Synthesis of azolyl-substituted adamantane derivatives and their coordination compounds

Article abstract of DOI:10.1007/s11172-020-2985-2

Reactions of adamantylazoles with nucleophiles (water, carbon monoxide, acetonitrile) in sulfuric acid were studied. New bifunctional adamantane derivatives containing one heterocyclic substituent and one hydroxyl or acetamide substituent were synthesized. The coordination compounds of copper(II) and zinc(II) with 1-adamantyl-1,2,4-triazole, 4-adamantylpyrazole, and 4-adamantyl-3,5-dimethylpyrazole were synthesized and structurally characterized. These complexes are first examples of coordination compounds of azolyladamantanes.

Full text of DOI:10.1007/s11172-020-2985-2

Russian Chemical Bulletin, International Edition, Vol. 69, No. 10, pp. 1953—1964, October, 2020
1953
Synthesis of azolyl-substituted adamantane derivatives
and their coordination compounds
D. I. Pavlov,а T. S. Sukhikh,b,c and A. S. Potapovb
aNational Research Tomsk Polytechnic University,
30 prosp. Lenina, 634050 Tomsk, Russian Federation
bNikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences,
3 prosp. Akad. Lavrentieva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 9489. E-mail: potapov@niic.nsc.ru
cNovosibirsk State University,
1 ul. Pirogova, 630090 Novosibirsk, Russian Federation
Reactions of adamantylazoles with nucleophiles (water, carbon monoxide, acetonitrile) in
sulfuric acid were studied. New bifunctional adamantane derivatives containing one heterocyclic
substituent and one hydroxyl or acetamide substituent were synthesized. The coordination
compounds of copper(II) and zinc(II) with 1-adamantyl-1,2,4-triazole, 4-adamantylpyrazole,
and 4-adamantyl-3,5-dimethylpyrazole were synthesized and structurally characterized. These
complexes are first examples of coordination compounds of azolyladamantanes.
Key words: adamantane, triazole, pyrazole, zinc, copper, coordination compounds, X-ray
diffraction.
Since the discovery of antiviral activity of amantadine,
a great diversity of molecules containing an adamantyl
moiety were synthesized.1—5 N-Adamantylazoles are
a specific class of compounds, which have attracted atten-
tion due to their potential biological activity. In particular,
adamantylpyrazoles were comprehensively investigated,
mainly by Elguero´s research team.6—10 Despite the fact
that the structures of adamantylazoles and their biological
activity were studied in sufficient detail,11 data on the
possibility of further functionalization of the adamantane
skeleton in adamantylazoles are scarce in the literature.
Meanwhile, adamantane is a very popular molecular
platform for the construction of rigid non-aromatic li-
gands, which are used in the synthesis of thermally stable
metal organic frameworks (MOFs).12—15 Most coordina-
tion compounds with azoles containing an adamantane
moiety belong to transition metal carbene complexes, with
1,3-diadamantylimidazole being their precursor. On the
contrary, only a few compounds are known in which
monoazolyladamantane is coordinated to a metal ion via
donor nitrogen atoms. Thus, a series of coordination
compounds of cadmium(II) with 4-(1-adamantyl)-1,2,4-
triazole and various counterions were synthesized in the
study.16 In all these compounds, the ligands serve as bridges
and are coordinated via nitrogen atoms of 1,2,4-triazole
rings at the 1 and 2 positions. In the anionic ruthenium(III)
complex with 1-adamantylimidazole, which has recently
been synthesized and structurally characterized,17 this
ligand is coordinated via the nitrogen atom at the 3 posi-
tion of the imidazole ring, and the octahedral coordination
environment of ruthenium(III) is completed by four chlor-
ide ions in the equatorial plane and a DMSO molecule.
Since unsymmetrically substituted adamantanes bear-
ing a heterocyclic moiety are of interest as ligands for
the construction of MOFs or unusual molecular com-
plexes,18—20 we examined the possibility of further func-
tionalizing the adamantane skeleton in adamantylazoles.
Results and Discussion
The starting adamantylazoles were synthesized accord-
ing to a known procedure8,11 with slight modifications.
Earlier, the fusion products of 1-bromoadamantane with
the corresponding azoles (AzH) were subjected to column
chromatography in order to isolate them in the pure form;
in the case of fusion with pyrazoles, the column chromato-
graphy allowed the separation of 1- and 4-adamantylpyr-
azoles, the ratio of which depends on the nature of pyr-
azole, the reagent ratio, and the reaction temperature.8
We found that the dissolution of the melt, obtained after
the reaction, in alcohol followed by the dilution of the
alcoholic solution with a large amount of water allowed
the extraction of the target compound with boiling hexane.
The product obtained after the concentration of the hex-
ane extract does not require additional purification. Upon
fusion with pyrazole derivatives, only 1-adamantylpyr-
azoles can be extracted, unlike 4-adamantylpyrazoles,
which are virtually insoluble in hexane, thereby making it
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1953—1964, October, 2020.
1066-5285/20/6910-1953 © 2020 Springer Science+Business Media LLC

Pavlov et al.
1954
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
possible to easily separate these isomers without using
column chromatography. The synthesized compounds are
shown in Scheme 1.
Under these conditions, the reaction with 1-adaman-
tylpyrazole is complicated by the nitration of the 4 position
of the pyrazole ring susceptible to electrophilic substitution
(Scheme 3). In the reactions of 1-adamantylpyrazole 1c
and 4-adamantylpyrazoles 1d,e, the C—C bond proved to
be unstable under the reaction conditions, resulting in that
1-adamantanol (A) is produced apart from target 1-(pyr-
azol-1-yl)-3-hydroxyadamantane (see Scheme 3).
Scheme 1
Scheme 3
i. Fusion.
We chose carboxyl, hydroxy, and amino groups, which
are most popular in coordination chemistry, as potentially
interesting functional moieties. In a large number of stud-
ies, these groups and some other were introduced into the
substituted adamantane skeleton.18—31
The reaction of 1-(adamantyl)-1,2,4-triazoles with
water in a mixture of sulfuric and nitric acids affords
3-hydroxy-1-(1,2,4-triazol-1-yl)adamantanes (2a,b)
(Scheme 2).
We intended to synthesize 3-amino-1-azolyladaman-
tanes through the intermediate formation of 3-acetamido-
1-azolyladamantanes and subsequent hydrolysis. However,
this approach allowed us to prepare only 1-(1,2,4-triazol-
1-yl)-3-acetamidoadamantane (3) in 20% yield (Scheme 4).
It should be noted that compound 3 can be synthesized
only using nearly anhydrous (fuming) nitric acid, whereas
the reaction with 68% nitric acid affords solely hydroxy
derivative 2а. The reactions with pyrazolyl- and imidazol-
yladamantanes gave only trace amounts of the target
product.
Scheme 2
The carboxylation of alkanes is generally performed
using the Koch—Haaf reaction.23 However, the reaction
of 1-adamantyl-1,2,4-triazoles with formic acid in a mix-
ture of nitric and sulfuric acids gives 3-hydroxy-1-(1,2,4-
triazol-1-yl)adamantanes as the major products. The
target product B was identified by GC-MS in trace
amounts (Scheme 5). The reaction of 1-adamantyl-1,2,4-
triazole using fuming nitric acid furnishes a mixture of
R = H (a), Me (b)

Heterocyclic adamantane derivatives
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
1955
Scheme 4
Complex 6 was synthesized by the reaction of ligand
1e with copper(II) nitrate in methanol (Scheme 7). In this
case, a small amount of complex 7 was isolated. This
compound is formed with the participation of 4-bromo-
3,5-dimethylpyrazole, which was present as an impurity
to compound 1e. Coordination compound 8 was prepared
by the reaction of ligand 1d with copper(II) chloride in
acetone (see Scheme 7).
Compound 4 crystallizes in the monoclinic crystal
system. The unit cell includes two symmetry-related mol-
ecules of the complex. The coordination polyhedron can
be described as a distorted trigonal bipyramid (Fig. 1)
characterized by the geometry index τ5 of 0.74 (Table 1);
for the ideal trigonal bipyramid, this index is equal to
unity.32 The equatorial positions of the bipyramid are
occupied by nitrogen atoms of the 1,2,4-triazole rings (at
the 4 position), and the axial positions are occupied by
oxygen atoms of monodentate nitrate ions. The inter-
atomic Zn—N distances are typical of such compounds
(2.01—2.03 Å). The Zn—O distances are 2.110(2) and
2.239(1) Å. One interatomic Zn—O distance is somewhat
larger than the typical value (2.00—2.20 Å) for five-coor-
1-adamantanecarboxylic acid and 1,3-di(1,2,4-triazol-
1-yl)adamantane. This reaction can be applied as an al-
ternative method for the synthesis of this compound, which
we have previously synthesized.18
To investigate the coordination ability of the synthe-
sized azolyladamantanes, we performed their reactions
with copper(II) and zinc(II) nitrates and chlorides, result-
ing in the formation of new coordination compounds,
which were structurally characterized. Thus, compounds
4 and 5 were prepared by the reaction of ligand 1a with
zinc nitrate or chloride in methanol (Scheme 6).
Scheme 5
R = H (a), Me (b)
Scheme 6

Pavlov et al.
1956
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
Scheme 7
dinate zinc with two nitrate ions due apparently to steric
factors.
Compound 5 crystallizes in the orthorhombic crystal
system. The unit cell includes four formula units of the
complex. There is one-half of the crystallographically
independent molecule per asymmetric unit. The zinc atom
occupies a special position 4d (Wyckoff symbol) with sym-
metry 2. The zinc atoms are in a tetrahedral environment
(Fig. 2), with the index τ433 close to unity (see Table 1). Two
coordination sites are occupied by nitrogen atoms of
1,2,4-triazole rings; two other sites, by chloride ions. The
interatomic Zn—N and Zn—Cl distances are 2.019(0) and
2.223(9) Å, respectively. The chlorine atoms form short con-
tacts with hydrogen atoms at the 3 positions of the 1,2,4-tri-
azole rings. The interatomic Cl···H distance is 2.774(0) Å,
which is typical of this type of contacts.34 The molecules
are linked via these contacts to form supramolecular lay-
ers lying parallel to the crystallographic plane ac (Fig. 3).
Compound 6 crystallizes in the monoclinic crystal
system. The unit cell includes two formula units of the
complex. Compound 6 is a binuclear complex. The asym-
Table 1. Geometric parameters of the coordination polyhedra in
compounds 4—8
Compound
α/deg
β/deg
τ index
4
5
6
7
126.2
114.2
167.9
170.7
114.2
169.9
τ5 = 0.74
τ4 = 0.93
τ4 = 0.16
161.9 (Cu(1)) 166.2 (Cu(1)) τ5 = 0.07 (Cu(1))
161.6 (Cu(2)) 168.2 (Cu(2)) τ5 = 0.11 (Cu(2))
160.3 (Cu(3)) 164.7 (Cu(3)) τ5 = 0.07 (Cu(3))
8
180.0
180.0
τ4 = 0

Heterocyclic adamantane derivatives
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
1957
N(5)
O(2)
O(3)
C(1)
N(1)
N(4)
N(3)
O(1)
С(2)
C(25)
N(10)
N(9)
Zn(1)
N(6)
C(26)
N(11)
O(4)
N(2)
С(13)
С(14)
O(6a)
N(7)
N(8)
O(5)
Fig. 1. Molecular structure of compound 4 with thermal ellipsoids drawn at 50% probability level. Hydrogen atoms and the atom
numbering of adamantane moieties are omitted for clarity.
metric unit contains one-half of the molecule located at
a center of inversion 2a (Wyckoff symbol). In this complex,
two Cu2+ ions are linked by bridging methoxide ions
OCH3–, two other coordination sites of each copper ion
are occupied by neutral organic ligands 1e, which are not
deprotonated during the reaction (Fig. 4). The ligand is
coordinated via nitrogen atoms at the 2 position of the
pyrazole rings. The copper ions are in a distorted square-
planar environment (τ4 = 0.16). The electroneutrality of
the complex is provided by two outer-sphere nitrate ions
(they are not shown in the figure). The interatomic Cu—N
distances are 1.981(3) and 1.967(3) Å; the Cu—O distance
is 1.921(2) Å.
Compound 7 crystallizes in the triclinic crystal system.
The asymmetric unit contains three crystallographically
independent copper(II) ions that form a trinuclear frag-
ment. In this fragment, two deprotonated 4-bromo-3,5-
dimethylpyrazole molecules serve as bridging ligands,
through which the Cu2+ ions are linked along two sides of
a non-equilateral triangle; besides, the copper ions are
linked by a methoxide ion along the third side of the tri-
angle. Additionally, all three Cu2+ ions are coordinated
Cl(1)
Zn(1)
С(1)
N(2)
N(1)
С(2)
N(3)
Fig. 2. Molecular structure of compound 5 with thermal ellipsoids drawn at 50% probability level. Hydrogen atoms and the number-
ing of symmetry-related atoms and atoms of adamantane moieties are omitted for clarity.

Pavlov et al.
1958
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
a
b
Fig. 3. Supramolecular layer in the crystal structure of compound 5 projected along the c (a) and b axes (b).
С(5)
С(1)
С(2)
С(3)
N(2)
С(4)
N(1)
Сu(1)
N(3)
O(1)
С(19)
С(16)
N(4)
С(18)
С(20)
C(31)
C(17)
Fig. 4. Molecular structure of compound 6 with thermal ellipsoids drawn at 50% probability level. Hydrogen atoms, outer-sphere
nitrate ions, and the numbering of symmetry-related atoms and atoms of adamantane moieties are omitted for clarity.

Heterocyclic adamantane derivatives
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
1959
С(9)
С(4)
a
Br(2)
Br(1)
С(41)
С(1)
C(7)
N(3)
N(1)
Cu(1)
C(2)
С(3)
С(8)
N(4)
O(1)
O(3)
O(4)
С(10)
С(5)
N(2)
Cu(3)
N(9)
O(2)
N(7)
N(6)
O(5)
N(8)
N(5)
С(13)
С(11)
C(28)
С(30)
С(42)
С(15)
С(12)
C(26)
С(27)
C(29)
С(14)
b
Fig. 5. Asymmetric unit of the crystal structure of compound 7 with thermal ellipsoids drawn at 50% probability level (а) and the molecular
structure of hexanuclear complex 7 (b). Hydrogen atoms and the atom numbering of adamantane moieties are omitted for clarity.
by another methoxide ion (Fig. 5, а). The coordination
polyhedron of the Cu(1) atom can be described as a dis-
torted square pyramid, with two nitrogen atoms of the
4-bromopyrazolate anion, two oxygen atoms of the an-
isobidentate chelating nitrate ion, and an oxygen atom of
the methoxide ion occupying the vertices. The Cu(2) and

Pavlov et al.
1960
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
С(1)
N(2)
Cl(1)
С(2)
N(1)
Cu(1)
С(3)
Fig. 6. Molecular structure of compound 8 with thermal ellipsoids drawn at 50% probability level. Hydrogen atoms and the number-
ing of symmetry-related atoms and atoms of adamantane moieties are omitted for clarity.
commercial 95% acid solution. Acetonitrile was dried over 4 Å
molecular sieves. The NMR spectra were recorded on a BRUKER
AVANCE III HD spectrometer (400 MHz). The GL-MS
analysis was performed on a Agilent 7890A GC gas chromato-
graph equipped with an Agilent 5975C quadrupole mass spectro-
meter. The IR spectra were recorded on an Agilent Cary 630
spectrometer equipped with an attenuated total reflectance ac-
cessory with diamond crystal.
Synthesis of adamantylazoles (general procedure). 1-Bromo-
adamantane (2.16 g, 10 mmol) was mixed with an appropriate
azole (10 mmol) in a thick-walled flask with Teflon screw cap.
The flask was closed and placed in an oven for 12 h at 120 °C to
prepare 1-adamantylazoles or at 180 °C to prepare 4-adaman-
tylpyrazoles. After cooling, the melt was dissolved in ethanol
(20 mL) and poured to distilled water (200 mL). The precipitate
was filtered off and dried. The products were extracted with boil-
ing hexane (3×20 mL). The combined extracts were concen-
trated. The resulting products did not require additional purifica-
tion. In the synthesis of 4-adamantylpyrazoles, the precipitate,
which remained after the heating of the reaction products in
hexane at reflux, was filtered off, dried, and used in the next step
without additional purification.
Functionalization of adamantylazoles (general procedure).
Adamantylazole (1 mmol) was dissolved in 98% sulfuric acid (1 mL).
Then fuming nitric acid (98%, 5 mmol) was added on cooling.
The mixture was stirred at room temperature for 2—4 h. Then
a water—anhydrous acetonitrile— anhydrous formic acid mixture
was added dropwise (10 mmol) depending on the target product.
The mixture was stirred for 12 h, poured onto ice, filtered, and
extracted with chloroform. The extract was concentrated, and
the target product with high purity was obtained.
Cu(3) atoms are also in a distorted square-pyramidal
environment, each atom being coordinated by one ligand
1e and two methoxide ions; the fifth coordination site is
occupied by an oxygen atom of the bridging nitrate ion,
through which the trinuclear moieties are linked together
to form a hexanuclear neutral complex (Fig. 5, b).
Compound 8 crystallizes in the monoclinic crystal
system. The unit cell contains four formula units of the
neutral complex. There is one crystallographically inde-
pendent copper(II) ion, one chloride ion, and one ligand
molecule per asymmetric unit. The copper(II) ion is in
a nearly ideal square-planar environment (Fig. 6), the
index τ4 is equal to zero. In the inner coordination sphere
of the complex, two ligand molecules are coordinated in
the protonated form via nitrogen atoms at the 2 position
of the pyrazole rings; two other trans positions are occupied
by chloride ions. The interatomic Cu—N distance is
1.99 Å, and the Cu—Cl distance is 2.256 Å. The angle
between the plane of the pyrazole rings and the plane of the
coordination unit is 14.5°. It is worth noting that ten of four-
teen known complexes of pyrazole derivatives (in the proto-
nated form) with copper(II) chloride have a distorted tetra-
hedral coordination environment and only in four com-
pounds, the copper atom is in a planar environment.35—38
To summarize, we modified the procedure for the
preparation of 1- and 4-adamantylazoles and examined
the applicability of the Ritter and Koch—Haaf reactions
for the functionalization of the adamantane skeleton in
1- and 4-adamantylazoles. It was shown that these proce-
dures are suitable only for the synthesis of hydroxy-sub-
stituted azolyladamantanes. Acetonitrile and carbon(II)
monoxide are not sufficiently nucleophilic for the success-
ful reactions giving products in high yields. The C—C bond
in 4-adamantylpyrazoles is unstable and is cleaved in acidic
media. New coordination compounds of zinc(II) and
copper(II) with 1-adamantyl-1,2,4-triazoles and 4-ada-
mantylpyrazoles were synthesized, and their structures
were determined by X-ray diffraction.
1-(1-Adamantyl)-1,2,4-triazole (1а). Colorless crystals. Yield
59%, m.p. 89—90 °C (hexane; cf. lit. data39: m.p. 87—88 °C).
1H NMR (DMSO-d6), δ: 1.72 (m, 6 H, Ad); 2.10 (m, 6 H, Ad);
2.17 (m, 3 H, Ad); 7.97 (s, 1 H, CTr(3)H); 8.58 (s, 1 H, CTr(5)H).
IR, ν/cm–1: 3319 (m), 2907 (s), 2853 (s), 1743 (w), 1497 (m),
1452 (m), 1308 (m), 1275 (s), 1211 (m), 1153 (s), 1102 (m),
1055 (w), 1042 (s), 958 (m), 870 (s), 665 (s).
1-(1-Adamantyl)-3-methyl-1,2,4-triazole (1b). Colorless
crystals. Yield 35%, m.p. 55—57 °C (hexane; cf. lit. data40: m.p.
1
52—53 °C). H NMR (DMSO-d6), δ: 1.70 (m, 6 H, Ad); 2.07
(m, 6 H, Ad); 2.15 (m, 3 H, Ad); 2.23 (s, 3 H, CH3); 8.36 (s, 1 H,
CTr(5)H). IR, ν/cm–1: 2906 (s), 2850 (s), 1517 (m), 1355 (m),
1309 (m), 1204 (m), 1104 (w), 1006 (m), 834 (w).
Experimental
1-(1-Adamantyl)pyrazole (1c). Colorless crystals. Yield 80%,
m.p. 54—55 °C (hexane; cf. lit. data41: m.p. 52—54 °C). 1H NMR
(CDCl3), δ: 1.76 (m, 6 H, Ad); 2.17 (m, 6 H, Ad); 2.22 (m, 3 H,
Ad); 6.23 (t, 1 H, CPz(4)H, J = 1.0); 7.51 (d, 1 H, CPz(3)H,
Solvents and reagents of reagent grade were used as received.
Anhydrous formic acid was prepared by freeze-drying of the

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Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
1961
Table 2. Crystallographic parameters and the X-ray diffraction data collection and refinement statistics for compounds 4—6
Parameter
4
5
6
Molecular formula
M/g mol–1
T/K
Space group
a/Å
C
36H51N11O6Zn
799.24
150(2)
Pc
10.6787(8)
13.1761(9)
13.0883(9)
90
C24H34Cl2N6Zn
542.84
C62H94Cu2N10O8
1234.55
150(2)
150(2)
Pnna
P21/c
10.1574(6)
28.4931(16)
8.8107(5)
90
16.102(6)
14.077(5)
13.938(5)
90
b/Å
c/Å
α/deg
β/deg
91.549(2)
90
90
90
93.436(13)
90
γ/deg
V/Å3
1840.9(2)
2
2550.0(3)
4
1.414
1.197
1136.0
3154(2)
Z
2
dcalc/g cm–3
μ/mm–1
F(000)
1.442
1.300
0.730
0.735
844.0
1316.0
Crystal size/mm
2θ-Scan range/deg
h, k, l ranges
0.4×0.35×0.32
3.816—55.898
–14 ≤ h ≤ 14,
–15 ≤ k ≤ 17
–16 ≤ l ≤ 17
0.39×0.27×0.08
4.84—51.398
–12 ≤ h ≤ 11,
–34 ≤ k ≤ 34,
–10 ≤ l ≤ 10
0.18×0.16×0.12
3.846—50.308
–19 ≤ h ≤ 17,
–14 ≤ k ≤ 16,
–16 ≤ l ≤ 15
Number of reflections
measured
unique
Rint
Rσ
Number of refined parameters
Number of restraints
GOOF based on F2
R-фактор (I > 2σ(I))
R1
20393
8518
0.0275
0.0441
498
14
1.034
16872
2421
0.0456
0.0315
150
29077
5557
0.0730
0.0617
0
0
1.075
1.036
0.0216
0.0548
0.0362
0.0802
0.0436
0.1030
wR2
R factor (all data)
R1
wR2
Residual electron density
(Δρmax/Δρmin)/e Å–3
Flack parameter
0.0224
0.0550
0.0502
0.0859
0.0750
0.1166
0.39/–0.22
0.91/–0.41
0.31/–0.32
0.022(7)
—
—
J = 1.0 Hz); 7.54 (d, 1 H, CPz(5)H, J = 1.0 Hz). IR, ν/cm–1
2905 (s), 2845 (s), 1448 (m), 1397 (m), 1309 (m), 1102 (m),
1055 (m), 743 (s).
4-(1-Adamantyl)pyrazole (1d). Colorless crystals. Yield 47%,
m.p. 208—209 °C (hexane; cf. lit. data39: m.p. 208—210 °C).
1H NMR (CDCl3), δ: 1.76 (m, 6 H, Ad); 1.85 (m, 6 H, Ad); 2.07
(m, 3 H, Ad); 7.47 (s, 2 H, CTr(3)H). IR, ν/cm–1: 3153 (m),
2900 (s), 2847 (s), 1450 (s), 1345 (m), 1153 (m), 1138 (m), 1102 (w),
1084 (m), 1038 (m), 989 (s), 958 (s), 934 (w), 852 (s), 804 (s),
676 (s), 632 (s).
:
(DMSO-d6), δ: 1.55 (m, 2 H, Ad); 1.64 (m, 4 H, Ad); 1.98 (t, 6 H,
Ad); 2.28 (t, 2 H, Ad); 4.77 (s, 1 H, OH); 7.94 (s, 1 H, CTr(3)H);
8.53 (s, 1 H, CTr(5)H). 13C NMR (DMSO-d6), δ: 30.0, 34.3,
41.0, 43.7, 49.7, 60.0, 67.4, 140.5, 150.7.
3-Methyl-1-(1,2,4-triazol-1-yl)-3-hydroxyadamantane (2b).
1
Yield 62%, m.p. 78—79 °C (MeOH). H NMR (DMSO-d6),
δ: 1.63 (s, 4 H, Ad); 1.96 (s, 4 H, Ad); 2.00 (s, 6 H, Ad); 2.27
(s, 3 H, CTr(3)CH3); 4.72 (s, 1 H, OH); 8.36 (s, 1 H, CTr(5)H).
1-(1,2,4-Triazol-1-yl)-3-acetamidoadamantane (3). Yield
1
20%. H NMR (DMSO-d6), δ: 1.63 (s, 2 H, Ad); 1.77 (s, 3 H,
3,5-Dimethyl-4-(1-adamantyl)pyrazole (1e). Colorless crys-
tals. Yield 70%, m.p. 219—220 °C (hexane; cf. lit. data42: m.p.
220—221 °C). 1H NMR (DMSO-d6), δ: 1.72 (m, 6 H, Ad); 2.10
(m, 6 H, Ad); 2.17 (m, 3 H, Ad); 7.97 (s, 1 H, CTr(3)H); 8.58
(s, 1 H, CTr(5)H). IR, ν/cm–1: 3167 (s), 2907 (s), 2898 (s), 2847
(s), 1433 (m), 1407 (m), 1292 (w), 1183 (w), 1027 (m), 816 (w).
1-(1,2,4-Triazol-1-yl)-3-hydroxyadamantane (2a). Pale-
CH3); 1.86 (m, 2 H, Ad); 2.03 (m, 4 H, Ad); 2.09 (m, 2 H, Ad);
2.28 (s, 2 H, Ad); 2.33 (s, 2 H, Ad); 7.55 (s, 1 H, NH); 7.96
(s, 1 H, CTr(3)H); 8.56 (s, 1 H, CTr(5)H).
Tris(1-adamantyl-1,2,4-triazole)dinitratozinc (4). Zin(II)
nitrate, Zn(NO3)2•6H2O (0.5 mmol), was mixed with compound
1a (1 mmol) and methanol (10 mL) in a 20 mL vial with screw
cap. The reaction solution was kept at room temperature for two
days. Then the colorless crystals that formed were filtered off and
1
brown powder. Yield 75%, m.p. 97—98 °C (MeOH). H NMR

Pavlov et al.
1962
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
Table 3. Crystallographic parameters and the X-ray diffraction data collection and refinement statistics for
compounds 7 and 8
Parameter
7
8
Molecular formula
M/g mol–1
T/K
Space group
a/Å
C
43H66Br2Cu3N10O9
1217.49
C26H36Cl2CuN4
539.03
150–(2)
298(2)
P1
P21/c
12.3332(12)
15.9699(16)
16.2701(17)
118.656(4)
92.101(4)
106.963(4)
2629.5(5)
2
16.067(8)
10.879(6)
7.143(4)
90
b/Å
c/Å
α/deg
β/deg
95.366(16)
90
γ/deg
V/Å3
1243.1(11)
2
Z
dcalc/g cm–3
μ/mm–1
F(000)
1.538
2.781
1246.0
1.440
1.116
566.0
Crystal size/mm
2θ-Scan range/deg
h, k, l ranges
0.36×0.23×0.12
2.978—51.358
–15 ≤ h ≤ 12,
–18 ≤ k ≤ 19,
–19 ≤ l ≤ 19
0.45×0.33×0.03
3.744—48.814
–18 ≤ h ≤ 18,
–12 ≤ k ≤ 12,
–8 ≤ l ≤ 5
Number of reflections
measured
unique
Rint
Rσ
22984
9919
0.0475
0.0749
616
12
1.043
6533
1987
0.0554
0.0649
152
Number of refined parameters
Number of restraints
0
GOOF based on F2
1.251
R factor (I > 2σ(I))
R1
wR2
R factor (all data)
R1
0.0490
0.1222
0.0968
0.2651
0.0750
0.1339
1.24/–0.99
0.1187
0.2961
2.13/–0.75
wR2
Residual electron density (Δρmax/Δρmin)/e Å–3
washed with a small amount of methanol and diethyl ether. Yield
41%. Found (%): C, 54.3; H, 6.4; N, 19.2. C36H51N11O6Zn.
1450 (w), 1286 (m), 1142 (s), 1101 (m), 994 (s), 683 (w), 836
(m), 683 (m), 655 (s).
1
Calculated (%): C, 54.1; H, 6.4; N, 19. H NMR (DMSO-d6),
Di-μ-methoxobis[bis(3,5-dimethyl-4-adamantylpyrazole)-
copper] (6). Copper(II) nitrate, Cu(NO3)2•3H2O (1 mmol), was
mixed with compound 1c (1 mmol) and methanol (10 mL) in
a 20 mL vial with screw cap. The solution was kept at 80 °C
overnight. Then the blue-green crystals were filtered off and
washed with a small amount of methanol and diethyl ether.
Several crystals of compound 7 were simultaneously obtained.
Found (%): C, 59.9; H, 7.4; N, 11.0. C62H94Cu2N10O8. Cal-
culated (%): C, 60.3; H, 7.7; N, 11.4. IR, ν/cm–1: 3189 (w),
2897 (s), 2850 (s), 1559 (w), 1522 (w), 1342 (s), 1282 (s), 1202 (m),
1035 (s), 815 (w), 683 (w).
Bis(4-adamantylpyrazole)dichlorocopper (8). A solution of
CuCl2•2H2O (0.2 mmol) in acetone (5 mL) was added to
a solution of compound 1b (0.2 mmol) in acetone (10 mL). The
reaction solution was kept at room temperature overnight. The
pale-green plate-like crystals that precipitated were filtered off,
δ: 1.71 (m, 6 H, Ad); 2.10 (m, 6 H, Ad); 2.17 (m, 3 H, Ad); 7.96
(s, 1 H, CTr(3)H); 8.54 (s, 1 H, CTr(5)H). 13C NMR (DMSO-d6),
δ: 28.8, 35.4, 41.9, 57.8, 140.5, 150.6. IR, ν/cm–1: 3150 (s), 3113
(s), 2928 (s), 2860 (s), 1522 (s), 1489 (s), 1460 (s), 1443 (s), 1395
(s), 1362 (s), 1304 (s), 1279 (s), 1250 (m), 1202 (m), 1136 (s),
1103 (m), 1042 (w), 1013(w), 1001 (s), 997 (s), 984 (w), 899 (m),
876 (m), 837 (m), 816 (m), 770 (m), 667 (s), 656 (s), 642 (m).
Bis(1-adamantyl-1,2,4-triazole)dichlorozinc (5) was synthe-
sized in a similar way to compound 4 starting from compound
1a and ZnCl2. Yield 39%. Found (%): C, 53.5; H, 6.0; N, 15.2.
C24H34Cl2N6Zn. Calculated (%): C, 53.1; H, 6.3; N, 15.5.
1H NMR (DMSO-d6), δ: 1.72 (m, 6 H, Ad); 2.10 (m, 6 H, Ad);
2.17 (m, 3 H, Ad); 7.99 (s, 1 H, CTr(3)H); 8.60 (s, 1 H, CTr(5)H).
13C NMR (DMSO-d6), δ: 28.7, 35.4, 41.8, 58.0, 140.5, 150.4.
IR, ν/cm–1: 3150 (w), 3319 (w), 2911 (s), 2850 (w), 1521 (s),

Heterocyclic adamantane derivatives
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
1963
washed with acetone, and dried. Yield 52%. Found (%): C, 58.3;
H, 6.4; N, 10.3. C26H36Cl2CuN4. Calculated (%): C, 57.9; H, 6.7;
N, 10.4. IR, ν/cm–1: 3287 (s), 2903 (s), 2847 (s), 1454 (s),
1400 (w), 1348 (w), 1341 (w), 1313 (w), 1287 (w), 1115 (s),
1092 (m), 1049 (s), 988 (s), 964 (s), 874 (s), 845 (w), 812 (m),
721 (s), 667 (m), 606 (m), 465 (w).
10. P. Cabildo, R.M. Claramunt, D. Sanz, M. C. Foces-Foces,
F. H. Cano, J. P. Fayet, M. C. Vertut, J. Elguero, J. Heterocycl.
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D. Sanz, J. Elguero, Eur. J. Med. Chem., 1985, 20, 359.
12. M. A. Khanfar, A. M. Jaber, M. A. AlDamen, R. A. Al-
Qawasmeh, M. A. Khanfar, A. M. Jaber, M. A. AlDamen,
R. A. Al-Qawasmeh, Molecules, 2018, 23, 701.
13. J. Z. Travis, B. L. Martinez, R. L. LaDuca, Z. Anorg. Allg.
Chem., 2018, 644, 33.
14. G. A. Senchyk, A. B. Lysenko, E. B. Rusanov, A. N.
Chernega, J. Jezierska, K. V Domasevitch, A. Ozarowski,
Eur. J. Inorg. Chem., 2012, 5802.
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Inorg. Chem., 2018, 57, 8735.
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Crystallogr., Sect. E Crystallogr. Commun., 2019, 75, 1145.
19. G. A. Senchyk, A. B. Lysenko, E. B. Rusanov, K. V. Domas-
evitch, Acta Crystallogr., Sect. E Crystallogr. Commun., 2019,
75, 808.
20. D. Pavlov, T. Sukhikh, E. Filatov, A. Potapov, Molecules,
2019, 24, 2717.
21. Y. N. Klimochkin, I. K. Moiseev, M. V. Leonova, S. N.
Nikolaeva, E. I. Boreko, Pharm. Chem. J., 2017, 51, 13.
22. R. Leiva, M. Barniol-Xicota, S. Codony, T. Ginex, E. Van-
derlinden, M. Montes, M. Caffrey, F. J. Luque, L. Naesens,
S. Vázquez, J. Med. Chem., 2018, 61, 98.
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46, 3217.
X-ray diffraction studies were performed by a standard pro-
cedure on a Bruker Apex DUO automated four-circle diffracto-
meter equipped with a CCD detector and a graphite monochrom-
ator using molybdenum radiation (λ = 0.71073 Å). The intensi-
ties of reflections were measured by ϕ- and ω-scanning of narrow
frames (0.5°). Absorption corrections were applied using the
SADABS program.43 The structures were solved by direct meth-
ods and refined by the full-matrix least-squares method with
anisotropic displacement parameters for all nonhydrogen atoms
using the SHELXT44 and SHEXL program suites45 via the Olex2
graphical interface.46 Hydrogen atoms were positioned geo-
metrically and refined using a rigid-body model. The O atom of
one nitrate ion of complex 7 was disordered over two positions
and refined using SIMU restraints. Crystallographic parameters
and the X-ray data collection and structure refinement statistics
are given in Table 2. The relatively high R factor and large re-
sidual electron density peaks for structure 8 are attributed to the
fact that the crystal was a twin, and it was refined using the twin
matrix (1 0 0.4 0 -1 0 0 0 -1) with BASF = 0.25 in the final refine-
ment steps. The X-ray diffraction data were deposited with the
Cambridge Crystallographic Data Centre (CCDC 1956464—
1956468), can be obtained from the authors, and are available
at http://www.ccdc.cam.ac.uk/conts/retrieving.html.
The study was performed within the framework of
the state assignment for the Nikolaev Institute of Inor-
ganic Chemistry of the Siberian Branch of the Russian
Academy of Sciences in the field of fundamental scientific
research.
25. E. A. Ivleva, I. M. Tkachenko, V. S. Gavrilova, Y. N.
Klimochkin, Russ. J. Org. Chem., 2016, 52, 1394.
26. E. A. Ivleva, I. M. Tkachenko, Y. N. Klimochkin, Russ. J.
Org. Chem., 2016, 52, 1558.
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Received October 1, 2019;
in revised form February 4, 2020;
accepted March 16, 2020