Novel bis[(1,2,3-triazolyl)methyl]carborane derivatives via regiospecific copper-catalyzed 1,3-dipolar cycloaddition

Article abstract of DOI:10.1016/j.poly.2012.05.036

1,2-Bis(azidomethyl) - carborane and 1,7-bis(azidomethyl)-m-carborane, prepared from the corresponding carboranylmethyl triflates and sodium azide, were conveniently functionalized by azide-alkyne cycloaddition affording novel bis[(1,2,3-triazolyl)methyl]

Full text of DOI:10.1016/j.poly.2012.05.036

Polyhedron 42 (2012) 302–306
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Polyhedron
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Novel bis[(1,2,3-triazolyl)methyl]carborane derivatives via regiospecific
copper-catalyzed 1,3-dipolar cycloaddition
a
a
a
Valentina A. Ol’shevskaya a, , Anton V. Makarenkov , Elena G. Kononova , Pavel V. Petrovskii ,
Egor V. Verbitskiy b, Gennady L. Rusinov b, Valery N. Charushin b, Evamarie Hey-Hawkins c,
Valery N. Kalinin a
⇑
a A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilova Str., Moscow 119991, Russia
b Postovsky Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences, ul. Kovalevskoi 22/20, Yekaterinburg 620041, Russia
c Universität Leipzig, Institut für Anorganische Chemie, Johannisallee 29, 04103 Leipzig, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
1,2-Bis(azidomethyl)-o-carborane and 1,7-bis(azidomethyl)-m-carborane, prepared from the corre-
sponding carboranylmethyl triflates and sodium azide, were conveniently functionalized by azide–alkyne
cycloaddition affording novel bis[(1,2,3-triazolyl)methyl]carborane derivatives. Regiospecificity of this
process was achieved by employing copper(II) acetate hydrate. Reaction of bis[(1,2,3-triazolyl)methyl]
carborane derivatives with MeI yielded 3-methyl-1,2,3-triazolium carborane salts.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 9 April 2012
Accepted 30 May 2012
Available online 9 June 2012
Keywords:
Carboranes
Carbaboranes
Triflates
Azides
Cycloaddition
1,2,3-Triazole carboranes
1. Introduction
rane polyhedra. Preparative routes to carborane heterocycles
include cross-coupling of iodocarboranes with appropriate deriva-
1,3-Dipolar cycloaddition reactions of organic azides with al-
kynes in the presence of copper(I) are important for the synthesis
of polynitrogen-containing heterocyclic compounds. This regiose-
lective reaction produces 1,4-disubstituted 1,2,3-triazoles in high
yields [1]. It employs stable and readily available chemical reagents
(azides and alkynes) that react rapidly at ambient temperature, tol-
erates a wide range of functional groups, including unprotected
alcohols, carboxylic acids, and amines, and shows little sensitivity
to steric factors [2]. A great number of compounds containing
1,2,3-triazole moieties are reported to show a broad spectrum of
biological activities, including fungicidal, antimicrobial, anticonvul-
sant, analgesic, and antitumor behavior [3]. Furthermore, a number
of 1,2,3-triazole derivatives have found wide use as agrochemicals
[4], polymers [5], and high-energy materials [6].
We recently reported the possibility of using a 1,3-dipolar cyclo-
addition (click reaction) to modify the closo-carborane polyhedron
with 1,2,3-triazole heterocycles [7]. Such a reaction is of particular
value, because in the family of icosahedral carboranes the heterocy-
clic derivatives are the least available. All methods reported are
based on direct introduction of heterocyclic fragments into carbo-
tives of heterocyclic compounds [8], nucleophilic displacement of
a halogen atom in heterocycles with carborane copper derivatives
[9], or the addition of carboranyllithium to highly electrophilic het-
erocycles followed by dehydrogenation of intermediates [10].
These methods have a number of synthetic restrictions imposed
by the sensitivity of carborane polyhedra toward bases [11] and
the availability of the corresponding heterocyclic component.
2. Experimental
2.1. General information
All solvents used in reactions were freshly distilled from appro-
priate drying agents before use. All other reagents were recrystal-
lized or distilled as necessary. Reactions were performed under an
atmosphere of dry argon. The purity of newly synthesized com-
pounds was checked by TLC on Sorbfil. Eluents: n-heptane/ethyl
acetate (15:1) for compounds 1–4 and dichloromethane for com-
pounds 6a–c and 7a–f. IR spectra were measured on a UR-20 spec-
trometer in KBr tablets. NMR spectra were recorded on a Bruker
Avance-400 spectrometer operating at 400 MHz for 1H (TMS),
128.28 MHz for 11B (BF3ꢀOEt2), and 376.5 MHz for 19F (BF3ꢀOEt2).
The solvent was deuterochloroform except where indicated
⇑
Corresponding author. Tel.: +7 499 1357933; fax: +7 095 1356549.
E-mail address: olshevsk@ineos.ac.ru (V.A. Ol’shevskaya).
0277-5387/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2012.05.036

V.A. Ol’shevskaya et al. / Polyhedron 42 (2012) 302–306
303
otherwise. The synthesis of triflate 3 was carried out according to
a known method [12]. Analytically pure samples of the compounds
were obtained by recrystallization from ethyl acetate/n-heptane
(1:5) and further drying in vacuum at room temperature.
solved in ethyl acetate (10 mL) and washed with water (25 mL).
The organic layer was dried over MgSO4 and evaporated. The
solvent was removed in vacuo and the residue purified by crystal-
lization from ethyl acetate/n-heptane.
2.5.1. 1,2-Bis[(40-acetoxymethyl-10,20,30-triazol-10-yl)methyl]-o-
2.2. Synthesis of 1,2-bis(azidomethyl)-o-carborane (1)
carborane (6a)
Yield: 28%. Colorless oil. IR (KBr, cmꢂ1
)
m
max: 2587 (BH) 1732
NaN3 (2.73 g, 42 mmol) was added to a solution of triflate 3 (1 g,
2.14 mmol) in acetone (10 mL) under argon atmosphere with vig-
orous stirring, and the reaction mixture was heated to reflux for
20 h. Then the reaction mixture was poured into water (50 mL)
and extracted with ethyl acetate (3 ꢁ 30 mL). The combined organ-
ic extracts were washed with water (3 ꢁ 10 mL) and dried over
anhydrous MgSO4, and the solvent removed in vacuo to give diaz-
ide 1. Yield: 0.29 g (55%). Yellow oil. IR (KBr, cmꢂ1
) mmax: 2585 (BH),
~
~
(C@O). 1H NMR (400 MHz, CDCl3): d 7.81 (s, 2H, @CH–N), 5.19 (s,
4H, C–CH2–N), 3.64 (s, 4H, C–CH2–O), 1.87 (s, 6H, CH3), 3.00–1.00
(m, 10H, BH). 11B (128.3 MHz, CDCl3): d ꢂ3.6 (d, 2B, J = 162 Hz),
ꢂ11.0 (d, 6B, J = 175 Hz), ꢂ11.7 (d, 2B, J = 174 Hz). Anal. Calc. for
C14H26B10N6O4 (450.5): C, 37.32; H, 5.82; B, 24.00; N, 18.65. Found:
C, 37.38; H, 6.01; B, 23.99; N, 18.16%.
2110 (N3). 1H NMR (400 MHz, CDCl3): d 4.04 (s, 4H, CH2), 3.50–1.50
(m, 10H, BH), 11B NMR (128.3 MHz, CDCl3): d ꢂ3.5 (d, 2B,
J = 150 Hz), ꢂ10.9 (d, 8B, J = 154 Hz). Anal. Calc. for C4H14B10N6
(254.3): C, 18.89; H, 5.55; B, 42.50; N, 33.05. Found: C, 19.05; H,
5.72; B, 41.85; N, 32.94%.
2.5.2. 1,2-Bis[(40-phenyl-10,20,30-triazol-10-yl)methyl]-o-carborane
(6b)
Yield: 32%. White powder. M.p. 175–176 °C (from AcOEt/n-hep-
tane). IR (KBr, cmꢂ1
)
max: 2590 (BH). 1H NMR (400 MHz, CDCl3): d
~
m
7.82 (m, 4H, o-Ph), 7.43 (m, 6H, m-Ph, p-Ph), 7.37 (s, 2H, @CH–N),
4.21 (s, 4H, CH2), 3.5–1.5 (m, 10H, BH). 11B NMR (128.3 MHz,
CDCl3): d ꢂ3.5 (d, 2B, J = 149 Hz), ꢂ11.0 (d, 8B, J = 150 Hz). Anal.
Calc. for C20H26B10N6 (458.6): C, 52.38; H, 5.71; B, 23.58; N,
18.33. Found: C, 52.44; H, 5.75; B, 23.43; N, 18.10%.
2.3. Synthesis of 1,7-bis(azidomethyl)-m-carborane (2)
NaN3 (1.37 g, 21.0 mmol) was added to a solution of triflate 4
(1 g, 2.14 mmol) in dry DMSO (10 mL) under argon atmosphere
with vigorous stirring. The resulting mixture was stirred for 3 h
at room temperature before being poured into water (50 mL) and
extracted with AcOEt (3 ꢁ 30 mL). The combined organic extracts
were washed with water (50 mL) and then dried over anhydrous
MgSO4, and the solvent was removed in vacuo to give diazide 2.
~
2.5.3. 1,2-Bis[(40-trimethylsilyl-10,20,30-triazol-10-yl)methyl]-o-carbo-
rane (6c)
Yield: 35%. White powder. M.p. 168–171 °C (from AcOEt/n-hep-
tane). IR (KBr, cmꢂ1
)
max: 2592 (BH), 842 (Si(CH3)3). 1H NMR
~
m
(400 MHz, CDCl3): d 7.72 (s, 2H, @CH–N), 4.23 (s, 4H, CH2), 3.00–
1.00 (m, 10H, BH), 0.33 (s, 18H, Si(CH3)3). 11B NMR (128.3 MHz,
CDCl3): d ꢂ3.4 (d, 2B, J = 145 Hz), ꢂ10.9 (d, 6B, J = 164 Hz), ꢂ11.4
(d, 2B, J = 157 Hz). Anal. Calc. for C14H34B10N6Si2 (450.7): C, 37.31;
H, 7.60; B, 23.98; N, 18.64; Si, 12.46. Found: C, 37.37; H, 7.62; B,
24.12; N, 18.74; Si, 12.53%.
Yield: 0.46 g (85%). Yellow oil. IR (KBr, cmꢂ1
) mmax: 2606 (BH),
2107 (N3). 1H NMR (400 MHz, CDCl3): d 3.55 (s, 4H, CH2), 1.4–3.2
(m, 10H, BH). 11B NMR (128.3 MHz, CDCl3): d ꢂ6.6 (d, 2B,
J = 163 Hz), ꢂ10.5 (d, 2B, J = 150 Hz), ꢂ11.4 (d, 4B, J = 158 Hz),
ꢂ14.5 (d, 2B, J = 180 Hz). Anal. Calc. for C4H14B10N6 (254.3): C,
18.89; H, 5.55; B, 42.50; N, 33.05. Found: C, 19.00; H, 5.61; B,
42.05; N, 32.95%.
2.5.4. 1,7-Bis[(40-acetoxymethyl-10,20,30-triazol-10-yl)methyl]-m-car-
borane (7a)
2.4. Synthesis of 1,7-bis(trifluormethanesulfonylmethyl)-m-carborane
(4)
Yield: 87%. Colorless oil. IR (KBr, cmꢂ1
)
m
max: 2590 (BH) 1733
~
(C@O). 1H NMR (400 MHz, CDCl3): d 7.56 (s, 2H, @CH–N); 5.15 (s,
4H, C–CH2–N); 4.68 (s, 4H, C–CH2–O), 2.03 (s, 6H, CH3). 11B
(128.3 MHz, CDCl3): d ꢂ6.4 (d, 2B, J = 154 Hz), ꢂ10.1 (d, 2B,
J = 147 Hz), ꢂ11.2 (d, 4B, J = 156 Hz), ꢂ14.3 (d, 2B, J = 172 Hz). Anal.
Calc. for C14H26B10N6O4 (450.5): C, 37.32; H, 5.82; B, 24.00; N,
18.65. Found: C, 37.35; H, 5.99; B, 24.05; N, 18.18%.
Trifluoromethanesulfonic anhydride (8.5 ml, 13.6 g, 51 mmol)
in dry dichloromethane (10 mL) and dry pyridine (4.2 ml,
51 mmol) was added to a solution of 1,7-bis(hydroxymethyl)-m-
carborane (10 g, 48.8 mmol) in dry dichloromethane (20 mL)
under argon atmosphere and the result mixture was stirred for 2
h at r.t. Then the reaction mixture was poured into water
(50 mL) and extracted with dichloromethane (3 ꢁ 30 mL). The
combined organic extracts were washed with water (3 ꢁ 10 mL)
and dried over anhydrous MgSO4, and the solvent was removed
in vacuo to give 4. Yield: 21.1 g (92%). Colorless oil, IR (KBr,
~
2.5.5. 1,7-Bis[(40-phenyl-10,20,30-triazol-10-yl)methyl]-m-carborane
(7b)
Yield: 90%. White powder. M.p. 170–172 °C (from AcOEt/n-hep-
tane). IR (KBr, cmꢂ1
)
m
max: 2590 (BH). 1H NMR (400 MHz, CDCl3): d
~
cmꢂ1 max: 2590 (BH). 1H NMR (400 MHz, CDCl3): d 4.54 (s, 4H,
) m
7.79 (m, 4H, o-Ph), 7.68 (s, 2H, @CH–N), 7.41 (m, 4H, m-Ph), 7.34
(m, 2H, p-Ph), 4.72 (s, 4H, C–CH2–N), 1.5–3.5 (m, 10H, BH). 11B
NMR (128.3 MHz, CDCl3): d ꢂ6.4 (d, 2B, J = 108 Hz), ꢂ10.1 (d, 2B,
J = 149 Hz), ꢂ11.2 (d, 4B, J = 146 Hz), ꢂ14.3 (d, 2B, J = 172 Hz). Anal.
Calc. for C20H26B10N6 (458.5): C, 52.38; H, 5.71; B, 23.58; N, 18.33.
Found: C, 52.32; H, 5.71; B, 23.55; N, 18.12%.
CH2), 3.50–1.50 (m, 10H, BH), 11B NMR (128.3 MHz, CDCl3): d
ꢂ5.6 (d, 2B, J = 165 Hz), ꢂ10.1 (d, 2B, J = 159 Hz), ꢂ11.4 (d, 4B,
J = 175 Hz), ꢂ14.8 (d, 2B, J = 182 Hz), 19F NMR (376.5 MHz, CDCl3):
ꢂ74.38 (s, 6F, CF3).
2.5. General procedure for the preparation of bis(1,2,3-
triazolyl)carborane derivatives (6a–c, 7a–f)
2.5.6. 1,7-Bis[(40-trimethylsilyl-10,20,30-triazol-10-yl)methyl]-m-
carborane (7c)
Copper acetate hydrate (2 mol%) was added to a solution of the
corresponding alkyne 5a–c (2.06 mmol) and diazide 1 or diazide 2
in toluene (5 mL). Then the reaction mixture was stirred at 40 °C
(diazide 1) or at room temperature (diazide 2) for 3–20 h until
the completion of the reaction (monitored by TLC). After evapora-
tion of the solvent under reduced pressure, the residue was dis-
Yield: 85%. White powder. M.p. 160–162 °C (from AcOEt/n-hep-
tane). IR (KBr, cmꢂ1
)
m
max: 2592 (BH), 840 (SiMe3). 1H NMR
~
(400 MHz, CDCl3): d 7.41 (s, 2H, @CH–N), 4.71 (s, 4H, C–CH2–N),
3.5–1.5 (m, 10H, BH), 0.32 (s, 18H, CH3). 11B NMR (128.3 MHz,
CDCl3): d ꢂ6.5 (d, 2B, J = 145 Hz), ꢂ10.2 (d, 2B, J = 148 Hz), ꢂ11.3
(d, 4B, J = 153 Hz), ꢂ14.3 (d, 2B, J = 182 Hz). Anal. Calc. for

304
V.A. Ol’shevskaya et al. / Polyhedron 42 (2012) 302–306
C14H34B10N6Si2 (450.7): C, 37.31; H, 7.60; B, 23.98; N, 18.64, Si,
12.46. Found: C, 37.38; H, 7.61; B, 24.11; N, 18.73; Si, 12.55%.
J = 177 Hz). Anal. Calc. for C10H24B10I2N6 (509.3): C, 20.35; H,
4.10; B, 18.32; N, 14.24. Found: C, 20.39; H, 4.13; B, 18.27; N,
14.21%.
2.5.7. 1,7-Bis[(40-carbdimethylhydroxy-10,20,30-triazol-10-yl)methyl]-
m-carborane (7d)
2.6.3. 1,10-[(m-Carboran-1,7-yl)bis(methylene)] bis(3-methyl-4-
pentyl-1,2,3-triazol-3-ium iodide) (8e)
Yield: 78%. White powder. M.p. 185–187 °C (from AcOEt/n-hep-
tane). IR (KBr, cmꢂ1
)
max: 2593 (BH). 1H NMR (400 MHz, THF-D8):
Yield: 93%. Yellow powder. M.p. 132–134 °C. 1H NMR (400 MHz,
CDCl3): d 8.71 (s, 2H, @CH–N), 5.32 (s, 4H, C–CH2–N), 4.43 (s, 6H,
N+–CH3), 3.02 (t, 4H, J = 7.56 Hz, CH2–CH2–CH2–CH2–CH3), 1.82
(tt, 4H, J = 7.94 Hz, J = 7.48 Hz, CH2–CH2–CH2–CH2–CH3), 1.41 (m,
8H, CH2–CH2–CH2–CH2–CH3), 3.00–1.00 (m, 10H, BH), 0.89 (t, 6H,
J = 6.72 Hz, –(CH2)3–CH2–CH3). 11B (128.3 MHz, CDCl3): d ꢂ6.4 (d,
2B, J = 146 Hz), ꢂ10.4 (d, 2B, J = 145 Hz), ꢂ11.0 (d, 4B, J = 142 Hz),
ꢂ14.0 (d, 2B, J = 182 Hz). Anal. Calc. for C30H48B10I2N6 (854.7): C,
42.16; H, 5.66; B, 12.65; N, 9.83. Found: C, 42.51; H, 5.87; B,
12.38; N, 9.79%.
~
m
d 7.62 (s, 2H, @CH–N); 4.80 (s, 4H, C–CH2–N); 4.54 (br s, 2H, OH),
1.52 (s, 12H, CH3). 11B NMR (128.3 MHz, THF-D8): d ꢂ6.7 (d, 2B,
J = 155 Hz), ꢂ10.8 (d, 2B, J = 147 Hz), ꢂ11.1 (d, 4B, J = 150 Hz),
ꢂ14.4 (d, 2B, J = 184 Hz). Anal. Calc. for C14H30B10N6O2 (422.5): C,
39.80; H, 7.16; B, 25.59; N, 19.89. Found: C, 40.32; H, 7.08; B,
25.10; N, 19.50%.
2.5.8. 1,7-Bis[(40-pentyl-10,20,30-triazol-10-yl)methyl]-m-carborane
(7e)
Yield: 79%. Colorless oil. IR (KBr, cmꢂ1
)
max: 2591 (BH). 1H NMR
~
m
(400 MHz, CDCl3): d 7.18 (s, 2H, @CH–N); 4.64 (s, 4H, C–CH2–N);
2.69 (t, 4H, J = 7.73 Hz, CH2–(CH2)3CH3); 1.69 (m, 4H, –CH2–CH2–
(CH2)2CH3); 1.32–1.42 (m, 8H, –(CH2)2–CH2–CH2–CH3); 0.88 (t,
6H, J = 6.58 Hz, CH2–CH3). 11B (128.3 MHz, CDCl3): d ꢂ6.5 (d, 2B,
J = 140 Hz), ꢂ10.2 (d, 2B, J = 149 Hz), ꢂ11.3 (d, 4B, J = 151 Hz),
ꢂ14.4 (d, 2B, J = 180 Hz). Anal. Calc. for C18H38B10N6 (446.6): C,
48.40; H, 8.58; B, 24.20; N, 18.82. Found: C, 48.76; H, 8.62; B,
23.98; N, 18.63%.
3. Results and discussion
3.1. Synthesis of bis(azidomethyl) carboranes
To explore further the scope of click reactions in carborane
chemistry, we prepared new representatives of carborane-substi-
tuted azides, namely, 1,2-bis(azidomethyl)-o-carborane 1 and
1,7-bis(azidomethyl)-m-carborane 2, and investigated their Cu-
catalyzed [3+2] cycloaddition reactions with terminal alkynes.
For the preparation of carborane diazides 1 and 2 we exploited
the high reactivity of 1,2-bis(trifluoromethanesulfonylmethyl)-o-
carborane (3) [12] and 1,7-bis(trifluoromethanesulfonylmethyl)-
m-carborane (4) toward nucleophilic reagents. When a mixture
of triflate 3 and sodium azide was heated to reflux in acetone, diaz-
ide 1 was obtained in 55% yield (Scheme 1).
Diazide 2 was easily prepared in good yield and isolated as an
oil by nucleophilic substitution of OTf in triflate 4 with sodium
azide in DMSO (Scheme 2). Triflate 4 was prepared from 1,7-dihy-
droxymethyl-m-carborane and triflic anhydride according to the
previously reported procedure [12].
2.5.9. 1,7-Bis[(40-adenino-10,20,30-triazol-10-yl)methyl]-m-carborane
(7f)
Yield: 68%. White powder. M.p. > 180 °C (with decomp.). IR
(KBr, cmꢂ1
)
max: 2928 (NH), 2597 (BH). 1H NMR (400 MHz, ace-
~
m
tone-D6): d 8.21 (s, 2H, 2-H adenine), 8.15 (s, 2H, 8-H adenine),
8.11 (s, 2H, @CH–N), 6.77 (br s, 4H, NH2), 5.54 (s, 4H, CH2–ade-
nine), 5.07 (d, 4H, C–CH2–N), 3.0–1.0 (m, 10H, BH). 11B NMR
(128.3 MHz, acetone-D6): d ꢂ6.8 (d, 2B, J = 162 Hz), ꢂ10.9 (d, 2B,
J = 146 Hz), ꢂ11.5 (d, 4B, J = 166 Hz), ꢂ14.1 (d, 2B, J = 181 Hz). Anal.
Calc. for C14H30B10N6O2 (600.6): C, 39.99; H, 4.70; B, 18.00; N,
37.31. Found: C, 40.12; H, 4.79; B, 17.88; N, 37.29%.
NaN3 in DMSO cannot be used for the preparation of diazide 1,
since under these reaction conditions an undesired deboronation
reaction of the closo-carborane derivative to give the corresponding
nido cluster occurred. It is noteworthy that diazide 1 is substantially
less stable than diazide 2 and must be kept in the refrigerator to pre-
vent fast decomposition. Therefore, it is important to use a freshly
prepared sample of diazide 1 for further chemical transformations.
2.6. General procedure for the preparation of bis(1,2,3-
triazolium)carborane salts (8b, 8c, 8e)
Methyl iodide (1.77 mmol) was added to a solution of corre-
sponding compound 7b, 7c, or 7e (0.44 mmol) in nitromethane
(7 mL) under argon atmosphere. The resulting mixture was heated
to reflux for 5–10 h. Nitromethane was removed in vacuo and the
residue washed with n-heptane (20 mL) and diethyl ether (10 mL)
to give the triazolium carborane derivatives in high yields.
3.2. Synthesis of carborane-substituted 1,2,3-triazoles
Cycloaddition of diazide 1 with alkynes 5a–c in toluene in the
presence of copper(II) acetate hydrate at room temperature under
argon atmosphere afforded carborane-substituted 1,2,3-triazoles
6a–c in moderate yields (Scheme 3).
The moderate yields of compounds 6a–c obtained in these reac-
tions are suggested to be due to steric hindrance in the formation
of 1,2,3-triazole moieties from diazide 1 and its parallel deborona-
tion reaction. The latter resulted in formation of nido clusters,
2.6.1. 1,10-[(m-Carboran-1,7-yl)bis(methylene)] bis(3-methyl-4-
phenyl-1,2,3-triazol-3-ium iodide) (8b)
Yield: 90%. Yellow powder. M.p. 140–143 °C. 1H NMR (400 MHz,
CDCl3): d 8.83 (s, 2H, @CH–N), 7.91 (m, 4H, o-Ph), 7.65 (m, 4H, m-
Ph), 7.42 (m, 2H, p-Ph), 4.42 (s, 6H, N+–CH3), 5.61 (c, 4H, C–CH2–N),
3.0–1.0 (m, 10H, BH). 11B (128.3 MHz, CDCl3): d ꢂ6.6 (d, 2B,
J = 149 Hz), ꢂ10.7 (d, 4B, J = 140 Hz), ꢂ11.1 (d, 2B, J = 148 Hz),
ꢂ13.9 (d, 2B, J = 177 Hz). Anal. Calc. for C22H32B10I2N6 (742.4): C,
35.59; H, 4.34; B, 14.56; N, 11.32. Found: C, 35.69; H, 4.19; B,
14.20; N, 11.25%.
2.6.2. 1,10-[(m-Carboran-1,7-yl)bis(methylene)] bis(3-methyl-1,2,3-
triazol-3-ium iodide) (8c)
Yield: 92%. Yellow powder. M.p. > 210 °C (with decomp.). 1H
NMR (400 MHz, CDCl3): d 8.65 (s, 2H, 4-CH–triazole), 8.61 (s, 2H,
5-CH–triazole), 5.28 (s, 4H, CH2), 4.37 (s, 6H, N+–CH3), 3.00–1.20
(m, 10H, BH). 11B (128.3 MHz, CDCl3): d ꢂ6.4 (d, 1B, J = 165 Hz),
ꢂ10.2 (d, 3B, J = 148 Hz), ꢂ11.3 (d, 4B, J = 150 Hz), ꢂ14.2 (d, 2B,
Scheme 1. Synthesis of 1,2-bis(azidomethyl)-o-carborane.

V.A. Ol’shevskaya et al. / Polyhedron 42 (2012) 302–306
305
of copper(I), are not suitable for carborane-substituted azides, as
deboronation occurs affording nido clusters.
The structures of all compounds synthesized were confirmed by
IR, 1H and 11B NMR spectroscopy and elemental analysis. The IR
spectra of compounds 1, 2, 6a–c and 7a–f showed intense absorp-
tion bands in the range of 2570–2600 cmꢂ1 corresponding to car-
borane BH groups. The azide absorption bands were detected at
2110 cmꢂ1 (1) and at 2107 cmꢂ1 (2) and were not observed in tri-
azoles 6a–c and 7a–f.
Scheme 2. Synthesis of 1,7-bis(azidomethyl)-m-carborane.
In the 1H NMR spectra the methylene protons of diazide 1 were
observed as a singlet at 4.05 ppm, and those in diazide 2 at
3.55 ppm, which is in good agreement with electron-withdrawing
effects of 1-o- and 1-m-carboranyl groups [11].
In products 6a–c and 7a–f, the signals of the methylene protons
appeared as a singlet between 4.7 and 4.8 ppm, depending on the
nature of the substituent in the 4-position of the triazole ring. The
presence of the methyne CH group, which indicated the formation
of a triazole ring, was confirmed by characteristic narrow singlets
between 7.4 and 7.8 ppm (compounds 6a–c and 7a–f), supporting
formation of only one regioisomer. 11B NMR signals of all products
are similar to those of diazides 1 and 2 and are in the range d ꢂ3.6
to ꢂ11.7 ppm (6a–c) and d ꢂ6.59 to ꢂ14.5 ppm (7a–f), confirming
the closo structures of the carborane polyhedra.
Scheme 3. Synthesis of 1,2-bis(triazolylmethyl)-o-carboranes.
3.3. Synthesis of carborane-substituted 1,2,3-triazolium salts
The novel bis(triazolylmethyl) carboranes were used to synthe-
size trisubstituted 1,2,3-triazolium salts, which have various appli-
cations in different fields [15]. N-Alkylation of triazoles7b, c, e with
methyl iodide in nitromethane afforded the expected 1,3,4-trialkyl-
1,2,3-triazolium carborane salts 8b, c, e in quantitative yields
(Scheme 5). All compounds were obtained as white powders.
1H NMR and 11B NMR spectra were obtained for salts 8b, c, e. In
the case of triazole 7c, desilylation of the starting material occurred
during alkylation and resulted in the 4-unsubstituted 1,2,3-triazo-
lium salt 8c. The formation of this compound was confirmed by 1H
NMR spectra in which the singlet at 0.32 ppm corresponding to the
methyl protons of the trimethylsilyl group of 7c disappeared in
triazolium derivative 8c. Furthermore, alkylation of the ring nitro-
gen atom was confirmed by downfield shifts (averaging 1.0 ppm)
observed for the signals of the C–H protons of the triazole ring as
compared to the corresponding neutral carborane heterocycles.
For all compounds, formation of only one regioisomer was ob-
served. The signals of the methyl protons in the 3-position of the
triazolium ring were observed at d 4.37–4.43 ppm [16]. Salts 8b,
c, e are soluble in polar solvents such as water, methanol, ethanol,
dimethylformamide, and dimethyl sulfoxide.
Scheme 4. Synthesis of 1,7-bis(triazolylmethyl)-m-carboranes.
Scheme 5. Synthesis of triazolium salts.
which can be precipitated from the aqueous solution as salts of
bulky cations, for example, tetrabutylammonium. Formation of a
nido-product is presumably due to nucleophilic attack of an azide
anion at the boron atom in the 3-position of the carborane
polyhedron.
Similarly, cycloaddition reactions of diazide 2 with alkynes 5a–f
under the same reaction conditions (i.e., toluene as solvent and
copper(II) acetate as catalyst) gave bis(triazolylmethyl)-m-carbor-
anes 7a–f in high yields as pure 1,4-regioisomers (Scheme 4).
Purification of all cycloadducts was achieved by extraction from
the reaction mixture with ethyl acetate after dilution with water,
concentrating the extracts, and crystallization from ethyl acetate/
n-heptane.
High regiospecificity of this cycloaddition reaction was
achieved by employing copper(II) acetate hydrate (1–2 mol%) as
catalyst under argon atmosphere. Oxygen-free conditions were
necessary to avoid oxidative coupling of terminal alkynes [13] dur-
ing the reaction. Many catalyst systems have been reported in re-
cent years which are efficient for [3+2] cycloaddition of azides with
alkynes [1]. Among them copper(I) catalysis is the most promising
method for preparation of 1,4-substituted 1,2,3-triazole heterocy-
cles [2]. However, treatment of carborane azides 1 or 2 with al-
kynes in the presence of a copper(I) salt prepared in situ by
reduction of CuSO4ꢀ5H2O with sodium ascorbate led to no reaction.
Alternative catalyst systems based on copper(I)/amine ligands,
which exhibit enhanced catalytic activity [14] due to stabilization
4. Conclusion
We have demonstrated the efficiency of 1,3-cycloaddition
reactions of bis(azidomethyl)carboranes with alkynes for the prep-
aration of bis[(1,2,3-triazolyl)methyl]-substituted o- and m-carbor-
anes. Use of copper(II) acetate hydrate led to regiospecific reactions
resulting in previously unavailable carborane-substituted hetero-
cycles. N-Alkylation of neutral bis(triazolylmethyl)carboranes with
methyl iodide resulted in water-soluble 1,2,3-triazolium carborane
compounds.
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