Mild and efficient strontium chloride hexahydrate-catalyzed conversion of ketones and aldehydes into corresponding gem-dihydroperoxides by aqueous H 2O2

Article abstract of DOI:10.3390/molecules15031433

SrCl₂·6H₂O has been shown to act as an efficient catalyst for the conversion of aldehydes or ketones into the corresponding gem-dihydroperoxides (DHPs) by treatment with aqueous H ₂O₂ (30%) in acetonitrile. The reactions proceed under mild and neutral conditions at room temperature to afford good to excellent yields of product.

Full text of DOI:10.3390/molecules15031433

Molecules 2010, 15, 1433-1441; doi:10.3390/molecules15031433
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Mild and Efficient Strontium Chloride Hexahydrate-Catalyzed
Conversion of Ketones and Aldehydes into Corresponding gem-
Dihydroperoxides by Aqueous H2O2
Davood Azarifar *, Kaveh Khosravi and Fatemeh Soleimanei
Faculty of Chemistry, Bu-Ali Sina University, 65178 Hamadan, Iran;
E-Mails: k_khosravi@basu.ac.ir (K.K.); f.soleimani61@yahoo.com (F.S.)
 Author to whom correspondence should be addressed; E-Mail: azarifar@basu.ac.ir.
Received: 15 January 2010; in revised form: 11 February 2010 / Accepted: 1 March 2010 /
Published: 8 March 2010
Abstract: SrCl2·6H2O has been shown to act as an efficient catalyst for the conversion of
aldehydes or ketones into the corresponding gem-dihydroperoxides (DHPs) by treatment
with aqueous H2O2 (30%) in acetonitrile. The reactions proceed under mild and neutral
conditions at room temperature to afford good to excellent yields of product.
Keywords: gem-dihydroperoxide; strontium chloride hexahydrate; ketone; aldehyde;
hydrogen peroxide
1. Introduction
In recent years, much research has been directed towards gem-dihydroperoxides (DHPs) [1], due to
their importance as useful intermediates in the synthesis of various peroxides, including tetraoxanes
[2–9], and their analogues such as silatetroxanes [10], spirobisperoxyketals [11], and
tetroxycycloalkanes [12], and epoxidation of α,β-unsaturated ketones [13]. These compounds have
also recently been utilized as effective reagents in: (i) oxidation of various compounds [14] such as
sulfides [15], (ii) enantioselective oxidation of 2-substituted 1,4-naphthoquinones [16], and (iii) as
initiators in polymerization reactions [17,18]. It is also remarkable that gem-dihydroperoxides are
relevant to peroxidic antimalarial drugs [2,19–23] possessing the gem-peroxy linkage as a salient
structural feature [23,24–26] in common with many well-known antimalarial cyclic organic peroxides
[1,2,27–35]. Most of the documented protocols for the synthesis of gem-dihydroperoxides in the

Molecules 2010, 15
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literature suffer from significant drawbacks such as the use of strong acidic media, concentrated H2O2
and low yields [1]. These methods mainly utilize a Brönsted or Lewis acid e.g., HCO2H [12,20,36],
NaHSO4-SiO2 [37], H2SO4 [38], F3CCO2H [39], H2WO4 [29,38], and BF3·OEt2 [30,39] to promote the
conversion of ketones, ketals or enol ethers into the corresponding DHPs on treatment with aqueous
H2O2. Other catalysts such as methyltrioxorhenium (prepared from Re2O7) [2], ceric ammonium nitrate
(CAN) [32], and iodine [33] have also been reported to promote such transformations. However, these
methods are not mild enough to offer general applicability and have limitations such as low yields,
long reaction times, use of high concentration of H2O2 and incompatibility with sensitive functional
groups. Recently, Dussault has reported a remarkably mild and highly efficient protocol for Re2O7-
catalyzed conversion of ketones, aldehydes or acetals into 1,1-dihydroperoxides by H2O2 which
represents a major improvement [34].
2. Results and Discussion
As part of our ongoing efforts to develop new methods for the synthesis of DHPs, we report here
another new and highly efficient and inexpensive catalyst SrCl2·6H2O to promote the synthesis of
gem-DHPs from ketones and aldehydes employing aqueous H2O2 (30%) at room temperature. To
achieve suitable reaction conditions, i.e., lower reaction times and higher yields, for the conversion of
the ketones and aldehydes into their corresponding DHPs, various Lewis acid catalysts and solvents
were investigated using 3-pentanone, cyclohexanone, acetophenone, and benzaldehyde as test
compounds at room temperature (Table 1).
Table 1. Effects of catalyst and solvent in the synthesis of gem-DHPs. a
Entry Ketone 1/Aldehyde 3
Catalyst
Solvent Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
3-pentanone
3-pentanone
3-pentanone
3-pentanone
3-pentanone
3-pentanone
3-pentanone
3-pentanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Acetophenone
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
SrCl3·6H2O
SrCl3·6H2O
SrCl3·6H2O
SrCl3·6H2O
SbCl3
CH3CN
CH2Cl2
Et2O
3
6
8
6
8
10
8
10
3
7
8
95
78
56
82
48
45
75
Trace
94
55
50
70
Trace
45
23
15
28
0
AcOEt
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CeO2
CrCl3·6H2O
KF-Al2O3
SrCl3·6H2O
SbCl3
CeO2
CrCl3·6H2O
KF-Al2O3
SrCl3·6H2O
SbCl3
6
10
10
12
12
10
20
10
15
15
12
20
CeO2
CrCl3·6H2O
KF-Al2O3
SrCl3·6H2O
SbCl3
CeO2
CrCl3·6H2O
KF-Al2O3
54
32
15
22
0
a Conditions: Ketone and aldehyde (1 mmol), solvent (4 mL), catalyst (0.1 mmol), 30% aq. H2O2 (3 mL),
reactions are carried out at rt. b Isolated yields.

Molecules 2010, 15
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As can be seen in Table 1, the reaction worked best in terms of yield and reaction time with
aqueous H2O2 (30%) when SrCl2·6H2O (10 mol %) was used as a catalyst. The other catalysts such as
SbCl3, CeO2 and CrCl3·6H2O gave moderate to low yields while KF-Al2O3 was found to be completely
unsuitable for the synthesis of these DHPs. Effects of the solvents such as CH2Cl2, Et2O, MeCN and
AcOEt on the yields of the products were tested and the results are summarized in Table 1.
Acetonitrile appeared as a much better solvent compared with other ones. This suggests that solvent
polarity plays an important role in the synthesis of DHPs.
This success encouraged us to extend these reaction conditions to a variety of cyclic and acyclic
aliphatic ketones 1a-g using aqueous H2O2 (30%) in the presence of 10 mol% amount of SrCl2·6H2O
as a chosen catalyst in acetonitrile at room temperature. The corresponding gem-dihydroperoxides
2a-g were produced in high to excellent yields (90–98%) within 3–12 h (Table 2, Scheme 1).
Similarly, aromatic ketones 1h-j and aromatic aldehydes 1l-p were converted to their corresponding
gem-DHPs 2h-j and 2l-p in (45–68%) and (52–75%) yields respectively (Table 1). However, under the
same reaction condition no conversion to gem-DHP was observed for benzophenone 1k and it was
recovered almost intact after 12 hours. This can possibly be accounted for by the strong resonance
stabilization and steric effects exerted by two phenyl groups.
Scheme 1. Synthesis of gem-dihydroperoxides 2a-g.
O
aq. H O (30%)
2
2
HOO
OOH
SrCl .6H O (cat)
2
2
1
2
MeCN, rt
1
2
R
R
R
R
2
1
As previously reported by Rieche [40] and Žmitek et al. [41], we observed in the present protocol
that simple, nonaromatic aldehydes such as octanal 3q and dihydrocinnamaldehyde 3r, which easily
undergo hydration [42], reacted differently from the ketones and aromatic aldehydes. Under the same
reaction conditions which converted ketones and aromatic aldehydes into their corresponding DHPs,
both alkyl aldehydes-octanal 3q and dihydrocinnamaldehyde 3r-were not converted into their
corresponding DHPs but instead into hydroxyl-hydroperoxides 4q and 4r in high yields (Table 1,
Scheme 2), that is the addition of only one molecule of hydrogen peroxide to the carbonyl group has
occurred. This implies that our protocol can furnish another hitherto unreported approach to
1,1-hydroxyhydroperoxides from aliphatic aldehydes.
Scheme 2. Syntheiss of hydroxyl-hydroperoxides 4q and 4r.
O
aq. H2O2 (30%)
SrCl2.6H2O (cat)
HO
R
OOH
H
MeCN, rt
R
H
4
3

Molecules 2010, 15
Table 2. Synthesis of gem-dihydroperoxides with SrCl2·6H2O (cat.)/30% aq. H2O2.
1436
a
Entry
Ketone 1/ Aldehyde 3
Product2 or 4 b
HOO OOH
Time (h)
Yield (%)c
O
4
96
a
O
O
O
O
HOO OOH
4
3
3
3
98
95
92
94
b
c
HOO OOH
HOO OOH
d
HOO OOH
e
f
O
OOH
OOH
HOO
HOO
4
97
O
3
90
45
g
OOH
O
HOO
10
h
OOH
O
HOO
9
8
68
62
i
j
Me
Me
OOH
O
HOO
MeO
MeO
O
12
10
k
OOH
HOO
CHO
54
52
l
OOH
HOO
CHO
m
11
Me
Me
CHO
HOO
OOH
n
o
9
9
75
72
Cl
Cl
CHO
HOO
OOH
MeO
OMe

Molecules 2010, 15
1437
Table 2. Cont.
CHO
HOO
OOH
Pd
10
73
NC
CN
O
HO OOH
q
5
5
90
92
H
H
O
HO OOH
r
H
H
a
Conditions: Ketone and aldehyde (1 mmol), acetonitrile (4 mL), SrCl2·6H2O (0.1 mmol), 30% aq. H2O2
b
(3 mL), reactions are carried out at rt. The structures of the products were established from their physical
properties and spectral (1H-, 13C-NMR and MS) analysis and compared with the literature. Isolated Yield.
c
d A new derivative.
3. Experimental
3.1. General
Chemicals were obtained from Merck. FT-IR spectra were recorded on a Shimadzu 435-U-04
13
spectrophotometer (KBr pellets). 1H- and C-NMR spectra were recorded on a 200 (50) MHz Varian
or JEOL FX 90 MHz spectrometers in CDCl3 and DMSO-d6 solution, and are reported in  units with
TMS as internal standard. Melting points were determined in open capillary tubes in a Stuart SMP3
apparatus and uncorrected.
3.2. General procedure for synthesis of gem-dihydroperoxides
Caution: Peroxidic compounds are potentially explosive and require precautions in handling
(shields, fume hoods, absence of transition metal salts and heating).
A mixture of carbonyl substrates 1 or 3 (1 mmol), 30% aqueous H2O2 (3 mL) and SrCl2·6H2O
(0.1 mmol) in MeCN (4 mL) was stirred at room temperature for 3-10 h (Table 1). After the
completion of the reaction, the mixture was diluted with water (5 mL), extracted with EtOAc
(3 × 5 mL). The combined organic layer was washed with saturated aqueous sodium bicarbonate
solution (3 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by
column chromatography (silica gel, hexane-EtOAc) to afford pure gem-dihydroperoxides 2 or
hydroxyl-hydroperoxides 4 (Table 1). The products were characterized on the basis of their physical
properties and spectral (1H-, 13C-NMR and MS) analyses and compared with literature data
[32,33,37,40,41]. The spectral (1H-, 13C-NMR and MS) data of some representative products are
given below.
1
Undecane-2,2-dihydroperoxide (2a) [32]. H-NMR (200 MHz, CDCl3):  9.51 (br s, 2H), 1.76–1.60
(m, 2H), 1.38 (s, 3H), 1.32–1.19 (br s,14H), 0.82 (t, J = 7 Hz, 3H); 13C-NMR (50 MHz, CDCl3): 112.3,
33.4, 32.0, 29.4, 29.1, 28.4, 23.6, 22.5, 17.6, 13.8, 13.5; FABMS: m/z 243 [M+Na]+.

Molecules 2010, 15
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1
4-Methylpentane-2,2-dihydroperoxide (2d) [32]. H-NMR (200 MHz, CDCl3):  9.54 (br s, 2H), 1.80
(m, 1H), 1.62 (d, J = 7 Hz, 2H), 1.42 (s, 3H), 0.98 (d, J = 7 Hz, 6H); FABMS: m/z 173 [M+Na]+.
Cyclohexane-1,1-dihydroperoxide (2e) [37]. 1H-NMR (200 MHz, CDCl3):  9.70 (br s, 2H), 1.93–1.70
(m, 4H), 1.67–1.39 (m, 6H); FABMS: m/z 171 [M+Na]+.
1
Methy-phenyl-1,1-dihydroperoxide (2h) [33]. H-NMR (200 MHz, CDCl3):  9.16 (br s, 2H),
7.50–7.43 (m, 2H), 7.38–7.26 (m, 3H), 1.69 (s, 3H); FABMS: m/z 193 [M+Na]+.
1
Phenylmethylene-1,1-dihydroperoxide (2l) [33]. H-NMR (200 MHz, CDCl3):  9.57 (br s, 2H),
7.42–7.28 (m, 5H), 6.24 (s, 1H); FABMS: m/z 179 [M+Na]+.
(4-Methylphenyl)methylene-1,1-dihydroperoxide (2m) [41]. 1H-NMR (200 MHz, CDCl3):  9.71 (br s,
13
2H), 7.30 (d, J = 8 Hz, 2H), 7.15 (d, J = 8 Hz, 2H), 6.28 (s,1H), 2.32 (s, 3H); C-NMR (50 MHz,
CDCl3): 139.5, 129.4, 129.0, 126.7, 109.8, 21.1; FABMS: m/z 193 [M+Na]+.
(4-Chlorophenyl)methylene-1,1-dihydroperoxide (2n) [32]. 1H-NMR (200 MHz, CDCl3):  9.94 (br s,
2H), 7.85–7.34 (m, 4H), 6.26 (s, 1H); 13C-NMR (50 MHz, CDCl3): 139.6, 129.4, 129.0, 126.8, 10.02;
FABMS: m/z 213 [M+Na]+.
(4-Cyanophenyl)methylene-1,1-dihydroperoxide (2p). White solid; m.p. 107–110 ºC; IR (KBr): 3,414,
1
2,916, 2,235, 1,611, 1,405, 1,333, 1,243, 1,199, 1,122, 1,083, 977, 824 cm-1; H-NMR (200 MHz,
CDCl3):  10.08 (s, 2H), 8.04–7.78 (m, 4H), 7.24 (s, 1H); 13C-NMR (50 MHz, CDCl3):  139.3, 129.4,
128.0, 126.1, 117.0, 112.1; FABMS: m/z 204 [M+Na]+; Anal. Calcd for C8H7NO4: C, 53.04; H, 3.86;
N, 7.73. Found: C, 53.15; H, 3.98; N, 7.78.
Octane-1,1-hydroxyhydroperoxide (4q) [42]. Colorless oil; IR (KBr): 3,374, 3,028, 2,931, 2,863,
1
1,496, 1,454, 1,357, 1,242, 1,078, 1,030, 924, 748, 699 cm-1; H-NMR (200 MHz, CDCl3):  8.20 (br
13
s, 1H), 7.00 (br s, 1H), 4.90 (t, J = 7 Hz, 1H), 2.10–0.70 (m, 15H); C-NMR (50 MHz, CDCl3): 
101.2, 32.6, 30.0, 28.5, 24.0, 20.1, 14.0; FABMS: m/z 185 [M+Na]+.
3-Phenylpropane-1,1-hydroxyhydroperoxide (4r) [42]. Colorless oil; IR (KBr): 3384, 3062, 3027,
1
2902, 2861, 1496, 1457, 1376, 1242, 1079, 1031, 923, 747, 700 cm-1; H NMR (200 MHz, CDCl3): 
9.78 (br s, 1H), 8.65 (br s, 1H), 7.60–7.00 (m, 5H), 5.10 (t, J = 7 Hz, 1H), 2.60 (t, J = 8 Hz, 2H),
2.15–1.60 (m, 2H); 13C NMR (50 MHz, CDCl3):  141.5, 127.5, 125.0, 100.0, 32.2, 28.5; FABMS: m/z
191 [M+Na]+.
4. Conclusions
In summary, a new efficient homogeneous catalyst SrCl2·6H2O has been shown to promote the
synthesis of gem-dihydroperoxides from aliphatic and aromatic ketones and aldehydes using aqueous
H2O2 (30%) in acetonitrile at room temperature. The attractive features of this new approach are the
readily available and non-expensive catalyst, high yields of the products, mild reaction conditions and
the operational simplicity of the procedure.

Molecules 2010, 15
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Acknowledgements
The authors are thankful to Bu-Ali Sina University research council for the financial support.
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Sample Availability: Samples of the compounds are available from the authors.
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