Stannous chloride dihydrate: A novel and efficient catalyst for the synthesis of gem-dihydroperoxides from ketones and aldehydes

Article abstract of DOI:10.1055/s-0029-1217394

Ketones and aldehydes undergo facile hydroperoxidation on treatment with aqueous hydrogen peroxide (30%) in the presence of 10 mol% stannous chloride dihydrate in acetonitrile under very mild conditions to afford the corresponding gem-dihydroperoxides in satisfactory yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217394

PAPER
2553
Stannous Chloride Dihydrate: A Novel and Efficient Catalyst for the
Synthesis of gem-Dihydroperoxides from Ketones and Aldehydes
S
ynthesis of gem-D
a
ihydropero
v
xides ood Azarifar,* Kaveh Khosravi, Fatemeh Soleimanei
Faculty of Chemistry, Bu-Ali Sina University, 65178 Hamadan, Iran
Fax +98(811)8257407; E-mail: azarifar@basu.ac.ir
Received 15 March 2009; revised 6 April 2009
DHPs are in demand. Recently, a new approach to synthe-
size gem-DHPs directly from ketones and aromatic alde-
hydes, using 30% aqueous H2O2 and iodine as catalyst has
been reported.16 Also, synthesis of gem-DHPs from ke-
tones and aldehydes by aqueous H2O2 (50%) in the pres-
ence of a catalytic amount of ceric ammonium nitrate
(CAN) is reported.17 However, for primary gem-DHPs
this method is restricted to electron-rich aromatic alde-
hydes. Other recently reported methods for the synthesis
of gem-DHPs include the use of H2O2 solution in THF un-
der acid catalysts18 and rhenium(VII) oxide in acetoni-
trile.19
Abstract: Ketones and aldehydes undergo facile hydroperoxida-
tion on treatment with aqueous hydrogen peroxide (30%) in the
presence of 10 mol% stannous chloride dihydrate in acetonitrile un-
der very mild conditions to afford the corresponding gem-dihydro-
peroxides in satisfactory yields.
Key words: ketones, aldehydes, gem-dihydroperoxides, aqueous
hydrogen peroxide, stannous chloride
gem-Dihydroperoxides (DHPs) are important chemical
building blocks that have numerous chemical and biolog-
ical applications. For example, in recent years, many re-
ports describe gem-dihydroperoxides as key intermediates
in the synthesis of peroxidic antimalarial drugs.1 gem-Di-
hydroperoxides are also useful precursors in the synthesis
of various organic peroxides such as trioxanes,2 tetraox-
anes,3 endoperoxides,4 and acyclic analogues with a vari-
ety of functional groups.5 Peroxides are also an important
group of organic compounds, which have gained much in-
terest in organic synthesis as radical initiators and oxi-
dants.6 Very recently, gem-DHPs have been utilized in
oxidation reactions and also in epoxidation of a,b-unsat-
urated ketones.7
Until recently, no synthesis of gem-DHPs from aliphatic
aldehydes was reported.20 The conversion of octanal into
hydroxyl-hydroperoxide was achieved using the reaction
condition under which benzaldehyde was transformed
into the corresponding gem-DHPs.16,21
In the present article, we describe the catalytic application
of SnCl2·2H2O in the reactions of various ketones and al-
dehydes with aqueous H2O2 (30%) in acetonitrile previ-
ously known as the most convenient solvent for these
reactions.16 We have observed that all the cyclic and acy-
clic aliphatic ketones 1a–f examined in this context were
effectively transformed into their corresponding gem-di-
hydroperoxides 2a–f in 90–95% yields at room tempera-
ture (Table 1, Scheme 1). This method was similarly
applied to aromatic ketones 1g–i and aromatic aldehydes
1j–n to produce the corresponding gem-DHPs 2g–h (45–
62%) and 2j–n (50–75%), respectively (Table 1,
Scheme 1). However, with benzophenone (1i) no conver-
sion was noticed and it was isolated intact after 12 hours.
This can be explained possibly by the strong resonance
stabilization caused by two phenyl groups.
Synthetic approaches to gem-DHPs have long been inves-
tigated.8 The general routes to gem-dihydroperoxides in-
volve (i) ozonolysis of ketone enol ethers or a-olefins in
the presence of aqueous H2O2;4,9 (ii) treatment of ketals
and ketones with H2O2 under acid catalysts such as tung-
stic acid,10 BF3·Et2O,11 and HCl,3e,12 while the synthesis of
4-tert-butylcyclohexyl-1,1-dihydroperoxide is reported
under neutral condition catalyzed by methyltrioxorheni-
um (MeReO3) in trifluoroethanol;1a and (iii) peroxidation
of ketones using an acidic solvent such as AcOH,13 or hy-
droperoxide rearrangement of bicyclic alcohols.14 Howev-
er, many of these methods are subject to certain
drawbacks including the need for the prior synthesis of
suitable starting substrates, use of concentrated H2O2 and
excess acid, low yields, restricted substrate range, and
production of mixtures of peroxidic products.15 In addi-
tion, poor selectivity of ozonolysis and the presence of
ozone-sensitive groups in the substrates pose further lim-
itations in ozonolysis reactions. To avoid these limita-
tions, new more robust protocols for the synthesis of
aq H2O2 (30%)
O
HOO
R1
OOH
R2
SnCl2⋅2H2O (cat.)
R1
R2
MeCN, r.t.
2
1
Scheme 1
Remarkably, when this method was extended to aliphatic
aldehydes 3o and 3p under the same reaction conditions,
no conversion to gem-DHPs was observed. Under the re-
action conditions which transformed benzaldehyde into
DHP, both alkyl aldehydes such as octanal (3o) and hy-
drocinnamaldehyde (3p) were not converted into their
corresponding gem-DHPs, but instead into hydroxyhy-
SYNTHESIS 2009, No. 15, pp 2553–2556
x
x.
x
x
.
2
0
0
9
Advanced online publication: 08.06.2009
DOI: 10.1055/s-0029-1217394; Art ID: Z04309SS
© Georg Thieme Verlag Stuttgart · New York

2554
D. Azarifar et al.
PAPER
droperoxides 4o and 4p (Table 1, Scheme 2). This implies aromatic ketones and aromatic aldehydes on treatment
that, the addition of only one molecule of hydrogen perox- with aqueous H2O2 (30%) in acetonitrile at room temper-
ide to the carbonyl group has occurred.
ature. The high yields of the products, mild reaction con-
ditions, and the use of less costly reagents and catalyst are
outstanding advantages of the present method.
In summary, we have introduced stannous chloride dihy-
drate as a new efficient catalyst for the synthesis of gem-
dihydroperoxides from the corresponding aliphatic and
Table 1 Synthesis of gem-Dihydroperoxidesa
Entry
Ketone 1/Aldehyde 3
Product 2 or 4b
Time (h)
5
Yield (%)c
95
a
O
HOO OOH
b
c
4
4
5
93
92
90
HOO OOH
HOO OOH
HOO OOH
O
O
d
O
e
f
4
4
94
90
O
OOH
OOH
HOO
HOO
O
g
11
9
45
62
OOH
O
HOO
h
OOH
O
HOO
MeO
MeO
O
i
–
12
12
–
j
50
CHO
OOH
OOH
HOO
HOO
k
12
10
52
75
CHO
l
CHO
HOO
OOH
Cl
Cl
Synthesis 2009, No. 15, 2553–2556 © Thieme Stuttgart · New York

PAPER
Synthesis of gem-Dihydroperoxides
2555
Table 1 Synthesis of gem-Dihydroperoxidesa (continued)
Entry
Ketone 1/Aldehyde 3
Product 2 or 4b
Time (h)
10
Yield (%)c
60
m
CHO
HOO
OOH
MeO
OMe
n
11
70
HOO
CHO
OOH
NC
CN
o
5
6
90
88
HO OOH
H
O
H
p
O
HO OOH
H
H
a Reaction conditions: SnCl2·2H2O (cat.), 30% aq H2O2.
b The structures of the products were established from their physical properties and spectral (1H, 13C NMR and IR) analyses by comparison with
the literature.16,17,22
c Isolated yield.
13C NMR (50 MHz, CDCl3/TMS): d = 110.02, 126.86, 129.00,
129.48, 139.65.
aq H2O2 (30%)
SnCl2⋅2H2O (cat.)
O
HO
R
OOH
H
MeCN, r.t.
R
H
4
(4-Cyanophenyl)methylene-1,1-dihydroperoxide (2n)
White solid (70%); mp 107–110 °C.
3
Scheme 2
IR (KBr): 3414, 2916, 2235, 1611, 1405, 1333, 1243, 1199, 1122,
1083, 977, 824 cm–1.
1H NMR (200 MHz, CDCl3/TMS): d = 7.24 (s, 1 H), 7.78–8.04 (m,
4 H), 10.08 (s, 2 H).
Chemicals were obtained from Merck chemical company. FT-IR
spectra were recorded on a Schimadzu 435-U-04 spectrophotometer
(KBr pellets). NMR spectra were recorded on a 200 (50) MHz Vari-
an spectrometers, and are reported in d with TMS as the internal
standard.
13C NMR (50 MHz, CDCl3/TMS): d = 112.12, 117.0, 126.00,
128.00, 129.44, 139.33.
Acknowledgment
Hydroperoxidation of Ketones and Aldehydes; General Proce-
dure
The authors wish to thank the Bu-Ali Sina University Research
Council for financial support.
A mixture of carbonyl substrate 1 or 3 (1 mmol), 30% aq H2O2 (3
mL), and SnCl2·2H2O (24.4 mg, 0.1 mmol) in MeCN (4 mL) was
stirred at r.t. for 4–12 h (Table 1). After the completion of the reac-
tion, the mixture was diluted with H2O (5 mL) and extracted with
EtOAc (3 × 5 mL). The combined organic layers were washed with
sat. aq NaHCO3 (3 mL), dried (Na2SO4), and concentrated in vacuo.
The residue was purified by column chromatography (silica gel,
hexane–EtOAc) to afford the pure gem-dihydroperoxide 2 or hy-
droxyhydroperoxide 4 (Table 1). The structures of the products
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Synthesis 2009, No. 15, 2553–2556 © Thieme Stuttgart · New York