Aromatic 3,6ꢀdiazahomoadamantanꢀ9ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 4, April, 2015
963
oxyphenyl)butanꢀ2ꢀone were purchased from SigmaꢀAldrich,
other reactants (reagent grade) and solvents used in the work
were made in Russia. IR spectra of compounds were recorded
on a Bruker IFSv spectrophotometer in KBr pellets. 1H and
13C NMR spectra of solutions of compounds in CDCl3 were
recorded on a Bruker AMꢀ300 spectrometer (300.13 MHz for
1H and 75.47 MHz for 13C), using SiMe4 as an internal standard.
Electron impact mass spectra were recorded on a MSꢀ30 Kratos
instrument with direct injection of the sample into the source of
ions at 70 eV energy of ionizing electrons and 200 C temperaꢀ
ture of the source of ions. Melting points were determined on
a PTPꢀM appliance.
1ꢀSubstituted 3,6ꢀdiazahomoadamantanꢀ9ꢀones 4a—d (genꢀ
eral procedure). A. A mixture of tetramethylenediethylenetetrꢀ
amine 3 (8.50 g, 50 mmol), ketone 1a—d (55 mmol), and AcOH
(9.00 g, 150 mmol) in PriOH (50 mL) was stirred for 72 h at room
temperature. The reaction mixture was concentrated in vacuo,
a dense residue was extracted with hot nꢀheptane (4×40 mL).
A warm extract was purified, passing through a layer of anꢀ
hydrous aluminum oxide (10 g, Brockmann activity II) placed
on a Shott filter. The solvent was evaporated, the residue was
recrystallized from nꢀheptane.
the synthesis of tetramethylenediethylenetetramine 3 and
its condensation with ketones 1a—d were carried out in
one vessel without isolation (method B). The yields of the
target products 4a—d obtained by either methods were
virtually the same and averaged about 30%.
The fragrant diazahomoadamantanones 4a—d can be
used not only in perfumery, but also as pheromones in agriꢀ
culture. Besides, they can serve as the intermediate prodꢀ
ucts in the synthesis of other diazahomoadamantanones.
It is known that ordinary phenol ethers undergo cleavꢀ
age under drastic conditions upon heating to 120—150 C
with concentrated solutions of hydrobromic or hydroiodꢀ
ic acid. It was found that the reflux of 1ꢀ(4ꢀmethoxybenzꢀ
yl)ꢀ (4c) and 1ꢀ(4ꢀhydroxyꢀ3ꢀmethoxybenzyl)ꢀ3,6ꢀdiꢀ
azahomoadamantanꢀ9ꢀone (4d) with concentrated hydroꢀ
bromic acid over 3 h resulted in their cleavage with the
formation of alcohols, 1ꢀ(4ꢀhydroxybenzyl)ꢀ3,6ꢀdiazaꢀ
homoadamantanꢀ9ꢀone (4b) and 1ꢀ(3,4ꢀdihydroxybenzꢀ
yl)ꢀ3,6ꢀdiazahomoadamantanꢀ9ꢀone (4e), respectively
(Scheme 3).
B. Paraform aldehyde (6.00 g, 200 mmol) was added to
a solution of ethylenediamine (6.00 g, 100 mmol) in PriOH
(50 mL), and the mixture was stirred until complete dissolution.
Then, ketone 1a—d (55 mmol) and AcOH (9.00 g, 150 mmol)
were added to this solution. The reaction mixture was stirred for
72 h at room temperature and concentrated in vacuo. A dense
residue was extracted with hot nꢀheptane (4×40 mL). A warm
extract was purified, passing through a layer of anhydrous alumiꢀ
num oxide (10 g, Brockmann activity II) placed on a Shott filter.
The extractant was evaporated in vacuo, the residue was recrysꢀ
tallized from nꢀheptane.
Scheme 3
1ꢀBenzylꢀ3,6ꢀdiazahomoadamantanꢀ9ꢀone (4a). The yield
was 4.10 g (32%) (A), 4.00 g (31%) (B), white crystals, m.p.
102—104 C (from nꢀheptane) (cf. Ref. 3: m.p. 102—104 C).
13C NMR (CDCl3), : 213.54 CO(9); 136.50, 130.34, 127.86,
127.82 (Ph); 60.41 (C(2), C(10)); 58.23 (C(4), C(5)); 57.10 (C(7),
C(11)); 49.77 C(8); 45.52 C(1); 41.62 (CH2Ar).
1ꢀ(4ꢀHydroxybenzyl)ꢀ3,6ꢀdiazahomoadamantanꢀ9ꢀone (4b).
The yield was 2.54 g (33%) (A), 4.40 g (32%) (B), white crystals,
m.p. 209—210 C (from nꢀheptane) (cf. Ref. 4: m.p. 209—210 C).
1ꢀ(4ꢀMethoxybenzyl)ꢀ3,6ꢀdiazahomoadamantanꢀ9ꢀone (4c).
The yield was 5.57 g (39%) (A), 4.88 g (34%) (B), white crystals,
m.p. 106—107 C (from nꢀheptane). Found (%): C, 71.43; H, 7.60;
N, 9.85. C17H22N2O2. Calculated (%): C, 71.30; H, 7.74;
N, 9.78. IR, /cm–1: 1711 (C=O); 1609 (Ar); 1251, 1041 (OCH3).
1H NMR (CDCl3), : 2.67 (br.s, 1 H, CH); 2.79 (s, 2 H, CH2Ar);
2.97, 3.48 (both d, 4 H, 2 NCH2C, J = 3.9 Hz); 3.15 (m, 4 H,
NCH2CH2N); 3.07—3.20 (m, 4 H, 2 NCH2CH); 3.80 (s, 3 H,
OCH3); 6.82, 7.00 (both d, 4 H, Ar, J = 8.8 Hz). MS, m/z
(Irel (%)): 286 [M]+ (76), 213 (73), 165 (14), 137 (19), 131 (21),
122 (20), 101 (50), 91 (72), 72 (99), 58 (100), 43 (41).
1ꢀ(4ꢀHydroxyꢀ3ꢀmethoxybenzyl)ꢀ3,6ꢀdiazahomoadamantanꢀ
9ꢀone (4d). The yield was 5.30 g (35%) (A), 4.85 g, 32%) (B),
white crystals, m.p. 180—182 C (from nꢀheptane). Found (%):
C, 67.44; H, 7.40; N, 9.32. C17H22N2O3. Calculated (%):
C, 67.53; H, 7.33; N, 9.26. IR, /cm–1: 1711 (C=O); 1609 (Ar);
1245, 1032 (OCH3), 3322 (OH). 1H NMR (CDCl3), : 2.71
(br.s, 1 H, CH); 2.78 (s, 2 H, CH2Ar); 3.03 (d, 2 H, NCH2C,
J = 13.9 Hz); 3.22 (m, 4 H, NCH2CH2N); 3.17—3.24 (m, 4 H,
2 NCH2CH); 3.53 (d, 2 H, NCH2C, J = 13.2 Hz); 3.88 (s, 3 H,
R = OMe, R´ = H (c);
R = OH, R´ = OMe (d), H (b), OH (e)
The structure of newly obtained compounds 4a—e was
confirmed by elemental analysis, NMR spectroscopy, and
mass spectrometry.
The synthesized fragrant 3,6ꢀdiazahomoadamantanꢀ
9ꢀones 4a—e are highꢀmelting crystalline compounds,
soluble in water. Together with 1,3ꢀdiazaadamantanꢀ6ꢀ
ones 2a—d, they belong to a new class of fragrant ketones,
fragrant diazaadamantanones. It can be suggested that they
inherited from the parent ketones 1a—d not only the odor,
but also therapeutic and other properties.5—10
Experimental
4ꢀPhenylbutanꢀ2ꢀone, 4ꢀ(4ꢀhydroxyphenyl)butanꢀ2ꢀone,
4ꢀ(4ꢀmethoxyphenyl)butanꢀ2ꢀone, and 4ꢀ(4ꢀhydroxyꢀ3ꢀmethꢀ
Kuznetsov
