Efficient synthesis of gem-dihydroperoxides with molecular oxygen and anthraquinone under visible light irradiation with fluorescent lamp

Article abstract of DOI:10.1039/c1gc15437k

We developed an efficient dihydroperoxidation protocol of various carbonyl compounds with molecular oxygen and anthraquinone in 2-propanol under visible light irradiation with a fluorescent lamp, which produced corresponding gem-dihydroperoxides in high yields.

Full text of DOI:10.1039/c1gc15437k

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COMMUNICATION
Efficient synthesis of gem-dihydroperoxides with molecular oxygen and
anthraquinone under visible light irradiation with fluorescent lamp†
Lei Cui, Norihiro Tada, Hiroaki Okubo, Tsuyoshi Miura and Akichika Itoh*
Received 20th April 2011, Accepted 27th June 2011
DOI: 10.1039/c1gc15437k
We developed an efficient dihydroperoxidation protocol of
various carbonyl compounds with molecular oxygen and
anthraquinone in 2-propanol under visible light irradiation
with a fluorescent lamp, which produced corresponding
gem-dihydroperoxides in high yields.
tant role as key intermediates in the synthesis of various
5–7
8
peroxides, as initiators for radical polymerization and as
9
10
oxidants for epoxidation and sulfoxidation. In general, gem-
dihydroperoxides can be synthesized from carbonyl compounds
or their derivatives with hydrogen peroxide in the presence of
11
catalysts such as acids, heavy metals and iodine. In addition,
we have recently reported a facile catalyst-free synthesis of
gem-dihydroperoxides from carbonyl compounds with aqueous
Light is an important factor in many reactions; therefore, it can
be described as a type of reagent. Because this clean reagent
exudes no residue and has neither shape nor weight, it is an
important component for examining environmentally benign
processes. Although organic synthesis with light has been
12
hydrogen peroxide. Hydrogen peroxide is an excellent oxidant
because of its excellent atom efficiency and because it produces
only water as a by-product in oxidation reactions; however,
its explosiveness and skin causticity require special handling.
To the best of our knowledge, our above-mentioned reaction
is the first example documented for the preparation of gem-
dihydroperoxides from carbonyl compounds by application of
photo-dihydroperoxidation with visible light from a general-
purpose fluorescent lamp. In this study, we detail the synthesis
of gem-dihydroperoxides.
Table 1 shows the study of reaction conditions for aerobic
dihydroperoxidation‡ of 4-tert-butylcyclohexanone (1) under
visible light irradiation from a fluorescent lamp. Among the
typical photosensitizers and solvents examined, we determined
AQN and 2-propanol to be the most effective for this reaction
1
previously studied, this research mainly involved UV light
because of its high energy. In addition, with new developments
in energy-conversion and energy-consumption technologies,
the effective use of visible light has gained importance. From
this perspective, we have developed synthetic organic chemistry
methods with visible light and have successfully reported several
photo-oxidation reactions using molecular oxygen as a terminal
2
oxidant. Molecular oxygen, as well as light, has received much
attention as a primary environmentally benign oxidant because
it is photosynthesized by plants, produces little waste, is inexpen-
2
sive and has greater atom efficiency than other oxidants. In the
course of our further study of gem-dihydroperoxide synthesis,
which has been previously accomplished under irradiation with a
(
entry 8). Although the reason is unclear, AQN was a more
3
5
00
W
xenon lamp, we have discovered that using
effective catalyst than anthracene in this visible light irradiation.
This is in contrast to results obtained with a 500 W xenon
lamp. It is noted that for all light irradiation conditions,
AQN and molecular oxygen were necessary for production of
dihydroperoxydation (entries 20, 21 and 23).
Table 2 shows the scope and limitation of this synthetic pro-
tocol using various carbonyl compounds under the optimized
reaction conditions mentioned above. Cyclic ketones including
anthraquinone (AQN) as a catalyst instead of anthracene
enables us to perform aerobic photo-dihydroperoxidation
of carbonyl compounds to the corresponding gem-
dihydroperoxides under visible light irradiation by a general-
purpose fluorescent lamp (eqn (1)).
(
1)
2
-adamantanone (13) and aliphatic ketones except acetophe-
gem-Dihydroperoxides have gained much interest in re-
cent years as a precursor of peroxidic antimalarial drugs.
In addition, from the view point of organic synthesis,
gem-dihydroperoxides have been known to play an impor-
none (23) produced the corresponding gem-dihydroperoxides
in good to excellent yields (entries 1–9 and 12). Conversely,
dodecanal (19) and p-anisaldehyde (21) were oxidized under
similar conditions to produce hydroperoxy hemiacetal 20 and
dihydroperoxide 22 in low yields because they were also good
substrates for aerobic photo-oxidation to obtain the correspond-
4
Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196,
Japan. E-mail: itoha@gifu-pu.ac.jp; Fax: +81 58-230-8108; Tel: +81
8-230-8108
Electronic supplementary information (ESI) available. See DOI:
0.1039/c1gc15437k
13
ing carboxylic acids (entries 10 and 11).
To clarify the mechanism, first we assayed the peroxides in
the solution by iodometry after reaction and discovered that a
substantial excess of peroxides was formed in comparison with
5
†
1
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Table 1 Study of reaction conditions
Table 2 Synthesis of gem-dihydroperoxides
a
EntrySubstrate
1
Time (h) Product
20
Yield (%)
a
Entry Sensitizer
mol (%) Solvent Time (h) Yield (%)
90
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
rose bengal
methylene blue 10
benzophenone
DCA
anthracene
2-t-Bu-AQN
10
i-PrOH 20
i-PrOH 20
i-PrOH 20
i-PrOH 20
i-PrOH 20
i-PrOH 20
i-PrOH 20
i-PrOH 20
0
0
0
0
77
85
95
100
0
0
0
10
10
10
10
10
10
10
10
10
10
10
10
10
10
20
5
2
3
4
20
20
15
85
58
76
AQN-2-CO
AQN
AQN
AQN
AQN
AQN
AQN
AQN
AQN
AQN
AQN
AQN
AQN
AQN
AQN
AQN
—
2
H
hexane
CH Cl
Et
AcOEt
MeCN
MeOH
EtOH
20
20
20
20
20
20
20
0
1
2
3
4
5
6
7
8
9
0
1
2
3
2
2
2
O
0
0
trace
30
0
76
84
73
0
0
11
0
t-BuOH 20
i-PrOH 20
i-PrOH 20
i-PrOH 15
i-PrOH 20
i-PrOH 20
i-PrOH 20
i-PrOH 20
10
10
10
10
—
b
5
6
10
48
97
72
c
d
a
1
Determined by H NMR using tetrachloroethane as an internal
b
c
standard. This reaction was carried out in the dark. This reaction
was carried out under an Ar atmosphere. This reaction was carried out
d
under an air atmosphere.
14
the substrate. This result suggests that peroxide was formed in
the solution. In addition, the formation of excess amounts of
acetone (2.54 mmol) was detected by H NMR measurement.
7
12
77
1
Furthermore, we studied the time course of this reaction. Fig. 1
shows result of our study of reaction time vs. product & acetone.
There is no inductive period and is linearity between time and
the yield of 2. The yield of 2 is nearly parallel to the amount of
8
9
30
10
71
73
acetone, which is formed in situ. These results indicate that H
2
O
2
is generated, and DHP is formed in the reaction mixture.
b
1
1
0
1
5
36
b
15
25
b
1
2
72
33
Fig. 1 Time course of synthesis of 2.
And also, rose bengal and methylene blue are well known
sensitizer as generators of singlet oxygen. And DCA is generally
thought to form an exciplex with electron donor to produce
a
b
1
Isolated yields. Determined by H NMR using tetrachloroethane as
an internal standard.
2
348 | Green Chem., 2011, 13, 2347–2350
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superoxide anion radical through SET mechanism. Since all
of them did not produce the corresponding DHP by our
examination, this reaction is thought to proceed through other
mechanism (Table 1). Since UV light was not irradiated from
the lamp as mentioned above, benzophenone, which is excited
by UV light, did not show any reactivity for this reaction.
On the other hand, anthracene, which is excited by UV light,
was found to be effective for this reaction since this is due to
generation of anthraquinone in situ, which could be detected by
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4
15
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2
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Conclusions
In conclusion, we have developed a facile and practical method
for preparation of gem-dihydroperoxides from various carbonyl
compounds in the presence of molecular oxygen and a catalytic
amount of AQN under visible light irradiation with a fluorescent
lamp. Further application of this dihydroperoxidation technique
and a detailed mechanistic study are currently in progress in our
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1
‡
2
The following is a typical procedure for dihydroperoxidation: A dry
-propanol solution (5 mL) of 4-tert-butylcyclohexanone (46.3 mg, 0.30
7
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mmol) and AQN (6.2 mg, 0.03 mmol) in a Pyrex tube equipped with an
2
O balloon was stirred and irradiated externally with a fluorescent lamp
for 20 h. The reaction mixture was concentrated under reduced pressure,
and the pure product (55.2 mg, 90%) was obtained by purification with
preparative TLC.
2
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1
1
2 N. Tada, L. Cui, H. Ohkubo, T. Miura and A. Itoh, Chem. Commun.,
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16 Hydrogen peroxide is generated by photosensitized oxidation of
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2
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2 2
been known that H O can be produced commercially through
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Blanco-Brieva and J. L. G. Fierro, Angew. Chem., Int. Ed., 2006, 45,
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2
019.
1
1
4 Na S O (5.58 mmol) was consumed for iodometry of the re-
2 2 3
ˇ
action mixture obtained under the optimal conditions (Table 2,
entry 1).
5 Anthraquinone absorbs light with wavelengths shorter than 450 nm,
and the fluorescent lamp radiates visible light with wavelengths longer
than 400 nm. Thus, anthraquinone absorbs light between 400 and
17 K. Zmitek, M. Zupan and J. Iskra, Org. Biomol. Chem., 2007, 5,
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18 Bubble was not observed when catalase was added to 2-propanol
solution of dihydroperoxide 2.
4
50 nm.
2
350 | Green Chem., 2011, 13, 2347–2350
This journal is © The Royal Society of Chemistry 2011