Synthesis of 1-hydroperoxy-1′-alkoxyperoxides by the iodine-catalyzed reactions of geminal bishydroperoxides with acetals or enol ethers

Article abstract of DOI:10.1039/b809661a

It was found that iodine-catalyzed reactions of geminal bishydroperoxides with acetals proceed with the replacement of only one alkoxy group by the peroxide group to give previously unknown structures of 1-hydroperoxy-1′- alkoxyperoxides in yields up to 64%. The same compounds are formed in the iodine-catalyzed reactions of geminal bishydroperoxides with enol ethers. The nature of the solvent has a decisive influence on the formation of 1-hydroperoxy-1′-alkoxyperoxides. In the series of Et₂O, THF, EtOH, CHCl₃, CH₃CN, and hexane, the best results were obtained with the use of Et₂O or THF as the solvent.

Full text of DOI:10.1039/b809661a

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Synthesis of 1-hydroperoxy-1¢-alkoxyperoxides by the iodine-catalyzed
reactions of geminal bishydroperoxides with acetals or enol ethers†
Alexander O. Terent’ev,*a Maxim M. Platonov,a Igor B. Krylov,a Vladimir V. Chernyshevb,c and
Gennady I. Nikishina
Received 9th June 2008, Accepted 1st September 2008
First published as an Advance Article on the web 20th October 2008
DOI: 10.1039/b809661a
It was found that iodine-catalyzed reactions of geminal bishydroperoxides with acetals proceed with the
replacement of only one alkoxy group by the peroxide group to give previously unknown structures of
1-hydroperoxy-1¢-alkoxyperoxides in yields up to 64%. The same compounds are formed in the
iodine-catalyzed reactions of geminal bishydroperoxides with enol ethers. The nature of the solvent has
a decisive influence on the formation of 1-hydroperoxy-1¢-alkoxyperoxides. In the series of Et2O, THF,
EtOH, CHCl3, CH3CN, and hexane, the best results were obtained with the use of Et2O or THF as the
solvent.
distinguishing feature of this reaction is that only one alkoxy
Introduction
group of acetals is replaced by the peroxide group under the
In the last decade, organic peroxides have attracted great attention
conditions used. This result is unexpected and differs from the
of chemists and researchers engaged in drug design due to
results obtained in our earlier studies, where the boron trifluoride-
catalyzed reaction of gem-bishydroperoxides and related 1,1¢-
their high antimalarial1–3 and antitumor4 activities. Tetraoxanes,
ozonides, and trioxanes having activity5 comparable to or higher
dihydroperoxyperoxides with acetals in diethyl ether has been
than the activity of artemisinin, which is the natural peroxide used
demonstrated to proceed with the replacement of both alkoxy
for the treatment of malaria, have been synthesized.
groups accompanied by the formation of cyclic products, such as
tetraoxanes12 and hexaoxonanes13 (Scheme 1).
Organic peroxides hold a leading position as radical polymeriza-
tion initiators in the industrial synthesis of such polymer materials
as polyacrylates, polystyrene, styrene-containing resins, and high-
pressure polyethylene and have found use as cross-linking reagents.
Geminal bishydroperoxides belong to a relatively new and
important class of organic peroxides. In the last two decades,
there has been considerable progress in the development of
methods for the preparation and the use of these compounds.6–8
Geminal bishydroperoxides containing six or more carbon atoms
are the key compounds in the synthesis of a wide range of
cyclic peroxides1–5 having antimalarial and antitumor activities
and can be used as oxidants9 or radical polymerization initiators.10
The easily accessible (unlike its high-molecular-weight analogs)
geminal bishydroperoxide methyl ethyl ketone peroxide (MEKPO)
is widely used in the manufacturing process of acrylic resins, as a
hardening agent for fiberglass reinforced plastics, and as a curing
agent for unsaturated polyester resins.11
An idea of combining iodine with hydroperoxides or hydrogen
peroxide proved to be successful. In recent years, this idea has
been advantageously realized in the synthesis of peroxides from
carbonyl compounds8 and alkenes.14 The I2-H2O2 system reveals
versatile reactivities. Thus, depending on the reaction conditions,
hydrogen peroxide involved in this system can act not only as the
reagent for the formation of the C–O–O fragment but also as an
activator for iodine in iodoalkoxylation of alkenes15 and iodination
of arenes,16 ketones,17 and alkynes.18 This system was also used for
the Baeyer–Villiger oxidation of ketones to lactones.19
The transformation of bishydroperoxides, acetals, and enol
ethers discovered in the present study is a new step in the
development of methods for the synthesis of compounds con-
taining the monoperoxyacetal fragment, which is of importance
for the antimalarial activity of artemisinin and ozonides. 1-
Hydroperoxy-1¢-alkoxyperoxides are of interest as intermediates
in the synthesis of structurally more complex peroxides because
they contain the following two active centers, whose reactivity is
well known: the nucleophilic bishydroperoxide center (containing
the free hydroperoxide group)3,20 and the “latent” electrophilic
monoperoxyacetal center.21 In addition, it is known that com-
pounds containing the monoperoxyketal fragment are convenient
radical reaction initiators.22
In the present study, we report a new transformation of gem-
inal bishydroperoxides, to be more precise, the iodine-catalyzed
reaction with acetals and enol ethers giving rise to previously
unknown structures of 1-hydroperoxy-1¢-alkoxyperoxides. The
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of
Sciences, 47 Leninsky prosp., 119991, Moscow, Russian Federation. E-mail:
terentev@ioc.ac.ru; Fax: +7 (499) 1355328
bDepartment of Chemistry, Moscow State University, 119992, Moscow,
Russian Federation
Results and discussion
cA.N. Frumkin Institute of Physical Chemistry and Electrochemistry,
Leninsky prospect 31, 119991, Moscow, Russian Federation
Peroxides 3c-f, 4a-e, 5a-c, and 6a,d were synthesized at 20–25 ◦C
by the addition of iodine as the reaction catalyst to a solution
of geminal bishydroperoxide 1a-d and acetal 2a-f. The reaction
mixture was kept for 24 h (Scheme 2).
† Electronic supplementary information (ESI) available: 1H and 13C NMR
spectra for peroxides 3c-f, 4a-e, 5a-c, 6a,d. CCDC reference number
689447]. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/b809661a
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Scheme 1 Boron trifluoride- and iodine-catalyzed reactions of acetals with bis- and dihydroperoxides.
Scheme 2 Synthesis of peroxides 3–6 by the iodine-catalyzed reaction of geminal bishydroperoxides 1 with acetals 2. Using the synthesis of peroxide 4e
as an example, the optimal conditions of this reaction, such as the ratio of 1b, 2e, and iodine, the reaction time, and the nature of the solvent, were found
(Table 1).
As can be seen from Table 1, the nature of the solvent has a
decisive influence on the condensation of bishydroperoxide 1b with
acetal 2e. The best results were obtained with the use of diethyl
ether as the solvent (runs 7–13). The reactions in tetrahydrofuran
(runs 5 and 6) are somewhat less efficient. In chloroform, hexane,
acetonitrile, and methanol (runs 1–4), the yields of the target
peroxide are 2–5 times lower (10–34%) than those achieved in
diethyl ether (60%). The reaction time is an important factor. For
example, the reaction is completed in 24 h at 20 ◦C; after 1 h the
conversion of the reagents is ca. 25%. An increase in the time of
storage of the reaction mixture to 48 h has virtually no effect on
the results.
The optimal iodine-to-acetal 2e ratio is evidently close to 0.4.
A decrease (runs 7–9) or an increase (runs 14 and 15) in this ratio
has a negative effect on the yield of peroxide 4e.
An attempt to prepare peroxide 4e directly from cycloheptanone
and, by this means, to eliminate the additional step involving the
synthesis of 1,1-dimethoxycycloheptane 2e failed. The reaction of
bishydroperoxide 1b with cycloheptanone in MeOH (run 16) and
in a MeOH-Et2O mixture (run 17) affords peroxide 4e in low yield
(6–8%). Hence, this procedure is unsuitable for the preparative
synthesis because it produces the target peroxide 4e in low yield.
Diethyl ether not only serves as the solvent but, judging from
the results, is also involved in the chemical reaction acting as an
activator for iodine. Other tested solvents exhibit this property to
a lesser extent (tetrahydrofuran), if at all.
The reaction giving rise to peroxide 4e proceeds through the
iodine-catalyzed replacement of the methoxy group in acetal
(Scheme 3).
Initially, iodine, which exists apparently as a complex with
diethyl ether (or tetrahydrofuran)23 where it behaves as a Lewis
acid, reacts with the methoxyl group of acetal 2e. Then gem-
inal bishydroperoxide attacks the electrophilic center that is
formed at the quaternary carbon atom. Finally, methanol is
eliminated to give the target peroxide 4e. The reaction stops with
the monosubstitution stage presumably as the result of steric
strain arising from 1,2,4,5-tetraoxane (disubstitution product)
forming.
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Scheme 3 Iodine-catalyzed reaction of acetal 2e with bishydroperoxide 1b in diethyl ether.
Table 1 Influence of the molar ratio of the reagents, the reaction time,
Table 2 Structures and yields of peroxides 3–6a
and the nature of the solvent on the yield of 4ea
Run
1
Structures of 3–6, yield%.b
Run
2
Structures of 3–6, yield%.b
3c, 48
3d, 45, 40c
3
4
Molar ratio
I2/2e
Molar ratio
1b/2e
Yield of
Run
Solvent
4e,%b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
CHCl3
Hexane
MeOH
CH3CN
THF
THF
Et2O
Et2O
Et2O
Et2O
Et2O
0.4
0.4
0.5
0.5
0.5
1.1
0.1
0.2
0.4
0.4
0.4
0.4
0.4
1.1
1.1
0.5
0.5
1
1
1
1
1
1
1
1
10c
34c
16c
10c
44
31
21
37
49
44
60
21d
59e
24
24
8c
3e, 64, 61c
3f, 61
5
7
9
6
8
4a, 54
4b, 55
1
0.8
1.2
1.2
1.2
1.2
0.8
1
Et2O
Et2O
Et2O
4c, 59
4d, 54, 53c
Et2O
MeOHf
MeOH-Et2Og
10
1
6
a Reaction conditions: I2 (0.13–0.35 g, 0.5–1.38 mmol) was added to a
solution of bishydroperoxide 1b (0.16–0.24 g, 1.00–1.50 mmol), and acetal
2e (0.2 g, 1.25 mmol) in Et2O, THF, MeOH, CHCl3, CH3CN, or hexane
(4 mL), and the reaction mixture was kept for 24 h. b The yield based on
the isolated product. c Iodocycloheptanone as the by-product; the yield
was 23% (run 1), 30% (run 2), 29% (run 3), 18% (run 4), and 17% (run 16).
d The reaction time was 1 h. e The reaction time was 48 h. f The reaction
of 1b with cycloheptanone in MeOH (4 mL). g The reaction of 1b with
cycloheptanone in MeOH (2 mL) + Et2O (2 mL).
4e, 60, 60c
5a, 64, 57d
11
13
12
14
5b, 63
5c, 62
Taking into account the conditions used for the synthesis of
4e (Table 1), we prepared peroxides 3–6 in yields from 45 to 64%
by the reaction of cyclic bishydroperoxides 1 (C6, C7, and C12)
with acetals generated from cyclic ketones 2c-f (C5, C6, and C7)
and linear ketones 2a and 2b (acetone and methyl heptyl ketone)
(Table 2).
It should be noted that the yield of peroxides depends only
slightly on the structures of the reagents, due to which the
results of application of this reaction to other structurally similar
compounds are predictable.
6a, 51, 57d
6d, 50, 53c, 59d
a Reaction conditions: I2 (0.13 g, 0.5 mmol; 0.4 mol/1 mol 2) was added to
a solution of bishydroperoxide 1 (1.5 mmol; 1.2 mol/1 mol 2) and acetal
2 (1.25 mmol) in Et2O (4 mL), and the reaction mixture was kept for 24 h.
b The yield based on the isolated product. c The yield in the reaction with 1-
methoxycyclohexene and 1-methoxycycloheptene under the same reaction
conditions. d The yield in the reaction with the use of THF as the solvent.
The reactions with the use of enol ethers 7 and 8 instead of
related acetals 2d and 2e afford the target peroxides 3d,e, 4d,e, and
6d in the same yields (Table 2, Scheme 4).
The reaction of bishydroperoxides with enol ethers is probably
catalyzed by HI formed in a little amount as the result of
interaction of iodine and bishydroperoxide.
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(10–20 Torr), the products contained a few weight percents of
iodine, but they were visually colorless. Apparently, peroxides and
iodine form rather strong complexes, in which the iodine molecule
is coordinated by the hydroperoxide and alkoxy groups. Similar
complexes of iodine with ethers were documented.23 The complete
removal of residual iodine (determined by elemental analysis) was
achieved after storage of peroxides under a vacuum of ~ 0.1–
0.5 Torr for one hour.
Scheme 4 Iodine-catalyzed synthesis of peroxides 3d,e, 4d,e, and 6d from
bishydroperoxides 1a, b, d and enol ethers 7 and 8.
Conclusions
The structures of peroxides 3–6 were established by NMR
spectroscopy and elemental analysis. The 13C NMR spectra
of peroxides show signals at 105–117 ppm characteristic of
monoperoxyacetal and bisperoxide fragments. The signals for
the protons of the OOH groups in the 1H NMR spectra are
observed at 9.7–10.2 ppm, which is consistent with the spectra
of structurally related 1,1-bishydroperoxycycloalkanes and 1,1¢-
dihydroperoxy(dicycloalkyl)peroxides.7,8,13 Compounds 4a-e were
Previously unknown 1-hydroperoxy-1¢-alkoxyperoxides were syn-
thesized in 45–64% yield by the iodine-catalyzed reaction of
geminal bishydroperoxides with acetals and enol ethers. The nature
of the solvent has a decisive influence on the yield of the target
peroxides. Good results were obtained in the reactions performed
in Et2O and THF. Under the optimal conditions, no replacement
of the second alkoxy group giving rise to cyclic peroxides
was observed. 1-Hydroperoxy-1¢-alkoxyperoxides can easily be
isolated from the reaction mixture by column chromatography.
1
synthesized as mixtures of diastereomers. The H NMR spectra
show twice the number of signals for the protons of the OOH
groups, and the 13C NMR spectra have twice the number of signals
with similar chemical shifts.
Experimental
The molecular structure of 6d (CCDC 689447) drawn with
ORTEP-III24 is presented in Fig. 1.
The NMR spectra were recorded on Bruker AC-200 (200.13 MHz
1
for H) and Bruker AM-300 (75.4 MHz for 13C) spectrometers
in CDCl3. The TLC analysis was carried out on Silufol UV-254
chromatographic plates. Flash chromatography was performed
on silica gel L 40/100 mm. Melting points were determined on
a Kofler hot stage. MeOH, Et2O, CH3CN, CHCl3, hexane, I2,
Na2S2O3, and MgSO4 of high-purity grade were home made.
Geminal bishydroperoxides were synthesized according to the
procedures described earlier.7,8 Acetals and enol ethers were
prepared according to a known procedure.28
Determination of the influence of the molar ratio of the reagents,
the reaction time, and the nature of the solvent on the yield of 4e
(Table 1, runs 1–15)
Fig. 1 Molecular structure of 6d.
Iodine (0.13–0.35 g, 0.5–1.38 mmol) was added to a solution of
bishydroperoxide 1b (0.16–0.24 g, 1.00–1.5 mmol) and acetal 2e
(0.2 g, 1.25 mmol) in Et2O, THF, MeOH, CHCl3, CH3CN, or
hexane (4 mL). The reaction mixture was kept at 20–25 ◦C for 1, 24,
or 48 h. Then hexane (30 mL) and a 2–5% Na2S2O3 solution were
added. The mixture was stirred until it became almost colorless
and then was washed with water (3 ¥ 5 ml). The organic layer
was dried with MgSO4 and filtered. The filtrate was concentrated
to the volume of approximately 1 mL. Peroxide 4e was isolated
by silica gel column chromatography using gradient elution in a
hexane–diethyl ether mixture, the ratio being changed from 20:1
to 7:1 (v/v).
All bond lengths and bond angles in 6d have typi-
cal values and are comparable with those observed in two
related compounds, 1,1-bis(hydroperoxy)cyclododecane25 and
1,1¢-dihydroperoxy-1,1¢-bis(cyclododecyl)peroxide.26 The hydroxy
group is involved in intramolecular O5-H5 ◊ ◊ ◊ O1 hydrogen bond-
˚
˚
ing (D ◊ ◊ ◊ A, H ◊ ◊ ◊ A, and D–H ◊ ◊ ◊ A are 2.763(4) A, 2.08 A, and
141 ◦, respectively). In the crystal, there are no intermolecular
˚
H ◊ ◊ ◊ O contacts shorter than 2.75 A. Hence, the crystal packing
is typical of branched hydrocarbons, with hydrophobic space-
filling contacts reflecting the simple close packing of hydrophobic
molecules.27
The removal of iodine is one of the difficulties in preparing
analytically pure compounds 3–6. We found that it is convenient
to perform isolation in the following way. After completion of the
reaction, hexane and an aqueous Na2S2O3 solution were added
to the reaction mixture, and the mixture was stirred until the
organic layer became almost colorless, after which peroxides were
easily isolated by column chromatography. During this work-up of
the reaction mixture, almost no reduction of the target peroxides
occurred. After chromatographic purification and drying in vacuo
The reactions of 1b with cycloheptanone in MeOH (4 mL; run
16) and a MeOH + Et2O mixture (2 mL + 2 mL; run 17) were
carried out analogously for 24 h.
General procedure for the synthesis of peroxides 3–6 (Table 2)
Iodine (0.13 g, 0.5 mmol; 0.4 mol/1 mol 2a-f) was added to a
solution of bishydroperoxide 1a-d (1.5 mmol; 1.2 mol/1 mol 2a-f)
and acetal 2a-f (1.25 mmol) in Et2O or THF (4 mL). The reaction
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mixture was kept for 24 h. Then the reaction mixture was worked
up and the target peroxides were isolated as described above.
Compounds 3d,e 4d,e, and 6d were synthesized analogously
with the use of 1-methoxycyclohexene 7 and 1-methoxycyclo-
heptene 8.
1-(1-Ethoxycyclopentylperoxy)-1-hydroperoxy-4-methylcyclo-
hexane, 4c. Oil. Rf 0.32 (hexane:EtOAc, 20:1). Calcd for
C14H26O5: C, 61.29; H, 9.55. Found: C, 61.45; H, 9.72. nmax/cm
1 (CCl4) 3385br (OOH). 1H NMR (300.13 MHz, CDCl3), d: 0.87–
0.95 (m, 3H, CH3), 1.15–1.89 (m, 16H, CH, CH2, CH3), 2.05–2.22
(m, 4H, CH2), 3.69–3.80 (m, 2H, CH2), 9.84, 9.89 (s, 1H, OOH).
13C NMR (75.48 MHz, CDCl3), d: 14.8, 14.9 (CH3), 21.4, 21.5,
23.38, 23.44, 29.4, 29.6, 30.7, 30.9, 31.7, 31.8, 34.0 (CH2), 59.5,
59.7 (OCH2) 109.2, 109.3 (COOH), 117.4, 117.5 (COEt).
1-(1-Ethoxycyclopentylperoxy)-1-hydroperoxycyclohexane, 3c.
Oil. Rf 0.30 (hexane:EtOAc, 20:1). Calcd for C13H24O5: C, 59.98;
H, 9.29. Found: C, 59.67; H, 9.64. nmax/cm 1 (CCl4) 3365br (OOH).
1H NMR (300.13 MHz, CDCl3), d: 1.22 (t, 3H, CH3, J = 7.3 Hz),
1.33–1.83 (m, 16H, CH2), 1.99–2.10 (m, 2H, CH2), 3.68 (q, 2H,
CH2, J = 7.3 Hz), 9.73 (s, 1H, OOH). 13C NMR (75.48 MHz,
CDCl3), d: 14.8 (CH3), 22.5, 23.3, 25.4, 29.9, 33.9 (CH2), 59.5
(OCH2) 109.1 (COOH), 117.3 (COEt).
1-Hydroperoxy-1-(1-methoxycyclohexylperoxy)-4-methylcyclo-
hexane (mixture of isomers), 4d. Oil. Rf 0.57 (hexane:EtOAc,
5:1). Calcd for C14H26O5: C, 61.29; H, 9.55. Found: C, 61.42; H,
1
1
9.37. nmax/cm (CCl4) 3330br (OOH). H NMR (300.13 MHz,
CDCl3), d: 0.82–0.89 (m, 3H, CH3), 1.09–1.83 (m, 17H, CH, CH2),
2.05–2.19 (m, 2H, CH2), 3.32, 3.34 (s, 3H, CH3), 9.89, 9.98 (s, 1H,
OOH). 13C NMR (75.48 MHz, CDCl3), d: 21.3, 21.4, 22.6, 22.7,
25.2, 25.3, 29.2, 29.4, 30.6, 30.8, 31.6, 31.7 (CH3, CH2, CH), 49.1,
49.2 (OCH3) 106.05, 106.10, 109.1, 109.2 (C).
1-Hydroperoxy-1-(1-methoxycyclohexylperoxy)cyclohexane, 3d.
Oil. Rf 0.33 (hexane:EtOAc, 20:1). Calcd for C13H24O5: C, 59.98;
H, 9.29. Found: C, 59.75; H, 9.53. nmax/cm 1 (CCl4) 3360br (OOH).
1H NMR (300.13 MHz, CDCl3), d: 1.35–1.91 (m, 20H, CH2), 3.38
(s, 3H, CH3), 10.0 (s, 1H, OOH). 13C NMR (75.48 MHz, CDCl3),
d: 22.5, 22.7, 25.3, 25.5, 29.9, 31.7 (CH2), 49.2 (OCH3) 106.1,
109.30 (C).
1-(1-Hydroperoxy-4-methylcyclohexylperoxy)-1-methoxycyclo-
heptane, 4e. Oil. Rf 0.60 (hexane:EtOAc, 5:1). Calcd for
C15H28O5: C, 62.47; H, 9.79. Found: C, 62.15; H, 9.71. nmax/cm
1 (CCl4) 3335br (OOH). 1H NMR (300.13 MHz, CDCl3), d: 0.85–
0.94 (m, 3H, CH3), 1.11–1.65 (m, 15H, CH, CH2), 1.85–2.01 (m,
4H, CH2), 2.10–2.20 (m, 2H, CH2), 3.36, 3.38(s, 3H, CH3), 9.96,
10.03 (s, 1H, OOH). 13C NMR (75.48 MHz, CDCl3), d: 21.4, 21.5,
22.2, 22.3, 29.3, 29.4, 29.6, 29.8, 30.7, 30.8, 31.7, 31.8 (CH3, CH2,
CH), 49.6, 49.7 (OCH3) 109.3, 109.4, 111.0, 111.3 (C).
1-[(1-methoxycycloheptyl)peroxy]cyclohexyl hydroperoxide, 3e.
Oil. Rf 0.52 (hexane:EtOAc, 5:1). Calcd for C14H26O5: C, 61.29; H,
1
9.55. Found: C, 61.43; H, 9.36. nmax/cm (CCl4) 3360br (OOH).
1H NMR (300.13 MHz, CDCl3), d: 1.33–1.93 (m, 22H, CH2), 3.35
(s, 3H, CH3), 9.89 (s, 1H, OOH). 13C NMR (75.48 MHz, CDCl3),
d: 22.2, 22.5, 25.4, 29.6, 29.8, 34.6, 35.1 (CH2), 49.6 (OCH3) 109.3
(COOH), 111.0 (COEt).
1-Hydroperoxy-1-(2-methoxypropan-2-ylperoxy)cycloheptane,
5a. White crystals. Mp 17–19 ◦C (hexane). Rf 0.37 (hex-
ane:EtOAc, 20:1). Calcd for C11H22O5: C, 56.39; H, 9.46. Found:
1-Ethoxy-1-(1-hydroperoxycyclohexylperoxy)cycloheptane, 3f.
1
1
Oil. Rf 0.57 (hexane:EtOAc, 5:1). Calcd for C15H28O5: C, 62.47; H,
C, 56.44; H, 9.61. nmax/cm (CCl4) 3340br (OOH). H NMR
(300.13 MHz, CDCl3), d: 1.25–1.60 (m, 14H, CH2, CH3), 1.85–
1.95 (m, 4H, CH2), 3.36 (s, 3H, CH3), 10.08 (s, 1H, OOH). 13C
NMR (75.48 MHz, CDCl3), d: 22.8 (CH3), 22.9, 30.0, 32.6 (CH2),
50.4 (OCH3), 105.6, 114.7 (C).
1
9.79. Found: C, 62.58; H, 9.57. nmax/cm (CCl4) 3355br (OOH).
1H NMR (300.13 MHz, CDCl3), d: 1.25 (t, 3H, CH3, J = 7.3 Hz),
1.32–1.98 (m, 22H, CH2), 3.67 (q, 2H, CH2, J = 7.3 Hz), 9.83 (s,
1H, OOH). 13C NMR (75.48 MHz, CDCl3), d: 14.7 (CH3), 22.3,
22.5, 25.5, 29.7, 29.9, 35.7 (CH2), 57.4 (OCH2) 109.1 (COOH),
111.0 (COEt).
1-Hydroperoxy-1-(2-methoxynonan-2-ylperoxy)cycloheptane,
5b. Oil. Rf 0.45 (hexane:EtOAc, 20:1). Calcd for C17H34O5: C,
64.12; H, 10.76. Found: C, 64.29; H, 10.91. nmax/cm 1 (CCl4) 3335br
(OOH). 1H NMR (200.13 MHz, CDCl3), d: 0.89 (t, 3H, CH3, J =
7 Hz), 1.21–2.00 (m, 27H, CH, CH2, CH3), 3.39 (s, 3H, OCH3),
10.11 (s, 1H, OOH). 13C NMR (50.32 MHz, CDCl3), d: 14.0 (CH3),
19.8, 22.6, 22.9, 24.2, 29.1, 29.7, 29.9, 31.7, 32.6, 35.8 (CH3, CH2),
50.1 (OCH3) 108.1, 114.5 (C).
1-Hydroperoxy-1-(2-methoxypropan-2-ylperoxy)-4-methylcyclo-
hexane (mixture of isomers), 4a. Oil. Rf 0.38 (hexane:EtOAc,
20:1). Calcd for C11H22O5: C, 56.39; H, 9.46. Found: C, 56.53; H,
1
1
9.31. nmax/cm (CCl4) 3340br (OOH). H NMR (300.13 MHz,
CDCl3), d: 0.85–0.92 (m, 3H, CH3), 1.14–1.65 (m, 13H, CH, CH2,
CH3), 2.10–2.21 (m, 2H, CH2), 3.37, 3,39 (s, 3H, CH3), 10.01,
10.05 (s, 1H, OOH). 13C NMR (75.48 MHz, CDCl3), d: 21.4, 21.6,
22.89, 22.94, 29.3, 29.4, 30.7, 30.8 (CH3, CH2, CH), 50.4, 50.5
(OCH3) 106.0, 109.4, 109.5 (C).
1-(1-Ethoxycyclopentylperoxy)-1-hydroperoxycycloheptane, 5c.
Oil. Rf 0.32 (hexane:EtOAc, 20:1). Calcd for C14H26O5: C, 61.29;
H, 9.55. Found: C, 61.41; H, 9.68. nmax/cm 1 (CCl4) 3325br (OOH).
1H NMR (300.13 MHz, CDCl3), d: 1.23 (t, 3H, CH3, J = 7.3 Hz),
1.47 -1.98 (m, 18H, CH2), 2.00–2.11 (m, 2H, CH2), 3.70 (q, 2H,
CH2, J = 7.3 Hz), 9.94 (s, 1H, OOH). 13C NMR (50.32 MHz,
CDCl3), d: 14.8 (CH3), 22.8, 23.3, 29.9, 32.7, 34.0 (CH2), 59.6
(OCH2), 114.3, 117.4 (C).
1-Hydroperoxy-1-(2-methoxynonan-2-ylperoxy)-4-methylcyclo-
hexane (the mixture of isomers), 4b. Oil. Rf 0.45 (hexane:EtOAc,
20:1). Calcd for C17H34O5: C, 64.12; H, 10.76. Found: C, 64.33; H,
1
1
10.54. nmax/cm (CCl4) 3355br (OOH). H NMR (200.13 MHz,
CDCl3), d: 0.77–0.92 (m, 6H, CH3), 1.11–1.75 (m, 22H, CH, CH2,
CH3), 2.06–2.21 (m, 2H, CH2), 3.33, 3.36 (s, 3H, CH3), 9.97, 10.02
(s, 1H, OOH). 13C NMR (50.32 MHz, CDCl3), d: 14.0 (CH3), 19.6,
19.7, 21.4, 21.5, 22.6, 24.2, 29.0, 29.1, 29.2, 29.4, 29.6, 29.8, 30.6,
30.7, 30.9, 31.7, 35.6, 35.7 (CH3, CH2, CH), 50.0, 50.1 (OCH3)
107.86, 107.91, 109.19, 109.30 (C).
1-Hydroperoxy-1-(2-methoxypropan-2-ylperoxy)cyclododecane,
6a. White crystals. Mp 77–78 ◦C (hexane). Rf 0.42 (hex-
ane:EtOAc, 20:1). Calcd for C16H32O5: C, 63.13; H, 10.60. Found:
1
1
C, 63.01; H, 10.47. nmax/cm (CCl4) 3360br (OOH). H NMR
(300.13 MHz, CDCl3), d: 1.21 -1.75 (m, 28H, CH2,CH3), 3.42 (s,
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3H, CH3), 10.18 (s, 1H, OOH). 13C NMR (75.48 MHz, CDCl3), d:
19.3, 21.8, 22.1, 22.9, 25.9, 26.1, 26.3 (CH2), 50.5 (OCH3) 105.9,
113.8 (C).
6 C. W. Jefford, Y. L. Amer Jaber and J. Boukouvalas, Synth. Commun.,
1990, 20, 2589–2596; B. Das, M. Krishnaiah, B. Veeranjaneyulu and
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1-Hydroperoxy-1-(1-methoxycyclohexylperoxy)cyclododecane,
6d. White crystals. Mp 85–87 ◦C (hexane). Rf 0.38 (hex-
ane:EtOAc, 20:1). Calcd for C19H36O5: C, 66.24; H, 10.53. Found:
1
1
C, 66.57; H, 10.83. nmax/cm (CCl4) 3330br (OOH). H NMR
(300.13 MHz, CDCl3), d: 1.25 -1.92 (m, 32H, CH2), 3.38 (s, 3H,
OCH3), 10.14 (s, 1H, OOH). 13C NMR (75.48 MHz, CDCl3),
d: 19.4, 21.9, 22.1, 22.8, 25.3, 25.9, 26.2, 26.3, 31.7 (CH2), 49.4
(OCH3) 106.2, 113.5 (C).
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Acknowledgements
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This work is supported by the Program for Support of Leading Sci-
entific Schools of the Russian Federation (Grant NSh 2942.2008.3)
and the Grant of the President of the Russian Federation (No.
MK-3515.2007.3).
10 (a) B. De Vries, A. P. Van Swieten, E. A. Syed, N. V. Akzo Nobel,
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