Use of carborane carboxylic acids in the synthesis of boronated nitrogen heterocycles

Article abstract of DOI:10.1016/j.poly.2012.12.035

A novel series of 5-substituted carborane tetrazoles was synthesized by acylation of 5-phenyl-1-H-tetrazole with the available o- and m-carborane carboxylic acid chlorides or o- and m-carborane acetic acid chlorides in the presence of pyridine. Successive thermolysis of the carborane tetrazoles in toluene followed by the extrusion of nitrogen resulted in a series of previously unknown carborane 1,3,4-oxadiazoles in good yield. Using 2,4-dichloroaniline as an example we showed that carborane-substituted 1,3,4-oxadiazoles can be converted into the corresponding 1,2,4-triazoles.

Full text of DOI:10.1016/j.poly.2012.12.035

Polyhedron 51 (2013) 235–242
Contents lists available at SciVerse ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Use of carborane carboxylic acids in the synthesis of boronated
nitrogen heterocycles
a
a
a
Valentina Ol’shevskaya a, , Anton Makarenkov , Elena Kononova , Pavel Petrovskii ,
⇑
Mikhail Grigoriev b, Valery Kalinin a
a A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilova Str., Moscow 119991, Russia
b A.N. Frumkin Institute of Physical Chemistry and Electrochemistry of Russian Academy of Sciences, 31 Leninskii Pr., Moscow 199071, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel series of 5-substituted carborane tetrazoles was synthesized by acylation of 5-phenyl-1-H-tetra-
zole with the available o- and m-carborane carboxylic acid chlorides or o- and m-carborane acetic acid
chlorides in the presence of pyridine. Successive thermolysis of the carborane tetrazoles in toluene fol-
lowed by the extrusion of nitrogen resulted in a series of previously unknown carborane 1,3,4-oxadiaz-
oles in good yield. Using 2,4-dichloroaniline as an example we showed that carborane-substituted 1,3,4-
oxadiazoles can be converted into the corresponding 1,2,4-triazoles.
Received 7 November 2012
Accepted 27 December 2012
Available online 11 January 2013
Keywords:
Carborane
Heterocycles
Tetrazoles
Oxadiazoles
Triazoles
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
methyl-o-carborane and terminal alkynes [9]. Our promising re-
sults in the synthesis of carborane 1,2,3-triazole derivatives
Five-membered nitrogen heterocycles are under extensive
investigation due to their numerous applications in biomedicine
as antimicrobial, antiallergic, anticancer, cardiovascular and CNS
agents [1]. Also, these compounds are known to be used as antiox-
idants, inhibitors of corrosion, luminophores, agents for informa-
tion recording systems and in agriculture [2]. Among the
nitrogen heterocycles, tetrazole derivatives are of special interest
because they possess a plethora of biological activities [3]. These
compounds can act as metabolically stable analogues of carboxylic
or amide groups, ligands in coordination chemistry [4], high energy
compounds [5] and are important precursors for preparing other
nitrogen-containing heterocycles [6]. The strategy for constructing
the tetrazole ring is based on a very efficient azide–nitrile cycload-
dition reaction developed by Sharpless and co-workers [7]. This
synthetic approach emerged as a common route for the design of
new types of molecules, especially conjugates of different subunits
that yield a variety of hybrid compounds.
prompted us to prepare novel 5-substituted carborane 1H-tetra-
zoles via the 1,3-dipolar cycloaddition reaction of 1-azidomethyl-
o-carborane with organic nitriles. This reaction requires nitriles
that possess electron-withdrawing groups and proceeds at high
temperature [10]. The carborane derivatives of the tetrazole het-
erocycles and the methods of their preparation have been un-
known until present. Moreover, the conjugation of the carborane
polyhedron, a moiety with remarkable thermal and chemical sta-
bility, to the tetrazole moiety may result in the formation of new
high energy compounds. Surprisingly, despite the fact that several
reaction conditions for the generation of tetrazole-containing car-
boranes have been used [11], including microwave-assisted prepa-
ration, no reaction was observed for 1-azidomethyl-o-carborane 1
and nitriles.
We obtained tetrazole 2 only from tosyl cyanide, containing the
strong electron-withdrawing and easily leaving tosyl group, capa-
ble of being substituted by various nucleophiles. However, the
reaction of 2 with even a mild nucleophile, for example thiophenol,
led to the substitution of the tosyl group and deboronation of the
Derivatization of carboranes and other polyhedral boranes
especially with heterocycles, is an active area of research in organic
and organometallic chemistry [8]. We have recently reported the
possibility of using the methodology of 1,3-dipolar cycloaddition
(the ‘click’ reaction) to modify the closo-carborane polyhedron,
C2B10H12, with 1,2,3-triazole heterocycles starting from 1-azido-
À
carborane polyhedron to the nido-form, C2B9H12 (Scheme 1).
These modifications were proven by IR spectra where the bands
of the BH groups were downshifted from 2600 to 2560 cmÀ1
.
Failure of the [2+3]cycloaddition approach to prepare the
carborane tetrazoles forced us to consider alternative routes, in
particular the direct conjugation of the tetrazole fragment to the
carborane polyhedra. We took advantage of carborane carboxylic
⇑
Corresponding author. Tel.: +8 499 1357933; fax: +8 499 1355085.
E-mail address: olshevsk@ineos.ac.ru (V. Ol’shevskaya).
0277-5387/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2012.12.035

236
V. Ol’shevskaya et al. / Polyhedron 51 (2013) 235–242
Scheme 1. Synthesis of 2-[(o-carboran-1-yl)methyl]-5-tosyltetrazole 2.
acids as attractive starting materials amongst the functionalized
carboranes. These acids are easy to prepare, and a variety of struc-
tures is available [12].
CH), 2605 (BH), 1592, 1355, 1156 (SO2). 1H NMR (400 MHz, CDCl3)
d (ppm): 8.00 (d, J = 8.1 Hz, 2H, o-Ph), 7.49 (d, J = 8.1 Hz, 2H, m-Ph),
5.47 (s, 2H, CH2), 4.24 (brs, 1H, carborane CH), 2.52 (s, 3H, CH3),
3.45–1.39 (m, 10H, BH). 11B NMR (128 MHz, CDCl3) d (ppm): 0.83
(d, J = 153 Hz, 1B), À3.65 (d, J = 148 Hz, 1B), À9.04 (d, J = 154 Hz,
2B), À11.21 (d, 159 Hz, 2B), À12.46 (d, J = 170 Hz, 4B). Anal. Calc.
for C11H20B10N4O2S (380.5): C, 34.72; H, 5.30; B, 28.41; N, 14.73.
Found: C, 35.08; H, 5.42; B, 28.35; N, 14.65%.
2. Experimental
2.1. General information
All solvents were freshly distilled from the appropriate drying
agents before use. All other reagents were recrystallized or distilled
if necessary. The reactions were performed in an atmosphere of dry
argon. The starting compounds 1 [9], 4, 5 [12a], 8 [12b], 10, 11
[12c] and 12 [12d] were prepared according to the published pro-
cedures. The purity of the newly synthesized compounds was
tested by TLC on Sorbfil. Eluents: CHCl3–MeOH (20:1) for com-
pounds 4, 5, 11–13 and CHCl3 for 14–21. IR spectra were registered
on a Brucker FTIR spectrometer Tensor 37 in KBr tablets. UV-irra-
diation of compounds 6, 7, 13–15 was carried out with a high-pres-
sure mercury lamp (IMQ-21, 300 W). NMR spectra were recorded
on a Bruker Avance-400 spectrometer operating at 400 MHz for
2.4. General procedure for the preparation of tetrazoles (6, 7, 13–15)
To
a solution of corresponding carboranyl acid chloride
(5.2 mmol) in dry CH2Cl2 (8–10 mL), Py (0.42 mL, 5.3 mmol) was
added dropwise at À40 to À50 °C in argon atmosphere. Then tetra-
zole 3 (0.76 g, 5.2 mmol) was added to the reaction mixture with
extensive stirring. The resulting mixture was left at À20 to
À30 °C for ꢀ1 h and then stirred at room temperature for 6–8 h un-
til the corresponding carboranyl acid chloride disappeared (moni-
tored by TLC). After the completion of the reaction, water (30 mL)
was added to the reaction mixture, and the solution was extracted
with EtOAc (2 Â 10 mL). The organic phase was washed with
water, dried over anhydrous MgSO4 and evaporated in vacuo. The
obtained solids were washed with n-heptane to give the corre-
sponding carborane tetrazoles 6, 7, 13–15 in good yields.
1H (TMS), 128.28 MHz for 11B (BF3 OEt2). The solvent was CDCl3 ex-
.
cept where indicated otherwise.
2.2. X-ray crystallography
2.4.1. (m-Carboran-9-yl)(5-phenyltetrazol-2-yl)ketone (6)
X-ray diffraction experiments for compound 16 were carried
Yield: 1.4 g (85%). White powder. M.p. (decomp) 107–110 °C. IR
out on a Bruker KAPPA APEX II autodiffractometer (Mo K
a radia-
(KBr, cmÀ1
) mmax: 3029 (carborane CH), 2615 (BH), 1721 (C@O).
tion, k = 0.71073 Å, graphite monochromator) at 100(2) K [13].
Data reduction was made using SAINT-Plus program [14]. The struc-
ture was resolved by direct method SHELXS97 and refined on F2 with
the full-matrix least-squares procedure (SHELXL97) [15] using all
reflections. All non-hydrogen atoms, except a disordered N atom
with a lower occupation factor in the structure of 16, were refined
with anisotropic displacement factors. All H-atoms were located
from difference Fourier maps and refined isotropically with dis-
1H NMR (400 MHz, CD3OD) d (ppm): 8.01 (m, 2H, Ph), 7.58 (m,
3H, Ph), 3.62 (brs, 2H, carborane CH), 3.25–1.20 (m, 9H, BH). 11B
NMR (128 MHz, CD3OD) d (ppm):–6.80 (d, J = 163 Hz, 2B), À7.28
(s, 1B, B9), À10.21 (d, J = 151 Hz, 1B), À13.04 (d, J = 167 Hz, 2B),
À13.51 (d, J = 166 Hz, 2B), À16.89 (d, J = 182 Hz, 1B), À17.51 (d,
J = 182 Hz, 1B). Anal. Calc. for C10H16B10N4O (316.3): C, 37.96; H,
5.10; B, 34.17; N, 17.71. Found: C, 37.58; H, 5.21; B, 33.63; N
17.76%.
iso
placement factors equal to 1.2 Ueq of their parent B or C atoms
and without any constraints or restraints for H atoms of the water
molecule.
2.4.2. (o-Carboran-9-yl)(5-phenyltetrazol-2-yl)ketone (7)
Yield: 1.28 g (77%). White powder. M.p. (decomp) 109–111 °C.
2.3. 2-[(o-Carboran-1-yl)methyl]-5-tosyltetrazole (2)
IR (KBr, cmÀ1
) mmax: 3063 (carborane CH), 2603 (BH), 1723
(C = O). 1H NMR (400 MHz, CD3OD) d (ppm): 8.01 (m, 2H, Ph),
7.58 (m, 3H, Ph), 4.47 (brs, 2H, carborane CH), 3.00–1.20 (m, 9H,
BH). 11B NMR (128 MHz, CD3OD) d (ppm): À0.87 (s, 1B, B9),
À3.11 (d, J = 150 Hz, 1B), À9.47 (d, J = 151 Hz, 2B), À13.86 (d,
J = 155 Hz, 2B), À14.21 (d, J = 158 Hz, 2B), À14.99 (d, J = 164 Hz,
2B). Anal. Calc. for C10H16B10N4O (316.3): C; 37.96; H, 5.10; B,
34.17; N, 17.71. Found: C, 38.10; H, 4.92; B, 34.29; N, 17.87%.
A mixture of carborane azide 1 (1 g, 5.0 mmol) and p-toluene-
sulfonyl cyanide (1.81 g, 10 mmol) was stirred for 8 h at 100 °C
in the absence of solvent under argon. Removal of the excess of
p-toluenesulfonyl cyanide by sublimation in vacuo (0.5 mbar)
afforded tetrazole 2 in 95% yield. White powder. M.p. 163–165 °C
(from EtOAc/n-heptane). IR (KBr, cmÀ1
) mmax: 3067 (carborane

V. Ol’shevskaya et al. / Polyhedron 51 (2013) 235–242
237
2.4.3. [(m-Carboran-9-yl)methyl](5-phenyltetrazol-2-yl)ketone (13)
Yield: 1.49 g (87%). White powder. M.p. 79–81 °C. IR (KBr, cmÀ1
m
(400 MHz, CDCl3) d (ppm): 8.08 (dd, J1 = 7.4, J2 = 1.8 Hz, 2H, Ph),
7.49 (m, 3H, Ph), 3.12 (brs, 2H, carborane CH), 3.23–1.12 (m, 9H,
BH). 11B NMR (128 MHz, CDCl3) d (ppm): À6.2 (d, J = 166 Hz, 2B),
À8.12 (s, 1B, B9), À9.61 (d, J = 154 Hz, 1B), À12.75 (d, J = 169 Hz,
1B), À13.17 (d, J = 167 Hz, 3B), À16.87 (d, J = 183 Hz, 1B), À17.34
(d, J = 181 Hz, 1B). Anal. Calc. for C10H16B10N2O (288.4): C, 41.65;
H, 5.59; B, 37.49; N 9.71. Found: C, 41.87; H, 5.55; B, 37.28; N,
9.79%.
)
max: 3052 (carborane CH), 2605 (BH), 1767 (C = O). 1H NMR
(400 MHz, CDCl3) d (ppm): 8.27 (m, 2H, Ph), 7.51 (m, 3H, Ph),
3.19 (brs, 2H, carborane CH), 2.94 (s, 2H, CH2), 3.00–1.15 (m, 9H,
BH). 11B NMR (128 MHz, CDCl3) d (ppm): À3.35 (s, 1B, B9), À6.50
(d, J = 163 Hz, 2B), À10.05 (d, J = 150 Hz, 1B), À12.89 (d,
J = 162 Hz, 2B), À13.63 (d, J = 164 Hz, 2B), À17.05 (d, J = 182 Hz,
1B), À19.08 (d, J = 184 Hz, 1B). Anal. Calc. for C11H18B10N4O
(330.4): C, 39.99; H, 5.49; B, 32.72; N, 16.96. Found: C, 40.18; H,
5.54; B, 32.25; N, 16.64%.
2.5.2. 2-(o-Carboran-9-yl)-5-phenyl-1,3,4-oxadiazole (17)
Yield: A, B – 77%, C – 65%. White powder. M.p. 135–138 °C. IR
(KBr, cmÀ1 3054 (carborane CH), 2585 (BH). 1H NMR
) mmax:
2.4.4. [(o-Carboran-9-yl)methyl](5-phenyltetrazol-2-yl)ketone (14)
(400 MHz, CDCl3) d (ppm): 8.00 (dd, 2H, J1 = 7.2, J2 = 1.8 Hz, Ph),
7.44 (m, 3H, Ph), 4.04 (brs, 1H, carborane CH), 3.74 (brs, 1H, carbo-
rane CH), 3.34–1.18 (m, 9H, BH). 11B NMR (128 MHz, CDCl3) d
(ppm): À1.61 (s, 1B, B9), À2.54 (d, J = 161 Hz, 1B), À8.92 (d,
J = 151 Hz, 1B), À9.29 (d, J = 148 Hz, 1B), À14.03 (d, J = 179 Hz,
6B). Anal. Calc. for C10H16B10N2O (288.4): C, 41.65; H, 5.59; B,
37.49; N, 9.71. Found: C, 42.05; H, 5.77; B, 36.99; N, 9.83%.
Yield: 1.34 g (80%). White powder. M.p. 83–85 °C. IR (KBr, cmÀ1
)
m
max: 3052 (carborane CH), 2602 (BH), 1773 (C = O). 1H NMR
(400 MHz, CDCl3) d (ppm): 8.26 (m, 2H, Ph), 7.51 (m, 3H, Ph),
3.59 (brs, 1H, carborane CH), 3.53 (brs, 1H, carborane CH), 3.04
(brs, 2H, CH2), 3.00–1.20 (m, 9H, BH). 11B NMR (128 MHz, CDCl3)
d (ppm): 3.34 (s, 1B, B9), À2.37 (d, J = 146 Hz, 1B), À9.31 (d,
J = 149 Hz, 2B), À13.51 (d, J = 164 Hz, 2B), À14.09 (d, J = 159 Hz,
2B), À14.87 (d, J = 183 Hz, 2B). Anal. Calc. for C11H18B10N4O
(330.4): C, 39.99; H, 5.49; B, 32.72; N, 16.96. Found: C, 40.09; H,
5.34; B, 32.69; N, 17.03%.
2.5.3. 2-[(m-Carboran-9-yl)methyl]-5-phenyl-1,3,4-oxadiazole (18)
Yield: A, B, C – 78%. White powder. M.p. 110–112 °C. IR (KBr,
cmÀ1 max: 3044 (carborane CH), 2587 (BH). 1H NMR (400 MHz,
) m
CDCl3) d (ppm): 8.02 (dd, 2H, J1 = 7.3, J2 = 1.9 Hz, Ph), 7.47 (m,
3H, Ph), 2.67 (brs, 2H, carborane CH), 2.46 (brs, 2H, CH2), 3.08–
1.10 (m, 9H, BH). 11B NMR (128 MHz, CDCl3) d (ppm): À2,21 (s,
1B, B9), À6.21 (d, J = 163 Hz, 2B), À9.56 (d, J = 151 Hz, 1B),
À12.95 (d, J = 164 Hz, 2B), À13.60 (d, J = 166 Hz, 2B), À17.33 (d,
J = 181 Hz, 1B), À19.55 (d, J = 182 Hz, 1B). Anal. Calc. for C11H18B10-
N2O, (302.4): C, 43.69; H, 6.00; B, 35.75; N, 9.26. Found: C, 43.81; H
6.15; B, 35.47; N, 9.11%.
2.4.5. [(o-Carboran-1-yl)methyl](5-phenyltetrazol-2-yl)ketone (15)
Yield: 1.34 g (80%). White powder. M.p. 82–83 °C. IR (KBr, cmÀ1
)
m
max: 3032 (carborane CH), 2579 (BH), 1724 (C = O). 1H NMR
(400 MHz, Acetone-D6) d (ppm): 8.04 (m, 2H, Ph), 7.63 (m, 3H,
Ph), 4.97 (brs, 1H, carborane CH), 4.20 (s, 2H, CH2), 3.00–1.00 (m,
10H, BH). 11B NMR (128 MHz, acetone-D6) d (ppm): À2.45 (d,
J = 147 Hz, 1B), À5.42 (d, J = 149 Hz, 1B), À9.26 (d, J = 150 Hz, 2B),
À11.14 (d, J = 182 Hz, 2B), À11.78 (d, J = 177 Hz, 2B), À12.64 (d,
J = 175 Hz, 2B). Anal. Calc. for C11H18B10N4O (330.4): C, 39.99; H,
5.49; B, 32.72; N, 16.96. Found: C, 40.12; H, 5.58; B, 32.59; N,
16.58%.
2.5.4. 2-[(o-Carboran-9-yl)methyl]-5-phenyl-1,3,4-oxadiazole (19)
Yield: A, B– 70%, C – 60%. White powder. M.p. 113–114 °C. IR
(KBr, cmÀ1 3061 (carborane CH), 2581 (BH). 1H NMR
) mmax:
(400 MHz, CDCl3) d (ppm): 7.99 (dd, 2H, J1 = 7.3, J2 = 1.9 Hz, Ph),
7.46 (m, 3H, Ph), 3.65 (brs, 1H, carborane CH), 3.58 (brs, 1H, carbo-
rane CH) 2.49 (brs, 2H, CH2), 3.14–1.15 (m, 9H, BH). 11B NMR
(128 MHz, CDCl3) d (ppm): 4.98 (s, 1B, B9), À1.93 (d, J = 149 Hz,
1B), À8.72 (d, J = 162 Hz, 2B), À13.65 (d, J = 166 Hz, 2B), À14.01
(d, J = 159 Hz, 2B), À15.16 (d, J = 178 Hz, 2B). Anal. Calc. for C11H18-
B10N2O, (302.4): C, 43.69; H, 6.00; B, 35.75; N, 9.26. Found: C 43.87;
H, 6.18; B, 35.40; N, 9.10%.
2.5. General procedure for the preparation of carborane oxadiazoles
16–20
A. Rearrangement of tetrazoles under UV irradiation.
A solution of the corresponding tetrazol (6, 7, 13–15) (3 mmol)
in dry MeCN (10 mL) was UV-irradiated for 1–2 h. After the evap-
oration of the solvent in vacuo the residue was purified by column
chromatography on silica gel using CHCl3 as the eluent to give oxa-
diazoles 16–20 in 69–78% yield.
2.5.5. 2-[(o-Carboran-1-yl)methyl]-5-phenyl-1,3,4-oxadiazole (20)
Yield: A, B – 69%, C – 63%. White powder. M.p. 150–152 °C. IR
B. Thermolysis of tetrazoles 6, 7, 13–15 in toluene.
The tetrazoles 6, 7 or 13–15 (3 mmol) were boiled in toluene
(10 mL) for 3–5 h until the completion of the reaction (monitored
by TLC). After the evaporation of the solvent in vacuo the residue
was crystallized from n-heptane or purified by column chromatog-
raphy on silica gel (using CHCl3 as the eluent, compound 20) to
give oxadiazoles 16–20 in 60–78% yield.
C. One pot preparation of carborane 1,3,4-oxadiazoles (16–20).
To a stirred solution of the corresponding carboranyl acid chlo-
ride (4, 5, 10–12) (5.2 mmol) in toluene (10 mL) dry pyridine
(0.62 mL, 7.8 mmol) was added at À40 °C under an argon atmo-
sphere. To this mixture tetrazol 3 (0.76 g, 5.2 mmol) was added,
and stirring was continued at room temperature for 1 h and then
the resulting mixture was boiled for 3–5 h. After the evaporation
of the solvent in vacuo the crude product was purified by column
chromatography on silica gel using CHCl3 as the eluent to give oxa-
diazoles 16–20 in 60–78% yield.
(KBr, cmÀ1 3031 (carborane CH), 2581 (BH). 1H NMR
) mmax:
(400 MHz, CDCl3) d (ppm): 8.04 (m, 2H, Ph), 7.63 (m, 3H, Ph),
4.02 (brs, 1H, carborane CH), 3.91 (s, 2H, CH2), 3.00–1.00 (m,
10H, BH). 11B NMR (128 MHz, CDCl3)
d
(ppm): À1.43 (d,
J = 150 Hz, 1B), À4.89 (d, J = 143 Hz, 1B), À8.96 (d, J = 153 Hz, 3B),
À10.95 (d, J = 174 Hz, 2B), À11.97 (d, J = 174 Hz, 1B), À12.49 (d,
J = 181 Hz, 2B). Anal. Calc. for C11H18B10N2O, (302.4): C, 43.69; H,
6.00; B, 35.75; N, 9.26. Found: C, 43.80; H, 6.08; B, 35.59; N, 9.19%.
2.6. General procedure for the preparation of carborane 1,2,4-triazoles
(21–23)
A mixture of corresponding carborane oxadiazole (18–20)
(3 mmol), 2,4-dichloroaniline (15 mmol) and p-toluenesulfonic
acid monohydrate (0.3 mmol) was stirred for 5–10 h at 140–
170 °C under argon atmosphere. The reaction mixture was cooled
to room temperature and the crude product was purified by col-
umn chromatography on silica gel using CH2Cl2 as the eluent to
give the carborane 1,2,4-triazoles in 65–80% yield.
2.5.1. 2-(m-Carboran-9-yl)-5-phenyl-1,3,4-oxadiazole (16)
Yield: A, B – 76%, C – 72%. White powder. M.p. 128–130 °C. IR
(KBr, cmÀ1 3038 (carborane CH), 2609 (BH). 1H NMR
) mmax:

238
V. Ol’shevskaya et al. / Polyhedron 51 (2013) 235–242
Scheme 2. Synthesis of carborane tetrazoles 6, 7.
carborane CH), 2.42 (d, J = 15.0 Hz, 1H, CHH), 1.94 (d, J = 15.0 Hz,
1H, CHH), 3.19–1.58 (m, 9H, BH). 11B NMR (128 MHz, CDCl3) d
(ppm): 5.58 (s, 1B, B9), À2.21 (d, J = 147 Hz, 1B), À8.88 (d,
J = 149 Hz, 2B), À13.58 (d, J = 164 Hz, 2B), À14.29 (d, J = 167 Hz,
2B), À15.14 (d, J = 182 Hz, 2B). Anal. Calc. for C17H21B10Cl2N3,
(446.4): C, 45.74; H, 4.74; B, 24.22; N, 9.41. Found: C, 45.48; H,
4.81; B, 23.89; N, 9.39%.
Scheme 3. Attempts to prepare carborane tetrazole 9.
2.6.2. 3-[(o-Carboran-1-yl)methyl]-4-(2,4-dichlorophenyl)-5-phenyl-
1,2,4-triazole (22)
Yield: 0.97 g (73%). White powder. M.p. 163–164 °C. IR (KBr,
cmÀ1 max: 3043 (carborane CH), 2587 (BH), 1489 (Ph). 1H NMR
) m
(400 MHz, CDCl3) d (ppm): 7.64 (d, J = 2.1 Hz, 1H, H3 in C6H3Cl2),
7.45 (m, 1H, Ph), 7.43–7.20 (m, 6H,), 4.68 (brs, 1H, carborane CH),
3.74 (d, J = 16.2 Hz, 1H, CHH), 3.42 (d, J = 16.2 Hz, 1H, CHH), 3.04–
1.50 (m, 10H, BH). 11B NMR (128 MHz, CDCl3) d (ppm): À1.77 (d,
J = 154 Hz, 1B), À5.01 (d, J = 149 Hz, 1B), À9.11 (d, J = 152 Hz, 2B),
À9.87 (d, J = 144 Hz, 2B), À11.12 (d, J = 176 Hz, 1B), À12.57 (d,
J = 173 Hz, 3B). Anal. Calc. for C17H21B10Cl2N3, (446.4): C, 45.74; H,
4.74; B, 24.22; N, 9.41. Found: C, 45.59; H, 4.65; B, 23.97; N, 9.38%.
2.6.3. 3-[(o-Carboran-9-yl)methyl]-4-(2,4-dichlorophenyl)-5-phenyl-
1,2,4-triazole (23)
Yield: 1.0 g (80%). White powder. M.p. 158–160 °C. IR (KBr,
cmÀ1 max: 3045 (carborane CH), 2600 (BH), 1488 (Ph). 1H NMR
) m
(400 MHz, CDCl3) d (ppm): 7.59 (d, J = 2.1 Hz, 1H, H3 in C6H3Cl2),
7.40–7.23 (m, 7H, Ph), 2.90 (brs, 2H, carborane CH), 2.58 (d,
J = 15.4 Hz, 1H, CHH), 2.14 (d, J = 15.4 Hz, 1H, CHH), 3.09–1.49
(m, 9H, BH). 11B NMR (128 MHz, CDCl3) d (ppm): À1.71 (s, 1B,
B9), À6.35 (d, J = 161 Hz, 2B), À9.88 (d, J = 150 Hz, 1B), À12.93 (d,
J = 164 Hz, 2B), À13.85 (d, J = 163 Hz, 2B), À17.41 (d, J = 181 Hz,
1B), À19.67 (d, J = 189 Hz, 1B). Anal. Calc. for C17H21B10Cl2N3,
(446.4): C, 45.74; H, 4.74; B, 24.22; N, 9.41 Found: C, 45.64; H,
4.79; B, 23.99; N, 9.35%.
Scheme 4. Synthesis of tetrazoles 13–15 based on carborane acetic acid chlorides.
2.6.1. 3-[(o-Carboran-9-yl)methyl]-4-(2,4-dichlorophenyl)-5-phenyl-
1,2,4-triazole (21)
Yield: 0.87 g (65%). White powder. M.p. 168–170 °C. IR (KBr,
cmÀ1 max: 3060 (carborane CH), 2587 (BH), 1490 (Ph). 1H NMR
) m
(400 MHz, CDCl3) d (ppm): 7.54 (d, J = 2.2 Hz, 1H, H3 in C6H3Cl2),
7.36–7.18 (m, 7H, Ph), 3.66 (brs, 1H, carborane CH), 3.56 (brs, 1H,
Scheme 5. Synthesis of carborane-substituted 1,3,4-oxadiazoles 16, 17.

V. Ol’shevskaya et al. / Polyhedron 51 (2013) 235–242
239
Scheme 6. Synthesis of carborane-substituted 1,3,4-oxadiazoles 18–20.
Scheme 7. Transformations of 1,3,4-oxadiazoles into 1,2,4-triazoles under the action of amines.
thionyl chloride [12]) afforded carborane tetrazoles (6, 7) in 70–
75% yield. The acylation reaction was carried out at room
temperature for 1–5 h in dry CH2Cl2 in the presence of a base, that
is Et3N or pyridine. The best results were obtained with the latter
agent, presumably due to better solubility of tetrazole 3 in pyri-
dine. At room temperature an undesired conversion of the closo-
carborane polyhedron into the nido-form, C2B9H12À, is prevented
(Scheme 2).
3. Results and discussion
3.1. Synthesis
Direct acylation of the tetrazole ring in the commercially avail-
able 5-phenyl-1H-tetrazole (3) with carborane carboxylic acid
chlorides (4, 5) (the latter compounds can be readily prepared from
the corresponding 9-o- and 9-m-carborane carboxylic acids and
Scheme 8. Synthesis of carborane 1,2,4-triazoles 21–23.

240
V. Ol’shevskaya et al. / Polyhedron 51 (2013) 235–242
Table 1
The same procedure starting from the tetrazoles 13–15 yielded
Crystal data and structure refinement details of 16.
the carborane oxadiazoles 18–20 with a methylene spacer be-
tween the boron atom of the polyhedron and the oxadiazole het-
erocycle (Scheme 6).
Formula
C10H17B10N2O1.5
297.36
Mr (g molÀ1
)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
monoclinic
P21/n
6.9245(13)
23.626(6)
19.153(4)
90.00
97.514(8)
90.00
3106.49
8
Oxadiazoles 16–20 can be prepared by a one-pot synthesis of
the carborane acid chlorides 4, 5, 10–12 with tetrazole 3 in reflux-
ing toluene without isolation of the pre-generated tetrazoles. How-
ever, owing to the presence of pyridine in the reaction mixture, the
yields decreased for the o-carborane derivatives due to partial deb-
oronation of the closo-carborane cluster into the nido-analogue,
C2B9H12À. The process of deboronation was not observed with UV
irradiation.
a
(°)
b (°)
c
(°)
V (Å3)
Z
T (K)
k (Mo K
100(2)
0.71073
1.272
The 1,3,4-oxadiazoles are known to react with nucleophiles. For
functionalization of the carborane polyhedron, amines seem to be
the most interesting because they allow new classes of heterocy-
clic compounds to be obtained. We studied nucleophilic substitu-
tions at the carbon atom in the oxadiazole ring of compounds
18–20 under the action of aromatic amines. In these reactions
the formation of 1,2,4-triazole is the most probable, including car-
borane derivatives (Scheme 7) [19].
Amines that can be used to prepare carborane 1,2,4-triazoles
are limited. This reaction can be convenient only for amines with
a decreased nucleophilicity of the amino group to avoid deborona-
tion of the carborane polyhedron. Heating of oxadiazoles 18–20
(containing the methylene spacer between the carborane polyhe-
dron and the oxadiazole moiety) with 2,4-dichloroaniline at 150–
160 °C in the presence of TsOH resulted in carborane 1,2,4-tria-
zoles 21–23 in good yield (Scheme 8).
a
) (Å)
)
qcalc (g cmÀ3
l
(mmÀ1
)
0.072
Crystal size
h Range (°)
Index range
0.30 Â 0.04 Â 0.03
4.13–25.00
À8 6 h 6 5
À28 6 k 6 28
À22 6 l 6 22
18330
5172
2471
0.957
0.1791, 0.1230
0.0670, 0.0954
Reflections collected
Independent reflections
Observed reflections
GOOF (S)
R1, wR2 (all)
R1, wR2 [I > 2r(I)]
Interestingly, acid chloride 8, containing a COCl group at the
carbon atom of the carborane polyhedron, did not interact with
tetrazole 3 (Scheme 3).
In similar reaction with carborane oxadiazoles 16, 17, without
the methylene spacer, the expected 1,2,4-triazoles were not ob-
tained; instead, a mixture of side products was detectable. This
can be associated with the strong electron donor effect of the
Following the same protocol the acid chlorides (10–12), ob-
tained from corresponding carborane acetic acids [12], were suc-
cessfully transformed into the corresponding tetrazoles (13–15)
in good yield by the reaction with tetrazole 3 in CH2Cl2 (Scheme 4).
The tetrazoles 6, 7, 13–15 are stable and can be purified on a sil-
ica gel column with CH2Cl2 as an eluent in high yield. These com-
pounds can be considered as key intermediates for the preparation
of 2,5-disubstituted 1,3,4-oxadiazoles, which are important for
biomedical purposes [16,17]. Furthermore, 2,5-diaryl-1,3,4-oxadi-
azoles are excellent electron-transporting units and might be
promising as optoelectronic materials [17].
We found that UV irradiation (40 °C) or thermolysis in refluxing
toluene of tetrazoles 6, 7 provided the corresponding 2,5-disubsti-
tuted-1,3,4-oxadiazoles in a very clean and efficient manner via the
extrusion of nitrogen and formation of 1,5-dipole (nitrileimine)
[18]. This agent underwent cyclization to form the desired carbo-
rane-substituted oxadiazoles 16, 17 in which the oxadiazole het-
erocycle is bound to the boron atom of the polyhedron (Scheme 5).
9-o-(
r
i = À0.23) and 9-m-carboranyl groups ( i = À0.12) [20]. In
r
turn, these groups increased the electron density on the oxadiaz-
ole carbon atoms and decreased their reactivity towards the
amines.
3.2. Spectroscopic data
The structures of all the newly synthesized compounds were
confirmed by IR, 1H and 11B NMR spectra, and elemental analysis.
All the compounds showed an intensive absorption band in the
infrared spectrum at 2581–2615 cmÀ1 assigned to the stretching
vibration of the BH-groups in the closo-polyhedron. A band at
3029–3062 cmÀ1 indicated the presence of a carborane CH-group.
For the tetrazoles 6, 7, 13–15, a band corresponding to the dis-
placement of the C@O group was observed at 1720–1770 cmÀ1
The 1H NMR spectra of tetrazoles 6, 7, 13–15 showed the signals
.
Fig. 1. Displacement ellipsoid plot (50%) of 16. The hydrogen atoms are included but unlabelled for clarity. The dashed lines indicate hydrogen bonding.

V. Ol’shevskaya et al. / Polyhedron 51 (2013) 235–242
241
Table 2
er electron-withdrawal effect of the oxadiazole ring compared to
the tetrazole system. The 1H NMR spectra of triazoles 21–23
showed the existence of phenyl protons as a multiplet in the range
d = 7.64–7.21 ppm. In addition, the 3-H proton of the 2,4-dichloro-
phenyl substituent exhibited a doublet signal with a coupling con-
stant of 2.0 Hz. The protons of the carborane CH-groups appeared
at d = 4.62–2.91 ppm. Unlike oxadiazoles 18–20, the protons of
the methylene group of 21–23 were observed as two doublets,
indicating their magnetic non-equivalence.
Hydrogen bonds observed for 16.
D–H. . .
A
d(D–H) (Å) d(HÁ Á ÁA) (Å) d(DÁ Á ÁA) (Å) (D–HÁ Á ÁA) (°)
O(1w)–H(1wb)Á Á ÁN(2a) 0.86(6)
O(1w)–H(1wa) Á Á ÁN(2b) 1.07(6)
2.13(6)
1.94(6)
2.967(5)
2.998(4)
164(5)
167(4)
Table 3
Values of the torsion angles.
1–2–3–4
Torsion
3.3. X-ray crystallography
B(3b)–B(1b)–C(3b)–N(1b)
B(3a)–B(1a)–C(3a)–N(1a)
C(6a)–C(5a)–C(4a)–N(2a)
C(6b)–C(5b)–C(4b)–N(2b)
À147.6(4)
À153.0(4)
À1.3(6)
The structure of oxadiazole 16 was confirmed by an X-ray struc-
ture determination at 100 K and was refined satisfactory. Single
crystals of 16 suitable for X-ray diffraction measurements were ob-
tained from toluene by slow evaporation at room temperature as
colorless needles. The crystallographic data of compound 16 are
shown in Table 1.
In the crystal structure two crystallographically independent
molecules of 16 are linked with one molecule of water by hydrogen
bonds, via the N(2) atoms of the oxadiazoles (Fig. 1).
Both bonds show DÁ Á ÁA distances significantly below the sum of
the van der Waals radii (rw(N) + rw(O) = 3.07 Å) [21] at 2.967(5) and
2.998(4) Å, therefore representing moderately strong hydrogen
bonds (Table 2).
In two molecules of 16 linked by water, the planes of the oxadi-
azole rings are differently oriented relatively to the phenyl group
and the carborane polyhedron. This can be illustrated by different
values of the torsion angles (Table 3).
The oxadiazole 16 crystallized in the monoclinic space group
P21/n with a cell volume of 3106.49 Å3 and eight molecular
moieties in the unit cell (Fig. 2).
À16.5(6)
of o-protons of the phenyl group in the range d = 8.00–8.25 ppm,
and the signals of m- and p-protons appeared in the range
d = 7.49–7.61 ppm. The signals of the carborane CH protons in 6,
7, 13–15 were observed at d = 3.52–5.01 ppm. In the 1H NMR spec-
tra of compounds 13 and 14, the protons of the methylene group
showed a broadened singlet resonance at d = 2.78–3.12 ppm that
determined a spin-spin interaction of these protons with the boron
atom of the polyhedron. In contrast, compound 15, containing the
methylene group at the carbon atom of the polyhedron, demon-
strated a narrow singlet. Transformation of tetrazoles 6, 7, 13–15
into the corresponding oxadiazoles 16–20 did not alter the posi-
tions of the phenyl protons. However, the proton signals of the car-
borane CH-groups moved upfield for 16–19 (0.5 ppm) and 20
(1.0 ppm). An upfield effect (0.5 ppm) was also observed for the
methylene protons (compounds 18 and 19), while for 20 the up-
field shift was only 0.3 ppm. Such a shift can be explained by a low-
Fig. 2. Presentation of the unit cell and the packing of compound 16 (ellipsoids set at 60% probability). Dashed lines indicate hydrogen bonding.

242
V. Ol’shevskaya et al. / Polyhedron 51 (2013) 235–242
(d) J. Zabrocki, G.D. Smith, J.B. Dunbar, H. Iijima, G.R. Marshall, J. Am. Chem.
4. Conclusions
Soc. 110 (1988) 5875.
[6] (a) Tetrazoles: R.N. Butler, in: A.R. Katritzky, C.W. Rees, E.F.V. Scriven (Eds.),
Comprehensive Heterocyclic Chemistry, vol. 5, Pergamon Press, Oxford, UK,
1984, pp. 791–843.;
We developed the synthesis of novel nitrogen-containing het-
erocyclic compounds with o- and m-carborane clusters starting
from the available carborane carboxylic acid chlorides, carboranyl-
acetic acid chlorides and 5-phenyl-1H-tetrazole. The carborane tet-
razoles formed in these reactions were subsequently transformed
under UV irradiation or thermolysis into the corresponding 1,3,4-
oxadiazole derivatives. Under the action of amines, the oxadiazoles
with carboranylmethyl substituents were converted to 1,2,4-tria-
zoles in high yield. Importantly, in the new compounds the hetero-
cyclic units are bound directly to the boron atom of the polyhedron
or separated from the carborane polyhedron by a methylene spacer
group. The suggested synthetic procedures allowed the avoidance
of deboronation of the nucleophile-sensitive closo-carborane
polyhedron.
(b) Yu.A. Efimova, T.V. Artamonova, G.I. Koldobskii, Russ. J. Org. Chem. 44
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(c) W. Song, Y. Wang, J. Qu, Q. Lin, J. Am. Chem. Soc. 130 (2008) 9654;
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[7] (a) Z.P. Demko, K.B. Sharpless, J. Org. Chem. 66 (2001) 7945;
(b) Z.P. Demko, K.B. Sharpless, Org. Lett. 4 (2002) 2525;
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(b) R.N. Grimes, Carborane Second Edition, Elsevier, New York/Oxford, 2011.
[9] (a) V.A. Ol’shevskaya, A.V. Makarenkov, E.G. Kononova, P.V. Petrovskii, E.V.
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(b) V.A. Ol’shevskaya, A.V. Makarenkov, E.G. Kononova, P.V. Petrovskii, E.V.
Verbitskiy, G.L. Rusinov, V.N. Charushin, E. Hey-Hawkins, V.N. Kalinin,
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Appendix A. Supplementary material
[10] (a) H. Zhao, Z.-R. Qu, H.-Y. Ye, R.-G. Xiong, Chem. Soc. Rev. 37 (2008) 84–100;
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[11] (a) Z.P. Demko, K.B. Sharpless, J. Org. Chem. 66 (2001) 7945–7950;
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CCDC 901027 contains supplementary crystallographic data for
16. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/con-
ts/retrieving.html, or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223336033, or e-mail: deposit@ccdc.cam.ac.uk.
(c) B. Das, C.R. Reddy, D.N. Kumar, M. Krishnaiah, R. Narender, Synlett (2010)
391–394;
(d) J. Roh, T.V. Artamonova, K. Vavrova, G.I. Koldobskii, A. Hrabalec, Synthesis
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