Reaction of levoglucosenone with (±)-α-terpineol and its acetate

Full text of DOI:10.1134/S1070428014120264

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ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 12, pp. 1848–1850. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © Yu.S. Galimova, Yu.A. Khalilova, B.T. Sharipov, L.V. Spirikhin, Sh.R. Rameev, R.L. Safiullin, F.A. Valeev, 2014, published in
Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 12, pp. 1864–1866.
SHORT
COMMUNICATIONS
Reaction of Levoglucosenone with (±)-α-Terpineol
and Its Acetate
Yu. S. Galimova, Yu. A. Khalilova, B. T. Sharipov, L. V. Spirikhin, Sh. R. Rameev,
R. L. Safiullin, and F. A. Valeev
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: sinvmet@anrb.ru
Received June 23, 2014
DOI: 10.1134/S1070428014120264
In continuation of our studies [1, 2], we focused on
the potential of levoglucosenone in the synthesis of
menthane derivatives as a separate problem and exam-
ined the possibility for direct introduction of a men-
thane fragment into levoglucosenone molecule via
reaction with (±)-α-terpineol.
ampule (metohd a). In fact, after 9 h, we succeeded in
isolating from the reaction mixture Diels–Alder adduct
V in 3% yield [calculated on the initial (±)-α-ter-
pineol]. Increase of the reaction time reduced the yield
of V, and we failed to detect it in the reaction mixture
after 30 h, presumably because of its decomposition.
A short synthetic route to (±)-α-terpineol is the two-
step procedure utilizing large-scale initial compounds,
isoprene and methyl acrylate [3]. The transformation
of (±)-α-terpineol into a chiral subunit requires its
preliminary optical resolution and introduction of
functional groups that could ensure subsequent trans-
formations.
We also tried to use as starting compounds
(±)-α-terpineol (I) and (±)-α-terpinyl acetate (II),
expecting generation of α-terpinene (III) in situ under
the given Diels–Alder reaction conditions. In the first
case, no cycloaddition products were detected in the
reaction mixture, and in the second case adduct V was
formed in 4% yield in 28 h (method b).
It is known that dehydration of α-terpineol leads to
the formation of a number of isomeric dienes, includ-
ing α-terpinene whose yield in some cases attains 25%
[4]. The use of such a mixture of menthane derivatives
as diene component and of levoglucosenone as dieno-
phile is attractive from the viewpoint of simultaneous
solution of both problems. For this purpose, a toluene
solution of levoglucosenone and diene mixture ob-
tained from (±)-α-terpineol according to the procedure
described in [4] was heated at 160°C in a sealed glass
The structure of V was determined on the basis of
1
the H and 13C NMR data. The coupling constant
between 5a-H and 9a-H equal to 8.6 Hz indicates cis
junction of the bicyclo[2.2.2]octane and pyran frag-
ments. The signal assignment was confirmed by the
HMBC technique. The 9a-H proton (δ 1.87 ppm)
showed couplings with C2 (δC 68.29 ppm), C5a
(49.29), C5 (200.96), C8 (138.26), and C9 (35.59), and
cross-peaks of 5a-H (δ 2.90 ppm) with C5, C6
(δC 44.98 ppm), C7 (135.53), and C11 (20.80) were
2
O
Me
Me
O
10
O
O
4
1
9a
11
6
O
Me
5
IV
9
O
5a
8
Me
7
Me
Me
OR
Me
Me
Me
I, II
III
V
I, R = H; II, R = Ac.
1848

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REACTION OF LEVOGLUCOSENONE WITH (±)-α-TERPINEOL
Table 1. Reaction of (±)-α-terpineol (I) with levoglucosenone (IV) in toluene (method c)
1849
Pressure, atm
Ratio IV:I
Temperature, °C
Reaction time, h
Yield of V,a %
6000
6000
1:2.5
1:2
100
100
100
150
100
6.0
1.5
3.0
3.0
3.0
4
0
10000
10000
10000
1:2
5
Tarry material
b5b
1:2
2:1
a
Calculated on the initial levoglucosenone.
Calculated on the initial (±)-α-terpineol.
b
Table 2. Reaction of (±)-α-terpinyl acetate (II) with levoglucosenone (IV) in toluene (method d; reaction time 3 h)
Pressure, atm
Ratio IV:II
Temperature, °C
Yield of V,a %
6000
6000
1:1
1:1
100
150
150
150
150
200
00
11
10000
10000
10000
6000
1.5:1
2:1
22
35
37
3:1
1:2
Tarry material
a
Calculated on the initial (±)-α-terpinyl acetate.
observed. The position of the double C=C bond and
orientation of the methyl and isopropyl substituents
were determined using NOESY technique. The
NOESY spectrum revealed correlations between the
9a-H proton, on the one hand, and 2-HA (δ 3.75 ppm),
5a-H, 10-H (1.40), and 9-CH3 (1.3), on the other, while
the 5a-H proton displayed correlations with 9a-H,
2-HA, and methyl protons in the isopropyl fragment
(δ 0.88 ppm). Nuclear Overhauser effects were also
observed for 1-H and 2-HB (δ 3.87 ppm) and 1-H and
9-CH3. Furthermore, protons of the 9-CH3 group were
coupled with 8-H (δ 6.03 ppm), and 7-H (δ 5.92 ppm)
was coupled with the CH proton of the isopropyl group
(δ 2.97 ppm). These findings allowed us to assign endo
position to the double bond and R and S configurations
to C6 and C9, respectively.
was cooled to 0°C, and a catalytic amount of p-tolu-
enesulfonic acid (10%) was added. When the reaction
was complete (TLC), the mixture was evaporated
under reduced pressure on a rotary evaporator, and the
residue was purified by silica gel column chromatog-
raphy. Yield 0.232 g (91%), colorless liquid, Rf 0.65
1
(petroleum ether–EtOAc, 1:1). H NMR spectrum, δ,
ppm: 1.22 m (1H, CH2), 1.38 s (3H, CH3), 1.40 s (3H,
CH3), 1.62 br.s (3H, CH3), 1.70–1.82 m (2H, CH2),
1.94 s (3H, CH3), 1.90–2.12 m (4H, CH, CH2),
5.38 br.s (1H, CH). 13C NMR spectrum, δC, ppm:
22.45 (CH3), 23.08 (CH3), 23.29 (CH3), 23.83 (CH3),
23.83 (C6), 26.34 (C2), 30.86 (C5), 42.53 (C1), 84.81
(CHO), 120.30 (C3), 133.91 (C4), 170.48 (C=O).
Found, %: C 73.42; H 10.36. C12H20O2. Calculated, %:
C 73.43; H 10.27.
Further optimization of the reaction conditions for
(±)-α-terpineol (I) and its acetate II was performed at
pressures of 6000 and 10000 atm (methods c and d;
Tables 1, 2). It is seen that the optimum conditions for
the formation of Diels–Alder adduct (V) containing
a menthane fragment are as follows: pressure
10000 atm, temperature 150°C, levoglucosenone–
(±)-α-terpinyl acetate ratio 3:1.
(1S,4R,5aS,6R,9S,9aR)-1,4-Epoxy-6-isopropyl-9-
methyl-6,9-ethano-1,2,5a,6,9,9a-hexahydrobenzo[d]-
oxepin-5(4H)-one (V). a. α-Terpineol (I), 0.6 g
(3.9 mmol), was added to a solution of 2.45 g
(27.2 mmol) of oxalic acid in 5.0 mL of water, and the
mixture was heated under reflux until the reaction was
complete (TLC). The mixture was cooled and extract-
ed with petroleum ether (3×10 mL), and the combined
extracts were dried over MgSO4 and evaporated under
reduced pressure on a rotary evaporator. The residue
was dissolved in 3.0 mL of toluene, 0.231 g (1.84 mmol)
2-(4-Methylcyclohex-3-en-1-yl)propan-2-yl
acetate (II). A solution of 0.200 g (1.3 mmol) of
(±)-α-terpineol (I) in 2.0 mL of isopropenyl acetate
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

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GALIMOVA et al.
1850
of levoglucosenone (IV) was added, and the mixture
was heated for 9 h in a sealed glass ampule at 160°C.
The ampule was cooled and opened, the mixture was
evaporated under reduced pressure on a rotary evapo-
rator, and the residue was subjected to silica gel
column chromatography. Yield 0.031 g (3%), colorless
crystals, mp 61°C, [α]D20 = –167.2° (c = 1.0, CHCl3),
Rf 0.5 (benzene). IR spectrum, ν, cm–1: 2963, 1725,
d. α-Terpinyl acetate (II), 0.080 g (0.4 mmol), was
added to a solution of 0.154 g (1.2 mmol) of levo-
glucosenone (IV) in 1.3 mL of toluene. The mixture
was heated for 3 h in a high-pressure reactor at 150°C
and 10000 atm and was then treated as described
above in a. Yield 0.040 g (37%).
The spectral and analytical data were obtained
using the equipment of the Khimiya Joint Center at the
Institute of Organic Chemistry, Ufa Research Center,
1
1465, 1372, 1120, 992, 676, 501. H NMR spectrum,
1
Russian Academy of Sciences. The H and 13C NMR
δ, ppm: 0.88 d (6H, CH3, J = 6.9 Hz), 1.10 d.d (1H,
12-HA, J = 3.1, 9.1 Hz), 1.30 s (3H, CH3), 1.25–1.33 m
(2H, 11-H), 1.42 t.d (1H, 12-HB, J = 2.5, 9.1 Hz),
1.87 d.d (1H, 9a-H, J = 0.9, 8.6 Hz), 2.90 d (1H, 5a-H,
J = 8.6 Hz), 2.97 s (1H, 1′-H), 3.75 d (1H, 2-HA, J =
7.3 Hz), 3.87 d.d (1H, 2-HB, J = 4.6, 7.3 Hz), 4.77 d.d
(1H, 1-H, J = 0.9, 4.6 Hz), 4.79 s (1H, 4-H), 5.92 d
(1H, 7-H, J = 8.4 Hz), 6.03 d (1H, 8-H, J = 8.4 Hz).
13C NMR spectrum, δC, ppm: 16.76 (C1″), 18.70 (C2″),
20.80 (C11), 22.76 (CH3), 29.97 (C1′), 35.59 (C9), 38.13
(C10), 44.98 (C6), 48.58 (C9a), 49.29 (C5a), 68.29 (C2),
73.12 (C1), 100.61 (C4), 135.53 (C7), 138.26 (C8),
200.96 (C=O). Mass spectrum: m/z 262.2 [M]+. Found,
%: C 73.28; H 8.47. C16H22O3. Calculated, %: C 73.25;
H 8.45. M 262.34.
spectra were recorded on Bruker AM-300 (300 MHz
1
13
for H and 75.47 MHz for C) and Bruker Avance III
(500 MHz) instruments from solutions in CDCl3. The
IR spectra were measured on Shimadzu IR Prestige-21
and Bruker Tensor 27 spectrometers from films or
Nujol mulls. The mass spectra were obtained on
a Hewlett Packard 6890 chromatograph coupled with
an HP 5973 mass-selective detector. The optical rota-
tions were measured on a Perkin Elmer 341 polarim-
eter. Analytical TLC was performed on Sorbfil
PTSKh-AF-A plates. The melting points were deter-
mined on a Boetius PHMK 05 melting point apparatus.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 13-00-14056, 14-03-97007-r_povolzh’e_a).
b. α-Terpinyl acetate (II), 0.135 g (0.69 mmol), was
added to a solution of 0.260 g (2.06 mmol) of levo-
glucosenone (IV) in 3.0 mL of toluene. The mixture
was heated in a sealed glass ampule for 28 h at 160°C
and was then treated as described above in a. Yield
0.007 g (4%).
REFERENCES
1. Pilipenko, A.N., Sharipov, B.T., and Valeev, F.A., Russ. J.
Org. Chem., 2014, vol. 50, p. 1504.
c. α-Terpineol (I), 0.240 g (1.58 mmol), was added
to a solution of 0.100 g (0.79 mmol) of levogluco-
senone (IV) in 1.3 mL of toluene. The mixture was
heated for 3 h in a high-pressure reactor at 100°C and
10000 atm and was then treated as described above
in a. Yield 0.011 g (5%).
2. Sharipov, B.T., Pilipenko, A.N., and Valeev, F.A., Russ. J.
Org. Chem., 2014, vol. 50, p. 1628.
3. Tietze, L.-F. and Eicher, T., Reaktionen und Synthesen im
organisch-chemischen Praktikum und Forschungs-
laboratorium, Stuttgart: Georg Thieme, 1991, 2nd ed.
4. Rudloff, E., Can. J. Chem., 1961, vol. 39, p. 1.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014