7,7-Dimethyl-2,10-epoxybicyclo[3.1.1]heptane. Synthesis, structure, and products of epoxide ring cleavage

Article abstract of DOI:10.1023/A:1013251021230

7,7-Dimethyl-2,10-epoxybicyclo[3.1.1]heptane obtained by treatment of (-)-β-pinene with peroxybenzimidic acid has α configuration.

Full text of DOI:10.1023/A:1013251021230

Russian Journal of General Chemistry, Vol. 71, No. 8, 2001, pp. 1161 1164. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 8, 2001,
pp. 1233 1237.
Original Russian Text Copyright
2001 by Nikitina, Dieva, Plemenkov, Lodochnikova, Gubaidullin, Kataeva, Litvinov.
7,7-Dimethyl-2,10-epoxybicyclo[3.1.1]heptane.
Synthesis, Structure, and Products of Epoxide Ring Cleavage
L. E. Nikitina, S. A. Dieva, V. V. Plemenkov, O. A. Lodochnikova,
A. T. Gubaidullin, O. N. Kataeva, and I. A. Litvinov
Kurashov Kazan State Medical University, Kazan, Tatarstan, Russia
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center,
Russian Academy of Sciences, Kazan, Tatarstan, Russia
Received January 31, 2000
Abstract 7,7-Dimethyl-2,10-epoxybicyclo[3.1.1]heptane obtained by treatment of ( )- -pinene with
peroxybenzimidic acid has
configuration.
Synthesis of functional derivatives of bicyclic
monoterpenes is complicated by the tendency of the
latter for isomerization. In this connection terpene
oxides can serve as prospective synthons. The steric
structure of epoxides derived from bicyclic terpenes
oxidation products is formed, while with peracetic
acid, a mixture of cis and trans isomers in comparable
amounts [2, 3]. The peracid syntheses of -pinene
oxide have been reported, and the oxide has been
assumed to be a trans isomer (the epoxide ring is
is determined by the method of their synthesis, whose cleaved from a side opposite to the gem-dimethyl
choice is dictated by structural features of the ter-
penoid. In particular, 3-karene trans-oxide is best
prepared using various peracids, such as peroxy-
phthalic, peroxybenzimidic, and peracetic [1].
fragment). However, no direct evidence for this
assumption is available, while spectral data provide
no information on the steric structure of this com-
pound [4].
At the same time, oxidation of camphene with
peroxyphthalic acid gives the corresponding diol.
With peroxybenzimidic acid, a complex mixture of
We prepared -pinene oxide (II) by treatment of
( )- -pinene (I) in situ with peroxybenzimidic acid
by a procedure similar to that described in [5].
8
9
7
4
PhCNH2O2
MeOH
RS(NH)NH2 HCl
5
3
1
CH2SR
6
EtONa, EtOH
2
10
OH
O
I
II
III V
O2
O
III
CH2SMe
OH
VI
R = Me (III), CH2Ph (IV), CH2C6H4OPh-m (V).
Oxide II was reacted with S-alkylisothiuronium
salts (R = Me, CH2Ph, CH2C6H4OPh-m) in the pre-
sence of sodium ethylate to obtain sulfides III V. On
contact with atmospheric air compound III converted
into sulfoxide VI within 2 months. The crystal and
molecular structures of compound VI were established
by X-ray diffraction. The fact that sulfide III quanti-
tatively converts into sulfoxide VI whose molecule
1070-3632/01/7108-1161$25.00 2001 MAIK Nauka/Interperiodica

1162
NIKITINA et al.
Kutchabsky [6] explained the fact that the angle is
O1
S1
larger than
by nonbonding interactions between
methyl protons at C9 and the hydrogen atom at C3.
Probably, the same interactions are responsible for
strongly increased bond angles C1C7C9 [123.0(3) ]
and C5C7C9 [118.8(3) ] compared with C1C7C8
[110.1(3) ] and C5C7C8 [111.8(3) ]. The conformation
along the C2 C10 bond is staggered [the corresponding
torsion angles are as follows: O2C2 C10S1 48.0(3),
O2
C2 C3
C1
3
2
C1C2C10S1 167.9(3), and C3C2C10S1 68.2(4) ],
which is probably explained by steric factors.
Molecules of compound VI in crystal form an
infinite chain along the z axis due to intermolecular
hydrogen bonds O2 H20 O1 (1/2 x, y, 1/2 + z)
with the following parameters: O2 H20 1.18, H20 O1
2.18, O2 O1 2.786(4) , and O2 H20 O1 108 .
1
Note that the S1 O2 distance (2.962 ) in much
smaller than the sum of the van der Waals radii of
sulfur and oxygen (3.3 [8]). At present a great body
of information is available on 1,4-S O short contacts
involving bivalent sulfur, including entries in the
Cambridge Crystallographic Database and quantum-
chemical calculations [9 11]. Burling and Goldstein
[9] explained the 1,4-S O short contacts by electro-
static attraction of differently charged sulfur and
oxygen atoms; from this viewpoint, the sulfoxide
sulfur atom that bears a much greater positive charge
have serious reasons to enter nonbonded interactions
with the oxygen atom. However, these interactions
will be hindered by a much stronger steric conges-
tion of the three-coordinate sulfur atom compared
with two-coordinate.
0
2.6 2.8 3.0 3.2 3.4 3.6 3.8 4.0 4.2
r(S1 O2),
Fig. 1. Histogram of distribution of S O nonbonded
distances (E).
comprises a natural terpene moiety and a sulfoxide
function which is prospective in terms of biological
activity deserves special attention, the more so that
directed oxidation of sulfides to sulfoxides presents a
certain problem because sulfides tend to partly or
completely convert to sulfones.
The conformation of the pinane skeleton of mo-
lecule VI can be represented by mutual arrangement
We retrieved from the Cambridge Crystallographic
Database structures containing a sulfoxide function
and an oxygen atom intervened by three C C bonds
and meeting the following additional conditions: (1)
the C1, C2, and C3 atoms are in the sp3 state and,
consequently, do not affect considerably the charge on
the key sulfur and oxygen atoms and (2) rotation
about the C2 C3 bond is free, and, therefore, C2 and
C3 are not involved in a common ring and have no
bulky substituents. A total of 21 structures were
retrieved. Examining their geometry we focused on
S1 O2 distances and S1C2C3O2 torsion angles. The
of four planes: C1C2C4C5 (1), C2C3C4 (2), C1C7C5 (3),
and C1C6C5 (4).
As follows from X-ray diffraction data, the
C1C2C4C5 fragment is planar within 0.014(4) , and
the C3 and C7 atoms deviate from this plane in one
side by 0.139(4) and 1.046(4) , respectively, and the
C6 atom, in the opposite side by 1.083(5) . Thus,
the conformation of the C1C2C3C4C5C6 cyclohexane
ring can be defined as unsymmetrical chair, and the
conformation of the C1C2C3C4C5C7 six-membered
ring, as unsymmetrical boat. The dihedral angles [
171.3(8), 113.1(3), 105.8(3) ] are close to those
reported in [6, 7]. The hydroxy group is axial, and the
S=O-containing substituent is equatorial. Reck and
histogram of distribution of
S1 O2 nonbonded
distances (Fig. 1) shows that 81% of 1,4-S O con-
tacts are shorter than 3.2 , and they relate to a
gauche conformation along the C2 C3 bond. These
data give grounds to propose that tetravalent three-
coordinate sulfur, too, may form 1,4 short contacts.
The main result of the X-ray diffraction study of
compound VI (see table and Fig. 2) is as follows: The
methylenethiocarbonyl group is on the same side with
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 8 2001

7,7-DIMETHYL-2,10-EPOXYBICYCLO[3.1.1]HEPTANE
1163
Atomic coordinates in molecule VI, equivalent iso-
tropic thermal parameters for non-hydrogen atoms
[3.1.1]heptan-2-ol (V) structures. Stereochemically,
the adducts are apparently similar to compound III.
3
3
Thus, the proposed method of epoxidation of
-pinene provides an efficient synthetic route to
stereoindividual -pinene -oxide, which, in its turn,
allows stereodirected synthesis of heterofunctional
derivatives of the pinane series, whereas attempted
synthesis of the latter derivatives by electrophilic
addition to the -pinene double bond not infrequently
results in isomerization of the molecular skeleton to
give bornane structures [12].
B = 4/3
(ai aj)B(i,j), and isotropic thermal parameters
i= 1j= 1
for hydrogen atoms Biso
B, Biso
,
Atom
x
y
z
S1
0.4559(1) 1.04131(4)
0.5418(5) 1.0328(1)
0.1599(4) 0.9486(1)
0.3192(6) 0.8680(2)
0.3366(6) 0.9210(2)
0.4069(6) 0.8991(2)
0.4084(8) 0.8293(2)
0.3710(6) 0.7944(2)
0.1933(7) 0.8200(2)
0.4779(6) 0.8203(2)
0.4625(6) 0.9707(2)
0.4702(7) 0.7775(2)
0.6810(7) 0.8377(2)
0.629(1)
0.2985
0.3856
0.0010
0.5333
0.3346
0.5224
0.3111
0.1064
0.1291
0.4247
0.5861
0.3597
0.4676
0.5830
0.7194
0.7526
0.7206
0.7509
0.5795
0.6720
0.9047(1) 3.62(2)
1.0869(3) 4.58(6)
0.8983(3) 3.75(5)
0.7399(4) 3.21(7)
0.8684(4) 2.91(7)
1.0527(4) 3.59(8)
1.0795(5) 4.69(9)
0.9124(6) 3.92(8)
0.8265(6) 4.50(9)
0.7515(5) 3.33(7)
0.7872(4) 3.16(7)
0.5899(6) 4.78(9)
0.7753(6) 4.14(9)
0.7739(7) 6.2(1)
O1
O2
C1
EXPERIMENTAL
C2
C3
1
The H NMR spectra were obtained on a Varian
C4
Unity-300 spectrometer (300 MHz) in CDCl3. Single-
crystal X-ray analysis was performed on an Enraf
Nonius CAD-4 automatic four-circle K-diffractometer.
C5
C6
C7
Crystals of compound VI are rhombic, at 20 C: a
7.231(5), b 22.09(2), c 7.514(3) ; V 1200(1) 3, Z 4,
dcalc 1.11 g/cm3, space group P212121.
C10
C8
C9
C11
H1
1.0787(3)
0.8879
0.7521
0.9499
0.9138
0.9185
0.8167
0.8194
0.8354
0.7937
0.9770
0.9554
0.7455
0.8012
0.7543
0.8630
0.8017
0.8593
1.0441
1.0891
1.1138
The unit cell parameters and the intensities of 1774
reflections, 1673 of which had I 3 , were measured
at 20 C ( CuK 1.5418 , graphite monochromator,
0.6280
0.9384
0.8700
1.0659
1.1425
1.1309
1.1665
0.9123
0.7476
0.6675
0.7878
0.5825
0.4860
0.5921
0.8776
0.7888
0.6746
0.7542
0.6595
0.8310
2
4
6
3
3
6
6
4
4
4
4
6
6
6
6
4
4
6
8
8
H5
H20
H31
H32
H41
H42
H61
H62
H101
H102
H81
H82
H83
H91
H92
H93
H111
H112
H113
/2 scanning,
74.3 ). No absorption corrections
1
were applied ( Cu 20.53 cm ). The structure was
solved by the direct method by the SIR program [13]
and refined first isotropically and then anisotropically.
Hydrogen atoms were revealed by difference synthesis,
and methyl H atoms were placed at calculated posi-
tions. In the final refinement step the contributions of
hydrogen atoms in structure amplitudes were included
with fixed positional and thermal parameters. The
absolute configuration was established via refinement
of the direct and inverted structures with allowance
for anomalous scattering for all non-hydrogen atoms.
C4
O1
C3
O2
C5
C6
C7
C2
S1
the endo-methylene bridge bearing the gem-methylene
group, while the hydroxy group is trans to the bridge.
These data suggest configuration of the parent oxide
II, since on base-induced cleavage of the oxirane ring
the oxygen atom does not change its position.
C10
C1
C11
C9
C8
Spectral evidence allows compounds IV and V to
be assigned the 7,7-dimethyl-2-[(2-hydroxyethylthio)-
methyl]bicyclo[3.1.1]heptan-2-ol (IV) and 7,7-di-
methyl-2-[(m-phenoxybenzylthio)methyl]bicyclo
Fig. 2. Molecular structure of 7,7-dimethyl-2-[(methyl-
sulfinyl)methyl]bicyclo[3.1.1]heptan-2-ol (VI) as given
by single-crystal X-ray diffraction.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 8 2001

1164
NIKITINA et al.
The divergence factors for the direct structure were R
0.047 and RW 0.056 and for the inverted structure, R
0.058 and RW 0.074. According to Hamilton’s test
[14], the direct structure fits the absolute configuration
with a probability of 95%. The final divergence
factors were R 0.048 and RW 0.058.
crystals by oxidation of compound III with atmos-
pheric oxygen for 2 months, yield 98%. IR spectrum,
1
1
, cm : 1040 (S=O), 3500 (OH). H NMR spectrum,
, ppm: 1.05 s, 1.42 s (6H, CH3C8,9), 2.95, 3.23 (2H,
C10H2, centers of AB system, J 13.0 Hz), 2.46 s (3H,
SCH3), 2.74 s (OH).
The atomic coordinates are listed in the table. All
calculations were performed using the MolEN
program complex [15] on DEC Alpha Station 200.
ACKNOWLEDGMENTS
The work was financially supported by the
INCO COPERNICUS Foundation (grant no. IC 15
CT 98 0150).
7,7-Dimethyl-2,10-epoxybicyclo[3.1.1]heptane
(II). To a solution of 92 mmol of -pinene and
99 mmol of benzonitrile in 137 ml of absolute me-
thanol we added 45 mmol of KHCO3, after which
0.28 mol of a 50% solution of H2O2 was added drop-
wise so that the temperature of the reaction mixture
was maintained below 20 C. The mixture was allowed
to stir at room temperature for 5 days and then diluted
by half with water, treated with diethyl ether, and the
ethereal extracts were dried with MgSO4. The solvent
was removed, the residue was diluted with 50 ml of
hexane, the precipitate was removed, and product II
was distilled in a vacuum, yield 74%, bp 74 79 C
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1
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absolute ethanol) we added with stirring 1.52 g of
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2-[(2-Hydroxyethylthio)methyl]-7,7-dimethylbi-
cyclo[3.1.1]heptan-2-ol (IV) and 7,7-dimethyl-2-
[(m-phenoxybenzylthio)methyl]bicyclo[3.1.1]-
heptan-2-ol (V) were obtained similarly to compound
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1
III. Compound IV, yield 67%. H NMR spectrum, ,
ppm: 0.75 s, 1.25 s (6H, CH3C8,9), 2.54, 2.62 (2H,
C10H2, centers of AB system, J 12.7 Hz), 3.62 s (2H,
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1
SCH2), 3.05 s (OH). Compound V, yield 82%. H
NMR spectrum, , ppm: 1.02 s, 1.21 s (6H, CH3C8,9),
2.85, 2.94 (2H, C10H2, centers of AB system, J
11.7 Hz), 3.63 s (2H, SCH2), 3.15 s (OH).
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 8 2001