Synthesis of diacetylamino and diamino derivatives of adamantane series

Article abstract of DOI:10.1134/S1070428017080024

1,3-Diacetylamino derivatives were synthesized directly from adamantane series hydrocarbons or from adamantan-1-ylacetic acids by a one-pot method with a succession of an oxidation stage and Ritter’s reaction in nitric acid and in a mixture of sulfuric and nitric acids. The hydrolysis of 1,3-diacetylamino derivatives in an acidic medium leads to scaffold diamines and diaminoacids.

Full text of DOI:10.1134/S1070428017080024

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 8, pp. 1170–1175. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © Yu.N. Klimochkin, E.A. Ivleva, A.S. Serzhantova, A.K. Shiryaev, I.K. Moiseev, 2017, published in Zhurnal Organicheskoi Khimii,
2017, Vol. 53, No. 8, pp. 1156–1161.
Synthesis of Diacetylamino and Diamino Derivatives
of Adamantane Series
Yu. N. Klimochkin, E. A. Ivleva,* A. S. Serzhantova, A. K. Shiryaev, and I. K. Moiseev
Samara State Technical University, Molodogvardeiskaya ul. 244, Samara, 443100 Russia
*e-mail: elena.a.ivleva@yandex.com
Received May 10, 2017
Abstract—1,3-Diacetylamino derivatives were synthesized directly from adamantane series hydrocarbons or
from adamantan-1-ylacetic acids by a one-pot method with a succession of an oxidation stage and Ritter’s
reaction in nitric acid and in a mixture of sulfuric and nitric acids. The hydrolysis of 1,3-diacetylamino
derivatives in an acidic medium leads to scaffold diamines and diaminoacids.
DOI: 10.1134/S1070428017080024
The practical importance of scaffold di- and
polyamines is due to their application as initial
substrates for the synthesis of new biologically active,
in particular, antiviral, substances [1–3], for the
preparation of polynitroadamantanes [4-6], as well as
additives improving service properties of polymers
[7–11]. On the basis of amines and amino acids of the
adamantane series structures of various degrees of
molecular complexity have been synthesized [12–20],
including macroheterocycles [21–25], which can be
used as photosensors, targeted drug delivery systems
for affected cells, materials for medical diagnosis, and
to possess other valuable applied properties.
annular cyclization of 1,3,5,7-tetramethylenecyclooc-
tane in a mixture of sulfuric acid and acetonitrile [36].
A one-step process is known for the preparation of
1,3-diacetylamino derivatives of adamantane by the
reaction of adamantane with acetonitrile with an initial
activation of the C-H bond of the scaffold by the action
of HIO3 in the presence of N-hydroxyphthalimide [37].
The existing methods of the preparation of 1,3-
diacetylamino derivatives suggest the use of
functionally substituted adamantanes, which must be
previously prepared in several stages, and they give
insufficiently high yields of the reaction products. In
this connection a necessity exists for modifying the
methods for the preparation of 1,3-diacetylamino
derivatives of adamantane.
The main methods for the preparation of adaman-
tane-1,3-diamines are as follows: the hydrolysis of
diacetylamino derivatives of adamantane [26, 27], the
reduction of 1,3-diazides [28], 1,3-dinitroadamantane
[29, 30], and dibenzyl adamantane-1,3-diylbiscarbama-
te [31], Hofmann degradation of diamide of adaman-
tane-1,3-dicarboxylic acid [32], amidation of 1,3-di-
bromadamantane with urea in trifluoroacetic acid [33].
In extension of the research on the development of
methods for the synthesis of functional derivatives of
adamantane in acidic media [38–44] we developed a
one-pot method for the synthesis of 1,3-diacetylamino
derivatives of the adamantane series directly from
hydrocarbons. Despite a rather wide range of different
synthetic methods based on the oxidative functiona-
lization of adamantane [45, 46], the oxidation with
nitric acid [40, 42, 44] or with a mixture of sulfuric
and nitric acids [47, 48] still remain among the main
methods that allow the preparation of polyfunctional
derivatives including those containing acceptor
substituents.
Among currently existing methods for the
preparation of adamantane-1,3-diamines, the
hydrolysis of the corresponding 1,3-diacetylamino
derivatives, which are obtained by the Ritter reaction
from 1,3-dihaloadamantane, is the optimal one
[26, 34]. Alternative methods for the preparation of 1,3
-diacetylamino derivatives are the electrolysis of
adamantane in acetonitrile in the presence of tetrame-
thylammonium tetrafluoroborate [35] and the trans-
The method involves the following successive
stages: nitroxylation of the initial scaffold substrates
1170

SYNTHESIS OF DIACETYLAMINO AND DIAMINO DERIVATIVES OF ADAMANTANE SERIES
1171
Conditions of the synthesis of 1,3-diacetylamino adaman-
tane derivatives 2a-2g
by fuming nitric acid, the reaction with acetonitrile by
the Ritter reaction, and the conversion of the in situ
formed monoacetamides into diacetylamino deriva-
tives of adamantane by the addition of sulfuric acid
[49]. The following compounds were used as initial
substrates: adamantane 1a and its homologs 1b–1d, as
well as adamantan-1-yl-acetic acids 1e–1g, including
alkyl-substituted ones, prepared according to a modified
procedure (Scheme 1).
Reaction HNO3, τ1, CH3CN,
H2SO4,
equiv
Yield,
%
τ2, h
τ3, h
product equiv
h
1
1
1
1
2
2
2
equiv
2.5
2.5
3
2a
2b
2c
2d
2e
2f
10
11
13
12
30
30
30
0.5
0.5
0.5
0.5
1
13
17
10
4
81
89
73
92
47
35
50
19
10
4
2.5
12
28
97
15
15
15
Scheme 1.
O
13
1
104
111
2g
14
1
HN
CH3
1. HNO3 (fum.)
2. CH3CN
3. H2SO4
O
R
R
carrying out the reactions and the quantity of reagents
required are shown in the table. 1,3-Diacetylamino
derivatives 2a–2d were synthesized in a sufficiently
high yield (73–92%).
20_25oC
CH3
N
H
R'
1a_1g
R'
2a_2g
R = R' = H (a); R = CH3, R' = (b); R = C2H5, R' = H (c), R =
R' = CH3 (d); R = CH2COOH, R' = H (e), R = CH2COOH,
R' = CH3 (f); R = CH2COOH, R' = C2H5 (g).
In extension of the research on the development of
methods for the functionalization of deactivated
scaffold structures [52–55], adamantan-1-ylacetic
acids 1e–1g were used as initial compounds. At the
stage of nitroxylation of compounds 1e–1g 30 equiv of
fuming nitric acid should be used [50]. In the
subsequent stage it is necessary to use 98% sulfuric
acid, because at the addition of the acid of a lower
concentration only monoacetylamine derivatives are
formed. The conditions for the synthesis of 1,3-di-
acetylamino adamantane 2e–2g from adamantane-1-yl-
acetic acids 1e–1g are shown in the table. Compounds
2e–2g were obtained in a 35–50% yield.
In 1H NMR spectra of compounds 2a-2g the
protons of NH groups appear as a singlet in the range
of 7.29–7.41 ppm. In 13C NMR spectra signals of
quaternary carbon atoms of C–N bonds appear in the
range of 52–53 ppm, signals of carbon atoms of the
The reactions proceed through the stage of the
formation of 1-nitroxy derivatives of adamantane [40,
44], which further are converted into 1-acetylamine
derivatives when acetonitrile is added to the reaction
mixture as a nucleophile. Further increase in the
acidity of the reaction medium by adding 96% sulfuric
acid leads to the oxidation of the tertiary bond of the
C–H scaffold to form an intermediate carbocation,
which then reacts with acetonitrile by the Ritter
reaction (Scheme 2).
Scheme 2.
ONO2
+
NHAc
Scheme 3.
NHAc
NHAc
O
_
NH+3Cl
HN
CH3
+
NHAc
H2O_HCl
reflux
O
R
R
_
NH3+Cl
N
H
CH3
To synthesize 1,3-diacetylamino derivatives 2a–2d
10-13 equiv of fuming nitric acid should be used [40,
44, 50, 51] with respect to the initial hydrocarbons
1a–1d at the nitroxylation stage. The conditions for
R'
R'
2a_2g
3a_3g
R = R' = H (a), R = CH3, R' = H (b); R =C2H5, R' = H (c); R =
R' = CH3 (d); R = CH2COOH, R' = H (e), CH3 (f), C2H5 (g).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017

KLIMOCHKIN et al.
1172
C=O group of acetamide fragments are observed in a
weak field at 169 ppm.
70 mL of 1,1-dichloroethane, and 210 mL of 96%
sulfuric acid. Yield 75.1 g (87%), mp 91–92°C [58].
Compounds 2a–2g. General procedure. To a
fuming nitric acid (see the table) compound 1a–1g was
added in portions with stirring at a temperature no
higher than 25°C. The resulting solution was stirred for
1.5 hours at 25°C. Then acetonitrile was added
dropwise to the reaction mixture, it was maintained for
1 hour, then conc. H2SO4 (96% for compounds 1a–1d
and 98% for compounds 1e–1g) was added dropwise
and the mixture was kept at room temperature for a
preset time. The solution was poured onto 600 g of
crushed ice and adjusted to pH 9 with NaHCO3 under
stirring and cooling to prepare compounds 2a–2d or
adjusted to pH 5 in the preparation of 2e–2j
compounds. Then, the aqueous layer was decanted
from the viscous oily reaction product, 30 mL of ethyl
acetate was added to the residue. The precipitate was
filtered off, washed with water, and dried.
Compounds 2a–2g were converted to the
corresponding amines by prolonged boiling (25 h) in
2% hydrochloric acid (Scheme 3). Hydrolysis did not
lead to the formation of side chloro and hydroxy
derivatives (cf. with [55, 56]).
Diamines were isolated as dihydrochlorides 3a–3g
in 92-98% yields. In 1H NMR spectra the signals of pro-
tonated amino groups appear as singlets at 8.4–8.5 ppm,
in 13C NMR spectra the signals of carbon atoms of the
adamantane fragment bound to protonated amino
groups resonate in the range of 52–53 ppm.
The developed effective method for the synthesis of
1,3-diacetylamino derivatives of the adamantane series
allows the preparation of reaction products in high
yields using available reagents. Diamines and diamino-
acids of the adamantane series obtained by the hydrolysis
of 1,3-diacetylamino derivatives are suitable as
building blocks in the synthesis of biologically active
compounds, conformationally rigid peptidomimetics
and other compounds with useful properties.
N,N'-(Adamantane-1,3-diyl)diacetamide (2a) was
prepared from 5 g of adamantane Ia. Yield 7.44 g (81%).
Colorless crystals, mp 226–228°C (mp 226–227°C [37]).
N,N'-(5-Methyladamantane-1,3-diyl)diacetamide
(2b) was prepared from 20 g of 1-methyladamantane
1b. Yield 29.70 g (89%). Colorless crystals, mp 242‒
244°C. IR spectrum, ν, cm–1: 3305 (NH), 2931, 2908,
EXPERIMENTAL
1H, 13C NMR spectra were recorded on a Jeol JNM
ECX-400 spectrometer (operating frequency 400 MHz)
in DMSO-d6. IR spectra were taken on a Shimadzu
IRAffinity-1 spectrophotometer from pellets with KBr.
Elemental analysis was performed on an analyzer
EuroVector 3000 EA, reference L-cystine. Melting
points were determined by the capillary method on an
OptiMelt MPA100 apparatus and were not corrected.
1
2897 (CHAd), 1651, 1546 (C=O). H NMR spectrum,
δ, ppm: 0.79 s (3H, CH3), 1.24 s (2H, CH2Ad), 1.49‒
1.59 m (4H, 2CH2Ad), 1.65‒1.77 m (4H, CH2Ad), 1.69 s
(6H, CH3), 2.03 s (2H, CH2Ad), 2.06 br.s (1H, CHAd),
7.29 s (2H, NH). 13C NMR spectrum, δ, ppm: 24.23
(CH3), 29.89 (CH), 30.32 (CH3), 32.76 (C), 39.90
(CH2), 42.69 (CH2), 44.48 (CH2), 47.51 (CH2), 53.01
(C), 169.19 (C). Found, %: C 68.13; H 9.12; N 10.58.
C15H24N2O2. Calculated, %: C 68.15; H 9.15; N 10.60.
3-Methyladamantan-1-ylacetic acid (1e). To a
suspension of 20 g (0.120 mol) of 3-methyladamanta-
ne-1-ol in 20 mL (0.249 mol) of 1,1-dichloroethane
and 15 mL of CH2Cl2 precooled to 0°C 50 mL of 98%
sulfuric acid was slowly added dropwise with stirring.
On the addition of the first portions of acid foaming
and a sharp increase in temperature to 30°C occurred.
The mixture was cooled to 15°C, the remaining
sulfuric acid was added, the mixture was kept for
1 h, and then it was poured onto 300 g of crushed ice.
The precipitate was filtered off, washed with water,
and dried. Yield 23 g (93%), mp 105–107°C (mp 106–
108°C [57]).
N,N'-(5-Ethyladamantane-1,3-diyl)diacetamide
(2c) was prepared from 1 mL of 1-ethyladamantane 1c.
Yield 1.15 g (73%). Colorless crystals, mp 219–220°C.
IR spectrum, ν, cm–1: 3255, 3207 (NH), 2960, 2918,
2902, 2891, 2860 (CHAd), 1639, 1558 (C=O). 1H NMR
spectrum, δ, ppm: 0.72 t (3H, CH3, J 7.32 Hz), 1.11 q (2H,
CH2CH3, J 7.32 Hz), 1.22 s (2H, CH2Ad), 1.47‒1.56 m
(4H, CH2Ad), 1.66‒1.78 m (4H, CH2Ad), 1.69 s (6H,
CH3), 2.01‒2.08 m (3H, CH2Ad, CHAd), 7.32 s (2H,
NH). 13C NMR spectrum, δ, ppm: 7.60 (CH3), 24.24
(CH3), 29.72 (CH), 35.40 (C), 35.50 (CH2), 40.12
(CH2), 40.28 (CH2), 44.82 (CH2), 45.06 (CH2), 53.00
(C), 169.19 (C). Found, %: C 69.00; H 9.39; N 10.04.
C16H26N2O2. Calculated, %: C 69.03; H 9.41; N 10.06.
Similarly, 3-ethyladamantan-1-yl-acetic acid (1f)
was obtained from 70 g of 3-ethyladamantane-1-ol,
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SYNTHESIS OF DIACETYLAMINO AND DIAMINO DERIVATIVES OF ADAMANTANE SERIES
1173
N,N'-(3,5-Dimethyladamantane-1,3-diyl)diacet-
amide (2d) was prepared from 3 mL of 1,3-dime-
thyladamantane 1d. Yield 4.20 g (92%). Colorless
crystals, mp 304–305°C (mp 301–303°C [36]).
compound 2a–2g, 28 mL of water, and 2 mL of 36%
hydrochloric acid was boiled for 25 hours and
evaporated to dryness. In the residue, compounds 3a–
3g were obtained.
[3,5-Bis(acetylamino)adamantan-1-yl]acetic acid
(2e) was obtained from 3 g of adamantan-1-ylacetic
acid 1e. Yield: 2.25 g (47%). Colorless crystals, mp
250°C (decomp.). IR spectrum, ν, cm–1: 3346, 3292,
3109 (NH); 2912, 2862 (CHAd), 1697, 1656 (C=O). 1H
NMR spectrum, δ, ppm: 1.38 s (2H, CH2Ad), 1.64‒1.78
m (6H, CH2Ad), 1.69 s (6H, CH3), 2.00 s (2H, CH2Ad),
2.04 s (2H, CH2COOH), 2.08 s (1H, CHAd), 7.36 s
(2H, NH), 11.89 s (1H, COOH). 13C NMR spectrum,
δ, ppm: 24.20 (CH3), 29.58 (CH), 35.08 (C), 39.92
(CH2), 40.58 (CH2), 44.52 (CH2), 45.22 (CH2), 47.59
(CH2), 52.81 (C), 169.24 (C), 172.78 (C). Found, %: C
62.29; H 7.81; N 9.05. C16H24N2O4. Calculated, %: C
62.32; H 7.84; N 9.08.
Adamantane-1,3-bis(aminium) dichloride (3a).
Yield (96%), colorless crystals, mp 330°C (decomp.) [59].
5-Methyladamantane-1,3-bis(aminium) dichloride
(3b). Yield 0.42 g (93%). Colorless crystals, mp 330°C
(decomp.). IR spectrum, ν, cm–1: 2945, 2904, 2858,
2831, 2819 (CHAd). 1H NMR spectrum, δ, ppm: 0.87 s
(3H, CH3), 1.27 s (2H, CH2Ad), 1.45–1.52 m (4H,
CH2Ad), 1.63–1.72 m (4H, CH2Ad), 1.92–1.99 m (2H,
+
CH2Ad), 2.26 s (1H, CHAd), 8.47 (6H, NH3 ). 13C NMR
spectrum, δ, ppm: 29.07 (CH3), 29.40 (CH), 32.96 (C),
38.10 (CH2), 41.09 (CH2), 42.21 (CH2), 45.56 (CH2),
52.72 (C). Found, %: C 52.15; H 8.73; N 11.03.
C11H22Cl2N2. Calculated, %: C 52.18; H 8.76; N 11.06.
5-Ethyladamantane-1,3-bis(aminium) dichloride
(3c). Yield 0.44 g (92%). Colorless crystals, mp 330°C
(decomp.). IR spectrum, ν, cm–1: 2947, 2908, 2875,
[3,5-Bis(acetylamino)-7-methyladamantan-1-yl]-
acetic acid (2f) was obtained from 3 g of 3-methyl-
adamantan-1-yl-acetic acid 1f. Yield 1.62 g (35%).
Colorless crystals, mp 247-249°C. IR spectrum, ν, cm–1:
3375, 3286, 3201 (NH), 2900, 2858 (CHAd), 1681,
1
2821 (CHAd). H NMR spectrum, δ, ppm: 0.73 t (3H,
CH3, J 7.32 Hz), 1.16–1.21 q (2H, CH2, J 7.32 Hz),
1.26 s (2H, CH2Ad), 1.48 s (4H, CH2Ad), 1.68 s (4H,
CH2Ad), 1.94–2.01 m (2H, CH2Ad), 2.27 s (1H, CHAd),
1
1650, 1608 (C=O). H NMR spectrum, δ, ppm: 0.80 c
(3H, CH3), 1.15 s (2H, CH2Ad), 1.43–1.59 m (6H,
CH2Ad), 1.69 s (8H, 2CH3, CH2Ad), 1.98 s (2H, CH2Ad),
2.02 s (2H, CH2COOH), 7.41 (2H, NH), 11.96 (1H,
COOH). 13C NMR spectrum, δ, ppm: 24.19 (CH3), 30.00
(CH3), 32.79 (C), 35.38 (C), 43.77 (CH2), 44.52 (CH2),
46.80 (CH2), 47.28 (CH2), 47.70 (CH2), 53.31 (C), 169.30
(C), 172.85 (C). Found, %: C 63.30; H 8.10; N 8.67.
C17H26N2O4. Calculated, %: C 63.33; H 8.13; N 8.69.
+
8.48 (6H, NH3 ). 13C NMR spectrum, δ, ppm: 7.51
(CH3), 28.91 (CH), 34.61 (CH2), 35.75 (C), 38.45
(CH2), 38.59 (CH2), 42.52 (CH2), 43.18 (CH2), 52.78
(C). Found, %: C 53.90; H 9.02; N 10.45.
C12H24Cl2N2. Calculated, %: C 53.93; H 9.05; N 10.48.
5,7-Dimethyladamantane-1,3-bis(aminium)
dichloride (3d). Yield (97%), colorless crystals, mp
330°C (decomp.) [45].
[3,5-Bis(acetylamino)-7-ethyladamantan-1-yl]-
acetic acid (2g) was prepared from 3 g of 3-ethyl-
adamantan-1-yl-acetic acid 1g. Yield: 2.27 g (50%).
Colorless crystals, mp 257–259°C. IR spectrum, ν, cm–1:
3360, 3282 (NH), 2966, 2916, 2850 (CHAd), 1720,
5-(Carboxymethyl)adamantane-1,3-bis(aminium)
dichloride (3e). Yield 0.5 g (93%). Colorless crystals,
mp 300°C (decomp.). IR spectrum, ν, cm–1: 2966,
1
2900, 2812 (CHAd), 1732 (C=O). H NMR spectrum,
1
1654, 1608 (C=O). H NMR spectrum, δ, ppm: 0.71 t
δ, ppm: 1.41 s (2H, CH2Ad), 1.59‒1.67 m (8H, CH2Ad),
1.89–2.00 m (2H, CH2Ad), 2.14 s (2H, CH2), 2.28 br.s
(3H, CH3, J 6.44 Hz), 1.09‒1.13 m (6H, CH2CH3,
2CH2Ad), 1.40‒1.43 m (2H, CH2Ad), 1.50‒1.59 m (4H,
CH2Ad), 1.69 s (8H, CH2Ad, 2CH3), 1.99 s (2H, CH2Ad),
2.02 s (2H, CH2COOH), 7.43 s (2H, NH). 13C NMR
spectrum, δ, ppm: 7.67 (CH3), 24.15 (CH3), 35.19
(CH2), 35.48 (C), 44.02 (CH2), 44.29 (CH2), 44.81
(CH2), 45.27 (CH2), 47.38 (CH2), 53.33 (C), 169.51
(C), 172.88 (C). Found, %: C 64.23; H 8.36; N 8.30.
C18H28N2O4. Calculated, %: C 64.26; H 8.39; N 8.33.
+
(1H, CHAd), 8.43 s (6H, NH3 ), 11.81 br.s (1H,
COOH). 13C NMR spectrum, δ, ppm: 28.76 (CH),
35.06 (C), 38.17 (CH2), 39.09 (CH2), 42.26 (CH2),
43.20 (CH2), 46.31 (CH2), 52.53 (C), 172.44 (C).
Found, %: C 48.47; H 7.43; N 9.40. C12H22Cl2N2O2.
Calculated, %: C 48.49; H 7.46; N 9.43.
5-(Carboxymethyl)-7-methyladamantane-1,3-bis-
(aminium) dichloride (3f). Yield 0.3 g (98%).
Colorless crystals, mp 300°C (decomp.). IR spectrum,
ν, cm–1: 2900, 2893, 2826 (CHAd), 1699 (C=O). 1H NMR
Hydrolysis of 1,3-diacetylamino derivatives of
the adamantane series (2a–2g). A mixture of 1 g of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017

KLIMOCHKIN et al.
1174
8. Novakov, I.A., Orlinson, B.S., Zaikov, G.E., and
Zaikov, V.G., Polymer Aging at the Cutting Edge, UK:
Nova Biomedical Books, 2002, vol. 6, p. 19.
spectrum, δ, ppm: 0.88 s (3H, CH3), 1.20 s (2H, CH2Ad),
1.41–1.48 m (4H, CH2Ad), 1.56–1.66 m (4H, CH2Ad),
1.86–1.94 m (2H, CH2Ad), 2.14 s (2H, CH2COOH), 8.51
(6H, NH3+). 13C NMR spectrum, δ, ppm: 29.05 (CH3),
33.01 (C), 35.39 (C), 41.59 (CH2), 42.55 (CH2), 44.92
(CH2), 46.04 (CH2), 46.29 (CH2), 52.95 (C), 172.45 (C).
Found, %: C 50.14; H 7.74; N 8.97. C13H24Cl2N2O2.
Calculated, %: C 50.17; H 7.77; N 9.00.
9. Novikov, S.S., Khardin, A.P., Radchenko, S.S., Orlin-
son, B.S., Novakov, I.A., Blinov, V.F., Gerashchenko, Z.V.,
Zimin, Yu.B., Voishchev, V.S., and Krupenin, N.V., RF
Patent no. 681865, 1996, Chem. Abstr., 1996, vol. 125,
p. 115535.
10. Novakov, I.A., Orlinson, B.S., Kuznechikov, O.A.,
Kulago, I.O., Pavlyuchko, A.I., Sabirov, Z.M.,
Urazbaev, V.N., and Monakov, Yu.V., Russ. Chem.
Bull., 1999, vol. 48, p. 282. doi 10.1007/BF02494548
5-(Carboxymethyl)-7-ethyladamantane-1,3-bis-
(aminium) dichloride (3g). Yield 0.46 g (95%).
Colorless crystals, mp 300°C (decomp.). IR spectrum,
ν, cm–1: 2958, 2910, 2852, 2814 (CHAd), 1710 (C=O). 1H
NMR spectrum, δ, ppm: 0.73 t (3H, CH3, J 7.32 Hz),
1.19‒1.23 m (4H, CH2CH3, CH2Ad), 1.39–1.48 m (4H,
CH2Ad), 1.57‒1.71 m (4H, CH2Ad), 1.88‒1.96 m (2H,
CH2Ad), 2.15 s (2H, CH2COOH), 8.50 (6H, NH3+). 13C
NMR spectrum, δ, ppm: 7.57 (CH3), 34.32 (CH2),
35.22 (C), 35.84 (C), 41.90 (CH2), 42.56 (CH2), 42.85
(CH2), 43.92 (CH2), 46.10 (CH2), 53.01 (C), 172.47 (C).
Found, %: C 51.67; H 8.03; N 8.58. C14H26Cl2N2O2.
Calculated, %: C 51.70; H 8.06; N 8.61.
11. Novakov, I.A., Popov, Yu.V., Korchagin, T.K.,
Ermakova, T.A., Novopol’tseva, O.M., and Tankov, D.Yu.,
RF Patent no. 2232782, 2004; Chem. Abstr., 2004,
vol. 141, p. 278874.
12. Šekutor, M., Štimac, A., Mlinarić-Majerski, K., and
Frkanec, R., Org. Biomol. Chem., 2014, vol. 12, p. 6005.
13. Averin, A.D., Ranyuk, E.R., Golub, S.L., Buryak, A.K.,
Savelyev, E.N., Orlinson, B.S., Novakov, I.A., and
Beletskaya, I.P., Synthesis, 2007, vol. 14, p. 2215.
14. Blazek, V., Mlinaric-Majerski, K., Qin, W., and
Basaric, N., J. Photochem. Photobiol. A: Chem., 2012,
vol. 229, p. 1.
ACKNOWLEDGMENTS
15. Averin, A.D., Ulanovskaya, M.A., Buryak, A.K.,
Savel’ev, E.N., Orlinson, B.S., Novakov, I.A., and
Beletskaya, I.P., Russ. J. Org. Chem., 2011, vol. 47,
p. 30. doi 10.1134/S107042801
The study was carried out with the financial support
of the Russian Science Foundation (grant no. 13-
00084) using the scientific equipment of the Center of
Joint Usage for Investigating the Physicochemical
Properties of Substances and Materials”.
16. Grigorova, O.K., Averin, A.D., Abel, A.S., Maloshits-
kaya, O.A., Butov, G.M., Savelyev, E.N., Orlinson, B.S.,
Novakov, I.A., and Beletskaya, I.P., Russ. J. Org.
Chem., 2012, vol. 48, p. 1495. doi 10.1134/S107042801
REFERENCES
1. Hoekstra, W.J., Beavers, M.P., Andrade-Gordon, P.,
Evangelisto, M.F., Keane, P.M., Press, J.B.,
Tomko, K.A., Fan, F., Kloczewiak, M., Mayo, K.H.,
Durkin, K.A., and Liotta, D.C., J. Med. Chem., 1995,
vol. 3, p. 1582.
2. Jimenenz, H.N., Li, G., Doller, D., Grenon, M.,
White, A.D., Ma, G., and Guo, M., US Patent
no. 20100022546, 2010.
3. Royalty, S.M., Burus, J.E., Scicinski, J.J., Fogle-
song, R.J., Jagdmann, G.E., Griffin, K.R., Dyakonov, T.,
and Middlemiss, D., WO Рatent no. 2006012441, 2006.
4. Zajac, W.W., Walters, T.R., and Woods, J.M., J. Org.
Chem., 1989, vol. 54, p. 2468.
17. Kapoerchan, V.V., Knijnenburg, A.D., Niamat, M.,
Spalburg, E., de Neeling, A.J., Nibbering, P.H., Mars-
Groenendijk, R.H., Noort, D., Otero, J.M., Llamas-
Saiz, A.L., van Raaij, M.J., van der Marel, G.A.,
Overkleeft, H.S., and Overhand, M., Chem. Eur. J.,
2010, vol. 16, p. 12174.
18. Knijnenburg, A.D., Kapoerchan, V.V., Spalburg, E.,
de Neeling, A.J., Mars-Groenendijk, R.H., Noort, D.,
van der Marel, G.A., Overkleeft, H.S., and Overhand, M.,
Bioorg. Med. Chem., 2010, vol. 18, p. 8403.
19. Wanka, L., Cabrele, C., Vanejews, M., and Schreiner, P.,
Eur. J. Org. Chem., 2007, vol. 9, p. 1474.
20. Horvat, S., Mlinaric-Majerski, K., Glavas-Obrovac, L.,
Jakas, A., Veljkovic, J., Marczi, S., Kragol, G., Roscic, M.,
Matkovic, M., and Milostic-Srb, A., J. Med. Chem.,
2006, vol. 49, p. 3136.
5. Sollot, G.P. and Gilbert, E.E., J. Org. Chem., 1980,
vol. 45, p. 5405.
6. Murray, R.W., Rajadhyaksha, S.N., and Mohan, L.,
J. Org. Chem., 1989, vol. 54, p. 5783.
7. Sidorenko, E.V., Stroganov, V.F., Mikhal’chuk, V.M.,
Bondar’, V.G., Kocherovskaya, E.S., Kretsul, I.I.,
Dorfman, G.A., and Kulagin, E.F., USSR Inventor’s
Certificate no. 1735329, 1990; Byull. Izobret., 1992,
no. 19.
21. Shokova, E.A. and Kovalev, V.V., Russ. J. Gen. Chem.,
2008, vol. 78, p. 614. doi 10.1134/S107036320
22. Averin, A.D., Ranyuk, E.R., Lukashev, N.V., Golub, S.L.,
Buryak, A.K., and Beletskaya, I.P., Tetrahedron Lett.,
2008, vol. 49, p. 1188.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017

SYNTHESIS OF DIACETYLAMINO AND DIAMINO DERIVATIVES OF ADAMANTANE SERIES
1175
23. Averin, A.D., Ranyuk, E.R., Buryak, A.K., Savelyev, E.N.,
Orlinson, B.S., Novakov, I.A., and Beletskaya, I.P.,
Mendeleev Commun., 2009, vol. 19, p. 136.
43. Osipov, D.V., Demidov, M.R., Osyanin, V.A., Skomo-
rokhov, M.Yu., and Klimochkin, Yu.N., Russ. J. Org.
Chem., 2016, vol. 52, p. 906. doi 10.1134/
S1070428016060257
24. Lindauer, D., Beckert, R., Billert, T., Doring, M., and
44. Moiseev, I.K., Bagrii, E.I., Klimochkin, Yu.N., Dol-
gopolova, T.N., Zemtsova, M.N., and Trakhtenberg, P.L.,
Russ. Chem. Bull., 1985, vol. 34, p. 1983. doi 10.1007/
BF00953951
45. Bagrii, E.I., Nekhaev, A.I., and Maksimov, A.L.,
Petroleum Chem., 2017, vol. 57, p. 183. doi 10.1134/
S0965544117020128
Gods, H., J. Prakt. Chem., 1995, vol. 337, p. 508.
25. Kobelev, S.M., Averin, A.D., Buryak, A.K., Savelyev, E.N.,
Orlinson, B.S., Butov, G.M., Novakov, I.A., Denat, F.,
Guilard, R., and Beletskaya, I.P., Arkivoc, 2012, vol. vii,
p. 196.
26. Stetter, Н. and Wulff, C., Chem. Ber., 1960, vol. 93,
p. 1366. doi 10.1002/cber.19600930619
46. Moiseev, I.K., Makarova, N.V., and Zemtsova, M.N.,
Russ. Chem. Rev., 1999, vol. 68, p. 1001. doi 10.1070/
RC1999v068n12ABEH000495
47. Novikov, S.S., Khardin, A.P., Butenko, L.N., Novakov, I.A.,
and Radchenko, S.S., Russ. Chem. Bull., 1976, vol. 25,
p. 2417. doi 10.1007/BF00973410
48. Novikov, S.S., Khardin, A.P., Butenko, L.N., Kulev, I.A.,
Novakov, I.A., Radchenko, S.S., and Burdenko, S.S.,
Zh. Org. Khim., 1980, vol. 16, p. 1433.
49. Klimochkin, Yu.N., Shiryaev, A.K., Matveev, A.I., and
Moiseev, I.K., USSR Inventor’s Certificate no. 1623130,
1989; Byull. Izobret., 2006, no. 23.
27. Wang, Y. and Larrick, J.W., US Patent
no. 20030045574, 2003.
28. Davis, M.C. and Nissan, D.A., Synth. Commun., 2006,
vol. 36, p. 2113.
29. Smith, G.W. and Williams, H.D., J. Org. Chem., 1961,
vol. 26, p. 2207. doi 10.1021/jo01351a011
30. Ishii, Y., Nakano, T., and Sakaguchi, S., EP Patent
no. 0897747, 1998.
31. Ciblat, S., Karbo, A., Leblanc, M., Leger, S., Marineau, J.J.,
Miller, T., Roy, S., Schmidt, D., Siddigui, M.A., Sprott, K.,
Winter, D.K., Ripka, A., Li, D., and Zhang, G., WO
Patent no. 2016058544, 2016.
50. Klimochkin, Yu.N. and Moiseev, I.K., Zh. Org. Khim.,
1988, vol. 24, p. 557.
51. Klimochkin, Yu.N., Abramov, O.V., and Moiseev, I.K.,
32. Zhu, H. and Zhong, X., Asian J. Chem., 2013, vol. 25,
p. 4119.
33. Zhu, H., Guo, J., and Yang, C., Asian J. Chem., 2012,
Neftekhimiya, 2000, vol. 40, p. 454.
vol. 24, p. 1756.
52. Ivleva, E.A., Gavrilova, V.S., Gnusarev, D.I.,
Osyanin, V.A., and Klimochkin, Yu.N., Russ.
J. Org. Chem., 2015, vol. 51, p. 180. doi 10.1134/
S1070428015020062
53. Gavrilova, V.S., Ivleva, E.A., Gnusarev, D.I.,
Osyanin, V.A., and Klimochkin, Yu.N., Russ.
J. Org. Chem., 2015, vol. 51, p. 1382. doi 10.1134/
S1070428015100048
54. Ivleva, E.A., Tkachenko, I.M., and Klimochkin, Yu.N.,
Russ. J. Org. Chem., 2016, vol. 52, p. 1558. doi
10.1134/S1070428016110026
55. Ivleva, E.A., Tkachenko, I.M., Gavrilova, V.S., and
Klimochkin, Yu.N., Russ. J. Org. Chem., 2016, vol. 52,
p. 1394. doi 10.1134/S1070428016100043
34. Lerman, B.M., Aref'eva, Z.Ya., Kuzyaev, A.R.,
Tolstikov, G.A., Khvostenko, V.I., and Sultanov, A.Sh.,
Russ. Chem. Bull., 1972, vol. 21, p. 1753. doi 10.1007/
BF00851192
35. Bewick, A., Edwards, G.J., Jones, S.R., and Mellor, J.M.,
J. Chem. Soc., Perkin Trans. 1, 1977, p. 1831.
36. Stepanov, F.N., Sukhoverkhov, V.D., and Baklan, V.F.,
USSR inventor’s Certificate no. 269923, 1967; Byull.
Izobret., 1974, no. 2.
37. Kiyokawa, K., Takemoto, K., and Minakata, S., Chem.
Commun., 2016, vol. 52, p. 13082.
38. Klimochkin, Yu.N., Moiseev, I.K., Shiryaev, A.K., and
Matveev, A.I., Zh. Org. Khim., 1988, vol. 24, p. 1410.
39. Klimochkin, Yu.N., Moiseev, I.K., Yudashkin, A.V.,
and Stulin, N.V., Zh. Obshch. Khim., 1985, vol. 55,
p. 1655.
40. Moiseev, I.K., Klimochkin, Yu.N., Zemtsov, M.N., and
Trakhtenberg, P.L., Zh. Org. Khim., 1984, vol. 20,
p. 1435.
56. Stepanov, F.N. and Srebrodol’skii, Yu.T., Zh. Org.
Khim., 1966, vol. 2, p. 1612.
57. Moiseev, I.K., Bagrii, E.I., Klimochkin, Yu.N.,
Dolgopolova, T.N., Trakhtenberg, P.L., and Zemtso-
va, M.N., Russ. Chem. Bull., 1985, vol. 34, p. 1980. doi
10.1007/BF00953950
41. Ivleva, E.A., Gavrilova, V.S., and Klimochkin, Yu.N.,
Russ. J. Org. Chem., 2016, vol. 52, p. 785. doi 10.1134/
S1070428016060051
58. Moiseev, I.K., Stulin, N.V., Yudashkin, A.V., and Klimo-
chkin, Yu.N., Zh. Obshch. Khim., 1985, vol. 55,
p. 1472.
59. Aldrich, P.E., Hermann, E.C., Meier, W.A., Paulshock, M.,
Prichard, W.W., Shyder, J.A., and Watts, J.C., J. Med.
Chem., 1971, vol. 14, p. 535.
42. Leonova, M.V., Skomorokhov, M.Yu., Moiseev, I.K.,
and Klimochkin, Yu.N., Russ. J. Org. Chem., 2015, vol. 51,
p. 1703. doi 10.1134/S1070428015120064
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017