Labelling of carbaboranyl compounds with a selenium atom with a view to applications in boron-neutron-capture therapy (BNCT) and positron-emission tomography (PET)

Article abstract of DOI:10.1002/1522-2675(20001108)83:11<2926::AID-HLCA2926>3.0.CO;2-6

We synthesized 2′-carbaboranyl-2.5′-bi-1H-benzimidazoles containing 10 B-atoms and labeled with Se or the positron-emitting radionuclide ⁷³Se (I_1/2=7.1 h). with a view to their application to cancer treatment by boron-neutron-capture

Full text of DOI:10.1002/1522-2675(20001108)83:11<2926::AID-HLCA2926>3.0.CO;2-6

2926
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Labelling of Carbaboranyl Compounds with a Selenium Atom with a
View to Applications in Boron-Neutron-Capture Therapy ꢀBNCT) and
Positron-Emission Tomography ꢀPET)
by Deborah F. dos Santosa), Mario Argentinib), Regin Weinreichb), and Hans-Jürgen Hansen*a)
a) Organisch-Chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
b) Paul Scherrer Institut, Laboratorium für Radio- und Umweltchemie, CH-5232 Villigen-PSI
In memoriam Professor Börje Larsson
We synthesized 2'-carbaboranyl-2,5'-bi-1H-benzimidazoles containing 10 B-atoms and labeled with Se or
the positron-emitting radionuclide 73Se 1t1/2 ˆ 7.1 h), with a view to their application to cancer treatment by
boron-neutron-capture therapy 1BNCT) and to compound-distribution measurements in vivo by positron-
emission tomography 1PET). Thus, 2,2'-{{2'-{4-[1,2-dicarba-closo-dodecaboran112)-2-ylmethoxy]phenyl}-[2,5'-
bi-1H-benzimidazol]-5-yl}imino}bis[ethanol] 126c) was obtained by the reaction of 2,2'-[13,4-diaminophenyl)-
imino]bis[ethanol] 119) with ethyl 2-{4-[1,2-dicarba-closo-dodecaboran112)-2-ylmethoxy]phenyl}-1H-benzimi-
dazole-5-carboximidate hydrochloride 125), as well as the analogues 26a and 26b 1Scheme 6). Tosylation of
compound 26c gave 4 regioisomers 27a± d, which, after selenation, produced 2'-{4-[1,2-dicarba-closo-dodeca-
boran112)-2-ylmethoxy]phenyl}-5-1tetrahydro-2H-1,4-selenazin-4-yl)-2,5'-bi-1H-benzimidazole 129) in 42%
yield 1Scheme 7).
Introduction. ± Boron-neutron-capture therapy 1BNCT) is a binary procedure for
the treatment of different types of tumors. The non-radioactive isotope 10B has a high
thermal neutron-capture cross section 13840 barns), and the capture results in
7
formation of an a-particle and Li nuclei with a path length of ca. 9 ± 10 mm 1one cell
diameter), and carrying 2.3 MeVof energy. Both particles are able to damage the DNA
or other essential parts of tumor cells.
Many compounds have been synthesized that are able to transport 10B atoms
into tumor cells [1]. Our approach consisted of coupling the well-known
DNA ligand 4-{5-14-methylpiperazin-1-yl)[2,5'-bi-1H-benzimidazol]-2'-yl}phenol 11)
1ꢀHoechst 33258ꢁ) [2 ± 3] with a carbaboranyl moiety [4]. While compound 1 was
synthesized by a classical linear route [3][5], we found that benzimidazoles with both
methylpiperazinyl and carbaboranyl residues can be prepared advantageously in a
convergent synthesis starting from the carbaboranyl moiety of the molecule as shown
by the synthesis of compound 1a [4]. In the present paper, we continued this work by
synthesizing two more 1,2-dicarbadodecaboranyl derivatives of 1, i.e. compounds 9a
and 9b.
Unfortunately, the atoms contained in these compounds have no radioactive
isotopes with half-lives suited to their uptake process in tumors. As a result, it is difficult
to study uptake and biodistribution of the BNCT drugs in patients by in vivo techniques
and consequently to estimate the dosage of the BNCT therapy. As an alternative, the
replacement of these atoms by heavier elements of the same group is desirable if the

Helvetica Chimica Acta ± Vol. 83 12000)
2927
physiological properties of the carrier molecules are not substantially changed. Some of
these elements have radioisotopes with the requisite physical properties to allow in vivo
imaging of the B-containing compounds. For example, if the drug molecule contains
an S-atom, this may be replaced by a Se-atom, which has the useful radioisotope 73Se
1t1/2 ˆ 7.1 h, 65% positron yield). Thus, we were looking for Se-containing compounds
that might carry the B-atoms into the tumor cell. In particular, our strategy was directed
towards the replacement of the 4-methylpiperazin-1-yl group in 1 by a tetrahydro-2H-
1,4-selenazin-4-yl 1selenomorpholin-4-yl) group. The synthesis of such a compound
would allow the introduction of the 73Se radioisotope instead of inactive Se-atoms in
natural abundance. However, the introduction of this short half-life radionuclide has to
be carried out in the last step.
It should be mentioned that 73Se can be produced in high yield by bombardment of
arsenic, preferably in the form of a Cu3As alloy, with 40 MeV protons in a cyclotron.
Under these conditions, the production yield is 1.22 Æ 0.12 GBq/mAh or 33 Æ 3.3 mCi/
mAh, the contaminations of 72Se 1t1/2 ˆ 8.5 d) and of 75Se 1t1/2 ˆ 120 d) being 0.34 and
0.026%, respectively [6].
Results and Discussion. ± 1,2-Dicarbadodecaboranyl Derivatives 9a,b of 4-{5-&4-
Methylpiperazin-1-yl)[2,5'-bi-1H-benzimidazol]-2'-yl}phenol 11). Compounds 9a,b
were synthesized by a convergent synthesis 1Scheme 1). Thus, 3a was obtained by the
reaction of 1,2-dicarbadodecaboran112)yllithium 2a with 4-1bromomethyl)benzoni-
trile, and 3b was prepared by the reaction of 4-ethynylbenzonitrile 12b; from silyl
derivative 1b) and the decaborane/bis-acetonitrile complex 6,9-1MeCN)2B10H12.
Transformation of compounds 3a,b to the ethyl carboximidate hydrochlorides 4a,b
followed by their reaction with 3,4-diaminobenzonitrile 15) led to the formation of the
1H-benzimidazolecarbonitriles 6a,b. In the same way, 7a,b obtained from 6a,b gave the
2,5'-bi-1H-benzimidazoles 9a,b after reaction with compound 8. Although the
preparation of the ethyl carboximidate analogues of 7a,b is easier and results in
higher yields, the overall yields of the bi-1H-benzimidazoles are much higher with the
2-methoxyethyl carboximidates [7], perhaps due to stabilizing effects of the lone
electron pairs of the O-atom of the MeO group.
Supposing the binding mechanism for compounds 9a,b to DNA in the cell is the
same as for compound 1 [8± 10] 1H-bridges of the NH groups of the bi-1 H-
benzimidazole moieties with adenine and thymine base pairs), these compounds
should be useful for studying the influence of spacers like 1CH2)n 1n ˆ 0, 1) positioned
between the bi-1H-benzimidazole group and the 1,2-dicarbadodecaborane112) moiety
in the derivatives 9a,b of Hoechst 33258.

2928
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Scheme 1
Li
a)
NC
NC
NC
Br
3a
2a
b)
c)
NC
Si(CH3)3
NC
H
Br
2b
1b
Cl H2N
C
C2H5O
e)
d)
e)
NC
R
3a
2b
4a,b
3b
R
4-9
a
NC
NH2
NH2
NC
N
H2C
f)
4a,b
R
N
H
5
6a,b
b
Cl
NH2
C
H3C
N
N
N
H3COC2H4
g)
R
6a,b
N
NH2
NH2
H
8
7a-b
h)
H3C
N
N
N
N
N
N
H
H
BH
CH
9a,b
a) 1,2-Dicarbadodecaborane112), BuLi, THF, 30 min at 08, 12 h at 258. b) Ethynyltrimethylsilane, Et3N, Ar,
CuI, [PdCl21Ph3P)2]. c) Aq. 1m K2CO3, MeOH. d) 6,9-1MeCN)2B10H12, toluene, reflux. e) EtOH, dry HCl. f)
AcOH, Ar, reflux. g) MeOCH2CH2OH, dry HCl. h) AcOH, Ar, reflux.
Model Compounds for the Preparation of Selenomorpholinyl-1H-benzimidazoles.
To replace the 4-methylpiperazin-1-yl group in 9a,b by a tetrahydro-2H-1,4-selenazin-
4-yl 1selenomorpholin-4-yl) group, the syntheses of some model compounds were
necessary. The preparation of the selenomorpholine moiety 1Scheme 2) was studied
starting from the commercially available 2,2'-1phenylimino)bis[ethanol]. Bis-tosyla-
tion [11][12] 1 ! 10) followed by nucleophilic reaction with lithium selenide [13 ± 16]
and ring closure gave 4-phenylselenomorpholine 111) in 40% yield.
Model compounds containing a 1H-benzimidazole such as 15 1from 12 via 13 and
14; Scheme 3) and a 1H-benzimidazole/1,2-dicarbadodecaborane moiety such as 21

Helvetica Chimica Acta ± Vol. 83 12000)
2929
Scheme 2
HO
HO
TsO
N
Se
N
N
a)
TsO
b)
10
11
a) CH2Cl2, Et3N, TsCl, 30 min at 08, 12 h at 5 ± 68. b) Li2Se, tBuOH, THF, N2, reflux, 4 h.
1see below) were designed to study the compatibility of these compounds in tosylation
and selenation. Thus, tosylation of 15 with 6 equiv. of TsCl 1any quantity less than that
produced many by-products) gave the two regioisomers 16a,b 1Scheme 4). Although
1
they could not be separated, the ratio 16a/16b 6 :4 could be assigned by H-NMR
spectroscopy and comparison with similar compounds cited in [17].
Scheme 3
O2N
NHCOCH3
NHCOCH3
H2N
NHCOCH3
NHCOCH3
O2N
NH2
NH2
a)
b)
12
13
HO
HO
HO
HO
N
NHCOCH3
NHCOCH3
N
N
d)
c)
CH3
N
13
H
15
14
a) AcCl, reflux, 6 h. b) 5% Ru/C, N2H4 ´ H2O, EtOH, reflux, 5 h. c) Oxirane, 25% AcOH/H2O, 2 ± 38, 5 h at 58. d)
18% HCl/H2O, reflux, 3 h.
In the 1H-NMR spectrum 1300 MHz, CDCl3) of 16a/16b 2s at 2.75 and 2.76 ppm in the ratio 6 :4 were
assigned to MeÀC12) of the 1H-benzimidazole ring. For the 6-ylimino regioisomer 16b, the signal of HÀC17) is
shifted to lower field 17.08ppm) compared to the analogous signal of H ÀC14) of 16a 16.59 ppm), due to the
peri-neighborhood of the tosyl group in 16b. Integration of this signal also amounts to 40% of the total integral
for HÀC14) and HÀC17) in the mixture.
The mixture 16a/16b was selenated by two different methods. Method A, with
NaHSe in EtOH, gave 17a/b in a yield of 33% and Method B, with Li2Se in THF,
produced 35% of 17a,b. Method B was finally preferred because 16a/b are soluble in
THF, but only slightly soluble in EtOH. Thus, in the case of automated processes with
radioactive 73Se, Method B would be applied. When 1 equiv. of Li2Se was used, com-
pound 18 was isolated in ca. 9% yield along with 35% of 17a,b. An additional equiv. 1in
total 2 equiv.) of Li2Se gave 18 in 53% yield1). In the present work, we did not deter-
1
)
The high yield of N-detosylated product 18 obtained by the treatment with 2 equiv. of Li2Se suggests that
the selenide anion acts as a strong electron donor 1Se ‡ 2eÀ>Se2À À 0.92 V) for the reductive cleavage of
the NÀSO2Ar bond in our system. The introduction of electron-withdrawing substituents at the aromatic
sulfonamide moiety instead of the Me group lower the reduction potential needed for the cleavage of the
NÀS bond and, as a consequence, increase the yield of the desulfonated product.

2930
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Scheme 4
TsO
TsO
TsO
TsO
Ts
4
5
N
N
6
N
N
N
N
a)
2
2
15
CH3
CH3
5
16b
16a
Ts
b)
Se
Se
Ts
N
N
N
N
N
CH3
CH3
N
17a
17b
Ts
c)
Se
N
N
CH3
N
18
H
a) Pyridine, 08, TsCl, 72 h at 58. b) Method A: NaHSe, EtOH, N2, 6 h reflux, 15 h at r.t.; Method B: Li2Se,
tBuOH, THF, N2, 12 h at r.t. c) Reductive cleavage by Li2Se or electrochemical reduction 1see text).
mine what excess of Li2Se would be best to obtain the detosylated compound 18 in
higher yield. Next, we studied the possibility to prepare 18 from the mixture 17a/17b by
electrochemical detosylation [18]. With this alternative method, 18 was obtained in
77% yield. Studies to cleave the N-tosyl group in presence of O-tosyl groups are under
way.
To examine the influence of 1,2-dicarbadodecaborane moiety in this process, we
synthesized the model compound 21 from 19 and 20 1Scheme 5). Tosylation of 21 with
6 equiv. of TsCl in pyridine gave the mixture 22a/22b in 74% yield. Identification was
possible only by MS 1ESI). 1H-NMR 1300 MHz, 1D6)acetone) gave the correct
number of 19 aromatic H-atoms after integration, but their signals were too
superimposed to be assigned to the respective regioisomers. After selenation with
2 equiv. of Li2Se, the detosylated compound 24 was obtained in 24% yield together with
some 23a,b.
Bi-1H-benzimidazole Precursors for Selenation and Preparation of the 2'-{4-[1,2-
Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}-5-&selenomorpholin-4-yl)-2,5'-bi-
1H-benzimidazole 129). Finally, one of the analogues of the Hoechst-carbaboranyl
derivatives 1a or 9a,b displaying a selenomorpholin-4-yl moiety instead of a 4-
methylpiperazin-1-yl residue was synthesized. The precursors 26a ± c were obtained by
the condensation of 2,2'-[13,4-diaminophenyl)imino]bis[ethanol] 119) with the car-
boximidates 7a,b or 25 [4] in 2-PrOH 1Scheme 6). The same reaction in glacial acetic
acid, however, did not lead to the desired compounds 26a ± c.
We then chose the synthesis of the selenomorpholinyl-carbaboranyl Hoechst
analogue 29 of compound 1a. Since 4 regioisomers are to be expected in the tosylation
of precursor 26c, a total of 32 equiv. of TsCl was applied to minimize side reactions,
which furnished compounds 27a ± d in 51% yield 1Scheme 7). The components of this

Helvetica Chimica Acta ± Vol. 83 12000)
2931
Scheme 5
HO
HO
N
NH2
Cl H2N
C
R
NH2
C2H5O
20
19
a)
HO
N
N
HO
R
N
H
R
O
21
b)
TsO
TsO
TsO
TsO
Ts
N
N
N
N
N
R
R
N
Ts
22a
22b
c)
Se
Se
Ts
N
N
N
N
N
R
R
N
Ts
23a
23b
Se
N
N
N
R
H
24
a) iPrOH, N2, reflux, 7 h. b) Pyridine, 08, TsCl, 72 h at 58. c) Li2Se, tBuOH, THF, N2, 2 h reflux and 12 h at r.t.
1
mixture could not be isolated, and an interpretation of the H-NMR spectrum of the
mixture was impossible on grounds of its complexity. However, identification was again
achieved by MS 1ESI). Selenation of the mixture 27a ± d with 4 equiv. of Li2Se gave the
final compound 29 in 42% yield.
Financial support by the Swiss Cancer League 1KFS 176-9-1995) and by the Swiss National Science
Foundation is gratefully acknowledged. We would like to thank Mr. Armin Guggisberg for all experiments of
electrochemical reduction and Wella Cosmital SA, CH-1723 Marly, for a generous gift of 2,2'-[14-amino-3-
nitrophenyl)imino]bis[ethanol].

2932
Helvetica Chimica Acta ± Vol. 83 12000)
Scheme 6
Cl
HO
HO
NH2
C
25
R1
N
NH2
NH2
N
N
R1
R
CH3CH2
O
H
7a,b, 25
19
a)
R
HO
N
N
N
R
26
a
HO
N
R
H2C
N
H
H
26a-c
b
c
O
i
a) PrOH, N2, reflux, 7 h.
Experimental Part
General. If not otherwise stated, reagent-grade solvents were used without further purification 1petroleum
ether of b.p. 30 ± 608 ˆ p.e.). Decaborane and 1,2-dicarba-closo-dodecaborane112) 1o-carborane) were
purchased from Alfa, a subsidiary of Johnson Matthey Co. Compounds 5, 8, 20, and 25 have been reported
previously [4], 2,2'-[14-amino-3-nitrophenyl)imino]bis[ethanol] was a generous gift from Wella Cosmital SA,
CH-1723 Marly, Switzerland. LiSe2 and NaHSe were synthesized according to [13][14]. The polarographic
measurements were carried out as described in [18]. Controlled-potential electrolysis was performed at 58 under
Ar in a cylindrical three electrode divided cell with an electronic potentiostat; cathode: stirred Hg pool 1area:
44 cm2); anode: graphite rod; reference electrode: aq. sat. calomel; solvent supporting electrode: 0.1m Me4NCl
in 94% EtOH as catholyte and anolyte. TLC: Merck silica gel 60 F254 plates 1Al support, 0.2 mm thickness);
detection of carbaborane compounds by PdCl2 in HCl as described elsewhere [4]. FC ˆ flash chromatography.
M.p.: Büchi 535 or Mettler-FP5 and -FP52 apparatus; uncorrected. IR Spectra: Perkin-Elmer-FT-1600-IR
spectrophotometer; KBr pellets; in cmÀ1 1H-NMR Spectra: Bruker-AC-300 or -ARX-300 or Varian-Gemini-
.
2000 spectrometer, all operating at 300 MHz; residual solvent peak 1CDCl3, 1D6)DMSO, CD3OD or
1D6)acetone) as internal reference rel. to SiMe4; d in ppm and coupling constants J in Hz. MS: Finnigan MAT 90
1CI, NH3), SSQ 700 1EI, 70 eV), Fision VG TRIO 2000 1ESI, 40 eV), and TSQ/SSQ 700 1ESI, NaI); m/z 1rel.
%). The Microanalytical Laboratory of the Institute of Organic Chemistry at the University of Zürich
performed the elemental analyses.
Syntheses. 1. 4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethyl]benzonitrile 13a). To a deaerated soln. of
1,2-dicarba-closo-dodecaborane112) 150 mmol, 7.2 g) in THF 1160 ml), 2.7m BuLi in heptane 130 ml) was added
dropwise under stirring at 08. To this soln., 4-1bromomethyl)benzonitrile 150 mmol, 9.8g) in THF 1100 ml) was
added dropwise. After stirring at r.t. under Ar for 12 h, the mixture was diluted with Et2O 1500 ml), the org.
phase washed with H2O 1250 ml) and 10% NaCl soln. 12 Â 250 ml), dried 1MgSO4), and evaporated, and the
resulting light brown oil purified by FC 1silica gel, CH2Cl2/hexane 1:1) to remove the non-reacted
dicarbadodecaborane. A second FC 1silica gel, AcOEt/p.e. 1:4) gave pure 3a 15.36 g, 41%) [19]. M.p. 131.3 ±
135.48. Rf 1CH2Cl2/hexane 1:1) 0.36; Rf 1AcOEt/p.e. 1 :4) 0.47; Rf 1AcOEt/hexane 2 :6) 0.51. IR: 2236, 2590.
1H-NMR 1CDCl3): 3.30 1s, CB10H10CH); 3.57 1s, CH2CB10H10CH); 7.30 ± 7.70 1AA'BB', 4 arom. H). CI-MS: 277

Helvetica Chimica Acta ± Vol. 83 12000)
2933
Scheme 7
26c
R
O
a)
TsO
TsO
TsO
Ts
Ts
N
5
6
N
N
N
N
TsO
2 5'
6'
2
6'
5'
N
N
N
2'
2'
6
R
R
R
5
N
N
Ts
Ts
27b
27a
TsO
TsO
TsO
Ts
Ts
5
N
6
N
N
N
N
2 6'
5'
TsO
N
2 5'
6'
N
2'
2'
6
5
R
N
N
N
Ts
Ts
27c
27d
b)
Se
Se
Ts
H
N
N
N
N
N
N
N
N
R
R
R
N
N
Ts
H
28a
28b
Se
Se
H
Ts
N
N
N
N
N
N
N
R
N
N
N
H
Ts
28c
28d
Se
N
N
N
N
N
O
H
H
29
a) Pyridine, 08, TsCl, 72 h at 58. b) Li2Se, tBuOH, THF, N2, 3 h at 708, 12 h at r.t.
‡
‡
1100, [M ‡ NH4] ), 260 111 [M ‡ H] ), 259 113). Anal. calc. for C9H14B10N 1259.36): C 46.31, H 6.61, N 5.40;
found: C 46.21, H 6.51, N 5.33.
2. Ethyl 4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethyl]benzenecarboximidate Hydrochloride 14a). Dry
HCl gas was bubbled through a soln. of 3a 118.28 mmol, 4.71 g) and dry EtOH 150 ml), until saturation. The

2934
Helvetica Chimica Acta ± Vol. 83 12000)
mixture, protected against moisture, was stirred overnight. After evaporation, the residue was triturated with
dry Et2O, filtered, and dried in vacuo: 4.98g 179.7%) of 4a. White crystals. M.p. 161 ± 1638. 1H-NMR
11D6)DMSO): 1.49 1t, J ˆ 6.9, MeCH2O); 3.781 s, CH2CB10H10CH); 4.64 1q, J ˆ 6.9, MeCH2O); 5.40
1s, CB10H10CH), 7.54 1AA'XX', JA1JX) ˆ 8.4, 2 Hm; 8.14 1AA'XX', JA1JX) ˆ 8.4, 2 Ho).
3. 2-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethyl]phenyl}-1H-benzimidazole-5-carbonitrile 16a). A
soln. of 5 123.39 mmol, 3.1 g) and 4a 123.39 mmol, 8g) in AcOH 1300 ml) was refluxed for 7 h. Thereafter, the
mixture was stirred overnight at r.t. The precipitate formed was filtered off and washed with Et2O 13 Â 250 ml).
The combined Et2O portions were dried 1Na2SO4) evaporated and the residue purified by FC 1silica gel,
acetone/p.e. 1:2): 5.40 g 153%) of 6a. Colorless crystalline solid. M.p. 283.3 ± 284.88. 1H-NMR 1CDCl3): 3.30 1br.
s, CB10H10CH); 3.60 1s, CH2CB10H10CH); 7.32 1AA'XX', JA1JX) ˆ 8.4, 2 Hm); 7.53 1dd, J14,6) ˆ 1.5, J 16,7 ˆ 8.4,
HÀC16)); 7.69 1d, J14,7) ˆ 0.6, J16,7) ˆ 8.4, HÀC17)); 7.96 1d, J14,7) ˆ 0.6, HÀC14)); 8.03 1AA'XX', JX1JA) ˆ
‡
8.4, 2 Ho). CI-MS: 376 1100, [M ‡ H] ), 375 164). Anal. calc. for C17H21B10N3 ´ CH3COOH 1435.54): C 52.40,
H 5.78, N 9.65; found: C 52.61, H 5.78, N 9.67.
4. 2-Methoxyethyl 2-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethyl]phenyl}-1H-benzimidazole-5-car-
boximidate Hydrochloride 17a). Dry HCl gas was bubbled through a soln. of 6a 10.40 mmol, 0.173 g) in 2-
methoxyethanol 130 ml) at 2 ± 38, until saturation. The mixture, protected against moisture, was stirred
overnight. The white precipitate formed was filtered off, dried in vacuo, and used without further purification in
the next step: 0.140 g 177%) of 7a. 1H-NMR 11D6)DMSO): 3.35 1s, MeO); 3.72 1m, MeOCH2CH2); 3.79
1s, CH2CB10H10CH); 4.47 1m, MeOCH2CH2); 5.39 1br. s, CH2CB10H10CH); 7.59 1AA'XX', JA1JX) ˆ 8.1, 2 Hm);
7.92 1d, J16,7) ˆ 8.6, HÀC17)); 8.08 1dd, J16,7) ˆ 8.6, HÀC16)); 8.35 1d, HÀC14)); 8.48 1AA'XX', JX1JA) ˆ 8.1,
2 Ho).
5. 2'-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethyl]phenyl}-5-&4-methylpiperazin-1-yl)-2,5'-bi-1H-
benzimidazole 19a). A mixture of 8 10.55 mmol, 0.112 g) and 7a 10.55 mmol, 0.250 g) in AcOH was refluxed
for 7 h under Ar. The mixture was stirred overnight at r.t. The precipitate was filtered off, dissolved in MeOH,
the soln. added slowly and dropwise to Et2O, and this soln. kept in the refrigerator overnight. The precipitate
1
formed was filtered off and dried in vacuo: 0.69 g 120%) of 9a. Yellow crystals. H-NMR 1CD3OD ‡ drops of
CF3COOD): 3.02 1s, MeN); 3.24 1t, J ˆ 12, 2 H, MeNCH2CH2); 3.381 t, J ˆ 12, 2 H, MeNCH2CH2); 3.70 1d, J ˆ
13, 2 H, MeNCH2CH2); 3.781 s, CH2CB10H10CH); 3.99 1d, J ˆ 13, 2 H, MeNCH2CH2); 4.60 1br. s, CB10H10CH);
7.37 1d, J14,6) ˆ 2, HÀC14)); 7.47 1dd, J14,6) ˆ 2, J16,7) ˆ 9, HÀC16)); 7.64 1AA'XX', JX1JA) ˆ 8.4, 2 Hm); 7.78
1d, J16,7) ˆ 9, HÀC17)); 8.12 1d, J16',7') ˆ 9, HÀC17')); 8.23 1AA'XX', JX 1JA) ˆ 8.4, 2 Ho); 8.27 1dd, J14',6') ˆ
‡
1.5, J16',7') ˆ 8.7, HÀC16')); 8.63 1br. s, HÀC14')). ESI-MS: 568154), 567 197, [ M ‡ 1] ), 566 1100), 565 159), 564
125).
6. 4-[1,2-Dicarba-closo-dodecaboran&12)-2-yl]benzonitrile 13b). 6.1. 4-&Trimethylsilylethynyl)benzonitrile
11b). To a stirred mixture of 4-bromobenzonitrile 119.5 mmol, 3.54 g) and ethynyltrimethylsilane 123.4 mmol,
3.1 ml) in dry Et3N 190 ml) under Ar, dichlorobis1triphenylphosphine)palladium1II) 10.71 mmol, 0.28g) and
CuI 10.1 mmol, 20 mg) were added. The mixture was allowed to stand for 7 h at r.t. and then filtered through a
pad of Celite and Al2O3 1toluene/hexane 1:1 used for rinsing). Evaporation of the filtrate gave gold-brown
crystals that were subjected to FC 1silica gel, toluene/hexane 1:1) to yield an oil, which crystallized immediately:
2.12 g 157.7%) of 1b. Colorless brilliant crystals. M.p. 100 ± 1018 1[20]: 111 ± 1128). 1H-NMR 1CDCl3): 0.26
‡
1s, Me3Si); 7.53 1AA'BB', 2 arom. H); 7.59 1AA'BB', 2 arom. H). CI-MS: 217 1100, [M ‡ NH4] ), 199 15). Anal.
calc. for C12H13NSi 1199.33): C 72.31, H 6.57, N 7.03; found: C 72.31, H 6.32, N 7.01.
6.2. 4-Ethynylbenzonitrile 12b). A mixture of 1b 128.9 mmol, 5.75 g), MeOH 170 ml), and aq. 1m K2CO3
110 ml) was stirred for 2 h at r.t. MeOH was evaporated and the crude product extracted from the aq. phase with
Et2O. The Et2O phase was dried 1Na2SO4) and evaporated and the residue subjected to FC 1silica gel; toluene/
p.e. 1:1): 3.15 186%) of 2b. White crystals. M.p. 156 ± 1588 1[20]: 156 ± 1578; [21]: 154 ± 1558). IR: 1456, 1498,
1
1601, 1798, 1926, 2103 1CꢀC), 22281C ˆN, CꢀC), 2853, 3089, 3236 1CꢀCH), 3442. H-NMR 1CDCl3): 3.30
‡
1br. s, CꢀCH); 7.581 AA'BB', 2 arom. H); 7.63 1AA'BB', 2 arom. H). CI-MS: 145 1100, [M ‡ NH4] ), 127 15).
Anal. calc. for C9H5N 1127.14): C 85.02, H 3.96, N 11.02; found: C 84.44, H 3.97, N 10.98.
6.3. Carbaboranylbenzonitrile 3b. A stirred mixture of the decaborane/bis1acetonitrile) complex 6,9-
1Me3CN)2B10H10 17.9 mmol, 1.45 g) and 2b 17.9 mmol, 1.0 g) in toluene was refluxed for 6 h under N2. The
resulting mixture was filtered through a pad of Celite and the filtrate evaporated. The residue was purified by FC
1silica gel, AcOEt/p.e. 1:9): 0.58g 130%) of 3b [22 ± 23]. Colorless crystals. M.p. 194 ± 1968. 1H-NMR 1CDCl3):
3.99 1br. s, CB10H10CH); 7.60 1m, 2 arom. H); 7.66 1m, 2 arom. H). Anal. calc. for C9H15B10N 1365.44): C 44.06,
H 6.16, N 5.71; found: C 43.72, H 5.96, N 5.51.
7. Ethyl 4-[1,2-Dicarba-closo-dodecaboran&12)-2-yl]benzenecarboximidate Hydrochloride 14b). As de-
scribed for 4a, with 3b 16.52 mmol, 1.61 g) and EtOH 120 ml): 1.5 g 170%) of 4b [23]. Colorless crystals.

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2935
1H-NMR 11D6)DMSO): 1.45 1t, J ˆ 6.9, MeCH2O); 4.59 1q, J ˆ 6.9, MeCH2O); 6.0 1br. s, CB10H10CH); 7.84
1AA'XX', JA1JX) ˆ 8.6, 2 Hm); 8.48 1AA'XX', JX1JA) ˆ 8.6, 2 Ho).
8. 2-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-yl]phenyl}-1H-benzimidazole-5-carbonitrile 16b). As de-
scribed for 6a, with 5 13.55 mmol, 0.473 g), 4b 13.55 mmol, 1.17 g), and AcOH 140 ml) under N2. Purification
of the crude product by FC 1silica gel, AcOEt/hexane 1 :1) gave 0.38g 130%) of pure 6b. Light pink crystals. Rf
1AcOEt/hexane 1 :1) 0.5 ± 0.52. 1H-NMR 11D6)acetone): 5.34 1br. s, CB10H10CH); 7.65 1dd, J14,6) ˆ 1.4, J16,7) ˆ
8.4, HÀC16)); 7.87 1d, J16,7) ˆ 8.4, HÀC17)); 7.89 1AA'XX', JA1JX) ˆ 8.7, 2 Hm); 8.16 1d, J14,7) ˆ 0.6, HÀC14));
8.31 1AA'XX', JX1JA) ˆ 8.7, 2 Ho).
9. 2-Methoxyethyl 2-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-yl]phenyl}-1H-benzimidazole-5-carboximi-
date Hydrochloride 17b). As described for 7a, with 6b 11.7 mmol, 0.62 g) in 2-methoxyethanol 130 ml): 0.46 g
156.8%) of 7b, which was used without further purification in the next step. 1H-NMR 11D6)DMSO): 3.38
1s, MeO); 3.85 1m, MeOCH2CH2); 4.77 1m, MeOCH2CH2); 5.96 1br. s, CB10H10CH); 7.85 1AA'XX', JA1JX) ˆ 9,
2 Hm); 7.89 1d, J ˆ 9, HÀC17)); 8.03 1dd, J14,6) ˆ 1.8, J16,7) ˆ 8.7, HÀC16)); 8.37 1AA'XX', JA1JX) ˆ 8.7, 2 Ho);
8.53 1s, J14,6) ˆ 1.8, HÀC14)).
10. 2'-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-yl]phenyl}5-&4-methylpiperazin-1-yl)-2,5'-bi-1H-benzimi-
dazole 19b). As described for 9a, with 8 10.62 mmol, 0.129 g), 7b 10.62 mmol, 0.30 g), and AcOH 120 ml):
0.140 g 147.4%) of 9b. Yellow crystals. 1H-NMR 1CD3OD ‡ drops of CF3COOD): 2.981 s, MeN); 3.24 1t, J ˆ 12,
2 H, MeNCH2CH2); 3.33 1t, J ˆ 12, 2 H, MeNCH2CH2); 3.67 1d, J ˆ 11, 2 H, MeNCH2CH2); 3.95 1d, J ˆ 12, 2 H,
MeNCH2CH2); 5.15 1s, CB10H10CH), 7.35 1d, J14,6) ˆ 2.1, HÀC14)); 7.41 1dd, J14,6) ˆ 2.1, J16,7) ˆ 9, HÀC16));
7.75 1d, J16,7) ˆ 9, HÀC17)); 7.94 1AA'XX', JA1JX) ˆ 9, 2 Hm); 8.14 1dd, J14',7') ˆ 0.6, J16',7') ˆ 9, HÀC17')); 8.23
1AA'XX', JA1JX) ˆ 9, 2 Ho); 8.31 1dd, J14',6') ˆ 1.8, HÀC16')); 8.67 1dd, J14',7') ˆ 0.6, J14',6') ˆ 1.8, HÀC14')).
‡
ESI-MS: 554 156), 553 1100, [M ‡ 1] ), 552 197), 551 157), 550 125).
11. Tetrahydro-4-phenyl-2H-1,4-selenazine 111). To a soln. of 2,2'-1phenylimino)bis[ethanol] 127.62 mmol,
5 g) in CH2Cl2 180 ml) and dry Et3N 13 equiv., 82.86 mmol, 11.41 ml) at 08, TsCl 12.5 equiv., 69.05 mmol, 13.16 g)
in CH2Cl2 166 ml) was added over 30 min. The soln. was stirred at 5 ± 68 overnight and then poured into
vigorously stirred ice-water. The crude product, which crystallized within 15 min, was filtered off and dissolved
in CH2Cl2. The soln. then was washed with H2O, dried 1MgSO4), and evaporated and the residue subjected to
FC 1silica gel, CH2Cl2): 9.25 g 170%) of 2,2'-&phenylimino)bis[ethanol] bis&4-methylbenzenesulfonate) 110).
Fine colorless powder. M.p. 89 ± 908. 1H-NMR 1CDCl3): 2.41 1s, 2 Me); 3.54 1t, J ˆ 6.0, N1CH2)2); 4.081 t, J ˆ 6.0,
2 CH2O); 6.42 1d, J ˆ 8.2, HÀC12), and HÀC16) 1Ph)); 6.69 1t, J ˆ 7.3, HÀC14)1Ph)); 7.12 1t, J ˆ 7.4, HÀC13),
HÀC15)1Ph)); 7.27 1AA'XX', JA1JX) ˆ 8.1, 4 H, Hm 1Ts)); 7.70 1AA'XX', JA1JX) ˆ 8.3, 4 H, Ho 1Ts)).
t
A soln. of 10 11.27 mmol, 0.63 g) and BuOH 10.5 ml, 5.3 mmol) in THF 111 ml) was added dropwise to
Li2Se 11.27 mmol) suspended in THF 17 ml). This soln. was stirred and refluxed under N2 for 4 h 1TLC 1silica
gel, CHCl3/hexane 1:2) monitoring: Rf 0.45). Et2O/H2O was added, the org. phase decanted, the aq. phase
extracted twice with Et2O, the combined Et2O phase dried 1MgSO4) and evaporated, and the residue subjected
to FC 1silica gel, CHCl3/hexane 1:2): 0.115 g 140%) of pure 11. Light cream-colored solid. M.p. 49 ± 518.
1H-NMR 1CDCl3): 2.71 1AA'XX', JA1JX) ˆ 5.2, N1CH2)2); 3.781 AA'XX', JA1JX) ˆ 5.2, Se1CH2)2); 6.8
‡
1m, HÀC12), HÀC14), HÀC16)); 7.24 1m, HÀC13), HÀC15)). CI-MS: 2281100, [ M ‡ H] ), 227 116), 226
149), 225 121). Anal. calc. for C10H13NSe 1226.18): C 53.10, H 5.79, N 6.19; found: C 52.87, H 6.10, N 6.33.
12. 2-Methyl-5-&tetrahydro-2H-1,4-selenazin-4-yl)-1H-benzimidazole 118). 12.1. N,N'-&4-Nitro-1,2-phenyl-
ene)bis[acetamide] 112). A mixture of 4-nitrobenzene-1,2-diamine 132.65 mmol, 5 g) and AcCl 155 ml) was
refluxed for 6 h. After cooling, the precipitate was filtered and dried under reduced pressure. The product was
1
crystallized from AcOH: 7.27 g 194%) of 12. Colorless needles. M.p. 249 ± 2518. H-NMR 11D6)DMSO): 2.14
1s, AcNHÀC11)); 2.16 1s, AcNHÀC12)); 8.02 1m, HÀC13), HÀC16)); 8.50 1m, HÀC15)); 9.65
1s, AcNHÀC11)); 9.681 s, AcNHÀC12)).
12.2. N,N'-&4-Amino-1,2-phenylene)bis[acetamide] 113). A mixture of 12 14.64 mmol, 1.1 g), 5% Ru/C
10.44 g, 40%), and N2H4 ´ H2O 199%, 2 ml) in EtOH 1150 ml) was refluxed for 5 h. The mixture was filtered
through a pad of Celite and the filtrate evaporated: 0.67 g 170%) of 13, which was used without further
purification in the next step. M.p. 209 ± 2108 1[7]: 204 ± 2058 1EtOH)). 1H-NMR 11D6)DMSO): 1.98
1s, AcNHÀC12)); 2.02 1s, AcNHÀC11)); 5.02 1s, NH2); 6.31 1dd, J13,5) ˆ 2.4, J15,6) ˆ 8.5, HÀC15)); 6.88
1d, J13,5) ˆ 2.2, HÀC13)); 6.97 1d, J15,6) ˆ 8.5, HÀC16)); 8.98 1s, AcNHÀC12)); 9.03 1s, AcNHÀC11)).
12.3. N,N'-{4-[Bis&2-hydroxyethyl)amino]-1,2-phenylene}bis[acetamide] 114). Oxirane 110 ml) was added
gradually to a soln. of 13 120.3 mmol, 4.2 g) in 25% aq. AcOH soln. 130 ml) cooled to 2 ± 38. The mixture was
stirred at 58 for 5 h. The excess oxirane was evaporated, the residue triturated in Et2O, and the final
compound purified by precipitation from MeOH/Et2O 1:4: 4.80 g 180.3%) of 14. M.p. 178± 180 8 1[7]: 174 ± 1758
1EtOH)). 1H-NMR 11D6)DMSO): 1.97 1s, Ac), 2.01 1s, Ac); 3.34 1m, N1CH2)2); 3.50 1m, 2 CH2O); 4.72

2936
Helvetica Chimica Acta ± Vol. 83 12000)
1t, J ˆ 5, 2 OH); 6.43 1dd, J15,6) ˆ 9, J13,5) ˆ 2.7, HÀC15)); 6.85 1d, J13,5) ˆ 2.7, HÀC13)); 7.10 1d, J15,6) ˆ 9,
HÀC16)); 8.95 1s, NH); 9.16 1s, NH).
12.4. 2,2'-[&2-Methyl-1H-benzimidazol-5-yl)imino]bis[ethanol] 115). A soln. of 14 110.17 mmol, 3 g) in
18% aq. HCl soln. 160 ml) was refluxed for 3 h. The mixture was cooled, neutralized with K2CO3, and extracted
with AcOEt. Pure 15 was obtained by precipitation from MeOH/Et2O 1:4: 0.72 g 130%). M.p. 151 ± 1538 1[7]:
149 ± 1518). 1H-NMR 1CD3OD): 2.49 1s, Me); 3.51 1t, J ˆ 6, N1CH2)2); 3.72 1t, J ˆ 6, 2 CH2O); 6.781 dd, J14,6) ˆ
2.4, J16,7) ˆ 8.8, HÀC16)); 6.83 1d, J14,6) ˆ 2.4, HÀC14)); 7.29 1dd, J14,7) ˆ 0.25, J16,7) ˆ 8.8, HÀC17)).
12.5. 2,2'-{{2-Methyl-1-[&4-methylphenyl)sulfonyl]-1H-benzimidazol-5-yl}imino}- and 2,2'-{{2-Methyl-1-
[&4-methylphenyl)sulfonyl]-1H-benzimidazol-6-yl}imino}bis[ethanol] Bis&4-methylbenzenesulfonate) 116a and
16b, resp.). A soln. of 15 15.45 mmol, 1.28g) in pyridine 160 ml) was cooled to 0 8, and solid TsCl 132.7 mmol,
6.25 g) was added portionwise. This soln. was stored at 58 for 72 h and then poured into stirred ice-water. The
crude product, which crystallized within 15 min, was filtered off and washed with H2O. The precipitate was dried
1
in vacuo: 2.4 g 162%) of 16a/16b. Cream-colored crystals. M.p. 127 ± 1288. H-NMR 1CDCl3): 2.36 1s, 6 H, Me
1TsO)); 2.39 1s, 3 H, Me 1TsN)); 2.75 1s, 1.8H, Me ÀC12) 116a)); 2.76 1s, 1.2 H, MeÀC12) 116b)); 3.59 1t, J ˆ 5.7,
2.4 H, CH2N); 3.60 1t, J ˆ 5.7, 1.6 H, CH2N); 4.10 1t, J ˆ 5.7, 2.4 H, CH2O); 4.13 1t, J ˆ 5.7, 1.6 H, CH2O); 6.40
1dd, J16,7) ˆ 8.9, J14,6) ˆ 2.5, 0.4 H, HÀC16) 116a)); 6.51 1dd, J16,7) ˆ 9, J14,6) ˆ 2.5, 0.6 H, HÀC15) 116b));
6.59 1d, J14,6) ˆ 2.5, 0.6 H, HÀC14) 116a)); 7.081 d, J14,6) ˆ 2.5, 0.4 H, HÀC17) 116b)); 7.19 ± 7.34 1m, 7 H,
arom. H 1Ts), HÀC14) 116b)); 7.65 ± 7.82 1m, 7 H, arom. H 1Ts), HÀC17) 116a)). ESI-MS: 700 123), 699 140),
‡
6981100, [ M ‡ 1] ).
12.6. 2-Methyl-1-[&4-methylphenyl)sulfonyl]-5- and -6-&tetrahydro-2H-1,4-selenazin-4-yl)-1H-benzimida-
zole 117a and 17b, resp.). Method A: A soln. of NaHSe 11.13 mmol, 0.79 g) in EtOH 125 ml) was added slowly
and dropwise to powdered 16a/16b 11.13 mmol, 0.050 g). The resulting mixture was stirred and refluxed for 6 h
under N2, followed by another 15 h of stirring at r.t. EtOH was removed under reduced pressure and the residue
suspended in H2O 15 ml). The crude product was extracted with CHCl3 115 ml), then purified by FC 1silica gel,
gradient CHCl3, CHCl3/MeOH 95 :5, CHCl3/MeOH 80 :20): 0.160 g 133%) of 17a/17b.
t
Method B: A mixture 16a/16b 11.27 mmol, 0.885 g) in THF 112 ml) and BuOH 10.5 ml) was slowly and
dropwise added to a suspension of Li2Se 11.27 mmol, 0.118g) in THF 14 ml). The resulting mixture was stirred
overnight under N2 at r.t. Workup as described in Method A: 10.190 g, 35%) of 17a/17b. 1H-NMR 1CDCl3): 2.38
1s, 6 H, Me 1TsN) 117a/17b)); 2.74 1s, 3 H, MeÀC12) 117a)); 2.76 1s, 3 H, MeÀC12) 117b)); 2.79 1AA'XX', 4 H,
N1CH2)2); 3.77 1AA'XX', 4 H, Se1CH2)2); 6.88 1d, J14,6) ˆ 2.1, 0.4 H, HÀC15) of 17b); 6.92 1dd, J16,7) ˆ 8.8,
J14,6) ˆ 2.1, 0.6 H, HÀC16) 117a)); 7.06 1d, J14,6) ˆ 2.1, 0.6 H, HÀC14) 117a)); 7.29 1AA'XX', JA1JX) ˆ 8.8, 4 H,
Hm 1Ts)); 7.47 1d, J16,7) ˆ 8.7, 0.4 H, HÀC14) 117b), and 0.6 H, HÀC17) 117b)); 7.781 AA'XX', JA1JX) ˆ 8.3, 4 H,
.
‡
Ho 1Ts)); 7.86 1d, J16,7) ˆ 9.0, 0.6 H, HÀC17) 117a)). EI-MS: 435 168, M ).
12.7. &Tetrahydro-2H-1,4-selenazinyl)-1H-benzimidazole 18. A soln. of 0.1m Me4NCl in 94% EtOH
1300 ml), in the electrolysis cell at 58, was flushed with a slow stream of Ar and electrolyzed at a potential
of À 2.3 V. To this pre-electrolyzed soln., 17a/17b 10.37 mmol, 0.160 g) in EtOH 15 ml) was added. After
90 min, at a potential of À 1.6 V, the current had dropped to 10 mA 1TLC 1silica gel, MeOH/CH2Cl2 1:9):
no starting material left). The solvent was evaporated and the residue dissolved in H2O. The pH of the aq.
soln. was adjusted to 9 ± 10 with 10% aq. K2CO3 soln. The crude product was extracted with CH2Cl2. FC
1silica gel, MeOH/CH2Cl2 1:9) gave pure 18 10.08g, 77%). Product 18 was also isolated in 53% yield as a
by-product in the synthesis of 17a/17b, when 2 equiv. of Li2Se for 1 equiv. of 16a/16b were used. 1H-NMR
1CDCl3): 2.581 s, Me); 2.81 1AA'XX', JA1JX) ˆ 5.1, N1CH2)2); 3.66 1AA'XX', JA1JX) ˆ 5.1, Se1CH2)2); 6.87
1dd, J16,7) ˆ 8.7, J14,6) ˆ 2.0, HÀC16)); 7.00 1d, J14,6) ˆ 2, HÀC14)); 7.42 1d, J16,7) ˆ 8.7, HÀC17)). EI-MS: 281
.
‡
141, M ).
13. 2,2'-[&3,4-Diaminophenyl)imino]bis[ethanol] 119). A mixture of 2,2'-[14-amino-3-nitrophenyl)imino]-
bis[ethanol] [24] 11.51 mmol, 0.364 g), 5% Ru/C 10.073 g, 20%), N2H4 ´ H2O 11 ml), and EtOH 130 ml) was
refluxed for 1.5 h. The mixture was filtered through a pad of Celite and the solvent evaporated: 0.28g 190%) of
19, which was used without further purification in the next step. Cream-colored solid. 1H-NMR 1CD3OD): 3.34
1t, J ˆ 6.0, N1CH2)2); 3.64 1t, J ˆ 6.0, 2 CH2O); 6.15 1dd, J13,5) ˆ 2.7, J15,6) ˆ 8.4, HÀC15)); 6.31 1d, J13,5) ˆ 2.7,
HÀC13)); 6.62 1d, J15,6) ˆ 8.4, HÀC16)).
14. 2-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}-5-&tetrahydro-2H-1,4-selenazin-4-yl)-
1H-benzimidazole 124). 14.1. 2,2'-{{2-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}-1H-benzi-
midazol-5-yl}imino}bis[ethanol] 121). A mixture of 19 12.75 mmol, 0.58g) and 20 12.75 mmol, 0.98g) in iPrOH
130 ml) was stirred and refluxed for 7 h under N2. The resulting soln. was stirred overnight under N2 at r.t. The
solvent was evaporated and the raw material subjected to FC 1silica gel, MeOH/CH2Cl2 2 :98, 5 :95, and 10 :90):
0.43 g 133%) of 24. Golden crystals. M.p.: darkening at 2698, no melting up to 3508. Rf 1MeOH/CH2Cl2 2 :8 )

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2937
0.79. 1H-NMR 1CD3OD): 3.55 1t, J ˆ 5.8, N1CH2)2); 3.76 1t, J ˆ 5.8, O1CH2)2); 4.59 1s, OCH2CB10H10CH); 4.79
1br. s, CB10H10CH); 6.84 1dd, J14,6) ˆ 2.3, J16,7) ˆ 8.9, HÀC16)); 6.88 1d, J14,6) ˆ 2.3, HÀC14)); 7.07 1AA'XX',
JA1JX) ˆ 8.9, 2 Hm); 7.42 1d, J16,7) ˆ 8.9, HÀC17)); 7.96 1AA'XX', JA1JX) ˆ 8.9, 2 Ho). ESI-MS: 472 155, [M ‡
‡
1] ), 471 198), 470 1100), 469 175), 468 133).
14.2. 2,2'-{{2-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}-1-[&4-methylphenyl)sulfonyl]-
1H-benzimidazol-5-yl}imino}- and 2,2'-{{2-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}-1-[&4-
methylphenyl)sulfonyl]-1H-benzimidazol-6-yl}imino}bis[ethanol] Bis&4-methylbenzenesulfonate) 122a and 22b,
resp.). As described for 16a/16b, with 21 10.48mmol, 0.23 g), pyridine 110 ml) and TsCl 12.88mmol, 0.55 g,
‡
6 equiv.): 0.33 g 174%) of 22a/22b. ESI-MS: 935 132), 934 167, [M ‡ 1] ), 933 197), 932 1100), 931 162), 930 133).
14.3. 2-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}-1-[&4-methylphenyl)sulfonyl]-5- and -
6-&tetrahydro-2H-1,4-selenazin-4-yl)-1H-benzimidazole 123a and 23b, resp.). A soln. of 22a/22b 10.32 mmol,
0.3 g) in THF 15 ml) and tBuOH 10.5 ml) was added dropwise to Li2Se 10.67 mmol, 0.053 g, 2 equiv.) suspended
in THF 15 ml). The mixture was stirred and refluxed under N2 for 2 h, then left overnight at r.t. Workup as
described for 11. The final product 23a/23b was purified by FC 1silica gel, acetone/hexane 4 :6). Rf 1acetone/
‡
hexane 5 :5) 0.54. ESI-MS: 673 130), 672 163), 671 192), 670 1100, [M ‡ 1] ), 669 195), 668178), 667 155), 666
133), 665 120).
14.4. [&Carbaboranylmethoxy)phenyl]&tetrahydro-2H-1,4-selenazinyl)-1H-benzimidazole 24 was obtained
as a by-product in the synthesis of 23a/23b as fine pale yellow crystals: 0.04 g 124%). M.p. 868 1dec.). Rf
1acetone/hexane 5 :5) 0.48. 1H-NMR 11D6)acetone): 2.77 1AA'XX', JA1JX) ˆ 5.1, N1CH2)2); 3.681 AA'XX',
JA1JX) ˆ 5.1, Se1CH2)2); 4.74 1s, OCH2CB10H10CH); 4.981br. s, CB10H10CH); 6.91 1dd, J14,6) ˆ 2.3, J16,7) ˆ 8.8,
HÀC16)); 7.01 1d, J14,6) ˆ 2.3, HÀC14)); 7.12 1AA'XX', JA1JX) ˆ 9.0, 2 Hm); 7.44 1d, J16,7) ˆ 8.8, HÀC17)); 8.13
‡
1AA'XX', JA1JX) ˆ 9.0, 2 Ho). ESI-MS: 519 119), 518150), 517 186), 516 1100, [ M ‡ 1] ), 515 194), 514 177), 513
156), 512 133).
15. 2,2'-{{2'-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethyl]phenyl}[2,5'-bi-1H-benzimidazol]-5-yl}imi-
i
no}bis[ethanol] 126a). A mixture of 19 10.52 mmol, 0.11 g) and 7a 10.52 mmol, 0.24 g) in PrOH 120 ml) was
stirred and refluxed for 7 h under N2. The resulting soln. was stirred overnight under N2 at r.t. The solvent was
evaporated and the red residue subjected to FC 1silica gel, MeOH/CH2Cl2 1:9): 0.10 g 134%) of 26a. Brilliant
yellow crystals. M.p.: darkening at 2038, no melting up to 3508. Rf 1MeOH/CH2Cl2 1 :9) 0.37. 1H-NMR
1CD3OD): 3.581 t, J ˆ 5.8, N1CH2)2); 3.63 1s, CH2CB10H10CH); 3.77 1t, J ˆ 5.8, O1CH2)2); 4.481 s, CB10H10CH);
6.88 1dd, J14,6) ˆ 2, J16,7) ˆ 8.8, HÀC16)); 6.92 1d, J14,6) ˆ 2, HÀC14)); 7.39 1AA'XX', JA1JX) ˆ 8.3, 2 Hm); 7.45
1d, J16,7) ˆ 8.8, HÀC17)); 7.71 1d, J16',7') ˆ 8.5, HÀC17')); 7.95 1dd, J14',6') ˆ 1.5, J16',7') ˆ 8.5, HÀC16')); 8.09
1AA'XX', JA1JX) ˆ 8.3, 2 Ho); 8.25 1d, J14',6') ˆ 1.5, HÀC14')).
16. 2,2'-{{2'-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-yl]phenyl}[2,5'-bi-1H-benzimidazol]-5-yl}imino}-
bis[ethanol] 126b). As described for 26a, with 19 10.33 mmol, 0.07 g), 7b 10.33 mmol, 0.16 g) and iPrOH
120 ml). FC 1silica gel, MeOH/CH2Cl2 1:9) gave 0.08g 144%) of 26b. Brilliant yellow crystals. M.p.: darkening
at 3128, no melting up to 3508. Rf 1MeOH/CH2Cl2 1:9) 0.33. 1H-NMR 1CD3OD): 3.57 1t, J ˆ 5.8, N1CH2)2); 3.78
1t, J ˆ 5.8, O1CH2)2); 5.181 s, CB10H10CH); 6.85 1dd, J14,6) ˆ 2, J16,7) ˆ 8.8, HÀC16)); 6.91 1d, J14,6) ˆ 2,
HÀC14)); 7.45 1d, J16,7) ˆ 8.8, HÀC17)); 7.70 1AA'XX', JA1JX) ˆ 8.5, 2 Hm); 7.72 1d, J16',7') ˆ 8.9, HÀC17'));
7.95 1d, J16',7') ˆ 8.9, HÀC16')); 8.09 1AA'XX', JA1JX) ˆ 8.5, 2 Ho); 8.25 1s, HÀC14')).
17. 2'-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}-5-&tetrahydro-2H-1,4-selenazin-4-yl)-
2,5'-bi-1H-benzimidazole 129). 17.1. 2,2'-{{2'-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}[2,5'-
bi-1H-benzimidazol]-5-yl}imino}bis[ethanol] 126c). As described for 26a, with 19 11.36 mmol, 0.29 g), 25
i
11.36 mmol, 0.6 g), and PrOH 140 ml). FC 1silica gel, MeOH/CH2Cl2 1:9) gave 0.34 g 143%) of 26c. Brilliant
yellow crystals. M.p.: darkening at 2478, no melting up to 3508. Rf 1MeOH/CH2Cl2 1 :4) 0.6 ± 0.7. 1H-NMR
1CD3OD): 3.55 1t, J ˆ 5.8, N1CH2)2); 3.77 1t, J ˆ 5.8, O1CH2)2); 4.55 1s, OCH2CB10H10CH); 4.75
1s, CB10H10CH); 6.85 1dd, J14,6) ˆ 2, J16,7) ˆ 8.8, HÀC16)); 6.88 1d, J14,6) ˆ 2, HÀC14)); 7.05 1AA'XX',
JA1JX) ˆ 8.9, 2 Hm); 7.42 1d, J16,7) ˆ 8.8, HÀC17)); 7.63 1d, J16',7') ˆ 8.5, HÀC17')); 7.86 1dd, J14',6') ˆ 1.5,
J16',7') ˆ 8.5, HÀC16')); 8.00 1AA'XX', JA1JX) ˆ 8.9, 2 Ho); 8.15 1d, J14',6') ˆ 1.5, HÀC14')). ESI-MS: 588 157,
‡
[M ‡ 1] ), 587 158), 586 1100), 585 164), 584 128).
17.2. 2,2'-{{2'-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl]-1,1'-bis[&4-methylphenyl]sul-
fonyl][2,5'-bi-1H-benzimidazol]-5-yl}imino}-, -[2,6'-bi-1H-benzimidazol]-6-yl}imino}-, -[2,6'-1H-benzimida-
zol]-5-yl}imino}-, and -[2,5'-bi-1H-benzimidazol]-6-yl}imino}bis[ethanol] Bis&4-methylbenzenesulfonate)
127a ± d). A soln. of 26c 10.31 mmol, 0.18g) in pyridine 140 ml) was cooled to 0 8, and solid TsCl 19.91 mmol,
32 equiv.) was added in portions. This soln. was left standing at 58 for 7 h. The mixture was poured into stirred
ice-water. The crude product, which crystallized within 15 min, was filtered off and washed with H2O. The

2938
Helvetica Chimica Acta ± Vol. 83 12000)
precipitate was dried in vacuo: 0.19 g 151%) of 27a ± d2). Cream-colored crystals. ESI-MS: 1205 125), 1204 145,
‡
[M ‡ 1] ), 1203 157), 1202 141), 1201 130).
17.3. 2'-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}-1-[&4-methylphenyl)sulfonyl]-5-&tet-
rahydro-2H-1,4-selenazin-4-yl)-2,5'-bi-1H-benzimidazole and -6-&tetrahydro-2H-1,4-selenazin-4-yl)-2,6'-bi-1H-
benzimidazole, and 2'-{4-[1,2-Dicarba-closo-dodecaboran&12)-2-ylmethoxy]phenyl}-1-[&4-methylphenyl)sulfon-
yl]-5-&tetrahydro-2H-1,4-selenazin-4-yl)-2,6'-bi-1H-benzimidazole and -6-&tetrahydro-2H-1,4-selenazin-4-yl)-
2,5'-bi-1H-benzimidazole 128a ± d). The mixture 27a ± d 10.15 mmol, 0.18g) in THF 15 ml) and tBuOH
10.5 ml) was slowly and dropwise added to a stirred suspension of Li2Se 10.6 mmol, 0.056 g, 4 equiv.) in THF
15 ml) under N2. The soln. was stirred at 708 for 3 h and left at r.t. overnight. H2O was added to the resulting
mixture and the soln. extracted with Et2O. The mixture was separated from by-products by FC 1silica gel,
acetone/hexane 1:1): 0.05 g 137%) of 28a ± d2). M.p. 271 ± 2738. Rf 1MeOH/CH2Cl2 1 :9) 0.90 ± 0.94. ESI-MS:
‡
788 160), 787 186), 786 1100, [M ‡ 1] ), 785 191), 784 193), 783 151).
17.4. [&Carbaboranylmethoxy)phenyl]&tetrahydro-2H-1,4-selenazin-4-yl)-2,5'-bi-1H-benzimidazole 29 was
obtained as a by-product in the synthesis of 28a ± d: 0.04 g 142%). M.p. 1408 1dec.). Rf 1MeOH/CH2Cl2 1 :9) 0.67.
1H-NMR 1CD3OD): 2.79 1AA'XX', JA1JX) ˆ 5.1, N1CH2)2); 3.66 1AA'XX', JA1JX) ˆ 5.1, Se1CH2)2); 4.54
1s, OCH2CB10H10CH); 4.74 1br. s, CB10H10CH); 6.95 1dd, J14,6) ˆ 2.2, J16,7) ˆ 8.8, HÀC16)); 7.04 1AA'XX',
JA1JX) ˆ 8.9, 2 Hm); 7.06 1d, J14,6) ˆ 2.5, HÀC14)); 7.47 1d, J16,7) ˆ 8.9, HÀC17)); 7.64 1d, J16',7') ˆ 8.4,
HÀC17')); 7.89 1dd, J14',6') ˆ 1.5, J16',7') ˆ 8.5, HÀC16')); 7.99 1AA'XX', JA1JX) ˆ 8.8, 2 Ho); 8.18
‡
1d, HÀC14')). ESI-MS: 634 153), 633 186), 632 1100, [M ‡ 1] ), 631 190), 630 173), 629 155), 628135).
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Received May 5, 2000
The 1H-NMR spectrum 1CDCl3) of the product mixture was too complex for a full interpretation, especially
with respect to the presence of the four isomers. Nevertheless, we conclude from our model reactions with
15 that all four isomers should have been formed.
2
)