Catalyst-free selective oxidation of alcohols to carbonyls using trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane as an efficient oxidant

Article abstract of DOI:10.1007/s13738-013-0235-3

A simple and efficient method for the selective oxidation of alcohols to ketones using trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane at room temperature is developed. The reactions were smoothly proceeded under catalyst-free conditions to provide ketones in quantitative yields within short reaction times. Also, this method is compatible with many functional groups including aldehydes, olefins, halogens, amines and esters. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s13738-013-0235-3

J IRAN CHEM SOC
DOI 10.1007/s13738-013-0235-3
ORIGINAL PAPER
Catalyst-free selective oxidation of alcohols to carbonyls
using trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane
as an efficient oxidant
Davood Azarifar
Kaveh Khosravi
•
Zohreh Najminejad
•
Received: 24 October 2012 / Accepted: 24 January 2013
Ó Iranian Chemical Society 2013
Abstract A simple and efficient method for the selective
oxidation of alcohols to ketones using trans-3,5-dihydrop-
eroxy-3,5-dimethyl-1,2-dioxolane at room temperature is
developed. The reactions were smoothly proceeded under
catalyst-free conditions to provide ketones in quantitative
yields within short reaction times. Also, this method is
compatible with many functional groups including alde-
hydes, olefins, halogens, amines and esters.
oxidizing agents have been reported throughout the litera-
ture for the oxidation of alcohols, but the use of oxygen
donors such as H O , m-CPBA, ozone, O and t-BuOOH
2
2
2
has become increasingly more important in the green
context [10–16]. Among these, aqueous H O is a high
2
2
atom-efficiency (47 %) and most attractive in the green
context as it is environmentally benign (only generates
water as the by-product) and safe in operation [17].
Moreover, it has high solubility in water and many organic
solvents that make it attractive in liquid-phase reactions
[18, 19]. However, H O exhibits lower oxidation power
Keywords Trans-3, 5-dihydroperoxy-3, 5-dimethyl-1,
-dioxolane Á Alcohols Á Oxidation Á Catalyst-free
2
2
2
for many purposes including the oxidation of alcohols, and
the use of various organic or transition metal-based Lewis
acid catalysts for activation of hydrogen peroxide is
essential [20–24]. Also, lanthanides [25, 26] such as cerium
salts have long been used as catalysts to activate the oxi-
dation of alcohols [27–29]. Many of these reagents and
catalysts suffer from certain drawbacks such as toxicity of
the transition metals present in these catalysts, long reac-
tion times, low selectivity and yield [14]. As a conse-
quence, the development of more effective and benign
methods to overcome these limitations is still an important
experimental challenge. In recent years, the obtained gem-
dihydroperoxides from H O [30] have received consider-
Introduction
Oxidation of alcohols is a well-documented and straight-
forward method for the synthesis of carbonyl compounds
that are important building blocks in a wide variety of
organic synthesis [1, 2]. Although several methods for the
oxidation of alcohols have been developed [3–6], only few
are sufficiently selective in tolerating the presence of other
sensitive functional groups [7, 8]. Historically, the most
common reagents used for the oxidation of secondary
alcohols include the Cr(VI) and Mn(VII) species which
environmentally result in considerable amounts of heavy
metal wastes [9]. During the last decades, wide varieties of
2
2
able attention owing to their relevance to peroxidic anti-
malarial agents [31, 32], which are structurally similar to
hydroperoxides. In contrast to H O , gem-dihydroperox-
2
2
ides act more efficiently as high-oxygen content oxidants in
various transformations including the oxidation of alcohols
D. Azarifar (&) Á Z. Najminejad
[
33, 34]. In 1962, Rieche and co-worker [35] reported the
Department of Chemistry, Bu-Ali Sina University,
Hamedan 5178, Iran
e-mail: dazarifar@gmail.com; azarifar@basu.ac.ir
preparation and use of trans-3,5-dihydroperoxy-3,5-dime-
thyl-1,2-dioxolane in oxidation reactions. Most recently,
we have reported the successful use of trans-3,5-dihydr-
operoxy-3,5-dimethyl-1,2-dioxolane (DHPDMDO) as a
novel oxidant [36], in selective sulfoxidation of sulfides,
K. Khosravi
Department of Chemistry, Faculty of Science,
Arak University, Arak 38156-8-8349, Iran
123

J IRAN CHEM SOC
the selective halogenation of aromatic compounds and
epoxidation of a,b-unsaturated ketones [36–38].
Experimental
Scheme 1 Oxidation of secondary alcohols to ketones by trans-3,5-
dihydroperoxy-3,5-dimethyl-1,2-dioxolane
Solvents, reagents, and chemical materials were obtained
from Aldrich and Merck chemical companies and purified
prior to use. Nuclear magnetic resonance spectra were
recorded on JEOL FX 90Q using tetramethylsilane (TMS)
as an internal standard. Infrared spectra were recorded on a
Perkin Elmer GX FT IR spectrometer (KBr pellets).
Caution: Although we did not encounter any problem
with trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane,
it is potentially explosive and should be handled with
precautions; all reactions should be carried out behind a
safety shield inside a fume hood and transition metal salts
or heating should be avoided.
Scheme 2 Silica sulfuric acid-catalyzed synthesis of trans-3,5-di-
hydroperoxy-3,5-dimethyl-1,2-dioxolane using aqueous H O (30 %)
2 2
Results and discussion
As a result of our continued interest in the synthesis of
gem-dihydroperoxides [39, 40] and their applications in
various transformations [37, 38], herein, we are encouraged
to examine the oxidative capacity of trans-3,5-dihydrop-
eroxy-3,5-dimethyl-1,2-dioxolane (DHPDMDO) in oxida-
tion of variously substituted secondary alcohols 1 to
respective ketones 2 at room temperature in high yields as
shown in Scheme 1.
Preparation of DHPDMDO [35]
To a stirred solution of acetylacetone (100 mg, 1 mmol) in
CH CN (4 mL) was added silica sulfuric acid (SSA)
3
(
100 mg) and stirring of the reaction mixture was continued
for 5 min at room temperature. Then, aqueous 30 % H O
2
2
(
5 mmol) was added to the reaction mixture and was
DHPDMDO has been prepared from silica sulfuric acid
allowed to stir for 30 min at room temperature. After com-
pletion of the reaction as monitored by TLC, the resulting
mixture was filtered and washed with EtOAc (2 9 5 mL) to
separate the solid catalyst. The combined filtrates were
diluted with water (5 mL) and extracted with EtOAc
(
SSA)-catalyzed reaction of acetylacetone with aqueous H O
2 2
(30 %) following our reported procedure (Scheme 2) [36].
To the best of our knowledge, the present study repre-
sents the first example, wherein trans-3,5-dihydroperoxy-
(
3 9 5 mL). The organic layer was separated, dried over
anhydrous Mg SO and evaporated under reduced pressure
2
Table 1 Screening the reaction parameters in model oxidation of
a
cyclohexanol with the oxidant DHPDMDO at room temperature
4
to give almost pure white crystalline product 1 (Scheme 2).
Entry Solvent DHPDMDO Time Catalyst
(mmol)
Yield
b
(%)
General experimental procedure for oxidation
of alcohols
(min)
1
2
3
4
5
6
7
8
9
1
1
1
1
a
EtOH
CH CN
1
1
1
1
1
1
200
35
None
None
None
None
None
None
None
None
None
Trace
94
3
To a solution of alcohol 1 (1 mmol) in MeCN (5 mL) was
AcOH
THF
100
80
30
added
trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxo-
30
lane (166 mg, 1 mmol). The mixture was stirred at room
temperature for an appropriate time (Table 2). After com-
pletion of the reaction as monitored by TLC, the remaining
peroxide was neutralized with saturated aqueous Na SO
PhMe
200
80
Trace
50
CH
CH
CH
CH
CH
CH
CH
CH
2
3
3
3
3
3
3
3
Cl
2
CN 0.5
CN 0.35
CN 0.25
CN 0.5
CN 0.35
CN 0.5
CN 0.5
200
250
350
60
45
2
3
30
solution (3 mL). The resulting mixture was diluted
15
with water (15 mL) and then extracted with CH Cl2
2
0
1
2
3
TiO
TiO
2
2
50
(
3 9 5 mL). The combined organic layer was washed with
80
35
water and dried over anhydrous MgSO . Then, the solvent
4
55
CuCl
30
was removed under reduced pressure to leave almost the
pure product. The known products were characterized on
80
Silica sulfuric acid 60
1
the basis of their physical and spectroscopic (IR, H NMR,
Conditions: cyclohexanol (1 mmol), solvent (5 mL), catalyst
1
3
and C NMR) data that were consistent with the previ-
ously reported data [3b].
(0.001 mmol)
b
Isolated yield
1
23

J IRAN CHEM SOC
Table 2 Catalyst-free
oxidation of the secondary
alcohols with DHPDMDO in
b
Entry
Substrate
Product 2
Time (min)
30
Yield (%)
90
a
OH
O
C
3
CH CN at room temperature
C
H
1
2
OH
OH
OH
O
O
O
3
3
3
5
5
5
94
88
3
4
86
92
OH
O
5
6
30
25
OH
C
O
C
O
C
O
C
96
H
OH
O
C
H
CH
3
C
CH3
7
8
30
30
97
96
OH
O
C CH
H
C CH3
3
Cl
Cl
O
S
S
OH
OH
9
30
28
28
96
92
94
1
1
0
1
OH
OH
O
O
OH OH
O
O
C
1
2
C
C
H
C
30
85
H
OH
O
CH3
CH3
1
1
3
4
30
20
92
90
OH
O
123

J IRAN CHEM SOC
a
Table 2 continued
b
Entry
Substrate
Product 2
Time (min)
35
Yield (%)
1
5
H
N
N
H
H
N
N
H
80
OH
O
Br
Br
1
1
6
7
28
25
85
86
O
OH
OH
OH
O
O
CH3
CH
3
1
1
8
9
40
40
90
80
OH
O
OH
OH
OH
O
OMe
OMe
2
0
20
86
O
O
OH
O
a
Conditions: alcohol 1
1 mmol), DHPDMDO
2
1
C
CH OH
C
CH OH
25
92
2
2
(
(
H
3
1 mmol), CH CN (5 mL),
a
room temperature
b
Isolated yield
Conditions: alcohol 1 (1 mmol), DHPDMDO (1 mmol), CH
3
CN (5 mL), room temperature.
b
Isolated yield.
3
,5-dimethyl-1,2-dioxolane (DHPDMDO) is effectively
condition using stoichiometric amount of DHPDMDO as the
used for selective conversion of secondary alcohols to
ketones. Initially, we used cyclohexanol as the test com-
pound for the oxidation using DHPDMDO at room tem-
perature. The effects of various reaction parameters on the
model reaction were investigated (Table 1). To study the
oxidant in CH CN at room temperature without any catalyst.
3
To establish the generality of the reagent and also to
extend the scope of the reaction, a series of secondary
alcohols carrying different functional groups were sub-
jected to oxidation under the optimized conditions. The
results summarized in Table 2 indicate that all the reactions
proceed with high yields and also with high compatibility
with the functional groups present in the reactions within
short reaction times. The results of Table 2 (entries 15–17)
demonstrate that the reaction is chemo selective and the
other functional groups like double bond, amino group, and
ester group are not oxidized under these reaction condi-
tions. Interestingly, it was noticed that the substrates con-
taining two or more hydroxyl groups undergo mono-
oxidation so that the cyclic and benzylic hydroxyl groups
react preferentially (entries 19, 21).
effect of solvent, different solvents such as EtOH, H O,
2
CH CN, AcOH, THF, PhMe and CH Cl were examined
3
2
2
using the oxidant DHPDMDO (1 mmol) in the absence of
any catalyst. CH CN proved to be a superior solvent among
3
all the solvents screened in this transformation (entry 2). It
was noted that the oxidant trans-3,5-dihydroperoxy-3,5-
dimethyl-1,2-dioxolane, apparently with high atom-effi-
ciency for containing three peroxide units, reacted most
efficiently only when used in one equimolar amount in the
reaction, reducing its amount resulted in higher reaction
times and lower yields (entries 7–9). In order to improve the
efficiency of the oxidant, various catalysts such as TiO2,
CuCl, and silica sulfuric acid were examined in the reaction
which did not have any significant improving effect on the
yield, although the reaction time was reduced considerably
A plausible mechanism to explain the transformation of
the secondary alcohols into corresponding carbonyl com-
pounds using trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-
dioxolane as the oxidant is depicted in Scheme 3. It is more
likely that a nucleophilic attack by the oxygen atom of
(
entries 10–13). Finally, we achieved an optimized reaction
1
23

J IRAN CHEM SOC
Scheme 3 Possible passway
for oxidation of alcohols with
DHPDMDO
hydroxyl group to the C-3 position of dioxolane ring of the
oxidant takes place (step 1). The driving force for such attack
comes from the strong electron affinity of C-3 carbon atoms
bearing two strong electron withdrawing peroxy groups. In
addition, opening the dioxolane ring as a result of this attack
relieves the ring strain and yields the more stable open chain
intermediate I. As shown in Scheme 3, the intermediate I
undergoes a-hydrogen abstraction by hydroperoxy group
along with C–O and O–O bond cleavages through a
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In summary, trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-
dioxolane (DHPDMDO) has been conveniently used as an
effective and high oxygen-content oxidant in selective
oxidation of variously substituted secondary alcohols. The
simplicity of the procedure, the mildness of the reaction
conditions, high yields and chemo selectivity, and the
absence of any expensive or toxic catalyst in the reaction
demonstrate the advantages of this method.
2
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Acknowledgments The authors wish to thank the Buali Sina Uni-
versity research council for the financial support.
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