Thermal transformations of 2H-benzimidazole 1,3-dioxides

Article abstract of DOI:10.1007/s11172-011-0257-x

Thermal transformations of 2H-benzimidazole 1,3-dioxides represented by spiro[2H-benz-imidazole-2,1′-cyclohexane] 1,3-dioxide and its 5-nitro derivative were studied. Their heating resulted in reversible isomerization to spiro[3H-[2,1,4]benzoxadiazine-3,1

Full text of DOI:10.1007/s11172-011-0257-x

Russian Chemical Bulletin, International Edition, Vol. 60, No. 8, pp. 1723—1728, August, 2011
1723
Thermal transformations of 2Hꢀbenzimidazole 1,3ꢀdioxides
V. A. Samsonov, I. Yu. Bagryanskaya, Yu. V. Gatilov, and V. A. Savel´ev
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 9752. Eꢀmail: Samson@nioch.nsc.ru
Thermal transformations of 2Hꢀbenzimidazole 1,3ꢀdioxides represented by spiro[2Hꢀbenzꢀ
imidazoleꢀ2,1´ꢀcyclohexane] 1,3ꢀdioxide and its 5ꢀnitro derivative were studied. Their heating
resulted in reversible isomerization to spiro[3Hꢀ[2,1,4]benzoxadiazineꢀ3,1´ꢀcyclohexane]
4ꢀoxides. More prolonged heating of 2Hꢀbenzimidazole 1,3ꢀdioxides caused sequential eliꢀ
mination of the first and then (at higher temperature) the second Nꢀoxide oxygen atom to form
2Hꢀbenzimidazole derivatives, which upon further heating were transformed to 7,8,9,10ꢀtetraꢀ
hydroꢀ6Hꢀazepino[1,2ꢀa]benzimidazoles. A scheme of the process was suggested, which
described the experimental data obtained. Spiro[3Hꢀ[2,1,4]benzoxadiazineꢀ3,1´ꢀcyclohexane]
4ꢀoxides on exposure to the sunlight were quantitatively transformed to 2Hꢀbenzimidazole
1,3ꢀdioxides.
Key words: 2Hꢀbenzimidazoles, 2,1,4ꢀbenzoxadiazines, heterocyclic Nꢀoxides, rearrangeꢀ
ments, phototransformation, oxidation.
2HꢀBenzimidazoles are known and relatively well studꢀ
ied heterocyclic compounds,1,2 while 2Hꢀbenzimidazole
1,3ꢀdioxides are studied considerably less. It was also
noted3 that these compounds possess unusual reactivity.
Recently,4—6 it was published that some 2Hꢀbenzimidꢀ
azole 1,3ꢀdioxides display high biological activity against
tripanosomic parasites (Tripanosoma cruzi and Leishmaꢀ
nia spp), whose action is comparable with that of known
drugs used for the treatment of diseases caused by these
parasites. In this connection, studies of properties of
2Hꢀbenzimidazole 1,3ꢀdioxides is an actual problem.
It is known7 that 2Hꢀbenzimidazoles upon heating unꢀ
dergo 1,5ꢀsigmatropic rearrangement to 2,3ꢀdisubstituted
1Hꢀbenzimidazoles. Information on the behavior of
2Hꢀbenzimidazole 1,3ꢀdioxides on heating is absent. The
purpose of the present work is to study thermal transforꢀ
mations of 2Hꢀbenzimidazole 1,3ꢀdioxides.
Heating of spiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane]
1,3ꢀdioxide (1) in the inert solvent, chlorobenzene, at
110 °C results in the reaction mixture, from which spiroꢀ
[3Hꢀ[2,1,4]benzoxadiazineꢀ3,1´ꢀcyclohexane] 4ꢀoxide (2)
and already known spiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcycloꢀ
hexane] 1ꢀoxide (3)3 were isolated (Scheme 1). Benzoxaꢀ
diazine 2 has proved very unstable (especially in solutions)
and was easy transformed to the starting dioxide 1 on
heating and in the light, that made difficult its isolation
from the reaction mixture and handling. The structure of
compound 2 was established based on the spectral and
analytical data (see Experimental). The TLC data show
that more prolonged heating of compound 1 in chloroꢀ
benzene leads to the formation of the intermediate spiroꢀ
[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane] (4), and already
known 7,8,9,10ꢀtetrahydroꢀ6Hꢀazepino[1,2ꢀa]benzimidꢀ
azole (5)8 was the only final product of the reaction (deꢀ
monstrated on the thermolysis of compound 3 in oꢀdiꢀ
chlorobenzene taken as an example).
Thus, it can be suggested that upon heating of comꢀ
pound 1, elimination of the Nꢀoxide oxygen atoms ocꢀ
curs initially to form 2Hꢀbenzimidazole 4, and then its
1,5ꢀsigmatropic rearrangement leads to compound 5.
Earlier,9 we have shown that the reaction of benzoꢀ
furoxanes with alcohols or alkyl halides in sulfuric or perꢀ
chloric acids smoothly gives 2Hꢀbenzimidazole 1,3ꢀdiꢀ
oxides. 5ꢀNitrobenzofuroxane easy leads to 5ꢀnitrospiroꢀ
[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane] 1,3ꢀdioxide (6).
Upon heating of compound 6 in chlorobenzene, the iniꢀ
tially dark blue solution rapidly turns bright red. Chroꢀ
matographic separation of the reaction mixture yielded, in
addition to the starting compound 6, four products: isoꢀ
meric 2,1,4ꢀbenzoxadiazine 4ꢀoxides 7 and 8 and 2Hꢀbenzꢀ
imidazole 1ꢀoxides 9 and 10. The structure of compound 7
has been established earlier9 based on the 1H and 13C NMR
data. We confirmed the structure of this compound by
Xꢀray crystallography. The structure of molecule 7 in the
crystal is shown in Fig. 1. Data on similar oxadiazines are
absent in the Cambrige Structural Database. Distribution
of the bond lengths corresponds to the conjugated system
of double bonds. The nitro group comes out of the plane of
the benzene ring by 2.1(1)°. The heterocycle is characterꢀ
ized by the twisted boat conformation with the atoms N(1)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1697—1702, August, 2011.
1066ꢀ5285/11/6008ꢀ1723 © 2011 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
Samsonov et al.
Scheme 1
R = H (1—5), NO2 (6—13)
and O(2) coming out of the plane C(3)N(4)C(4a)C(8a)
by 0.382 and 0.782 Å, respectively, whereas, the cycloꢀ
hexane ring has the chair conformation. Molecules in
the crystal form layers by the weak hydrogen bonds
C(8)—H(8)...N(1) (H...N, 2.46(2) Å; C—H...N, 167(2)°),
C(5)—H(5)...O(1) (H...O, 2.54(2) Å; C—H...O, 145(2)°),
C(13)—H(13A)...O(4) (H...O, 2.55(2) Å; C—H...O,
160(2)°) and by the interaction O(2)...π (C(4a)C(5)C(6)—
C(7)C(8)C(8a)) with the distance O—centroid equal
to 3.248 Å.
The structure of compound 9 was also established by
us by Xꢀray crystallography. The spatial structure of the
molecule of compound 9 is shown in Fig. 2. The atoms of
the 6ꢀnitrobenzimidazole 1ꢀoxide fragment are on the mirꢀ
ror plane. The cyclohexane fragment spiroꢀjointed with it
is divided by this plane along the atoms C(2) and C(10) to
the two dependent parts and has the chair conformation. The
Cambrige Structural Database10,11 has only three strucꢀ
tures with similar tricyclic framework: 5,6ꢀ(N,N´ꢀdiꢀ
piperidino)isobenzimidazoleꢀ2ꢀspirocyclohexane,12 dispiroꢀ
[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexaneꢀ4´,2″ꢀ[2H]benzꢀ
imidazole] 1,1″ꢀdioxide,13 and 4ꢀbromoꢀ6ꢀ(2,3ꢀdichloroꢀ
phenoxy)ꢀ2Hꢀbenzimidazoleꢀ2ꢀspirocyclohexane.14 Analysis
of geometry of compound 9 showed that its bond lengths
and bond angles are close to the corresponding values in
the found compounds and agree with the literature data.15
O(3)
N(1)
O(2)
C(8)
C(7)
N(2)
O(4)
C(8A)
C(12)
C(13)
C(11)
C(5)
C(3)
N(4)
C(10)
C(9)
C(6)
C(4A)
O(1)
Fig. 1. The spatial structure of 7ꢀnitrospiro[3Hꢀ[2,1,4]benzoxaꢀ
diazineꢀ3,1´ꢀcyclohexane] 4ꢀoxide (7) molecule according to
the Xꢀray crystallographic data.

Thermal transformations of benzimidazoldioxides
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1725
O(1)
C(8A)
from these data, it would have been suggested that 2Hꢀbenzꢀ
imidazole 1ꢀoxides 9 and 10 are formed through the interꢀ
mediate 2,1,4ꢀbenzoxadiazine 4ꢀoxides 7 and 8. However,
heating of compounds 7 or 8 in chlorobenzene shows the preꢀ
sence of products 6—10 in the reaction mixture (TLC data).
Apparently, 2,1,4ꢀbenzoxadiazine 4ꢀoxides are not the interꢀ
mediate compounds in the elimination reaction of oxygen.
Heating of 2Hꢀbenzimidazole 1ꢀoxides 9 and 10 in
oꢀdichlorobenzene at higher temperature furnished 2ꢀspiroꢀ
cyclohexylꢀ2Hꢀbenzimidazole 11 and a mixture of azeꢀ
pino[1,2ꢀa]benzimidazoles 12 and 13 (see Scheme 1).
Based on the facts mentioned above, we suggested the
following scheme describing the transformations observed.
It is possible that heating of 2Hꢀbenzimidazole 1,3ꢀdiꢀ
oxides 1 and 6 forms nitroso nitrones A and B as the
intermediates (see Scheme 1), which are able either to
reversibly cyclize to 1,2,4ꢀbenzoxadiazine 4ꢀoxides 2, 7,
and 8 or lose oxygen with the formation of nitroso imines
C and D as the intermediates. The latter, in turn, can
irreversibly cyclize to 2Hꢀbenzimidazole 1ꢀoxides 3, 9,
and 10. Further heating of compounds 3, 9, and 10 at
higher temperature eliminates another oxygen atom to furꢀ
nish 2Hꢀbenzimidazoles 4 and 11, which are transformed
to azepino[1,2ꢀa]benzimidazoles 5, 12, and 13 by the
known 1,5ꢀsigmatropic rearrangement7 (see Scheme 1).
The oxygen atoms in heterocyclic Nꢀoxides in the abꢀ
sence of oxygen acceptors can be removed by heating, but
this occurs at high temperature.15,16 At the same time, it is
known17,18 that all the nitrones are more or less thermally
labile, for which the Cope rearrangement, i.e., transforꢀ
mation of nitrones to the oxime ethers on heating, was
described.19—22 Apparently, in this case 2,1,4ꢀbenzoxadiꢀ
azine 4ꢀoxides 2, 7, and 8 are formed as a result of rearꢀ
rangement similar to the Cope rearrangement, which is
O(2)
N(1)
C(7A)
C(7)
C(6)
C(9A)
C(2)
N
C(10)
O(3)
C(8)
C(3A)
C(9)
C(5)
N(3)
C(4)
Fig. 2. The spatial structure of 6ꢀnitrospiro[2Hꢀbenzimidazoleꢀ
2,1´ꢀcyclohexane] 1ꢀoxide (9) molecule according to the Xꢀray
crystallographic data.
The Xꢀray crystallographic results together with other
spectral and analytical data also confirm the structures of
compounds 8 and 10, which are isomeric to compounds 7
and 9.
We studied how composition of the reaction products
changes with time. For this, we collected aliquots during
reflux of 2Hꢀbenzimidazole 1,3ꢀdioxide 6 in chlorobenzꢀ
ene through the certain periods of time and recorded
1H NMR spectra for them (Fig. 3). Composition of the
mixture was calculated based on the relative integral inꢀ
tensities of the signals for the aromatic protons characterꢀ
istic of each compound. The data obtained are shown in
Fig. 4. It is seen that the amount of the starting compound
6 monotonously decreases during reflux of the solution
(see Fig. 4) with simultaneous accumulation of 2Hꢀbenzꢀ
imidazole monoꢀNꢀoxides 9 and 10 in the reaction mixꢀ
ture. The amount of 2,1,4ꢀbenzoxadiazine 4ꢀoxides 7 and
8 rapidly grows in the initial period, reaches the maxiꢀ
mum, and then gradually decreases until complete disapꢀ
pearance after the dioxide 6 was consumed. Proceeding
10
8
9
7
6
8.3
8.2
8.1
8.0
7.9
7.8
7.7
7.6
7.5
7.4
7.3
7.2
7.1
7.0
δ
Fig. 3. The fragment of the 1H NMR spectrum of the reaction mixture during thermolysis of 5ꢀnitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcycloꢀ
hexane] 1,3ꢀdioxide (6) in chlorobenzene after 1.5 h. Characteristic signals for the protons of each component of the mixture are marked.

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Samsonov et al.
Proportion of components
in the reaction mixture
spectrometer in CDCl3 and DMSOꢀd6 for 10% solutions at 25 °C.
Chemical shifts were measured relatively to the residual signals
of the solvents: CHCl3 (δ 7.24, δ 76.90) and DMSOꢀd6
H
C
(δ 2.50, δ 39.50). Splitting of the signals in the 13C NMR
60
50
H
C
10
9
spectra was determined using Jꢀmodulation (JMOD) and 13C—H
correlations. Mass spectra were recorded on a Thermo—Scienꢀ
tific DFS instrument (70 eV, a direct injection of compounds,
the temperature of the source of ions was 180 °C); the peaks
whose intensities are higher than 10% are reported. The reaction
progresses and individuality of compounds were monitored by
TLC on Sorbfil UVꢀ254 plates (Sorbpolimer, Krasnodar, Russia);
the plates were visualized by UV light and in iodine vapors.
Compounds 1 and 6 were synthesized according to the known
procedure.9 Chlorobenzene and oꢀdichlorobenzene were freshly
distilled. Melting points were determined on a Kofler microꢀ
heating stage. Elemental analysis was performed in the Laboraꢀ
tory of Microanalysis of the Novosibirsk Institute of Organic
Chemistry SB RAS.
40
6
30
20
10
7
8
30 60 90 120 180 240 300 360 480 t/min
Fig. 4. The changes in the concentration of the reaction prodꢀ
ucts 7—10 with time during reflux of 5ꢀnitrospiro[2Hꢀbenzimidꢀ
azoleꢀ2,1´ꢀcyclohexane] 1,3ꢀdioxide (6) in chlorobenzene.
Thermolysis of spiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane]
1,3ꢀdioxide (1). A solution of diꢀNꢀoxide 1 (2.54 g, 0.012 mol) in
chlorobenzene (50 mL) was heated for 2.5 h at 110 °C. The
solvent was evaporated in vacuo, the residue was subjected to
chromatography on SiO2 (hexane—ethyl acetate (10 : 1)) to obꢀ
tain three fractions. The first fraction was for the second time
subjected to chromatography on SiO2 (hexane) to isolate spiroꢀ
[3Hꢀ[2,1,4]benzoxadiazineꢀ3,1´ꢀcyclohexane] 4ꢀoxide (2) (0.09 g,
3.5%). The second fraction yielded spiro[2Hꢀbenzimidazoleꢀ
2,1´ꢀcyclohexane] 1ꢀoxide (3) (1.6 g, 63.0%). The third fraction
(0.6 g, 23.6%) was the starting compound 1.
characteristic of nitrones. The easy enough elimination of
the Nꢀoxide oxygen atom in 2Hꢀbenzimidazole 1,3ꢀdiꢀ
oxides upon moderate heating also indicates that these
compounds resemble nitrones in their properties. Thus,
2Hꢀbenzimidazole 1,3ꢀdioxides 1 and 6 on heating disꢀ
play properties typical of nitrones.
It should be noted that exposure of solutions or powꢀ
ders of benzoxadiazines 2, 7, or 8 to the sunlight leads to
2Hꢀbenzimidazole 1,3ꢀdioxides 1 or 6, respectively. The
photochemical isomerization of benzoxadiazines can be
formally called the retroꢀCope rearrangement (transforꢀ
mation of the oxime ether to the nitrone). We have no
information on such transformations, and, apparently, this
is the first example of such a rearrangement. Earlier,9 we
have reported that compound 7 is converted to compound
6 on keeping in sulfuric acid.
It is known17,23 that Nꢀoxides of heterocyclic comꢀ
pounds are oxidants. 2HꢀBenzimidazole 1,3ꢀdioxides are
no exception. Heating of compound 6 in benzene with
hydroquinone in the equivalent amount gives benzoquinoꢀ
ne in 60% isolated yield.
In conclusion, elimination of the oxygen atoms from
2Hꢀbenzimidazole 1,3ꢀdioxides takes place sequentially.
The first step presumably includes formation of a nitroso
nitrone as the intermediate (the evidence is formation of
2,1,4ꢀbenzoxadiazines), which then eliminate the oxygen
atom to furnish 2Hꢀbenzimidazole 1ꢀoxides. Further, the
second oxygen atom is eliminated at higher temperature
to yield 2Hꢀbenzimidazole. Apparently, elimination of the
second oxygen atom follows the mechanism similar to
that characteristic of heterocyclic compound Nꢀoxides.16
Spiro[3Hꢀ[2,1,4]benzoxadiazineꢀ3,1´ꢀcyclohexane] 4ꢀoxide
(2). M.p. 78—80 °C (from hexane). Found (%): C, 66.06; H,
6.42; N, 12.84. C12H14N2O2. Calculated (%): C, 66.03; H, 6.47;
N, 12.84. UV, λmax/nm (logε): 379 (3.55), 440 (3.53). IR, ν/cm–1
:
1
1612 (C=N). H NMR (CDCl3), δ: 1.20—1.32 (m, 1 H, CH);
1.68—2.05 (m, 9 H, CH, 4 CH2); 6.55—6.68 (m, 2 H, 2 CH);
6.81—6.85, 7.11—7.15 (both m, 1 H each, 2 CH). 13C NMR
(CDCl3), δ: 28.30, 24.19, 21.60 (all CH2); 118.06, 123.88, 127.88,
128.86 (all CH); 96.08 (C(3)); 128.86 (C(8a)); 150.77 (C(4a)).
MS, m/z (Irel (%)): 218 [M]+ (76), 202 (18), 201 (13), 185 (44),
171 (13), 164 (10), 148 (18), 147 (19), 127 (20), 131 (21), 120 (33),
98 (100). HRMS, found: m/z 218.1052 [M]+. C12H14N2O2. Calꢀ
culated: M = 218.1050.
Spiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane] 1ꢀoxide (3). M.p.
84—86 °C (from benzene) (cf. Ref. 3: m.p. 86 °C).
Thermolysis of spiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane]
1ꢀoxide (3). A solution of monoꢀNꢀoxide 3 (0.57 g, 0.0028 mol)
in oꢀdichlorobenzene (10 mL) was heated for 3 h at 165 °C. The
solvent was evaporated in vacuo, the residue was subjected to
chromatography on SiO2 (benzene—acetone (10 : 1)) to isolate
the starting compound 3 (0.1 g, 17.5%), spiro[2Hꢀbenzimidꢀ
azoleꢀ2,1´ꢀcyclohexane] (4) (0.07 g, 12.5%), and 7,8,9,10ꢀtetraꢀ
hydroꢀ6Hꢀazepino[1,2ꢀa]benzimidazole (5) (0.2 g, 35%).
Spiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane] (4). M.p. 63—65 °C
(from benzene) (cf. Ref. 3: m.p. 65 °C).
7,8,9,10ꢀTetrahydroꢀ6Hꢀazepino[1,2ꢀa]benzimidazole (5).
M.p. 125—126 °C (from benzene) (cf. Ref. 8: m.p. 125—126 °C).
1H NMR (CDCl3), δ: 1.70—1.95 (m, 6 H, 3 CH2); 3.00—3.10,
4.05—4.15 (both m, 2 H each, 2 CH2); 7.12—7.22 (m, 3 H,
3 CH); 7.62—7.70 (m, 1 H, CH). 13C NMR (CDCl3), δ: 25.43,
28.56, 29.97, 30.79, 44.27 (all CH2); 108.61, 119.07, 121.30,
121.70 (all CH); 135.68, 142.28, 157.36 (all C).
Experimental
IR spectra were recorded on a Bruker Vectorꢀ22 spectroꢀ
meter in KBr pellets (the concentration was 0.25%), UV spectra
were recorded on a HewlettꢀPackard 4853 instrument in ethaꢀ
nol. 1H and 13C NMR spectra were recorded on a Bruker AVꢀ300

Thermal transformations of benzimidazoldioxides
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1727
Thermolysis of 5ꢀnitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcycloꢀ
hexane] 1,3ꢀdioxide (6). A. A solution of diꢀNꢀoxide 6 (6.18 g,
0.023 mol) in chlorobenzene (150 mL) was refluxed for 6 h, the
solvent was evaporated in vacuo. The residue was subjected to
chromatography on SiO2 (hexane—ethyl acetate (5 : 1)) to seꢀ
quentially isolate 7ꢀnitrospiro[3Hꢀ[2,1,4]ꢀbenzoxadiazineꢀ3,1´ꢀ
cyclohexane] 4ꢀoxide (7) (0.25 g, 4%), 6ꢀnitrospiro[3Hꢀ[2,1,4]ꢀ
benzoxadiazineꢀ3,1´ꢀcyclohexane] 4ꢀoxide (8) (0.5 g, 8%),
6ꢀnitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane] 1ꢀoxide (9)
(1.50 g, 26%), and 5ꢀnitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcycloꢀ
hexane] 1ꢀoxide (10) (2.6 g, 46%). On the TLC plates, the folꢀ
lowing spots were also visualized (hexane—ethyl acetate (5 : 1)):
the dark blue one with Rf 0.23 (the starting compound 6), the
orange one with Rf 0.25 (compound 9), the yellow one with
Rf 0.42 (compound 10), the orange one with Rf 0.53 (compound 8),
and the yellow one with Rf 0.61 (compound 7).
δ: 1.19—1.26 (m, 2 H, CH2); 1.43—1.52 (m, 1 H, CH); 1.75—2.10
(m, 7 H, 3 CH2, CH); 7.30 (dd, 1 H, H(7), J7,6 = 10.0 Hz,
J7,4 = 0.8 Hz); 7.44 (dd, 1 H, H(6), J6,7 = 10.0 Hz, J6,4 = 1.9
Hz); 8.16 (dd, 1 H, H(4), J4,6 = 1.9 Hz, J4,7 = 0.8 Hz). 13C NMR
(CDCl3), δ: 23.35, 24.32, 35.18 (all CH2); 115.20, 126.79, 128.24
(all CH); 109.29, 133.40, 146.45, 160.64 (all C). MS, m/z
(Irel (%)): 247 [M]+ (65), 230 (100), 218 (16), 202 (12), 193 (14),
192 (11), 184 (42), 176 (30), 143 (10). HRMS, found: m/z
247.0954 [M]+. C12H13N3O3. Calculated: M = 247.0951.
B. A solution of diꢀNꢀoxide 6 (0.8 g, 0.003 mol) in chloroꢀ
benzene (30 mL) was refluxed for 8 h, collecting aliquots (2 mL)
through the certain periods of time. Each portion was concenꢀ
trated in vacuo, followed by recording an 1H NMR spectrum.
The composition of the mixture was calculated based on the
ratio of integral intensities of signals for the protons of aromatic
rings characteristic of each compound (see Figs 3 and 4).
Thermolysis of 2,1,4ꢀbenzoxadiazine 4ꢀoxides 7 and 8. A soluꢀ
tion of 2,1,4ꢀbenzoxadiazine 8 (0.1 g, 0.00038 mol) in chloroꢀ
benzene (5 mL) and a solution of 2,1,4ꢀbenzoxadiazine 7 (0.15 g,
0.00057 mol) in chlorobenzene (5 mL) was refluxed for 1 h.
According to the TLC data, each reaction mixture contained
a combination of compounds 6—10.
Thermolysis of 6ꢀnitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexꢀ
ane] 1ꢀoxide (9). A solution of monoꢀNꢀoxide 9 (0.45 g, 0.0018 mol)
in oꢀdichlorobenzene (15 mL) was refluxed for 30 min. The
solvent was evaporated in vacuo, the residue was subjected
to chromatography on SiO2 (hexane—ethyl acetate (3 : 1),
then ethyl acetate) to obtain a mixture of compounds 9 and 11
(0.06 g) in the ratio 10 : 4 (1H NMR data) and a mixture of
azepino[1,2ꢀa]benzimidazoles 12 and 13 (0.25 g) in the ratio
10 : 3 (1H NMR data).
Thermolysis of 5ꢀnitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcycloꢀ
hexane] 1ꢀoxide (10). A solution of monoꢀNꢀoxide 10 (0.8 g,
0.0032 mol) in oꢀdichlorobenzene (30 mL) was refluxed for 2 h.
The solvent was evaporated in vacuo, the residue was subjected
to chromatography on SiO2 (hexane—ethyl acetate (3 : 1), then
ethyl acetate) to isolate the starting compound 10 (0.1 g, 12.5%),
5ꢀnitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane] (11) (0.03 g,
4.0%), and a mixture of 6Hꢀazepino[1,2ꢀa]benzimidazoles 12
and 13 (0.45 g) in the ratio 10 : 3 (1H NMR data). The mixture of
6Hꢀazepino[1,2ꢀa]benzimidazoles 12 and 13 was separated by
chromatography on SiO2 (ethyl acetate) to obtain 3ꢀnitroꢀ
7,8,9,10ꢀtetrahydroꢀ6Hꢀazepino[1,2ꢀa]benzimidazole (12) (0.12 g,
16%) and 2ꢀnitroꢀ7,8,9,10ꢀtetrahydroꢀ6Hꢀazepino[1,2ꢀa]benzꢀ
imidazole (13) (0.3 g, 40%).
Compound 6. 1H NMR (CDCl3), δ: 1.50—1.52 (m, 2 H,
CH2); 1.80—2.10 (m, 8 H, 4 CH2); 7.32 (d, 1 H, H(7), J7,6
=
= 10.0 Hz); 7.59 (dd, 1 H, H(6), J6,7 = 10.0 Hz, J6,4 = 1.7 Hz);
8.18 (dd, 1 H, H(4), J4,6 = 1.9 Hz, J7,4 = 1.7 Hz).
7ꢀNitrospiro[3Hꢀ[2,1,4]ꢀbenzoxadiazineꢀ3,1´ꢀcyclohexane]
4ꢀoxide (7). M.p. 171—173 °C (from benzene) (cf. Ref. 9: m.p.
1
171—173 °C). H NMR (CDCl3), δ: 1.10—1.40 (m, 1 H, CH);
1.70—2.10 (m, 9 H, CH, 4 CH2); 7.28 (dd, 1 H, H(6), J6,5 = 10.0 Hz,
J6,8 = 2.0 Hz); 7.35 (d, 1 H, H(5), J5,6 = 10.0 Hz); 7.94 (d, 1 H,
H(8), J8,6 = 2.0 Hz). MS, m/z (Irel (%)): 263 [M]+ (49), 247 (19),
230 (48), 209 (13), 192 (23), 184 (27), 176 (19), 98 (100), 80 (26).
HRMS, found: m/z 263.0896 [M]+. C12H13N3O4. Calculated:
M = 263.0901.
6ꢀNitrospiro[3Hꢀ[2,1,4]benzoxadiazineꢀ3,1´ꢀcyclohexane]
4ꢀoxide (8). M.p. 118—120 °C (from ethyl acetate—hexane (1 : 3)).
Found (%): C, 55.09; H, 4.96; N, 16.13. C12H13N3O4. Calculatꢀ
ed (%): C, 54.75; H, 4.98; N, 15.96. UV, λmax/nm (logε): 260
(3.98), 332 (3.68), 493 (3.30). IR, ν/cm–1: 1611 (C=N), 1359,
1550 (NO2). 1H NMR (CDCl3), δ: 1.45—1.68 (m, 1 H, CH);
1.70—2.40 (m, 9 H, CH, 4 CH2); 7.06 (dd, 1 H, H(8), J8,7 = 10.0 Hz,
J8,5 = 0.8 Hz); 7.38 (dd, 1 H, H(7), J7,8 = 10.0 Hz, J7,5 = 2.0 Hz);
8.15 (dd, 1 H, H(5), J5,7 = 2.0 Hz, J5,8 = 0.8 Hz). 13C NMR
(CDCl3), δ: 21.75, 24.31, 28.47 (all CH2); 117.30, 122.46, 126.88
(all CH); 98.15, 128.34, 146.81, 150.24 (all C). MS, m/z (Irel (%)):
263 [M]+ (7), 230 (11), 186 (13), 185 (16), 98 (22), 85 (65),
83 (100). HRMS, found: m/z 263.0899 [M]+. C12H13N3O4. Calꢀ
culated: M = 263.0901.
6ꢀNitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane] 1ꢀoxide
(9). M.p. 132—135 °C (from hexane). Found (%): C, 58.12;
H, 5.30; N, 16.95. C12H13N3O3. Calculated (%): C, 58.29; H, 5.30;
5ꢀNitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane] (11). M.p.
100 °C (from benzene) (cf. Ref. 7: m.p. 100 °C).
N, 17.00. UV, λmax/nm (logε): 278 (4.06), 447 (3.55). IR, ν/cm–1
:
1608 (C=N); 1326, 1513 (NO2). 1H NMR (CDCl3), δ: 1.25—1.34
(m, 2 H, CH2); 1.40—1.65 (m, 1 H, CH); 1.80—2.10 (m, 7 H,
3 CH2, CH); 7.34 (dd, 1 H, H(4), J4,5 = 10.0 Hz, J4,7 = 0.8 Hz);
7.83 (dd, 1 H, H(5), J5,4 = 10.0 Hz, J5,7 = 1.9 Hz); 8.21 (dd, 1 H,
H(7), J7,4 = 1.9 Hz, J7,5 = 0.8 Hz). 13C NMR (CDCl3), δ: 23.42,
24.42, 35.17 (all CH2); 118.58, 120.85, 123.18 (all CH); 108.64,
135.26, 153.48, 160.75 (all C). MS, m/z (Irel (%)): 247 [M]+ (58),
230 (100), 218 (10), 193 (14), 192 (10), 184 (42), 176 (30). HRMS,
found: m/z 247.0958 [M]+. C12H13N3O3. Calculated: M = 247.0951.
5ꢀNitrospiro[2Hꢀbenzimidazoleꢀ2,1´ꢀcyclohexane] 1ꢀoxide
(10). M.p. 172—175 °C (from hexane). Found (%): C, 58.21;
H, 5.41; N, 17.01. C12H13N3O3. Calculated (%): C, 58.29; H, 5.30,
N, 17.00. UV, λmax/nm (logε): 272 (4.13), 329 (3.68), 453 (3.50).
IR, ν/cm–1: 1607 (C=N); 1326, 1513 (NO2). 1H NMR (CDCl3),
3ꢀNitroꢀ7,8,9,10ꢀtetrahydroꢀ6Hꢀazepino[1,2ꢀa]benzimidꢀ
azole (12). M.p. 173—175 °C (cf. Ref. 8: m.p. 174—175 °C). UV,
λ
max/nm (logε): 241 (4.23), 311 (3.88). IR, ν/cm–1: 1334,
1472 (NO2). 1H NMR (CDCl3), δ: 1.72—2.00 (m, 6 H, 3 CH2);
3.07—3.11 (m, 2 H, CH2); 4.15—4.19 (m, 2 H, CH2); 7.24 (d, 1 H,
H(1), J1,2 = 9.0 Hz); 8.08 (dd, 1 H, H(2), J1,2 = 9.0 Hz,
J2,4 = 2.0 Hz); 8.47 (d, 1 H, H(4), J2,4 = 2.0 Hz). 13C NMR
(CDCl3), δ: 25.44, 28.71, 30.38, 30.87, 45.43 (all CH2); 108.81,
115.98, 118.13 (all CH); 140.10, 141.91, 143.34, 161.59 (all C).
MS, m/z (Irel (%)): 231 [M]+ (100), 230 (10), 201 (24), 185 (18),
184 (10). HRMS, found: m/z 231.1004 [M]+. C12H13N3O2. Calꢀ
culated: M = 231.1002.
2ꢀNitroꢀ7,8,9,10ꢀtetrahydroꢀ6Hꢀazepino[1,2ꢀa]benzimidꢀ
azole (13). M.p. 196—198 °C (cf. Ref. 8: m.p. 196—197 °C). UV,

1728
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
Samsonov et al.
λ
max/nm (logε): 237 (4.19), 313 (4.05). IR, ν/cm–1: 1334, 1518
Crystallographic data for compounds 7 and 9 were deposited
with the Cambrige Structural Database (CCDC 821921 and
CCDC 821922, respectively).
(NO2). 1H NMR (CDCl3), δ: 1.70—2.00 (m, 6 H, 3 CH2);
3.07—3.11 (m, 2 H, CH2); 4.15—4.20 (m, 2 H, CH2); 7.26
(d, 1 H, H(4), J3,4 = 9.0 Hz); 8.06 (dd, 1 H, H(3), J3,4 = 9.0 Hz,
J1,3 = 2.0 Hz); 8.46 (d, 1 H, H(1), J1,3 = 2.0 Hz). 13C NMR
(CDCl3), δ: 25.23, 28.55, 30.39, 30.73, 45.25 (all CH2); 105.93,
117.69, 119.13 (all CH); 135.18, 143.15, 147.17, 162.86 (all C).
MS, m/z (Irel (%)): 231 [M]+ (100), 230 (8), 201 (26), 185 (27),
184 (10). HRMS, found: m/z 231.0994 [M]+. C12H13N3O2. Calꢀ
culated: M = 231.1002.
References
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Exposure of compound 7 to the light. A solution of compound 7
(0.3 g, 0.0012 mol) in benzene (20 mL) was exposed to the scatꢀ
tered sunlight (June, 55 latitude). The starting orange solution
rapidly turned dark and the starting compound 7 disappeared
within ~4 h (TLC data). The solvent was evaporated, the residue
was triturated with small amount of pentane and filtered to obꢀ
tain a dark blue compound 6 (0.29 g, 97%), m.p. 122—124 °C
(cf. Ref. 9: m.p. 122—124 °C). The IR spectrum of the comꢀ
pound was identical to that of compound 6 synthesized earlier.
Benzoxadiazine 4ꢀoxides 2 and 8 reacted with the light similarly.
Oxidation of hydroquinone with compound 6. Hydroquinone
(1.10 g, 0.01 mol) was added to a solution of compound 6 (2.63 g,
0.01 mol) in benzene (50 mL) and the mixture obtained was
refluxed until the starting compound 6 was completely conꢀ
sumed (~4 h). The solvent was evaporated to 10 mL in volꢀ
ume. The residue was subjected to chromatography on SiO2
(benzene). Benzoquinone (0.60 g, 60%) was isolated from the
first fractions.
Xꢀray diffraction experiment was performed on a Bruker P4
diffractometer (MoꢀKα radiation, graphite monochromator,
2θ/θꢀscanning). The structures were solved by the direct method
using the SHELXSꢀ97 program.24 Parameters of the structure
were refined by the least squires method on all the reflections in
the fullꢀmatrix anisotropic approximation using the SHELXLꢀ97
program.24
The crystals of compound 9 were obtained by crystallization
from the AcOEt—hexane (1 : 4) solvent mixture, the crystals of
compound 7, by recrystallization from hexane.
8. K. H. Saunders, J. Chem. Soc., 1955, 3275.
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Geterotsikl. Soedin., 1994, 524 [Chem. Heterocycl. Compd.
(Engl. Transl.), 1994, 30, 460].
10. F. H. Allen, Acta Crystallogr., 2002, B58, 380.
11. I. J. Bruno, J. C. Cole, P. R. Edgington, M. Kessler, C. F.
Macrae, P. McCabe, J. Pearson, R. Taylor, Acta Crystallogr.,
2002, B58, 389.
12. J. C. Barnes, A. Hetherington, Acta Crystallogr., Sect. B:
Struct. Crystallogr. Cryst. Chem., 1978, 34, 2146.
13. M. Kaftory, V. Shteiman, M. Botoshansky, Acta Crystallogr.,
Sect. C: Cryst. Struct. Commun., 2002, 58, o183.
14. J. C. Hazelton, B. Iddon, A. D. Redhouse, H. Suschitzky,
Tetrahedron, 1995, 51, 5597.
15. F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G.
Orpen, R. Taylor, J. Chem. Soc., Perkin Trans 2, 1987, S1.
16. A. Albini, S. Pietra, Heterocyclic NꢀOxides, CRC Press, Boca
Raton—Ann Arbor—Boston, 1991, 312.
17. Yu. A. Gubarev, N. Sh. Lebedeva, V. P. Andreev, Ya. P.
Nizhnik, A. I. V´yugin, Zh. Obshch. Khim., 2007, 77, 1006
[Russ. J. Gen. Chem. (Engl. Transl.), 2007, 77, 1093].
18. J. Hamer, A. Macaluso, Chem. Rev., 1964, 64, 473.
19. W. Rundel, in HoubenꢀWeyl, Thieme Verlag, Stuttgart, 1968,
Band X/4, Teil 4, 315.
20. A. C. Cope, A. C. Haven, Jr, J. Am. Chem. Soc., 1950,
72, 4896.
21. A. H. Blatt, J. Org. Chem., 1950, 15, 869.
22. E. J. Grubbs, J. D. McCullough, Jr, B. H. Weber, J. R.
Maley, J. Org. Chem., 1966, 31, 1098.
23. D. F. Ioffe, L. S. Efros, Usp. Khim., 1961, 30, 1325 [Russ.
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24. G. M. Sheldrick, SHELXLꢀ97, SHELXSꢀ97, Programs for
Crystal Structure Determination and Refinement, Göttingen
University, Göttingen (Germany), 1997.
The crystallographic data for compound 7 are as follows:
a triclinic crystal system, a = 5.8845(3) Å, b = 9.1128(6) Å,
c = 11.6075(8) Å, α = 104.–285(5)°, β = 93.013(6)°, γ = 101.271(4)°,
V = 588.23(6) Å3, a P1 space group, C12H13N3O4, Z = 2,
dcalc = 1.486 g cm–3, μ = 0.114 mm–1, 2θ < 55°, the sample size
0.24×0.43×0.66 mm. Intensities of 2675 independent reflections
were measured. Allowance for the absorption was made by the
method of integration on the crystal faceting (transmission
0.957—0.979). Parameters of the hydrogen atoms were refined
in the isotropic approximation. The results of refinement are as
follows: wR2 = 0.1123, S = 1.038, 225 parameters, R = 0.0391
for 2429 reflections with F > 4σ .
F
The crystallographic data for compound 9 are as follows: an
orthorhombic crystal system, a = 21.119(1) Å, b = 6.5679(4) Å,
c = 8.3401(4) Å, V = 1156.9(1) Å3, a Pnma space group,
C12H13N3O3, Z = 4, dcalc = 1.420 g cm–3, μ = 0.105 mm–1
2θ < 52°, the sample size 0.2×0.2×0.5 mm. Intensities of 1241
independent reflections were measured. No allowance was made
for the absorption. Parameters for the hydrogen atoms were calꢀ
culated in each cycle of refinement using coordinates of the
corresponding carbon atoms (the riding model). The results of
refinement are as follows: wR2 = 0.1071, S = 1.021, 103 paraꢀ
,
Received June 28, 2010;
meter, R = 0.0429 for 947 reflections with F > 4σ .
in revised form May 23, 2011
F