there exist several modifications of the
Swern oxidation.
1
,3
In order to investigate our assumption, benzyl alcohols
were reacted with DMSO catalyzed by acid at 100 °C. The
acids for investigation were H SO , H PO , CeCl , TsOH
1
2). Additional aq HBr was required to accelerate the lat-
2
4
3
4
3
ter reactions. Bulky groups and ortho substituents reduced
the reaction rates (entry 4 vs. entry 5, entries 7 and 8 vs.
entry 9). All the oxidations produced a pure product as de-
termined by TLC and GC. All the products are known
and aq HBr. All the acid catalyzed reactions led to the for-
mation of aldehydes. But only the reaction catalyzed by aq
HBr gave a pure product with excellent yields. Among the
–
acids investigated, Br seems to be the best conjugate base
1
compounds and were fully identified by IR and H NMR.
to effect the deprotonation of the benzyloxydimethylsul-
fonium salt. The pathway for the formation of benzyl bro-
mide followed by the DMSO substitution is uncertain
In conclusion, we have developed a convenient and effi-
cient method for oxidation of benzyl alcohols to the cor-
responding aldehydes. It is not necessary to add a weak
base such as TEA to the reaction, as required in the Swern
oxidation. The products were not contaminated with any
side products, such as Pummerer rearrangement products.
Exclusion of moisture from the reaction was not necessary
and commercial DMSO was adequate. In most cases, the
yields were excellent. Its synthetic applications are cur-
rently under investigation.
5
according to the report by Kornblum et al. They failed to
make benzaldehyde from benzyl bromide and DMSO but
succeeded in converting p-nitrobenzylbromide into p-ni-
Synlett 2002, No. 12, 02 12 2002. Article Identifier:
1
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