Selective reductive dimerization of homocubane series oximes

Article abstract of DOI:10.1134/S1070428011110078

The mixture of di- and monoethylene ketals obtained by the reaction of 1,9-dibromopentacyc lo[5.4.0.0^2,6.0^3,10.0 ^5,9]-undeca-8,11-dione followed by hydrolysis and ring contraction by Faworsky method was converted into a mixture of ethylene ketals of 7-bromopentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decan-6- one-4- and 5-bromopentacyclo[5.3.0.0^2,5.0^3,9.0 ^4,8]decan-6-one-8-carboxylic acid where the carboxy group was replaced by bromine along the procedure of Hunsdiecker-Borodine-Cristol. 6-Ethylene ketal of the pentacyclo[5.3.0.0^2,5.0^3,9.0 ^4,8] decan-6-one obtained by the debromination of ethylene ketals of 4,7- and 5,8-dibromopentacyclo[5.3.0.0^2,5.0^3,9.0 ^4,8] decan-6-one was hydrolyzed to ketone whose oxime was selectively reduced on a platinum catalyst into the di-6-pentacyclo[5.3.0.0 ^2,5.0^3,9.0^4,8]decylamine. The reaction of reductive dimerization was also characteristic of pentacyclo[4.3.0.0 ^2,5.0^3,8.0^4,7]-nonan-9-one and pentacyclo[6.3.0.0^2,6.0^3,10.0^5,9]undecan-4-one oximes, whereas the composition of the reduction products of pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecan-8-one oxime depended on the amount of the catalyst.

Full text of DOI:10.1134/S1070428011110078

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 11, pp. 1695−1702. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.N. Rodionov, A.S. Sklyarova, T.V. Shamota, P.R. Schreiner, A.A. Fokin, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 11, pp. 1662−1668.
Selective Reductive Dimerization
of Homocubane Series Oximes
V. N. Rodionova, A. S. Sklyarovaa, T. V. Shamotaa,
P. R. Schreinerb, and A. A. Fokina
aNational Technical University of Ukraine “Kiev Polytechnic Institute,” Kiev, 03056 Ukraine
e-mail: vnr@xtf.ntu-kpi.kiev.ua
bJustus Liebig Universitaet, Heinrich Baff Ring 58, 35392 Gissen, BRD
Received December 24, 2010
Abstract—The mixture of di- and monoethylene ketals obtained by the reaction of 1,9-dibromopentacyc
lo[5.4.0.02,6.03,10.05,9]-undeca-8,11-dione followed by hydrolysis and ring contraction by Faworsky method
was converted into a mixture of ethylene ketals of 7-bromopentacyclo[5.3.0.02,5.03,9.04,8]decan-6-one-4- and
5-bromopentacyclo[5.3.0.02,5.03,9.04,8]decan-6-one-8-carboxylic acid where the carboxy group was replaced by
bromine along the procedure of Hunsdiecker–Borodine–Cristol. 6-Ethylene ketal of the pentacyclo[5.3.0.02,5.03,9.04,8]
decan-6-one obtained by the debromination of ethylene ketals of 4,7- and 5,8-dibromopentacyclo[5.3.0.02,5.03,9.04,8]
decan-6-one was hydrolyzed to ketone whose oxime was selectively reduced on a platinum catalyst into the di-
6-pentacyclo[5.3.0.02,5.03,9.04,8]decylamine. The reaction of reductive dimerization was also characteristic of
pentacyclo[4.3.0.02,5.03,8.04,7]-nonan-9-one and pentacyclo[6.3.0.02,6.03,10.05,9]undecan-4-one oximes, whereas
the composition of the reduction products of pentacyclo[5.4.0.02,6.03,10.05,9]undecan-8-one oxime depended on
the amount of the catalyst.
DOI: 10.1134/S1070428011110078
The potential for medicine of framework polycylic
amines was discovered by revealing the antiviral activ-
ity of 1-aminoadamantane (amantadine). Nowadays
diverse amines of the adamantsne series {amantadine,
rimantadine [1-(1-aminoethyl)adamantane], meman-
tine (1-amino-3,5-dimethyladamantane), adapromine
(α-ethyl-1-adamantylmethylamine)} are commercial
drugs widely ued in the prophylactics and treatment of
various viral diseases like grippe А, hepatitis С, herpes,
and also of Alzheimer and Parkinson illness [1–3].
investigated. The anticataleptic activity was also found
in СS-trishomocubyl-8-amines but their use is prevented
by the high toxicity [6].
Since the moment of the discovery of the activ-
ity of NGP1-01 (8-benzylamino-8,11-oxapentacyc
lo[5.4.0.02,6.03,10.05,9]-undecane) as calcium antagonist [7]
the biological activity of the aminopentacycloundecanes
started to be more thoroughly investigated. The high effi-
ciency was proved of NGP1-01 and a series of substituted
pentacycloundecylamines as antagonists of the receptor of
N-methyl-D-aspartate (NMDA) [8], and also the possibil-
ity was found to use NGP1-01 as a neuroprotector at the
focal ischemia [9]. It was also proved that the efficiency
of the pentacycloundecylamines as antagonists of the
NMDA-receptors depended directly on the volume and
the character of the framework substituent and also on
the extent of its distance from the other functional groups
(e.g., from the benzyl in the case of NGP1-01) [8].
The constantly growing interest in homocubanes,
moderately strained framework hydrocarbons, is due first
of all to their availability and the possibility of further
functionalization, and also to the topological variety of
the potential physiologically active substances prepared
therefrom. Especial interest is attracted by the derivatives
of the most accessible pentacyclo-[5.4.0.02,6.03,10.05,9]
undecane (СS-trishomocubane) and С11Н14-stable iso-
mer of pentacyclo[6.3.0.02,6.03,10.05,9]undecane (D3-
trishomocubane). The anticataleptic [4] and antiviral
[5] activity of D3-trishomocubyl-4-amines was lately
Although the studies on the biological activity of the
homocubylamines are continuously growing the set of
the available structures is very limited. This stimulates
1695

RODIONOV et al.
1696
the mother liquor by adding concentrated hydrochloric
acid under the pH control (4–5). The yield of compounds
V and VI depends on the degree of powdering the ketal
mixture before the reaction and on the amount of water
used in the treatment of the reaction mixture apparently
because of the considerable solubility in water of carboxy
derivatives V and VI.
the search for simple and convenient methods of prepara-
tion of new derivatives, especially of secondary amines
structurally similar to the NGP1-01 drug.
The traditional procedure for the preparation of the
secondary amines is the ammonolysis of the appropriate
haloderivatives or alcohols, but the selectivity of these re-
actions is commonly poor.Another way to the framework
dialkylamines is the reduction of amides obtained from
the framework amines and the corresponding framework
carboxylic acids [10]. However this method affords only
dialkylamines where the framework is separated from the
amino group by one or two CH2 units.
It turned out that bisethylene ketal of 1,9-dibromope
ntacylo[5.4.0.02,6.03,10.05,9]undeca-8,11-dione (ІV) was
hydrolyzed by a mixture of 10% sulfuric acid and THF
at the ratio 4:1, v/v, at 80°С [17] to form quantitatively
a mixture of monoethylene ketals without the admixture
of diketone I. Evidently the hydrolysis of one ethylene
ketal protective group proceeds relatively easily due to
the considerale stain in compound ІV arising from the
sterical repulsion of the oxolane moieties which is absent
in monoketals ІІ and ІІІ. In turn, the hydrolysis of the
second group is impeded by the presence of a bromine
in the α-position with respect to the carbonyl substitu-
ent. This fact is well consistent with the published data
on the hydrolysis in the concentrated sulfuric acid of
α-bromo-substituted ethylene ketalеs of the structures
of the homocubane and С2-bishomocybane [15]. The
obtained result made it possible to optimize the proce-
dure of the synthesis of isomeric carboxy derivatives V
and VI by performing the partial hydrolysis of diketone
bisethylene ketal ІV directly after the synthesis of the
mixture of compounds II–IV thus simplifying the treat-
ment of the reaction mixture and increasing the yield of
compounds V and VI.
By the Leuckart reaction from the adamantanone with
1- or 2-aminoadamantane in severe conditions [11, 12]
the corresponding diadamantylamines were obtained.
No published data exist on the synthesis of any other
diframework amines.
We report here on a simple and selective procedure
for the synthesis of di-6-pentacyclo-[5.3.0.02,5.03,9.04,8]
decylamine and some its homologs where the identical
framework fragments are directly bound to the nitrogen
atom.
We selected as the initial compound for the synthesis
of di-6-pentacyclo[5.3.0.02,5.03,9.04,8]decylamine (XII)
1,9-dibromopentacyclo[5.4.0.02,6.03,10.05,9]undeca-
8,11-dione (І) prepared along the described four-stage
procedure [13] from hydroquinone and cyclopentadiene.
The boiling of compound I with excess ethylene glycol
in benzene afforded two isomeric monoketals II and III,
and also bisketal IV. According to the chromatographic
data, the approximate weight ratio of the products of
mono- and diketalization was 3 : 2. The attempt to
carry out the reaction at the molar ratio of compound
I and ethylene glycol equal 1:1 in order to obtain only
monoketals as had been described for unsubstituted
diketone [14] was unsuccessful since the formation of
significant amounts of bisktal started at the conversion
of initial dibromodiketone I of 10–15%.
By the decarboxylation of monoethylene ketals V
and VI by the method of Hunsdiecker–Borodine in
Cristol modification [18] with bromine in the boiling
dibromomethane in the presence of the red mercury oxide
we obtained the mixture of ethylene ketals of 4,7- and
5,8-dibromopentacyclo-[5.3.0.02,5.03,9.04,8]decan-6-one
(VII) and (VIII) respectively.
The 13С NMR spectra of pairs of isomers V and
VI), VII and VIII contain double sets of signals of the
carbon atoms with the intensity ratio ~5 : 1 indicating
unequal content of the isomer in the mixture. In order
to assign the carbon signals in the 13С NMR spectrum
to the definite isomer we carried out an independent
synthesis of isomer VI from 5-bromo-8-carbomethoxy-
pentacyclo[5.3.0.02,5.03,9.04,8]decan-6-one (XIII) whose
synthesis had been described in [19−21]. The boiling of
compound XIII in benzene with excess ethylene glycol
provided 6-ethylene ketal of 5-bromo-8-carbomethoxpe
The Faworsky ring contraction performed in con-
centrated alkali water solutions is a common procedure
for the synthesis of more strained homocubanes from
their less strained homologs [15, 16]. In the mixture of
compounds II–IV only monoethylene ketals underwent
the reaction giving the corresponding isomeric carboxy
derivatives V and VI, whereas the bisethylene ketal re-
mained intact and therefore was easily filtered off from the
reaction mixture. Acids V and VI were precipitated from
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

SELECTIVE REDUCTIVE DIMERIZATION OF HOMOCUBANE SERIES OXIMES
1697
Scheme 1.
13
15
O
O
O
O
O
O
O
O
14
12
8
O 11
Br
1
7
O
Br
O
Br
O
HO(CH2)2OH
H+
+
9 Br
10
Br
Br
Br
Br
+
6
2
5
3
4
II
III
IV
I
.
,
10% H2SO4 THF
THF
(1) 20% NaOH
(2) 35% HCl
O
11
O
6
O
12
5
4
O
Br
O
O
Br
7 Br
+
COOH
(1) NaOH
(2) H+
8
HOOC
COOCH3
2
3
1
9
10
V
VI
XIV
HO(CH2)2OH
H+
,
Br2 HgO
CH2Br2
O
O
O
O
Br
O
Br
Br
Br
COOCH3
+
Br
VII
VIII
XIII
Li, t-BuOH
THF
H
N
O
O
O
NOH
.
.
10% H2SO4
THF
H2
NH2OH HCl
NaOH, EtOH
PtO2
IX
X
XIb
XIIb
ntacyclo[5.3.0.02,5.03,9.04,8]decan-6-one (XIV) that was
hydrolyzed to 6-ethylene ketal of 5-bromopentacyc-
lo[5.3.0.02,5.03,9.04,8]decan-6-one-8-carboxylic acid VI.
Acid VI was converted into dibromide VIII similarly
to the procedure of the treatment of the mixture of
compounds V and VI.
The hydrolysis of ethylene ketal of pentacyc-
lo-[5.3.0.02,5.03,9.04,8]decan-6-one (IX) by the mixture
of 10% sulfuric acid and THF at the ratio 4:1, v/v, at
80°С furnished ketone X that by the procedure [22] was
converted into pentacyclo[5.3.0.02,5.03,9.04,8]decan-6-one
oxime (XIb).
Dehalogenation of the mixture of dibromoketal VII
and VIII was carried out by the system lithium–tert-
butanol in THF. The completeness of the reduction was
monitored by the capillary GLC, and the tert-butanol was
added when required to complete the reaction.
The reduction of oxime XIb with hydrogen at the
atmospheric pressure in methanol in the presence of
3–5% of Adams catalyst at 20°С led to the quantitative
formation of di-6-pentacyclo[5.3.0.02,5.03,9.04,8]decyl-
amine (XIІb).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

RODIONOV et al.
1698
The high selectivity of the reduction of oxime XIb
two five-membered cyclic fragments of the framework,
whereas in the oxime of СS-trishomocubanone it belongs
to five- and six-membered cyclic fragments, and the six-
membered ring is present in the boat conformation. It is
presumable that the selectivity in reduction of oxime XId
is decreased due to the steric hindrances arising in the
reaction between monoalkylamine and monoalkylimine
at the formation of the key intermediate in the synthesis
of the secondary amines XIIа–XIId (Scheme 2).
into the bisframework amine XIІb prompted us to study
the reduction under the same conditions of the oximes
of the nearest homologs of pentacyclo[5.3.0.02,5.03,9.04,8]
decan-6-one: pentacyclo-[4.3.0.02,5.03,8.04,7]nonan-9-one
(homocubanone) (XIа), pentacyclo[6.3.0.02,6.03,10.05,9]
undecan-4-one (D3-trishomocubanone) (XIc), and
pentacyclo-[5.4.0.02,6.03,10.05,9]undecan-8-one (СS-
trishomocubanone) (XId). It proved that the oximes of
the homocubanone and D3- trishomocubanone behave
analogously to oxime XIb, whereas the reduction of the
oxime of СS-trishomocubanone in the presence of 3–5%
of catalyst yielded as the main product the corresponding
amine, and the dialkylamine formed in the amount not
exceeding 5–7%. On increasing the catalyst quantity
to 8–10% the dialkylamine prevailed in the reduction
product (60–75%).
Owing to the high internal symmetry of the proper
substituent and also due to the СS-symmetry of the
secondary amine the simplest 1Н and 13С NMR spectra
were observed for di-9-pentacyclo[4.3.0.02,5.03,8.04,7]-
nonylamine (XIIа). The 1Н NMR spectrum contains four
singlets with the integral intensity ratio 2:4:2:1, and in the
13С NMR spectrum only four carbon signal are observed.
13С NMR spectrum of amine XIІb contains a large
number of signals of various intensity complicating its
structural analysis.Actually, pentacyclo[5.3.0.02,5.03,9.04,8]
decane (С2-bisnomocubane), substituted at the secondary
carbon atom exists in the form of sуn- and anti-epimers
with the latter usually prevailing [25, 26]. It is presumable
that amine XIІb forms as three isomers as confirmed
by the presence in the 13С NMR spectrum of three
pairs of carbon nuclei signals with the intensity ratio
~9:3:1 in the region of 66 ppm, belonging to carbon
By the data of GC-MS analysis the reaction mixtures
after 2–4 h from the start of the process contained
the following compounds: initial oximes XIа–XId,
monoalkylamines XVа–XVd, dialkylamines XIIа–
XIId, and alkylideneimines XVIа–XVId. The set of
compounds present in the reaction mixture suggests that
the reduction of oximes XIа–XId proceedes along the
pathway considered for the reduction of the oximes from
the aliphatic-aromatic series [23, 24].
1
Oximes XIа–XId are distinguished only by the
structure of the hydrocarbon residue. In the oximes of
homocubanone XIа, С2-bishomocubanone XIb, and
D3-trishomocubanone XIc the C=N bond belongs to
atoms attached to the nitrogen atom. In the Н NMR
spectrum this assumption is confirmed by the presence
of three АВ systems in the region 1.25–1.55 ppm with
the same intensity ratio corresponding to the protons at
Scheme 2.
R
R
R
H2
H2
H
N OH
N H
_H2O
NH2
R'
R'
R'
XIа_XId
XVа_XVd
R'
R
R'
R'
R
R
H
H
H
N
R
H2
R
R
N
H
HN
HN
NH2
R
_NH3
R'
R'
H
R'
R'
XVIа_XVId
XIIа_XIId
4
9
10
9
3
8
R
7
4
1
5
6
(d).
=
(а),
(b),
(c),
11
3
2
7
2
6
1
R'
5
8
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

SELECTIVE REDUCTIVE DIMERIZATION OF HOMOCUBANE SERIES OXIMES
1699
the secondary carbon atoms of the framework fragment.
measured on an instrument Finnigan MAT 95.
1 3 С N M R s p e c t r u m o f d i - 4 - p e n t a c y c
lo[6.3.0.02,6.03,10.05,9]undecylamine (XIІc) consists of
the double set of carbon nuclei signals belonging to
two diastereomers (RR/SS and RS) formed from the D3-
symmetric oxime XIc in the ratio 1 : 1.
1,9-Dibromopentacyclo[5.4.0.02,6.03,10.05,9]-undeca-
8,11-dione (І) was obtained from 26.4 g (0.1 mol) of
2,5-dibromo-p-benzoquinone by procedure [11]. Yield
29.2 g (89%), mp 185–186°C. Spectral characteristics
were identical to those published in [27].
Considering the difficulties in the interpretation of
the 13С NMR spectra of amines XIIb, XIIc we measured
their high-resolution mass spectra to confirm their
homogeneity and purity.
R e a c t i o n o f 1 , 9 - d i b r o m o p e n t a c y c -
lo[5.4.0.02,6.03,10.05,9]undeca-8,11-dione (I) with
ethylene glycol. A mixture of 15 g (0.045 mol) of
compound I, 12.4 g (0.2 mol) of ethylene glycol, and
0.3 g of p-toluenesulfonic acid monohydrate in 250 ml of
anhydrous benzene was boiled with a Dean–Stark trap for
6 h. The benzene solution was washed in succession with
water, 10% water solution of sodium carbonate, and with
brine, dried with Na2SO4, the solvent was distilled off in
a vacuum. We obtained 17.2 g of viscous oily mixture of
substances II–IV that crystallized within 24 h.
Whereas the bisframework amines XIІа–XIIc were
obtained in the preparative yield no less than 90%, di-8-
pentacyclo[5.4.0.02,6.03,10.05,9]undecylamine (XIІd) was
obtained in the mixture with the monoalkylamine and
was not isolated in the pure state. Therefore the structural
assignments were done based on the corresponding mass
spectra and the 13С NMR spectrum of the mixture of
mono- and dialkylamines in the ratio 2 : 3.
Ethylene ketals of 7-bromopentacyc-
lo-[5.3.0.02,5.03,9.04,8]decan-6-one-4-carboxylic acid
(V) and 5-bromopentacyclo[5.3.0.02,5.03,9.04,8]decan-
6-one-8-carboxylic acid (VI) were obtained by boiling
11.8 g of finely dispersed mixture of ketals II–IV in 160
ml of 20% water solution of KОН at stirring over 4 h. The
reaction mixture was cooled, bisethylene ketal IV was
filtered off, washed on the filter with water (2 × 10 ml),
and dried in air till constant weight. We obtained 4.8 g
of colorless or slightly colored crystals. The filtrate was
extracted with ethyl ether, the water layer was returned
to the reactor, and at vigorous stirring and cooling with
an ice−NaCl mixture a calculated quantity of sulfuric
acid was added dropwise maintaining the temperature
of the reaction mixture below 10°С. When the pH of the
mixture attained 4–5 the separated precipitate was filtered
off, washed with ice water (2 × 10 ml), and dried in air.
Yield of the mixture of compounds V and VI 4.9 g.
Thus we developed a selective method of the synthesis
of di-9-pentacyclo[4.3.0.02,5.03,8.04,7]nonylamine, di-6-
pentacyclo[5.3.0.02,5.03,9.04,8]decylamine, and di-4-pen
tacyclo[6.3.0.02,6.03,10.05,9]undecylamine consisting in
the reduction of oximes of the corresponding ketones
by hydrogen under the atmospheric pressure and room
temperature in the presence of the platinum catalyst.
It was also shown that the reduction of the oxime of
CS-trishomocubane-8-one under the same conditions
resulted in the mixture of the corresponding mono- and
dialkylamines. Besides the preparative methods are
developed for the synthesis of intermediate compounds
that can be used for obtaining diverse mono- and
disubstituted derivatives of С2-bishomocubane.
EXPERIMENTAL
1Н and 13С NMR spectra were registered on a spec-
trometer Bruker DPX-400 at operating frequencies 400.13
and 100.61 MHz respectively, solvent СDCl3, internal
reference TMS. GC-MS measurements were performed
on an instrument Hewlett Packard 5971A(electron impact
70 eV, mass-selective detector), a chromatograph НР
5890, column HP-5 (5% of phenylmethylsilicone), va-
porizer temperature 250°С, oven temperature 60–250°С,
heating rate 20 deg/min. GLC analysis was carried
out on a capillary chromatograph Shimadzu GC-14B,
flame-ionization detector, column Optima-1, vaporizer
temperature 275°С, oven temperature 80–250°С, heat-
ing rate 20 deg/min. High-resolution mass spectra were
(а) A mixture of 4.8 g (0.0114 mol) of bisethylene
ketal IV, 120 ml of 10% sulfuric acid, and 30 ml of THF
was heated at 80°С with stirring for 3–4 h. The reaction
mixture was cooled, extracted with dichloromethane
(3 × 100 ml). The organic layer was washed with water
and 10% water solution of sodium carbonate, dried with
Na2SO4, the solvent was removed in a vacuum. Yield
4.2 g (97%) of a mixture of monoketals II and III. After
the reaction with aqueous alkali we obtained 3.15 g (90%)
of the mixture of carboxylic acids V and VI. Overall yield
yield 8.05 g (83% calculated on compound I).
(b) A mixture of 5.4 g of ethylene ketals ІІ–IV
was hydrolyzed by procedure а described above for
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

RODIONOV et al.
1700
bisethylene ketal IV. Yield 5.05 g of a mixture of
monoketals II and III. After the reaction with aqueous
alkali we obtained 4 g of the mixture of carboxylic acids
V and VI (90% calculated on compound I).
9 : 1 v/v. The solvents were removed in a vacuum. Yield
12.4 g (96%) of the mixture of compounds VII, VIII.
Ethylene ketal of 5,8-dibromopentacyc
lo-[5.3.0.02,5.03,9.04,8]decan-6-one (VIII) was obtained
from 0.75 g (0.0024 mol) of ethylene ketal of bromoacid
VI by the above described procedure. Yield 0.75 g
(90%), mp 57–58°С (from methanol). 1Н NMR spectrum
(CDCl3), δ, ppm: 1.45 d, 1.98 d (АВ system, 2Н, СН2,
J 11 Hz), 2.40 br.s (1Н, СН), 2.90–3.30 m (5Н, СН),
3.92–4.36 m (4Н, СН2). 13С NMR spectrum, δ, ppm:
37.4 (С3), 39.1 (С10), 45.5 (С1), 50.7 (С9), 53,1 (С7),
55.9 (С2), 58.0 (С4), 59.1 (С8), 62.6 (С5), 65.9 (С11),
66.0 (С12), 118.4 (С6). Mass spectrum, m/z (Irel, %): 350
(5.4) [M(81Br)]+, 348 (10.7) [M(81Br79Br)]+, 346 (5.3)
[M(79Br)]+, 269 (88.1) [M – Br(79Br)]+, 267 (91.7) [M –
Br(81Br)]+, 223 (13.3), 187 (32.5), 144 (21.2), 116 (100),
115 (96.5), 66 (20.8) [C5H6]+. Found, %: C 41.31; H 3.51.
С12H12Br2O2. Calculated, %: C 41.41; H 3.48. M 348.030.
Ethylene ketal of pentacyclo[5.3.0.02,5.03,9.04,8]-
decan-6-one (IX) was obtained from 10.8 g (0.031
mol) of the mixture of dibromides VII, VIII along the
procedure [28]. Yield 5.6 g (95%), bp 123–126°С (14
mm Hg) [26]. Spectral characteristics were identical to
published in [29].
Pentacyclo[5.3.0.02,5.03,9.04,8]decan-6-one (X) was
obtained from 5.5 g (0.029 mol) of ketal IX by the
method [17]. Yield 4.1 g (97%), mp 126–127°C. Spectral
characteristics were identical to those published in [30].
E t h y l e n e k e t a l o f 5 - b ro m o p e n t a c y c
lo[5.3.0.02,5.03,9.04,8]decan-6-one-8-carboxylic acid
(VI) was obtained by dissolving 0.5 g of NaOH in
0.5 ml of water, adding 12.5 ml of methanol and to
the solution thus prepared adding a solution of 1.24 g
(3.8 mmol) of ethylene ketal of 7-bromo-4-carbomethoxy-
pentacyclo[5.3.0.02,5.03,9.04,8]decan-6-one (XIV) in 7 ml
of methanol. The reaction mixture was stirred at room
temperature over 15 h, methanol was distilled off in a
vacuum, the residue was dissolved in 4 ml of water, and
at stirring while cooling the concn. sulfuric acid was
added dropwise till weakly acidic pH. The precipitate
was filtered off, washed on the filter with ice water (2 ×
3 ml), and dried in air. Yield 1.01 g (85%), mp 138–140°С
1
(from hexane). Н NMR spectrum, δ, ppm: 1.55 d, 1.90 d
(АВ system, 2Н, СН2, J 12 Hz), 2.50 br.s (1Н, СН),
2.95–3.32 m (5Н, СН), 3.95–4.35 m (4Н, СН2), 10.35
br.s (1Н, СООН). 13С NMR spectrum, δ, ppm: 36.9 (С3),
40.3 (С10), 44.9 (С1), 46.0 (С9), 47.1 (С7), 50.8 (С2),
52.1 (С4), 55.9 (С8), 62.8 (С5), 66.0 (С11), 66.6 (С12),
119.3 (С6), 176.1 (С13). Mass spectrum, m/z (Irel, %):
314 (18.5) [M(81Br)]+, 312 (18.3) [M(79Br)]+, 297 (13.6)
[M – OH(81Br)]+, 295 (13.9) [M – OH(79Br)]+, 269 (43.6)
[M – COOH(81Br)]+, 267 (45.1) [M – COOH(79Br)]+, 233
(100) [M – Br]+, 187 (15.5), 143 (22.2), 116 (48.6), 115
(68.1), 77 (14.8) [C6H5]+, 73 (29.3) [C3H5O2]+. Found,
%: C 49.79; H 4.17. С13H13BrO4. Calculated, %: C 49.86;
H 4.18. M 313.144.
Pentacyclo[5.3.0.02,5.03,9.04,8]decan-6-one oxime
(XIb) was obtained from 3.65 g (0.25 mol) of ketone X
by the procedure [31]. Yield 3.54 g (88%), mp 99–100°C.
Spectral characteristics were identical to those published
in [31].
Ethylene ketals of 4,7-dibromopentacyc
lo-[5.3.0.02,5.03,9.04,8]decan-6-one (VII) and 5,8-dibr
omopentacyclo[5.3.0.02,5.03,9.04,8]decan-6-one (VIII).
A solution of 9 g (3 ml, 0.056 mol) of bromine in 50 ml
if dibromomethane was added dropwise to a vigorously
stirred solution of 11.5 g (0.037 mol) of the mixture
of carboxylic acids V and VI in 120 ml of boiling
dibromomethane in the presence of 8.9 g (0.041 mol) of
red mercury oxide. The mixture was boiled for 3 h, cooled
to the room temperature, the separated precipitate was
filtered off and washed on the filter with dibromomethane
(2 × 10 ml). Dibromomethane was distilled off in
a vacuum of a water-jet pump, the residue was treated
with boiling hexane (4 × 75 ml), hexane was evaporated
in a vacuum, and the residue was subjected to column
chromatography on silica gel, eluent hexane–ethyl ether,
Di-6-pentacyclo[5.3.0.02,5.03,9.04,8]decylamine
(XIIb). To a solution of 0.32 g (0.02 mol) of oxime XIb
in 30 ml of anhydrous methanol was added a catalytic
quantity of platinum(IV)oxide. The reactor flask was
several times flushed with hydrogen and was left at
stirring at the hydrogen pressure in the gasometer for
24 h. The reaction mixture was filtered from the catalyst
through a silica gel bed, methanol was evaporated in
a vacuum, the residue was dissolved in a minimum
volume of ethyl ether, and the amine was precipitated
by the gradual addition of a saturated solution of gaseous
hydrogen chloride in ethyl ether. The obtained amine
hydrochloride was treated with 10% water solution of
KОН, extracted with ethyl ether, the extract was dried
with KОН, the solvent was evaporated in a vacuum. Yield
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011

SELECTIVE REDUCTIVE DIMERIZATION OF HOMOCUBANE SERIES OXIMES
1701
0.25 g (90%), mp 138–150°C. 1Н NMR spectrum, δ,
ppm: 1.25–1.33 m, 1.50 d (part of АВ system. J 12 Hz),
1.60–1.70 m (4Н, СН2), 2.65–3.63 m (19Н, СН, NH).
13С NMR spectrum, δ, ppm: 36.6, 36.7, 36.8, 37.1, 37.8,
37.9, 38.0, 38.2, 38.6, 38.7, 39.5, 39.6, 39.7, 39.8, 39.9,
40.0, 40.9, 41.0, 41.1, 41.2, 41.3, 41.4, 41.5, 41.6, 41.6,
41.7, 41.7, 41.8, 41.9, 42.1, 42.2, 42.2, 42.3, 42.4, 42.9,
45.1, 45.2, 45.3, 45.4, 45.5, 48.2, 48.3, 48.5, 48.6, 49.0,
49.2, 49.4, 49.5, 49.9, 66.0, 66.2, 66.3, 66.4, 66.7, 67.2.
Mass spectrum, m/z (Irel, %): 277 (100) [M]+, 212 (53.4)
[M – C5H5]+, 211 (26.9) [M – C5H6]+, 160 (27.5), 146
(21.8) [M – C10H11]+, 131 (79.3) [C10H11]+, 116 (34.8),
115 (29.3), 91 (82.3) [C7H7]+, 65 (11.8) [C5H5]+. Found
M 277.1827. С20H23N. Calculated M 277.1830.
The reaction mixture was washed with water and with
10% sodium carbonate solution, dried with Na2SO4, the
solvent was distilled off in a vacuum. Yield 1.8 g (92%),
1
mp 53–54°C (from methanol). Н NMR spectrum, δ,
ppm: 1.53 d, 1.88 d (сисtеmа АВ, 2Н, СН2, J 12 Hz),
2.54 br.s (1Н, СН), 2.92–3.02 m (2Н, СН), 3.05–3.15 m
(2Н, СН), 3.25 t (1Н, СН, J 3 Hz), 3.73 s (3Н, СН3)
3.88–4.32 m (4Н, СН2). 13С NMR spectrum, δ, ppm:
37.0 (С3), 40.3 (С10), 44.7 (С1), 46.7 (С9), 46.8 (С7),
50.9 (С2), 52.0 (С4), 52.1 (С8), 55.9 (С5), 63.3 (OCH3),
65.9 (С11), 66.4 (С12), 119.1 (С6), 173.1 (СOO). Mass
spectrum, m/z (Irel, %): 328 (18.0) [M(81Br)]+, 326 (18.2)
[M(79Br)]+, 297 (8.6) [M – OCH3(81Br)]+, 295 (8.5) [M –
OCH3(79Br)]+, 269 (58.2) [M – COOCH3(81Br)]+, 267
(55.1) [M – COOCH3(79Br)]+, 247 (100) [M – Br]+, 203
(14.5), 187 (20.1), 143 (18.5), 116 (44.5), 115 (56.4), 73
(20.3) [C3H5O2]. Found, %: C 51.40; H 4.57. С14H15BrO4.
Compounds XIIа, XIIc were obtained similarly.
Di-9-pentacyclo[4.3.0.02,5.03,8.04,7]nonylamine
(XIIа) was obtained from 0.3 g (0.002 mol) of oxime
1
Calculated, %: C 51.40; H 4.62. M 327.170.
XIa [22]. Yield 0.23 g (92%), mp 157–160°C. Н NMR
spectrum, δ, ppm: 3.22 s (4Н, СН), 3.45 s (4Н, СН),
3.52 s (8Н, СН), 3.79 s (1Н, NH). 13С NMR spectrum,
δ, ppm: 40.7 (С4,5), 41.2 (С2,3,6,7), 43.9 (С1,8), 72.0 (С9).
Mass spectrum, m/z (Irel, %): 249 (6.0) [M]+, 132 (13.4)
[M – C9H9]+, 130 (11.9) [C9H8N]+, 117 (39.5) [C9H9]+,
115 (100.0) [C9H7]+, 91 (87.9) [C7H7]+, 77 (27.9) [C6H5]+,
65 (36.4) [C5H5]+. Found, %: C 86.61; H 7.72. С18H19N.
Calculated, %: C 86.70; H 7.68. M 249.350.
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1
XIc [32]. Yield 0.27 g (90%), mp 161–170°C. Н NMR
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239 (39.2) [M – C5H6]+, 238 (28.0), 160 (25.2) [M –
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 11 2011