A simple and efficient synthesis of gem-dihydroperoxides from ketones using aqueous hydrogen peroxide and catalytic ceric ammonium nitrate

Article abstract of DOI:10.1016/j.tetlet.2007.07.012

Ketones were efficiently converted into the corresponding gem-dihydroperoxides in high yields within a short period of time on treatment with aqueous H₂O₂ (50%) in the presence of a catalytic amount of CAN in acetonitrile at room temperature.

Full text of DOI:10.1016/j.tetlet.2007.07.012

Tetrahedron Letters 48 (2007) 6286–6289
A simple and efficient synthesis of gem-dihydroperoxides
from ketones using aqueous hydrogen peroxide and catalytic
ceric ammonium nitrateI
Biswanath Das,* Maddeboina Krishnaiah, Boyapati Veeranjaneyulu and
Bommena Ravikanth
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 2 June 2007; revised 26 June 2007; accepted 5 July 2007
Available online 30 July 2007
Abstract—Ketones were efficiently converted into the corresponding gem-dihydroperoxides in high yields within a short period of
time on treatment with aqueous H2O2 (50%) in the presence of a catalytic amount of CAN in acetonitrile at room temperature.
ꢀ 2007 Elsevier Ltd. All rights reserved.
gem-Dihydroperoxides have gained much importance in
recent years due to their relevance to peroxidic anti-
O
aq. H2O2 (50%)
CAN (cat)
OOH
R1
HOO
R
malarial drugs.1 They are useful intermediates in the
synthesis of various peroxides such as tetraoxanes1a,2
and endoperoxides.3 They have also recently been
utilized as oxidants.4 gem-Dihydroperoxides can be
prepared by ozonolysis of ketone enol ethers or a-olefins
in the presence of H2O25 or by hydroperoxide rearrange-
ment of bicyclic alcohols.6 However, these methods
suffer from disadvantages such as the requirement of
suitable starting materials, use of concentrated H2O2
and excess acid and unsatisfactory yields. Recently, a
method for the conversion of ketones into gem-dihydr-
operoxides using aqueous H2O2 in the presence of iodine
was reported.7 The time required for this conversion was
typically 24 h.
R
R1
MeCN, r. t.,
1-4 h
2
1
Scheme 1.
(Table 1). The conversions were complete within 1–4 h.
CAN, being a Lewis acid, activates the carbonyl group
and increases the electrophilic character of the carbonyl
C-atom. It also enhances the nucleophilic character of
H2O2. Both acylic and cyclic aliphatic ketones afforded
the desired products in excellent yields. Cyclododecanone
was converted into the corresponding gem-dihydroperox-
ide in 1 h in 92% yield (Table 1, entry l). Previously, the
same conversion using H2O2/I2 required7 24 h to form
the same product in only 60% yield (Scheme 2).
In continuation of our work8 on the development of
useful synthetic methodologies we have observed that
gem-dihydroperoxides can be prepared from ketones
on treatment with aqueous H2O2 (50%) using a catalytic
amount of CAN (Scheme 1).
The present method was also applied for the hydro-
peroxidation of aromatic ketones. Thus acetophenone
afforded the corresponding gem-dihydroperoxide within
2 h in a yield of 48% (entry o). Previously, hydropero-
xidation of acetophenone using aqueous H2O2/I2
required 24 h and the yield was only 16%.7 Different
acetophenone derivatives containing both electron-
donating (e.g., OMe and Cl, entries p and q) and
electron-withdrawing groups (e.g., NO2, entry r) affor-
ded the corresponding dihydroperoxides in appreciable
quantities. However, purification of the product derived
from acetophenone with an electron-withdrawing group
Various ketones were successfully converted into the cor-
responding gem-dihydroperoxides at room temperature
Keywords: Ketone; gem-Dihydroperoxide; Aqueous H2O2; CAN.
q Part 149 in the series, ‘Studies on novel synthetic methodologies’.
*
Corresponding author. Tel./fax: +91 40 7160512; e-mail:
biswanathdas@yahoo.com
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.012

B. Das et al. / Tetrahedron Letters 48 (2007) 6286–6289
6287
a
Table 1. Synthesis of dihydroperoxides with CAN/50% aq H2O2
Entry
Ketone/aldehyde 1
Product 2
Time (h)
1
Yieldb (%)
O
OOH
HOO
a
96
OOH
O
HOO
b
1
95
OOH
OOH
O
HOO
HOO
c
d
e
2
3
2
96
89
90
O
OOH
OOH
O
O
HOO
HOO
f
3
2
85
87
O
O
O
O
HOO
HOO
HOO
HOO
OOH
OOH
OOH
OOH
g
h
2.5
82
85
i
2
j
2
2
1
4
90
86
92
O
HOO
OOH
k
OOH
OOH
O
l
HOO
OOH
CHO
m
51
(continued on next page)

6288
B. Das et al. / Tetrahedron Letters 48 (2007) 6286–6289
Table 1 (continued)
Entry
Ketone/aldehyde 1
Product 2
Time (h)
Yieldb (%)
CHO
HOO
OOH
n
4
74
OMe
OMe
OOH
O
HOO
o
p
2
2
48
60
HOO OOH
O
MeO
MeO
OOH
HOO
O
q
r
2
4
62
Cl
Cl
HOO OOH
O
25c
O2N
O2N
a The structures of the products were established from their spectral (1H, 13C NMR and MS) data.
b Isolated yield.
c The crude 1H NMR spectrum of the reaction mixture showed formation of the product in a yield of 55%, however, it decomposed during isolation.
aqueous H2O2 and a catalytic amount of CAN. The
aq. H2O2 (50%)
CAN (cat.)
OOH
OOH
O
high yields of products, mild reaction conditions, short
conversion times and the use of less costly reagents are
notable advantages of the present method.
MeCN, r.t., 1 h
92%
General procedure: A mixture of ketone (1 mmol), 50%
aqueous H2O2 (1 mL) and CAN (0.1 mmol) in MeCN
(4 mL) was stirred at room temperature for 1–4 h. The
reaction was quenched with water (5 mL) and the
mixture was extracted with EtOAc (3 · 5 mL). The com-
bined organic extract was dried (Na2SO4) and concen-
trated in vacuo. The residue, on purification by
column chromatography (silica gel, hexane–EtOAc),
afforded pure gem-dihydroperoxide.
Scheme 2.
by column chromatography using silica gel resulted in
decomposition.
Hydroperoxidation of aldehydes is quite difficult. Benz-
aldehyde was earlier converted using aqueous H2O2/I2
into the corresponding gem-dihydroperoxide in 24 h in
a yield of 55%.7 In the present method the same conver-
sion was carried out in 4 h to furnish the gem-dihydro-
peroxide in 51% yield (entry m). The presence of an
electron-donating group (e.g., OMe) on benzaldehyde
afforded the product in higher yield (entry n) while the
presence of an electron-withdrawing group (e.g., NO2)
resulted in no product.
The spectral (1H, 13C NMR and MS) data of some
representative products are given below.
Compound 2a: 1H NMR (200 MHz, CDCl3): d 9.52
(2H, br s), 1.78–1.62 (2H, m), 1.39 (3H, s), 1.34–1.20
(14H, br s), 0.83 (3H, t, J = 7.0 Hz); 13C NMR
(50 MHz, CDCl3): 112.5, 33.5, 32.0, 29.5, 29.0, 28.5,
23.8, 22.6, 17.8, 13.9; LC–MS: m/z 243 [M+Na]+.
In conclusion, we have developed a simple and highly
efficient method for the synthesis of gem-dihydroperoxi-
des from the corresponding ketones on treatment with
Compound 2d: 1H NMR (200 MHz, CDCl3): d 9.35
(2H, br s), 1.62 (4H, q, J = 7.0 Hz), 0.85 (6H, t, J =
7.0 Hz); LC–MS: m/z 159 [M+Na]+.

B. Das et al. / Tetrahedron Letters 48 (2007) 6286–6289
6289
Compound 2e: 1H NMR (200 MHz, CDCl3): d 9.56 (2H,
References and notes
br s), 1.82 (1H, m), 1.63 (2H, d, J = 7.0 Hz), 1.44
(3H, s), 0.98 (6H, d, J = 7.0 Hz); LC–MS: m/z 173
[M+Na]+.
1. (a) Iskra, J.; Bonnet-Delpon, D.; Begue, J. P. Tetrahedron
Lett. 2003, 44, 6309–6312; (b) Tang, Y. Q.; Dong, Y. X.;
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Declereq, J. P.; Kyle, D. E.; Milhous, W. K.; Solaja, B. A.
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Kutkin, A. V.; Starikova, Z. A.; Antipin, M. Y.; Ogibin, Y.
N.; Nikishina, G. I. Synthesis 2004, 2356–2366.
Compound 2i: 1H NMR (200 MHz, CDCl3): d 9.22 (2H,
br s), 2.20 (2H, br d, J = 13.0 Hz), 1.80–1.22 (5H, m),
1.12–0.81 (2H, m) 0.98 (3H, d, J = 7.0 Hz); LC–MS:
m/z 185 [M+Na]+.
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McCullough, K. J. Tetrahedron 2003, 59, 525–536.
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Compound 2l: 1H NMR (200 MHz, CDCl3 + DMSO-d6):
d 10.39 (2H, br s), 1.62–1.24 (m, 22H); 13C NMR
(50 MHz, DMSO-d6): d 112.4, 25.9, 25.8, 25.5, 24.2,
23.8, 21.7, 21.5, 21.4, 21.3, 19.2, 18.5; LC–MS: m/z
255 [M+Na]+.
1
Compound 2m: H NMR (200 MHz, CDCl3): d 9.59
(2H, br s), 7.44–7.30 (5H, m), 6.26 (1H, s); LC–MS:
m/z 179 [M+Na]+.
Compound 2o: 1H NMR (200 MHz, CDCl3): d 9.18
(2H, br s), 7.52–7.44 (2H, m), 7.40–7.28 (3H, m), 1.71
(3H, s); LC–MS: m/z 193 [M+Na]+.
Acknowledgement
The authors thank CSIR, New Delhi, for financial
assistance.