Reactions of 3-substituted 3-azabicyclo[3.3.1]nonan-9-ones with nitrogen-containing nucleophiles

Article abstract of DOI:10.1134/S1070428009060165

Condensation of 3-substituted 3-azabicyclo[3.3.1]nonan-9-ones with hydroxylamine and hydrazine hydrate gave the corresponding oximes, hydrazones, and azines. Reductive amination of the title compounds in the presence of sodium triacetoxyhydridoborate led

Full text of DOI:10.1134/S1070428009060165

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 6, pp. 895–899. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.I. Moskalenko, V.I. Boev, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 6, pp. 907–911.
Reactions of 3-Substituted 3-Azabicyclo[3.3.1]nonan-9-ones
with Nitrogen-Containing Nucleophiles
A. I. Moskalenko and V. I. Boev
Lipetsk State Pedagogical University, ul. Lenina 42, Lipetsk, 398020 Russia
e-mail: kaf_himii@lspu.lipetsk.ru
Received February 13, 2008
Abstract—Condensation of 3-substituted 3-azabicyclo[3.3.1]nonan-9-ones with hydroxylamine and hydrazine
hydrate gave the corresponding oximes, hydrazones, and azines. Reductive amination of the title compounds in
the presence of sodium triacetoxyhydridoborate led to the formation of 3-substituted 3-azabicyclo[3.3.1]nonan-
9-amines which were converted into the corresponding dihydrochlorides by treatment with dry hydrogen
chloride. Treatment of 3-tert-butoxycarbonyl derivatives with HCl under analogous conditions was accom-
panied by elimination of the tert-butoxycarbonyl group to produce 3-azabicyclo[3.3.1]nonan-9-amine dihydro-
chlorides.
DOI: 10.1134/S1070428009060165
We previously [1] developed a convenient proce-
dure for the synthesis of 3-substituted 3-azabicyclo-
[3.3.1]nonan-9-ones whose reactivity was studied very
poorly [2]. Molecules of these compounds include
a pharmacophoric piperidine fragment, and they attract
interest as potential biologically active substances [3].
and VIII (Scheme 1). Ketones I and II smoothly re-
acted with primary and secondary amines under condi-
tions of reductive amination (in the presence of excess
sodium triacetoxyhydridoborate) to give diamines IX–
XVIII (Scheme 2).
Treatment of compounds III, V, IX–XI, XV, and
XVI dissolved in diethyl ether with a saturated solu-
tion of dry hydrogen chloride in dioxane resulted in
quantitative formation of crystalline dihydrochlorides
(azine VII gave rise to the corresponding tetrahydro-
chloride). Under more severe conditions, i.e., on heat-
ing solutions of IV, VI, VIII, XII–XIV, XVII, and
XVIII in ethanol with a saturated solution of hydrogen
chloride in dioxane, the salt formation was accom-
panied by elimination of the tert-butoxycarbonyl
group, and the products were crystalline secondary bis-
In the present article we report on new reactions of
bicyclic ketones I and II at the carbonyl group with
conventional nitrogen-containing nucleophiles, hy-
droxylamine and hydrazine. The reactions were carried
out by heating the reactants in boiling ethanol. Ketones
I and II reacted with hydroxylamine to produce the
corresponding oximes III and IV (Scheme 1). Depend-
ing on the reactant ratio, the reactions of I and II with
hydrazine led to the formation of hydrazones V and VI
(with large excess of hydrazine hydrate) or azines VII
Scheme 1.
NH2OH, EtOH, 78°C
–H2O
N
N
R
R
O
NOH
I, II
III, IV
N2H4 ·H2O, EtOH, 78°C
I, II
or
–H2O
N
N
N
R
R
R
NNH2
N
N
V, VI
VII, VIII
I, III, V, VII, R = PhCH2; II, IV, VI, VIII, R = t-BuOCO.
895

MOSKALENKO, BOEV
896
Scheme 2.
NaBH(OAc)3
CH2Cl2, 20°C
R'
R'
I, II
+
N
R
N
H
H2N
IX–XIV
NaBH(OAc)3
CH2Cl2, 20°C
( )n
I, II
+
N
N
N
( )n
H
R
XV–XVIII
IX–XI, XV, XVI, R = PhCH2; XII–XIV, XVII, XVIII, R = t-BuOCO; IX, XII, R′ = H; X, XIII, R′ = Cl; XI, XIV, R′ = Br;
XV, XVII, n = 1; XVI, XVIII, n = 2.
amine dihydrochlorides XIX, XX, and XXII–XXVI
and tetrahydrochloride XXI having no substituent on
N3 (Scheme 3).
EXPERIMENTAL
The IR spectra were recorded on a Specord 75IR
spectrometer from samples prepared as thin films or
The structure and purity of compounds III–XXVI
were confirmed by elemental analyses, IR, 1H NMR,
and mass spectra, and TLC data (see Experimental).
1
dispersions in mineral oil. The H NMR spectra were
measured on a Varian Mercury Plus-400 instrument
(400 MHz) in CDCl3 or DMSO-d6 (XIX–XXVI) using
hexamethyldisiloxane as internal reference. The mass
spectra (atmospheric pressure chemical ionization)
were obtained on a Thermo Finnigan Surveyor MSQ
mass spectrometer (USA). The purity of the products
was checked by TLC on Silufol UV-254 plates using
It should be noted that most of the synthesized
compounds contain functional amino groups capable
of reacting with various electrophiles; therefore, they
can be used in fine organic synthesis for the prepara-
tion of potential biologically active substances.
Scheme 3.
HCl/EtOH–C4H8O2
–CO2, –Me3CCl
HCl/EtOH–C4H8O2
IV
·2HCl
VI
·2HCl
–CO2, –Me3CCl
HN
HN
NOH
NNH2
XIX
XX
HCl/EtOH–C4H8O2
–CO2, –Me3CCl
VIII
·4HCl
HN
NH
N
N
XXI
HCl/EtOH–C4H8O2
–CO2, –Me3CCl
R
XII–XIV
·2HCl
HN
N
H
XXII–XXIV
HCl/EtOH–C4H8O2
–CO2, –Me3CCl
XVII, XVIII
·2HCl
N
HN
( )n
XXV, XXVI
XXII, R = H; XXIII, R = Cl; XXIV, R = Br; XXV, n = 1; XXVI, n = 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 6 2009

REACTIONS OF 3-SUBSTITUTED 3-AZABICYCLO[3.3.1]NONAN-9-ONES
897
[M + H]+. Found, %: C 74.12; H 8.56; N 17.42.
C15H21N3. Calculated, %: C 74.09; H 8.64; N 17.27.
hexane–ethyl acetate (1:1) as eluent; spots were visu-
alized under UV light.
tert-Butyl 9-hydrazono-3-azabicyclo[3.3.1]non-
ane-3-carboxylate (VI) was synthesized in a similar
way. Yield 71%, mp 61–62°C, Rf 0.21. IR spectrum, ν,
cm–1: 3250 (NH2), 1681 (C=O), 1614 (C=N). 1H NMR
spectrum, δ, ppm: 1.32 s (9H, t-Bu), 1.45–2.12 m (6H,
CH2), 2.38–2.44 m (2H, CH), 3.45 d (2H, NCH2),
3.64 d (2H, NCH2), 5.98 br.s (2H, NH2). Mass spec-
trum, m/z: 254 [M + H]+, 197 [M – 57 + H]+, 153 [M –
101 + H]+. Found, %: C 61.57; H 9.03; N 16.52.
C13H23N3O2. Calculated, %: C 61.68; H 9.09; N 16.59.
3-Benzyl-3-azabicyclo[3.3.1]nonan-9-one oxime
(III). Ketone I [1, 2], 1.15 g (5 mmol), was dissolved
in 10 ml of ethanol, 10 ml of an aqueous solution of
hydroxylamine [prepared from 0.49 g (7 mmol) of
hydroxylamine hydrochloroide and 0.59 g (7 mmol) of
sodium hydrogen carbonate] was added, and the mix-
ture was stirred for 3 h on heating under reflux. The
mixture was cooled, diluted with 100 ml of water, and
extracted with methylene chloride (3×40 ml). The ex-
tracts were combined and dried over anhydrous sodi-
um sulfate, the solvent was distilled off, and the resi-
due was subjected to column chromatography on silica
gel using hexane–ethyl acetate (1:1, by volume) as
eluent. Yield 1.00 g (82%), mp 101–102°C. IR spec-
trum, ν, cm–1: 3350 (OH), 1635 (C=N). 1H NMR spec-
trum, δ, ppm: 1.48–2.10 m (6H, CH2), 2.32–2.37 m
(2H, CH), 2.87 d (2H, NCH2), 2.98 d (2H, NCH2),
3.46 s (2H, PhCH2N), 7.23–7.41 m (5H, C6H5), 10.84 s
(1H, OH). Mass spectrum: m/z 245 [M + H]+. Found,
%: C 73.65; H 8.23; N 11.54. C15H20N2O. Calculated,
%: C 7379; H 8.19; N 11.47.
3-Benzyl-3-azabicyclo[3.3.1]nonan-9-one azine
(VII). Hydrazine hydrate, 0.125 g (2.5 mmol), was
added to a solution of 1.15 g (5 mmol) of ketone I in
5 ml of ethanol, and the mixture was heated for 10 h
under reflux on stirring. The mixture was cooled,
diluted with 20 ml of water, and left to stand overnight
in a refrigerator at 5–6°C. The precipitate was filtered
off, dried, and recrystallized from hexane–ethyl acetate
(1 : 1, by volume). Yield 0.54 g (48%), colorless
crystalline substance, mp 164–165°C. IR spectrum:
1
ν 1610 cm–1 (C=N). H NMR spectrum, δ, ppm: 1.41–
2.11 m (12H, CH2), 2.32–2.41 m (4H, CH), 2.82–
2.92 m (4H, NCH2), 2.99–3.08 m (4H, NCH2), 3.42–
3.53 m (4H, PhCH2N), 7.22–7.41 m (10H, C6H5).
Mass spectrum: m/z 455 [M + H]+. Found, %: C 79.28;
H 8.44; N 12.38. C30H38N4. Calculated, %: C 79.31;
H 8.36; N 12.33.
tert-Butyl 9-hydroxyimino-3-azabicyclo[3.3.1]-
nonane-3-carboxylate (IV) was synthesized in a simi-
lar way. Yield 87%, mp 143–144°C. IR spectrum, ν,
1
cm–1: 3352 (OH), 1683 (C=O), 1638 (C=N). H NMR
spectrum, δ, ppm: 1.32 s (9H, t-Bu), 1.46–2.10 m (6H,
CH2), 2.38–2.46 m (2H, CH), 3.44 d (2H, NCH2),
3.63 d (2H, NCH2), 10.88 s (1H, OH). Mass spectrum,
m/z: 255 [M + H]+, 198 [M – 57 + H]+, 154 [M – 101 +
H]+. Found, %: C 61.42; H 8.57; N 10.98. C13H22N2O3.
Calculated, %: C 61.44; H 8.66; N 11.02.
Di-tert-butyl 9,9′-hydrazine-1,2-diylidenebis(3-
azabicyclo-[3.3.1]nonane-3-carboxylate) (VIII) was
synthesized in a similar way. Yield 62%, mp 182–
183°C. IR spectrum, ν, cm–1: 1683 (C=O), 1610 (C=N).
1H NMR spectrum, δ, ppm: 1.31 s (18H, t-Bu), 1.44–
2.13 m (12H, CH2), 2.36–2.45 m (4H, CH), 3.48–
3.52 m (4H, NCH2), 3.68–3.77 m (4H, NCH2). Mass
spectrum, m/z: 475 [M + H]+, 418 [M – 57 + H]+, 374
[M – 101 + H]+, 361 [M – 114 + H]+, 273 [M – 202 +
H]+. Found, %: C 65.75; H 8.82; N 11.63. C26H42N4O4.
Calculated, %: C 65.84; H 8.86; N 11.81.
3-Benzyl-N-phenyl-3-azabicyclo[3.3.1]nonan-9-
amine (IX). Ketone I, 1.15 (5 mmol), was dissolved in
20 ml of anhydrous methylene chloride, 0.47 g
(5 mmol) of freshly distilled aniline and 0.2 ml of
glacial acetic acid were added, and the mixture was
heated for 1 h under reflux on stirring. The mixture
was cooled to room temperature, 3.37 g (16 mmol) of
sodium triacetoxyhydridoborate was added, the mix-
ture was stirred for 24 h, 20 ml of 20% aqueous potas-
sium carbonate was added, the mixture was stirred for
0.5 h, 30 ml of water was added, and the organic phase
3-Benzyl-3-azabicyclo[3.3.1]nonan-9-one hydra-
zone (V). Hydrazine hydrate, 2.5 g (50 mmol), was
added to a solution of 1.15 g (5 mmol) of ketone I
[1, 2] in 15 ml of ethanol, and the mixture was heated
for 5 h under reflux on stirring. The mixture was
cooled, diluted with 100 ml of water, and extracted
with methylene chloride (3×50 ml). The extracts were
combined and dried over anhydrous sodium sulfate,
the solvent was distilled off, and the residue was sub-
jected to column chromatography on silica gel using
hexane–ethyl acetate (1:1, by volume) as eluent. Yield
0.78 g (64%), colorless oily substance, Rf 0.38. IR
1
spectrum, ν, cm–1: 3252 (NH2), 1612 (C=N). H NMR
spectrum, δ, ppm: 1.39–2.04 m (6H, CH2), 2.30–
2.35 m (2H, CH), 2.86 d (2H, NCH2), 2.95 d (2H,
NCH2), 3.44 s (2H, PhCH2N), 6.24 br.s (2H, NH2),
7.21–7.38 m (5H, C6H5). Mass spectrum: m/z 244
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 6 2009

MOSKALENKO, BOEV
898
was separated. The aqueous phase was extracted with
methylene chloride (2×30 ml), the extracts were com-
bined with the organic phase and dried over anhydrous
sodium sulfate, the solvent was distilled off, and the
residue was subjected to column chromatography on
silica gel using hexane–ethyl acetate (1:1, by volume)
as eluent. Yield 1.42 g (93%), colorless oily substance,
mp 72–75°C, Rf 0.41. IR spectrum, ν, cm–1: 3325
(NH), 1683 (C=O). H NMR spectrum, δ, ppm: 1.31 s
1
(9H, t-Bu), 1.46–2.11 m (6H, CH2), 2.39–2.47 m (2H,
CH), 3.11 br.s (1H, NH), 3.48 d (2H, NCH2), 3.72 d
(2H, NCH2), 4.05 m (1H, NCH), 7.08 d and 7.64 d (2H
each, C6H4, J = 7.5 Hz). Mass spectrum, m/z: 350 [M +
H]+, 293 [M – 57 + H]+, 249 [M – 101 + H]+. Found,
%: C 65.18; H 7.36; N 7.94. C19H26ClN2O2. Calculat-
ed, %: C 65.25; H 7.44; N 8.01.
1
Rf 0.58. IR spectrum: ν 3325 cm–1 (NH). H NMR
spectrum, δ, ppm: 1.45–2.09 m (6H, CH2), 2.28–
2.36 m (2H, CH), 2.82 d (2H, NCH2), 2.93 d (2H,
NCH2), 3.45 s (2H, PhCH2N), 3.96 m (1H, NCH),
6.98–7.08 m (5H, NC6H5), 7.21–7.43 m (5H,
C6H5CH2). Mass spectrum: m/z 306 [M + H]+. Found,
%: C 82.51; H 8.23; N 9.06. C21H25N2. Calculated, %:
C 82.63; H 8.19; N 9.17.
tert-Butyl 9-(4-bromophenylamino)-3-azabicyclo-
[3.3.1]nonane-3-carboxylate (XIV). Yield 87%,
mp 75–76°C, Rf 0.45. IR spectrum, ν, cm–1: 3327 (NH),
1
1682 (C=O). H NMR spectrum, δ, ppm: 1.31 s (9H,
t-Bu), 1.45–2.10 m (6H, CH2), 2.37–2.45 m (2H, CH),
3.12 br.s (1H, NH), 3.47 d (2H, NCH2), 3.81 d (2H,
NCH2), 4.03 m (1H, NCH), 7.06 d and 7.59 d (2H
each, C6H4, J = 7.8 Hz). Mass spectrum, m/z: 395 [M +
H]+, 338 [M – 57 + H]+, 294 [M – 101 + H]+. Found,
%: C 58.03; H 6.71; N 7.04. C19H26BrN2O2. Calculat-
ed, %: C 57.89; H 6.60; N 7.10.
Compounds X–XVIII were synthesized in a similar
way.
3-Benzyl-N-(4-chlorophenyl)-3-azabicyclo[3.3.1]-
nonan-9-amine (X). Yield 91%, colorless oily sub-
stance, Rf 0.52. IR spectrum: ν 3328 cm–1 (NH).
1H NMR spectrum, δ, ppm: 1.47–2.12 m (6H, CH2),
2.31–2.38 m (2H, CH), 2.88 d (2H, NCH2), 3.02 d
(2H, NCH2), 3.59 s (2H, PhCH2N), 3.97 m (1H,
NCH), 7.04 d (2H, NC6H4), 7.18–7.63 m (7H, NC6H4,
C6H5). Mass spectrum: m/z 340 [M + H]+. Found, %:
C 74.18; H 7.13; N 8.15. C21H24ClN2. Calculated, %:
C 74.24; H 7.06; N 8.24.
3-Benzyl-9-(pyrrolidin-1-yl)-3-azabicyclo[3.3.1]-
nonane (XV). Yield 90%, colorless oily substance,
1
Rf 0.72. H NMR spectrum, δ, ppm: 1.42–2.15 m
(10H, CH2), 2.29–2.38 m (2H, CH), 2.81–3.12 m (8H,
NCH2), 3.46 s (2H, PhCH2N), 3.98 m (1H, NCH),
7.19–7.45 m (5H, C6H5). Mass spectrum: m/z 284 [M +
H]+. Found, %: C 80.47; H 9.51; N 9.73. C19H27N2.
Calculated, %: C 80.58; H 9.53; N 9.89.
3-Benzyl-N-(4-bromophenyl)-3-azabicyclo[3.3.1]-
nonan-9-amine (XI). Yield 88%, light yellow oily sub-
stance, Rf 0.61. IR spectrum: ν 3324 cm–1 (NH).
1H NMR spectrum, δ, ppm: 1.46–2.08 m (6H, CH2),
2.32–2.37 m (2H, CH), 2.87 d (2H, NCH2), 3.01–
3.06 m (3H, NCH2, NH), 3.61 s (2H, PhCH2N), 3.98 m
(1H, NCH), 7.05 d (2H, NC6H4), 7.20–7.59 m (7H,
NC6H4, C6H5). Mass spectrum: m/z 385 [M + H]+.
Found, %: C 65.48; H 6.22; N 7.21. C21H24BrN2. Cal-
culated, %: C 65.64; H 6.28; N 7.29.
3-Benzyl-9-piperidino-3-azabicyclo[3.3.1]nonane
(XVI). Yield 91%, colorless oily substance, Rf 0.74.
1H NMR spectrum, δ, ppm: 1.40–2.18 m (12H, CH2),
2.30–2.41 m (2H, CH), 2.79–3.15 m (8H, NCH2),
3.48 s (2H, PhCH2N), 3.99 m (1H, NCH), 7.20–7.48 m
(5H, C6H5). Mass spectrum: m/z 298 [M + H]+. Found,
%: C 80.78; H 9.64; N 9.41. C20H29N2. Calculated, %:
C 80.82; H 9.76; N 9.42.
tert-Butyl 9-(pyrrolidin-1-yl)-3-azabicyclo[3.3.1]-
nonane-3-carboxylate (XVII). Yield 88%, colorless
oily substance, Rf 0.64. IR spectrum: ν 1682 cm–1
tert-Butyl 9-phenylamino-3-azabicyclo[3.3.1]-
nonane-3-carboxylate (XII). Yield 95%, colorless
oily substance, Rf 0.43. IR spectrum, ν, cm–1: 3328
1
(C=O). H NMR spectrum, δ, ppm: 1.29 s (9H, t-Bu),
1
(NH), 1683 (C=O). H NMR spectrum, δ, ppm: 1.30 s
1.40–2.18 m (10H, CH2), 2.30–2.41 m (2H, CH),
2.83–3.15 m (8H, NCH2), 3.88 m (1H, NCH). Mass
spectrum, m/z: 294 [M + H]+, 237 [M – 57 + H]+, 193
[M – 101 + H]+. Found, %: C 69.57; H 9.83; N 9.48.
C17H29N2O2. Calculated, %: C 69.64; H 9.89; N 9.55.
(9H, t-Bu), 1.44–2.09 m (6H, CH2), 2.38–2.45 m (2H,
CH), 3.04 br.s (1H, NH), 3.46 d (2H, NCH2), 3.66 d
(2H, NCH2), 4.01 m (1H, NCH), 7.01–7.12 m (5H,
C6H5). Mass spectrum, m/z: 316 [M + H]+, 259 [M –
57 + H]+, 215 [M – 101 + H]+. Found, %: C 72.27;
H 8.63; N 8.91. C19H27N2O2. Calculated, %: C 72.40;
H 8.57; N 8.88.
tert-Butyl 9-piperidino-3-azabicyclo[3.3.1]non-
ane-3-carboxylate (XVIII). Yield 92%, colorless oily
substance, Rf 0.65. IR spectrum: ν 1682 cm–1 (C=O).
1H NMR spectrum, δ, ppm: 1.30 s (9H, t-Bu), 1.42–
2.24 m (12H, CH2), 2.32–2.45 m (2H, CH), 2.84–
tert-Butyl 9-(4-chlorophenylamino)-3-azabicyclo-
[3.3.1]nonane-3-carboxylate (XIII). Yield 92%,
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REACTIONS OF 3-SUBSTITUTED 3-AZABICYCLO[3.3.1]NONAN-9-ONES
899
3.17 m (8H, NCH2), 3.91 m (1H, NCH). Mass spec-
trum, m/z: 308 [M + H]+, 251 [M – 57 + H]+, 207 [M –
101 + H]+. Found, %: C 70.26; H 10.03; N 9.14.
C18H31N2O2. Calculated, %: C 70.38; H 10.09; N 9.12.
m/z 215 [M + H]+. Found, %: C 58.07; H 7.53; N 9.74.
C14H22Cl2N2. Calculated, %: C 58.15; H 7.61; N 9.68.
N-(4-Chlorophenyl)-3-azabicyclo[3.3.1]nonan-9-
amine dihydrochloride (XXIII). Yield 94%, mp 208–
209°C. IR spectrum, ν, cm–1: 3378–3391 (+NH2).
1H NMR spectrum, δ, ppm: 1.53–2.41 m (6H, CH2),
2.34–2.50 m (2H, CH), 4.15 d (2H, NCH2), 4.24 d
(2H, NCH2), 5.11 m (1H, NCH), 7.43 d and 8.09 d
(2H each, C6H4, J = 8.0 Hz), 9.48 br.s (2H,
H2N+C6H4), 9.91 br.s (2H, H2N+). Mass spectrum:
m/z 250 [M + H]+. Found, %: C 51.93; H 6.38; N 8.57.
C14H21Cl3N2. Calculated, %: C 51.95; H 6.49; N 8.65.
3-Azabicyclo[3.3.1]nonan-9-one oxime dihydro-
chloride (XIX). Oxime IV, 1.27 g (5 mmol), was dis-
solved in 5 ml of anhydrous ethanol, 10 ml of a ~15–
16% solution of hydrogen chloride in dioxane was
added, and the mixture was left to stand for 12 h and
was then heated for 10 min under reflux. The solvent
was distilled off, and 30 ml of anhydrous diethyl ether
was added to the residue. After 20–30 h, the precipitate
was filtered off, washed with 20 ml of diethyl ether,
and dried in a vacuum desiccator over anhydrous
calcium chloride until constant weight. Yield 1.05 g
(93%), mp 185–186°C. IR spectrum, ν, cm–1: 3364
N-(4-Bromophenyl)-3-azabicyclo[3.3.1]nonan-9-
amine (XXIV). Yield 91%, mp 218–219°C. IR spec-
trum: ν 3374–3389 cm–1 (+NH2). 1H NMR spectrum, δ,
ppm: 1.52–2.43 m (6H, CH2), 2.36–2.52 m (2H, CH),
4.18 d (2H, NCH2), 4.26 d (2H, NCH2), 5.09 m (1H,
NCH), 7.39 d and 8.06 d (2H each, C6H4, J = 7.5 Hz),
9.46 br.s (2H, H2N+C6H4), 9.90 br.s (2H, H2N+). Mass
spectrum: m/z 295 [M + H]+. Found, %: C 45.61;
H 5.48; N 7.59. C14H21BrCl2N2. Calculated, %:
C 45.67; H 5.70; N 7.61.
1
(+NH2), 1648 (C=N). H NMR spectrum, δ, ppm:
1.52–2.31 m (6H, CH2), 2.58–2.67 m (2H, CH), 4.12 d
(2H, NCH2), 4.21 d (2H, NCH2), 9.81 br.s (2H, H2N+),
11.93 s (1H, OH). Mass spectrum: m/z 154 [M + H]+.
Found, %: C 42.51; H 6.18; N 12.56. C8H14Cl2N2O.
Calculated, %: C 42.69; H 6.22; N 12.44.
Compounds XX–XXVI were synthesized in a sim-
ilar way.
9-(Pyrrolidin-1-yl)-3-azabicyclo[3.3.1]nonane
dihydrochloride (XXV). Yield 89%, mp 174–175°C.
1
IR spectrum: ν 3369 cm–1 (+NH2). H NMR spectrum,
3-Azabicyclo[3.3.1]nonan-9-one hydrazone dihy-
drochloride (XX). Yield 87%, mp 167–168°C. IR
spectrum, ν, cm–1: 3371–3386 (+NH2), 1622 (C=N).
1H NMR spectrum, δ, ppm: 1.56–2.34 m (6H, CH2),
2.56–2.64 m (2H, CH), 4.15 d (2H, NCH2), 4.20 d
(2H, NCH2), 8.74 br.s (3H, H3N+), 9.84 br.s (2H,
H2N+). Mass spectrum: m/z 153 [M + H]+. Found, %:
C 42.76; H 6.57; N 18.63. C8H15Cl2N3. Calculated, %:
C 42.88; H 6.69; N 18.74.
δ, ppm: 1.48–2.64 m (10H, CH2), 2.72–2.86 m (2H,
CH), 4.23–4.42 m (8H, NCH2), 5.12 m (1H, NCH),
8.83 s (1H, HN+), 9.89 br.s (2H, H2N+). Mass spec-
trum: m/z 194 [M + H]+. Found, %: C 54.04; H 8.89;
N 10.63. C12H24Cl2N2. Calculated, %: C 53.95; H 8.98;
N 10.48.
9-Piperidino-3-azabicyclo[3.3.1]nonane dihydro-
chloride (XXVI). Yield 90%, mp 188–189°C. IR spec-
trum: ν 3372 cm–1 (+NH2). 1H NMR spectrum, δ, ppm:
1.51–2.68 m (12H, CH2), 2.71–2.86 m (2H, CH),
4.22–4.46 m (8H, NCH2), 5.08 m (1H, NCH), 8.85 s
(1H, HN+), 9.90 br.s (2H, H2N+). Mass spectrum:
m/z 208 [M + H]+. Found, %: C 55.43; H 9.18; N 9.85.
C13H26Cl2N2. Calculated, %: C 55.54; H 9.25; N 9.96.
3-Azabicyclo[3.3.1]nonan-9-one azine tetrahy-
drochloride (XXI). Yield 95%, mp 211–212°C. IR
spectrum, ν, cm–1: 3372–3386 (+NH2), 1620 (C=N).
1H NMR spectrum, δ, ppm: 1.55–2.36 m (12H, CH2),
2.58–2.66 m (4H, CH), 4.12–4.23 m (4H, NCH2),
4.31–4.42 m (4H, NCH2), 9.24 br.s (2H, NH+),
9.82 br.s (2H, H2N+). Mass spectrum: m/z 273 [M + H]+.
Found, %: C 45.64; H 7.47; N 13.12. C16H30Cl4N4.
Calculated, %: C 45.73; H 7.14; N 13.33.
REFERENCES
1. Moskalenko, A.I. and Boev, V.I., Russ. J. Org. Chem.,
N-Phenyl-3-azabicyclo[3.3.1]nonan-9-amine di-
hydrochloride (XXII). Yield 96%, mp 204–205°C. IR
2009, vol. 45, p. 472.
2. Lowe, J.A., Drozda, S.E., McLean, S., Bryce, D.K.,
Crawford, R.T., Snider, M.R., Longo, K.P., Nagahisa, A.,
and Tsuchiya, M., J. Med. Chem., 1994, vol. 37, p. 2831.
3. Yakhontov, L.N. and Glushkov, R.G., Sinteticheskie
lekarstvennye sredstva (Synthetic Medicines), Moscow:
Meditsina, 1983.
1
spectrum: ν 3375–3388 cm–1 (+NH2). H NMR spec-
trum, δ, ppm: 1.51–2.36 m (6H, CH2), 2.31–2.48 m
(2H, CH), 4.12 d (2H, NCH2), 4.23 d (2H, NCH2),
5.08 m (1H, NCH), 7.84–8.05 m (5H, C6H5), 9.45 br.s
(2H, H2N+Ph ), 9.88 br.s (2H, H2N+). Mass spectrum:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 6 2009