Chemoselectivity of Nitroxylation of Cage Hydrocarbons

Article abstract of DOI:10.1134/S107042802010005X

Abstract: The composition of reaction mixtures obtained by nitroxylation of 13 cage hydrocarbons with 100% nitric acid and its mixtures with acetic acid, acetic anhydride, and methylene chloride has been studied. More reactive substrates react with lowest

Full text of DOI:10.1134/S107042802010005X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 10, pp. 1702–1710. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Organicheskoi Khimii, 2020, Vol. 56, No. 10, pp. 1516–1526.
Chemoselectivity of Nitroxylation of Cage Hydrocarbons
Yu. N. Klimochkina, M. V. Leonovaa, and E. A. Ivlevaa,*
a Samara State Technical University, Samara, 443100 Russia
*e-mail: ivleva.ea@samgtu.ru
Received June 15, 2020; revised June 27, 2020; accepted July 2, 2020
Abstract—The composition of reaction mixtures obtained by nitroxylation of 13 cage hydrocarbons with
100% nitric acid and its mixtures with acetic acid, acetic anhydride, and methylene chloride has been studied.
More reactive substrates react with lowest selectivity regardless of the reaction medium. The primary nitroxyla-
tion products of cage hydrocarbons are nitrooxy derivatives. The compositions of reaction mixtures obtained in
the reactions of some cage hydrocarbons with nitric anhydride in carbon tetrachloride have been determined.
Keywords: chemoselectivity, nitroxylation, cage hydrocarbons, fuming nitric acid, nitric anhydride, nitrooxy
derivatives
DOI: 10.1134/S107042802010005X
Polyfunctional adamantane derivatives have found
application as key building blocks for the design of
materials possessing a combination of practically
important properties. In particular, molecular electronic
devices [1], flame-resistant polycarbonate materials
[2], metal–organic coordination polymers [3–5], gas
adsorbents [6], and catalysts [7, 8] have been devel-
oped. 1,3,5,7-Tetrasubstituted polyfunctional adaman-
tanes are frequently used for these purposes [9].
derivatives by reactions of cage hydrocarbons and their
functional derivatives with nitric acid and its mixtures
[33–44], and the kinetics of nitroxylation have been
studied [45, 46]. One-electron transfer from adaman-
tane to nitronium cation gives rise to adamantyl radical
cation [47] which undergoes deprotonation to ada-
mantyl radical, and the latter is rapidly oxidized with
NO2+ to the corresponding carbenium ion. However,
some features of the nitroxylation process related to the
solvent nature and state of nitric acid in different media
remain unclear.
On the other hand, the synthesis of polysubstituted
adamantanes is complicated by difficulties in the
search for readily accessible starting materials. There is
a need of a chemical functionality vector that could
make it possible to easily modify an initial molecule
with a good yield. Such vector may be the presence of
a nitrooxy (ONO2) group therein. Nitrooxy derivatives
seem to be more appropriate substrates than halogen
and hydroxy derivatives in the synthesis of polyfunc-
tionalized adamantanes. Cage nitrooxy derivatives
have already been used as starting materials to develop
preparative methods for the synthesis of structurally
diverse compounds [10–24], which have already found
(or could find) application in the preparation of
materials and biologically active compounds [25–28].
Some polyfunctional adamantanes with a nitrooxy
group on the carbon skeleton showed biological
activity [29–32].
Reactions of cage hydrocarbons with nitrogen-
containing electrophiles and oxidants are characterized
by low chemoselectivity [48], and the product com-
position depends on the reagent nature and reaction
conditions. The reaction of adamantane with nitric acid
in acetic acid at 140°C [49], as well as passing nitrogen
dioxide through alkyladamantanes heated to the boiling
point (200°C) [50], led to the formation of mixtures of
mono- and dinitro derivatives and small amounts of
hydroxy and oxo derivatives. The reaction of adaman-
tane with dinitrogen tetroxide at room temperature
gave a mixture of nitro and nitroxy derivatives;
polynitroadamantanes can be obtained by heating with
nitrogen dioxide under pressure at elevated temperature
(160°C) [51].
Nitronium salts are excellent reagents for C–H bond
cleavage. Adamantane reacted with nitronium tetra-
fluoroborate in nitromethane [52] very slowly (4–
7 days) to produce a mixture of 1-nitroadamantane,
1-fluoroadamantane, adamantan-1-ol, 3-fluoroadaman-
Nitrooxy derivatives of cage compounds are gen-
erally synthesized by the action of nitrogen-containing
electrophiles and oxidants. Methods have been pro-
posed for the synthesis of a wide range of nitrooxy
1702

CHEMOSELECTIVITY OF NITROXYLATION OF CAGE HYDROCARBONS
1703
tan-1-ol, and adamantan-2-one. Initially, the reaction
mixture contained only fluorination and oxidation
products which were converted to 1-nitroadamantane
several days after. As noted in [53], nitro compounds
are not kinetically controlled products in the reactions
of adamantane with complex nitronium salts. The
process was illustrated by Scheme 1 [52].
The concentration of any component in a reaction
mixture is determined by its stability to further trans-
formations, as well as by selectivity of stabilization of
intermediates by different species. Furthermore, the
product composition depends on the contributions of
competing reactions and transformations occurring
during the isolation procedure. In this work we studied
the chemoselectivity of nitroxylation of cage hydro-
carbons in fuming nitric acid and its mixtures with
acetic acid, acetic anhydride, and methylene chloride,
as well as in the system dinitrogen pentoxide–carbon
tetrachloride.
The substrates were adamantane (1), 1-ethylada-
mantane (2), 1-(propan-2-yl)adamantane (3), 1,3,5-tri-
methyladamantane (4), diamantane (5), homoadaman-
tane (6), protoadamantane (7), bicyclo[3.3.1]nonane
(8), 2-methyladamantane (9), 2-ethyladamantane (10),
2-(propan-2-yl)adamantane (11), 2,6-dimethyladaman-
tane (12), and 2,2-dimethyladamantane (13). The reac-
tion systems were selected so that to elucidate the
effects of solvent and state of nitric acid in different
media on the reaction selectivity. The nitroxylation
was carried out in 100% nitric acid and its mixtures
with acetic acid (87:13 mol %), acetic anhydride
(75:25 mol %), and methylene chloride (79:21 mol %).
In addition, the product compositions in the reactions
of cage hydrocarbons with dinitrogen pentoxide in
carbon tetrachloride were determined.
Photochemical reaction of adamantane with dinitro-
gen pentoxide in methylene chloride [54] gave a mix-
ture of isomeric nitroadamantanes, adamantan-1-yl
nitrate, and adamantan-2-one. The reaction of adaman-
tane with nitrogen dioxide in carbon tetrachloride at
20°C, promoted by visible laser radiation, afforded
a mixture of equal amounts of 1-nitroadamantane and
adamantan-1-yl nitrite [55], which confirmed ambident
reactivity of nitrogen dioxide in radical processes.
Adamantane reacted with ceric ammonium nitrate in
acetonitrile under photochemical initiation to produce
a mixture of isomeric nitrates and acetamido deriva-
tives [56]. Isomeric hydroxyadamantanes and adaman-
tan-2-one were formed in the photolysis of adamantane
in the presence of nitric acid [57].
Low-temperature generation of highly electrophilic
nitrogen trioxide radical is possible via reaction of
ozone with nitrogen dioxide, which underlies a nitra-
tion method known as Kyodai-nitration. The reaction
of adamantane and its derivatives with nitrogen dioxide
and ozone in methylene chloride at –78°C [58] gave
preferentially bridgehead-substituted nitro derivatives.
The ratio of nitroxylation products depends on the
contributions of competing reactions and further trans-
Scheme 1.
NO2
–H+
H
H
NO2
NO2
NO2
–HNO2
H2O
H
OH
ONO
HONO
NO+
–H+
H+
ONO
OHNO
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

KLIMOCHKIN et al.
1704
formations, including those occurring in the isolation
stage. Taking into account that, as applied to nitroxyla-
tion, the above factors cannot be distinguished, the
chemoselectivity was qualitatively estimated by
analysis of product mixtures obtained by dilution of
the reaction mixtures and subsequent extraction. The
mixtures were analyzed by GLC under the conditions
excluding thermal decomposition of labile products.
The products were identified by comparing their reten-
tion times with those of authentic samples prepared by
independent methods.
2.52 ppm (cf. δ 1.68, 2.10, and 2.22 ppm in the spec-
trum recorded in CDCl3), i.e., a 0.3-ppm downfield
shift of the CH proton signal was observed in nitric
acid. This indicates that the nitrooxy group in nitric
acid is protonated or protosolvated. Furthermore,
fuming nitric acid possesses a high oxidation potential
[61], which increases the probability of radical side
processes.
The nitroxylation in a mixture of nitric and acetic
acids features increased formation of hydroxy deriv-
atives. The reaction rate in the presence of acetic acid
is appreciably lower due to decomposition of nitric
acid self-associates as a result of complex formation
and inhibition of autoprotolysis; therefore, the electro-
philicity and acidity of nitric acid are reduced [62]. The
hydrolysis of nitrates is also favored by the fact that
liberated water is not bound in the given medium. In
addition, alcohols can be formed via direct elimination
of nitronium ion from the protonated nitrate.
Apart from nitrates, nitro derivatives and the corre-
sponding alcohols can be formed and isolated [59].
Hydroxy derivatives are formed as a result of hydro-
lysis of nitrooxy derivatives, and their concentration is
much lower in the nitroxylation of substrates con-
taining electron-withdrawing substituents. Nitro com-
pounds are formed only from most reactive substrates.
The examined reactions produced mixtures con-
sisting of nitroso compounds, alcohols, nitrites, un-
known components, nitrates, and nitro compounds.
Nitroso derivatives were formed in a few cases and in
trace amounts. Nitro compounds and nitrites are likely
to arise from secondary reactions of adamantyl cation
with liberated nitrogen oxides (nitrous acid). For
example, a standard sample of adamantan-1-ol reacted
with 10 equiv of 98% nitric acid and 1 equiv of sodium
nitrite (20°C, 1 h) to give 0.2% of 1-nitrosoadamantane,
25.9% of adamantan-1-yl nitrite, 0.5% of an uniden-
tified product, 43.0% of adamantan-1-yl nitrate, and
3.6% of 1-nitroadamantane; the product mixture also
contained 26.8% of unreacted adamantan-1-ol. The
concentration of nitro compounds increased in parallel
with the substrate conversion. In the nitroxylation of
adamantane (1) with nitric acid in methylene chloride,
the fraction of 1-nitroadamantane increased from 0.1%
at a conversion of 14% to 2.7% by the end of the
reaction.
The maximum concentration of nitrooxy derivatives
among the products was observed when the nitroxyla-
tion was carried out in a mixture of nitric acid and
acetic anhydride. High electrophilicity of this reaction
medium in combination with reduced acidity [37]
increases the stability of nitrates. The probability of
alcohol formation is low due to low degree of pro-
tonation of nitrooxy groups in the presence of acetic
anhydride and binding of water by the latter. Increased
fraction of nitro compounds in this system can be
rationalized by completely suppressed nitrolysis of
tertiary nitro groups [38].
A convenient nitroxylation system is a solution of
nitric acid in methylene chloride where the reaction
mixture is homogeneous. This system provides a fairly
high concentration of nitrates among the products.
Complex formation between methylene chloride and
nitric acid [63] reduces the acidity of the medium and
increases stability of nitrooxy derivatives. In addition,
the use of methylene chloride prevents nitrates from
contact with water during the isolation procedure.
Table 1 shows the compositions of nitroxylation
products of cage hydrocarbons 1–13 in different media.
The products are readily interconvertible both during
the reaction and in the isolation stage, which com-
plicates unambiguous interpretation of the results.
The formation of nitro compounds from nitrooxy
derivatives is related to easy generation and further
transformations of carbenium ions in nitric acid
medium (Scheme 2). The absence of nitro derivatives
among the products obtained from low reactive
substrates may be explained by preferential attack of
the oxygen atom in the reaction of a harder carbocation
with nitrite anion (nitrous acid). We can conclude that
nitrooxy derivatives are kinetically controlled products
in reactions of hydrocarbons with nitric acid and its
mixtures.
High selectivity was not observed in the reactions
with 100% nitric acid. The fraction of nitrooxy deriv-
atives was relatively low. This may be due to high
protonating ability of nitric acid [60], which favors fast
establishment of the alcohol–nitrate equilibrium. The
1H NMR spectrum of adamantan-1-yl nitrate in
100% DNO3 showed signals at δ 1.59, 2.12, and
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CHEMOSELECTIVITY OF NITROXYLATION OF CAGE HYDROCARBONS
1705
Table 1. Composition (%, GLC) of the reaction mixtures in the nitroxylation of cage hydrocarbons 1–8
R–H
Nitroxylation system Time, min RONO2
ROH
RNO2
RONO
RX
Unreacted R–H
HNO3
20
60
30
40
63.7
61.3
77.7
67.4
15.2
18.3
8.5
7.2
4.5
1.4
2.7
13.5
15.0
9.0
–
0.9
3.4
0.4
0.4
–
HNO3–AcOH
HNO3–Ac2O
HNO3–CH2Cl2
1
–
11.5
18.0
–
HNO3
15
40
20
20
62.3
38.6
37.3
66.0
29.2
41.1
31.5
24.0
–
0.8
4.0
0.4
6.3
15.5
10.2
5.4
–
1.5
3.2
–
2.2
2.5
HNO3–AcOH
HNO3–Ac2O
HNO3–CH2Cl2
2
3
4
5
6
7
8
13.8
4.2
HNO3
10
30
15
15
11.4
30.5
55.9
72.2
63.0
42.7
22.3
14.5
6.1
1.2
7.7
3.4
19.5
20.5
6.4
–
1.9
5.4
–
–
3.2
2.3
0.7
HNO3–AcOH
HNO3–Ac2O
HNO3–CH2Cl2
9.2
HNO3
40
60
50
60
73.6
11.1
82.4
22.4
16.8
10.1
2.1
0.7
0.3
5.0
–
8.6
8.7
–
0.6
4.9
–
0.3
69.2
3.3
HNO3–AcOH
HNO3–Ac2O
HNO3–CH2Cl2
2.3
44.4
29.9
3.3
HNO3
30
45
60
45
67.7
52.0
67.7
73.2
23.0
20.3
8.5
5.4
25.8
15.7
10.5
–
1.9
5.8
–
–
–
–
–
3.9a
–
2.3a
0.7a
HNO3–AcOH
HNO3–Ac2O
HNO3–CH2Cl2
15.6
HNO3
7
25
12
15
52.8
58.5
87.5
71.4
23.4
14.0
4.6
7.8
5.0
1.5
5.2
7.2
5.3
8.8
17.1
4.8
–
0.1
–
HNO3–AcOH
HNO3–Ac2O
HNO3–CH2Cl2
1.6
7.9
11.6
3.9
–
HNO3
50
120
30
82.5
86.4
90.7
89.0
10.2
12.5
0.5
1.1
0.4
1.4
0.5
–
–
–
–
0.4
0.2
5.7
0.2
5.8
0.5
1.7
0.4
HNO3–AcOH
HNO3–Ac2O
HNO3–CH2Cl2
80
9.9
HNO3
10
40
15
20
48.8
60.8
84.5
71.0
30.0
24.8
4.6
8.9
6.2
3.8
2.9
12.3
6.6
–
1.6
4.3
2.0
–
–
–
–
HNO3–AcOH
HNO3–Ac2O
HNO3–CH2Cl2
2.8
13.1
11.0
a 16 equiv of HNO3 was used; 0.5–3% of disubstituted products was also present.
The product composition was similar in the reac-
tions of cage hydrocarbons with an equimolar amount
of dinitrogen pentoxide (0.8 M) in carbon tetrachloride.
In this weakly polar system, hydroxy derivatives pre-
dominated among the products, and the concentration
of nitro compounds was also relatively high, which
indicated high probability of radical processes. Here,
the reactive species is likely to be nitrogen trioxide
radical NO3·, and the product ratio is determined by the
reaction of intermediate adamantyl radical with am-
bident nitrogen dioxide. This reaction directly produces
nitro compounds and nitrites.
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KLIMOCHKIN et al.
1706
Scheme 2.
R
OH
NO2
R
H
R
ONO2
R+
R
ONO
R
NO2
Despite homolytic character of dissociation of nitric
anhydride in carbon tetrachloride, substitution of
hydrogen only at the bridgehead carbon atoms was
observed, which is consistent with the data of [58] on
the nitration of adamantane in the system nitrogen
dioxide–ozone. However, the reaction of adamantane
(1) with 10 equiv of dinitrogen pentoxide gave a com-
plex mixture of products containing (according to the
GC/MS data) both 1,3- and 1,4-disubstituted deriva-
tives (Scheme 3). Significant formation of bridge-
substitution products may be explained assuming that
introduction of a first strong electron-withdrawing
substituent into the bridgehead position considerably
decreases the difference in the stabilities of the corre-
sponding bridge and bridgehead intermediates.
For reactions of compounds 1–8 with nitric acid and
its mixtures and of compounds 1 and 6–8 with dinitro-
gen pentoxide in carbon tetrachloride: oven tempera-
ture programming from 75 to 135°C at a rate of 6 deg×
min–1; injector temperature 150°C; carrier gas helium,
flow rate 3.6 L/h;
For reaction of adamantane (1) with 10 equiv of
dinitrogen pentoxide in carbon tetrachloride: oven
temperature programming from 100 to 175°C at a rate
of 6 deg/min; injector temperature 150°C; carrier gas
helium, flow rate 3.6 L/h;
For nitroxylation of alkyladamantanes 9–13: oven
temperature programming from 75 to 140°C at a rate of
6 deg/min; injector temperature 150°C; carrier gas
helium, flow rate 3.2 L/h.
EXPERIMENTAL
The products were identified by GC/MS data which
were obtained with a Thermo Electron Finnigan Trace
DSQ instrument (USA) (electron impact, 70 eV).
The product mixtures were analyzed by GLC on
a Thermo Scientific Focus gas chromatograph (USA)
equipped with a 0.5-m×3-mm glass column packed
with 5% SE-30 + 3% SKTFT-100 on Inerton AW-
HMDS (0.20–0.25 mm). Samples were injected
directly into the column. The conditions for GLC
analyses were as follows:
The melting points were measured in capillaries on
an MPM-H2 melting point apparatus (Germany) and
are uncorrected. The refractive indices were measured
with an IRF-454 B2M refractometer at 20°C. Adaman-
tane (1) was a commercial product. Diamantane (5)
Scheme 3.
OH
OH
HO
O
N2O5, CCl4
+
+
+
+
NO2
OH
OH
OH
ONO2
28.9%
4.7%
9.0%
+
3.0%
+
11.0%
OH
ONO2
NO2
NO2
O2N
+
+
+
NO2
OH
ONO2
ONO2
NO2
16.5%
9.6%
5.0%
8.9%
3.4%
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CHEMOSELECTIVITY OF NITROXYLATION OF CAGE HYDROCARBONS
1707
was provided by I. Yanku (Higher School of Chemical
Technology, Prague). 1-Ethyladamantane (2) [64],
1,3,5-trimethyladamantane (4) [65], and 2,2-dimethyl-
adamantane (13) [66] were synthesized according to
reported procedures; their purity was no less than
98.0%. Dinitrogen pentoxide was prepared as described
in [67] in a preliminarily weighed amount of carbon
tetrachloride.
Bicyclo[3.3.1]nonane (8) was synthesized in
a similar way from bicyclo[3.3.1]nonane-3,7-dione.
Yield 2.5 g (90%), mp 139–140°C [72].
Protoadamantane (7). A mixture of 3 g (0.02 mol)
of protodamantan-4-one, 30 mL of dimethyl sulfoxide,
30 mL of ethylene glycol, 30 g (0.53 mol) of potassium
hydroxide, and 30 mL (0.2 mol) of hydrazine hydrate
was refluxed for 15 h, while intermittently washing off
the sublimed product from the reflux condenser with
pentane. The pentane solution was washed with
a 10% solution of acetic acid, dried over sodium
sulfate, and evaporated. The residue was purified by
silica gel column chromatography using pentane as
eluent. Yield 2.4 g (89%), mp 208–210°C [73].
2-Methyladamantane (9). 2-Methyladamantan-2-
ol, 30 g (0.18 mol), was dissolved in 40 mL of trifluoro-
acetic acid, and a mixture of 30 mL of GKZh-94
organosilicon oligomer and 40 mL of hexane was
added dropwise at a temperature not exceeding 25°C.
The mixture was stirred for 1 h and kept at 45–50°C
for 50 h. The mixture was cooled, neutralized with
120 mL of a 20% solution of sodium hydroxide,
refluxed for 5 h, and steam-distilled. The distillate was
extracted with pentane, and the extract was passed
through a silica gel column and evaporated. Yield 25 g
(92%), mp 151–153°C (from acetone) [68].
Sample preparation for GLC analysis of prod-
ucts of reactions of cage hydrocarbons with nitric
acid and its mixtures. Hydrocarbon 1–4 or 6–8,
0.003 mol, was added to 0.03 mol of 100% nitric acid
at such a rate that the temperature did not exceed 15°C
(compound 5 was added to 0.048 mol of 100% nitric
acid). In the case of mixtures of nitric acid with acetic
acid (0.0044 mol), acetic anhydride (0.011 mol), and
methylene chloride (0.008 mol), the nitric acid mixture
was added to cage hydrocarbon. The reaction mixture
was kept at 20–25°C until the reaction was complete
(TLC, hexane–acetone, 8:3), poured onto ice, and
extracted with 10 mL of methylene chloride. The
extract was washed with a 10% solution of sodium
hydrogen carbonate, dried over sodium sulfate, and
analyzed by GLC. The compositions of nitroxylation
products are given in Table 1.
1-(Propan-2-yl)adamantane (3) was synthesized
in a similar way from 2-(adamantan-1-yl)propan-2-ol.
Yield 14.1 g (77%), bp 245–247°C, n2D0 = 1.5002 [64].
2-Ethyladamantane (10) was synthesized in
a similar way from 2-ethyladamantan-2-ol. Yield 8.1 g
(89%), nD20 = 1.5023 [69].
2-(Propan-2-yl)adamantane (11) was synthesized
in a similar way from 2-(propan-2-yl)adamantan-2-ol.
Yield 7.9 g (86%), nD20 = 1.4952 [69].
2,6-Dimethyladamantane (12) was synthesized in
a similar way from 2,6-dimethyladamantane-2,6-diol.
Yield 6.3 g (75%), nD20 = 1.5019 [70].
Reaction of cage hydrocarbons with an equi-
molar amount of dinitrogen pentoxide in carbon
tetrachloride. A freshly prepared solution of 1.5 mmol
of dinitrogen pentoxide in 1.5 mL of carbon tetra-
chloride (N2O5 concentration 0.8 M) was added to
a solution of 1.5 mmol of compound 1 or 6–8 in 2 mL
of carbon tetrachloride at a temperature not exceeding
15°C. The mixture was kept at 20°C for 1 h and poured
onto ice, and the organic layer was washed with
a 10% solution of sodium hydrogen carbonate and
dried over sodium sulfate. The product mixture was
analyzed by GLC.
Homoadamantane (6). Homoadamantan-4-one,
3.88 g (0.024 mol), was added to a solution of 11.6 mL
(0.23 mol) of hydrazine hydrate and 6.6 g (0.12 mol) of
potassium hydroxide in 21 mL (0.22 mol) of diethylene
glycol, and the mixture was refluxed for 3 h. During
the reaction, the sublimed product was washed off from
the refluxed condenser with methylene chloride.
A Dean–Stark trap was then mounted, and excess
hydrazine was distilled off, while intermittently wash-
ing off the sublimed product from the reflux condenser
with methylene chloride. The combined organic ex-
tracts were washed with a 10% solution of acetic acid,
dried over sodium sulfate, and evaporated, and the
residue was purified by silica gel column chromatog-
raphy using hexane as eluent. Yield 2.9 g (82%),
mp 253–254°C [71].
Composition of products (%, GC/MS) obtained
from adamantane (1): adamantan-1-yl nitrate, 20.7;
adamantan-1-ol, 56.1; 1-nitroadamantane, 13.3; 1-ni-
trosoadamantane, 9.8; from homoadamantane (6):
homoadamantan-3-yl nitrate, 19.7; homoadamantan-3-
ol, 42.3; 3-nitrohomoadamantane, 17.4; 3-nitrosohomo-
adamantane, 20.6; from protoadamantane (7): proto-
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KLIMOCHKIN et al.
1708
adamantan-6-yl nitrate, 15.8; protoadamantan-6-ol,
59.2; 6-nitroprotoadamantane, 14.9; 6-nitrosoprotoada-
mantane, 10.1; from bicyclo[3.3.1]nonane (8): bicy-
clo[3.3.1]non-1-yl nitrate, 23.0; bicyclo[3.3.1]nonan-1-
ol, 36.4; 1-nitrobicyclo[3.3.1]nonane, 30.0; 1-nitroso-
bicyclo[3.3.1]nonane, 10.6.
ciably predominated among the nitroxylation products
of relatively inert 1,3,5-trimethyladamantane and
protoadamantane. The rate of substitution of nitro
group in the bridgehead position by nitrooxy group
(nitrolysis) should be proportional to the general reac-
tivity. Therefore, rapid formation of nitro compounds
from nitrooxy derivatives of some substrates is related
to easy generation and further transformations of car-
benium ions in nitric acid medium. The absence of
nitro derivatives among the products obtained from
weakly reactive substrates can be rationalized by
preferential attack by the oxygen atom of nitrite ion
(nitrous acid) on a harder carbocation. Thus, the
primary nitroxylation products of cage hydrocarbons
are nitrooxy derivatives.
The reaction of adamantane (1) with 10 equiv of di-
nitrogen pentoxide in carbon tetrachloride was carried
out in a similar way (N2O5 concentration 1.126 M,
20–25°C, 4 h). Composition of products (GC/MS), %:
1-nitroadamantane, 4.7; adamantane-1,3-diol, 9.0;
cis/trans-adamantane-1,4-diols, 3.0; 5-hydroxyada-
mantan-2-one, 11.0; 3-hydroxyadamantan-1-yl nitrate,
28.6; 3-nitroadamantan-1-ol, 16.5; cis/trans-4-nitro-
adamantan-1-ol, 9.6; adamantane-1,3-diyl dinitrate,
5.0; 3-nitroadamantan-1-yl nitrate, 8.9; 1,3-dinitroada-
mantane, 3.4.
ACKNOWLEDGMENTS
This study was performed using the facilities of the
“Physicochemical Properties of Substances and Materials”
joint center.
Nitroxylation of alkyladamantanes 9–13. Nitric
acid (100%), 0.06 mol, was added dropwise to a mix-
ture of 0.006 mol of compound 9–13, 0.031 mol of
acetic anhydride, and 3 mL of methylene chloride at
a temperature not exceeding 15°C. The mixture was
kept for 1.5 h at 20°C, poured onto ice, and extracted
with diethyl ether. The extract was washed with
a 10% solution of sodium hydrogen carbonate, dried
over sodium sulfate, and analyzed by GLC.
FUNDING
This study was performed under financial support by the
Ministry of Science and Higher Education of the Russian
Federation in the framework of project part of state
assignment no. 0778-2020-0005. The synthetic part was
financially supported by the Russian Foundation for Basic
Research (project no. 19-03-00973).
Composition of products (%, GC/MS) obtained
from 2-methyladamantane (9): cis/trans-4-methylada-
mantan-1-yl nitrate, 54.0; cis/trans-4-methyladaman-
tan-1-ol, 25.5; cis/trans-4-methyl-1-nitroadamantane,
20.5; from 2-ethyladamantane (10): cis/trans-4-ethyl-
adamantan-1-yl nitrate, 55.0; cis/trans-4-ethyladaman-
tan-1-ol, 29.0; cis/trans-4-ethyl-1-nitroadamantane,
16.0; from 2-(propan-2-yl)adamantane (11): cis/trans-
4-(propan-2-yl)adamantan-1-yl nitrate, 62.0; cis/trans-
4-(propan-2-yl)adamantan-1-ol, 27.0; cis/trans-1-nitro-
4-(propan-2-yl)adamantane, 11.0; from 2,6-dimethyl-
adamantane (12): cis/trans-2,6-dimethyladamantan-1-
yl nitrate, 58.0; cis/trans-2,6-dimethyladamantan-1-ol,
28.0; cis/trans-2,6-dimethyl-1-nitroadamantane, 14.0;
from 2,2-dimethyladamantane (13): cis/trans-4,4-di-
methyladamantan-1-yl nitrate, 60.0; cis/trans-4,4-di-
methyladamantan-1-ol, 28.0; cis/trans-4,4-dimethyl-1-
nitroadamantane, 12.0.
CONFLICT OF INTEREST
The authors declare the absence of conflict of interest.
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