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Shiryaev et al.
resulting precipitate was collected by filtration, dissolved in
water (20 mL), acidified with acetic acid to pH 5, and extracted
with benzene. The extract was dried with sodium sulfate, the
solvent was removed in vacuo. Recrystallization of the residue
from water afforded compound 2 in the yield of 0.43 g (5%),
colorless crystals, m.p. 234—236 °C. IR, ν/cm–1: 3352 m (NH),
2901 v.s (C—H), 2580 v.s (C—H), 1736 v.s (C=O). 1H NMR, δ:
1.67—1.79 (m, 12 H, Ad); 1.86—1.90 (m, 12 H, Ad); 2.06—2.10
(m, 6 H, Ad); 8.34 (s, 1 H, NH). 13C NMR, δ,: 28.0 (Ad), 36.3
(Ad), 39.1 (Ad), 42.9 (Ad), 175.2 (C=O). Found (%): C, 77.42;
H, 9.11; N, 4.03. C24H31NO2. Calculated (%): C, 77.38; H, 9.15;
N, 4.10.
3ꢀ(1ꢀAdamantyl)ꢀ3ꢀoxopropanenitrile (3a). To a mixture of
methyl adamantaneꢀ1ꢀcarboxylate (1a) (3 g, 15 mmol), acetoꢀ
nitrile (9.5 mL, 179 mmol), toluene (25 mL), and NaH (a 60%
dispersion in mineral oil, 0.725 g, 17.6 mmol) was added under
argon. The stirred reaction mixture was refluxed for 8 h. The
precipitate formed was collected by filtration, washed with 10%
aqueous acetic acid (6 mL), and dried. Recrystallization from
petroleum ether afforded compound 3a in the yield of 2.35 g
(75%), colorless crystals, m.p. 98—100 °C (cf. Ref. 8: m.p. 112 °C).
IR, ν/cm–1: 2909 v.s (C—H), 2851 v.s (C—H), 2261 w (CN),
1705 v.s (C=O). 1H NMR, δ: 1.50—1.70 (m, 12 H, Ad); 2.00—2.10
(m, 3 H, Ad); 3.59 (s, 2 H, CH2). 13C NMR, δ: 27.2 (CH2CN),
27.7 (Ad), 36.2 (Ad), 38.0 (Ad), 46.9 (Ad), 114.4 (CN), 202.5
(C=O). Found (%): C, 76.89; H, 8.46; N, 6.82. C13H17NO.
Calculated (%): C, 76.81; H, 8.43; N, 6.89.
4ꢀ(1ꢀAdamantyl)ꢀ3ꢀoxobutanenitrile (3b) and 2ꢀ(1ꢀadamanꢀ
tyl)ꢀNꢀ(Eꢀ1ꢀcyanopropꢀ1ꢀeneꢀ2ꢀyl)acetamide (4). Compound 3b
was synthesized in the yield of 2.2 g (42%) similarly to comꢀ
pound 3a from methyl (1ꢀadamantyl)acetic acid (1b) (5 g,
24 mmol), colorless crystals, m.p. 44—45 °C (petroleum ether).
IR, ν/cm–1: 2905 v.s (C—H), 2851 v.s (C—H), 2257 w (CN),
1717 v.s (C=O). 1H NMR, δ: 1.58—1.64 (m, 9 H, Ad); 1.65—1.72
(m, 3 H, Ad); 1.94—1.98 (m, 3 H, Ad); 2.30 (s, 2 H, AdCH2);
3.43 (s, 2 H, CH2CN). 13C NMR, δ: 28.5 (Ad), 34.0 (CH2), 34.5
(CH2), 36.6 (Ad), 42.3 (Ad), 55.0 (Ad), 114.0 (CN), 196.9
(C=O). Found (%): C, 77.32; H, 8.87; N, 6.39. C14H19NO.
Calculated (%): C, 77.38; H, 8.81; N, 6.45.
The insoluble residue on recrystallization from ethanol
afforded amide 4 in the yield of 1.4 g (22%), yellow crystals, m.p.
175—176 °C. IR, ν/cm–1: 3283 s (NH), 3209 m (NH), 3140 m
(NH), 3090 m (NH), 3024 w (NH), 2901 v.s (CH), 2847 v.s
(CH), 2218 v.s (CN), 1708 v.s (C=O), 1639 s (C=N), 1519 v.s
(NH). 1H NMR, δ: 1.55—1.75 (m, 12 H, Ad); 1.80—2.00 (m, 3 H,
Ad); 2.03 (s, 2 H, AdCH2); 2.15 (s, 3 H, CH3); 6.44 (s, 1 H,
CH); 7.49 (s, 1 H, NH). 13C NMR, δ: 20.7 (CH3), 28.6 (CH,
Ad), 33.6 (C, Ad), 36.7 (CH2, Ad), 42.5 (CH2, Ad), 52.5
(AdCH2), 80.9 (CHCN), 119.0 (CN), 151.8 (C=NH), 171.1
(C=O). Found (%): C, 74.44; H, 8.63; N, 10.78. C16H22N2O.
Calculated (%): C, 74.38; H, 8.58; N, 10.84.
Table 1. Crystallographic characteristics and selected parameters
of Xꢀray diffraction experiment
Parameter
Value
Molecular formula
Molecular weight
C16H22N2O
258.36
Crystal system
Space group
Monoclinic
C2/c
a/Å
b/Å
c/Å
24.578(4)
10.2967(16)
13.636(3)
120.530(10)
2972.5(10)
8
β/deg
V/Å3
Z
dcalc/g cm–3
1.155
0.566
μ/cm–1
Scanning range
4.176 ≤ θ ≤ 74.889
3062 (0.0745)
2203
Number of measured reflections (Rint
Number of reflections with I > 2σ(I)
Number of refined parameters
R1 (I > 2σ(I))
)
178
0.0501
wR2 (all data)
0.1447
were refined by full matrix leastꢀsquares first isotropically, then
anisotropically. Hydrogen atoms were placed in geometrically
calculated positions. All calculations were performed employing
SHELXLꢀ2013 software.16 Visualization of the molecule geoꢀ
metry was carried out with PLATON program package.17
In crystal, molecules of 4 are bound by classical N(3)—
H(3)...N(7)i Hꢀbonds with the following parameters: N(3)—H(3) =
= 0.882(19) Å, H(3)...N(7)i = 2.07(2) Å, N(3)...N(7)i = 2.944(2) Å,
angle N(3)—H(3)...N(7)i = 173.2(19)°. Symmetry operation (i)
x, –y, z + × was applied to generate the coordinates of the N(7)i
from the N(7) atom.
1ꢀAcetyladamantane (6). To a water—sulfuric acid mixture
(1 : 1, 10 mL), 3ꢀ(1ꢀadamantyl)ꢀ3ꢀoxopropanenitrile (3a) (1.25 g,
7 mL) was added. The reaction mixture was heated at 140—145 °C
for 5 h, and extracted with benzene. Steam distillation, filtration
of the product from water layer, and drying afforded compound 6
in the yield of 0.6 g (55%), m.p. 53—54 °C (cf. Ref. 18: m.p. 54 °C).
This work was financially supported by the Russian
Science Foundation (Project No. 15ꢀ13ꢀ00084).
References
1. H. F. Anwar, M. H. Eln, ARKIVOC, 2009, (i), 198—250.
2. L. Johnson, J. Powers, F. Ma, K. Jendza, B. Wang,
E. Meredith, N. Mainolfi, Synthesis, 2013, 45, 171—173.
3. A. G. Mikhailovskii, Chem. Heterocycl. Compd. (Engl. Transl.),
2000, 2, 223 [Khim. Geterotsikl. Soedin., 2000, 2, 264].
4. I. S. Morozov, V. I. Petrov, Farmacologiya adamantanov
[Pharmacology of Adamantanes], Bolgograd, 2001, 161 pp.
(in Russian).
5. O. N. Zefirova, E. V. Nurieva, H. Lemcke, A. A. Ivanov,
D. V. Shishov, D. G. Weiss, S. A. Kuznetsov, N. S. Zefirov,
Bioorg. Med. Chem. Lett., 2008, 18, 5091—5094.
6. Eur. Pat. 0558145 B1.
A single crystal of compound 4 was obtained by crystallizaꢀ
tion from ethanol. XꢀRay diffraction experiment was carried out
with a Enraf—Nonius CADꢀ4 diffractometer15 (graphite monoꢀ
chromator, λ(CuꢀKα) = 1.5418 Å, temperature of 295 K, ω scan
mode). Crystallographic parameters, details of the Xꢀray experiꢀ
ments, structure solution, and refinement parameters for comꢀ
pound 4 are summarized in Table 1. The absorption was acꢀ
counted for using the experimental azimuthal scanning curves
(Tmin/Tmax). The structure was solved by the direct method.
Positions and displacement parameters for nonꢀhydrogen atoms