Transformations of epoxide derived from nopol over askanite-bentonite clay

Article abstract of DOI:10.1007/s11178-005-0036-y

Transformations of epoxide derived from nopol in the presence of natural askanite-bentonite clay were studied. The major products of the isomerization in the cold are diols possessing a p-menthane skeleton, which are readily converted into bicyclic ethers when the reaction is carried out at room temperature.

Full text of DOI:10.1007/s11178-005-0036-y

Russian Journal of Organic Chemistry, Vol. 40, No. 10, 2004, pp. 1432–1436. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 10, 2004,
pp. 1483–1487.
Original Russian Text Copyright © 2004 by Il’ina, Volcho, Korchagina, Salakhutdinov, Barkhash.
Transformations of Epoxide Derived from Nopol
over Askanite–Bentonite Clay
I. V. Il’ina, K. P. Volcho, D. V. Korchagina, N. F. Salakhutdinov, and V. A. Barkhash
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: volcho@nioch.nsc.ru
Received March 11, 2004
Abstract—Transformations of epoxide derived from nopol in the presence of natural askanite–bentonite clay
were studied. The major products of the isomerization in the cold are diols possessing a p-menthane skeleton,
which are readily converted into bicyclic ethers when the reaction is carried out at room temperature.
Reactions of pinane terpenoids with carbonyl com-
pounds over askanite–bentonite clay involve unusual
transformations leading to fairly complex polyhetero-
cyclic compounds from simple and accessible initial
substances [1]. The use of clays as catalysts in these
processes considerably improves their ecological
safety, simplifies treatment of the reaction mixtures,
and sometimes gives rise to novel reaction paths which
have been unknown previously for homogeneous reac-
tions. For example, by reactions of verbenol (I) with
salicylaldehyde and α-methylacrolein over askanite–
bentonite clay we obtained unusual products II and
III, respectively (Scheme 1).
formation of a large number of products (according to
the GLC data).
We previously showed [1, 3] that epoxidation of
the double bond in a terpenoid molecule considerably
enhances its reactivity under conditions of hetero-
geneous acid catalysis. For instance, α-pinene does not
react with aldehydes in the presence of askanite–ben-
tonite clay, whereas the corresponding epoxy deriva-
tive readily undergoes intermolecular transformations
to give various polyheterocyclic products. In some
cases, introduction of an epoxy group into terpenoids
essentially changed the reaction direction, as compared
with the parent olefin. As a result, we succeeded in
obtaining acetals with a fused polycyclic skeleton, keto
and aldo ethers, spirocyclic acetals, and polycyclic
diethers by reactions of aldehydes and ketones with
epoxides derived from terpenoids.
Epoxy derivative V was synthesized in 88% yield
by oxidation of (R)-nopol (IV) with peroxyacetic acid
according to the procedure reported in [4]. It is known
[5] that heating of compound V in boiling toluene in
the presence of anhydrous ZnBr2 gives 61% of
aldehyde VI (Scheme 2) [5]. We have found no other
published data on the reactivity of epoxy derivative V
In the present work we continued our studies on the
reactivity of alcohols of the pinane series in the pres-
ence of a natural montmorillonite, askanite–bentonite.
As subject for study we selected (R)-nopol (IV) which
is readily available from (–)-β-pinene by the Prins
reaction [2]. Unlike verbenol (I), nopol (IV) failed to
react with acrolein, crotonaldehyde, butyraldehyde,
and salicylaldehyde in the presence of askanite–bento-
nite clay. It remained almost unchanged on keeping at
0°C over askanite-bentonite, while raising the tempera-
ture to 20°C resulted in slow isomerization of IV with
Scheme 1.
OH
O
HO
CH2=C(CH3)CHO
O
CHO
O
II
I
III
1070-4280/04/4010-1432 © 2004 MAIK “Nauka/Interperiodica”

TRANSFORMATIONS OF EPOXIDE DERIVED FROM NOPOL
1433
Scheme 2.
CH3COOOH
H+
~C–C
HO
O
OH
OH
OH
OH
OH
IV
V
A
B
4
5
1
7
11
~C–C
~C–C
–H+
OCH
3
OH
A
2
10
6
8
9
OH
OH
VI
10
9
10
10
11
11
11
9
9
Hax
5
4
5
4
6
1
6
4
3
3
2
5
6
~H
–H+, –H2O
+
B
–H+
1
3
HO
HO
2
2
1
OH
OH
OH
7
7
7
8
8
8
VII
VIII
IX
under conditions of acid catalysis. When compound V
was kept for 45 min in methylene chloride over aska-
nite–bentonite at –25±5°C, apart from the expected
aldehyde VI (yield 19.5%), we obtained diols VII and
VIII at a ratio of ~1:3 in an overall yield of 34.8%.
Raising the temperature to 0°C resulted in slight
decrease in the yields of diols VII and VIII (28.8%,
ratio 1:1) and aldehyde VI (16.0%). In addition, we
isolated a small amount (5.5%) of fatty–aromatic al-
cohol IX (Scheme 2). According to the GLC data, no
appreciable changes in the qualitative and quantitative
composition of the reaction mixture were observed
upon replacement of natural askanite–bentonite by
commerciably available K10 montmorillonite.
benzene which was converted into the corresponding
Grignard compound, and the latter was treated with
oxirane; in this case, the overall yield of IX did not
exceed 25% [7]. These data show that alcohol IX is
a fairly difficultly accessible compound and that
development of a procedure for its preparation from
epoxide V may be promising provided that consider-
able amounts of compound IX would be required.
When the transformation of compound V over
askanite–bentonite was performed at 20°C, the overall
yield of the products considerably decreased, and their
composition sharply changed. The major products
were compound IX (10.2%) and aldehyde VI (7.2%),
and a small amount of a mixture of bicyclic ethers X
and XI was isolated (ratio 1:1, overall yield 3.7%;
Scheme 3). No compounds VII and VIII were de-
tected in the reaction mixture. Like diols VII and VIII,
compounds X and XI were not reported previously. It
should be noted that, unlike the reaction at reduced
temperature, the transformation of epoxide V at room
temperature requires a large excess of askanite–ben-
tonite clay to be used in order to obtain reproducible
results.
Diols VII and VIII were not reported previously,
while compound IX was synthesized by several
methods [6, 7]. One of these included chloromethyla-
tion of cumene, treatment of 1-chloromethyl-4-iso-
propylbenzene thus obtained with sodium cyanide,
hydrolysis of the resulting nitrile to the corresponding
acid, and reduction of the acid to alcohol IX; the over-
all yield was less than 5% [6]. According to another
procedure, p-bromoacetophenone was brought into
reaction with methylmagnesium iodide, the resulting
alcohol was heated with a mixture of iodine, phos-
phorus, and acetic acid to obtain p-bromoisopropyl-
Presumably, ethers X and XI are formed through
intermediate diols VII and VIII, as shown in
Scheme 3. To verify this assumption, a mixture of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

IL’INA et al.
1434
Scheme 3.
11
12
11
12
10
10
4
4
3
2
3
2
5
6
5
6
+
+
HO
HO
O
O
1
1
O
OH
OH
OH
9
9
8
8
V
VII
VIII
X
XI
compounds VII and VIII at a ratio of ~1:1 was kept
for 1 h over askanite–bentonite at 20°C. During this
period, diols VII and VIII were consumed completely,
and a ~1:1 mixture of bicyclic ethers X and XI was
formed in an overall yield of 19.6%.
group on C1 and isopropenyl group on C5 are arranged
trans with respect to each other.
The C1/C4, C2/C6, and C3/C5 signals in the 13C
NMR spectrum of IX were assigned by analogy with
published data for structurally related compounds
XII and XIII [8].
Unlike epoxy derivative of α-pinene, compound V
failed to react with aldehydes (such as salicylaldehyde,
butyraldehyde, or acrolein) over askanite–bentonite.
Our attempts to effect such reactions resulted in
formation of only products of isomerization of initial
compound V.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Bruker AM-400 spectrometer operating at 400.13
and 100.61 MHz, respectively; a ~1:1 (by volume)
mixture of CDCl3 and CCl4 was used as solvent, and
the chemical shifts were measured relative to the sol-
vent signals (CHCl3: δ 7.24 ppm, δC 76.90 ppm). The
The structure of the isolated compounds was
1
proved by the H and 13C NMR, IR, and mass spectra.
1
The H and 13C NMR spectral parameters of com-
1
signals were identified using H–1H double resonance
pound VI were similar to those reported in [5];
however, in the present work we give a more detailed
1H NMR spectrum of this compound. The C5 and C9
signals in the 13C NMR spectrum of VII were assigned
using the LRJMD technique. Suppression of the signal
from the olefinic 3-H proton (δ 5.57 ppm) led to
appearance in the LRJMD spectrum of a signal at
δC 122.60 ppm (among two downfield signals at
δC 122.60 and 126.08 ppm), so that it was assigned to
C5. In the upfield region of the spectrum, signals from
the C1, C4, and C7 atoms were located at δC 68.94,
29.74, and 38.57 ppm, respectively; their positions are
similar to the corresponding signals of VIII.
technique, off-resonance 13C NMR spectra, two-
dimensional correlation with direct 13C–1H coupling
1
constants (COSY, JCH = 135 Hz), and one-dimen-
sional correlation with long-range 13C–1H coupling
n
constants (LRJMD, JCH = 10 Hz, n = 2, 3). The high-
resolution mass spectra were obtained on a Finnigan
MAT 8200 instrument. The optical rotations [α]580
were measured on a Polamat A spectropolarimeter
from solutions in CHCl3 (given are the concentrations
in grams per 100 ml of the solution). The IR spectra
were recorded on a Bruker Vector 22 spectrometer
from solutions in carbon tetrachloride.
Pseudoequatorial orientation of the 1-H proton and
axial orientation of the 5-H proton in molecule VIII
follow from the corresponding vicinal coupling con-
stants: 3J1,6-ax = 4 Hz, 3J1,6-eq = 2.5 Hz; 3J5,6-ax = 13 Hz,
3J5,4'-ax = 11 Hz. These data indicate that the hydroxy
The initial compounds and products were analyzed
by GLC on a Model 3700 chromatograph equipped
with a flame ionization detector; VC-30 quartz capil-
lary column, 15000×0.22 mm; carrier gas helium,
inlet pressure 1 atm.
Askanite–bentonite clay used as catalyst was pre-
pared by acid activation of bentonite clay from the
Askan deposite (TU 113-12-86-82) and K10 montmor-
rilonite (from Fluka). The catalyst was heated for 3 h
at 110°C prior to use. The solvent was dried by passing
through a column charged with calcined aluminum
oxide. The products were isolated by column chro-
matography on silica gel (40–100 µm) using diethyl
OH
XII
XIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

TRANSFORMATIONS OF EPOXIDE DERIVED FROM NOPOL
1435
20
1
ether–hexane mixtures containing 0 to 100% of the
Compound VIII. [α] = +8.2° (c = 2.7). H NMR
580
2
spectrum, δ, ppm (J, Hz): 1.50 d.d.d (6-Hax, J = 13,
former.
J6-ax, 5-ax = 13, J6-ax,1'-eq = 4), 1.71 br.s (C11H3),
1.84 d.d.d.m (4'-Hax, 2J = 18, J4'-ax,5-ax = 11, J4'-ax,3 = 2),
1.89 d.d.d.d (6-Heq, 2J = 13, J6-eq,5-ax = 3, J6-eq,1'-eq = 2.5,
J6-eq,4'-eq = 1.5), 2.15 d.d.d.m (4'-Heq, 2J = 18, J4'-eq,3 = 5,
20
Nopol (IV) from Fluka was used, [α] = –43.6°
580
(c = 8.3); epoxy derivative V was synthesized by treat-
20
580
ment of IV with peroxyacetic acid, [α] = –85.5°
(c = 7.3); published data [5]: [α]D20 = –98°.
J4'-eq,5-ax = 5), 2.18 d.d.d.d (7-H, 2J = 14, J7,8 = 9, J7,8'
=
Transformations of compound V over askanite–
bentonite at –25±5°C. A solution of 0.210 g of com-
pound V in 5 ml of methylene chloride was added
under stirring to a suspension of 0.22 g of askanite–
bentonite clay in 5 ml of methylene chloride, cooled to
–25°C, and the mixture was stirred for 45 min, main-
taining the temperature at –25±5°C. The catalyst was
filtered off, the solvent was distilled off under reduced
pressure, and the residue, 0.20 g, was subjected to
chromatography on a column charged with 8 g of silica
gel. We isolated 0.041 g (19.5%) of 2-[(R)-3-(2-hy-
droxyethyl)-2,2-dimethyl-3-cyclopentenyl]acetalde-
hyde (VI) and 0.073 g (34.8%) of a mixture of (1R)-2-
(2-hydroxyethyl)-5-(1-methylethylidene)-2-cyclo-
hexenol (VII) and (1R,5S)-2-(2-hydroxyethyl)-5-iso-
propenyl-2-cyclohexenol (VIII) at a ratio of ~1:3
2
4.5, J7,4'-ax = 1.5), 2.34 d.d.d (7'-H, J = 14, J7',8' = 4.5,
J7',8 = 3.5), 2.39 m (5-Hax, J5-ax,6-ax = 13, J5-ax,4'-ax = 11,
J5-ax,4'-eq = 5, J5-ax,6-eq = 3), 3.52 d.d.d (8-H, J = 10.5,
2
2
J8,7 = 9, J8,7' = 3.5), 3.75 d.d.d (8'-H, J = 10.5, J8',7
=
4.5, J8', 7' = 4.5), 4.01 br.d.d (1'-Heq, J1'-eq, 6-ax = 4,
J1'-eq,6-eq = 2.5), 4.32 br.s (2H, OH), 4.68 m (2H, 10-H),
5.62 d.d (3-H, J3,4'-eq = 5, J3,4'-ax = 2). 13C NMR spec-
trum, δC, ppm: 67.14 d (C1), 136.61 s (C2), 127.96 d
(C3), 31.24 t (C4), 34.87 d (C5), 36.29 t (C6), 39.47 t
(C7), 62.71 t (C8), 148.83 s (C9), 109. 21 t (C10),
20.96 q (C11). Found, m/z: 180.11561 [M – H2]+.
C11H16O2. Calculated: M 180.11502.
Transformations of compound V over askanite–
bentonite at 0°C. A solution of 0.570 g of compound
V in 15 ml of methylene chloride was cooled to 0°C
and added under stirring to a suspension of 0.6 g of
askanite–bentonite clay in 15 ml of CH2Cl2 cooled to
0°C, and the mixture was stirred for 45 min at 0°C.
The catalyst was filtered off, the solvent was distilled
off under reduced pressure, and the residue, 0.570 g,
was subjected to chromatography on a column charged
with 25 g of silica gel. We isolated 0.091 g (16%) of
aldehyde VI, 0.164 g of a mixture of compounds VII
(according to the 1H NMR data).
20
580
Compound VI. [α] = +6.5° (c = 1.2); published
data [5]: [α]D20 = +6.4 (c = 2.1, CHCl3). IR spectrum:
ν(C=O) 1729 cm–1. 1H NMR spectrum, δ, ppm (J, Hz):
2
0.79 s (C8H3), 1.00 s (C9H3), 1.92 d.d.t.d (5-H, J =
15.5, J5,1 = 9, J5,10 = 2.5, J5,4 = 2), 2.22 m (2H, 10-H),
2.26 m (1-H, J1,6 = 10, J1,5 = 9, J1,5' = 7, J1,6' = 4),
2
2.37 d.d.d (6-H, J = 15, J6, 1 = 10, J6, 7 = 2.5),
2
1
2.45 d.d.d.t (5'-H, J = 15.5, J5',1 = 7, J5',4 = 3, J5',10
=
and VIII at a ratio of ~1:1 (according to the H NMR
data; overall yield 28.8%), and 0.028 g (5.5%) of
2-(4-isopropylphenyl)ethanol (IX).
2
1.5), 2.53 d.d.d (6'-H, J = 15, J6', 1 = 4, J6', 7 = 2),
3.75 m (2H, 11-H), 5.34 m (4-H, J4, 5' = 3, J4,5 = 2,
J4,10 = 1.5), 9.78 d.d (7-H, J7,6 = 2.5, J7,6' = 2). Found,
m/z: [M]+ 182.13085. C11H18O2. Calculated:
M 182.13067.
1
Compound IX. H NMR spectrum, δ, ppm (J, Hz):
1.22 d (C10H3, C11H3, J = 7), 2.83 br.t (2H, 7-H, J7,8
=
6), 2.87 sept (9-H, J = 7), 3.85 br.t (2H, 8-H, J8,7 = 6),
7.10–7.18 m (4H, Harom). 13C NMR spectrum, δC, ppm:
135.54 s (C1), 128.85 d (C2, C6), 126.52 d (C3, C5),
146.97 s (C4), 38.65 t (C7), 63.64 t (C8), 33.60 d
(C9), 23.91 q (C10, C11). Found, m/z: [M]+ 164.12018.
C11H16O. Calculated: M 164.12011.
Compound VII was not isolated in the pure state.
The NMR spectra were recorded for a mixture of VII
1
and VIII at a ratio of ~1:0.7. H NMR spectrum of
VII, δ, ppm (J, Hz): 1.66 br.s and 1.71 br.s (C10H3,
C11H3), 2.23 m and 2.37 m (2H, 7-H), 2.29 br.d (6-H,
2
2J = 14), 2.63 br.d (4-H, J = 20), 2.67 d.d (6'-H,
2
2J = 14, J6',1 = 4), 2.90 br.d.d (4'-H, J = 20, J4',3 = 4),
Transformations of compound V over askanite–
bentonite at 20°C. A solution of 0.480 g of compound
V in 15 ml of methylene chloride was added under
stirring to a suspension of 2.5 g of askanite–bentonite
clay in 15 ml of methylene chloride, and the mixture
was stirred for 1 h at 20°C. The catalyst was filtered
off, the solvent was distilled off under reduced pres-
sure, and the residue, 0.48 g, was subjected to
chromatography on a column charged with 25 g of
2
3.17 br.s (2H, OH), 3.59 d.d.d (8-H, J = 11, J8,7 = 8,
2
J8,7' = 4), 3.73 d.d.d (8'-H, J = 11, J8',7' = 6, J8',7
=
4.5), 4.08 d.d (1-H, J1,6' = 4, J1,6 = 3.5), 5.57 d.d.d.d
(3-H, J3,4' = 4, J3,4 = 3, J3,7 = 1, J3,7' = 1). 13C NMR
spectrum, δC, ppm: 68.94 d (C1), 137.38 s (C2),
127.03 d (C3), 29.74 t (C4), 122.60 s (C5), 35.30 t (C6),
38.57 t (C7), 62.26 t (C8), 126.08 s (C9), 20.04 q and
19.77 q (C10, C11).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004

IL’INA et al.
1436
silica gel. We isolated 0.034 g (7.2%) of compound VI,
0.044 g (10.2%) of compound IX, and 0.016 g (3.7%)
of a mixture of (R)-6-(1-methylethylidene)-2,3,5,6,-
7,7a-hexahydrobenzofuran (X) and (6S,7aR)-6-(1-
methylethenyl)-2,3,5,6,7,7a-hexahydrobenzofuran (XI)
at a ratio of ~1:1 (according to the 1H NMR data).
2 ml of methylene chloride was added to a suspension
of 0.06 g of askanite–bentonite in 2 ml of methylene
chloride, and the mixture was stirred for 45 min at
20°C. The catalyst was filtered off, the solvent was
distilled off under reduced pressure, and the residue,
0.04 g, was subjected to chromatography on a column
charged with 4 g of silica gel. We isolated 0.009 g
(19.6%) of a mixture of bicyclic ethers X and XI at
a ratio of ~1:1 (according to the 1H NMR data).
20
1
Compound X. [α] = –24.6° (c = 3.7). H NMR
580
spectrum, δ, ppm (J, Hz): 1.65 m and 1.71 br.s (C11H3,
C12H3), 1.66 m (5-H), 2.42–2.58 m (2H, 9-H),
2
2
This study was performed under financial support
by the Ministry of Industry, Science, and Technology
of the Russian Federation (grant of the President of
the Russian Federation no. MK-771.2003.03) and by
the Foundation for Support of Domestic Science
(grant “Young Candidates of Science of the Russian
Academy of Sciences”).
2.61 br.d (3-H, J = 20), 2.84 d.m (3'-H, J = 20),
2
3.10 d.d (5'-H, J = 12, J5',6 = 5.5), 3.79 d.d.d (8-H,
2J = 8.5, J8,9' = 8.5, J8,9 = 6.5), 3.87 m (6-H), 3.89 d.d.d
2
(8'-H, J = 8.5, J8',9 = 8, J8',9' = 6), 5.49 m (2-H, J =
1.5–3.5 Hz). 13C NMR spectrum, δC, ppm: 140.61 s
(C1), 117.38 d (C2), 29.44 t (C3), 125.87 s and 124.20 s
(C4, C10), 33.51 t (C5), 76.65 d (C6), 66.49 t (C8),
30.65 t (C9), 20.43 q and 20.52 q (C11, C12). Found, m/z:
[M]+ 164.12007. C11H16O. Calculated: M 164.12011.
REFERENCES
20
1
Compound XI. [α] = +6.5° (c = 1.2). H NMR
1. Il’ina, I.V., Korchagina, D.V., Salakhutdinov, N.F., and
Barkhash, V.A., Russ. J. Org. Chem., 2000, vol. 36,
p. 1446.
580
2
spectrum, δ, ppm (J, Hz): 1.40 d.d.d (5-H, J = 12,
J5,6 = 9.5, J5,4 = 4), 1.77 br.s (C12H3), 2.18 d.m (3-H,
2J = 20), 2.26 d.m (3'-H, 2J = 20), 2.22 d.d.d (5'-H, 2J =
2. Bain, J.P., J. Am. Chem. Soc., 1946, vol. 68, p. 638.
2
3. Volcho, K.P., Tatarova, L.E., Korchagina, D.V., Salakhut-
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6. Bost, J.J., Kepner, R.E., and Webb, A.D., J. Org. Chem.,
1957, vol. 22, p. 51.
12, J5',6 = 5.5, J5,4' = 4), 2.43 d.d.d.m (9-H, J = 15,
2
J9,8' = 8, J9,8 = 6.5), 2.52 d.m (9'-H, J = 15), 2.47 m
2
(4-H), 3.72 d.d.d (8-H, J = 8.5, J8,9' = 8.5, J8,9 = 6.5),
3.76 m (6-H), 3.86 d.d.d (8'-H, 2J = 8.5, J8',9 = 8, J8',9'
=
5.5), 4.61 br.s and 4.74 br.s (2H, 11-H), 5.47 m (2-H,
J = 2–3.5 Hz). 13C NMR spectrum, δC, ppm: 138.71 s
(C1), 117.34 d (C2), 29.40 t (C3), 37.50 d (C4), 30.38 t
(C5), 73.34 d (C6), 65.72 t (C8), 30.62 t (C9), 146.81 s
(C10), 109.93 t (C11), 22.15 q (C12). Found, m/z:
[M]+ 164.12007. C11H16O. Calculated: M 164.12011.
7. Adachi, K., Nippon Kagaku Zasshi, 1971, vol. 92, p. 654;
Chem. Abstr., 1972, vol. 76, no. 59286.
8. Bohlmann, F., Zeistery, R., and Klein, E., Org. Magn.
Reson., 1975, vol. 7, p. 426.
Transformations of a mixture of diols VII and
VIII over askanite–bentonite at 20°C. A solution of
0.051 g of a ~1:1 mixture of diols VII and VIII in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 10 2004