A new and efficient transition metal-free oxidation of secondary alcohols to ketones using aqueous HBr and H2O2

Article abstract of DOI:10.1055/s-2004-836047

Aqueous HBr/H₂O₂ was found to be an efficient and green system for the oxidation of secondary alcohols in excellent yields under very mild conditions.

Full text of DOI:10.1055/s-2004-836047

LETTER
173
A New and Efficient Transition Metal-Free Oxidation of Secondary Alcohols
to Ketones Using Aqueous HBr and H2O2
O
xidation of Secon
i
dar
y
A
s
lcohols to
h
K
etones al B. Sharma, Suman L. Jain, Bir Sain*
Chemical and Biotechnology Division, Indian Institute of Petroleum, Dehradun-248005, India
E-mail: birsain@iip.res.in
Received 24 August 2004
R1
R2
H
R1
R2
H2O2, HBr (20 mol%)
CH3CN, reflux
Abstract: Aqueous HBr/H2O2 was found to be an efficient and
green system for the oxidation of secondary alcohols in excellent
yields under very mild conditions.
C
O
OH
1
2
Key words: oxidation, secondary alcohols, ketones
Scheme 1
The oxidation of secondary alcohols to carbonyl com-
pounds is an important synthetic transformation1 and in
the recent past emphasis is being given towards the use of
environmentally benign oxidants such as molecular oxy-
gen with a view to developing green methodology.2 In this
context aerobic oxidation of secondary alcohols to ke-
tones by using metal catalysts such as hydrated RuCl3,3
RuO2·H2O,4 a combination of cobalt and ruthenium,5
tetrapropylammonium perruthenate,6 Ru+3-exchanged hy-
droxyapatite,7 a ruthenium complex along with Co-salen,8
Ru-Al-Mg hydrotalcites,9 Pd (II) hydrotalcite10 and cobalt
complexes with 2-methylpropanal as the sacrificial
aldehyde11 have been reported in the literature. However,
these procedures suffer from one or more drawbacks in-
cluding the use of expensive metal catalysts such as ruthe-
nium and palladium, oxidation of only activated alcohols
such as benzylic and allylic alcohols, the need for a sacri-
ficial aldehyde, and severe reaction conditions, for exam-
ple, high pressure. The development of transition metal-
free ecofriendly synthetic transformations is an area of
current interest as such methods avoid the use of toxic and
expensive metals and their complexes.
H2O2
HBr
HOBr
+
+
R
CH R1
+
H2O
HOBr
R
CH R1
OH
OBr
3
R
C
O
R1
+
HBr
Scheme 2
carbonyl compounds using aqueous HBr and H2O2 as
green oxidant system under very mild reaction conditions
(Scheme 1 and Scheme 2).
Treatment of a variety of secondary alcohols both activat-
ed and non-activated with a catalytic amount of aqueous
HBr (20 mol%) and H2O2 (2 mmol) in acetonitrile yielded
the corresponding ketones in very good yields.19 All the
alcohols studied were smoothly converted to the corre-
sponding ketones in excellent yields, (see Table 1).
Among the various alcohols studied, benzoins were found
to be the most reactive and required shorter reaction times
for their oxidation (Table 1, entries 12 and 13). Further-
more, aromatic substituted alcohols were found to be
more reactive than aliphatic alcohols (Table 1, entries 1
and 2). Oxidation of 2-ethyl-1,3-hexanediol and 1-phe-
nyl-1,2-ethanediol under these conditions yielded corre-
sponding hydroxyl-ketones, 2-ethyl-1-hydroxy-3-hex-
anone and 2-hydroxy-1-phenylethanone, respectively, in
good yields showing the usefulness of this method for the
selective oxidation of secondary alcohols in the presence
of primary alcohols (Table 1, entries 10 and 11). To eval-
uate the effect of solvent, aerobic oxidation of benzhydrol
was carried out under similar reaction conditions but
using different solvents. Among the various solvents such
as xylene, acetonitrile, methanol, toluene and 1,2-di-
chloroethane studied, acetonitrile was found to be the
most suitable for this transformation. The oxidation of
secondary alcohols to the corresponding ketones was
found to be very slow at room temperature and could be
carried out more efficiently in refluxing acetonitrile.
In this context, oxidation of secondary alcohols to ketones
by using dimethyl sulfoxide, dicyclohexylcarbodiimide
and various acids,12 dimethyl sulfoxide activated with
oxalyl chloride,13 sodium hypochlorite in acetic acid,14
NaBrO3–NH4Cl,15 N-chlorosuccinimide with catalytic
amounts of N-tert-butylbenzenesulfenamide16 and molec-
ular bromine with catalytic amounts of N-t-butyl-2-
nitrobenzenesulfenamide17 have been reported in the liter-
ature. A recent report by Neumann et al.18 on the use of a
combination of hydrogen peroxide and hydrohalic acid as
a green halogenating agent for arenes inspired us to ex-
plore the potential of this transition metal-free system for
oxidation of secondary alcohols. In this letter, we wish to
report for the first time a new transition metal-free, effi-
cient method for the oxidation of secondary alcohols to
SYNLETT 2005, No. 1, pp 0173–0175
0
5.
0
1.
2
0
0
5
Advanced online publication: 29.11.2004
DOI: 10.1055/s-2004-836047; Art ID: D24704ST
© Georg Thieme Verlag Stuttgart · New York

174
V. B. Sharma et al.
LETTER
Table 1 Oxidation of Secondary Alcohols to Ketones Using H2O2/
Table 1 Oxidation of Secondary Alcohols to Ketones Using H2O2/
HBr Systema
HBr Systema (continued)
Entry Substrate
Reaction Yield
time (h) (%)
Entry Substrate
Reaction Yield
time (h) (%)
H
C
1
0.75
1.00
9220
13
0.17
OCH3
9724
H3CO
CH
OH
C
O
OH
CH3
H3C(H2C)12
C
C(CH2)12CH3
14
3.00
3.50
8525
7525
2
9020
CHOH
OHO
H3C(H2C)14
C
C(CH2)14CH3
15
OHO
OH
a Reaction conditions: secondary alcohol (1 mmol), 30% H2O2
(2 mmol), 48% HBr (20 mol%) in MeCN (5 mL) at reflux temperature
under atmospheric pressure.
3
3.00
7820
Although the mechanism of this reaction is not clear at
this stage, the reaction probably involves the formation of
hypobromous acid by the reaction of aqueous hydrogen
peroxide with hydrobromic acid,18 which then reacts with
the secondary alcohol 1 to afford hypobromite species 3
followed by the abstraction of hydrogen to yield the
corresponding ketone.
4
5
5.00
5.00
8221
70
OH
H
H3C(H2C)4
CH3
C
C
CH
OH
In summary, we have developed a simple oxidation pro-
cedure for the selective oxidation of both activated and
non-activated secondary alcohols to the corresponding
ketones. The simplicity of the system and the versatility of
the method towards a range of activated and non-activated
alcohols make the HBr/H2O2 system an attractive, metal-
free, synthetic tool for the oxidation of secondary alcohols
to ketones.
6
5.50
6521
OH
OH
7
8
3.50
7.00
7522a,23a
Acknowledgment
CH3
OH
We are thankful to the Director, IIP for his kind permission to
publish these results. Suman L. Jain, Vishal B. Sharma are grateful
to CSIR, New Delhi for the award of Research Fellowships.
6522c,23b
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LETTER
Oxidation of Secondary Alcohols to Ketones
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