Selective Nitroxylation of Adamantane Derivatives in the System Nitric Acid–Acetic Anhydride

Article abstract of DOI:10.1134/S1070428020090055

Abstract: A number of new nitroxyadamantanes have been synthesized by nitroxylation of the corresponding substrates with nitric acid in acetic anhydride. High electrophilicity and reduced acidity of the system HNO₃–Ac₂O increases the stability of nitrates and significantly decreases the probability of formation of alcohols. In some cases, nitrolysis and oxidation of functional groups in the substrate are observed.

Full text of DOI:10.1134/S1070428020090055

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 9, pp. 1532–1539. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Organicheskoi Khimii, 2020, Vol. 56, No. 9, pp. 1353–1362.
Selective Nitroxylation of Adamantane Derivatives
in the System Nitric Acid–Acetic Anhydride
Yu. N. Klimochkina, E. A. Ivlevaa,*, and I. K. Moiseev†a
a Samara State Technical University, Samara, 443100 Russia
*e-mail: elena.a.ivleva@yandex.com
Received May 15, 2020; revised May 26, 2020; accepted May 28, 2020
Abstract—A number of new nitroxyadamantanes have been synthesized by nitroxylation of the corresponding
substrates with nitric acid in acetic anhydride. High electrophilicity and reduced acidity of the system HNO3–
Ac2O increases the stability of nitrates and significantly decreases the probability of formation of alcohols. In
some cases, nitrolysis and oxidation of functional groups in the substrate are observed.
Keywords: nitroxylation, fuming nitric acid, acetic anhydride, nitrolysis, nitrates, adamantane
DOI: 10.1134/S1070428020090055
Functional adamantane derivatives are basic struc-
tural units of physiologically active compounds and
advanced materials [1–12]. Over the past decades, the
problem of activation of C–H bonds in cage compounds
has been important [13] in view of searching for readily
accessible starting materials for the synthesis of com-
pounds with a high degree of molecular complexity
and structural diversity. Nitroxy derivatives of the ada-
mantane series are among such functional derivatives.
They are used to obtain carboxylic acids by the Koch–
Haaf [14, 15] and Bott reactions [16], 1-adamantyl-
arenes by the Friedel–Crafts reaction [17, 18], alcohols
[19, 20], and other compounds containing an adaman-
tane fragment [21–25]. Nitroxyadamantanes are inter-
mediate products in the synthesis of cage alcohols [26]
and amines [27, 28]. Some adamantane derivatives
with a nitroxy group in the bridgehead position exhibit
biological activity [29] or are precursors to biologically
active compounds [30–33]. Polynitroxyadamantanes
have found application as a new class of energetic
materials [34–36].
system which could provide the possibility of not only
extending the series of available nitroxyadamantane
derivatives with various substituents but also im-
proving the yield of already known compounds due to
minimization of side processes.
The system nitric acid–acetic anhydride meets the
above requirements. Its efficiency is determined by the
following two factors. First, the system HNO3–Ac2O is
characterized by a considerably lower protonating
power and almost zero equilibrium concentration of
water, so that the fraction of alcohols in the products is
low. Second, when the system contains more than
50 mol % of nitric acid, the concentration of acetyl
nitrate decreases, and highly electrophilic nitric anhy-
dride is formed in the reaction mixture; at an acetic
anhydride concentration of lower than 18 mol %, the
equilibrium concentration of nitronium cations sharply
increases [42], and fast nitroxylation is observed even
with substrates containing electron-withdrawing sub-
stituents.
Several examples of successful application of the
system HNO3–Ac2O for the synthesis of some nitroxy
derivatives of polycyclic hydrocarbons have been
reported [43–45]. In some cases, reactions of the same
substrate with nitric acid and its mixture with acetic
anhydride gave different products. In particular,
2-mono- and 2,2-disubstituted adamantane derivatives
reacted with 100% HNO3 to give adamantan-2-one
regardless of the substituent nature, whereas no nitro-
lysis of functional groups was observed in HNO3–
Ac2O [46, 47]. In the present work we extended the
scope of application and experimentally proved selec-
The main procedure for the introduction of a nitroxy
group into the bridgehead position of adamantane
molecule is based on nitroxylation with fuming nitric
acid [37–41]. However, side formation of alcohols in
this reaction inevitably reduces the yield of nitroxy
derivatives. Furthermore, this method is inapplicable to
a number of substrates in which functional groups are
unstable toward nitric acid. Therefore, there is a neces-
sity of searching for a more selective nitroxylation
†
Deceased.
1532

SELECTIVE NITROXYLATION OF ADAMANTANE DERIVATIVES
1533
Scheme 1.
R1
R1
HNO3–Ac2O (78–88 mol % HNO3)
10–25°C
R2
R2
ONO2
R3
1–13
R3
18–30
1, R1 = MeCH(OH), R2 = R3 = H; 2, R1 = R2 = HOCH2, R3 = H; 3, 20, R1 = Ac, R2 = R3 = H; 4, 21, R1 = EtC(O), R2 = R3 = H; 5, 22,
R1 = i-PrC(O), R2 = R3 = H; 6, 23, R1 = HOC(O), R2 = R3 = H; 7, 24, R1 = HOC(O), R2 = Me, R3 = H; 8, 25, R1 = HOC(O), R2 = Et,
R3 = H; 9, 26, R1 = HOC(O), R2 = R3 = Me; 10, 27, R1 = HOC(O)CH2, R2 = R3 = H; 11, 28, R1 = O2N, R2 = R3 = Me; 12, 29, R1 =
N≡C, R2 = R3 = H; 13, 30, R1 = AcNH, R2 = R3 = H; 18, R1 = MeCH(ONO2), R2 = R3 = H; 19, R1 = R2 = MeOC(O)CH2, R3 = H.
Scheme 2.
R1
R1
ONO2
HNO3–Ac2O (59–78 mol % HNO3)
5–20°C
+
R2
ONO2
31–34
ONO2
14–17
35
14, R1 = H, R2 = F; 31, R1 = H; 15, R1 = R2 = F; 32, R1 = F; 16, R1 = R2 = Cl; 33, R1 = Cl; 17, R1 = R2 = Br; 34, R1 = Br.
tivity of the system HNO3–Ac2O by using a wide series
of adamantane substrates containing electron-with-
drawing substituents in the bridgehead positions.
The substrates were alcohols 1 and 2, ketones 3–5,
carboxylic acids 6–10, nitrogen-containing compounds
11–13, and halogen derivatives 14–17. The reactions
were carried out in a mixture of nitric acid and acetic
anhydride containing 59–78 mol % of HNO3 at 5–25°C
(Schemes 1, 2). The detailed conditions of the synthesis
of nitroxy derivatives 18–34 are collected in Table 1. In
Table 1. Reaction of adamantane derivatives 1–4 and 6–17 with nitric acid in acetic anhydride
Concentration of HNO3
in a HNO3–Ac2O mixture, mol %
Substrate no. HNO3, equiv
Temperature, °C
Reaction time, h
Yield, %
1
2
3
4
6
7
8
9
10
11
12
13
14
15
16
17
30
90
40
40
40
45
50
60
40
25
40
25
25
20
25
10
78
78
78
78
88
88
88
88
78
78
78
78
78
78
78
59
10
20
10
10
20
25
20
25
20
10
10
10
10
20
5
2
15
2
2
5
5
5
6
1
3
4
3
3
1
2
1
84a
86
67
87
94
91
87
89
81
43
47
42
57b
59c
46d
21e
5
a
b
c
d
e
Compound 20 (7%) was also isolated.
Compound 35 (33%) was also isolated.
Compound 35 (12%) was also isolated.
Compound 35 (23%) was also isolated.
Compound 35 (22%) was also isolated.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 9 2020

KLIMOCHKIN et al.
Table 2. Reaction of adamantane derivatives 1, 3–5, 7–9, and 13 with nitric acid
1534
Substrate no.
HNO3, equiv
Temperature, °C
Reaction time, h
Product
Yield, %
3
23
23
85
7
87
1
3
40
70
–5
20
1
3
21
23
46
22
4
40
20
3
5
7
8
9
13
40
70
70
70
50
20
20
20
20
15
3
2
2
2
5
22
24
25
26
30
92
70
68
67
66
parallel, compounds 1, 3–5, 7–9, and 13 were reacted
with nitric acid in the absence of acetic anhydride (for
details, see Table 2).
21 and 23, respectively. No oxidation occurred in the
system HNO3–Ac2O, and keto nitrate 21 was obtained
in 87% yield. It should be noted that 1-adamantyl iso-
propyl ketone (5) is quite stable in 100% HNO3 and is
smoothly nitroxylated to keto nitrate 22. Such effect
of the substrate structure on the reaction direction
suggests increased steric hindrances to enolization in
ketones 4 and 5.
In fact, 1-(adamantan-1-yl)ethanol (1) and (adaman-
tane-1,3-diyl)dimethanol (2) differently reacted with
nitric acid and its mixture with acetic anhydride. The
reaction of 1 with nitric acid involved mainly oxidation
to 1-acetyladamantane (3), and minor 3-nitroxyada-
mantane-1-carboxylic acid (23) was also isolated
(yield 7%). Nitroxy derivative 18 was formed in the
reaction of 1 with HNO3–Ac2O; however, oxidation
processes could not be suppressed completely. Diol 2
in the system HNO3–Ac2O was converted to 3,5-bis-
(acetoxymethyl)adamantan-1-yl nitrate (19), whereas
only 1,3-bis(nitroxymethyl)adamantane was formed in
98% HNO3, in keeping with the data reported pre-
viously [48].
Carboxylic acids 6–10 were converted into the
corresponding nitroxy derivatives 23–27 in both nitric
acid and its mixture with acetic anhydride. The yields
of 23–26 in the system HNO3–Ac2O were higher on
the average by 20% than in nitric acid where hydroxy
acids were formed as by-products. The yield of 3-ni-
troxyadamantane-1-carboxylic acid (23) in the reaction
of 6 with HNO3 was 71% [43]. The yields of 2-(3-ni-
troxyadamantan-1-yl)acetic acids (27) in HNO3–Ac2O
in HNO3 were comparable (80 and 81%) [40].
The nature of products formed in the reactions of
adamantyl alkyl ketones 3–5 with nitric acid is deter-
mined by the relative rates of nitroxylation and
enolization of initial ketone. The latter process is the
limiting step of oxidation of ketones, and its rate
increases with rise in the acidity of the medium [49].
Fairly readily enolizable 1-acetyladamantane (3) in
nitric acid is completely converted to nitroxy carbox-
ylic acid 23, and only the use of HNO3–Ac2O makes it
possible to obtain nitroxy ketone 20 in 67% yield.
1-Adamantyl ethyl ketone (4) reacted with HNO3 to
give a mixture of nitroxylation and oxidation products
It was previously found [43] that 1-nitroadamantane
in the reaction with nitric acid undergoes slow ni-
trolysis with the formation of adamantan-1-yl nitrate
and that the corresponding nitro nitrate is formed in
HNO3–Ac2O. In fact, the reaction of 3,5-dimethyl-1-
nitroadamantane (11) with nitric acid in acetic anhy-
dride afforded 43% of 3,5-dimethyl-7-nitroadamantan-
1-yl nitrate (28).
Electrophilically induced oligomerization of ada-
mantane-1-carbonitrile (12) in 98% nitric acid led to
Scheme 3.
ONO2
CN
O
HNO3
H
N
NH2
O
n
12
n = 1–3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 9 2020

SELECTIVE NITROXYLATION OF ADAMANTANE DERIVATIVES
1535
the formation of a mixture of poorly soluble high-
melting amide oligomers containing 2 to 4 cage frag-
ments (according to spectral data; Scheme 3). It seemed
interesting to obtain in this way a polyamide with
a higher molecular weight. Nitrile 12 in HNO3–Ac2O
was converted to cyano nitrate 29, whereas no Ritter
reaction was observed.
Compounds 14 and 15 were provided by
A.M. Aleksandrov (Kukharʼ Institute of Bioorganic
and Petroleum Chemistry, National Academy of
Sciences of Ukraine).
3,5-Dimethyl-1-nitroadamantane (11). 1,3-Di-
methyladamantane, 15 mL (0.08 mol), was heated to
the boiling point, 3.4 mL (0.085 mol) of 100% nitric
acid was slowly added dropwise, and the mixture was
heated at 200°C for 1.5 h until nitrogen oxides no
longer evolved. After cooling, the solidified material
was treated with 50 mL of diethyl ether, the solution
was dried over solid sodium hydroxide and evaporated,
and the residue was purified by chromatography using
pentane as eluent; the first fraction was collected. Yield
6.65 g (39%), bp 125–127°C (5 torr); published data
[57]: bp 114–115°C (2 torr).
General procedure for the oxidation of com-
pounds 1–4 and 6–17 in the system HNO3–Ac2O.
Compound 1–4 or 6–17, 0.01 mol, was added to a mix-
ture of 98% nitric acid and acetic anhydride. The
mixture was kept under the conditions indicated in
Table 1 and poured onto crushed ice. Compounds
18–21 and 31–34 were extracted with diethyl ether
(3×10 mL), the combined extracts were washed with
a solution of sodium hydrogen carbonate and water
until neutral washings, dried over sodium sulfate, and
evaporated. Compounds 23–30 precipitated and were
filtered off, washed with water until neutral washings,
and dried.
N-(Adamantan-1-yl)acetamide (13) in 100% HNO3
underwent nitroxylation to 3-acetamidoadamantan-1-yl
nitrate (30). In addition, minor nitrolysis products,
adamantan-1-yl nitrate (31) and adamantane-1,3-diyl
dinitrate (35) were detected (Scheme 2). The reaction
of 13 with HNO3–Ac2O gave 42% of 30.
Nitrate 31 and dinitrate 35 were formed as the only
products in the reactions of both 1-fluoroadamantane
(14) and 1-bromo- and 1-chloroadamantanes with both
HNO3 and HNO3–Ac2O [43]. 1,3-Dihaloadamantanes
were expected to exhibit a lower reactivity. In fact,
1,3-dihaloadamantanes 15–17 in the system HNO3–
Ac2O gave rise to the corresponding haloadamantyl
nitrates 32–34 in addition to dinitrate 35. The highest
yield was observed for fluoro nitrate 32, whereas the
yield of bromo nitrate 34 was as low as 21% even
under mild nitrolysis conditions.
Nitroxy derivatives 18–34 were isolated in 21–94%
yield. In the 13C NMR spectra of 18–34, the quaternary
carbon atom bearing the ONO2 group resonated at
δC 86– 90 ppm.
1-(3-Nitroxyadamantan-1-yl)ethyl nitrate (18)
was obtained from alcohol 1 and was purified by
column chromatography using hexane as eluent. Yield
84%, nD20 = 1.5125. IR spectrum, ν, cm–1: 1628, 1285
EXPERIMENTAL
The IR spectra were recorded on a Shimadzu IR
Affinity-1 spectrometer (Japan). The 1H and 13C NMR
spectra were recorded on a JEOL NMR-ECX400
spectrometer (Japan) at 400 and 100 MHz, respectively,
using tetramethylsilane as internal standard. The
melting points were measured in capillaries on
an MPM-H2 melting point apparatus (Germany) and
are uncorrected. The elemental analyses were carried
out with a EuroVector 3000 EA analyzer (Italy) using
L-cystine as standard. 1-(Adamantan-1-yl)ethanol (1)
[50], (adamantane-1,3-diyl)dimethanol (2) [29],
1-(adamantan-1-yl)ethanone (3) [51], 1-(adamantan-1-
yl)propan-1-one (4) and 1-(adamantan-1-yl)-2-methyl-
propan-1-one (5) [52], adamantane-1-carbonitrile (12)
[53], N-(adamantan-1-yl)acetamide (13) [54], 1,3-di-
chloroadamantane (16) [55], and 1,3-dibromoadaman-
tane (17) [56] were synthesized according to reported
procedures. Carboxylic acids 6–10 were taken from the
collection of chemicals at the Organic Chemistry
Department of the Samara State Technical University.
1
(ONO2). H NMR spectrum (CDCl3), δ, ppm: 1.51 d
(3H, CH3, J = 6.5 Hz), 1.35–2.50 m (14H, Ad), 5.52 q
(1H, CH, J = 6.5 Hz). 13C NMR spectrum (CDCl3),
δC, ppm: 17.7 (CH3), 30.2 (CH), 37.0 (CH2), 38.8
(CH2), 41.3, 42.1 (CH2), 43.4 (CH2), 85.6 (CH), 89.1.
Found, %: C 50.41; H 6.40; N 9.85. C12H18N2O6.
Calculated, %: C 50.35; H 6.34; N 9.79.
In addition, 3-acetyladamantan-1-ylnitrate (20) was
isolated by column chromatography. Yield 7%, nD20
=
1.5113. IR spectrum, ν, cm–1: 1705 (C=O), 1625, 1290
1
(ONO2). H NMR spectrum (CDCl3), δ, ppm: 1.70–
2.55 m (14H, Ad), 2.11 s (3H, CH3). 13C NMR spec-
trum (CDCl3), δC, ppm: 25.3 (CH3), 27.4 (CH), 34.4
(CH2), 37.0 (CH2), 40.1 (CH2), 42.9, 48.7 (CH2), 88.6,
210.7. Found, %: C 60.30; H 7.22; N 5.92. C12H17NO4.
Calculated, %: C 60.24; H 7.16; N 5.85.
3,5-Bis(acetoxymethyl)adamantan-1-yl nitrate
(19) was obtained from diol 2 and was purified by
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 9 2020

KLIMOCHKIN et al.
1536
column chromatography using carbon tetrachloride–
ethyl acetate (4:1) as eluent. Yield 86%, nD20 = 1.5177.
IR spectrum, ν, cm–1: 1740 (C=O), 1625, 1270 (ONO2).
1H NMR spectrum (CDCl3), δ, ppm: 1.20–2.44 m
(13H, Ad), 2.06 s (6H, CH3), 3.78 s (4H, CH2).
13C NMR spectrum (CDCl3), δC, ppm: 20.9 (CH3),
29.9 (CH), 37.3, 37.4 (CH2), 38.6 (CH2), 39.9 (CH2),
40.9 (CH2), 72.0 (CH2), 89.7, 171.0. Found, %:
C 56.36; H 6.86; N 4.17. C16H23NO7. Calculated, %:
C 56.30; H 6.79; N 4.10.
(CH2), 44.3 (CH2), 45.7 (CH2), 48.7 (CH2), 86.3, 89.2.
Found, %: C 53.39; H 6.78; N 10.42. C12H18N2O5.
Calculated, %: C 53.33; H 6.71; N 10.36.
3-Cyanoadamantan-1-yl nitrate (29) was syn-
thesized from nitrile 12. Yield 47%, mp 86–88°C (from
hexane). IR spectrum, ν, cm–1: 2225 (CN), 1615, 1280
1
(ONO2). H NMR spectrum (CDCl3), δ, ppm: 1.72–
2.46 m (14H, Ad). 13C NMR spectrum (CDCl3), δC,
ppm: 29.5 (CH), 33.0, 33.9 (CH2), 38.1 (CH2), 38.4
(CH2), 41.3 (CH2), 86.3, 122.7. Found, %: C 59.52;
H 6.42; N 12.69. C11H14N2O3. Calculated, %: C 59.45;
H 6.35; N 12.61.
3-Acetyladamantan-1-yl nitrate (20) was obtained
from 1-acetyladamantane (3). Yield 67%, nD20 = 1.5113.
The spectral characteristics were identical to those
given above.
3-Acetamidoadamantan-1-yl nitrate (30) was
obtained from acetamide 13. Yield 42%, mp 130–
132°C (from hexane). IR spectrum, ν, cm–1: 3180
(NH), 1635, 1555 (C=O), 1615, 1275 (ONO2).
1H NMR spectrum (CDCl3), δ, ppm: 1.70 s (3H, CH3),
1.55–2.35 m (14H, Ad), 7.55 s (1H, NH). 13C NMR
spectrum (CDCl3), δC, ppm: 24.2 (CH3), 30.5 (CH),
34.7 (CH2), 38.6 (CH2), 40.1 (CH2), 43.1 (CH2), 54.2,
89.4, 169.5. Found, %: C 56.75; H 7.20; N 11.09.
C12H18N2O4. Calculated, %: C 56.68; H 7.14; N 11.02.
3-Propanoyladamantan-1-yl nitrate (21) was ob-
tained from ketone (4) and was purified by column
chromatography using pentane as eluent. Yield 87%,
nD20 = 1.5025. IR spectrum, ν, cm–1: 1715 (C=O), 1625,
1
1290 (ONO2). H NMR spectrum (CDCl3), δ, ppm:
1.01 t (3H, CH3, J = 7.1 Hz), 1.55–2.45 (14H, Ad),
2.50 q (2H, CH2, J = 7.1 Hz). 13C NMR spectrum
(CDCl3), δC, ppm: 8.7 (CH3), 26.9 (CH), 32.9 (CH2),
34.4 (CH2), 37.6 (CH2), 40.6 (CH2), 41.7, 49.1 (CH2),
88.1, 213.4. Found, %: C 61.70; H 7.62; N 5.59.
C13H19NO4. Calculated, %: C 61.64; H 7.56; N 5.53.
Adamantan-1-yl nitrate (31) was obtained from
1-fluoroadamantane (14) and was purified by column
chromatography using hexane as eluent. Yield 57%,
mp 102–104°C [43]). In addition, adamantane-1,3-
diyl dinitrate (35) was isolated. Yield 33%, mp 114–
115°C [43].
3-Nitroxyadamantane-1-carboxylic acid (23) was
obtained from acid 6. Yield 94%, mp 135–137°C (from
hexane); published data [44]: mp 145–147°C.
3-Fluoroadamantan-1-yl nitrate (32) was ob-
tained from 1,3-difluoroadamantane (15) and was
purified by column chromatography using hexane as
eluent. Yield 59%, mp 68–70°C (from MeOH).
5-Methyl-3-nitroxyadamantane-1-carboxylic
acid (24) was obtained from acid 7. Yield 91%,
mp 85–87°C (from hexane); published data [48]:
mp 85–86°C.
1
IR spectrum, ν, cm–1: 1620, 1280 (ONO2). H NMR
5-Ethyl-3-nitroxyadamantan-1-carboxylic acid
(25) was obtained from acid 8. Yield 87%, mp 88–90°C
(from hexane); published data [48]: mp 88–89°C.
spectrum (CDCl3), δ, ppm: 1.65–2.37 m (14H, Ad).
13C NMR spectrum (CDCl3), δC, ppm: 31.2 (CH), 34.1
(CH2), 38.2 (CH2), 41.2 (CH2), 44.9 (CH2), 89.6, 92.4
(J = 203 Hz). Found, %: C 55.89; H 6.63; N 6.58.
C10H14FNO3. Calculated, %: C 55.81; H 6.56; N 6.51.
In addition, dinitrate 35 was isolated in 12% yield.
3,5-Dimethyl-7-nitroxyadamantane-1-carboxylic
acid (26) was obtained from acid 9. Yield 89%,
mp 98–100°C (from hexane); published data [48]:
mp 99–100°C.
3-Chloroadamantan-1-yl nitrate (33) was ob-
tained from 1,3-dichloroadamantane (16) and was
purified by column chromatography using hexane as
eluent. Yield 46%, mp 41–42°C (from MeOH).
2-(3-Nitroxyadamantan-1-yl)acetic acid (27) was
obtained from acid 10. Yield 81%, mp 123–125°C
(from hexane); published data [40]: mp 136–138°C.
1
3,5-Dimethyl-7-nitroadamantan-1-yl nitrate (28)
was obtained from 3,5-dimethyl-1-nitroadamantane
(11). Yield 43%, mp 89–90°C (from hexane). IR spec-
trum, ν, cm–1: 1630 (ONO2), 1540 (NO2), 1365 (NO2),
IR spectrum, ν, cm–1: 1625, 1275 (ONO2). H NMR
spectrum (CDCl3), δ, ppm: 1.61–2.59 m (14H, Ad).
13C NMR spectrum (CDCl3), δC, ppm: 32.4 (CH), 34.2
(CH2), 38.3 (CH2), 46.2 (CH2), 49.3 (CH2), 66.4, 89.2.
Found, %: C 51.90; H 6.16; N 6.13. C10H14ClNO3.
Calculated, %: C 51.84; H 6.09; N 6.05. In addition,
dinitrate 35 was isolated in 23% yield.
1
1280 (ONO2). H NMR spectrum (CDCl3), δ, ppm:
1.08 s (6H, CH3), 1.28–2.54 m (12H, Ad). 13C NMR
spectrum (CDCl3), δC, ppm: 28.8 (CH3), 35.2, 41.3
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SELECTIVE NITROXYLATION OF ADAMANTANE DERIVATIVES
1537
3-Bromoadamantan-1-yl nitrate (34) was ob-
tained from 1,3-dibromoadamantane (17) and was
purified by column chromatography using hexane as
eluent. Yield 21%, mp 36–38°C (from MeOH).
5-Methyl-3-nitroxyadamantane-1-carboxylic
acid (24) was obtained from acid 7 in 70% yield.
5-Ethyl-3-nitroxyadamantane-1-carboxylic acid
(25) was obtained from acid 8 in 68% yield.
1
IR spectrum, ν, cm–1: 1620, 1275 (ONO2). H NMR
3,5-Dimethyl-7-nitroxyadamantane-1-carboxylic
acid (26) was obtained from acid 9 in 67% yield.
spectrum (CDCl3), δ, ppm: 1.65–2.67 m (14H, Ad).
13C NMR spectrum (CDCl3), δC, ppm: 32.9 (CH2),
33.7 (CH), 37.8 (CH2), 47.2 (CH2), 50.3 (CH2), 60.9,
88.6. Found, %: C 43.58; H 5.19; N 5.14.
C10H14BrNO3. Calculated, %: C 43.50; H 5.11; N 5.07.
In addition, dinitrate 35 was isolated in 22% yield.
CONCLUSIONS
The system nitric acid–acetic anhydride has been
proposed for nitroxylation of adamantane derivatives
and shown to ensure better selectivity than nitric acid.
In some cases, the proposed system suppressed
nitrolysis and oxidation of functional groups that are
unstable to nitric acid. In addition, the formation of
alcohols as by-products is minimized due to lower
degree of protonation of the nitroxy group and binding
of liberated water.
General procedure for the oxidation of com-
pounds 1, 3–5, 7–9, and 13 with fuming nitric acid.
Compound 1, 3–5, 7–9, or 13, 0.01 mol, was added in
portions to 98% nitric acid. The mixture was kept
under the conditions indicated in Table 2 and poured
onto crushed ice. Compounds 3, 21, and 2 were
extracted with diethyl ether (3×10 mL), the combined
extracts were washed with a 10% solution of sodium
hydroxide and with water until neutral washings, dried
over sodium sulfate, and evaporated. Compounds 23–
26 and 30 precipitated and were filtered off, washed
with water until neutral washings, and dried.
ACKNOWLEDGMENTS
This study was performed using the facilities of the
“Physicochemical Properties of Substances and Materials”
joint center of the Sanara State Technical University.
1-(Adamantan-1-yl)ethanone (3) was obtained
from alcohol 1. Yield 85%, mp 50–51°C; published
data [49]: mp 53–54°C. Acidification of the alkaline
extract with concentrated aqueous HCl gave 3-nitroxy-
adamantane-1-carboxylic acid (23), yield 7%.
FUNDING
This study was performed under financial support by the
Ministry of Science and Higher Education of the Russian
Federation (project part of state assignment no. 0778-2020-
0005). The study of nitroxylation of haloadamantane deriva-
tives was financially supported by the Russian Foundation
for Basic Research (project no. 20-03-00869).
3-Nitroxyadamantane-1-carboxylic acid (23) was
obtained from ketone 3. Yield 87%.
3-Propanoyladamantan-1-yl nitrate (21) was
obtained from ketone 4. Yield 46%. Its spectral
characteristics were identical to those given above.
Acidification of the alkaline extract with concentrated
aqueous HCl gave 22% of acid 23.
CONFLICT OF INTEREST
The authors declare the absence of conflict of interest.
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