Synthesis of peroxide compounds by the BF3-catalyzed reaction of acetals and enol ethers with H2O2

Article abstract of DOI:10.1023/B:RUCB.0000035657.58776.cc

Aliphatic and alicyclic gem-bis-hydroperoxides and their derivatives, bis(1-hydroperoxycycloalkyl) and bis(1-hydroperoxyalkyl) peroxides, dispiro- and tetraalkyl-1,2,4,5-tetroxanes were synthesized by the reaction of aliphatic and alicyclic acetals and enol ethers with H₂O₂ in the presence of BF₃ in anhydrous Et₂O.

Full text of DOI:10.1023/B:RUCB.0000035657.58776.cc

Russian Chemical Bulletin, International Edition, Vol. 53, No. 3, pp. 681—687, March, 2004
681
Synthesis of peroxide compounds by the BF3ꢀcatalyzed reaction of
acetals and enol ethers with H2O2*
A. O. Terent´ev,a A. V. Kutkin,a M. M. Platonov,a I. I. Vorontsov,b
a
M. Yu. Antipin,b Yu. N. Ogibin,a and G. I. Nikishin
ꢀ
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: ogibin@ioc.ac.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Aliphatic and alicyclic gemꢀbisꢀhydroperoxides and their derivatives, bis(1ꢀhydroperoxyꢀ
cycloalkyl) and bis(1ꢀhydroperoxyalkyl) peroxides, dispiroꢀ and tetraalkylꢀ1,2,4,5ꢀtetroxanes
were synthesized by the reaction of aliphatic and alicyclic acetals and enol ethers with H2O2 in
the presence of BF3 in anhydrous Et2O.
Key words: acetals, enol ethers, boron trifluoride complexes with Et2O and MeOH, gemꢀ
bisꢀhydroperoxides, bis(1ꢀhydroperoxycycloalkyl) and bis(1ꢀhydroperoxyalkyl) peroxides,
dispiroꢀ and tetraalkylꢀ1,2,4,5ꢀtetroxanes.
In recent years, the enhanced interest of chemists arose
in organic bisꢀhydroperoxides and 1,2,4,5ꢀtetroxanes reꢀ
lated to the high pharmacological activity of the latter, in
particular, an antimalarial activity.2—9
ethers 4 and 5 (Scheme 1); for acetophenone, αꢀtetralone,
and adamantanꢀ2ꢀone acetals (6a,b); 4ꢀmethylpetanꢀ2ꢀ
one (7а) and pentadecanꢀ8ꢀone (7b) ketals, and enol
ethers 8а,b.
Bisꢀhydroperoxides are usually prepared by ozoꢀ
nization of enol ethers or αꢀolefins in the presence of
H2O2,7—10 by the reaction of H2O2 with ketones in
HCO2H, EtCO2H, MeCN, and other solvents,7—11 and
by hydroperoxidation of acetals catalyzed by tungstic
acid.12 None of these methods complies with the upꢀtoꢀ
date requirements due to the low or moderate yields of
the target products, experimental complexity, and long
process durations. In addition, the selectivity of ozonizaꢀ
tion is low and its use is limited to enol ethers and olefins
that contain no other groups sensitive to ozone. Thereꢀ
fore, studies directed at the development of more perfect
approaches to organic gemꢀbisꢀhydroperoxides remain
topical.
Scheme 1
Here we report two new methods for the synthesis of
bisꢀhydroperoxides and their derivatives, viz., bis(1ꢀhydroꢀ
peroxycycloalkyl) and bis(1ꢀhydroperoxyalkyl) peroxides
and dispiroꢀ and tetraalkylꢀ1,2,4,5ꢀtetroxanes, which alꢀ
low one to prepare these compounds simpler, faster, and
in higher (or comparable) yields (70—95%) than the methꢀ
ods described previously.7—12 The methods are based on
reactions of acetals and enol ethers with H2O2 in anhyꢀ
drous ether catalyzed by BF3 complexes. We studied these
reactions for compounds obtained from the correspondꢀ
ing cycloalkanones 1, namely, acetals 2 and 3 and enol
1—5 a
b
c
d
e
f
g
h
i
n
R1
1
H
2
H
3
H
4
H
8
H
1
2
8
8
n
n
C8H17
Me C9H19 PhCH2
R = Me (2a—i, 4b,e,g,h), Et (3a,b,e, 5b,e)
R = Me (6a), Et (6b); R1 = H, R2 = CHMe2 (7a, 8a);
R1 = R2 = C6H13n (7b, 8b)
* For preliminary communication, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 650—656, March, 2004.
1066ꢀ5285/04/5303ꢀ0681 © 2004 Plenum Publishing Corporation

682
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Terent´ev et al.
Table 1. Products of BF3•OEt2ꢀcatalyzed reaction of acetals
with H2O2
The reactions were carried out at 20 °C, acetals or
a
enol ethers being gradually added to a solution of H2O2
in anhydrous diethyl ether containing a catalytic
amount (usually 0.1—0.3 equivalents) of BF3•OEt2 or
BF3•МеOH. Under these conditions with a 2.5—3ꢀfold
molar excess of H2O2, ketals and enol ethers obtained
from cyclododecanone (2е, 3е, 4е, 5е) were selectively
converted into (cyclododecylidene)bishydroperoxide (9е),
adamantanꢀ2ꢀone acetals 6a,b were transformed into
bis(2ꢀhydroperoxyadamantanꢀ2ꢀyl) peroxide (10), and
ether 4е gave bis(1ꢀhydroperoxycyclododecyl) peroxide
(12е) (Scheme 2). Acetals of adamantanꢀ2ꢀone (6а),
2ꢀnonylcyclododecanone (2h), and 5—8ꢀmembered
cycloalkanones (2а—d,f, 3a,b) and enol ethers derived
from 5—8ꢀmembered cycloalkanones (4b,g, 5b),
4ꢀmethylpentanꢀ2ꢀone (8a), and pentadecanꢀ8ꢀone (8b)
can selectively be transformed into the corresponding
bis(hydroperoxides) (11, 9а—d, 9f—h, 13a,b) only in the
presence of a 7—8ꢀfold excess of H2O2. This approach
allowed the preparativeꢀscale synthesis of a dozen of bisꢀ
hydroperoxides in yields from 48 to 95% (Tables 1 and 2);
almost half of these compounds have not been described
previously.
Run
Acetalb
Acetal :
: Н2О2
BF3•ОEt2
/equiv.
Product
yield
(%)
(method)c
1
1 : 2.5
0.2 (А)
9а (60),
12a (30—32)
9a (79)
2
3
1 : 8
1 : 3
0.4 (B)
0.2 (A)
9b (62—65),
12b (25)
4
5
6
1 : 2.5
1 : 3
1 : 8
0.2d (A) 9b (61), 12b (29)
0.3 (A)
0.3 (B)
9b (30), 12b (59)
9b (86)
7
1 : 7
0.3 (A)
9c (80)
8
9
1 : 2.5
1 : 7
0.2 (B)
0.3 (B)
9d (9), 12d (59)
9d (71)
10
11
1 : 2.5
1 : 2.5
0.2 (C)
0.2d (C) 9е (91)
9е (92—95)
Scheme 2
12
13
1 : 7
0.4 (B)
0.2 (B)
9f (77)
1 : 1.5
9g (70), 12g (15),
14g (6)
14
15
1 : 3
1 : 8
0.2 (B)
0.2 (B)
9h (19), 1h (70)
9h (64)
16
17
1 : 8
1 : 3
0.2 (B)
0.15 (A) 10 (64)
11 (84)
18
19
1 : 2.5
1 : 8
0.3 (A)
0.2 (B)
12a (54), 15a (11)
12a (78)
20
21
22
1 : 3
1 : 3
1 : 8
0.3 (A)
0.4 (A)
0.2 (B)
12b (44), 15b (22),
16b (19)
12b (32), 15b (16),
16b (27)
12b (48)
a Et2O (40—70 mL) as the solvent, ~20 °C, 1—2 h.
b R = Me (2, 6a), Et (3, 6b).
R1 = H, R2 = CHMe2 (7a, 8a, 13a); R1 = R2 = C6H13n (7b, 8b, 13b)
c Methods A, B, and C are described in the Experimental.
d Catalyzed by BF3•MeOH.
Reagents and conditions: a. Et2O, H2O2 (2.5—3 equiv.),
BF3•Et2O (МеOH) (0.1—0.3 equiv.), ~20 °C, 1—3 h; b. Et2O,
H2O2 (7—8 equiv.), BF3•Et2O (0.2—0.4 equiv.), ~20 °C, 1 h;
c. Et2O, H2O2 (1 equiv.), BF3•Et2O (1 equiv.), ~20 °C, 15
min; (for the indices of compounds 9a—h, see Scheme 1).
The reactions of the majority of enol ethers and acꢀ
etals studied with a less than a sevenꢀfold molar excess of

Synthesis of peroxides from acetals and enol ethers
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
683
Table 2. Products of the BF3•OEt2ꢀcatalyzed reaction of enol
ethers (EE) 4, 5, and 8 with H2O2
acetals 2g and 7b and enol ethers 4g and 8а,b, in adꢀ
dition to expected bisꢀhydroperoxides 9g and 13а,b,
bis(1ꢀhydroperoxyꢀ2ꢀmethylcyclohexyl) peroxide (12g),
and bis(hydroperoxyalkyl) peroxides 15а,b, the reactions
give dispirotetroxane 14g and tetraalkyltetroxanes 16а,b
in yields of 6, 44, and 19—51%, respectively (Scheme 3,
see Tables 1 and 2).
The ratio of bisꢀhydroperoxides to their derivatives
changes in favor of the latter with an increase in the
catalyst concentration (see Table 1, runs 3 and 5, 20
and 21), which attests indirectly that the BF3•OEt2 and
BF3•МеOH complexes catalyze both the transformation
of acetals and enol ethers into bisꢀhydroperoxides and the
further transformation of bisꢀhydroperoxides into their
derivatives. The experimental proof of this assumption
carried out for bisꢀhydroperoxide 13a confirmed that
BF3•OEt2 does actually catalyze its conversion into perꢀ
oxide 15a and tetroxane 16a.
The optimum amount of the catalyst with respect to
acetal or enol ether is 0.1—0.2 moles, as shown for
hydroperoxidation of acetal 2е and enol ether 5е. The
BF3•OEt2 and BF3•МеOH complexes catalyze these reꢀ
actions with approximately equal efficiencies; the reacꢀ
tions involve apparently the intermediate formation of
boronꢀtrifluoride complexes of acetals and H2O2 adducts
with enol ethers (Scheme 4).
a
Enol
etherb
EE : Н2О2 BF3•ОEt2
/equiv.
Product
yield
(%)
(method)c
1 : 3
1 : 3
1 : 3e
1 : 7
0.3 (A)
0.3d (A)
0.3 (B)
0.2 (B)
9b (49), 12b (24)
9b (55), 12b (29)
9b (55)
9b (76ꢀ83)
1 : 2.5
1 : 2.5
1 : 2.5
1 : 2.5e
1 : 2.5
1 : 1
1 : 1
1 : 7
1 : 3
1 : 3
0.05 (C)
0.1 (C)
0.2 (C)
0.3 (C)
0.5 (C)
0.6 (C)
1.0 (A)
0.3 (C)
0.1f (C)
0.2g (C)
0.4d (C)
9e (71)
9e (86)
9e (89)
9e (79)
9e (93)
9e (7), 12e (52)
12е (50)
9e (99)
9e (20)
9e (68)
1 : 3
9e (90)
1 : 2.5
1 : 7
0.2 (A)
0.3 (B)
9g (71), 12g (12),
14g (6)
9g(79)
1 : 7
0.3 (B)
9h (64)
It is noteworthy that the new methods of synthesis of
bisꢀhydroperoxides and their derivatives are inapplicable
to acetals and enol ethers obtained from arylꢀsubstituted
acetones (acetophenone, αꢀtetralone, and 2ꢀbenzylcycloꢀ
dodecanone (1i)), apparently, because they cannot form
boron trifluoride complexes upon ligand exchange with
boronꢀtrifluoride etherate.
1 : 3
1 : 2.5
1 : 8
0.3 (A)
0.3 (B)
0.3 (B)
12a (73), 15a (15)
15a (16),
12a (81), 16a (44)
1 : 3
0.2 (A)
12b (55), 15b (29),
16b (51)
12b (64)
The structures of bisꢀhydroperoxides and their derivaꢀ
1
tives were determined on the basis of H and 13C NMR
1 : 2.5
1 : 8
0.15 (B)
0.3 (B)
spectra, in particular, from the presence of signals with
δC 111—122 typical of an sp3ꢀhybridized carbon atom
bearing two oxygen functions and the correspondence of
these spectra to published data. The presence of hydroꢀ
peroxide groups in products 9—13 and 15 also followed
from the IR absorption band at 3210—3429 cm–1 typical
of these groups. The structure of bisꢀhydroperoxide 9e
was proved unambiguously by Xꢀray diffraction (Fig. 1).
The principal geometric parameters are listed in Table 3.
A specific feature of the crystal structure of this comꢀ
pound is layered packing in which the molecules of 9е are
connected by intermolecular hydrogen bonds.
Bisꢀhydroperoxides 9a—h, 11, and 13a,b are fairly
stable at room temperature, their stabilities increase with
the increase in the molecular mass. Thus 9е and 9h can be
stored at room temperature without noticeable decompoꢀ
sition for 6 months, while 9с and 11 are stable for
3—4 months when stored at –5—0 °C, while the halfꢀlife
of 9а is about a month even when kept in the cold. The
stabilities of bis(1ꢀhydroperoxycycloalkyl) peroxides 10
15b (8)
a Et2O (40—70 mL) as the solvent, ~20 °C, 0.5—1 h.
b R = Me (4b,e), Et (5b,e).
c The variants of the workup of the reaction mixture A, B, and C
are described in the Experimental.
d Catalyzed by BF3•MeOH.
e The reaction was carried out at 0 °C.
f Catalyzed by H2SO4.
g Catalyzed by TsOH.
H2O2 afforded not only the expected bisꢀhydroperoxides,
but also their derivatives, namely, bis(1ꢀhydroperoxyꢀ
cycloalkyl)ꢀ and bis(1ꢀhydroperoxyalkyl) peroxides and
dispiroꢀ and tetraalkylꢀ1,2,4,5ꢀtetroxanes. Indeed, with a
1.5ꢀ to 3ꢀfold molar excess of H2O2, acetals 2а,b,d, 3а,b,
and 7а and enol ether 5b give rise to bisꢀhydroperoxides
9a,b,d and 13а, bis(hydroperoxycycloalkyl) peroxides
12a,b,d, and bis(2ꢀhydroperoxyꢀ4ꢀmethylpentanꢀ2ꢀyl)
peroxide 15а in an overall yield of 73—92%. In the case of

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Terent´ev et al.
Scheme 3
Reagents and conditions: Et2O, Н2О2 (2.5—3 equiv.), BF3•Et2O (МеОН) (0.1—0.3 equiv.), ~20 °С, 1—3 h.
Scheme 4
and 12, bis(1ꢀhydroperoxyalkyl) peroxides 15a,b, and
tetraalkylꢀ1,2,4,5ꢀtetroxanes 16a,b vary in a similar way.
The presence of acid admixtures sharply decreases the
stabilities of both bisꢀhydroperoxides and their derivaꢀ
tives. It is significant that bisꢀhydroperoxides 9, 11, and 13
and their derivatives 10, 12, and 14—16 are shockꢀ and
scratchꢀsensitive and require careful handling. Dispiroꢀ
tetroxane 14g and tetraalkyltetroxanes 16a,b decompose
with explosion on heating to ≥100 °C.
Thus, this study dealing with the reactions of acetals
and enol ethers with H2O2 catalyzed by boron trifluoride
complexes resulted in the development of two new methꢀ
ods for the synthesis of aliphatic and alicyclic bisꢀhydropꢀ
eroxides and their derivatives, namely, bis(1ꢀhydroꢀ
peroxycycloalkyl) and bis(1ꢀhydroperoxyalkyl) peroxides
and dispiroꢀ and tetraalkylꢀ1,2,4,5ꢀtetroxanes. The most
important advantages of the new methods over the known
C(4)
C(5)
O(4)
C(3)
C(2)
C(1)
C(6)
O(3)
O(1)
C(7)
C(8)
C(12)
C(11)
O(2)
C(9)
C(10)
Fig. 1. Molecular structure of compound 9е.

Synthesis of peroxides from acetals and enol ethers
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
685
Table 3. Selected bond lengths (d) and bond angles (ω) in peroxide 9е
Bond
d/Å
Bond
d/Å
Angle
ω/deg
O(1)—C(1)
O(1)—O(2)
O(3)—C(1)
O(3)—O(4)
C(1)—C(2)
C(1)—C(12)
C(2)—C(3)
C(3)—C(4)
C(4)—C(5)
C(5)—C(6)
C(6)—C(7)
C(7)—C(8)
C(8)—C(9)
C(9)—C(10)
C(10)—C(11)
C(11)—C(12)
C(2)—H(2A)
C(2)—H(2B)
C(3)—H(3A)
C(3)—H(3B)
1.4368(16)
1.4572(14)
1.4099(17)
1.4655(15)
1.5187(19)
1.5209(18)
1.533(2)
1.532(2)
1.522(3)
1.526(2)
1.522(3)
1.529(3)
1.528(2)
1.527(2)
1.531(2)
1.527(2)
1.00(2)
C(4)—H(4A)
C(4)—H(4B)
C(5)—H(5A)
C(5)—H(5B)
C(6)—H(6A)
C(6)—H(6B)
C(7)—H(7A)
C(7)—H(7B)
C(8)—H(8A)
C(8)—H(8B)
C(9)—H(9A)
C(9)—H(9B)
C(10)—H(10A)
C(10)—H(10B)
C(11)—H(11A)
C(11)—H(11B)
C(12)—H(12A)
C(12)—H(12B)
O(2)—H(2O)
O(4)—H(4O)
1.02(2)
1.01(2)
0.98(2)
1.00(2)
0.93(2)
1.01(2)
1.00(2)
0.99(2)
0.94(2)
0.98(2)
0.98(2)
1.06(2)
1.00(2)
0.91(2)
0.93(2)
0.98(2)
0.964(17)
1.035(19)
0.87(2)
0.83(2)
O(1)—C(1)—C(2)
O(1)—C(1)—O(3)
O(1)—C(1)—C(12)
O(3)—C(1)—C(2)
O(3)—C(1)—C(12)
C(1)—O(1)—O(2)
C(1)—O(3)—O(4)
C(1)—C(2)—C(3)
102.32
110.05
112.50
114.42
102.48
110.08
109.09
114.19
C(1)—C(12)—C(11) 114.63
C(2)—C(3)—C(4)
C(3)—C(4)—C(5)
C(4)—C(5)—C(6)
C(5)—C(6)—C(7)
C(6)—C(7)—C(8)
C(7)—C(8)—C(9)
C(8)—C(9)—C(10)
112.33
114.59
114.70
114.34
114.04
114.47
113.68
C(10)—C(11)—C(12) 112.14
O(1)—O(2)—HO(2) 103.10
0.966(17)
1.02(2)
0.92(2)
methods7—12 include simplicity of the reaction procedures,
short time required (1—2 h), and higher (or comparable)
product yields (70—95%).
8,8ꢀDimethoxypentadecane (7b). Oil, b.p. 114—116 °C
(10 Torr). 1H NMR, δ: 0.87 (t, 3 H, Me, J = 7.2 Hz); 1.15—2.10
(m, 24 H, CH2, Me); 3.12 (s, 6 H, OMe).
8ꢀMethoxypentadecꢀ7ꢀene (8b). Oil, b.p. 161—165 °C
(10 Torr). 1H NMR, δ: 0.87—2.15 (m, 22 H, CH2, Me); 3.82 (s,
3 H, OМе); 4.41—4.46 (m, 1 H, CH).
Experimental
Synthesis of bisꢀhydroperoxides and their derivatives (genꢀ
eral procedure, see Tables 1 and 2). A. A solution of a acetal or
enol ether (10 mmol) in 40 mL of Et2O was added dropwise at
~20 °C over a period of ∼5 min to a stirred solution conꢀ
taining H2O2 (1.5—8 equiv.) and BF3•OEt2 or BF3•МеOH
(0.1—0.3 equiv.) in Et2O (50 mL). The reaction mixture was
stirred up to complete conversion of the acetal or enol ether
(1—2 h for acetals and 0.5—1 h for enol ethers, TLC), then
К2CO3 (2 equiv.) and water (40—50 mL) were added, the reꢀ
sulting twoꢀphase system was stirred for 0.5—1 h, and the orꢀ
ganic phase was separated. The aqueous phase was extracted
with Et2O (3×10 mL), the extracts were combined with the
organic phase, and the combined solution was dried with anꢀ
hydrous MgSO4 and concentrated. Flash chromatography of
the residue (gradient elution with a light petroleum—Et2O mixꢀ
ture with the ether content increasing from 30 to 70%) gave
target bisꢀhydroperoxides 9, 11, and 13 and their derivatives 10,
12, and 14—16.
NMR spectra were recorded on Bruker WMꢀ250
1
(250.13 МHz for H) and Bruker AMꢀ300 (75.4 МHz for 13C)
spectrometers for solutions in CDCl3. IR spectra were measured
on a URꢀ20 spectrometer (Carl Zeiss, Jena) in thin films. TLC
analysis was performed on Silufol UVꢀ254 plates. For flash chroꢀ
matography, silica gel L 40/100 µm was used.
Cycloalkanones 1а—е,g, 4ꢀmethylpentanꢀ2ꢀone, pentaꢀ
decanꢀ7ꢀone (Aldrich), acetals 6а and 7a,b, BF3•OEt2, and
BF3•МеOH (Acros) were commercial chemicals. Ketones 1f,13
1h,14 and 1i 15 were prepared by reported procedures.
The starting acetals and enol ethers were synthesized by
known methods from the corresponding ketones,16—18 and soluꢀ
tions of H2O2 in Et2O were prepared by a known procedure.19
The physical and spectral properties of known compounds correꢀ
sponded to published data;20 those for new compounds are preꢀ
sented below.
1,1ꢀDimethoxyꢀ2ꢀoctylcyclopentane (2f). Oil, b.p.
151—153 °C (10 Torr). 1H NMR, δ: 0.88 (t, 3 H, Me, J =
7.2 Hz); 1.16—1.93 (m, 21 H, CH2, CH); 3.18, 3.22 (both s,
3 H each, OMe).
B. Potassium carbonate (2 equiv.) was added to the reaction
mixture obtained according to procedure A after completion of
the conversion of the acetal or enol ether, the resulting heteroꢀ
geneous mixture was stirred for 0.5 h and filtered, and the filꢀ
trate was concentrated. Flash chromatography of the residue
gave the target bisꢀhydroperoxides and their derivatives.
C. A solution of NaOH (3 equiv.) in 30—50 mL of water was
added to the reaction mixture obtained according to proceꢀ
dure A after completion of the conversion of the acetal or enol
ether, the aqueous phase was separated and washed with Et2O
(3×15 mL) to remove organic material from the bisꢀhydroperꢀ
1,1ꢀDimethoxyꢀ2ꢀnonylcyclododecane (2h). Oil, b.p.
1
115—118 °C (0.01 Torr). H NMR, δ: 0.87 (t, 3 H, Me, J =
7.2 Hz); 1.16—1.93 (m, 39 H, CH2, CH); 3.18, 3.19 (both s,
3 H each, OMe).
2ꢀMethylꢀ1ꢀmethoxycyclohexene (4g). Oil, b.p. 61—64 °C
(10 Torr). 1H NMR, δ: 1.42—2.30 (m, 11 H, CH2, Me); 3.52 (s,
3 H, OMe).

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Terent´ev et al.
oxide Na salt. Then Et2O (50—70 mL) was added, and a 2—5%
aqueous solution of H2SO4 was added with cooling and stirring
to рH 5—6. The ethereal layer was separated, washed with water
(2×10 mL), a saturated aqueous solution of NaHCO3 (2×10 mL),
and again with water (10 mL), dried with anhydrous MgSO4,
and concentrated to give white crystals of bisꢀhydroperoxide 9е
and/or its derivative 12е containing a small amount of water.
Analytical samples were obtained by evacuation of these prodꢀ
ucts for 3—4 h (0.1 Torr) at ~20 °C.
2,2ꢀDihydroperoxyadamantane (11).8 Oil. Found (%):
C, 59.66; H, 7.98. C10H16O4. Calculated (%): C, 59.98; H, 8.05.
1
IR (NaCl), ν/cm–1: 3420 (OOH). H NMR, δ: 1.62—2.06 (m,
14 H, CH2); 9.02—9.11 (br.s, 2 H, OOH). 13C NMR, δ: 26.9,
31.1 (CH), 33.6, 36.9 (CH2), 112.9 (C).
Bis(1ꢀhydroperoxycyclopentyl) peroxide (12a).12 Oil.
Found (%): C, 51.41; H, 7.79. C10H18O6. Calculated (%):
C, 51.27; H, 7.75. IR (NaCl), ν/cm–1: 3428 (OOH). 1H NMR,
δ: 1.71—1.82 (m, 4 H, C—CH2); 1.93—2.12 (m, 4 H, CH2);
9.85—10.02 (br.s, 2 H, OOH). 13C NMR, δ: 24.5, 33.3 (CH2),
122.2 (C).
1,1ꢀDihydroperoxycyclopentane (9a).12 Oil. Found (%):
C, 44.90; H, 7.57. C5H10O4. Calculated (%): C, 44.77; H, 7.51.
1
IR (NaCl), ν/cm–1: 3420 (OOH). H NMR, δ: 1.68—1.80 (m,
Bis(1ꢀhydroperoxycyclohexyl) peroxide (12b)12,21,22. Oil.
Found (%): C, 55.13; H, 8.49. C12H22O6. Calculated (%):
4 H, CH2); 1.93—2.11 (m, 4 H, C—CH2); 9.89—9.94 (br.s, 2 H,
OOH). 13C NMR, δ: 24.6, 33.4 (CH2), 122.6 (C).
C, 54.95; H, 8.45. IR, NaCl), ν/cm–1: 3422 (OOH). H NMR
1
1,1ꢀDihydroperoxycyclohexane (9b).12 Oil. Found (%):
C, 48.95; H, 8.20. C6H12O4. Calculated (%): C, 48.64; H, 8.16.
(δ: 1.43—1.67 (m, 6 H, CH2); 1.79—1.93 (m, 4 H, C—CH2);
9.40—9.62 (br.s, 2 H, OOH). 13C NMR (δ: 22.5, 25.4, 29.9
(CH2), 111.2 (C).
1
IR, NaCl), ν/cm–1: 3424 (OOH). H NMR, δ: 1.32—1.60 (m,
6 H, CH2); 1.74—1.87 (m, 4 H, C—CH2); 9.44—9.60 (br.s, 2 H,
OOH). 13C NMR, δ: 22.3, 25.1, 29.3 (CH2), 111.0 (C).
1,1ꢀDihydroperoxycycloheptane (9с).8 Oil. Found (%):
C, 52.12; H, 8.84. C7H14O4. Calculated (%): C, 51.84; H, 8.70.
Bis(1ꢀhydroperoxycycloоctyl) peroxide (12d). Oil.
Found (%): C, 59.66; H, 7.98. C16H30O6. Calculated (%):
1
C, 60.35; H, 9.50. IR (NaCl), ν/cm–1: 3448 (OOH). H NMR,
δ: 1.52—1.69 (m, 8 H, C—CH2); 1.80—2.06 (m, 20 H, CH2);
9.48—9.60 (br.s, 2 H, OOH). 13C NMR, δ: 21.9, 24.9, 27.7, 27.9
(CH2), 115.5 (C).
Di(1ꢀhydroperoxyꢀ2ꢀmethylcyclohexyl) peroxide (12g). Oil.
Found (%): C, 65.22; H, 9.31; C14H26O6. Calculated (%):
C, 65.60; H, 9.44. IR (NaCl), ν/cm–1: 3415 (OOH). 1H NMR,
δ: 0.83—2.31 (m, 24 H, CH, CH2, Me); 9.47—9.60 (br.s, 2 H,
OOH). 13C NMR, δ: 22.0 (Me), 29.2, 30.5, 31.6, 34.0, 37.6
(CH, CH2), 111.6 (C).
1
IR (NaCl), ν/cm–1: 3429 (OOH). H NMR, δ: 1.51—1.65 (m,
8 H, CH2); 1.86—2.00 (m, 4 H, C—CH2); 9.80—9.90 (br.s, 2 H,
OOH). 13C NMR, δ: 22.5, 29.9, 32.4 (CH2), 115.8 (C).
1,1ꢀDihydroperoxycyclooctane (9d).8 Oil. IR (NaCl),
ν/cm–1: 3400 (OOH). 1H NMR, δ: 1.45—1.62 (m, 10 H, CH2);
1.78—1.99 (m, 4 H, C—CH2); 9.59—9.70 (br.s, 2 H, OOH).
13C NMR, δ: 21.7, 24.8, 27.1, 27.8 (CH2), 114.6 (C). Found (%):
C, 54.74; H, 9.18. C8H16O4. Calculated (%): C, 54.53; H, 9.15.
1,1ꢀDihydroperoxycyclododecane (9e).8,10,12 White crystals,
m.p. 138—142 °C (diethyl ether), 140—141 °C (benzene).8
Found (%): C, 62.12; H, 10.40. C12H24O4. Calculated (%):
C, 62.04; H, 10.41. IR (NaCl), ν/cm–1: 3410 (OOH). 1H NMR,
δ: 1.21—1.82 (m, 22 H, CH2); 9.98—10.04 (br.s, 2 H,
OOH). 13C NMR, δ: 20.0, 22.2, 22.5, 26.4, 26.5, 27.4 (CH2),
113.6 (C).
2,2ꢀDihydroperoxyꢀ4ꢀmethylpentane (13a). Oil. Found (%):
C, 47.70; H, 9.51. C6H14O4. Calculated (%): C, 47.99; H, 9.40.
1
IR (NaCl), ν/cm–1: 3340 (OOH). H NMR, δ: 0.92—0.99 (d,
6 H, Me); 1.46 (s, 3 H, C—Me); 1.66—1.70 (d, 2 H, CH2);
1.76—1.80 (m, 1 H, CH); 9.19—9.31 (br.s, 2 H, OOH).
13C NMR, δ: 18.0 (CH), 23.7 (2 Me), (Me), 41.1 (CH2),
112.7 (C).
1,1ꢀDihydroperoxyꢀ2ꢀoctylcyclopentane (9f). Oil. Found (%):
C, 63.49; H, 10.66. C13H26O4. Calculated (%): C, 63.38;
H, 10.64. IR (NaCl), ν/cm–1: 3428 (OOH). 1H NMR, δ:
0.86—0.91 (t, 3 H, Me); 1.15—1.33 (m, 21 H, CH, CH2);
9.63—9.70 (br.s, 2 H, OOH). 13C NMR, δ: 14.0 (Me), 21.9,
22.6, 28.1, 29.2, 29.3, 29.5, 29.7, 31.0, 31.8, 32.7 (CH2), 46.4
(CH), 121.2 (C).
8,8ꢀDihydroperoxypentadecane (13b). Oil. Found (%):
C, 65.32; H, 11.72. C15H32O4. Calculated (%): C, 65.18;
H, 11.67. IR (NaCl), ν/cm–1: 3405 (OOH). 1H NMR, δ:
0.83—0.83 (t, 6 H, Me); 1.23—1.40 (m, 20 H, CH2); 1.52—1.67
(m, 4 H, C—CH2); 9.60—9.80 (br.s, 2 H, OOH). 13C NMR, δ:
14.0 (Me), 22.6, 23.8, 29.0, 29.2, 29.6, 31.6 (CH2), 113.4 (C).
1,10ꢀDimethylꢀ7,8,15,16ꢀtetraoxadispiro[5.2.5.2]hexaꢀ
decane (14g). Oil. Found (%): C, 65.91; H, 9.50. C14H24O4.
1,1ꢀDihydroperoxyꢀ2ꢀmethylcyclohexane
(9g).
Oil.
1
Found (%): C, 52.06; H, 8.82. C7H14O4. Calculated (%):
Calculated (%): C, 65.60; H, 9.44. H NMR, δ: 0.85—0.93 (d,
1
C, 51.84; H, 8.70. IR (NaCl), ν/cm–1: 3418 (OOH). H NMR,
6 H, Me); 1.20—1.75 (m, 18 H, CH, CH2) 13C NMR, δ: 19.9
(Me), 28.9, 30.5, 31.9, 34.0 (CH2), 37.7 (CH), 113.2 (C).
Bis(2ꢀhydroperoxyꢀ4ꢀmethylpentanꢀ2ꢀyl) peroxide (15а). Oil.
Found (%): C, 53.95; H, 9.71. C12H26O6. Calculated (%):
C, 54.12; H, 9.84. IR (NaCl), ν/cm–1: 3416 (OOH). 1H NMR,
δ: 0.96 (d, 12 H, Me, J = 6.6 Hz); 1.45 (s, 6 H, CMe); 1.69 (d,
4 H, CH2, J = 5.8 Hz); 1.75—1.89 (m, 2 H, CH); 8.10—8.41
(br.s, 2 H, OOH). 13C NMR, δ: 17.8, 23.6, 24.1, 41.2 (CH,
CH2, Me), 112.2 (C).
δ: 0.89—0.94 (d, 3 H, Me); 1.33—1.71 (m, 9 H, CH, CH2);
8.72—8.83 (br.s, 2 H, OOH). 13C NMR, δ: 22.0 (Me), 29.4,
30.5, 31.5, 34.0 (CH2), 37.4 (CH), 111.5 (C).
1,1ꢀDihydroperoxyꢀ2ꢀnonylcyclododecane (9h). Oil.
Found (%): C, 69.97; H, 11.58; C21H42O4. Calculated (%):
C, 70.34; H, 11.81. IR (NaCl), ν/cm–1: 3415 (OOH). 1H NMR,
δ: 0.18—1.82 (m, 40 H, CH, CH2, Me); 8.75—9.20 (br.s, 2 H,
2 OOH). 13C NMR, δ: 14.2 (Me), 19.4, 20.0, 21.8, 22.0, 22.1,
22.2, 22.3, 22.4, 22.5, 22.8, 25.4, 26.0, 26.2, 26.5, 27.4, 29.2,
29.4, 29.8, 32.0 (CH, CH2), 115.2 (C).
Bis(8ꢀhydroperoxypentadecanꢀ8ꢀyl) peroxide (15b). Oil.
Found (%): C, 69.68; H, 12.13. C30H62O6. Calculated (%):
C, 69.45; H, 12.05. IR (NaCl), ν/cm–1: 3416 (OOH). 1H NMR,
δ: 0.83—0.97 (t, 12 H, Me); 1.21—1.44 (m, 54 H, CH2);
1.63—1.75 (m, 8 H, C—CH2); 9.59—9.64 (br.s, 2 H, OOH).
13C NMR, δ: 14.1 (Me), 22.6, 23.5, 29.0, 29.3, 29.6, 31.7 (CH2),
114.6 (C).
Bis(2ꢀhydroperoxyadamantanꢀ2ꢀyl) peroxide (10). Oil.
Found (%): C, 65.71; H, 8.17; C20H30O6. Calculated (%):
1
C, 65.55; H, 8.25. IR (NaCl), ν/cm–1: 3420 (OOH). H NMR,
δ: 1.62—2.16 (m, 28 H, CH2); 9.02—9.15 (br.s, 2 H, OOH).
13C NMR, δ: 27.2, 31.3 (CH), 33.8, 37.2 (CH2), 112.0 (C).

Synthesis of peroxides from acetals and enol ethers
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 3, March, 2004
687
3,6ꢀDiisobutylꢀ3,6ꢀdimethylꢀ1,2,4,5ꢀtetroxane (16а). Oil.
Found (%): C, 62.31; H, 10.52. C12H24O4. Calculated (%):
C, 62.04; H, 10.41. IR (NaCl), ν/cm–1: 3342 (OOH). 1H NMR,
δ: 0.96 (d, 12 H, Me, J = 6.6 Hz); 1.43 (s, 6 H, Me); 1.67 (d,
4 H, CH2, J = 5.9 Hz); 1.74—1.87 (m, 2 H, CH). 13C NMR, δ:
17.9, 23.7, 24.1, 41.3 (CH, CH2, Me), 112.7 (C).
3. C. W. Jefford, Adv. Drug Res., 1997, 29, 271.
4. Y. Dong, H. Matile, J. Chollet, R. Kaminsky, J. K. Wood,
and J. L. Vennerstrom, J. Med. Chem., 1999, 42, 1477.
5. H.ꢀS. Kim, Y. Shibata, Y. Wataya, K. Tsuchiya,
A. Masuyama, and M. Nojima, J. Med. Chem., 1999,
42, 2604.
3,3,6,6ꢀTetraheptylꢀ1,2,4,5ꢀtetroxane (16b). 1H NMR, δ:
0.84—0.93 (t, 12 H, Me); 1.22—1.43 (m, 54 H, CH2); 1.52—1.71
(m, 8 H, C—CH2). 13C NMR, δ: 14.0 (Me), 22.6, 23.5, 29.0,
29.5, 29.6, 31.7 (CH2), 114.7 (C).
Transformations of bisꢀhydroperoxide 13a on treatment with
BF3•OEt2. A solution of 13а (1 mmol) and BF3•OEt2
(0.2 mmol) in ether (10 mL) was stirred for 15 min at ~20 °C.
After the workup and analysis of the reaction mixture carried
out by procedure А, unchanged bisꢀhydroperoxide (0.4 mmol)
and approximately equal amounts of peroxide 15а and tetroxane
16а were identified. Under analogous conditions in the absence
of BF3•OEt2, the transformation of 13а into 15а and 16а did
not take place.
XꢀRay diffraction analysis of 1,1ꢀdihydroperoxycyclododecane
(9e). The crystals of compound 9e (C12H24O4) are orthorhomꢀ
bic. At 170 K, a = 5.9243(14), b = 13.211(3), c = 16.271(3) Å,
V = 1273.5(5) Å3, dcalc = 1.212 g cm–3, µ = 0.089 mm–1, space
group P212121, Z = 4.
The intensities of the 2160 independent reflections were meaꢀ
sured on a Syntex P21 fourꢀcircle diffractometer (λ(MoꢀKα) =
0.71073 Å, graphite monochromator, θ/2θ scan mode, 2θmax 60°,
completeness of the collected reflections 100%) equipped with a
lowꢀtemperature nitrogen attachment. The reflection intensities
were corrected using Lorentzian and polarization factors. No
absorption corrections were applied.
The structure of molecule 9е (see Fig. 1) was solved by the
direct method. The nonhydrogen atoms were refined by the fullꢀ
matrix leastꢀsquares method over F 2 in the anisotropic approxiꢀ
mation. The hydrogen atoms were located from the difference
Fourier synthesis and refined isotropically. The final Rꢀfactors
were R1 = 0.035 (calculated over F for 1875 reflections with
I > 2σ(I )), wR2 = 0.087 (calculated over F 2 for all the 2160 reꢀ
flections involved in the final refinement stage), the number of
refined parameters was 241, GOOF 0.968. All calculations were
carried out using the SHELXTLꢀ97 program package.23 The
crystal data and structure refinement parameters of compound
9е are deposited with the Cambridge Structural Database.
6. H.ꢀS. Kim, K. Tsuchiya, Y. Shibata, Y. Wataya, Y. Ushigoe,
A. Masuyama, M. Nojima, and K. McCullough, J. Chem.
Soc., Perkin Trans. 1, 1999, 1867.
7. K. Tsuchiya, Y. Hamada, A. Masuyama, M. Nojima, K. J.
McCullough, H.ꢀS. Kim, Y. Shibata, and Y. Wataya, Tetraꢀ
hedron Lett., 1999, 40, 4077.
8. H.ꢀS. Kim, Y. Nagai, K. Ono, K. Begum, Y. Wataya,
Y. Hamada, K. Tsuchiya, A. Masuyama, M. Nojima, and
K. McCullough, J. Med. Chem., 2001, 44, 2357.
9. Y. Hamada, H. Tokuhara, A. Masuyama, M. Nojima, H.ꢀS.
Kim, K. Ono, N. Ogura, and Y. Wataya, J. Med. Chem.,
2002, 45, 1374.
10. T. Ledaal and T. Solbjor, Acta Chem. Scand., 1967, 21, 1658.
11. H. Kropf, in Methoden der organische Chemie (HoubenꢀWeyl),
Ed. H. Kropf, Bd. E13, Part 1, 1988, 548.
12. C. W. Jefford, Synth. Comm., 1990, 20, 2589.
13. G. V. Somov, Ph.D. Thesis, D. I. Mendeleev Moscow Instiꢀ
tute of Chemical Technology, Moscow, 1962 (in Russian).
14. L. I. Zakharkin, I. M. Churilova, and U. V. Anikina, Izv.
Akad. Nauk SSSR. Ser. Khim., 1990, 1089 [Bull. Acad. Sci.
USSR, Div. Chem. Sci., 1990, 39, 976 (Engl. Transl.)].
15. F. Elsinger, in Org. Synth., Ed. H. Baumgarten, Wiley, New
York, 1973, Coll. Vol. 5, 76.
16. WeygandꢀHilgetag, Organischꢀchemische experimentier kunst.
Herstellung von Acetalen, 3 Aufg., Eds. G. Hilgetag and
A. Martini, Ambrosius Barth Verlag, Leipzig, 1964.
17. Organikum. Organischeꢀchemisches Grundpraktikum, Reacꢀ
tions of Carbonyl Compounds, 18 Aufg., VEB Deutscher Verlag
Wissenschaften, Berlin, 1990, Ch. 7.
18. H. Meerwein, in Methoden der organische Chemie (Houbenꢀ
Weyl), Ed. E. Muller, Thieme Verlag, Stuttgart, 1965,
Bd. VI/3, p. 199.
19. I. Saito, R. Nagata, K. Yuba, and T. Matsuura, Tetrahedron
Lett., 1983, 24, 1737.
20. Dictionary of Organic Compounds, Ed. 5, Chapman&Hall,
New York—London—Toronto, 1982, 1—7; 1983—1988,
Supll. 1—6.
21. V. L. Antonovskii, Zh. Prikl. Khim., 1967, 40, 2555 [J. Appl.
Chem. USSR, 1967, 40 (Engl. Transl.)].
This work was carried out with the financial support of
President of the Russian Federation (Program for the
Support of Leading Scientific Schools of the Russian Fedꢀ
eration, project NSh 02121.2003.3).
22. V. L. Antonovskii, L. F. Nesterov, Kh. V. Tsubina, and I. M.
Al´shits, Uspekhi khimii organicheskikh perekisnykh soedinenii
i autookisleniya [Advances in the Chemistry of Organic Perꢀ
oxide Compounds and SelfꢀOxidation] Khimiya, Moscow,
1969, 100 (in Russian).
23. M. Sheldrick, SHELXTLꢀ97, Program for Solution and Reꢀ
finement of Crystal Structure, Bruker AXS Inc., Madison
(WIꢀ53719, USA), 1997.
References
1. A. O. Terent´ev, A. V. Kutkin, M. M. Platonov, Yu. N.
Ogibin, and G. I. Nikishin, Tetrahedron Lett., 2003, 44, 7359.
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Wood, S. L. Andersen, L. Gerena, and W. K. Milhous,
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Received December 4, 2003;
in revised form January 26, 2004