Synthesis and isomerization of tricyclo[7.3.1.02,7]tridecen-13-ones

Article abstract of DOI:10.1023/A:1013423205456

Dehydration of 2-hydroxy-8-R-tricyclo[7.3.1.0^2,7]tridecan-13-ones (R = H, Me, Ph) effected by various reagents provided 8-R-tricyclo[7.3.1.0^2,7]tridecen-13-ones with different positions of the double bond. In the presence of phosphoric acid arise isomers with the double bond in 2(3) position, a mixture of hydrochloric and acetic acid primarily affords isomers with the double bond in 2(7) position that further migrates into 7(8) position at R = Me, Ph.

Full text of DOI:10.1023/A:1013423205456

Russian Journal of Organic Chemistry, Vol. 37, No. 10, 2001, pp. 1414 1417. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 10, 2001,
pp. 1483 1487.
Original Russian Text Copyright
2001 by Rostovskaya, Vysotskaya, Grigorchuk, Vysotskii.
Synthesis and Isomerization
of Tricyclo[7.3.1.02,7]tridecen-13-ones*
2
M. F. Rostovskaya1, T. A. Vysotskaya , V. P. Grigorchuk2, and V. I. Vysotskii2
1Far-Eastern Academy of Economics and Management, Vladivostok, 690600 Russia
2Far-Eastern State University, Vladivostok, 690600 Russia
Received September 15, 2000
Abstract Dehydration of 2-hydroxy-8-R-tricyclo[7.3.1.02,7]tridecan-13-ones (R = H, Me, Ph) effected by
various reagents provided 8-R-tricyclo[7.3.1.02,7]tridecen-13-ones with different positions of the double bond.
In the presence of phosphoric acid arise isomers with the double bond in 2(3) position, a mixture of
hydrochloric and acetic acid primarily affords isomers with the double bond in 2(7) position that further
migrates into 7(8) position at R = Me, Ph.
From the plants of Meliaceae family were isolated
so-called limonoids (mexicanolide, sweetenin etc.)
[1]. The basic part of their structure is a tricyclo-
[7.3.1.02,7]tridecan-13-one system (I) where in the
positions 2(3), 2(7) or 6(7) can be located a double
bond.
ketones II IV, ketols V VII, and the products of
dehydration thereof VIII X. The first representatives
of these compounds were prepared by condensation of
cyclohexanone with aldehydes [2].
Previously it was supposed a priori that the double
bond in compounds VIII X was located in 2(7)
position [3].
The problem of the double bond location was first
considered in [4], and it was shown that at R = CH3
the double bond might be both in 2(7) and 7(8)
positions. It was shown in [5] that the position of he
double bond depended on the dehydration agent used
in the reaction with ketol. The problem of ketols
V VII dehydration was treated in more detail by
Cocker and Shannon [6]. They concluded that dehydr-
ation by different reagents gave rise to unsaturated
ketones with dissimilar location of the double bond.
The possibility of the double bond migration in the
unsaturated ketones remained unclear.
As a convenient model for the study of specific
features inherent to structure I may serve the products
of intramolecular condensation of alicyclic 1,5-di-
We found that dehydration of ketols V VII by
acidic reagents afforded mixtures of unsaturated
ketones with predominant content of some component
(Table 1). We carried out dehydration of 2-hydroxy-
8-R-tricyclo[7.3.1.02,7]tridecan-13-ones
in
the
presence of phosphoric acid. In this case ketol V
yielded a single enone VIIIa that we separated in a
considerably high yield (70%), ketol VI afforded a
mixture of compounds IXa and IXb in 7: 2 ratio, and
ketol VII gave rise to a mixture of compounds Xa
and Xb. No migration of double bonds in compounds
VIIIa Xb occurred under the condition of synthesis.
R= H (II, V, VIII), CH3 (III, VI, IX), C6H5 (IV, VII,
X).
*
The work was carried out under financial support from the
Scientific and Educational Center for Fundamental Studies on
Sea Biota (grant REC=003)
At the use as dehydrating agent of a mixture of
hydrochloric and acetic acids [3] arise compounds
Deceased.
1070-4280/01/3710-1414$25.00 2001 MAIK Nauka/Interperiodica

SYNTHESIS AND ISOMERIZATION OF TRICYCLO[7.3.1.02,7]TRIDECEN-13-ONES
1415
VIIIb Xb. Unsubstituted ketol V afforded compound
VIIIb; we did not detect its isomer VIIIc. In the
course of time the double bond in compounds
IXb, Xb gradually migrated into 7(8) position
providing compounds IXc, Xc. In dehydration of
ketol VI at 60 C in 30 min in the mixture appeared
only unsaturated ketone IXb, whereas after 3 h the
ratio of compounds IXb : IXc was 3 : 1. In reaction
of ketol VII with the mixture HCl CH3COOH we
failed to isolate compound Xb, and its presence in the
reaction mixture within the initial 3 h of reaction was
Table 1. The ratio of dehydration products IXa c, Xa c
from ketols VI, VII depending on conditions of the
reactiona
Reaction Ketol VI in a mixture
Ketol VII in
time, h
HCl CH3COOH
phosphoric acid
IXa
IXb
IXc
Xa
Xb
Xc
0.25
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
1.0
1.0
1.0
1.0
1.0
1.0
5.0
5.0
4.7 0.4
4.3 0.6
3.6 0.9
3.5 1.0
0
0
1.0
0.9
0.8
0.6
0.35 0.97
0.15 1.0
0.07 0.97
0.03 0.98
0.9
0.9
0.95
1
only detected by GLC and H NMR spectroscopy.
Besides was obtained a product of hydroxy group
replacement by halogen XI.
1.0
1.0
1.0
1.0
1.0
1.0
a Intensity of chromatographic peaks of compounds IXa and Xa
were taken equal to unity.
of signals was performed taking into account the GLC
data indicating the relative content of compounds in
the mixture.
R = CH3 (XII), C6H5 (XIII).
At the attempt to carry out the dehydration of
ketols VI, VII by treating with gaseous hydrogen
chloride, p-toluenesulfonic acid, or iodine in toluene
In the IR spectra of compounds VIII X appear the
1
absorption bands of C=O groups at 1711 1713 cm .
1
we obtained respectively 9-R-octahydroxanthenes XII, A weak absorption band at 1653 cm (C=C) was
XIII. The dehydration products were characterized
observed only in the spectra of compounds VIII, Xa,
in the spectra of compounds with tetrasubstituted
double bonds this absorption band was not present.
1
by IR, H and 13C NMR, and mass spectra. When the
spectra were registered from mixtures the assignment
Table 2. 13C NMR spectra of compounds VIII X
Chemical shift, , ppm
C6 C7 C8
Compd.
no.
R
C1
C2
C3
C4
C5
C9
C10
C11
C12
C13
CR
VIIIa
IXa
Xa
H
48.91 124.45 118.25 28.23 27.90 25.05 42.29 41.90 47.67 35.25 24.77 34.29 213.78
CH3 53.57 137.30 124.76 30.06 28.74 27.36 51.62 36.29 53.40 35.73 26.92 31.49 216.76 17.51
C6H5 55.07 140.64 125.77 29.45 25.66 22.19 53.89 38.84 58.40 37.25 21.12 30.40 217.26 126.75,
128.10,
128.60,
140.45
VIIIb
IXb
IXc
Xc
H
52.10 128.60 29.00 23.72 23.31 28.80 131.30 41.30 45.50 36.50 19.00 32.00 214.80
CH3 52.50 127.81 28.38 22.76 22.76 27.02 134.62 41.95 50.76 31.38 17.92 29.77 217.19 14.68
CH3 137.80 122.80 216.44
C6H5 53.20 51.07 31.24 27.61 26.60 31.46 140.65 128.50 53.31 36.38 17.40 35.68 214.70 127.9,
128.40,
140.4
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

1416
ROSTOVSKAYA et al.
1
The band at 3060 cm in the spectrum of compound
VIIIa may be attributed to the = C H group; in the
spectrum of compound Xa the band is overlapped by
the absorption of C H bonds of the benzene ring.
performed every 30 min, sample of 0.3 ml was
treated with 25% ammonia solution till neutral, then
several drops of water were added, the reaction pro-
ducts were extracted into ether, the extract was dried
with magnesium sulfate and charged into chromato-
graph.
Tricyclo[7.3.1.02,7]tridec-2-en-13-one (VIIIa).
A mixture of 5.1 g of ketol V and 2 ml of 85%
phosphoric acid was stirred at 60 C for 5 h. The
viscous reaction mixture was diluted with water and
treated with 25% ammonia solution till neutral. The
organic compounds were extracted into ether, the
extract was dried, and on removing ether the residue
was distilled in a vacuum. The fraction boiling at
145 147 C (4 mm Hg) was collected. We obtained
3.3 g (70%) of oily compound VIIIa that crystallized
on storage. At similar procedure performed with
ketol VI we obtained a mixture of compounds IXa
and IXb in 7: 2 ratio.
Tricyclo[7.3.1.02,7]tridec-2(7)-en-13-one (VIIIb)
[3]. A mixture of 5.7 g of ketol V, 3 ml of hydro-
chloric and 3 ml of acetic acid was stirred at 60 C
for 40 min and then poured into 12 ml of 25% water
solution of ammonia. The reaction product was
extracted into ether, the extract was washed with
water, dried on magnesium sulfate, the ether was
evaporated, and the residue was distilled in a vacuum
at 129 130 C (4 mm Hg). We obtained 4.1 g (78%)
of compound VIIIb. GLC showed the presence of a
single substance.
1
In the H NMR spectra the signals of vinyl protons
appear at 5.27 (compound VIIIa, J1 6.0, J2 2.0 Hz),
5.46 (compound IXa, J1 6.1, J2 2.5 Hz), and 5.60 ppm
[compound Xa, J1 6.3, J2 3.5 Hz). In the spectra of
compounds with tetrasubstituted double bonds the
signals of vinyl protons are naturally lacking.
The 13C NMR spectra of compounds VIII X are
given in Table 2. The signals were assigned taking
into account the published data [6, 7].
Apparently the dissimilar dehydration results at
the use of different catalysts are due to different reac-
tion mechanisms.
Since we did not study the reaction mechanisms
we can only make some suggestions. Note that only
at the C3 carbon close to the C2 OH group is present
an equatorial hydrogen atom. This fact provides a
possibility of formation of a cyclic transition state
with participation of phosphoric acid hydroxy group
or B F group as occurs under the other conditions
[6]. This transition state is a precursor of a compound
with a double bond in 2(3) position. Dehydration
effected by hydrochloric acid presumably proceeds
through a carbocation at the C2 atom that stabilizes by
proton ejection from the C7 position (process with
thermodynamic control). The compounds formed
possess a tetrasubstituted double bond. In compounds
IX, X the double bond is tetrasubstituted both in
position 2(7) and 7(8) providing a possibility of its
migration. Pyran formation apparently is due to
retroaldol cleavage of ketols.
A similar treatment of ketol VI afforded a mixture
of compounds IXa, IXb, and IXc in 1.1 : 3.5 : 1 ratio.
8-Phenyltricyclo[7.3.1.02,7]tridec-2-en-13-one
(Xa) and 8-phenyltricyclo[7.3.1.02,7]tridec-7-en-13-
one (Xc). A mixture of 11.5 g of ketol VII and 4 ml
of 85% phosphoric acid was stirred for 2 h at 100 C.
The solid reaction product was separated from the
liquid, washed with water, dried, and boiled with
hexane. The hot solution was filtered; on cooling
separated crystals of compound Xa, yield 3.2 g, mp
126 128 C (publ. 127 128.5 C [6]). The mother
liquor was evaporated, the viscous residue was
ground with ethyl ether to obtain more 0.5 g of
crystalline compound Xa, overall yield 31%. The
ether was evaporated, and the residue was distilled in
a vacuum, collecting the fraction of bp 291 203 C
(3 mm Hg). We obtained 4.1 g (38%) of compound
Xc, mp 102 104 C (from petroleum ether).
EXPERIMENTAL
1H and 13 NMR spectra were recorded on spectro-
meter Bruker WM 250 from solutions in deutero-
chloroform, internal reference TMS. The identifica-
tion and assignment of peaks was carried out with the
help of J-modulation and off-resonance procedure.
IR spectra were registered from thin films or chloro-
form solutions on Perkin-Elmer Spectrum BX 2
instrument. Chromatograms of substances and their
mass spectra were measured on HP 5972 MSD/HP
instrument. The m/z values for the molecular ions of
all compounds synthesized corresponded to the cal-
culated molecular weights. The reactions were
monitored by GLC on JanacoG-1800 device equipped
with a flame-ionization detector, CPB-5 column, even
at 200 250 C,carrier gas helium. The sampling was
8-Phenyltricyclo[7.3.1.02,7]tridec-7(8)-en-13-one
(Xc). A mixture of 10 g of ketol VII, 10 ml of
hydrochloric and 10 ml of acetic acid was stirred at
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001

SYNTHESIS AND ISOMERIZATION OF TRICYCLO[7.3.1.02,7]TRIDECEN-13-ONES
1417
60 C for 2 h. Then the reaction mixture was
neutralized with 25% water solution of ammonia. The
solidified organic substances were separated and dis-
solved in ether. The ether solution was washed with
water and stored in refrigerator for 24 h; therewith
separated 6 g (56%) of compound XI, after recrystal-
lization from ethanol acetone mixture mp 166 170 C
(decomp.) (publ. 166 171 C [3]). The ether filtrate
after separation of chloroketone XI was dried with
magnesium sulfate, the ether was evaporated, and the
residue was ground with water. We obtained 4 g
(43%) of compound Xc with a little chloroketone XI
impurity. On recrystallization from petroleum ether
we obtained 2.9 g of compound Xc, mp 102 104 C.
IR spectrum: 1711 cm 1 (C=O). Found, %: C 85.57,
85.80; H 8.21, 8.55. C19H22O. Calculated, %: C
85.66; H 8.32.
moderate intensity, C=C O C=C). Found, %: C
82.35, 82.39; H 9.59, 9.68. C14H20O. Calculated, %:
C 82.35; H 9.80.
9-Phenyl-2,3,4,5,6,7,8,9-octahydro-1H-xanthene
(XIII) was obtained from ketol VII along procedure
a in 37% yield, mp 94 96 C (96.5 97.5 C [8]).
We are grateful to L.I.Sokolova for performing the
chromatographic analyses and to G.M.Svistunov for
measuring GC-MS data.
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9-Methyl-2,3,4,5,6,7,8,9-octahydro-1H-xanthene
(XII). (a) In a flask equipped with a Dean Stark trap
was mixed 10 g of ketol VI and 95 ml of toluene. The
mixture was saturated with hydrogen chloride and
boiled for 2 h in a constant flow of HCl. On cooling
the precipitate of the unreacted ketol was separated,
the filtrate was treated with a saturated sodium
carbonate solution, the water layer was separated, and
it was extracted with toluene. The extract was
combined with the organic layer, dried with
magnesium sulfate, evaporated, and the residue was
subjected to a fractional distillation in a vacuum to
collect the fraction of bp 120 128 C (3 mm Hg). We
obtained 3.25 g (34%) of compound XII.
(b) In a flask equipped with a Dean Stark trap was
boiled for 20 h a mixture of 20 g of ketol VI, 60 ml
of toluene, and 0.005 g of iodine. On cooling the
mixture was filtered to separate the unreacted ketol,
toluene was distilled off from the filtrate, and the
residue was distilled in a vacuum. We obtained 8.8 g
(43%) of compound XII, bp 140 145 C (7 mm Hg).
(c) In a flask equipped with a Dean Stark trap was
boiled for 1 h a mixture of 10 g of ketol VI, 50 ml of
toluene, and 0.7 g of p-toluenesulfonic acid. The
amount of separated water was consistent with cal-
culations. On cooling the toluene solution was treated
with saturated sodium carbonate solution, dried with
magnesium sulfate, toluene was distilled off, and the
residue was distilled in a vacuum. We obtained 6.95 g
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(83%) of compound XII, bp 132 C (8 mm Hg), nD20
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J. Chem. Soc., C, 1970, no. 6, p. 771.
1
1.5261. IR spectrum: 1714, 1675 cm (bands of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 10 2001