Synthesis of peroxides from β,δ-triketones under heterogeneous conditions

Article abstract of DOI:10.1134/S1070428015120027

Heterogeneous reactions of β,δ-triketones with ethereal hydrogen peroxide in nonpolar solvents, catalyzed by phosphomolybdic acid, afforded mixtures of stereoisomeric ozonides, tricyclic monoperoxides, and bridged tetraoxanes. The trioxolane ring is forme

Full text of DOI:10.1134/S1070428015120027

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 12, pp. 1681–1687. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © A.O. Terent’ev, I.A. Yaremenko, A.P. Glinushkin, G.I. Nikishin, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51,
No. 12, pp. 1716–1722.
Synthesis of Peroxides from β,δ-Triketones
under Heterogeneous Conditions
A. O. Terent’eva, I. A. Yaremenkoa, A. P. Glinushkinb, and G. I. Nikishinb
a Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Leninskii pr. 47, Moscow, 119991 Russia
e-mail: terentev@ioc.ac.ru
b All-Russia Research Institute of Phytopathology, Bol’shie Vyazemy, Moscow oblast, 143050 Russia
Received July 10, 2015
Abstract—Heterogeneous reactions of β,δ-triketones with ethereal hydrogen peroxide in nonpolar solvents,
catalyzed by phosphomolybdic acid, afforded mixtures of stereoisomeric ozonides, tricyclic monoperoxides,
and bridged tetraoxanes. The trioxolane ring is formed by the carbonyl groups located in the δ-position with
respect to each other.
DOI: 10.1134/S1070428015120027
The chemistry of organic peroxides is largely based
on reactions of carbonyl compounds, i.e., ketones and
aldehydes, with hydrogen peroxide and hydroperox-
ides [1, 2]. Aldehydes and ketones are accessible com-
pounds, and they readily react through the carbonyl
carbon atom with highly nucleophilic hydroperoxide
oxygen atom. In recent time, the chemistry of organic
peroxides has developed especially vigorously since
some of them have been found to exhibit antimalarial
[3–6] and antihelminthic activity [7–9]. Natural per-
oxide artemisinin and its semisynthetic derivatives
(artemether, arteether, and artesunate) have been used
over several decades for the treatment of malaria [10].
Organic peroxides are produced on a large-scale
from ketones and are used as radical polymerization
initiators [11, 12] and cross-linking agents [13, 14].
The need of low-cost and efficient radical initiators, as
well as of biologically active peroxides stimulates
development of new methods of synthesis of peroxides
from ketones and their derivatives with the use of hy-
drogen peroxide and hydroperoxides [15–25]. Perox-
idation of monocarbonyl compounds has been studied
in detail [15–21]. Considerably less data are available
on the peroxidation of di- and tricarbonyl compounds
with hydrogen peroxide [22–26]; these reactions are
often nonselective and provide low yields.
Scheme 1.
O
O
Me
Me
R
R
O
O
1
2
H2O2/Et2O, PMA
O
O
Me
Me
Me
Me
Me
3
+
O
O
R
O
O
4
5
O
Me
Me
1a–1e
2a–2e
3a–3e
Me
O
Me
7
O5
7a
1
4'
2O
3 O
Me
O1
6
O6
O5
3a
3'
+
+
R
7
Me
4
O2
R
O
4
3
Me
4a–4e
Me
5a–5e
R = PhCH2 (a), 4-O2NC6H4CH2 (b), 4-MeC6H4CH2 (c), 4-ClC6H4CH2 (d), 4-BrC6H4CH2 (e).
1681

TERENT’EV et al.
1682
In the present study we have shown that phospho-
active sites for the interactions with hydrogen peroxide
and carbonyl groups of β,δ-triketone and increases
porosity and specific surface area of the catalyst.
molybdic acid catalyzes peroxidation of β,δ-triketones
under heterogeneous conditions with formation of mix-
tures of three types of peroxides, namely ozonides,
tricyclic monoperoxides, and bridged tetraoxanes.
Heterogeneous conditions allow the catalyst to be re-
cycled, considerably simplify the isolation procedure,
and make the process more economic.
Likewise, heterogeneous peroxidation of β,δ-trike-
tones 1b–1e with H2O2 gave mixtures of stereoiso-
meric ozonides 2b–2e and 3b–3e, tricyclic monoper-
oxides 4b–4e, and bridged tetraoxanes 5b–5e.
The described reaction may be regarded as a novel
unique one-pot method of synthesis of three different
peroxides whose preparation by known methods
requires more complicated experimental procedures.
The trioxolane ring in 2 and 3 is formed from two
carbonyl groups occurring in the δ position with
respect to each other, whereas the formation of tetra-
oxanes 5 involves the β-dicarbonyl fragment of the
substrate. The resulting peroxides can be separated by
column chromatography on silica gel. It was surprising
that one carbonyl group of initial β,δ-triketones 1
remained unchanged in the described transformation,
since just carbonyl functionality is generally highly
reactive toward hydrogen peroxide. We have found
only one reference to and one publication on the syn-
thesis of ozonides from ketones [27, 28].
Peroxidation of β,δ-triketones 1a–1e with a solution
of hydrogen peroxide in diethyl ether, catalyzed by
phosphomolybdic acid (PMA), in benzene, toluene, or
carbon tetrachloride led to the formation of stereoiso-
meric ozonides 2a–2e and 3a–3e, tricyclic monoperox-
ides 4a–4e, and bridged tetraoxanes 5a–5e (Scheme 1).
The effects of the amount of the catalyst and solvent
nature on the product yields and ratio was studied in
the peroxidation of 3-acetyl-3-benzylheptane-2,6-dione
(1a) (see table). The reaction of 1a with H2O2/Et2O in
the presence of PMA in benzene, toluene, and CCl4
afforded a mixture of steroisomeric peroxides 2a and
3a, tricyclic monoperoxide 4a, and tetraoxane 5a (see
table, run nos. 1–10); the yields were comparable with
those obtained under homogeneous conditions [26].
The use of preliminarily modified catalyst favored
formation of 4a and 5a in higher yields (run nos. 3, 7)
than in the reaction with commercial PMA. The cata-
lyst morphology was studied by field-emission scan-
ning electron microscopy (FESEM; see figure).
The scientific novelty of the peroxidation of
organic compounds with hydrogen peroxide consists of
the use of solid catalysts (metal salts) under hetero-
geneous conditions. Heterogeneous peroxidation is
more advantageous than homogeneous catalysis due to
the possibility for recycling of the catalyst without
additional regeneration procedure or utilization after
single application. Furthermore, the proposed proce-
It was presumed that thermal treatment of com-
mercial phosphomolybdic acid hydrate (H3PMo12O40 ·
n H2O) removes crystallization water, which opens
Synthesis of peroxides 2a–5a from triketone 1a and H2O2
Yield,a %
Run no.
Reaction time, h
Co-solvent
Benzene
2a
3a
4a
5a
01
08
24
08
24
08
24
08
24
08
08
10
10
08
10
15
15
17
18
02
Benzene
03b
04b
05
Benzene
12
10
26
27
Benzene
10
11
29
27
Toluene
11
09
21
20
06
Toluene
11
08
22
22
07b
08b
09
Toluene
14 (11)
12
11 (9)
12
28 (25)
28
29 (24)
31
Toluene
Carbon tetrachloride
Carbon tetrachloride
09
09
35
26
10b
07
08
29
21
a
According to the NMR data; isolated yield is given in parentheses.
Phosphomolybdic acid was preliminarily dissolved in ethanol (10 mL), the solvent was distilled off, and the residue was heated for 2 h at
120°C under atmospheric pressure.
b
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SYNTHESIS OF PEROXIDES FROM β,δ-TRIKETONES
1683
(a)
(b)
FESEM images of phosphomolybdic acid: (a) commercial sample and (b) after treatment.
dure is economic and more compliable to the “green
chemistry” principles. Its experimental simplicity pro-
vides the basis for large-scale syntheses of peroxides.
stirring at 20–25°C to a solution of 0.30 g (1.15 mmol)
of triketone 1a in 4 mL of benzene, toluene, or
carbon tetrachloride. The mixture was stirred for 8 h
(24 h in run nos. 2, 6) at 20–25°C and applied to
a column charged with silica gel (1×10 cm), and the
sorbent was eluted with petroleum ether–ethyl acetate
(1:3). The solvent was removed under reduced pres-
sure (watr-jet pump), and the yields of 2a–5a were
determined by NMR.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Bruker AM 300 spectrometer at 300.13 and
75.48 MHz, respectively, using CDCl3 as solvent. The
procedure for FESEM study was described in [29].
The melting points were measured on a Kofler hot
stage. Silica gel (0.060‒0.200 mm, 60 Å, CAS
no. 7631-86-9) was used for column chromatography.
Benzene, toluene, carbon tetrachloride, petroleum ether
(bp 40‒70°C), ethyl acetate, phosphomolybdic acid
hydrate (80%), acetylacetone, methyl vinyl ketone,
alkyl bromides, and sodium sulfate were commercial
products (Acros Organics). A solution of hydrogen per-
oxide in diethyl ether (5.8 wt %) was prepared by
extraction of 37% aq. H2O2 (100 mL) with Et2O
(5×100 mL), followed by drying of the extract over
MgSO4. β,δ-Triketones 1a [30] and 1b–1e [31] were
synthesized according to known procedures.
b (See table; run nos. 3, 4, 7, 8, 10). A solution of
hydrogen peroxide in diethyl ether (1.57 mL,
1.73 mmol, c = 1.10 M; 1.5 mol of H2O2 per mole of
1a) and 0.21 g (10 mol %) of preliminarily treated
PMA were added in succession under stirring at 20–
25°C to a solution of 0.30 g (1.15 mmol) of triketone
1a in 4 mL of benzene, toluene, or carbon tetra-
chloride. The mixture was stirred for 8 h (24 h in run
nos. 4, 8) at 20–25°C, the solution was separated from
the catalyst by decanting, and the catalyst (which
resided on the walls of the flask due to its high
adhesion to glass) was washed with the corresponding
solvent (2×2 mL). The organic phases were combined
and applied to a column charged with silica gel
(1×10 cm), and the column was eluted with petroleum
ether–ethyl acetate (1:3). The solvent was removed
under reduced pressure, and the yields of 2a–5a were
determined by NMR. In run no. 7, compounds 2a–5a
were isolated by column chromatography on silica gel
(gradient elution with petroleum ether–ethyl acetate,
10 to 80 vol % of the latter).
Treatment of the catalyst. Commercial phospho-
molybdic acid was dissolved in 10 mL of ethanol, the
solvent was distilled off, and the residue was heated
for 2 h at 120°C under atmospheric pressure. The orig-
inally yellow sample turned green and lost 20% of the
initial weight.
Peroxidation of 3-acetyl-3-benzylheptane-2,6-di-
one (1a) over phosphomolybdic acid. a (See table;
run nos. 1, 2, 5, 6, 9). A solution of hydrogen peroxide
in diethyl ether (1.57 mL, 1.73 mmol, c = 1.10 M;
1.5 mol of H2O2 per mole of 1a) and 0.26 g (10 mol %)
of commercial PMA were added in succession under
Heterogeneous peroxidation of triketones 1b–1f.
The procedure was the same as described above in b
(toluene, 20‒25°C, 8 h). The organic phases were
combined and applied to a column charged with silica
gel (1×7 cm), and the column was eluted with 40 mL
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 12 2015

TERENT’EV et al.
1684
of petroleum ether–ethyl acetate (1:3). The solvent
was removed under reduced pressure, and the products
were isolated by column chromatography on silica gel
(gradient elution with petroleum ether–ethyl acetate,
10 to 80 vol % of the latter). The yields of 2b–5b and
2c–5c were almost the same when the catalyzed was
recycled. The NMR spectra of 2–5 were identical to
those given in [26].
1-[(1R,2S,5S)-1,5-Dimethyl-2-(4-nitrobenzyl)-
6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone (3b).
Yield 0.038 g (12%), white crystals, mp 133–134°C
1
(from EtOAc) [26]. H NMR spectrum, δ, ppm: 1.48‒
1.61 m (4H, 5-CH3, 3-H), 1.66 s (3H, 1-CH3), 1.89‒
2.09 m (2H, 4-H), 2.13‒2.31 m (4H, CH3C=O, 3-H),
2.67 d and 3.54 d (1H each, 2-CH2, J = 13.2 Hz),
7.25 d (2H, Harom, J = 8.8 Hz), 8.09 d (2H, Harom, J =
8.8 Hz). 13C NMR spectrum, δC, ppm: 18.5 (1-CH3),
20.6 (5-CH3), 25.5 (C3), 30.1 (CH3C=O), 32.8 (C4),
40.6 (2-CH2), 58.3 (C2), 109.0 (C5), 110.6 (C1), 123.3
and 131.1 (Co, Cm), 144.3 (Ci), 147.0 (Cp), 209.5
(C=O). Found, %: C 59.90; H 5.90; N 4.38.
C16H19NO6. Calculated, %: C 59.81; H 5.96; N 4.36.
1-[(1R,2R,5S)-2-Benzyl-1,5-dimethyl-6,7,8-trioxa-
bicyclo[3.2.1]octan-2-yl]ethanone (2a). Yield 0.035 g
(11%), colorless oily material, nD22 = 1.5162 (1.5160
1
[26]). H NMR spectrum, δ, ppm: 1.47 s (3H, 1-CH3),
1.52‒1.62 m (4H, 5-CH3, 3-H), 1.75‒1.85 m and 1.90‒
2.03 m (1H each, 4-H), 2.14 s (3H, CH3C=O), 2.56‒
2.70 m (1H, 3-H), 2.88 d and 3.53 d (1H each, CH2Ph,
J = 13.2 Hz), 7.03‒7.09 m (2H, Harom), 7.15‒7.26 m
(3H, Harom). 13C NMR spectrum, δC, ppm: 18.4
(1-CH3), 20.8 (5-CH3), 22.3 (C3), 30.3 (CH3C=O),
31.0 (C4), 36.2 (CH2Ph), 59.2 (C), 109.2 (C5), 111.4
(C1); 126.6, 128.3, 130.2 (CHarom); 137.7 (Carom), 210.9
(C=O). Found, %: C 69.50; H 7.40. C16H20O4. Cal-
culated, %: C 69.54; H 7.30.
1-[(1R,2R,5S)-1,5-Dimethyl-2-(4-methylbenzyl)-
6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone (2c).
Yield 0.044 g (14%), yellow oily material, nD22
=
1
1.5214 (1.5215 [26]). H NMR spectrum, δ, ppm:
1.48 s (3H, 1-CH3), 1.51‒1.65 m (4H, 5-CH3, 3-H),
1.74‒1.86 m and 1.90‒2.04 m (1H each, 4-H), 2.14 s
(3H, CH3C=O), 2.28 s (3H, CH3C6H4), 2.55‒2.71 m
(1H, 3-H), 2.85 d and 3.49 d (1H, 2-CH2, J = 13.2 Hz),
6.95 d (2H, Harom, J = 8.1 Hz), 7.03 d (2H, Harom, J =
8.1 Hz). 13C NMR spectrum, δC, ppm: 18.4 (1-CH3),
20.8 (5-CH3), 20.9 (CH3C6H4), 22.3 (C3), 30.3
(CH3C=O), 30.9 (C4), 35.8 (2-CH2), 59.1 (C2), 109.2
(C5), 111.4 (C5), 129.0 and 130.0 (Co, Cm), 134.5 (Cp),
136.1 (Ci), 211.0 (C=O). Found, %: C 70.30; H 7.68.
C17H22O4. Calculated, %: C 70.32; H 7.64.
1-[(1R,2S,5S)-2-Benzyl-1,5-dimethyl-6,7,8-trioxa-
bicyclo[3.2.1]octan-2-yl]ethanone (3a). Yield 0.029 g
(9%), white crystals, mp 89–90°C (from EtOAc) [26].
1H NMR spectrum, δ, ppm: 1.50 s (3H, 5-CH3), 1.61‒
1.78 m (4H, 1-CH3, 3-H), 1.86‒1.96 m (2H, 4-H),
2.07 s (3H, CH3C=O), 2.18‒2.34 m (1H, 3-H), 2.59 d
and 3.35 d (1H each, CH2Ph, J = 13.2 Hz), 7.00‒
7.10 m (2H, Harom), 7.15‒7.29 m (3H, Harom). 13C NMR
spectrum, δC, ppm: 18.9 (1-CH3), 20.6 (5-CH3), 25.8
(C3), 30.0 (CH3C=O), 33.0 (C4), 41.4 (CH2Ph), 58.3
(C2), 109.0 (C5), 111.3 (C1); 126.7, 128.3, 130.1
(CHarom); 136.0 (Carom), 210.3 (C=O). Found, %:
C 69.45; H 7.35. C16H20O4. Calculated, %: C 69.54;
H 7.30.
1-[(1R,2S,5S)-1,5-Dimethyl-2-(4-methylbenzyl)-
6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone (3c).
Yield 0.032 g (10%), white crystals, mp 90‒91°C
1
(from EtOAc) [26]. H NMR spectrum, δ, ppm: 1.50 s
(3H, 5-CH3), 1.62‒1.78 m (4H, 1-CH3, 3-H), 1.85‒
1.96 m (2H, 4-H), 2.07 m (3H, CH3C=O), 2.13‒2.35 m
(4H, CH3C6H4, 3-H), 2.56 d and 3.30 d (1H each,
2-CH2, J = 13.2 Hz), 6.93 d (2H, Harom, J = 8.1 Hz),
7.04 d (2H, Harom, J = 8.1 Hz). 13C NMR spectrum, δC,
ppm: 18.9 (1-CH3), 20.6 (5-CH3), 21.0 (CH3C6H4),
25.8 (C3), 30.0 (CH3C=O), 33.1 (C4), 41.0 (2-CH2),
58.3 (C2), 109.0 (C5), 111.3 (C1), 128.9 and 130.0
(Co, Cm), 132.8 (Cp), 136.3 (Ci), 210.4 (C=O). Found,
%: C 70.40; H 7.70. C17H22O4. Calculated, %: C 70.32,
H 7.64.
1-[(1R,2R,5S)-1,5-Dimethyl-2-(4-nitrobenzyl)-
6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone (2b).
Yield 0.044 g (14%), white crystals, mp 115–116°C
1
(from EtOAc) [26]. H NMR spectrum, δ, ppm: 1.37‒
1.49 m (4H, 1-CH3, 3-H), 1.58 s (3H, 5-CH3), 1.77‒
2.03 m (2H, 4-H), 2.21 s (3H, CH3C=O), 2.64‒2.79 m
(1H, 3-H), 3.00 d and 3.66 d (1H each, CH2C6H4, J =
13.2 Hz), 7.27 d (2H, Harom, J = 8.8 Hz), 8.08 d (2H,
Harom, J = 8.8 Hz). 13C NMR spectrum, δC, ppm: 18.2
(1-CH3), 20.7 (5-CH3), 22.2 (C3), 29.9 (CH3C=O),
30.8 (C4), 35.4 (2-CH2), 59.6 (C2), 109.2 (C5), 110.8
(C1), 123.4 and 131.2 (Co, Cm), 145.8 (Ci), 146.8 (Cp),
210.3 (C=O). Found, %: C 59.74; H 5.82; N 4.40.
C16H19NO6. Calculated, %: C 59.81; H 5.96; N 4.36.
1-[(1R,2R,5S)-2-(4-Chlorobenzyl)-1,5-dimethyl-
6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone (2d).
Yield 0.060 g (19%), white crystals, mp 121‒122°C
1
(from EtOAc) [26]. H NMR spectrum, δ, ppm: 1.44 s
(3H, 1-CH3), 1.48‒1.62 m (4H, 5-CH3, 3-H), 1.76‒
1.99 m (2H, 4-H), 2.17 s (3H, CH3C=O), 2.59‒2.73 m
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SYNTHESIS OF PEROXIDES FROM β,δ-TRIKETONES
1685
(1H, 3-H), 2.85 d and 3.51 d (1H each, 2-CH2, J =
13.6 Hz), 7.01 d (2H, Harom, J = 8.4 Hz), 7.19 d (2H,
3a-Benzyl-3,6,7a-trimethyltetrahydro-3H,4H-
3,6-epoxy[1,2]dioxolo[3,4-b]pyran (4a). Yield
0.080 g (25%), white crystals, mp 94–95°C (from
H
arom, J = 8.4 Hz). 13C NMR spectrum, δC, ppm: 18.3
1
(1-CH3), 20.8 (5-CH3), 22.2 (C3), 30.2 (CH3C=O),
30.9 (C4), 35.2 (2-CH2), 59.3 (C2), 109.2 (C5), 111.1
(C1), 128.4 and 131.6 (Co, Cm), 132.5 (Cp), 136.2 (Ci),
210.7 (C=O). Found, %: C 61.92; H 6.23; Cl 11.51.
C16H19ClO4. Calculated, %: C 61.84; H 6.16; Cl 11.41.
EtOAc) [26]. H NMR spectrum, δ, ppm: 1.37 s (3H,
6-CH3), 1.42 s (6H, 3-CH3, 7a-CH3), 1.64‒1.77 m (2H,
5-H), 1.78‒1.89 m (2H, 4-H), 2.86 s (2H, 3a-CH2),
7.16‒7.33 m (5H, Harom). 13C NMR spectrum, δC, ppm:
16.1 (3-CH3, 7a-CH3), 18.9 (C4), 24.7 (6-CH3), 30.9
(C5), 36.8 (3a-CH2), 51.8 (C3a), 93.7 (C6), 107.5
(C3, C7a); 126.8, 128.1, 131.2 (CHarom); 136.5 (Ci).
Found, %: C 69.47; H 7.32. C16H20O4. Calculated, %:
C 69.54; H 7.30.
1-[(1R,2S,5S)-2-(4-Chlorobenzyl)-1,5-dimethyl-
6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone (3d).
Yield 0.032 g (10%), white crystals, mp 105‒106°C
1
(from EtOAc) [26]. H NMR spectrum, δ, ppm: 1.48‒
3,6,7a-Trimethyl-3a-(4-nitrobenzyl)tetrahydro-
3H,4H-3,6-epoxy[1,2]dioxolo[3,4-b]pyran (4b). Yield
0.069 g (22%), white crystals, mp 149–150°C (from
1.73 m (7H, 1-CH3, 5-CH3, 3-H), 1.87‒2.01 m (2H,
4-H), 2.08–2.29 m (4H, CH3C=O, 3-H), 2.54 d and
3.35 d (1H each, 2-CH2, J = 12.9 Hz), 6.98 d (2H,
1
EtOAc) [26]. H NMR spectrum, δ, ppm: 1.40 s (3H,
H
arom, J = 8.3 Hz), 7.20 d (2H, Harom, J = 8.3 Hz).
13C NMR spectrum, δC, ppm: 18.7 (1-CH3), 20.6
(5-CH3), 25.6 (C3), 30.1 (CH3C=O), 32.9 (C4), 40.5
(2-CH2), 58.2 (C2), 109.0 (C5), 111.0 (C1), 128.4 and
131.5 (Co, Cm), 132.7 (Cp), 134.6 (Ci), 210.0 (C=O).
Found, %: C 61.92; H 6.22; Cl 11.53. C16H19ClO4.
Calculated, %: C 61.84; H 6.16; Cl 11.41.
6-CH3), 1.43 s (6H, 3-CH3, 7a-CH3), 1.69‒1.80 m (2H,
5-H), 1.80‒1.92 m (2H, 4-H), 2.98 s (2H, 3a-CH2),
7.43 d (2H, Harom, J = 8.8 Hz), 8.17 d (2H, Harom, J =
8.8 Hz). 13C NMR spectrum, δC, ppm: 16.7 (3-CH3,
7a-CH3), 19.0 (C4), 24.6 (6-CH3), 30.7 (C5), 36.8
(3a-CH2), 51.9 (C3a), 93.8 (C6), 107.2 (C3, C7a), 123.3
and 131.9 (Co, Cm), 144.4 (Ci), 147.0 (Cp). Found, %:
C 59.90; H 5.84; N 4.40. C16H19NO6. Calculated, %:
C 59.81; H 5.96; N 4.36.
1-[(1R,2R,5S)-2-(4-Bromobenzyl)-1,5-dimethyl-
6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone (2e).
Yield 0.035 g (11%), white crystals, mp 109‒110°C
3,6,7a-Trimethyl-3a-(4-methylbenzyl)tetrahydro-
3H,4H-3,6-epoxy[1,2]dioxolo[3,4-b]pyran (4c). Yield
0.063 g (20%), white crystals, mp 106‒107°C (from
1
[26]. H NMR spectrum, δ, ppm: 1.35–1.63 m (7H,
1-CH3, 5-CH3, 3-H), 1.74–2.00 m (2H, 4-H), 2.18 s
(3H, CH3C=O), 2.57–2.75 m (1H, 3-H), 2.84 d and
3.50 d (1H each, 2-CH2, J = 13.2 Hz), 6.96 d (2H,
1
EtOAc) [26]. H NMR spectrum, δ, ppm: 1.38 s (3H,
6-CH3), 1.42 s (6H, 3-CH3, 7a-CH3), 1.64‒1.74 m (2H,
5-H), 1.76‒1.88 m (2H, 4-H), 2.32 s (3H, CH3C6H4),
2.82 s (2H, 3a-CH2), 7.04‒7.12 m (4H, Harom).
13C NMR spectrum, δC, ppm: 16.6 (3-CH3, 7a-CH3),
18.9 (C4), 21.0 (CH3C6H4), 24.7 (6-CH3), 30.9 (C5),
36.3 (3a-CH2), 51.7 (C3a), 93.7 (C6), 107.5 (C3, C7a),
128.8 and 131.0 (Co, Cm), 133.2 (Cp), 136.4 (Ci).
Found, %: C 70.25; H 7.55. C17H22O4. Calculated, %:
C 70.32; H 7.64.
H
arom, J = 8.1 Hz), 7.35 d (2H, Harom, J = 8.1 Hz).
13C NMR spectrum, δC, ppm: 18.3 (1-CH3), 20.8
(5-CH3), 22.2 (C3), 30.2 (CH3C=O), 30.9 (C4), 35.3
(2-CH2), 59.2 (C2), 109.2 (C5), 111.1 (C1), 120.6 (Cp),
131.4 and 132.0 (Co, Cm), 136.8 (Ci), 210.7 (C=O).
Found, %: C 54.05; H 5.46; Br 22.59. C16H19BrO4.
Calculated, %: C 54.10; H 5.39; Br 22.49.
1-[(1R,2S,5S)-2-(4-Bromobenzyl)-1,5-dimethyl-
6,7,8-trioxabicyclo[3.2.1]octan-2-yl]ethanone (3e).
Yield 0.028 g (8%), white crystals, mp 107‒108°C
3a-(4-Chlorobenzyl)-3,6,7a-trimethyltetrahydro-
3H,4H-3,6-epoxy[1,2]dioxolo[3,4-b]pyran (4d). Yield
0.079 g (25%), white crystals, mp 120‒121°C (from
1
[26]. H NMR spectrum, δ, ppm: 1.46–1.72 m (7H,
1
1-CH3, 5-CH3, 3-H), 1.87–1.98 m (2H, 4-H), 2.11 s
(3H, CH3C=O), 2.13–2.28 m (1H, 3-H), 2.52 d and
3.33 d (1H each, 2-CH2, J = 12.8 Hz), 6.93 d (2H,
EtOAc) [26]. H NMR spectrum, δ, ppm: 1.32 s (3H,
6-CH3), 1.35 s (6H, 3-CH3, 7a-CH3), 1.59–1.69 m (2H,
5-H), 1.69–1.80 m (2H, 4-H), 2.77 s (2H, 3a-CH2),
7.09 d (2H, Harom, J = 8.4 Hz), 7.19 d (2H, Harom, J =
8.4 Hz). 13C NMR spectrum, δC, ppm: 16.7 (3-CH3,
7a-CH3), 18.9 (C4), 24.6 (6-CH3), 30.8 (C5), 36.2
(3a-CH2), 51.7 (C3a), 93.7 (C6), 107.4 (C3, C7a), 128.3
and 132.4 (Co, Cm), 132.9 (Cp), 134.9 (Ci). Found, %:
C 61.80; H 6.21; Cl 11.53. C16H19ClO4. Calculated, %:
C 61.84; H 6.16; Cl 11.41.
H
arom, J = 8.3 Hz), 7.35 d (2H, Harom, J = 8.3 Hz).
13C NMR spectrum, δC, ppm: 18.7 (1-CH3), 20.6
(5-CH3), 25.6 (C3), 30.1 (CH3C=O), 32.9 (C4), 40.6
(2-CH2), 58.1 (C2), 109.0 (C5), 111.0 (C1), 120.8 (Cp),
131.4 and 131.9 (Co, Cm), 135.2 (Ci), 210.0 (C=O).
Found, %: C 54.15; H 5.45; Br 22.60. C16H19BrO4.
Calculated, %: C 54.10; H 5.39; Br 22.49.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 12 2015

TERENT’EV et al.
1686
4-[7-(4-Chlorobenzyl)-1,4-dimethyl-2,3,5,6-tetra-
3a-(4-Bromobenzyl)-3,6,7a-trimethyltetrahydro-
oxabicyclo[2.2.1]heptan-7-yl]butan-2-one (5d). Yield
0.076 g (23%), white crystals, mp 96‒97°C (from
EtOAc) [26]. H NMR spectrum, δ, ppm: 1.23 s (6H,
3H,4H-3,6-epoxy[1,2]dioxolo[3,4-b]pyran (4e). Yield
0.079 g (25%), white crystals, mp 123‒124°C (from
EtOAc) [26]. H NMR spectrum, δ, ppm: 1.38 s (3H,
1
1
CH3), 2.01‒2.13 m (2H, 4′-H), 2.19 s (3H, CH3C=O),
2.64‒2.73 m (2H, 3′-H), 2.97 s (2H, 7-CH2), 7.19 d
(2H, Harom, J = 8.4 Hz), 7.28 d (2H, Harom, J = 8.4 Hz).
13C NMR spectrum, δC, ppm: 9.3 (CH3), 21.6 (C4′),
30.2 (CH3C=O), 33.7 (7-CH2), 38.1 (C3′), 60.1 (C7),
111.9 (C1, C4), 128.6 and 132.3 (Co, Cm), 133.3 (Cp),
133.7 (Ci), 206.9 (C=O). Found, %: C 58.86; H 5.93;
Cl 10.98. C16H19ClO5. Calculated, %: C 58.81; H 5.86;
Cl 10.85.
6-CH3), 1.41 s (6H, 3-CH3, 7a-CH3), 1.64‒1.74 m (2H,
5-H), 1.75‒1.86 m (2H, 4-H), 2.81 s (2H, 3a-CH2),
7.09 d (2H, Harom, J = 8.2 Hz), 7.40 d (2H, Harom, J =
8.2 Hz). 13C NMR spectrum, δC, ppm: 16.7 (3-CH3,
7a-CH3), 18.9 (C4), 24.7 (6-CH3), 30.8 (C5), 36.3
(3a-CH2), 51.6 (C3a), 93.7 (C6), 107.4 (C3, C7a), 120.9
(Cp), 131.3 and 132.8 (Co, Cm), 135.4 (Ci). Found, %:
C 54.05; H 5.45; Br 22.53. C16H19BrO4. Calculated, %:
C 54.10; H 5.39; Br 22.49.
4-[7-(4-Bromobenzyl)-1,4-dimethyl-2,3,5,6-tetra-
oxabicyclo[2.2.1]heptan-7-yl]butan-2-one (5e). Yield
0.066 g (20%), white crystals, mp 82‒83°C (from
4-(7-Benzyl-1,4-dimethyl-2,3,5,6-tetraoxabicyclo-
[2.2.1]heptan-7-yl)butan-2-one (5a). Yield 0.081 g
(24%), white crystals, mp 69–70°C (from EtOAc)
1
EtOAc) [26]. H NMR spectrum, δ, ppm: 1.23 s (6H,
1
[26]. H NMR spectrum, δ, ppm: 1.22 s (6H, CH3),
CH3), 1.98‒2.13 m (2H, 4′-H), 2.19 s (3H, CH3C=O),
2.62‒2.73 m (2H, 3′-H), 2.95 s (2H, 7-CH2), 7.13 d
(2H, Harom, J = 8.4 Hz), 7.43 d (2H, Harom, J = 8.4 Hz).
13C NMR spectrum, δC, ppm: 9.3 (CH3), 21.5 (C4′),
30.2 (CH3C=O), 33.8 (7-CH2), 38.0 (C3′), 60.0 (C7),
111.9 (C1, C4), 121.3 (Cp), 131.6 and 132.6 (Co, Cm),
134.2 (Ci), 206.9 (C=O). Found, %: C 51.85; H 5.29;
Br 21.65. C16H19BrO5. Calculated, %: C 51.77; H 5.16;
Br 21.52.
2.04‒2.15 m (2H, 4′-H), 2.18 s (3H, CH3C=O), 2.62‒
2.73 m (2H, 3′-H), 3.00 s (2H, 7-CH2), 7.16‒7.35 m
(5H, Harom). 13C NMR spectrum, δC, ppm: 9.2 (CH3),
21.5 (C4′), 30.1 (CH3C=O), 34.1 (7-CH2), 38.1 (C3′),
60.1 (C7), 112.0 (C1, C4); 127.2, 128.4, 130.9 (CHarom);
135.2 (Carom), 206.9 (C=O). Found, %: C 65.68;
H 7.02. C16H20O5. Calculated, %: C 65.74; H 6.90.
4-[1,4-Dimethyl-7-(4-nitrobenzyl)-2,3,5,6-tetra-
oxabicyclo[2.2.1]heptan-7-yl]butan-2-one (5b). Yield
0.083 g (25%), white crystals, mp 121–122°C (from
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 15-29-05820ofi_m).
1
EtOAc) [26]. H NMR spectrum, δ, ppm: 1.22 s (6H,
CH3), 2.04‒2.17 m (2H, 4′-H), 2.21 s (3H, CH3C=O),
2.67‒2.77 m (2H, 3′-H), 3.10 s (2H, 7-CH2), 7.46 d
(2H, Harom, J = 8.1 Hz), 8.18 d (2H, Harom, J = 8.1 Hz).
13C NMR spectrum, δC, ppm: 9.3 (CH3), 21.6 (C4′),
30.2 (CH3C=O), 34.3 (7-CH2), 37.9 (C3′), 60.2 (C7),
111.8 (C1, C4), 123.6 and 131.9 (Co, Cm), 143.1
(Ci), 147.3 (Cp), 206.6 (C=O). Found, %: C 56.87;
H 5.60; N 4.25. C16H19NO7. Calculated, %: C 56.97;
H 5.68; N 4.15.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 12 2015

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