[4+2] Cycloaddition reactions of 1,2,4,5-tetrazines with allylcarboranes

Article abstract of DOI:10.1007/s11172-010-0053-z

The [4+2] cycloaddition reactions of 3,6-disubstituted 1,2,4,5-tetrazines with 9-allyl-1,7-, 9-allyl-1,2-dicarba-closo-dodecaboranes and 1-allyl-2-isopropyl-1,2-dicarba-closo-dodecaborane have been studied. The pyridazines containing carborane cage have b

Full text of DOI:10.1007/s11172-010-0053-z

Russian Chemical Bulletin, International Edition, Vol. 59, No. 1, pp. 116—121, January, 2010
116
[4+2] Cycloaddition reactions of 1,2,4,5ꢀtetrazines with allylcarboranes
G. L. Rusinov,а R. I. Ishmetova,а S. G. Tolshchina,а N. K. Ignatenko,а I. N. Ganebnykh,а P. A. Slepukhin,а
V. A. Ol'shevskaya,b V. N. Kalinin,b and V. N. Charushinа
aI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22 ul. S. Kovalevskoi, 620990 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 1189. Eꢀmail: rusinov@ios.uran.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6549.
The [4+2] cycloaddition reactions of 3,6ꢀdisubstituted 1,2,4,5ꢀtetrazines with 9ꢀallylꢀ1,7ꢀ,
9ꢀallylꢀ1,2ꢀdicarbaꢀclosoꢀdodecaboranes and 1ꢀallylꢀ2ꢀisopropylꢀ1,2ꢀdicarbaꢀclosoꢀdodecabꢀ
orane have been studied. The pyridazines containing carborane cage have been synthesized for
the first time.
Key words: 3,6ꢀdisubstituted 1,2,4,5ꢀtetrazines, allylcarboranes, pyridazines, [4+2] cycꢀ
loaddition.
Схема 1
One of the promising ways of the search for compounds
for the boron neutron capture therapy of cancer is modifiꢀ
cation of carboranes with functionalized nitrogenꢀconꢀ
taining heterocycles.1—3 Such modification is needed for
targeted delivery of carboraneꢀcontaining molecules to the
cancer cells and specific binding to them.
For this purpose, we studied the Diels—Alder reaction
(inverted electronic demand) of symmetrically 3,6ꢀdisubꢀ
stituted tetrazines 1а—f with 9ꢀallylꢀmꢀ and 9ꢀallylꢀoꢀcarꢀ
boranes (2, 3), as well as with 1ꢀallylꢀ2ꢀisopropylꢀoꢀcarꢀ
borane (4) (Scheme 1).
The reaction was carried out under reflux in toluene,
oꢀxylene or mesitylene (Table 1). The [4+2] cycloaddition
of allylcarborane to the tetrazine ring and subsequent elimꢀ
ination of molecular nitrogen results in dihydropyridazines
5a—f, 6a, 7a. In the reactions with tetrazines 1a,b having
3,5ꢀdimethylpyrazolyl or indazolyl substituents, the exꢀ
pected dihydropyridazines 5a,b and 6a form. In the other
cases, dihydropyridazines 5с—e, 7a produced in the reacꢀ
tion are oxidized by the starting tetrazines to aromatic
compounds 8с—e and 10a (see Scheme 1). 1,2,4,5ꢀTetraꢀ
zines can act as oxidants due to their high electrophilicity.
For example, initial tetrazine 1а has the electrochemical
reduction potential (ϕ) in acetonitrile equal to –1.040 V
and the energy of its LUMO is 3.841 eV (see Ref. 4).
The reaction of 3,6ꢀbis(2ꢀpyridyl)ꢀ1,2,4,5ꢀtetrazine (1f)
with 9ꢀallylꢀmꢀcarborane (2) affords a mixture of dihydroꢀ
pyridazine 5f and aromatic pyridazine 8f (1Н NMR data).
It is known that 4,5ꢀdihydropyridazines formed upon
[4+2] cycloaddition of ethylene derivatives to 1,2,4,5ꢀtetꢀ
razines are generally isomerized to more stable 1,4ꢀdihyꢀ
dropyridazines.5—8 Carboraneꢀcontaining 4,5ꢀdihydro deꢀ
1—9: R1
=
(a),
(b),
(c),
(d),
(e),
(f);
B, BH
C, CH
R2
=
[O] =
,
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 116—121, January, 2010.
1066ꢀ5285/10/5901ꢀ0116 © 2010 Springer Science+Business Media, Inc.

Cycloaddition of tetrazines to allylcarboranes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
117
Table 1. Yields and conditions for the synthesis of compounds
5a,b, 6a, 8a—f, 9a, 10a
C(20)
B(2)
B(5)
τ/ha
Product
Yield
(%)
B(1)
B(7)
B(8)
Starting
compound
Solvent
C(1)
C(2)
N(2)
C(3)
1a
1b
1a
1ab
5a
1bb
5b
1c
Toluene
oꢀXylene
Toluene
oꢀXylene
oꢀXylene
oꢀXylene
oꢀXylene
oꢀXylene
Mesitylene
oꢀXylene
Toluene
Toluene
Toluene
Toluenec
oꢀXylene
5
7
2
2.5
3
6
5a
5b
6a
8a
8a
8b
8b
8c
8d
8e
8f
9a
10a
10a
10a
52
35
41
44
64
39
58
26
34
44
42
47
33
34
46
B(6)
B(10)
B(9)
C(19)
N(1)
C(7)
C(6)
C(4)
C(5)
C(8)
N(3)
N(4)
C(9)
C(10)
C(11)
N(6)
C(12)
5
8
N(5)
C(18)
1d
1e
3.5
0.5
0.5
1.5
10
4
C(13)
C(14)
1fb
6a
1a
1a
1a
C(17)
C(16)
C(15)
4
Fig. 2. Crystal sturcture of 5b (the thermal ellipsoids are shown
with 50% probability).
a
τ is reaction time.
b 1 equivalent of chloranil was added to the reaction mixture.
c The reaction was carried out in an autoclave at 200 °С.
The signals for the proton Н(5) of the aromatic pyridazine
ring of compounds 8a—f, 9a, 10a are present in the region
of δ 7.39—8.39. The 1Н NMR spectra of dihydropyrazines
5a,b, 6a are characterized by the presence of multiplets at
δ 3.46—4.31 and 2.67—2.98. The signals for the protons of
the methylene bridges are present at δ 0.89—1.25 in the
case of dihydropyridazines and are shifted to the region of
δ 2.57—4.13 on passing to the aromatic systems.
Product 8d crystallizes as colorless triclinic crystals.
The pyridazine ring is planar, the deviations of atoms from
the meanꢀsquare plane is no more than 0.03 Å. Both pheꢀ
nyl substituents have planar geometry (to within 0.01 Å)
and are turned relative the plane of the heterocycle: the
dihedral angles are 23.70° and 42.51°. The increase in one
rivatives 5a,b and 6a are stable and, according to the
1Н NMR data, do not transform to 1,4ꢀdihydropyridazines
even upon prolonged heating in oꢀxylene at 143 °С.
The structures of aromatic pyridazines and dihydropyꢀ
ridazines containing the carborane fragments were conꢀ
firmed by elemental analysis, 1Н NMR spectroscopy,
chromatoꢀmass spectrometry, and Xꢀray diffraction analꢀ
ysis (Figs 1—3). The 1Н NMR spectra of compounds
5a,b, 6a, 8a—f, 9a, 10a (Table 2) contain the ВН signals
as weaklyꢀresolved multiplets in the region of δ 0.8—3.7.
C(11)
C(12)
C(10)
C(11)
C(10)
C(13)
C(20)
C(18)
N(4)
N(3)
C(19)
C(15)
N(1)
C(9)
C(9)
C(8)
C(14)
N(2)
C(2)
C(15)
C(16)
C(12)
N(5)
C(7)
N(6)
B(3)
C(8)
N(2)
C(14)
C(13)
C(6)
C(7)
C(6)
C(16)
C(17)
B(7)
C(3)
C(4)
N(1)
C(1)
B(6)
B(7)
B(10)
C(4)
C(1)
B(10)
C(5)
C(17)
B(2)
C(18)
C(5)
C(3)
C(2)
B(6)
B(5)
B(4)
B(1)
B(8)
B(9)
B(4)
B(1)
B(5)
B(9)
B(2)
C(19)
H(10)
Fig. 1. Crystal structure of 8d (the thermal ellipsoids are shown
Fig. 3. Crystal structure of 10а (the thermal ellipsoids are shown
with 50% probability).
with 50% probability).

118
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
Rusinov et al.
Table 2. The 1Н NMR spectra (СDCl3) of compounds 5a,b, 6a, 8a—f, 9a, 10a
Compound
δ (J/Hz)
5a
0.98—3.46 (m, 9 Н, 9 BH); 1.05 (m, 2 Н, СН2); 2.26 (s, 6 Н, 2 MePz*); 2.65, 2.69 (both s, 3 Н each, 2 MePz);
2.73 (m, 1 Н, Н(4) pyridazine); 2.91 (br.s, 2 Н, Н(1), Н(7) carborane); 3.94, 4.00 (both m, 1 Н each,
2 Н(5) pyridazine); 5.99 (s, 2 Н, 2 Н(4) pyrazole)
5b
1.36—4.02 (m, 9 Н, 9 ВН); 1.25 (m, 2 Н, СН2); 2.94 (br.s, 2 Н, Н(1), Н(7) carborane); 2.98 (m, 1 Н,
Н(4) pyridazine); 4.16, 4.31 (both m, 1 Н each, 2 Н(5) pyridazine); 7.34, 7.58, 7.78, 8.21 (all m, 2 Н each,
8 СН indazole); 8.89, 8.95 (both m, 1 Н each, 2 СН indazole)
6a
0.90—3.28 (m, 9 Н, 9 BH); 0.89 (m, 2 Н, СН2); 2.26, 2.27, 2.62, 2.66 (all s, 3 Н each, 4 MePz);
2.67 (m, 1 Н, Н(4) pyridazine); 3.46, 3.53 (both br.s, 1 Н each, Н(1), Н(2) carborane); 3.83, 3.89 (both m,
1 Н each, 2 Н(5) pyridazine); 5.97 (s, 2 Н, 2 Н(4) pyrazole)
8a•0.5 DHB**
8b•0.5 DHB
8c
0.53—3.30 (m, 9 Н, 9 BH); 2.31, 2.32, 2.39, 2.74 (all s, 3 Н each, 4 MePz); 2.84 (br.s, 4 H,
СН2, Н(1), Н(7) carborane); 5.99 (br.s, 1 Н, OH 2,3,5,6ꢀtetrachloroꢀ1,4ꢀdihydroxybenzene);
6.03, 6.05 (both s, 1 Н each, 2 Н(4) pyrazole); 8.04 (s, 1 Н, Н(5) pyridazine)
0.82—3.03 (m, 9 Н, 9 BH); 2.69 (br.s, 2 Н, Н(1), Н(7) carborane); 3.08 (s, 2 Н, СН2); 5.74 (br.s, 1 Н,
OH 2,3,5,6ꢀtetrachloroꢀ1,4ꢀdihydroxybenzene); 7.27, 7.35, 7.48, 7.59, 7.99, 9.01 (all m, 1 Н each,
6 СН indazole); 7.81, 8.29 (both m, 2 Н each, 4 СН indazole); 8.28 (s, 1 Н, Н(5) pyridazine)
0.78—3.62 (m, 9 Н, 9 ВН); 2.34, 2.35 (both s, 3 Н each, 2 Me imidazole); 2.57 (s, 2 Н, СН2);
2.93 (br.s, 2 Н, Н(1), Н(7) carborane); 7.10, 7.45, 7.87, 8.35 (all s, 1 Н each, 2 Н(2), 2 Н(5) imidazole);
7.39 (s, 1 Н, Н(5) pyridazine)
8d
8e
0.88—3.70 (m, 9 Н, 9 ВН); 2.60 (s, 2 Н, СН2); 2.83 (br.s, 2 Н, Н(1), Н(7) carborane); 7.43—7.56 (m, 6 Н,
6 СН, Ph); 7.65, 8.14 (both m, 2 Н each, 4 СН, Ph); 7.69 (s, 1 Н, Н(5) pyridazine)
1.10—3.05 (m, 9 Н, 9 ВН); 2.62 (s, 2 Н, СН2); 2.87 (br.s, 2 Н, Н(1), Н(7) carborane); 7.49—7.55,
8.74—8.77 (both m, 2 Н each, 4 СН pyridyl); 8.05, 8.59, 8.93, 9.29 (all m, 1 Н each, 4 СН pyridyl);
7.75 (s, 1 Н, Н(5) pyridazine)
8f•DHB
9a
0.95—2.69 (m, 9 Н, 9 ВН); 2.75 (br.s, 2 Н, Н(1), Н(7) carborane); 3.13 (s, 2 Н, СН2); 6.00 (br.s, 2 Н,
OH 2,3,5,6ꢀtetrachloroꢀ1,4ꢀdihydroxybenzene); 7.36—7.41, 7.85—7.91, 8.75 (all m, 2 Н each, 6 СН pyridyl);
8.07, 8.72 (both m, 1 Н each, 2 СН pyridyl); 8.39 (s, 1 Н, Н(5) pyridazine)
0.89—3.35 (m, 9 Н, 9 ВН); 2.30, 2.32, 2.38, 2.73 (all s, 3 Н each, 4 MePz); 2.68 (s, 2 H, СН2);
3.41, 3.46 (both br.s, 1 Н each, Н(1), Н(7) carborane); 6.01, 6.04 (both s, 1 Н each, 2 Н(4) pyrazole);
7.95 (s, 1 Н, Н(5) pyridazine)
10a
1.02—2.94 (m, 10 Н, 10 ВН); 1.19 (д, 6 Н, 2 Me, Pri, J = 7.4); 2.26 (m, 1 Н, СН, Pri); 2.27, 2.33, 2.51,
2.79 (all s, 3 Н each, 4 MePz); 4.13 (s, 2 H, СН2); 6.09, 6.13 (both s, 1 Н each, 2 Н(4) pyrazole);
8.22 (s, 1 Н, Н(5) pyridazine)
* Pz is pyrazolꢀ1ꢀyl.
** DHB is 2,3,5,6ꢀtetrachloroꢀ1,4ꢀdihydroxybenzene.
of the dihedral angles by ~20° and in the bond angle
С(16)—С(15)—С(9) up to 125.9° is associated with the
steric interference of the carborane polyhedron on the closꢀ
est phenyl substituent. The values of other geometric paꢀ
rameters are close to the standard ones. It is noteworthy
that shortened intermolecular contact (IMC) is present
between the proton Н(10) of the carborane polyhedra and
twist conformation, the deviations of the atoms С(9) and
С(10) from the meanꢀsquare plane passing through the
atoms С(8)—N(3)—N(4)—C(11) are 0.367 and 0.189 Å,
respectively. The carborane substituent occupies the pseuꢀ
doꢀaxial position. The indazolyl substituents do not virtuꢀ
ally exit from the plane of conjugation. No equalization of
conjugated double bond lengths in the pyridazine ring was
observed (N(3)—N(4) 1.424(2) Å, N(4)=С(11) 1.268(2) Å,
N(3)=С(8) 1.275(2) Å). The values of the other geometric
parameters are close to the standard ones.
Product 10а crystallizes as colorless triclinic crystals.
The pyridazine ring has a planar geometry. One of the
pyrazolyl rings lies in the plane of conjugation with pyꢀ
ridazine, the deviations of atoms from the meanꢀsquare
plane passing through both heterocycles are no more than
0.07 Å. The second pyrazolyl substituent is turned relative
...
the atoms N(1), N(2) of the pyridazine ring (N(1) H(10)
2.16 Å, [1 + x,y,z], N(2)...H(10) 2.30 Å, [1 + x,y,z]).
Taking into account the specific character of the С—Н
bond in the carborane polyhedra, one can speak on the
formation of intermolecular hydrogen bond (IMHB) havꢀ
...
ing triangular geometry with virtually equal distances Н
for both donor atoms.
N
Product 5b crystallizes as colorless monoclinic crysꢀ
tals. Dihydropyridazine ring is nonplanar and has pseudoꢀ

Cycloaddition of tetrazines to allylcarboranes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
119
(СDCl3, δ): 7.45, 7.68, 7.89, 8.72 and 8.52 (all m, 2 Н each,
2 indazolyls).
to the plane of the azine (dihedral angle is ~47°) due to the
steric interaction with the carborane polyhedron. The valꢀ
ues of the other geometric parameters are close to the
standard ones.
3,6ꢀDiꢀ(4ꢀmethylimidazolꢀ1ꢀyl)ꢀ1,2,4,5ꢀtetrazine (1с). The
yield was 48%. M.p. 208—209 °С. Found (%): С, 49.66; H, 4.00;
N, 46.54. С10H10N8. Calculated (%): С, 49.58; Н, 4.16; N, 46.26.
1Н NMR (СDCl3, δ): 2.37 (s, 6 Н, 2 С(4)Ме); 7.71 (s, 2 Н,
2 Н(5)); 8.65 (s, 2 Н, 2 Н(2)).
The carbonꢀsubstituted 1ꢀallylꢀ2ꢀisopropylꢀoꢀcarboꢀ
rane (4) undergoes the [4+2] cycloaddition reaction with
1,2,4,5ꢀtetrazines considerably more slowly than boronꢀ
substituted allylcarboranes 2 and 3, which apparently is
associated with the influence of the carborane cage, as
well as with the steric hindrance caused by the isopropyl
substituent. By the example of reaction of 3,6ꢀbis(3,5ꢀ
dimethylpyrazolꢀ1ꢀyl)ꢀ1,2,4,5ꢀtetrazine (1a) with carboꢀ
rane 4, it was shown that the increase in the reaction
temperature to 200 °С reduces the process time from 10 h
to 4 h (see Table 1).
Dihydropyridazines 5a,b,f and 6a can be oxidized to
the corresponding aromatic derivatives 8a,b,f and 9a by
chloranil. It was established that pyridazines 8a,b,f, havꢀ
ing the mꢀcarborane fragment, contrary to pyridazine 9а
having the oꢀcarborane cage, form 1 : 1 and 1 : 2 molecuꢀ
lar complexes with the reduction product of chloranil,
viz., 2,3,5,6ꢀtetrachloroꢀ1,4ꢀdihydroxybenzene (DHB).
Oxidation can be carried out both after isolation and puriꢀ
fication of dihydropyridazines and under their synthesis
conditions. In situ oxidation allows reduction of the losses
of the target products in the intermediate steps.
1ꢀAllylꢀ2ꢀisopropylꢀ1,2ꢀdicarbaꢀclosoꢀdodecaborane (4). To
a solution of 1ꢀisopropylꢀoꢀcarborane (3.72 g, 20 mmol) in anꢀ
hydrous diethyl ether (30 mL), a 1.62 М solution of BuLi
(13.0 mL, 21 mmol) in hexane was added with stirring in an
argon atmosphere at 10 °С and the reaction mixture was stirred
at 20 °С for 30 min. Allyl bromide (2.54 g, 21 mmol) was added
to the obtained lithium derivative at 0 °С. The reaction mixture
was stirred at 25 °С for 4 h, then poured into water and extracted
with hexane (2×15 mL). The extract was dried with Na2SO4.
After evaporation of the solvent in vacuo and distillation, 1ꢀallylꢀ
2ꢀisopropylꢀoꢀcarborane was obtained in a yield of 3.8 g (84%).
B.p. 91—92 °С (1 Torr). Found (%): С, 42.21; Н, 9.82; В, 47.90.
С8Н22В10. Calculated (%): С, 42.48; Н, 9.73; В, 47.79. 1Н NMR
(СDCl3, δ): 1.22 (d, 6 Н, 2 Me, Pri, J = 6.9 Hz); 2.33 (hept, 1 Н,
СН, Pri, J = 6.9 Hz); 1.53—2.90 (m, 10 Н, 10 ВН); 2.94 (d, 2 Н,
СН2—СН=СН2, J = 7.2 Hz); 5.13 (m, 2 Н, СН2—СН=СН2);
5.76 (m, 1 Н, СН2—СН=СН2).
Preparation of pyridazines 5a,b, 6a, 8a—f, 10a (general
procedure). A solution of 3,6ꢀdisubstituted 1,2,4,5ꢀtetrazine
(1 mmol) and allylcarborane (1.1 mmol) in a solvent (15 mL)
was refluxed for 0.5—10 h. For the synthesis of 8a,b,f, chloranil
(270 mg, 1.1 mmol) was added. The course of the reacꢀ
tion was monitored by TLC. The solvent was removed and
the obtained crystalline residue was purified by recrystallizaꢀ
tion from methanol, ethyl acetate, benzene or acetonitrile.
The 1H NMR spectra of the obtained compounds are presented
in Table 2.
Thus, it was shown that [4+2] cycloaddition reaction
(inverted electronic demand) of allylcarboranes with
1,2,4,5ꢀtetrazines is very a convenient method for the prepꢀ
aration of carboraneꢀcontaining dihydropyridazines and
aromatic pyridazines. The process is influenced by the
substituents in positions 3 and 6 of the tetrazine ring, as
well as by the structure of allylcarborane.
3,6ꢀBis(3,5ꢀdimethylpyrazolꢀ1ꢀyl)ꢀ4ꢀ[(1,7ꢀdicarbaꢀclosoꢀ
dodecaboranꢀ9ꢀyl)methyl]ꢀ4,5ꢀdihydropyridazine (5а). M.p.
180—182 °C (from methanol). Found (%): C, 47.87; H, 7.18;
N, 19.57. C17H30B10N6. Calculated (%): C, 47.86; H, 7.09;
N, 19.70. MS, m/z (Irel (%)): 428 [MH]+ (100).
Experimental
3,6ꢀDi(indazolꢀ1ꢀyl)ꢀ4ꢀ[(1,7ꢀdicarbaꢀclosoꢀdodecaboranꢀ9ꢀ
yl)methyl]ꢀ4,5ꢀdihydropyridazine (5b). M.p. 234 °C (from ethyl
acetate). Found (%): C, 53.28; H, 5.45; N, 17.82. C21H26B10N6.
Calculated (%): C, 53.60; H, 5.57; N, 17.86. MS, m/z (Irel (%)):
471 [MH]+ (100).
3,6ꢀBis(3,5ꢀdimethylpyrazolꢀ1ꢀyl)ꢀ4ꢀ[(1,2ꢀdicarbaꢀclosoꢀ
dodecaboranꢀ9ꢀyl)methyl]ꢀ4,5ꢀdihydropyridazine (6a). M.p.
202—205 °C (from methanol). Found (%): C, 47.46; H, 7.19;
N, 19.74. C17H30B10N6. Calculated (%): C, 47.86; H, 7.09;
N, 19.70. MS, m/z (Irel (%)): 427 [M]+ (100).
Molecular complex of 3,6ꢀbis(3,5ꢀdimethylpyrazolꢀ1ꢀyl)ꢀ4ꢀ
[(1,7ꢀdicarbaꢀclosoꢀdodecaboranꢀ9ꢀyl)methyl]pyridazine with
2,3,5,6ꢀtetrachloroꢀ1,4ꢀdihydroxybenzene (8а•0.5 DHB). M.p.
181—183 °C (from acetonitrile). Found (%): C, 44.05; H, 5.37;
N, 15.62. C17H28B10N6•0.5 C6H2Cl4O2. Calculated (%):
C, 43.79; H, 5.33; N, 15.32.
Molecular complex of 3,6ꢀdi(indazolꢀ1ꢀyl)ꢀ4ꢀ[(1,7ꢀdicarꢀ
baꢀclosoꢀdodecaboranꢀ9ꢀyl)methyl]pyridazine with 2,3,5,6ꢀtetꢀ
rachloroꢀ1,4ꢀdihydroxybenzene (8b•0.5 DHB). M.p. 213 °C
(from benzene). Found (%): С, 48.44; Н, 4.31; N, 14.03.
C21H24B10N6•0.5 C6H2Cl4O2. Calculated (%): C, 48.65; H, 4.25;
N, 14.18.
Tetrazines 1a,9 1b,c,10 1d—f 11 and allylcarboranes 2 and 312
were synthesized according to the known procedures.
The NMR spectra were recorded on a Bruker Avance DRXꢀ400
spectrometer (400 MHz) using SiMe4 as the internal standard.
The chemical shifts are presented in the δ scale. The mass specꢀ
tra were measured on a Shimadzu LCMSꢀ2010 liquid chromatoꢀ
mass spectrometer after chromatographic separation (Supelcosil
LCꢀ18 (250×4.6 mm, 5 μm) column, a MeCN—H2O (85 : 15)
mixture as a mobile phase, the flow rate 1 mL min–1, the column
temperature 60 °C, the APCI ionization mode, the source temꢀ
perature 400 °C; the gas flow rate was 2.5 L min–1, the other
parameters of massꢀspectrometer were established according to
the autotuning procedure). The melting points were measured
on a Boetius heating table. The elemental analysis was carried
out on a Perkin Elmer PEꢀ2400 autoanalyzer. The course of the
reaction was monitored, and the purity of the products was
checked, by TLC on plates with a Sorbfil fixed layer in a benzꢀ
ene—acetonitrile (1 : 1) solvent system.
3,6ꢀDi(indazolꢀ1ꢀyl)ꢀ1,2,4,5ꢀtetrazine (1b). The yield was
81%. M.p. 274—275 °С. Found (%): С, 61.23; H, 3.14; N, 36.02.
C16H10N8. Calculated (%): С, 61.14; H, 3.21; N, 35.65. 1Н NMR

120
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
Rusinov et al.
Table 3. Crystallographic data and main details of structure refinement
Parameter
5b
8d
10a
Molecular weight
Crystal system
Space group
a/Å
b/Å
c/Å
α/deg
β/deg
470.58
Monoclinic
P2(1)/n
13.0829(17)
10.6332(12)
17.753(2)
90
92.218(10)
90
2467.8(5)
4
388.50
Triclinic
P1
466.63
Triclinic
P1
10.5095(4)
11.3783(11)
11.5337(16)
62.008(12)
81.750(9)
65.167(8)
1102.77(19)
2
12.2628(2)
13.5304(3)
23.4623(4)
84.092(2)
86.567(2)
88.114(2)
3863.85(13)
6
γ/deg
V/Å3
Z
dcalc
μ/mm–1
1.267
0.072
1.170
0.061
1.203
0.068
Scan interval
Number of reflections measured
26.38 ≥ θ ≥ 2.75
13345
26.37 ≥ θ ≥ 2.83
7584
26.37 ≥ θ ≥ 2.62
32665
(Rint
)
(0.0584)
4955
(0.0182)
4342
(0.0412)
15662
Number of independent reflections
with I > 2σ(I)
1997
2358
9706
Number of parameters in refinement
R1 (with I > 2σ(I))
wR2 (with I > 2σ(I))
R1 (for all reflections)
wR2 (for all reflections)
378
0.0563
0.0813
0.1581
282
0.0535
0.1421
0.0969
1378
0.0427
0.0891
0.0787
0.0963
0.0916
0.1562
3,6ꢀBis(4ꢀmethylimidazolꢀ1ꢀyl)ꢀ4ꢀ[(1,7ꢀdicarbaꢀclosoꢀdodeꢀ
3,6ꢀBis(3,5ꢀdimethylpyrazolꢀ1ꢀyl)ꢀ4ꢀ[(1,2ꢀdicarbaꢀclosoꢀ
dodecaboranꢀ9ꢀyl)]methylpyridazine (9a). M.p. 218—220 °C
(from acetonitrile). Found (%): C, 47.92; H, 6.93; N, 19.82.
C17H28B10N6. Calculated (%): C, 48.09; H, 6.65; N, 19.80. MS,
m/z (Irel (%)): 426 [MH]+ (100).
caboranꢀ9ꢀyl)methyl]pyridazine (8c). M.p. 194 °C (from methaꢀ
nol). Found (%): C, 45.43; H, 6.23; N, 21.17. C15H24B10N6.
Calculated (%): C, 45.44; H, 6.10; N, 21.20.
3,6ꢀDiphenylꢀ4ꢀ[(1,7ꢀdicarbaꢀclosoꢀdodecaboranꢀ9ꢀyl)meꢀ
thyl]pyridazine (8d). M.p. 140—141 °C (from acetonitrile).
Found (%): C, 58.60; H, 6.26; N, 7.41. C19H24B10N2. Calculatꢀ
ed (%): C, 58.73; H, 6.23; N, 7.21.
3,6ꢀBis(3ꢀpyridyl)ꢀ4ꢀ[(1,7ꢀdicarbaꢀclosoꢀdodecaboranꢀ9ꢀ
yl)methyl]pyridazine (8e). M.p. 159—161 °C (from methanol).
Found (%): C, 52.22; H, 6.37; N, 14.27. C17H22B10N4. Calcuꢀ
lated (%): C, 52.02; H, 6.16; N, 14.28. MS, m/z (Irel (%)): 391
[MH]+ (100).
Molecular complex of 3,6ꢀbis(2ꢀpyridyl)ꢀ4ꢀ[(1,7ꢀdicarbaꢀ
closoꢀdodecaboranꢀ9ꢀyl)methyl]pyridazine with 2,3,5,6ꢀtetraꢀ
chloroꢀ1,4ꢀdihydroxybenzene (8f•DHB). M.p. 170—172 °C
(from acetonitrile). Found (%): C, 43.29; H, 3.59; N, 8.73.
C17H22B10N4•С6H2Cl4O2. Calculated (%): C, 43.27; H, 3.79;
N, 8.78. MS, m/z (Irel (%)): 391 [MH]+ (100).
Xꢀray diffraction study. The single crystals of compounds 5b,
8d, 10а were prepared by crystallization from MeCN. Xꢀray
diffraction analysis was performed on an Xcaliburꢀ3 Xꢀray difꢀ
fractometer equipped with a CCDꢀdetector (λ(MoꢀKα) =
= 0.71073 Å, graphite monochromator, ω scan mode, scanning
step 1°). The temperature of experiment was 295(2) К for 5b, 8d
and 100(2) К for 10а. The structures were solved by the direct
method using the SHELXSꢀ97 program and refined using the
SHELXLꢀ97 program. The positional and temperature parameꢀ
ters for the nonhydrogen atoms were refined using the fullꢀmaꢀ
trix leastꢀsquares method, first, in the isotropic approximation
and, then, in the anisotropic approximation. The hydrogen atꢀ
oms were localized at the maxima of the electron density and
included in the refinement within a riding model. The main
crystallographic data and parameters of the structure solution
and refinement are presented in Table 3.
3,6ꢀBis(3,5ꢀdimethylpyrazolꢀ1ꢀyl)ꢀ4ꢀ[(2ꢀisopropylꢀ1,2ꢀdiꢀ
carbaꢀclosoꢀdodecaboranꢀ1ꢀyl)methyl]pyridazine (10a). M.p.
207—208 °C (from methanol). Found (%): C, 51.57; H, 7.20;
N, 17.97. C20H34B10N6. Calculated (%): C, 51.48; H, 7.35;
N, 18.01. MS, m/z (Irel (%)): 467 [MH]+ (100).
The results of Xꢀray diffraction studies were deposited with
the Cambridge Structural Database (CCDC Nos. 735714ꢀ735716
for compounds 5b, 8d, 10а, respectively)*.
Preparation of pyridazines 8a,b, 9a (general procedure). Chloꢀ
ranil (1 mmol) was added to a solution of dihydropyridazine
(0.5 mmol) in оꢀxylene (5 mL) (in the case of 5a,b) or toluene (5 mL)
(in the case of 6a). The reaction mixutre was kept under reflux
for 1.5—5 h. The solvent was removed and the obtained crystalꢀ
line residue was recrystallized from acetonitrile or benzene.
The characteristics of compounds 8а,b are presented above,
the 1H NMR spectra of 8a,b, 9a are presented in Table 2.
This work was financially supported by the Russian
Foundation for Basic Research (Project Nos. 07ꢀ03ꢀ
96112ꢀr_ural_a, 07ꢀ03ꢀ96113ꢀr_ural_a, 08ꢀ03ꢀ99084ꢀ
r_ofi), the Government of the Sverdlovsk region (Agreeꢀ
* This data can be obtained free of charge on application to the
CCDC via www.ccdc.cam.ac.uk/data_request/cif.

Cycloaddition of tetrazines to allylcarboranes
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
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Received June 18, 2008;
in revised form July 7, 2009