Heteroadamantanes and their derivatives: XXV. Synthesis of 3,6-diazahomoadamantane-9-spirothiiranes

Article abstract of DOI:10.1023/B:RUJO.0000003172.96050.93

By treating 3,6-diazahomoadamantane-9-spirooxiranes with potassium thiocyanate 3,6-diazahomoadamantane-9-spirothiiranes were obtained which further by reductive desulfuration were converted into 3-methyl- and 9-methylene-3,6-diazahomoadamantanes.

Full text of DOI:10.1023/B:RUJO.0000003172.96050.93

Russian Journal of Organic Chemistry, Vol. 39, No. 6, 2003, pp. 897 899. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 6, 2003,
pp. 946 948.
Original Russian Text Copyright
2003 by Kuznetsov, Serova, Azzheurova.
Heteroadamantanes and Their Derivatives: XXV.* Synthesis
of 3,6-Diazahomoadamantane-9-spirothiiranes
A. I. Kuznetsov1, T. M. Serova2, and I. A. Azzheurova1
1Lomonosov State Academy of Fine Chemical Technology, Moscow, Russia
2Institute of Physiologically Active Compounds, Russian Academy of Sciences,
Chernogolovka, Moscow Oblast, 142432 Russia
Received November 15, 2002
Abstract By treating 3,6-diazahomoadamantane-9-spirooxiranes with potassium thiocyanate 3,6-diazahomo-
adamantane-9-spirothiiranes were obtained which further by reductive desulfuration were converted into
3-methyl- and 9-methylene-3,6-diazahomoadamantanes.
We formerly carried out a reaction of 3,6-diaza-
homoadamantan-9-ones [2, 3] with trimethylsulf-
oxonium iodide and solid alkali in tert-butanol to
obtain 3,6-diazahomoadamantane-9-spirooxiranes (I).
Here we report on synthesis from oxiranes I of
3,6-diazahomoadamantane-9-spirothiiranes (II).
R = H, R = C6H5 (a); R = H, R = CH3 (b); R= R
= CH3 (c).
To convert 3,6-diazahomoadamantane-9-spiro-
oxiranes (I) into the respective spirothiiranes II we
reacted the oxiranes I with potassium thiocyanate
[5 8]. This reaction is known to proceed via forma-
tion of iminooxathiolanes [9]. This assumption was
confirmed by reaction of oxirane Ia with ammonium
thiocyanate in acetic acid at 50 60 C that afforded
3,6-diazahomoadamantane-9-spiro-5 -(2 -imino-1 ,3 -
oxathiolane) (IIIa) which on heating was converted
into thiirane IIa.
The desulfuration of spirothiirane IIa on Raney
nickel in 2-propanol resulted in formation of 1-phenyl-
3,6-diazahomoadamantane (IVa) with a methyl group
attached to the bridging (C9) carbon atom. By reac-
tion of 1-phenyl-3,6-diazahomoadamantane-9-spiro-
thiirane (IIa) with sodium borohydride we were first
to synthesize 3,6-diazahomoadamantane Va with a
*
For communication XXIV see [1].
1070-4280/03/3906-0897$25.00 2003 MAIK Nauka/Interperiodica

898
KUZNETSOV et al.
compound IIb 0.83 g (77%), mp 62 61 C. IR spec-
methylene group attached to the bridging (C9) carbon.
Compounds Va, b were also obtained by reductive
desulfuration of 3,6-diazahomoadamantane-9-spirothi-
iranes (IIa, b) with triphenylphosphine.
1
1
trum, , cm : 3047, 1250 (C S). H NMR spec-
trum, , ppm: 3.18 m (4H, NCH2CH2N); 3.33 d,
3.18 d, 2.98 d, 2.74 d, 3.12 2.28 m (8H, 4NCH2C,
2J 14.0 Hz); 1.35 br.s (1H, CH); 0.79 s (3H, CH3);
2.12 br.s, 2.24 br.s (2H, CH2). Mass spectrum, m/z
(Irel, %): 210 [M]+ (100), 178 (45), 177 (86), 161
(21), 146 (16), 115 (14), 103 (27), 58 (64), 57 (32),
43 (68), 41 (29).
The structure of compounds II V was confirmed
by IR, mass spectra. and also by 1H NMR spectra.
EXPERIMENTAL
IR spectra were recorded on spectrophotometer
Bruker IFSv from samples pelletized with KBr.
1H NMR spectra of compounds synthesized were
registered on spectrometer WM Bruker at operating
frequency 250.13 MHz from solutions in CDCl3,
internal reference TMS. Mass spectra were measured
on Finnigan MAT 90 instrument with direct sample
admission into the ion source, accelerating voltage
5 kV, emission current 100 A, ionizing electrons
energy 70eV, ionizing chamber temperature 200 C.
Perfluorokerosene was used as standard. Resolution
M/ M attained 10000.
1,8-Dimethyl-3,6-diazahomoadamantane-9-spiro-
thiirane (IIc) was prepared in the same way as
compound IIa from 0.20 g (0.96 mmol) of 1,8-di-
methyl-3,6-diazahomoadamantane-9-spirooxirane (Ic)
and 0.93 g of potassium thiocyanate in 10 ml of
water. Yield of compound IIc 0.17 g (77%), mp 108
1
109 C. H NMR spectrum, , ppm: 3.15 m (4H,
NCH2CH2N); 3.08 d, 2.93 d, 2.88 d, 2.65 d (8H,
2
4NCH2C, J 14.0 Hz); 2.39 s (2H, CH2); 0.58 s (6H,
2CH3). Mass spectrum, m/z (Irel, %): 224 [M]+ (100),
240 (43), 239 (93), 149 (94), 135 (28), 134 (56), 121
(24), 120 (21), 72 (45), 58 (41), 42 (18).
1-Phenyl-3,6-diazahomoadamantane-9-spirothi-
irane (IIa). (a) To a solution of 0.20 g (0.78 mmol)
of 1-phenyl-3,6-diazahomoadamantane-9-spirooxirane
(Ia) in 10 ml of 2-propanol was added a solution of
0.68 g (7.00 mmol) of potassium thiocyanate in 4 ml
of water. The mixture was boiled for 20 h, the
solvent was removed in a vacuum. The dry residue
was treated with hot heptane (5 15 ml), and heptane
was distilled off. The residue was recrystallized from
heptane. We obtained 0.19 g (91%) of compound IIa,
1-Phenyl-3,6-diazahomoadamantane-9-spiro-5 -
(2 -imino-1 ,3 -oxathiolane) (IIIa). To a solution of
1.45 g (19 mmol) of ammonium thiocyanate in 25 ml
of acetic acid at 50 60 C while stirring was added by
small portions 1.00 g (3.90 mmol) of 1-phenyl-3,6-di-
azahomoadamantane-9-spirooxirane (Ia). The mixture
was kept for 1.5 h, and then a saturated solution of
potassium carbonate was added to pH 9. The reaction
product was extracted into ether (6 5 ml). The
extracts were dried with potassium hydroxide, ether
was distilled off. We obtained 0.62 g (50%) of com-
1
mp 137 138 C. IR spectrum, , cm : 3051, 1251
1
1
(C S); 1595, 1498 (arom). H NMR spectrum,
,
pound IIIa, mp 164 165 C. IR spectrum, , cm :
ppm: 3.17 m (4H, NCH2CH2N); 3.88 d, 3.87 d,
3.61 d, 3.46 d, 3.10 2.90 m (8H, 4NCH2C, 2J
14.0 Hz); 7.10 7.50 m (5H, arom); 2.24 br.s,
2.13 br.s (2H, CH2). Mass spectrum, m/z (Irel, %):
272 [M]+ (100), 240 (43), 239 (93), 197 (80), 196
(35), 184 (31), 182 (54), 58 (34), 57 (47), 43 (33),
42 (35).
3284 (NH); 1645 (C=N); 1496 (arom). Mass spec-
trum, m/z (Irel, %): 315 [M]+ (11), 272 (95), 240 (51),
239 (100), 197 (89), 196 (44), 182 (66), 72 (41), 58
(45), 43 (40), 42 (47).
9-Methyl-1-phenyl-3,6-diazahomoadamantane
(IVa). To a solution of 0.27 g (1.00 mmol) of
1-phenyl-3,6-diazahomoadamantane-9-spirothiirane
(IIa) in 15 ml of 2-propanol was added 2 g of freshly
prepared Raney nickel, and the mixture was heated at
reflux for 24 h with adding every 5 h (thrice) 2 g of
fresh Raney nickel. The nickel was filtered off,
washed with 2-propanol, the filtrate was evaporated
in a vacuum. After recrystallization from heptane we
obtained 0.17 g (71%) of compound IVa, mp 186
(b) A solution of 0.2 g (0.67 mmol) of 1-phenyl-
3,6-diazahomoadamantane-9-spiro-5 -(2 -imino-1 ,3 -
oxathiolane) (IIIa) was heated in 2-propanol for 1 h,
the solvent was removed in a vacuum, the solid
residue was treated with hot heptane. On recrystalliz-
ation from heptane 0.14 g (82%) of compound IIa
was obtained.
1
1
187 C. IR spectrum, , cm : 1460 (arom). H NMR
spectrum, , ppm: 2.90 m (4H, NCH2CH2N); 3.88
2.22 m (8H, 4NCH2C); 6.95 7.27 m (5H, arom);
1-Methyl-3,6-diazahomoadamantane-9-spirothi-
irane (IIb) was prepared in the same way as com-
pound IIa from 1.0 g (5 mmol) of 1-methyl-3,6-di-
azahomoadamantane-9-spirooxirane (Ib) and 4.5 g of
potassium thiocyanate in 15 ml of water. Yield of
3
2.15 br.s (1H, CHCH3); 0.75 d (3H, CH3, J 7.0 Hz).
Mass spectrum, m/z (Irel, %): 242 [M]+ (57), 227 (38),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 6 2003

HETEROADAMANTANES AND THEIR DERIVATIVES: XXV.
899
151 (41), 149 (63), 93 (25), 72 (86), 58 (100), 56
(76), 55 (87), 42 (43), 41 (22).
9-Methylene-1-methyl-3, 6-diazahomoada-
mantane (Vb) was obtained similarly to compound
Va from 0.16 g (0.76 mmol) of 1-methyl-3,6-diaza-
homoadamantane-9-spirothiirane (IIb) and 0.02 g of
sodium borohydride in 10 ml of 2-propanol within
10 h. Yield of compound Vb 0.12 g (75%), mp 94
9-Methylene-1-phenyl-3, 6-diazahomoada-
mantane(Va). (a)To a solution of 0.2 g (0.73 mmol)
of 1-phenyl-3,6-diazahomoadamantane-9-spirothiirane
(IIa) in 10 ml of 2-propanol was added 0.02 g of
sodium borohydride, and the reaction mixture was
heated at reflux for 10 h. The reaction mixture was
evaporated in a vacuum, the solid residue was treated
with minimum amount of water, water was distilled
off, and the reaction product was extracted with hot
heptane. We obtained 0.14 g (79%) of compound Va,
1
1
95 C. IR spectrum, , cm : 1641 (C=C). H NMR
spectrum, , ppm: 3.13 m (4H, NH2CH2N); 3.51 d,
2
3.38 d, 2.87 d, 2.72 d (8H, 4NCH2C, J 14.0 Hz);
3
2.51 br.s (1H, CH); 4.76 d, 4.24 d (2H, CH2, J
1.5 Hz); 0.86 s (3H, CH3). Mass spectrum, m/z (Irel,
%): 178 [M]+ (52), 162 (43), 153 (23), 152 (67), 121
(78), 72 (100), 71 (39), 57 (31), 56 (23), 42 (37),
41 (57).
1
mp 109 110 C. IR spectrum, , cm : 1635 (C=C),
1
1500 (arom). H NMR spectrum, , ppm: 3.19 m
REFERENCES
(4H, NCH2CH2N); 3.62 d, 3.40 d, 3.05 d, 2.98 d
(8H, 4NCH2C, 2J 14.0 Hz); 7.12 7.50 m (5H,
arom); 4.83 d, 4.24 d (2H, CH2, 2J 1.5 Hz);
2.53 br.s (1H, CH). Mass spectrum, m/z (Irel, %):
240 [M]+ (60), 239 (39), 198 (14), 197 (100), 196
(20), 182 (11), 168 (9), 167 (11), 155 (8), 72 (9),
58 (15).
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(b) A solution of 0.20 g (0.73 mmol) of 1-phenyl-
3,6-diazahomoadamantane-9-spirothiirane (IIa) and
0.19 g (0.73 mmol) of triphenylphosphine in 19 ml of
anhydrous ether was heated at weak boiling till pre-
cipitated colorless crystals. The crystals were separat-
ed. We obtained 0.16 g (76%) of (C6H5)3PS, mp
151 152 C. The mother liquor was evaporated, the
residue was subjected to TLC on glass plates (90
120) with unfixed layer of alumina, eluent chloroform.
We obtained 0.12 g (67%) of compound Va.
9. Sander, M., Thiiranes Chem. Rev., 1996, vol. 66,
p. 297.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 6 2003