Synthesis and study of new 2-aryl-1-(4-nitrophenyl)-1,1a-dihydroazireno[1, 2-a]quinoxaline derivatives

Article abstract of DOI:10.1007/s11172-006-0261-8

New derivatives of photochromic 2-aryl-1-(4-nitrophenyl)-1,1a- dihydroazireno[1,2-a]quinoxalines were synthesized by condensation of 4-methyl-and 4,5-dimethyl-1,2-phenylenediamine with 1,3-diaryl-2,3- dibromopropan-1-ones. The reactions of 4-methyl-1,2-ph

Full text of DOI:10.1007/s11172-006-0261-8

Russian Chemical Bulletin, International Edition, Vol. 55, No. 2, pp. 362—368, February, 2006
362
Synthesis and study of new
2ꢀarylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ1,1aꢀdihydroazireno[1,2ꢀa]quinoxaline derivatives
A. I. Zbruyev,a F. G. Yaremenko,b V. A. Chebanov,aꢀ S. M. Desenko,a
O. V. Shishkin,a E. V. Lukinova,a and I. V. Knyazevaa
aState Scientific Institution "Institute for Single Crystals," National Academy of Sciences of Ukraine,
60 prosp. Lenina, 61001 Kharkov, Ukraine.
Fax: +38 (057) 340 9343. Eꢀmail: chebanov@isc.kharkov.com
bV. Ya. Danilevsky Institute of Endocrine Pathology Problems, Academy of Medical Sciences of Ukraine,
10 ul. Artema, 61002 Kharkov, Ukraine
New derivatives of photochromic 2ꢀarylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ1,1aꢀdihydroazireꢀ
no[1,2ꢀa]quinoxalines were synthesized by condensation of 4ꢀmethylꢀ and 4,5ꢀdimethylꢀ1,2ꢀ
phenylenediamine with 1,3ꢀdiarylꢀ2,3ꢀdibromopropanꢀ1ꢀones. The reactions of 4ꢀmethylꢀ
1,2ꢀphenylenediamine produce mixtures of regioisomers. The chemical properties of the reacꢀ
tion products were studied. The structure of one of the latter was established by Xꢀray difꢀ
fraction.
Key words: 1,3ꢀdiarylꢀ2,3ꢀdibromopropanꢀ1ꢀones, 1,2ꢀdiarylꢀ1,1aꢀdihydroazireꢀ
no[1,2ꢀa]quinoxalines, 2ꢀarylquinoxalines, 4ꢀarylꢀ1,2ꢀbis(4ꢀnitrophenyl)ꢀ1,2ꢀdihydroꢀ3aHꢀ
oxazolo[3,2ꢀa]quinoxalines, Xꢀray diffraction study.
Aziridines are widely used for the synthesis of various
practically important compounds.1 Bicyclic aziridine deꢀ
rivatives have attracted attention primarily due to the presꢀ
ence of the strained threeꢀmembered ring, which readily
undergoes cleavage under external factors. In particular,
the photochromic properties of azireno[1,2ꢀc]imidazoles,
azireno[1,2ꢀa]pyrazines, and azireno[1,2ꢀa]quinoxalines
are accounted for by the aziridine ring opening.2
First data on photochromic fused aziridines3 were obꢀ
tained when synthesizing azireno[1,2ꢀc]imidazoles by the
reactions of transꢀ3ꢀaroylꢀ2ꢀarylaziridines with aldehydes
or ketones in ammoniaꢀsaturated alcoholic solutions.
Photoꢀ4 and thermochromic5 diarylꢀ1,1aꢀdihydroꢀ
azireno[1,2ꢀa]quinoxalines (DAQ) were synthesized
from α,βꢀchalcone dibromides and 1,2ꢀphenylenediamine
in the presence of tertiary organic bases (triethylamine
and N,Nꢀdimethylbenzylamine). 1ꢀFluoroalkyl derivaꢀ
tives6 also extend the range of known 1,1aꢀdihydroazireꢀ
no[1,2ꢀa]quinoxalines.
1ꢀ(4ꢀNitrophenyl)ꢀsubstituted dihydroazirenoquinꢀ
oxalines are poorly soluble, which hinders their use in
lightꢀsensitive composite materials.
In the present study, we report methods for the synꢀ
thesis of previously unknown methylꢀ and dimethylꢀsubꢀ
stituted DAQ (see the preliminary communication7). In
our opinion, the introduction of additional alkyl and
alkoxy substituents can substantially increase the solubilꢀ
ity of DAQ.
For the reactions of 4ꢀsubstituted 1,2ꢀphenyleneꢀ
diamines, the main question is about the reaction pathꢀ
way. In early studies on this problem,8,9 only one regioꢀ
isomer was detected and isolated in moderate yield. Apꢀ
parently, the second regioisomer was not found because
of instrumental limitations.
The reactions of methylꢀsubstituted oꢀphenylenediꢀ
amines 1 and 2 with erythroꢀ1,3ꢀdiarylꢀ2,3ꢀdibromoꢀ
propanꢀ1ꢀones 3—9 (Scheme 1) and 2ꢀbromoꢀ3ꢀ
(4ꢀnitrophenyl)ꢀ1ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (21) afforded
new representatives of 1,2ꢀdiarylꢀ1,1aꢀdihydroazireꢀ
no[1,2ꢀa]quinoxalines 10—20. The reactions were carꢀ
ried out by heating the starting compounds in methanol
in the presence of triethylamine.
The positions and multiplicities of the signals in the
1H NMR spectra of compounds 10—14 (two doublets
with the spinꢀspin coupling constants of 2.7—2.9 Hz at
δ 2.9—3.0 and 3.4—3.5 belonging to the transꢀaziridine
protons at positions 1a and 1, characteristic doublets of
the terminal aryl substituents, and singlets of the H(4)
(δ 7.32—7.40) and H(7) (δ 7.00—7.19) protons of the
annelated phenylene moiety) agree well with the data for
various 1,2ꢀdiarylꢀ1,1aꢀdihydroazireno[1,2ꢀa]quinoxaꢀ
lines studied earlier.4,5,8 The signal at lower field was
unambiguously assigned to the proton at position 4 due to
the electronꢀwithdrawing effect of the C=N fragment.
The reactions of 4ꢀmethylꢀ1,2ꢀphenylenediamine (2)
give compounds 15—20 as mixtures of regioisomers A
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 350—356, February, 2006.
1066ꢀ5285/06/5502ꢀ0362 © 2006 Springer Science+Business Media, Inc.

New 1,1aꢀdihydroazireno[1,2ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
363
Scheme 1
Table 1. Ratio of regioisomers and chemical shifts of the H(4)
and H(7) protons in the 1H NMR spectra of compounds 10 and
15—20
Comꢀ
pound
δ
Ratio of regioisomers (%)
H(4) (A) H(7) (B)
А
В
10
15
16
17
18
19
20
7.35
7.35
7.33
7.34
7.33
7.32
7.36
7.18
7.19
7.19
7.18
7.18
7.18
7.19
—
65
60
65
55
60
55
—
35
40
35
45
40
45
integrated intensities of two singlets (or doublets with the
coupling constants <2 Hz), which are observed in the
resonance region of aromatic protons and belong to the
H(4) proton of isomer A (δ 7.32—7.36) and the H(7)
proton of isomer B (δ 7.18—7.19). The assignment of the
signals was made based on the above data for 4,5ꢀdiꢀ
methylꢀsubstituted compounds 10—14.
1, 10—14: R1 = R2 = Me
The reaction of αꢀbromochalcone 21 with diamine 2
afforded the target compound 15 in the same yield and
with the same ratio of regioisomers 15A : 15B as those
obtained in the reaction of dibromochalcone 3. Conseꢀ
quently, the formation of the aziridine fragment of the
bicyclic system is not accompanied by the direct replaceꢀ
ment of the βꢀbromine atom; otherwise the ratio of isoꢀ
mers would be changed. Hence, there is no sense in isoꢀ
lating intermediate αꢀbromochalcones in the synthesis
of DAQ.
Crystalline dihydroazireno[1,2ꢀa]quinoxalines 10—20
are reversibly photochromic. Being paleꢀyellow in the
dark, these compounds turned green (R = F or Br) or
darkꢀviolet (R = C5H11) under UV light (or, to a lesser
degree, under visible light). Compounds 13, 14, 17, and
18 are highly soluble in usual organic solvents.
2, 15—20: R1 = Me, R2 = H
Comꢀ
R3
Yield
Comꢀ
pound
R3
Yield
(%)
pound
(%)
3
4
5
6
7
8
9
10
11
H
Br
Et
C5H11
F
Ph
OCHF2
H
74
82
64
66
63
61
80
45
45
12
13
14
15
16
17
18
19
20
F
39
30
39
38
43
26
30
37
16
OCHF2
C5H11
H
Br
Et
C5H11
F
Ph
Br
1
and B (see Scheme 1). This is evident from the H NMR
spectra, in which almost all signals are doubled. Attempts
to isolate individual isomers by highꢀperformance liquid
chromatography failed. However, control by HPLC demꢀ
onstrated that the ratio of isomers in solution differs from
that in the crystalline product by at most 2%.
The resulting azirenoquinoxalines are unstable upon
storage. Silica gel chromatography of samples, which
were obtained upon storage of compound 10 in air for
6—12 months, afforded 6,7ꢀdimethylꢀ3ꢀphenylꢀ1,2ꢀ
dihydroquinoxalinꢀ2ꢀone (22) and 6,7ꢀdimethylꢀ2ꢀpheꢀ
For mixtures of isomers A and B of azireno[1,2ꢀa]quinꢀ
oxalines 15—20, the ratios of isomers (Table 1) were deꢀ
1
termined from the H NMR spectra by analyzing the

364
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
Zbruyev et al.
Scheme 2
nylquinoxaline (23) (Scheme 2). These compounds were
identified by 1H NMR spectroscopy and mass spectromꢀ
etry and by comparing with the data published in the
literature.10,11 Quinoxalines 23—25 were prepared also by
refluxing compounds 10—12 in methanol in the presence
of sulfuric acid. In refluxing acetone in the presence of
traces of hydrochloric acid, azirenoquinoxalines 10
and 11 undergo a known rearrangement12 into the correꢀ
sponding 2ꢀarylꢀ3ꢀ(4ꢀnitrobenzyl)quinoxalines 26 and 27.
Quinoxaline 23 was also prepared by the independent
synthesis from phenylglyoxal and 1.
The 1,3ꢀdipolar cycloaddition is typical of cyclic anils
of aziridinyl ketones.4 4ꢀNitrobenzaldehyde can serve as
an active dipolarophile, which reacts with DAQ to give
the corresponding cycloadducts.5
The reaction of 7,8ꢀdimethyldihydroazirenoquinꢀ
oxaline 10 with 4ꢀnitrobenzaldehyde (28) produced
cycloadduct 29, whose structure was established by specꢀ
troscopic methods (Scheme 3).
In the 1H NMR spectrum of compound 29, the signals
for the protons of the dihydroazole fragment form an AB
pair at δ 5.14 and 5.22 with the spinꢀspin coupling conꢀ
stant of 6.3 Hz. This spectral pattern rules out the strucꢀ
ture of regioisomer C for the cycloadduct. To make an
unambiguous assignment of the singlets at δ 6.41 and 6.46,
we used the nuclear Overhauser effect. Additional irradiaꢀ
tion at the resonance frequency of the methyl protons at
δ 2.08 leads to a decrease in the intensity of the singlet at
δ 6.46. Consequently, this signal corresponds to the proꢀ
R = H (23, 26), F (24), Br (25, 27)
Scheme 3
Comꢀ
R1
R2
R3
Yield
Ratio of regioisomers (%)
pound
(%)
A
B
29
30
31
Me
Me
Me
Me
H
H
H
H
Br
39
31
53
—
60
60
—
40
40

New 1,1aꢀdihydroazireno[1,2ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
365
ton at position 9, and the singlet at δ 6.41 belongs to the
proton at position 3a. This experiment also enabled us to
make an unambiguous assignment of the signals of the
Me groups. The signal at lower field (δ 2.16) was assigned
to the Me group at position 7, and the signal at higher
field (δ 2.08) belongs to the Me group at position 8, which
is attributed to the anisotropic effect of the adjacent
nitrophenyl substituent.
the C(6) and C(7) atoms deviating from the mean
N(1)C(5)C(8)N(2) plane by –0.08 and –0.20 Å, respecꢀ
tively. The fiveꢀmembered ring adopts an envelope conꢀ
formation with the C(7) atom deviating from the plane
through the other atoms of the ring by –0.51 Å. The N(2)
atom has a pyramidal configuration (the sum of the
bond angles is 347.3(4)°). Hence, the partially hydrogeꢀ
nated rings are cisꢀfused (the C(6)—C(7)—N(2)—C(8)
and O(1)—C(7)—N(2)—C(10) torsion angles are
12.7(6)° and 35.1(4)°, respectively). As a whole, the triꢀ
In the cycloaddition reaction, aziridines 15 and 16
were used as mixtures of isomers. Adducts 30 and 31 were
also obtained as mixtures of regioisomers, which differ
only in the position of the Me group in the dihydroꢀ
quinoxaline fragment. In particular, this is evidenced by a
doubling of the signals of the dihydrooxazole fragment
with equal spinꢀspin coupling constants (~6 Hz) in the
1H NMR spectra. The orientation of the nitrophenyl subꢀ
stituents remains unchanged. The ratio of the regioisomers
was estimated from the integrated intensities of the sinꢀ
glets for the H(6) proton of isomer A (δ 7.30—7.40) and
the H(9) proton of isomer B (δ 6.40—6.50), which were
also assigned based on the nuclear Overhauser effect. Adꢀ
ditional irradiation at the resonance frequency of the meꢀ
thyl protons at δ 2.23 leads to a decrease in the intensity of
the singlet at δ 7.32 (H(6), isomer A) and the doublet at
δ 6.95 (H(8), isomer A). The ratio of regioisomers apꢀ
peared to be identical to that of the starting compounds.
One crystal of the isomeric mixture of cycloadduct 30
was studied by Xꢀray diffraction (Fig. 1). This compound
was found to have the structure of 8ꢀmethylꢀ1,2ꢀbis(4ꢀ
nitrophenyl)ꢀ4ꢀphenylꢀ1,2ꢀdihydroꢀ3aHꢀ[1.3]oxazoꢀ
lo[3,2ꢀa]quinoxaline (minor regioisomer B). The dihydroꢀ
pyrazine ring adopts a distorted sofa conformation with
cyclic system adopts
a bent conformation (the
C(1)—C(8)—N(2)—C(10) torsion angle is 34.5(6)°) due to
the presence of the shortened intramolecular H(1)...C(10)
(2.70 Å) (the sum of the van der Waals radii is 2.87 Å)13
and H(1)...H(10) (2.20 Å (2.32 Å)) contacts.
The phenyl group (C(12)...C(17)) is twisted with
respect to the N(1)=C(6) bond by 11.4(6)° (the
N(1)—C(6)—C(12)—C(13) torsion angle) due, apparꢀ
ently, to the shortened intramolecular H(13)...N(1)
(2.48 Å (2.66 Å)) and H(17)...C(7) (2.58 Å) contacts.
The aryl substituents in the fiveꢀmembered ring are
in a trans orientation with respect to each other (the
C(18)—C(9)—C(10)—C(24) torsion angle is 115.8(4)°).
Their mutual repulsion leads to an elongation of the
C(9)—C(10) bond to 1.574(6) Å. The phenyl ring
(C(18)...C(23)) is in the sp conformation relative to the
C(9)—H(9) bond (the H(9)—C(9)—C(18)—C(23) torꢀ
sion angle is 12(1)°).
The nitrophenyl moiety at the C(10) atom is twisted
by 58(1)° with respect to the C(10)—H(10) bond in spite
of the shortened intramolecular H(29)...N(2) contact
(2.48 Å). As a result of this orientation, the Me group at
the C(2) atom is located above the plane of the nitrophenyl
ring, which accounts for the aboveꢀdescribed features of
the 1H NMR spectra.
O(2)
N(3)
O(3)
To summarize, the reactions of 4ꢀmethylꢀ and 4,5ꢀdiꢀ
methylꢀ1,2ꢀphenylenediamine with 1,3ꢀdiarylꢀ2,3ꢀdiꢀ
bromopropanꢀ1ꢀones afforded new 2ꢀarylꢀ1ꢀ(4ꢀnitroꢀ
phenyl)ꢀ1,1aꢀdihydroazireno[1,2ꢀa]quinoxaline derivaꢀ
tives. It was demonstrated that the reaction of 4ꢀmethylꢀ
1,2ꢀphenylenediamine produces a mixture of 5ꢀ and
6ꢀmethylꢀsubstituted dihydroazireno[1,2ꢀa]quinoxalines.
The chemical properties of the reaction products were
studied. 1,2ꢀDihydroquinoxalinꢀ2ꢀone, 3ꢀ(4ꢀnitrobenꢀ
zyl)quinoxaline, and 4ꢀarylꢀ1,2ꢀbis(4ꢀnitrophenyl)ꢀ1,2ꢀ
dihydroꢀ3aHꢀoxazolo[3,2ꢀa]quinoxaline derivatives were
synthesized. The structures of the resulting compounds
C(22)
C(21)
C(23)
C(20)
C(18)
C(19)
C(25)
C(26)
O(4)
C(9)
C(24)
N(4)
O(1)
C(10)
C(27)
C(17)
C(16)
C(15)
C(29)
C(7)
C(6)
1
were established by H NMR spectroscopy, mass specꢀ
N(2)
C(28)
O(5)
C(8)
trometry, and Xꢀray diffraction.
C(1)
C(11)
C(12)
N(1)
Experimental
C(5)
C(4)
C(2)
C(3)
C(13)
C(14)
The 1H NMR spectra were recorded on Varian Mercury
VXꢀ200 (200 MHz) and Bruker AMꢀ300 (300 MHz) spectromꢀ
eters in CDCl3 and DMSOꢀd6 (Me4Si as the internal standard).
Fig. 1. Structure of compound 30 (minor isomer B) established
by Xꢀray diffraction.

366
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
Zbruyev et al.
The mass spectra were obtained on a Varian 1200L instrument
(70 eV). The purity of the reaction products was checked by
TLC on Silufol UVꢀ254 plates with the use of chloroform, ethyl
acetate, or their mixture as the solvent. The ratio of regioisomers
was monitored on a Bischoff module liquid chromatograph
equipped with a Prontosil 120ꢀ3ꢀSi column with the use of
dichloromethane as the eluent. The melting points were meaꢀ
sured on a Boetius hotꢀstage apparatus and are uncorrected.
Substituted oꢀphenylenediamines, 4ꢀfluorophenylglyoxal,
and 4ꢀnitrobenzaldehyde were commercial reagents (Aldrich),
which were used without additional purification.
J = 2.8 Hz); 3.41 (d, 1 H, C(1)H, J = 2.8 Hz); 7.14—8.27 (m,
10 H, H arom.).
2ꢀ(4ꢀFluorophenyl)ꢀ5,6ꢀdimethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ1,1aꢀ
dihydroazireno[1,2ꢀa]quinoxaline (12). The yield was 39%,
m.p. 139—145 °C (from acetone). Found (%): N, 10.82.
C23H18FN3O2. Calculated (%): N, 10.85. 1H NMR (CDCl3), δ:
2.26 and 2.27 (both s, 3 H each, Me); 2.95 (d, 1 H, C(1a)H, J =
2.8 Hz); 3.43 (d, 1 H, C(1)H, J = 2.8 Hz); 7.10—8.27 (m, 10 H,
H arom.).
2ꢀ(4ꢀDifluoromethoxyphenyl)ꢀ5,6ꢀdimethylꢀ1ꢀ(4ꢀnitropheꢀ
nyl)ꢀ1,1aꢀdihydroazireno[1,2ꢀa]quinoxaline (13). The yield was
30%, m.p. 127—130 °C (from acetone). Found (%): N, 9.66.
1,3ꢀDiarylꢀ2,3ꢀdibromopropanꢀ1ꢀones 3—9 were syntheꢀ
sized according to a known procedure.14 The characteristics of
new chalcone dibromides are given below.
1
C24H19FN3O3. Calculated (%): N, 9.65. H NMR (CDCl3), δ:
2.29 and 2.30 (both s, 3 H each, Me); 2.96 (d, 1 H, C(1a)H, J =
2.8 Hz); 3.44 (d, 1 H, C(1)H, J = 2.8 Hz); 6.58 (t, 1 H, OCHF2,
J = 73.0 Hz); 7.17—8.27 (m, 10 H, H arom.).
2,3ꢀDibromoꢀ3ꢀ(4ꢀnitrophenyl)ꢀ1ꢀ(4ꢀpentylphenyl)propanꢀ1ꢀ
one (6). The yield was 66%, m.p. 143—144 °C (from an
MeOH—CHCl3 mixture). Found (%): N, 2.88. C20H21Br2NO3.
Calculated (%): N, 2.90. 1H NMR (DMSOꢀd6), δ: 0.85 (t,
3 H, Me(CH2)4, J = 6.6 Hz); 1.24—1.36 (m, 4 H,
MeCH2CH2(CH2)2); 1.61 (quint, 2 H, Me(CH2)2CH2CH2, J =
7.2 Hz); 2.68 (t, 2 H, Me(CH2)3CH2, J = 7.5 Hz); 5.95 (d, 1 H,
C(3)H, J = 11.3 Hz); 6.73 (d, 1 H, C(2)H, J = 11.3 Hz); 7.45
and 8.19 (both d, 2 H each, C6H4C5H11, J = 8.2 Hz); 8.14 and
8.29 (both d, 2 H each, C6H4NO2, J = 8.9 Hz).
5,6ꢀDimethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ2ꢀ(4ꢀpentylphenyl)ꢀ1,1aꢀ
dihydroazireno[1,2ꢀa]quinoxaline (14). The yield was 39%, m.p.
123—127 °C (from acetone). Found (%): N, 9.60. C28H29N3O2.
Calculated (%): N, 9.56. 1H NMR (CDCl3), δ: 0.88 (t,
3 H, Me(CH2)4, J = 6.8 Hz); 1.28—1.34 (m, 4 H,
MeCH2CH2(CH2)2); 1.59—1.67 (m, 2 H, Me(CH2)2CH2CH2);
2.29 and 2.30 (both s, 3 H each, Me); 2.62 (t, 2 H,
Me(CH2)3CH2, J = 7.7 Hz); 2.96 (d, 1 H, C(1a)H, J = 2.8 Hz);
3.44 (d, 1 H, C(1)H, J = 2.8 Hz); 7.17—8.27 (m, 10 H, H arom.).
5(6)ꢀMethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ2ꢀphenylꢀ1,1aꢀdihydroaziꢀ
reno[1,2ꢀa]quinoxaline (15) (a mixture of isomers A and B). The
yield was 38%, m.p. 135—136 °C (from acetone). Found (%):
N, 11.87. C22H17N3O2. Calculated (%): N, 11.82. 1H NMR
(CDCl3), δ: 2.35 (s, 3 H, Me (B)); 2.36 (s, 3 H, Me (A)); 2.98
(d, 1 H, C(1a)H (A), J = 2.8 Hz); 3.01 (d, 1 H, C(1a)H (B), J =
2.8 Hz); 3.47 (d, 1 H, C(1)H (B), J = 2.8 Hz); 3.48 (d, 1 H,
C(1)H (A), J = 2.8 Hz); 7.02—8.28 (m, 12 H, H arom. (A + B)).
MS, m/z (Irel (%)): 355 [M]+ (100), 308 [M – NO2 – H]+ (20),
270 (13), 233 [M – C6H4NO2]+ (19), 220 [M – CHC6H4NO2]+
(60), 193 (12), 192 (14), 178 (11), 165 (21).
2ꢀ(4ꢀBromophenyl)ꢀ5(6)ꢀmethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ1,1aꢀ
dihydroazireno[1,2ꢀa]quinoxaline (16) (a mixture of isomers A
and B). The yield was 43%, m.p. 136—140 °C (from acetone).
Found (%): N, 9.73. C22H16BrN3O2. Calculated (%): N, 9.68.
1H NMR (CDCl3), δ: 2.36 (s, 3 H, Me (B)); 2.37 (s, 3 H,
Me (A)); 2.97 (d, 1 H, C(1a)H (A), J = 2.8 Hz); 3.00 (d, 1 H,
C(1a)H (B), J = 2.8 Hz); 3.43 (d, 1 H, C(1)H (A + B), J =
2.8 Hz); 7.03—8.28 (m, 11 H, H arom. (A + B)).
2ꢀ(4ꢀEthylphenyl)ꢀ5(6)ꢀmethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ1,1aꢀdiꢀ
hydroazireno[1,2ꢀa]quinoxaline (17) (a mixture of isomers A
and B). The yield was 26%, m.p. 132—142 °C (from acetone).
Found (%): N, 10.89. C24H21N3O2. Calculated (%): N, 10.96.
1H NMR (CDCl3), δ: 1.25 (t, 3 H, CH2Me (A + B), J =
7.5 Hz); 2.34 (s, 3 H, Me (B)); 2.36 (s, 3 H, Me (A)); 2.70
(quart, 2 H, CH2Me (A + B), J = 7.5 Hz); 2.96 (d, 1 H,
C(1a)H (A), J = 2.8 Hz); 2.99 (d, 1 H, C(1a)H (B), J = 2.8 Hz);
3.47 (d, 1 H, C(1)H (B), J = 2.8 Hz); 3.48 (d, 1 H, C(1)H (A),
J = 2.8 Hz); 7.00—8.27 (m, 11 H, H arom. (A + B)).
2,3ꢀDibromoꢀ1ꢀ(4ꢀfluorophenyl)ꢀ3ꢀ(4ꢀnitrophenyl)propanꢀ
1ꢀone (7). The yield was 63%, m.p. 182—184 °C (from
an MeOH—CHCl3 mixture). Found (%): N, 3.21.
C
15H10Br2FNO3. Calculated (%): N, 3.25. 1H NMR
(DMSOꢀd6), δ: 5.96 (d, 1 H, C(3)H, J = 11.3 Hz); 6.78 (d, 1 H,
C(2)H, J = 11.3 Hz); 7.44—7.53 and 8.34—8.42 (both m,
2 H each, C6H4F); 8.13 and 8.30 (both d, 2 H each, C6H4NO2,
J = 8.9 Hz).
2,3ꢀDibromoꢀ1ꢀ(4ꢀdifluoromethoxyphenyl)ꢀ3ꢀ(4ꢀnitropheꢀ
nyl)propanꢀ1ꢀone (9). The yield was 80%, m.p. 108—110 °C
(from an MeOH—CHCl3 mixture). Found (%): N, 2.95.
C16H11Br2F2NO4. Calculated (%): N, 2.92. 1H NMR
(DMSOꢀd6), δ: 5.96 (d, 1 H, C(3)H, J = 11.1 Hz); 6.77 (d, 1 H,
C(2)H, J = 11.1 Hz); 7.47 (t, 1 H, OCHF2, J = 73.2 Hz); 7.40
and 8.37 (both d, 2 H each, C6H4OCHF2, J = 8.5 Hz); 8.13 and
8.29 (both d, 2 H each, C6H4NO2, J = 8.9 Hz).
5,6ꢀDimethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ2ꢀphenylꢀ1,1aꢀdihydroꢀ
azireno[1,2ꢀa]quinoxaline (10). A solution of chalcone dibroꢀ
mide 3 (12 g, 29 mmol), diamine 1 (3.95 g, 29 mmol), and
triethylamine (8.16 mL, 116 mmol) in methanol (460 mL) was
refluxed for 50 min and then kept at ~20 °C in the dark for 1 day.
The precipitate that formed was filtered off and washed with
methanol (10 mL) and 50% aqueous methanol (20 mL). The
mother liquor was concentrated under reduced pressure to 1/3
of the initial volume. After 1 day, the second portion of the
reaction product was filtered off and also washed with methanol
and aqueous methanol. The portions were combined. Comꢀ
pound 10 was obtained in a yield of 5.0 g (45%), m.p. 141—143 °C
1
(from acetone). H NMR (CDCl3), δ: 2.30 and 2.31 (both s,
3 H each, Me); 3.00 (d, 1 H, C(1a)H, J = 2.7 Hz); 3.51 (d, 1 H,
C(1)H, J = 2.7 Hz); 7.18—8.30 (m, 11 H, H arom.).
5(6)ꢀMethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ2ꢀ(4ꢀpentylphenyl)ꢀ1,1aꢀdiꢀ
hydroazireno[1,2ꢀa]quinoxaline (18) (a mixture of isomers A
and B). The yield was 30%, m.p. 116—118 °C (from hexane).
Found (%): N, 9.88. C27H27N3O2. Calculated (%): N, 9.87.
1H NMR (CDCl3), δ: 0.88 (t, 3 H, Me(CH2)4 (A + B), J =
6.8 Hz); 1.28—1.34 (m, 4 H, MeCH2CH2(CH2)2 (A + B));
1.59—1.67 (m, 2 H, Me(CH2)2CH2CH2 (A + B)); 2.35 (s, 3 H,
Compounds 11—20 were synthesized analogously.
2ꢀ(4ꢀBromophenyl)ꢀ5,6ꢀdimethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ1,1aꢀ
dihydroazireno[1,2ꢀa]quinoxaline (11). The yield was 45%,
m.p. 150—154 °C (from acetone). Found (%): N, 9.39.
C23H18BrN3O2. Calculated (%): N, 9.37. 1H NMR (CDCl3), δ:
2.26 and 2.27 (both s, 3 H each, Me); 2.95 (d, 1 H, C(1a)H,

New 1,1aꢀdihydroazireno[1,2ꢀa]quinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
367
Me (B)); 2.36 (s, 3 H, Me (A)); 2.65 (t, 2 H, Me(CH2)3CH2
(A + B), J = 7.6 Hz); 2.96 (d, 1 H, C(1a)H (A), J = 2.8 Hz); 2.99
(d, 1 H, C(1a)H (B), J = 2.8 Hz); 3.47 (d, 1 H, C(1)H (B), J =
2.8 Hz); 3.48 (d, 1 H, C(1)H (A), J = 2.8 Hz); 7.00—8.27 (m,
11 H, H arom. (A + B)).
2ꢀ(4ꢀFluorophenyl)ꢀ5(6)ꢀmethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ1,1aꢀdiꢀ
hydroazireno[1,2ꢀa]quinoxaline (19) (a mixture of isomers A
and B). The yield was 37%, m.p. 133—140 °C (from acetone).
Found (%): N, 11.31. C22H16FN3O2. Calculated (%): N, 11.25.
1H NMR (CDCl3), δ: 2.35 (s, 3 H, Me (B)); 2.36 (s, 3 H,
Me (A)); 2.97 (d, 1 H, C(1a)H (A), J = 2.6 Hz); 3.00 (d, 1 H,
C(1a)H (B), J = 2.6 Hz); 3.43 (d, 1 H, C(1)H (B), J = 2.6 Hz);
3.44 (d, 1 H, C(1)H (A), J = 2.6 Hz); 7.02—8.24 (m, 11 H,
H arom. (A + B)).
5(6)ꢀMethylꢀ1ꢀ(4ꢀnitrophenyl)ꢀ2ꢀ(4ꢀphenylphenyl)ꢀ1,1aꢀ
dihydroazireno[1,2ꢀa]quinoxaline (20) (a mixture of isomers A
and B). The yield was 16%, m.p. 123—130 °C (from acetone).
Found (%): N, 9.71. C28H21N3O2. Calculated (%): N, 9.74.
1H NMR (CDCl3), δ: 2.36 (s, 3 H, Me (B)); 2.37 (s, 3 H,
Me (A)); 3.00 (d, 1 H, C(1a)H (A), J = 2.7 Hz); 3.03 (d, 1 H,
C(1a)H (B), J = 2.7 Hz); 3.53 (d, 1 H, C(1)H (A + B), J =
2.7 Hz); 7.02—8.28 (m, 16 H, H arom. (A + B)).
C23H18BrN3O2. Calculated (%): N, 9.37. 1H NMR (DMSOꢀd6),
δ: 2.47 (s, 6 H, Me); 4.51 (s, 2 H, CH2); 7.28—8.09 (m, 10 H,
H arom.).
7,8ꢀDimethylꢀ1,2ꢀbis(4ꢀnitrophenyl)ꢀ4ꢀphenylꢀ1,2ꢀdihydroꢀ
3aHꢀ[1.3]oxazolo[3,2ꢀa]quinoxaline (29). A solution of comꢀ
pound 10 (1.0 g, 2.58 mmol) and 4ꢀnitrobenzaldehyde (28)
(0.39 g, 2.6 mmol) in toluene (30 mL) was refluxed for 30 min.
Then the reaction solution was concentrated to oneꢀhalf of the
initial volume and kept at ~20 °C for 2 days. The precipitate that
formed was filtered off and washed on a filter with acetone. The
mother liquor was concentrated under reduced pressure to 1/3
of the initial volume and the second portion of the reaction
product was isolated. The portions were combined. Compound
29 was obtained in a yield of 0.52 g (39%), m.p. 183—186 °C
(from a MeCN—PhCH3 mixture, 10 : 1). Found (%): N, 10.81.
C30H24N4O5. Calculated (%): N, 10.76. 1H NMR (DMSOꢀd6),
δ: 2.08 and 2.16 (both s, 3 H each, Me); 5.14 and 5.22 (both d,
1 H each, H(1), H(2), J = 6.3 Hz); 6.41 (s, 1 H, H(3a)); 6.46 (s,
1 H, H(9)); 7.31 (s, 1 H, H(6)); 7.50—8.33 (m, 13 H, H arom.).
MS, m/z (Irel (%)): 518 [M – 2 H]+ (14), 370 (19), 234
[M – (C6H4NO2)2CHCHO]+ (94), 233 (42), 219 (17), 207
(14), 192 (9), 151 (16), 150 (17), 103 (86).
2ꢀ(4ꢀFluorophenyl)ꢀ6,7ꢀdimethylquinoxaline (24). Comꢀ
pound 12 (330 mg, 0.85 mmol) was refluxed in methanol
(150 mL) in the presence of concentrated H2SO4 (0.15 mL) for
50 min. The reaction solution was concentrated under reduced
pressure to 5 mL, neutralized with a 25% aqueous ammonia
solution, and cooled. The precipitate that formed was filtered
off and washed on a filter with methanol. Compound 24 was
obtained in a yield of 155 mg (73%), m.p. 168 °C (from methaꢀ
nol). Found (%): N, 11.07. C16H13FN2. Calculated (%):
7(8)ꢀMethylꢀ1,2ꢀbis(4ꢀnitrophenyl)ꢀ4ꢀphenylꢀ1,2ꢀdihydroꢀ
3aHꢀ[1.3]oxazolo[3,2ꢀa]quinoxaline (30) (a mixture of isomers
A and B). A solution of compound 15 (2.5 g, 7 mmol) and
4ꢀnitrobenzaldehyde (28) (1.1 g, 7.3 mmol) in toluene (25 mL)
was refluxed for 45 min and then kept at ~20 °C for 2 days. The
precipitate that formed was filtered off and washed on a filter
with acetone. Compound 30 was obtained in a yield of 1.1 g
(31%), m.p. 179—182 °C (from MeCN). Found (%): N, 11.07.
1
C29H22N4O5. Calculated (%): N, 11.06. H NMR (CDCl3), δ:
1
N, 11.10. H NMR (DMSOꢀd6), δ: 2.48 (s, 6 H, Me); 7.41 (t,
2.22 (s, 3 H, Me (B)); 2.33 (s, 3 H, Me (A)); 4.90—5.00 (m, 2 H,
H(1), H(2) (A + B)); 6.20 (s, 1 H, H(3a) (B)); 6.28 (s, 1 H,
H(3a) (A)); 6.34—8.35 (m, 16 H, H arom. (A + B)). MS,
m/z (Irel (%)): 504 [M – 2 H]+ (5), 371 (4), 356 (5), 355 (5), 220
[M – (C6H4NO2)2CHCHO]+ (100), 192 (15), 165 (15).
2 H, mꢀH arom., J = 8.7 Hz); 7.86 and 7.88 (both s, 1 H each,
H(5), H(8)); 8.35 (dd, 2 H, oꢀH arom., 3J = 8.7 Hz, 4J =
6.1 Hz); 9.42 (s, 1 H, H(3)). MS, m/z (Irel (%)): 252 [M]+ (100),
237 [M – CH3]+ (28), 225 [M – CCH3]+ (24), 210 [M –
CCH3 – CH3]+ (17), 183 (6), 121 (22), 103 (51).
Compounds 23 and 25 were synthesized analogously. The
characteristics of the previously unknown compound 25 are
given below.
4ꢀ(4ꢀBromophenyl)ꢀ7(8)ꢀmethylꢀ1,2ꢀbis(4ꢀnitrophenyl)ꢀ1,2ꢀ
dihydroꢀ3aHꢀ[1.3]oxazolo[3,2ꢀa]quinoxaline (31) (a mixture of
isomers A and B). A solution of compound 16 (550 mg,
1.27 mmol) and 4ꢀnitrobenzaldehyde (28) (196 mg, 1.3 mmol)
in toluene (15 mL) was refluxed for 30 min. Then the reaction
solution was concentrated to oneꢀhalf of the initial volume
and kept at ~20 °C for 2 days. The precipitate that formed
was filtered off and washed on a filter with acetone. Comꢀ
pound 31 was obtained in a yield of 400 mg (53%), m.p.
179—185 °C (from an MeCN—CHCl3 mixture). Found (%):
N, 9.61. C29H21BrN4O5. Calculated (%): N, 9.57. 1H NMR
(DMSOꢀd6), δ: 2.15 (s, 3 H, Me (B)); 2.23 (s, 3 H, Me (A));
5.13—5.23 (m, 2 H, H(1), H(2) (A + B)); 6.42—8.32 (m,
16 H, H(3a) (A + B) + H arom. (A + B)). MS, m/z (Irel (%)):
584, 582 [M – 2 H]+ (2); 434 (10); 300 (45), 298
[M – (C6H4NO2)2CHCHO]+ (46); 219 (22); 165 (16).
2ꢀ(4ꢀBromophenyl)ꢀ6,7ꢀdimethylquinoxaline (25). The yield
was 77%, m.p. 141—142 °C (from MeOH). Found (%): N, 8.97.
1
C16H13BrN2. Calculated (%): N, 8.94. H NMR (DMSOꢀd6),
δ: 2.47 (s, 6 H, Me); 7.77 (d, 2 H, mꢀH arom., J = 8.8 Hz); 7.87
and 7.89 (both s, 1 H each, H(5), H(8)); 8.24 (d, 2 H, oꢀH arom.,
J = 8.8 Hz); 9.44 (s, 1 H, H(3)). MS, m/z (Irel (%)): 314,
312 [M]+ (100); 299 (5), 297 (6) [M – CH3]+; 287, 285
[M – CCH3]+ (4); 233 [M – Br]+ (80); 218 [M – Br – CH3]+
(12); 206 [M – Br – CCH3]+ (23); 191 [M – Br – CCH3 –
CH3]+ (24); 183 (26), 181 (30); 157 (16); 103 (51).
3ꢀArylꢀ6,7ꢀdimethylꢀ2ꢀ(4ꢀnitrobenzyl)quinoxalines 26 and 27
were synthesized according to a known procedure.12
6,7ꢀDimethylꢀ2ꢀ(4ꢀnitrobenzyl)ꢀ3ꢀphenylquinoxaline (26).
The yield was 74%, m.p. 167—168 °C. Found (%): N, 11.34.
C23H19N3O2. Calculated (%): N, 11.37. H NMR (CDCl3), δ:
2.54 and 2.56 (both s, 3 H each, Me); 4.50 (s, 2 H, CH2);
7.17—8.07 (m, 11 H, H arom.). MS, m/z (Irel (%)): 252 [M]+
(100), 237 [M – CH3]+ (28), 225 [M – CCH3]+ (24), 210
[M – CCH3 – CH3]+ (17).
3ꢀ(4ꢀBromophenyl)ꢀ6,7ꢀdimethylꢀ2ꢀ(4ꢀnitrobenzyl)quinoxaꢀ
line (27). The yield was 72%, m.p. 160 °C. Found (%): N, 9.40.
Xꢀray diffraction study. Xꢀray diffraction data were collected
from one single crystal, which was grown by crystallization of a
mixture of isomers 30 from acetonitrile. The crystals belong
to the orthorhombic system. At 20 °C, a = 36.98(2) Å,
1
b = 10.552(7) Å, c = 13.016(9) Å, V = 5079(6) Å3, dcalc
=
1.325 g cm–3, space group Pbcn, Z = 8. The unit cell parameters
and intensities of 4384 independent reflections (Rint = 0.038)
were measured on an automated Siemens P3/PC diffractometer
(MoꢀKα radiation, graphite monochromator, θ/2θꢀscanning

368
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
Zbruyev et al.
technique, 2θ
= 50°). The profile analysis of the Xꢀray difꢀ
geterotsiklov" [Abstrs of Papers, Ukrainian Conf. "Chemistry of
NitrogenꢀContaining Heterocycles"], Kharkov, 1997, 24 (in
Russian).
max
fraction data was performed with the use of the PROFIT
program.
The structure was solved by direct methods with the use of
the SHELXTL PLUS program package.15 The positions of the
H atoms were calculated geometrically and refined using a riding
model with fixed Ui = nUeq of the corresponding pivot nonꢀ
hydrogen atoms (n = 1.5 for Me groups and 1.2 for other
H atoms). The structure was refined by the fullꢀmatrix leastꢀ
squares method against F 2 with anisotropic displacement paꢀ
rameters for all nonhydrogen atoms to wR2 = 0.208 (R1 = 0.084
based on reflections with F > 4σ(F ), S = 1.00).
8. V. D. Orlov, N. P. Vorob´eva, N. N. Demenkova, V. S.
Chesnovskii, and F. G. Yaremenko, Khim. Geterotsikl.
Soedin., 1988, 328 [Chem. Heterocycl. Compd., 1988, 24, 267
(Engl. Transl.)].
9. N. N. Kolos, V. D. Orlov, E. Ya. Yuzefovskaya, F. G.
Yaremenko, N. P. Vorob´eva, O. V. Shishkin, Yu. T.
Struchkov, and S. M. Ivkov, Khim. Geterotsikl. Soedin., 1995,
950 [Chem. Heterocycl. Compd., 1995, 31, 827 (Engl.
Transl.)].
10. A. Gazit, H. App, G. McMahon, J. Chen, A. Levitzki, and
F. D. Bohmer, J. Med. Chem., 1996, 39, 2170.
11. A. A. H. Saeed and E. K. Ebraheem, J. Heterocycl. Chem.,
1983, 20, 1739.
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Received July 25, 2005;
in revised form December 13, 2005