Synthesis of gem-dihydroperoxides from ketones and aldehydes using silica sulfuric acid as heterogeneous reusable catalyst

Article abstract of DOI:10.1080/00397911.2011.610549

Silica sulfuric acid (SSA) was found to efficiently catalyze the conversion of aldehydes and ketones directly into the corresponding gem-dihydroperoxides (DHPs) on treatment with aqueous 30% H₂O₂ at room temperature. Mild reaction conditions, good to excellent yields, short reaction times, low environmental impact, and recyclability of the catalyst are the main advantages of this synthetic method.

Full text of DOI:10.1080/00397911.2011.610549

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Synthesis of gem-Dihydroperoxides
from Ketones and Aldehydes Using Silica
Sulfuric Acid as Heterogeneous Reusable
Catalyst
Davood Azarifar a , Zohreh Najminejad a & Kaveh Khosravi a
a Department of Chemistry, University of Bu-Ali Sina, Hamedan, Iran
Accepted author version posted online: 22 Feb 2012.Version of
record first published: 21 Dec 2012.
To cite this article: Davood Azarifar , Zohreh Najminejad & Kaveh Khosravi (2013): Synthesis of gem-
Dihydroperoxides from Ketones and Aldehydes Using Silica Sulfuric Acid as Heterogeneous Reusable
Catalyst, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 43:6, 826-836
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Synthetic Communications1, 43: 826–836, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.610549
SYNTHESIS OF GEM-DIHYDROPEROXIDES FROM
KETONES AND ALDEHYDES USING SILICA SULFURIC
ACID AS HETEROGENEOUS REUSABLE CATALYST
Davood Azarifar, Zohreh Najminejad, and Kaveh Khosravi
Department of Chemistry, University of Bu-Ali Sina, Hamedan, Iran
GRAPHICAL ABSTRACT
Abstract Silica sulfuric acid (SSA) was found to efficiently catalyze the conversion of
aldehydes and ketones directly into the corresponding gem-dihydroperoxides (DHPs) on
treatment with aqueous 30% H2O2 at room temperature. Mild reaction conditions, good
to excellent yields, short reaction times, low environmental impact, and recyclability of
the catalyst are the main advantages of this synthetic method.
Keywords Aldehydes; gem-dihydroperoxides; heterogeneous catalyst; ketones; silica
sulfuric acid
INTRODUCTION
In recent years, gem-dihydroperoxides (DHPs), as stable derivatives of ketones
and aldehydes,[1] have attracted much interest because of their importance as
peroxidic antimalarial drugs.[2,3] They are also useful intermediates in the synthesis
of trioxanes,[4] tetraoxanes,[2,5,6] and their analogs such as silatetraoxanes,[7] spirobis-
peroxyketals,[8] and 1,2,4,5-tetraoxacycloalkanes.[9] Also, very recently, DHPs have
been utilized as important oxidants in epoxidation of a,b-unsaturated ketones,[10]
as radical initiators in polymerization reactions,[11,12] in oxidation of various organic
molecules,[13] such as sulfides,[14,15] and as precursors for the synthesis of dicarbo-
xylic acid diesters.[16]
Of the methods described for the synthesis of gem-dihydroperoxides,[1] the
reaction of hydrogen peroxide with ketones and aldehydes is the most straightfor-
ward method. However, in most cases, mixtures of peroxidic products were
obtained.[17,18] Most of these methods used a Brønsted or Lewis acid catalyst, such
as HCO2H,[19] concentrated. H2SO4,[20] F3CCO2H,[21] NaHSO4 ꢀ SiO2,[22] H2WO4,[23]
Received April 29, 2011.
Address correspondence to Davood Azarifar, Department of Chemistry, University of Bu-Ali Sina,
Hamedan 65178, Iran. E-mail: azarifar@basu.ac.ir
826

SYNTHESIS OF GEM-DIHYDROPEROXIDES
827
BF3 ꢀ Et2O,[24] or camphorsulfunic acid (CSA).[25] In other reported methods
Ce(NH4)2(NO3)6 (CAN),[21] I2,[26] methyltrioxorhenium (MTO),[2] and Re2O7 in
MeCN,[27] have also been utilized to promote dihydroperoxidation of ketones and
aldehydes in reaction with H2O2. However, almost all these methods suffer from
one or more drawbacks such as severe reaction conditions, longer reaction times,
poor yields, use of highly concentrated H2O2, incompatibility with sensitive func-
tionalities, and nonrecyclability of the catalyst.[27] One of the general methods
for the synthesis of gem-dihydroperoxides is ozonolysis of ketone enol ether or
a-olefines in the presence of aqueous H2O2.[28] Ozonolysis of alkenes is also reported
for the preparation of DHPs under neutral conditions but requires the use of organic
solutions of H2O2 and is limited to ozone-compatible substrates.[8,29]
RESULTS AND DISCUSSION
In our ongoing efforts to develop new and benign synthetic methodologies for
the synthesis,[30,31] and application of gem-dihydroperoxides,[32–34] we found that sil-
ica sulfuric acid (SSA) acts as an efficient and recyclable heterogeneous solid acid
catalyst to convert ketones and aldehydes into the corresponding gem-dihydroperox-
ides when treated with 30% aqueous H2O2 in CH3CN at room temperature
(Scheme 1).
SSA has been used as a versatile and reusable heterogeneous catalyst in various
organic transformations.[35] This catalyst can be easily prepared by treatment of sil-
ica with neat chlorosulfonic acid, according to the literature.[36] The number of acidic
sites is 3.5 mmol per 1 g of support. The recycling potential of the catalyst SSA was
examined, as explained in the experimental section.
To study the effects of the catalyst concentration and solvent on the titled
reaction, we initially examined the conversion of cyclohexanone, acetophenone,
and benzaldehyde as test compounds using 30% aqueous H2O2 at room temperature
separately using various amounts of SSA catalyst in different solvents such as
CH3CN, EtOAc, Et2O, and CH2Cl2 (Table 1). As seen in Table 1, the best result
in terms of reaction time and yield was obtained when 100 mg catalyst was used in
CH3CN as the solvent of choice (entry 2). It appears that the yield improves as
the polarity of the solvent increases.
The effect of catalyst was also examined for these model reactions using 30%
aqueous H2O2 in CH3CN at room temperature in the presence of various hetero-
geneous catalysts such as SSA, NaHSO4 ꢀ SiO2, Al(HSO4)3 FeCl3 ꢀ SiO2, KF-Al2O3,
CeO2, P2O5 ꢀ SiO2, Amberlyst-15, montmorillonite clay, silica-supported phospho-
molybdic acid (PMA ꢀ SiO2), and also some homogeneous catalysts such as concen-
trated H2SO4 and camphorsulfonic acid (CSA) (Table 2). Considering reaction times
Scheme 1. Conversion of ketones into gem-dihydroperoxides 2.

828
D. AZARIFAR, Z. NAJMINEJAD, AND K. KHOSRAVI
Table 1. Screening the amount of the catalyst (SSA) and solvent on separate reactions of cyclohexanone,
a
acetophenone, and benzaldehyde with 30% aqueous H2O2
Entry
SSA (mg)
Solvent
Time (min)b
Yield (%)c
1
2
3
4
5
6
7
8
50
100
200
300
400
100
100
100
MeCN
MeCN
MeCN
MeCN
MeCN
EtOAc
Et2O
30, 150, 80
20, 120, 50
60, 120, 80
90, 180, 120
180, 240, 120
60, 300, 150
150, 420, 300
85, 360, 210
45, 50, 60
95, 75, 85
84, 60, 75
65, 55, 45
60, 50, 40
85, 60, 75
45, 30, 38
68, 45, 55
CH2Cl2
aKetone or aldehyde (1 mmol) and 30% aqueous H2O2 (3 mL) in solvent (4 mL) were used at rt.
bReaction times for the conversion of cyclohexanone, acetophenone, and benzaldehyde, respectively.
cIsolated yields for the conversion of cyclohexanone, acetophenone, and benzaldehyde, respectively.
and yields of the corresponding DHPs, in all three cases, SSA was found to be the
most active catalyst. The other catalysts cerium oxide, Amberlyst-15, montmorillon-
ite clay, and PMA ꢀ SiO2 produced moderate to poor yields for preparation of
cyclohexanone-1,1-diyl dihydroperoxide. KF-Al2O3 was found to be completely
inactive for conversion of all three carbonyl compounds into the corresponding
gem-dihydroperoxides. These other catalysts also proved unsuitable for preparation
of DHPs from aromatic ketones and aldehydes.
To develop the scope of these reactions, a series of aliphatic and aromatic
ketones 1a–n and aldehydes 1o–x were reacted with 30% aqueous H2O2 under opti-
mized conditions to obtain the corresponding gem-dihydroperoxides, and the experi-
mental results are summarized in Table 3. As seen in this table, both cyclic and
acyclic aliphatic ketones 1a–i furnished the corresponding DHPs 2a–i in excellent
Table 2. Catalyst screening for model reactions of cyclohexanone, acetophenone, and benzaldehyde with
30% aqueous H2O2 in CH3CN using various heterogeneous catalystsa
Entry
Catalyst
Time (min)b
Isolated yield (%)c
1
2
SSA
20, 120, 50
300, 480, 360
60, 240, 80
98, 75, 85
FeCl3 ꢀ SiO2
NaHSO4 ꢀ SiO2
Al(HSO4)3
CSA
Trace, trace, trace
92, 70, 68
44, 0, 0
3
4
240,360, 200
960, –, 960
20, 200, 50
5
44, –, 77
70, trace, 70
64, 70, 80
6
H2SO4
7
P2O5 ꢀ SiO2
KF-Al2O3
CeO2
180, 300,180
600, 360, 240
360, 600, 720
90, 240, 300
120, 240, 300
120, 300, 300
8
Trace, trace, trace
45, 10, 15
9
10
11
12
Amberlyst-15
Montmorillonite clay
PMA ꢀ SiO2
60, 0, trace
30, 0, 0
65, 20, 35
aKetone and aldehyde (1 mmol), 30% aqueous H2O2 (3 mL), and CH3CN (4 mL) were used in the pres-
ence of the catalyst (100 mg) at rt.
bReaction times for the conversion of cyclohexanone, acetophenone, and benzaldehyde, respectively.
cIsolated yields for the conversion of cyclohexanone, acetophenone, and benzaldehyde, respectively.

SYNTHESIS OF GEM-DIHYDROPEROXIDES
829
a
Table 3. Synthesis of gem-dihydroperoxides with SSA (cat.) = 30% aqueouss H2O2
Entry
Ketone 1=aldehyde 3
Productb 2 and 4
Time (min) Yieldc (%) Ref.
a
20
98
[22]
b
c
17
18
96
95
[39]
[27]
d
25
38
85
75
New
New
e
f
19
16
17
98
95
94
[40]
[41]
[41]
g
h
i
j
40
90
75
[15]
[41]
120
(Continued )

830
D. AZARIFAR, Z. NAJMINEJAD, AND K. KHOSRAVI
Table 3. Continued
Entry
Ketone 1=aldehyde 3
Productb 2 and 4
Time (min) Yieldc (%) Ref.
k
130
85
[26]
l
200
200
—
—
—
m
—
—
92
n
55
New
o
p
60
45
90
95
[37]
[37]
q
50
65
85
90
[41]
[40]
r
s
50
95
[39]
(Continued )

SYNTHESIS OF GEM-DIHYDROPEROXIDES
Table 3. Continued
831
Entry
Ketone 1=aldehyde 3
Productb 2 and 4
Time (min) Yieldc (%) Ref.
t
75
80
86
88
[40]
u
New
v
160
120
120
75
70
75
New
New
[30]
w
x
aKetone and aldehyde (1 mmol), CH3CN (4 mL), SSA (100 mg), and 30% aqueous H2O2 (3 mL); reac-
tions are carried out at rt.
bThe structures of the products were established from their physical properties and spectral (1H NMR,
13C NMR, and IR) analysis and compared with the data reported in the literature.
cIsolated yield.
yields (75–98%). Aromatic ketones carrying electron-donation groups afforded the
corresponding DHPs in good yields, while those having electron-withdrawing groups
generally gave the corresponding products in lower or no detectable yields, as was
observed in the case of p-nitroacetophenone 1 l. However, under similar reaction
conditions, no conversion to DHPs occured for benzophenone 1 m after longer
(200 min) reaction time. Generally, aromatic aldehydes 3q–x undergo these reactions
to furnish the corresponding gem-dihydroperoxides 4q–x in relatively poor yields
(70–95%) in longer reaction times (Scheme 2). As we previously noted,[30,31] and
was also reported by others,[37,38] this method proved unsuitable for converting ali-
phatic aldehydes such as octanal 3o and hydrocinnamaldehyde 3p into respective

832
D. AZARIFAR, Z. NAJMINEJAD, AND K. KHOSRAVI
Scheme 2. Conversion of aldehydes into gem-dihydroperoxides 4.
DHPs. Instead, these aldehydes were converted into the corresponding
1,1-hydroxy-hydroperoxides (Table 3). This implies that the addition of only one
molecule of hydrogen peroxide to the carbonyl group has occurred.
CONCLUSION
In summary, SSA has been explored as an efficient and reusable catalyst 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 good to excellent yields of the products,
easy workup, and stability, reusability, nontoxicity, easy preparation, and low cost
of the catalyst.
EXPERIMENTAL
Solvents, reagents, and chemical materials were obtained from Aldrich and
Merck chemical companies and purified prior to use. Melting points were deter-
mined in open capillary tubes in a Stuart SMP3 apparatus and are uncorrected.
Nuclear magnetic resonance spectra were recorded on a Jeol FX 90Q spectrometer
using tetramethylsilane (TMS) as an internal standard. Infrared (IR) spectra were
recorded on a Perkin-Elmer GX Fourier transform (FT)–IR spectrometer (KBr
pellets).
Caution: Although we did not encounter any problem with these reactions, per-
oxidic compounds are potentially explosive and should be handled with caution; all
reactions should be carried out behind a safety shield inside a fume hood, and
transition-metal salts and heating should be avoided.
General Procedure for Conversion of Ketones and Aldehydes into
Corresponding gem-Dihydroperoxides
To a mixture of carbonyl compound 1 or 3 (1 mmol) and SSA (100 mg) in
MeCN (4 mL) was added 30% aqueous H2O2 (3 mL), and the mixture was stirred
at room temperature for an appropriate time (Table 3). After completion of the reac-
tion as monitored by thin-layer chromatography (TLC), the resulting mixture was
filtered and washed with EtOAc (2 ꢁ 5 mL) to separate the solid catalyst. The com-
bined filtrates was diluted with water (5 mL) and extracted with EtOAc (3 ꢁ 5 mL).
The organic layer was separated, dried over anhydrous Mg2SO4, and evaporated
under reduced pressure. The residue was purified by silica-packed column chroma-
tography (hexane–EtOAc) to afford pure gem-dihydroperoxides (Table 3). The

SYNTHESIS OF GEM-DIHYDROPEROXIDES
833
products were characterized on the basis of their physical properties and spectral
(1H, 13C NMR and IR) data, which were in accord with those reported in the litera-
ture (Table 3).
Catalyst Recovery and Reuse
The reusability potential of the catalyst was examined in reaction of cyclohex-
anone with 30% aqueous H2O2 at room temperature in the presence of SSA. The
catalyst SSA was easily separated simply by filtration of the reaction mixture and
reused after washing with CHCl3 and drying at 60 ꢂC. It was noticed that the catalyst
could be used for at least four consecutive runs without noticeable drop in its cata-
lytic activity. The isolated yields of the product for these four consecutive runs were
98, 95, 92, and 90% respectively.
Spectral Data of New Compounds
2,2-Dihydroperoxy-1,7,7-trimethyl-bicyclo[2.2.1]heptane (2d). Colorless
oil; IR (KBr), n: 3473 (O-H stretching of hydroperoxy groups), 2973, 2853, 1589,
1448, 1385, 1268, 1146, 1017 cmꢃ1; MS (FABMS, 70 ev): m=z (%): 225 (M þ Na)þ;
1H NMR (CDCl3, 90 MHz): d 4.45 (brs, 2H, OOH), 2.46–0.72 (m, 16H, aliph-H);
13C NMR (CDCl3, 22.5 MHz): d 114.2, 52.0, 45.4, 39.5, 37.0, 24.6, 23.5, 21.0, 8.6.
Anal. calcd. for C10H18O4: C, 59.40; H, 8.91%. Found: C, 59.34; H, 8.87%.
3-Bromo-2,2-dihydroperoxy-1,7,7-trimethyl-bicyclo[2.2.1]heptane (2e).
Colorless solid; mp 68–70 ꢂC; IR (KBr), n: 3410 (O-H stretching of hydroperoxy
groups), 2956, 2853, 1618, 1478, 1384, 1316, 1205, 1034, 910, 768 cmꢃ1; MS
(FABMS, 70 ev): m=z (%): 304 (MþNa)þ; 1H NMR (CDCl3, 90 MHz): d 4.56
(brs, 2H, OOH), 2.27–0.91 (m, 15H, aliph-H); 13C NMR (CDCl3, 22.5 MHz): d
120.3, 54.0, 46.8, 40.0, 38.3, 26.6, 24.7, 22.4, 9.6. Anal. calcd. for C10H17BrO4: C,
42.70; H, 6.05%. Found: C, 42.63; H, 5.97%.
Methyl-(naphthalen-1-yl)-1,1-dihydroperoxide (2n). Colorless oil; IR
(KBr), n: 3324, 3052 (O-H stretching of hydroperoxy groups), 2922, 2853, 1594,
1573, 1508, 1461, 1356, 1279, 1240, 1192, 1128, 941, 863, 802, 775, 591 cmꢃ1; MS
(FABMS, 70 ev): m=z (%): 243 (M þ Na)þ; 1H NMR (CDCl3, 90 MHz): d
8.83–8.75 (brs, 2H, OOH), 8.10–7.20 (m, 7H, Ar-H), 2.66 (s, 3H, CH3); 13C NMR
(CDCl3, 22.5 MHz): d 136.0, 134.4, 131.1, 129.9, 127.8, 126.6, 125.5, 123.0, 107.0,
20.5. Anal. calcd. for C12H12O4: C, 65.45; H, 5.45%. Found: C, 65.42; H, 5.40%.
(4-Bromophenyl)methylene-1,1-dihydroperoxide (4u). Colorless solid;
mp 88–90 ꢂC; IR (KBr), n: 3426, 3085 (O-H stretching of hydroperoxy groups),
=
2909, 1608, 1528, 1411 (C C stretching of aromatic ring), 1353, 1236, 1195, 1083,
973, 856, 828, 753, 706, 601 cmꢃ1; MS (FABMS, 70 ev): m=z (%): 258 (M þ Na)þ;
1H NMR (CDCl3, 90 MHz): d 9.96 (brs, 2H, OOH), 7.90–7.00 (m, 4H, Ar-H),
6.26 (s, 1H, CH); 13C NMR (CDCl3, 22.5 MHz): d 141.0, 132.5, 130.5, 120.0,
111.0. Anal. calcd. for C7H7BrO4: C, 35.74; H, 2.97%. Found: C, 35.72; H, 2.94%.
(4-Fluorophenyl)methylene-1,1-dihydroperoxide (4v). Colorless solid;
mp 110–112 ꢂC; IR (KBr), n: 3464, 3082 (O-H stretching of hydroperoxy groups),

834
D. AZARIFAR, Z. NAJMINEJAD, AND K. KHOSRAVI
=
2905, 1625, 1601, 1564, 1453 (C C stretching of aromatic ring), 1353, 1303, 1071,
1025, 844, 720, 685 cmꢃ1; MS (FABMS, 70 ev): m=z (%): 197 (M þ Na)þ; 1H
NMR (CDCl3, 90 MHz): d 9.21 (brs, 2H, OOH), 8.14–7.14 (m, 4H, Ar-H), 6.14
(s, 1H, CH); 13C NMR (CDCl3, 22.5 MHz): d 161.62, 137.0, 128.5, 118.5, 112.0.
Anal. calcd. for C7H7FO4: C, 48.27; H, 4.02%. Found: C, 48.23; H, 3.97%.
(2-Methoxyphenyl)methylene-1,1-dihydroperoxide (4w). Colorless oil;
IR (KBr), n: 3226, 3085 (O-H stretching of hydroperoxy groups), 2853, 1647,
=
1603, 1493, 1465 (C C stretching of aromatic ring), 1372, 1245, 1177, 1017, 844,
758 cmꢃ1; MS (FABMS, 70 ev): m=z (%): 209 (M þ Na)þ; 1H NMR (CDCl3,
90 MHz): d 9.35 (brs, 2H, OOH), 8.18–6.84 (m, 4H, Ar-H), 6.04 (s, 1H, CH), 4.05
(s, 3H, OCH3); 13C NMR (CDCl3, 22.5 MHz): d 157.4, 139.1, 128.5, 123.0, 118.5,
102.0, 57.5. Anal. calcd. for C8H10O5: C, 51.61; H, 5.37%. Found: C, 51.57; H,
5.34%.
ACKNOWLEDGMENT
We thank the research council of the University of Bu-Ali Sina for financial
support to carry out this research.
REFERENCES
1. For a review, see Zmitek, K.; Zupan, M.; Iskra, J. a-Substituted organic peroxides:
Synthetic strategies for a biologically important class of gem-dihydroperoxide and perke-
tal derivatives. Org. Biomol. Chem. 2007, 5, 3895–3908.
2. Iskra, J.; Bonnet-Delpon, D.; Begue, J. P. One-pot synthesis of non-symmetric
tetraoxanes with the H2O2=MTO=fluorous alcohol system. Tetrahedron Lett. 2003, 44,
6309–6312.
3. Wiesner, J.; Ortmann, R.; Jomaa, H.; Schlitzer, M. New antimalarial drugs. Angew.
Chem., Int. Ed. 2003, 42, 5274–5293.
4. Masuyama, A.; Wu, J. M.; Nojima, M.; Kim, H. S.; Wataya, Y. 1,2,4,5-Tetraoxacycloalk-
anes: Synthesis and antimalarial activity. Mini-Rev. Med. Chem. 2005, 5, 1035–1043.
5. Opsenica, I.; Terzic, N.; Opsenica, D.; Angellovski, G.; Lehning, M.; Eilbrachi, P.; Tinant,
B.; Juranic, Z.; Smith, K. S.; Yang, Y. S.; Diaz, D. S.; Smith, P. L.; Milhous, W. K.;
Dokovic, D.; Solaja, B. A. Tetraoxane antimalarials and their reaction with Fe(II).
J. Med. Chem. 2006, 49, 3790–3799.
6. Terent’ev, A. O.; Kutkin, A. V.; Starikova, Z. A.; Antipia, M. Y.; Ogibin, Y. N.;
Nikishina, G. I. New preparation of 1,2,4,5-tetraoxanes. Synthesis 2004, 2356–2366.
7. Terent’ev, A. O.; Platonov, M. M.; Tursina, A. I.; Chemyshev, V. V.; Nikishin, G. I.
Synthesis of cyclic peroxides containing the Si-gem-bisperoxide fragment 1,2,4,5,7,8-
hexaoxa-3-silonanes as a new class of peroxides. J. Org. Chem. 2008, 73, 3169–3174.
8. Ghorai, P.; Dussault, P. H.; Hu, C. Synthesis of spiro-bisperoxyketals. Org. Lett. 2008, 10,
2401–2404.
9. Kim, H. S.; Nagai, Y.; Ono, K.; Begum, K.; Wataya, Y.; Hamada, Y.; Tsuchiya, K.;
Masuyama, A.; Nojima, M.; McCullough, K. J. Synthesis and antimalarial activity of
novel medium-sized 1,2,4,5-tetraoxacycloalkanes. J. Med. Chem. 2001, 44, 2357–2361.
10. Jakka, K.; Liu, J.; Zhao, C. G. Facile epoxidation of a, b-unsaturated ketones with cyclo-
hexylidenebishydroperoxide. Tetrahedron Lett. 2007, 48, 1395–1398.

SYNTHESIS OF GEM-DIHYDROPEROXIDES
835
11. Adam, W. Peroxide Chemistry: Mechanistic and Preparative Aspects of Oxygen Transfer;
Wiley-VCH: Weinheim, Germany, 2000.
12. Ando, W. Organic Peroxides; John Wiley & Sons: Chichester, UK, 1992.
13. Saneyyoshi, H.; Miyata, K.; Seio, K.; Sekine, M. 1,1-Dihydroperoxycyclododecane as a
new, crystalline nonhygroscopic oxidizer for the chemical synthesis of oligodeoxyribonu-
cleotides. Tetrahedron Lett. 2006, 47, 8945–8947.
14. Selvam, J.; Suresh, V.; Rajesh, K.; Chanti Babu, D.; Suryakiran, N.; Venkateswarlu, Y. A
novel rapid sulfoxidation of sulfides with cyclohexylidenebishydroperoxide. Tetrahedron
Lett. 2008, 49, 3463–3465.
15. Azarifar, D.; Khosravi, K. Trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane as a novel
and efficient reagent for selective sulfoxidation of sulfides under catalyst-free conditios. Eur.
J. Chem. 2010, 1, 15–19.
16. Terent’ev, A. O.; Platonov, M. M.; Kukin, A. V. A new oxidation process: Transform-
ation of gem-bishydroperoxides into esters. Cent. Eur. J. Chem. 2006, 4, 207–215.
17. Kharasch, M. S.; Sosnovsky, G. Structure of peroxides derived from cyclohexanone and
hydrogen peroxide. J. Org. Chem. 1958, 23, 1322–1326.
18. Criegee, R.; Schnorrenberg, W.; Becke, J. Zur Konstitution von Ketonperoxyden. Liebigs
Ann. Chem. 1949, 565, 7–21.
19. Ledaal, T.; Solbjor, T. 1,1-Dihydroperoxycyclododecane. Acta Chem. Scand. 1967, 21,
1658–1659.
20. Terent’ev, A. O.; Platonov, M. M.; Ogibin, Y. N.; Nikishin, G. I. Convenient synthesis of
geminal bishydroperoxides by the reaction of ketones with hydrogen peroxide. Synth.
Cmmun. 2007, 37, 1281–1287.
21. Ramirez, A.; Woerpel, K. A. Synthesis of 1,2-dioxolanes by annulation reactions of
peroxzcarbenium ions with alkenes. Org. Lett. 2005, 7, 4617–4620.
22. Das, B.; Veeranjaneyulu, B.; Krishnaiah, M.; Balasubramanyam, P. Synthesis of
gem-dihydroperoxides from ketones using silica-supported sodium hydrogen sulfate as a
heterogeneous catalyst. J. Mol. Catal. A 2008, 284, 116–119.
23. Jefford, C. W.; Li, W.; Jaber, A.; Boukouvalas, J. A new method for the synthesis of
gem-dihydroperoxides. Synth. Commun. 1990, 20, 2589–2596.
24. Terent’ev, A. O.; Kutkin, A. V.; Platonov, M. M.; Ogibin, Y. N.; Nikishin, G. I. A
new method for the synthesis of bishydroperoxides based on a reaction of ketals with
hydrogen peroxide catalyzed by boron trifluoride complexe. Tetrahedron Lett. 2003, 44,
7359–7363.
25. Bunge, A.; Hamann, H. J.; Liebscher, J. A simple, efficient, and versatile synthesis of pri-
mary gem-dihydroperoxides from aldehydes and hydrogen peroxide. Tetrahedron Lett.
2009, 50, 524–526.
26. Zmitek, K.; Zupan, M.; Stavber, S.; Iskra, J. Iodine as a catalyst for efficient conversion of
ketones to gem-dihydroperoxides by aqueous hydrogen peroxide. Org. Lett. 2006, 8,
2491–2494.
27. Ghorai, P.; Dussault, P. H. Mild and efficient Re(VII)-catalyzed synthesis of 1,1-dihydro-
peroxides. Org. Lett. 2008, 10, 4577–4579.
28. Kim, H. S.; Tsuchiya, K.; Shibata, Y.; Wataya, Y.; Ushigoe, Y.; Masuyama, A.; Nojima,
M.; McCullough, K. J. Synthetic methods for unsymmetrically-substituted 1,2,4,5-tetrox-
anes and of 1,2,4,5,7-pentoxocanes. J. Chem. Soc., Perkin Trans. 1 1999, 1867–1870.
29. Zhange, Q.; Li, Y.; Wu, Y.-K. Synthesis of a 1,2,7,8-tetraoxa-spiro[5.5]undecane. Chin. J.
Chem. 2007, 25, 1304–1308.
30. Azarifar, D.; Khosravi, K.; Soleimanei, F. Stannyl chloride trihydrate: A novel and
efficient catalyst for synthesis of gem-dihydroperoxides from ketones and aldehydes using
aqueous hydrogen peroxide. Synthesis 2009, 2553–2556.

836
D. AZARIFAR, Z. NAJMINEJAD, AND K. KHOSRAVI
31. Azarifar, D.; Khosravi, K.; Soleimanei, F. Mild and efficient strontium chloride
hexahydrate–catalyzed conversion of ketones and aldehydes into corresponding gem-
dihydroperoxides by aqueous H2O2. Molecules 2010, 15, 1433–1441.
32. Azarifar, D.; Khosravi, K. Trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane as a
novel and efficient reagent for selective sulfoxidation of sulfides under catalyst-free con-
dition. Eur. J. Chem. 2010, 1, 15–19.
33. Azarifar, D.; Khosravi, K. Facile epoxidation of a,b-unsaturated ketones with trans-
3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane as an efficient oxidant. Synlett 2010,
2755–2758.
34. Azarifar, D.; Khosravi, K.; Najminejad, Z.; Soleimani, K. Synthesis of 1,2-disubstituted
benzimidazoles and 2-substituted benzothiazoles catalyzed by HCl-treated trans-
3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane. Heterocycles 2010, 81, 2855–2863.
35. Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Otokesh, S.; Baghbanzadeh, M. Selective synthesis
of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles in water at ambient temperature. Tetra-
hedron Lett. 2006, 47, 2557–2560, and references cited therein.
36. Zolfigol, M. A. Silica sulfuric acid=NaNO2 as a novel heterogeneous system for pro-
duction of thionitrites and disulfides under mild conditions. Tetrahedron 2001, 57,
9509–9511.
¨
37. Rieche, A. Uber Oxyalkyl-hydroperoxyde, VII. Mitteil. u¨ber Alkylperoxyde). Chem. Ber.
1931, 64, 2328–2335.
38. McClelland, R. A.; Coe, M. Structure–reactivity effects in the hydration of benzaldehydes.
J. Am. Chem. Soc. 1983, 105, 2718–2725.
39. Li, Y.; Hao, H.-D.; Zhang, Q.; Wu, Y. A broadly applicable mild method for the synthesis
of gem-diperoxides from corresponding ketones or 1,3-dioxolanes. Org. Lett. 2009, 11,
1615–1618.
40. Zmitek, K.; Zupan, M.; Stavber, S.; Iskra, J. The effect of iodine on the peroxidation of
carbonyl compounds. J. Org. Chem. 2007, 72, 6534–6540.
41. Das, B.; Krishnaiah, M.; Veeranjaneyulu, B.; Ravikanth, B. A simple and efficient
synthesis of gem-dihydroperoxides from ketones using aqueous hydrogen peroxide and
catalytic ceric ammonium nitrate. Tetrahedron Lett. 2007, 48, 6286–6289.