3-Indolizin-2-ylquinoxalines and the derived monopodands

Article abstract of DOI:10.1007/s11172-006-0165-7

The reactions of 3-acetylquinoxalin-2-one with methyl- and benzylpyridines in the presence of iodine produce the corresponding 3-(2-alkylpyridinioacetyl) quinoxalin-2(1H)-one iodides. Treatment of the latter with triethylamine affords the corresponding 3-

Full text of DOI:10.1007/s11172-006-0165-7

2616
Russian Chemical Bulletin, International Edition, Vol. 54, No. 11, pp. 2616—2625, November, 2005
3ꢀIndolizinꢀ2ꢀylquinoxalines and the derived monopodands*
V. A. Mamedov,ꢀ A. A. Kalinin, V. V. Yanilkin, A. T. Gubaidullin, Sh. K. Latypov, A. A. Balandina,
O. G. Isaikina, A. V. Toropchina, N. V. Nastapova, N. A. Iglamova, and I. A. Litvinov
A. E. Arbuzov Institute of Organic and Physical Chemistry,
Kazan Research Center of the Russian Academy of Sciences,
8 ul. Akad. Arbuzova, 420088 Kazan, Russian Federation.
Eꢀmail: mamedov@iopc.kcn.ru
The reactions of 3ꢀacetylquinoxalinꢀ2ꢀone with methylꢀ and benzylpyridines in the presꢀ
ence of iodine produce the corresponding 3ꢀ(2ꢀalkylpyridinioacetyl)quinoxalinꢀ2(1H )ꢀone
iodides. Treatment of the latter with triethylamine affords the corresponding 3ꢀindolizinꢀ2ꢀ
ylquinoxalinꢀ2ꢀones. Due to the presence of the endocyclic carbamoyl group, the reactions of
these compounds with bisalkylating reagents give quinoxalineꢀcontaining monopodands and
monoalkylation products containing spacers with different lengths and of different nature.
Key words: 3ꢀacetylquinoxalinꢀ2ꢀone, pyridinium salts, Chichibabin reaction, indolizines,
quinoxalines, monopodands, structure, IR spectra, 1D and 2D NMR spectroscopy.
Positions 1 and 3 of the indolizine system are characꢀ
with αꢀpicoline or 2ꢀbenzylpyridine giving rise to pyriꢀ
dinium salts, and subsequent intramolecular condensaꢀ
tion of the latter.
terized by high reactivity in electrophilic substitution reꢀ
actions due to high local and overall πꢀexcessive densiꢀ
ties.1 This fact was observed in studies of alkylation, acylaꢀ
tion, nitration, nitrosation,2,3 cycloaddition,4 and Michael
addition to electronꢀdeficient olefins5,6 and diazonium
salts.7 Certain indolizine derivatives were used for the
preparation of dyes8—11 and lightꢀsensitive compounds in
photoemulsions.12 The synthesis of bisꢀindolizines is also
of considerable interest. These compounds are reversible
twoꢀstep redox systems,13,14 which facilitate the occurꢀ
rence of atropoisomerism15 and serve as the starting
compounds in the synthesis of heterocyclophanes and
ligands16,17 possessing the desired properties. The introꢀ
duction of the indolizine fragment containing the free
locally πꢀexcessive active reaction centers C(1) and C(3)
into functionalized heterocyclic systems will extend the
synthetic potential of these compounds. The aim of the
present study was to synthesize 3ꢀindolizinꢀ2ꢀylquinoxaꢀ
line derivatives containing the C(1) and C(3) centers havꢀ
ing high reactivity under the redox conditions and to preꢀ
pare monopodands based on these compounds
Initially, we used a bromine—dioxane complex as a
halogenating reagent. Bromination was performed in a
dioxane solution at 10—15 °C for 1.5 h. 3ꢀBromoacetylꢀ
quinoxalinꢀ2ꢀ(1H )one was prepared in 30% yield. The
reaction also afforded a compound containing two broꢀ
mine atoms (one atom in the acetyl fragment and another
atom in the benzo fragment of the quinoxaline system) as
a byꢀproduct, whose percentage was 1—20% of the major
product. Subsequent reactions always gave an impurity of
the corresponding product containing the bromine atom
in the benzo fragment of the quinoxaline system. We failed
to separate these products. Attempts to change the reacꢀ
tion conditions of bromination (the reactions were perꢀ
formed in the presence of AlCl3, in different solvents,
with the use of a deficient amount of bromine, or at
lower temperature) did not lead to the desired results. We
only succeeded in increasing the yield of 3ꢀpicolinioꢀ
acetylquinoxalinꢀ2(1H )ꢀone bromide from 27% (in the
first procedure) to 50% by performing the oneꢀpot reacꢀ
tion of 3ꢀacetylquinoxalinꢀ2ꢀone with the bromine—diꢀ
oxane complex followed by the addition of a twofold exꢀ
cess of picoline (to neutralize HBr) in chloroform. Hence,
we used iodine instead of molecular bromine because
iodine is a milder halogenating reagent, which reacts with
3ꢀacetylquinoxalinone without heating and does not give
a byꢀproduct, which could be formed as a result of haloꢀ
genation at the benzo fragment of the quinoxaline system.
Although we failed to isolate 3ꢀiodoacetylquinoxalinꢀ2ꢀ
one, the oneꢀpot reaction of 3ꢀacetylquinoxalinꢀ2ꢀone (1)
Indolizine derivatives were synthesized by the modiꢀ
fied Chichibabin method involving condensation of the
3ꢀacetyl derivative of quinoxaline with 2ꢀmethylꢀ and
2ꢀbenzylpyridines in the presence of molecular iodine.
3ꢀAcetylquinoxalinꢀ2ꢀ(1H )one was transformed into
3ꢀindolizinylꢀsubstituted quinoxalines in several steps,
such as halogenation, the reaction of the resulting iodide
* Dedicated to Professor Ya. A. Levin on the occasion of his
70th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2534—2542, November, 2005.
1066ꢀ5285/05/5411ꢀ2616 © 2005 Springer Science+Business Media, Inc.

3ꢀIndolizinꢀ2ꢀylquinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2617
Scheme 1
R = H (a), Ph (b)
with a twofold excess of 2ꢀmethylꢀ or 2ꢀbenzylpyridine
and one equivalent of iodine yielded crystalline products,
viz., 2ꢀmethylpyridinioꢀ (2a) and 2ꢀbenzylpyridinioꢀ
acetylquinoxalinꢀ2(1H )ꢀone iodides (3b) in 75 and 32%
yields, respectively (Scheme 1).
the reactions of quinoxalinones 4a and 4b with such
bisalkylating reagents as 1,5ꢀdibromoꢀ3ꢀoxapentane,
1,11ꢀdibromoꢀ3,6,9ꢀtrioxaundecane, and α,α´ꢀdibromoꢀ
metaꢀxylene at room temperature (in DMSO as the solꢀ
vent) or in refluxing dioxane in the presence of KOH gave
the bisalkylated derivative (6—10) as the major product
and the monoalkylated derivative as a byꢀproduct. Byꢀ
products 11 and 12, which were obtained in the reaction
with the phenylindolizinyl derivative of quinoxaline 4b,
were isolated and characterized (Scheme 2).
In most cases, the positions of the signals in the NMR
spectra of indolizine derivatives strongly depend on the
nature of the substituents.13—18 Hence in the present study,
we made the assignment of the signals in the 1H and
13C NMR spectra of the reaction products with the use
of DEPT, 2D COSY, 2D HSQC, 2D HMBC,19 and
1D DPFGNOE20 experiments. Let us consider a detailed
analysis of the assignment only for compound 5a, whose
structure was established by Xꢀray diffraction. The strucꢀ
tures of the other compounds were determined analoꢀ
gously.
The geometry of molecule 5a in the crystal structure is
shown in Fig. 1. In this molecule, the indolizine fragment
contains no bulky substituents and is planar to within
experimental error (0.035(4) Å). In the quinoxaline fragꢀ
ment of molecule 5a, the bicyclic system is slightly
nonplanar. The bulky ethyl group and the indolizine
fragment at the N(1) and C(3) atoms adjacent to the
C(2)=O(2) carbonyl group cause substantial steric hinꢀ
drances, the latter being reduced due to the perpendicular
arrangement of the ethyl substituent with respect to the
plane of the heterocycle, a slight twist of the quinoxaline
fragment (the maximum deviation from the mean plane
In the crystalline state and in a deuterated dimethyl
sulfoxide solution, methylpyridinium salt 2 exists in keto
form 2a, whereas benzylpyridinium salt 3 exists in enol
form 3b, as evidenced by the presence of an absorption
band ν(CO) = 1719 cm–1 in the IR spectrum of comꢀ
pound 2 and an absorption band ν(OH) = 3339 cm–1 in
the IR spectrum of compound 3. In addition, the 1H NMR
spectrum of compound 2 shows, along with other signals,
two singlets at δ 6.42 and 12.90 corresponding to the
protons of the CH2 and NH groups, whereas the 1H NMR
spectrum of compound 3 has three singlets at δ 6.02,
11.82, and 12.36 assigned to the protons of the CH, OH,
and NH groups. It should also be noted that the protons
of the CH2 group of the benzyl fragment in compound 3
are nonequivalent due to the presence of the double bond,
with the result that these protons resonate as an AB sysꢀ
tem with large geminal coupling constants (J = 14.12 Hz).
After stirring of pyridinium salts 2 and 3 in a 20%
triethylamine solution in chloroform for 3 and 4 days,
respectively, these compounds were transformed into
indolizinylquinoxalines 4, which were readily alkylated at
the carbamoyl group with ethyl bromide in the presence
of KOH in DMSO to give compounds 5a and 5b (see
Scheme 1).
Alkylation of 3ꢀindolizinꢀ2ꢀylquinoxalinone 4 at the
carbamoyl group with α,ωꢀdihalo derivatives made it posꢀ
sible to synthesize quinoxalineꢀcontaining monopodands
with the πꢀexcessive indolizine substituents. For example,

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005
Mamedov et al.
Scheme 2
Reagents: i. DMSO or dioxane, KOH; ii. DMSO, KOH.
R = H (6, 8), Ph (7, 9); n = 0 (6, 7, 11), 1 (8, 9, 12)
(–0.086(4) Å) is observed for the C(2) atom), a slight
twist of the indolizine and quinoxaline fragments about
the C(3)—C(12) bond (the C(2)—C(3)—C(12)—C(11)
torsion angle is 14.3(5)° and the dihedral angle between
the planes of these fragments is 14.1(1)°), and an increase
in the exocyclic bond angles at the C(12) atom (the
C(3)—C(12)—C(11) torsion angle (128.7(3)°) is larger
than the C(3)—C(12)—C(13) torsion angle (123.3(3)°)).
A system of intermolecular interactions in the crystal
of compound 5a consists, apparently, of C—H...O hydroꢀ
gen bonds and π—π interactions between the aromatic
systems. The molecules are linked into centrosymmetric
dimers by pairs of identical hydrogen bonds between the
O(2) atom of the carboxy group and the proton H(17´) of
the fused pyridine ring with the following parameters:
d(O(2)...H(17´)), 2.46 Å; d(O(2)...C(17´)), 3.420(5) Å;
O(2)...H(17´)—C(17´), 162°; the symmetry code (2 – x,
1 – y, –z) (Fig. 2). The involvement of the O(2) atom in a
bifurcated C—H...O hydrogen bond with the proton H(6″)
of the fused benzene ring of another adjacent molecule
results in the formation of twoꢀlayer chains (with an antiꢀ
parallel arrangement of the molecules) consisting of
hydrogenꢀbonded dimers along the crystallographic 0y
direction, because each molecule is involved in two conꢀ
tacts (as a donor and an acceptor). The parameters of this
interaction are as follows: d(O(2)...H(6″)), 2.66 Å;
C(2)—O(2)...H(6″), 137°; the symmetry code (x, 1 + y, z).
The molecular packing of compound 5a in the crystals
can be described as a parallel packing of the aboveꢀdeꢀ
C(10)
O(2)
C(17)
N(8)
C(16)
C(9)
N(1)
C(2)
C(11)
C(3)
C(8)
C(7)
C(4A)
C(12)
C(13)
C(8A)
C(15)
C(14)
C(13A)
N(4)
C(6)
C(5)
Bond
d/Å
Bond
d/Å
O(2)—C(2)
N(1)—C(2)
N(1)—C(8a)
N(1)—C(9)
N(4)—C(3)
N(4)—C(4a)
N(8)—C(11)
N(8)—C(13a)
N(8)—C(17)
C(2)—C(3)
C(3)—C(12)
C(4a)—C(5)
C(4a)—C(8a)
1.222(4)
1.397(4)
1.337(4)
1.497(4)
1.295(4)
1.397(4)
1.386(4)
1.380(4)
1.415(4)
1.492(5)
1.474(5)
1.377(5)
1.436(5)
C(5)—C(6)
C(6)—C(7)
C(7)—C(8)
C(8a)—C(8)
C(9)—C(10)
C(11)—C(12)
C(12)—C(13)
C(13)—C(13a) 1.360(5)
C(13a)—C(14) 1.428(5)
C(14)—C(15)
C(15)—C(16)
C(16)—C(17)
1.385(5)
1.385(6)
1.377(6)
1.413(5)
1.497(6)
1.372(5)
1.416(5)
1.363(5)
1.388(6)
1.358(6)
Fig. 1. Molecular geometry of compound 5a in the crystal.

3ꢀIndolizinꢀ2ꢀylquinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2619
vided evidence that there are no cavities accessible for
solvent molecules.
1
The H NMR spectrum of compound 5a has signals
H(6)
for the aromatic protons and signals for the protons of the
ethyl group, which are observed at δ 4.48 and δ 1.32 as a
doublet of quartet of quartets and a doublet of doublets,
respectively, rather than the expected quartet and triplet.
This is evidence for the presence of an A3MX spin system
associated, as mentioned above, with hindered rotation
about the N(1)—CH2 bond on the NMR time scale. The
signals for the following three groups of protons are unꢀ
ambiguously distinguished in the aromatic region of the
2D COSY spectrum (Fig. 4, a): the quinoxaline fragment
(H(5), H(6), H(7), and H(8)), the pyridine ring (H(5´),
H(6´), H(7´), and H(8´)), and the pyrrole ring (H(1´)
and H(3´)) of the indolizine fragment. Two singlets at
δ 8.68 and 7.21 are assigned to the individual protons of
the pyrrole ring of the indolizine fragment, the lowerꢀ
O(2)
H(17)
Fig. 2. Hydrogen bond network and π—π contacts in the crystal
structure of compound 5a. Only hydrogen atoms involved in
hydrogen bonds (dashed lines) are shown.
scribed supramolecular structures along the crystalloꢀ
graphic 0y axis so that the planes of the heterocyclic fragꢀ
ments of the molecules are coplanar with the crystalloꢀ
graphic plane (–101) (Fig. 3). The aromatic fragments of
the molecules in these chains form π—π contacts not only
with fragments of the corresponding centrosymmetric
molecules within the chain but also with the molecules of
the adjacent chains. The shortest distances between
the centers of the aromatic rings are in the range of
3.38—3.60 Å. Therefore, the supramolecular structure that
exists in the crystals is characterized by the presence of
different types of intermolecular interactions, C—H...O
and π—π, in two mutually perpendicular directions.
In spite of the fact that the methyl group of the ethyl
substituent at the N(1) atom deviates from the plane of
the heterocycle, the packing coefficient of this crystal
structure is rather high (71.1%), and the calculations proꢀ
a
H(3´)
H(8,7)
H(5)
H(1´)
H(8´)
H(6)
H(6´)
H(5´)
H(7´)
δ
H(7´)/H(6´)
6.4
H(5´)/H(6´)
H(6´)
H(7´)
H(8´)/H(7´)
7.0
7.6
8.2
8.8
H(1´)
H(7)/H(6)
H(6)
H(5)/H(6)
H(8´)
H(8)/H(7)
H(8,7)
H(5)
H(5´)
H(3´)
8.8
8.2
7.6
7.0
δ
H(8´)
H(6)
H(3´)
H(1´)
H(8,7)
b
H(6´)
H(5´)
H(7´)
H(5)
δ
C(1´)
C(6´)
H(1´)/C(1´)
100
110
120
130
H(6´)/C(6´)
H(7´)/C(7´)
H(8)/C(8)
C(8)
C(3´)
C(7´)
C(8´)
C(6)
C(5´)
H(3´)/C(3´)
H(5´)/C(5´)
H(8´)/C(8´)
H(6)/C(6)
H(5)/C(5)
C(5)
C(7)
H(7)/C(7)
8.6
8.0
7.4
6.8
δ
Fig. 3. Fragment of the molecular packing in the crystal strucꢀ
ture of compound 5a projected along the crystallographic 0y
axis. Hydrogen bonds are indicated by dashed lines.
Fig. 4. Fragments of the 2D COSY (a) and 2D HSQC (b) specꢀ
tra of compound 5a.

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Mamedov et al.
field signal corresponding to the proton H(3´) in the
α position with respect to the electronꢀwithdrawing nitroꢀ
gen atom.
For example, the resonance of the carbon atoms
N(1)—CH2, CH3, C(3´), and C(1´) is revealed from the
2D HSQC spectrum (see Fig. 4, b).
The protonꢀcontaining carbon atoms can easily be
determined with the use of DEPT and 2D HSQC spectra.
The 2D HMBC spectrum (Figs 5 and 6) shows a crossꢀ
peak between H(3´) and the signal for the C(5´) atom of
CH3
H(1´)
H(3´)
H(5´)
CH2
a
H(5)
δ
CH3
CH2/CH3
20
CH2
CH3/CH2
40
60
80
100
120
140
CH2/C(8a)
CH2/C(2)
C(3)
C(2)
H(1´)/C(3)
8
7
6
5
4
3
2
δ
H(8,7)
H(1´)
H(3´)
H(8´)
H(6´)
H(5)
H(5´)
H(7´)
b
H(6)
δ
C(1´)
100
105
110
115
120
125
130
135
H(3´)/C(1´)
H(8´)/C(6´)
H(5´)/C(6´)
H(5´)/C(7´)
H(7´)/C(6´)
C(6´)
H(6)/C(8)
H(1´)/C(3´)
C(8)
C(3´)
C(7´)
C(8´)
H(6´)/C(7´)
H(6´)/C(5´)
H(1´)/C(8´)
H(8)/C(6)
H(3´)/C(2´)
H(3´)/C(5´)
C(6)
H(1´)/C(2´)
H(7´)/C(5´)
C(2´)
C(5´)
C(5)
H(8´)/C(8a´)
H(5)/C(7)
H(3´)/C(8a´)
C(7)
C(8a)
C(8a´)
C(4a)
H(1´)/C(8a´)
H(5´)/C(8a´)
H(7´)/C(8a´)
H(5)/C(8a)
H(6)/C(4a)
H(7)/C(8a)
H(8)/C(4a)
8.8
8.4
8.0
7.6
7.2
6.8
6.4
δ
Fig. 5. 2D HMBC spectrum of compound 5a (a) and its fragment (b).

3ꢀIndolizinꢀ2ꢀylquinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2621
atoms of quinoxaline were determined using the 2D COSY
spectrum. The resonances of the carbon atoms of this
fragment were determined from the 2D HSQC spectrum
(see Fig. 4, b). In addition, the 2D HMBC spectrum
shows a crossꢀpeak between the signals for the protons
H(6) at δ 7.40 and H(8) at δ 7.61 and the resonance of the
C(4a) atom at δ 132.70 (see Figs 5, b and 6). Therefore,
we made the complete assignment of the signals of the
quinoxaline fragment in 5a.
In addition, the 2D HMBC experiment unambiguꢀ
ously confirmed the presence of covalent bonds between
all fragments of the molecule (see Figs 5 and 6), viz.,
between the indolizine and quinoxaline fragments and
between the ethyl group and quinoxaline fragment.
To confirm the spatial proximity of the fragments in
compound 5a, we also performed nuclear Overhauser efꢀ
fect (NOE) experiments (Fig. 7).
Fig. 6. Main HMBC correlations between the protons and the
carbon atoms for compound 5a.
the CH group at δ 125.90 as well as a crossꢀpeak between
H(1´) and the C(8´) carbon of the CH group at δ 119.00.
This made it possible to unambiguously identify the C(5´)
and C(8´) atoms. The assignment of the corresponding
protons H(5´) (δ 8.32) and H(8´) (δ 7.44) was additionꢀ
ally confirmed using the 2D HSQC experiment. The other
protons of the indolizine fragment (H(6´) and H(7´))
were determined from the COSY spectrum (see Fig. 4, a).
Analysis of the 2D HSQC spectrum made it possible to
differentiate the signals of the corresponding carbon atꢀ
oms in the 13C NMR spectrum (see Fig. 4, b). In the
2D HMBC spectrum (see Figs 5 and 6), there is a correlaꢀ
tion between the protons H(1´), H(3´), H(5´), H(7´), and
H(8´) and the resonance of the C(8a´) atom at δ 131.67
and a correlation between the signal for the protons H(3´)
and H(1´) and the resonance of the C(2´) atom at δ 123.80.
In addition, the 2D HMBC spectrum (see Figs 5, a and 6)
shows a crossꢀpeak between H(1´) and the resonance of
the C(3) atom at δ 149.44. Therefore, we made the comꢀ
plete assignment of the signals of the indolizine fragment
in the molecule.
We are coming now to the quinoxaline fragment. In
the 2D HMBC spectrum (see Figs 5 and 6), there is a
correlation between the signal for the protons of the
N(1)—CH2 group and two resonances of the quaternary
carbon atoms (δ 152.89/131.08), which can be assigned to
the C(8a)/C(2) (or vice versa) atoms because crossꢀpeaks
are observed only for these atoms, the intensity of the
crossꢀpeaks being proportional to the coupling constant.
In the systems under consideration, the coupling conꢀ
stant 3J is larger than 2,4J.21 In addition, the presence of a
crossꢀpeak between the signal at δ 131.08 and two protons
at δ 7.86 (dd) and δ 7.60 (m) allowed us to differentiate
the C(8a) and C(2) atoms. Thus, the signal at δ 131.08
was assigned to the C(8a) atom, and the signal at δ 152.89
was attributed to the C(2) atom. Taking into account the
multiplicities of the signals for the protons, the presence
of the latter crossꢀpeaks in the HMBC spectrum made it
possible to identify H(5) (doublet, δ 7.86) and H(7) (mulꢀ
tiplet, δ 7.60). Then, the signals for the H(6) and H(8)
As mentioned above, alkylation of the phenylꢀ
indolizine derivative of quinoxaline 4b with bisꢀ
alkylating reagents ABr2 (A = (CH2)2O(CH2)2 or
(CH2)2O(CH2)2O(CH2)2O(CH2)2) afforded, along with
the major products, monoalkylated derivatives as byꢀprodꢀ
ucts. The formation of monoalkylated derivatives 11 and
12 is evidenced by the integrated intensities of the signals
for the protons of the aromatic fragments and the methylꢀ
1
ene groups in the H NMR spectrum as well as by the
presence of a set of lines (24 signals in the spectrum of
compound 11 and 28 signals in the spectrum of comꢀ
pound 12) in the 13C NMR spectrum. The fact that the
2D HMBC spectrum shows crossꢀpeaks between the proꢀ
tons of CH2(1″) and the C(2) and C(8a) atoms of the
quinoxaline system (Fig. 8) is indicative of the formaꢀ
tion of Nꢀalkylated rather than Oꢀalkylated derivatives,
as in the case of formation of bisalkylated compounds
(podands).
The structure of the 11ꢀbromoꢀ3″,6″,9″ꢀtrioxaundecyl
substituent was confirmed based on the 2D COSY and
2D HMBC spectra. The former shows a correlation beꢀ
tween the methylene protons in the O(CH2)2O unit. In
Fig. 7. Principal NOE and their correlations with the strucꢀ
ture of 5a.

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Mamedov et al.
ment operating at 400.13 MHz using the residual signal of DMSO
as the internal standard (δH 2.54 and δC 40.45).
3ꢀ(2´ꢀMethylpyridinioacetyl)quinoxalinꢀ2(1H )ꢀone iodide
(2a). 2ꢀPicoline (2.40 g, 25.8 mmol) was added to a solution of
3ꢀacetylquinoxalinꢀ2(1H )ꢀone (2.40 g, 12.8 mmol) (1) in chloꢀ
roform (25 mL). Then the reaction mixture was cooled to 15 °C,
and I2 (3.00 g, 11.8 mmol) was added. The reaction mixture was
stirred at 15 °C for 1 h and allowed to stand for 7 days. The
crystals that precipitated were filtered off and washed with chloꢀ
roform. The yield was 3.9 g (75%), m.p. 205—207 °C. Found (%):
C, 47.25; H, 3.63; N, 10.21; I, 31.02. C16H14N3O2I. Calcuꢀ
lated (%): C, 47.19; H, 3.47; N, 10.32; I, 31.16. IR, ν/cm–1
:
472, 569, 591, 551, 895, 950, 1141, 1186, 1311, 1494, 1515,
1578, 1612, 1637, 1656, 1719, 2500—3220. 1H NMR, δ: 6.42 (s,
2 H, CH2); 7.46 (d, 1 H, H(8), J = 7.56 Hz); 7.47 (dd, 1 H,
H(6), J = 8.70 and 7.56 Hz); 7.77 (dd, 1 H, H(7), J = 7.52 and
7.52 Hz); 7.96 (d, 1 H, H(5), J = 7.52); 8.10 (dd, 1 H, H(5) Py,
J = 6.76 and 5.28 Hz); 8.18 (d, 1 H, H(3) Py, J = 7.52 Hz); 8.62
(dd, 1 H, H(4) Py, J = 7.52 and 7.56 Hz); 8.96 (d, 1 H, H(6) Py,
J = 6.00 Hz); 12.90 (br.s, 1 H, NH).
Fig. 8. Principal correlations: HMBC (thick arrows, between
the protons and the carbon atoms), COSY (dashed arrows), and
NOE (thin solid arrows) for compound 12.
3ꢀ[βꢀ(2´ꢀBenzylpyridinio)ꢀαꢀhydroxyvinyl]quinoxalinꢀ
2(1H )ꢀone iodide (3b). 2ꢀBenzylpyridine (3.60 g, 21.30 mmol)
was added to a solution of 3ꢀacetylquinoxalinꢀ2(1H )ꢀone (1)
(2.00 g, 10.63 mmol) in chloroform (15 mL). The reaction mixꢀ
ture was cooled to 15 °C, I2 (3.00 g, 11.8 mmol) was added, and
the mixture was stirred at 15 °C for 1 h and allowed to stand for
7 days. The crystals that precipitated were filtered off and washed
with chloroform. The yield was 1.6 g (32%), m.p. 254—256 °C.
Found (%): C, 56.55; H, 3.84; N, 8.76; I, 26.09. C22H18N3O2I.
the 2D HMBC spectrum there are correlations between
the protons and the carbon nuclei (through three bonds)
of the adjacent CH2—O—CH2 groups, which provides
evidence for the presence of a covalent bond between the
units through the oxygen atoms. For example, there are
correlations between the CH2(1″) and CH2(2″) groups
(2D COSY, see Fig. 8), between CH2(2″) and CH2(4″)
(2D HMBC), between CH2(4″) and CH2(5″) (2D COSY),
and then analogously up to CH2(11″) (see Fig. 8).
The attachement of the linear fragment to the
quinoxaline system is additionally confirmed by the presꢀ
ence of NOE between the closely spaced protons of the
CH2(1″)/CH2(2″) groups and H(8) (see Fig. 8).
The chemical shifts of the triplets for the terminal
methylene groups (δ = 3.77 and 3.50 for compounds 11
and 12, respectively) are characteristic of this class of
compounds,21 which is indicative of the presence of the
bromine atom in these groups.
Calculated (%): C, 56.67; H, 3.75; N, 8.69; I, 26.26. IR, ν/cm–1
:
420, 473, 497, 637, 705, 746, 772, 824, 890, 929, 1097, 1151,
1167, 1237, 1302, 1345, 1497, 1560, 1578, 1616, 1629, 1666,
1
2500ꢀ3220, 3339. H NMR, δ: 5.36 (d, 1 H, —CHAHBPh, J =
14.12 Hz); 5.61 (d, 1 H, —CHAHBPh, J = 14.12 Hz); 6.02 (s,
1 H, CHCOH); 7.08—7.18 (m, 1 H, Hp, Ph); 7.22—7.45 (m,
6 H, H(6), H(8), 2 Ho, 2 Hm, Ph); 7.64 (ddd, 1 H, H(7), J =
7.84, 7.72, and 0.96 Hz); 7.73 (d, 1 H, H(5), J = 7.84 Hz); 7.88
(d, 1 H, H(3) Py, J = 8.20 Hz); 8.15 (dd, 1 H, H(5) Py, J =
7.24 and 6.56 Hz); 8.58 (dd, 1 H, H(4) Py, J = 8.20 and 7.56 Hz);
9.27 (d, 1 H, H(6) Py, J = 5.92 Hz); 11.82 (br.s, 1 H, OH); 12.36
(br.s, 1 H, NH).
3ꢀ(Indolizinꢀ2ꢀyl)quinoxalinꢀ2(1H )ꢀone (4a). Triethylamine
(10 mL) was added to a mixture of compound 2a (2.0 g,
0.49 mmol) and chloroform (40 mL). The reaction mixture was
stirred for 2 h and kept for 3 days. Then chloroform and Et3N
were evaporated in vacuo, and water (30 mL) was added to the
residue. The crystals that precipitated were filtered off, washed
with water, dried, suspended in chloroform (5 mL), passed
through a column (300×25 mm) packed with silica gel (6 g), and
eluted with chloroform (250 mL). The solvent was evaporated
in vacuo, and analytically pure compound 4a was obtained in a
yield of 0.49 g (39%), m.p. 261—263 °C. Found (%): C, 73.49;
H, 4.38; N, 16.03. C16H11N3O. Calculated (%): C, 73.55;
H, 4.24; N, 16.08. IR, ν/cm–1: 421, 472, 543, 586, 639, 726,
745, 788, 813, 919, 1021, 1142, 1178, 1300, 1500, 1543, 1595,
1610, 1670. 1H NMR, δ: 6.56 (dd, 1 H, H(6´), J = 7.02 and
6.60 Hz); 6.71 (dd, 1 H, H(7´), J = 6.96 and 6.50 Hz); 7.20 (s,
1 H, H(1´)); 7.31 (dd, 1 H, H(6), J = 8.34 and 6.96 Hz); 7.44 (d,
1 H, H(8´), J = 7.92 Hz); 7.36 (d, 1 H, H(8), J = 7.92 Hz); 7.48
(dd, 1 H, H(7), J = 7.92 and 7.44 Hz); 7.81 (dd, 1 H, H(5), J =
8.28 and 0.9 Hz); 8.33 (d, 1 H, H(5´), J = 7.02 Hz); 8.72 (s, 1 H,
The compositions of the reaction products were also
confirmed by elemental analysis.
To summarize, we developed a convenient procedure
for the synthesis of the indolizinylquinoxaline system and
examined the possibilities of synthesizing quinoxalineꢀ
containing monopodands by alkylation with various
bisalkylating reagents.
Experimental
The melting points were determined on a Boetius hot stage.
The IR spectra of all compounds were recorded on a Bruker
Vectorꢀ22 Fourierꢀtransform spectrometer in Nujol mulls.
The 1H and 13C NMR and 2D spectra, including COSY, HSQC,
HMBC, and NOESY spectra, of compounds 4a, 5a, 6, 9, and 12
were measured on a Bruker AVANCEꢀ600 Fourierꢀtransform
spectrometer operating at 600.00 (1H) and 150.86 (13C) MHz in
DMSOꢀd6 at 50 °C. The 1H NMR spectra of compounds 2a, 3b,
4b, 5b, and 6—10 were recorded on a Bruker MSLꢀ400 instruꢀ

3ꢀIndolizinꢀ2ꢀylquinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2623
H(3´)); 12.54 (s, 1 H, NH). 13C NMR, δ: 98.74 (C(1´)), 110.84
(C(6´)), 114.81 (C(8)), 116.70 (C(3´)), 117.85 (C(7´)), 118.98
(C(8´)), 123.00 (C(6)), 123.66 (C(2´)), 125.91 (C(5´)), 127.81
(C(5)), 128.87 (C(7)), 131.01 (C(8a)), 131.68 (C(8a´)), 132.08
(C(4a)), 150.80 (C(3)), 154.00 (C(2)).
745, 762, 1021, 1082, 1089, 1098, 1135, 1187, 1251, 1274, 1285,
1309, 1422, 1497, 1602, 1652. 1H NMR, δ: 1.28 (dd, 3 H, CH3,
J = 7.04 and 6.63 Hz); 4.33 (dq, 2 H, CH2, J = 7.04 and
6.63 Hz); 6.64 (dd, 1 H, H(6´), J = 6.68 and 5.84 Hz); 6.75 (dd,
1 H, H(7´), J = 6.28 and 6.28 Hz); 7.20—7.60 (m, 10 H, Ph,
H(5), H(6), H(7), H(8), H(5´)); 8.37 (d, 1 H, H(5´), J =
7.04 Hz); 8.56 (s, 1 H, H(3´)).
3ꢀ(3ꢀPhenylindolizinꢀ2ꢀyl)quinoxalinꢀ2(1H )ꢀone (4b). Triꢀ
ethylamine (8 mL) was added to a mixture of compound 3b
(0.4 g, 0.083 mmol) and chloroform (32 mL). The reaction
mixture was stirred for 2 h and kept for 3 days. Then chloroform
and Et3N were evaporated in vacuo, and water (20 mL) was
added to the residue. The crystals that precipitated were filtered
off, washed with water, dried, suspended in chloroform (10 mL),
passed through a column (300×15 mm) packed with silica gel
(2 g), and eluted with chloroform (80 mL). The solvent was
evaporated in vacuo, and analytically pure compound 4b was
obtained in a yield of 0.2 g (71%), m.p. 243—245 °C. Found (%):
C, 74.65; H, 5.28; N, 14.43. C18H15N3O. Calculated (%):
C, 74.72; H, 5.23; N, 14.52. IR, ν/cm–1: 422, 472, 556, 594,
663, 702, 744, 769, 788, 912, 1149, 1176, 1276, 1317, 1490,
1544, 1597, 1666, 2500—3220. 1H NMR, δ: 6.64 (dd, 1 H,
H(6´), J = 6.80 and 6.76 Hz); 6.76 (dd, 1 H, H(7´), J = 6.76 and
6.08 Hz); 7.20 (dd, 1 H, H(6), J = 7.44 and 6.80 Hz); 7.26 (d,
1 H, H(8), J = 8.16 Hz); 7.30 (d, 1 H, H(5), J = 8.80 Hz);
7.31—7.40 (m, 6 H, Ph, H(5´)); 7.45 (dd, 1 H, H(7), J =
8.12 and 6.80 Hz); 8.38 (d, 1 H, H(5´), J = 6.76 Hz); 8.59 (s,
1 H, H(3´)); 12.33 (s, 1 H, NH).
1ꢀEthylꢀ3ꢀ(indolizinꢀ2ꢀyl)quinoxalinꢀ2ꢀone (5a). Ethyl broꢀ
mide (0.046 mL, 0.62 mmol) was added to a mixture of comꢀ
pound 4a (101 mg, 0.39 mmol), KOH (0.1 g, 1.8 mmol), and
DMSO (1 mL). The reaction mixture was stirred for 5 h and
kept for 2 days. The crystals that precipitated were filtered off
and washed with water, and analytically pure compound 5a was
obtained. The filtrate was poured into water. The crystals that
precipitated were filtered off and washed with water, and an
additional amount of compound 5a was obtained. The latter was
dissolved in chloroform (1 mL), passed through a column
(300×15 mm) packed with silica gel (1 g), and eluted with chloꢀ
roform (40 mL). The solvent was evaporated in vacuo, and anaꢀ
lytically pure compound 5a was obtained in a yield of 0.62 g
(55%), m.p. 167—168 °C. Found (%): C, 74.67; H, 5.26;
N, 14.49. C18H15N3O. Calculated (%): C, 74.80; H, 5.19;
N, 14.53. IR, ν/cm–1: 418, 427, 469, 549, 642, 651, 725, 742,
746, 780, 808, 1115, 1150, 1191, 1246, 1304, 1371, 1498, 1543,
1581, 1633, 1648. 1H NMR, δ: 1.32 (dd, 3 H, CH3, J = 7.28 and
6.94 Hz); 4.48 (dq, 2 H, CH2, J = 7.28 and 6.94 Hz); 6.57 (dd,
1 H, H(6´), J = 6.52 and 6.16 Hz); 6.73 (dd, 1 H, H(7´), J = 6.52
and 6.48 Hz); 7.24 (s, 1 H, H(1´)); 7.37—7.44 (m, 1 H, H(6));
7.44 (d, 1 H, H(8´), J = 8.92 Hz); 7.58—7.65 (m, 1 H, H(7));
7.61 (dd, 1 H, H(8), J = 8.7 and 1.7 Hz); 7.86 (dd, 1 H, H(5),
J = 7.88 and 1.0 Hz); 8.32 (d, 1 H, H(5´), J = 7.3 Hz); 8.68 (s,
1 H, H(3´)). 13C NMR, δ: 12.08 (CH3), 36.67 (CH2), 98.97
(C(1´)), 110.88 (C(6´)), 113.97 (C(8)), 116.82 (C(3´)), 117.86
(C(7´)), 119.00 (C(8´)), 123.14 (C(6)), 123.80 (C(2´)), 125.90
(C(5´)), 129.00 (C(5)), 129.32 (C(7)), 131.08 (C(8a)), 131.67
(C(8a´)), 132.70 (C(4a)), 149.44 (C(3)), 152.89 (C(2)).
1,5ꢀBis[3ꢀ(indolizinꢀ2ꢀyl)ꢀ2ꢀoxoquinoxalinꢀ1ꢀyl]ꢀ3ꢀoxaꢀ
pentane (6). 1,5ꢀDibromoꢀ3ꢀoxapentane (49 mg, 0.21 mmol)
was added to a mixture of compound 4a (100 mg, 0.39 mmol),
KOH (0.1 g, 1.8 mmol), and DMSO (2 mL). The reaction
mixture was stirred for 5 h and kept for 2 days. The crystals that
precipitated were filtered off, washed with water, dried, disꢀ
solved in chloroform (1 mL), and passed through a column
(300×15 mm) packed with silica gel (2 g) with the use of chloroꢀ
form (60 mL) as the eluent. The solvent was removed in vacuo,
and analytically pure compound 6 was obtained. The yield was
0.23 g (20%), m.p. 232—234 °C. Found (%): C, 72.85; H, 4.70;
N, 14.26. C36H28N6O3. Calculated (%): C, 72.96; H, 4.76;
N, 14.18. IR, ν/cm–1: 421, 447, 550, 643, 730, 741, 753, 782,
810, 1107, 1120, 1224, 1305, 1364, 1499, 1545, 1603, 1659.
1H NMR, δ: 3.86 (t, 2 H, OCH2, J = 5.63 Hz); 4.49 (t, 2 H,
NCH2, J = 5.63 Hz); 6.57 (ddd, 1 H, H(6´), J = 7.17, 6.14, and
1.03 Hz); 6.77 (dd, 1 H, H(7´), J = 6.66 and 6.65 Hz); 7.22 (s,
1 H, H(1´)); 7.34 (dd, 1 H, H(6), J = 8.19 and 7.17 Hz); 7.45
(dd, 1 H, H(7), J = 7.46 and 7.45 Hz); 7.46 (d, 1 H, H(8´), J =
9.22 Hz); 7.56 (d, 1 H, H(8), J = 8.19 Hz); 7.79 (d, 1 H, H(5),
J = 8.20 Hz); 8.31 (d, 1 H, H(5´), J = 6.15 Hz); 8.63 (s, 1 H,
H(3´)). 13C NMR, δ: 41.43 (NCH2), 67.12 (OCH2), 98.98
(C(1´)), 110.87 (C(6´)), 114.40 (C(8)), 116.79 (C(3´)), 117.84
(C(7´)), 118.99 (C(8´)), 123.13 (C(6)), 123.75 (C(2´)), 125.88
(C(5´)), 128.78 (C(5)), 128.95 (C(7)), 131.67 (C(8a)), 131.81
(C(8a´)), 132.55 (C(4a)), 149.30 (C(3)), 153.36 (C(2)).
1,5ꢀBis[2ꢀoxoꢀ3ꢀ(1ꢀphenylindolizinꢀ2ꢀyl)quinoxalinꢀ1ꢀyl]ꢀ3ꢀ
oxapentane (7) and 1ꢀ(5ꢀbromoꢀ3ꢀoxapentꢀ1ꢀyl)ꢀ3ꢀ(1ꢀphenylꢀ
indolizinꢀ2ꢀyl)quinoxalinꢀ2ꢀone (11). A mixture of compound 4b
(0.40 g, 1.19 mmol), KOH (0.10 g, 1.79 mmol), and dioxane
(10 mL) was refluxed for 5 min. Then 1,5ꢀdibromoꢀ3ꢀoxapentane
(0.17 g, 0.73 mmol) was added. The reaction mixture was reꢀ
fluxed for 12 h, cooled, and poured into water (40 mL). The
crystals that precipitated were filtered off and washed with waꢀ
ter. The resulting mixture of compounds 4b, 7, and 11 was
separated by silica gel column chromatography (m 20 g,
L 100/160µ) using chloroform as the eluent.
The yield of compound
138—140 °C. Found (%): C, 77.29; H, 4.81; N, 11.39.
48H36N6O3. Calculated (%): C, 77.40; H, 4.87; N, 11.28. IR,
7 was 80 mg (18%), m.p.
C
ν/cm–1: 586, 670, 762, 1083, 1123, 1229, 1311, 1528, 1544,
1581, 1602, 1654. 1H NMR, δ: 3.77 (t, 4 H, 2 OCH2, J =
5.48 Hz); 4.40 (t, 4 H, 2 NCH2, J = 5.48 Hz); 6.60 (ddd, 2 H,
2 H(6´), J = 7.56, 6.16, and 1.36 Hz); 6.73 (dd, 2 H, 2 H(7´), J =
7.52 and 6.80 Hz); 7.12—7.40 (m, 16 H, 2 Ph, 2 H(5), 2 H(6),
2 H(5´)); 7.37 (ddd, 2 H, H(7), J = 8.24, 6.88, and 1.40 Hz);
7.46 (d, 2 H, 2 H(8), J = 8.24 Hz); 8.29 (d, 2 H, 2 H(5´), J =
6.84 Hz); 8.49 (s, 2 H, H(3´)).
1ꢀEthylꢀ3ꢀ(3ꢀphenylindolizinꢀ2ꢀyl)quinoxalinꢀ2ꢀone (5b) was
prepared analogously to compound 5a from phenylindolizinꢀ2ꢀ
ylquinoxalinꢀ2ꢀone (4b) (0.2 g, 0.59 mmol). The yield was 0.1 g
(46%), m.p. 167—169 °C. Found (%): C, 78.96; H, 5.40;
N, 11.39. C24H19N3O. Calculated (%): C, 78.88; H, 5.24;
N, 11.50. IR, ν/cm–1: 419, 432, 463, 501, 584, 670, 701, 732,
The yield of compound 11 was 58 mg (10%), m.p.
121—123 °C. Found (%): C, 64.01; H, 4.38; N, 8.43; Br, 16.25.
26H22BrN3O2. Calculated (%): C, 64.12; H, 4.51; N, 8.62;
Br, 16.40. IR, ν/cm–1: 672, 707, 752, 763, 1134, 1185, 1289,
1311, 1497, 1529, 1582, 1601, 1654. 1H NMR, δ: 3.77 (t,
2 H, N(CH2)2OCH2CH2Br, J = 5.48 Hz); 3.77 (t, 2 H,
C

2624
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005
Mamedov et al.
N(CH2)2OCH2CH2Br,
NCH2CH2O(CH2)2Br,
J
J
=
=
5.48 Hz); 3.82 (t,
6.20 Hz); 4.51 (t,
2
2
H,
H,
2 H, C(7″)H2); 3.45—3.48 (m, 4 H, C(5″)H2, C(8″)H2); 3.50 (t,
2 H, C(11″)H2, J = 5.86 Hz); 3.54 (t, 2 H, C(4″)H2, J = 5.86 Hz);
3.67 (t, 2 H, C(10″)H2, J = 5.87 Hz); 3.75 (t, 2 H, C(2″)H2, J =
5.87 Hz); 4.47 (t, 2 H, C(1″)H2, J = 5.86 Hz); 6.63 (dd, 1 H,
H(6´), J = 6.60 and 6.60 Hz); 6.75 (dd, 1 H, H(7´), J = 6.61 and
6.60 Hz); 7.22—7.29 (m, 3 H, H(5), H(6), Hp); 7.30—7.35 (m,
5 H, 2 Ho, 2 Hm, H(8´)); 7.53 (ddd, 1 H, H(7), J = 6.61, 6.60,
and 2.20 Hz); 7.62 (d, 1 H, H(8), J = 8.07 Hz); 8.36 (d, 1 H,
H(5´), J = 6.60 Hz); 8.53 (s, 1 H, H(3´)). 13C NMR, δ: 31.79
(C(11)H2), 41.58 (C(1)H2), 67.01 (C(2)H2), 69.34 (C(8)H2),
69.54 (C(7)H2), 69.57 (C(5)H2), 69.85 (C(4)H2), 70.13
(C(10)H2), 111.34 (C(6´)), 113.85 (C(1´)), 114.58 (C(8)),
117.04 (C(3´)), 117.33 (C(8´)), 118.52 (C(7´)), 120.92 (C(2´)),
122.98 (C(6)), 125.25 (Cp), 125.88 (C(5´)), 127.35 (2 Cm),
128.67 (C(5)), 129.29 (C(7)), 129.60 (C(8a´)), 129.95 (2 Co),
135.36 (Ci), 132.00 (C(8a)), 132.08 (C(4a)), 150.32 (C(3)),
153.47 (C(2)).
NCH2CH2O(CH2)2Br, J = 5.48 Hz); 6.64 (ddd, 1 H, H(6´), J =
6.86, 6.16, and 1.36 Hz); 6.76 (ddd, 1 H, H(7´), J = 9.24, 6.20,
and 1.36 Hz); 7.18—7.40 (m, 8 H, Ph, H(5), H(6), H(5´)); 7.54
(ddd, 1 H, H(7), J = 8.24, 6.88, and 1.40 Hz); 7.65 (d, H,
H(8), J = 8.20 Hz); 8.37 (d, 1 H, H(5´), J = 6.88 Hz); 8.54
(s, 1 H, H(3´)).
1,11ꢀBis(3ꢀindolizinꢀ2ꢀylꢀ2ꢀoxoquinoxalinꢀ1ꢀyl)ꢀ3,6,9ꢀtriꢀ
oxaundecane (8) was prepared analogously to compound 7 from
indolizinylquinoxaline 4a (0.2 g, 0.76 mmol) and 1,11ꢀdibromoꢀ
3,6,9ꢀtrioxaundecane (0.2 g, 0.62 mmol). The yield was 30 mg
(11%), m.p. 70—71 °C. Found (%): C, 70.44; H, 5.37; N, 12.30.
C40H36N6O5. Calculated (%): C, 70.57; H, 5.33; N, 12.35.
IR, ν/cm–1: 622, 742, 782, 810, 941, 1037, 1183, 1223,
1301, 1355, 1498, 1602, 1648. 1H NMR, δ: 3.36—3.41
(m,
2 H, N(CH2)2OCH2CH2O); 3.46—3.50 (m, 2 H,
N(CH2)2OCH2CH2O); 3.76 (t, 2 H, NCH2CH2O(CH2)2O, J =
5.84 Hz); 4.49 (t, 2 H, NCH2CH2O(CH2)2O, J = 5.84 Hz); 6.55
(dd, 1 H, H(6´), J = 6.88 and 6.16 Hz); 6.71 (dd, 1 H, H(7´), J =
8.92 and 6.16 Hz); 7.22 (s, 1 H, H(1´)); 7.36 (dd, 1 H, H(6), J =
7.52 and 6.88 Hz); 7.43 (d, 1 H, H(8´), J = 8.92); 7.53 (dd, 1 H,
H(7), J = 8.24 and 7.52 Hz); 7.62 (d, 1 H, H(8), J = 8.24 Hz);
7.82 (d, 1 H, H(5), J = 8.20 Hz); 8.30 (d, 1 H, H(5´), J =
7.20 Hz); 8.66 (s, 1 H, H(3´)).
1,3ꢀBis[3ꢀ(indolizinꢀ2ꢀyl)ꢀ2ꢀoxoquinoxalinꢀ1ꢀylmethyl]benꢀ
zene (10) was prepared analogously to compound 7 from
indolizinylquinoxaline 4a (100 mg) and α,α´ꢀdibromoꢀmꢀxyꢀ
lene (52 mg). The yield was 67 mg (28%), m.p. 247—249 °C.
Found (%): C, 76.99; H, 4.67; N, 13.63. C40H28N6O2. Calcuꢀ
lated (%): C, 76.90; H, 4.52; N, 13.45. IR, ν/cm–1: 530, 562,
644, 755, 783, 812, 1123, 1179, 1220, 1304, 1496, 1546, 1529,
1
1603, 1655. H NMR (DMSOꢀd6), δ: 5.62 (s, 4 H, CH2); 6.58
1,11ꢀBis[2ꢀoxoꢀ3ꢀ(1ꢀphenylindolizinꢀ2ꢀyl)quinoxalinꢀ1ꢀyl]ꢀ
3,6,9ꢀtrioxaundecane (9) and 1ꢀ(11ꢀbromoꢀ3,6,9ꢀoxaundecꢀ1ꢀ
yl)ꢀ3ꢀ(1ꢀphenylindolizinꢀ2ꢀyl)quinoxalinꢀ2ꢀone (12). A mixture of
compound 4b (0.70 g, 2.09 mmol), KOH (0.18 g, 3.14 mmol),
and dioxane (20 mL) was refluxed for 5 min. Then 1,5ꢀdibromoꢀ
3ꢀoxapentane (0.40 g, 1.25 mmol) was added. The reaction mixꢀ
ture was refluxed for 12 h, cooled, and poured into water (40 mL).
The crystals that precipitated were filtered off and washed with
water, and a mixture of compounds 4b, 9, and 12 was obtained.
The compounds were separated by silica gel column chromatoꢀ
graphy (m 20 g, L 100/160µ) using chloroform as the eluent.
The yield of compound 9 was 0.64 g (37%), m.p. 168—169 °C.
Found (%): C, 75.07; H, 5.38; N, 10.00. C52H44N6O5. Calcuꢀ
lated (%): C, 74.98; H, 5.32; N, 10.09. IR, ν/cm–1: 670, 702, 753,
1007, 1125, 1183, 1228, 1289, 1311, 1494, 1529, 1581, 1602,
(dd, 2 H, H(6´), J = 6.66 and 6.65 Hz); 6.74 (dd, 2 H, H(7´), J =
6.66 and 6.65 Hz); 7.27 (s, 2 H, H(1´)); 7.29—7.39 (m, 10 H,
2 H(6), 2 H(7), 2 H(8), C6H4); 7.43 (d, 2 H, H(8´), J = 8.19 Hz);
7.82 (d, 2 H, H(5), J = 6.65 Hz); 8.21 (d, 2 H, H(5´), J =
7.17 Hz); 8.67 (s, 2 H, H(3´)).
Xꢀray diffraction study of compound 5a was carried out on an
automated fourꢀcircle EnrafꢀNonius CADꢀ4 diffractometer.
Paleꢀbrown prismatic crystals of 5a, C18H14N3O, belong to the
triclinic system, crystal dimensions were 0.3×0.3×0.3 mm. At
20 °C, a = 7.75(1), b = 9.49(1), c = 9.734(9) Å, α = 90.18(6),
β = 97.68(6), γ = 89.96(5)°, V = 709(1) Å3, Z = 2, dcalc
=
1.35 g cm–3, space group P–1. The unit cell parameters and the
intensities of 2577 reflections, of which 1130 reflections were
with I ≥ 3σ, were measured at 20 °C (λ(MoꢀKα), graphite monoꢀ
chromator, ω/2θ scanning technique, θ ≤ 26.31°). The intensiꢀ
ties of three check reflections showed no decrease in the course of
Xꢀray data collection. The absorption correction was not applied
because the absorption coefficient was small (µMo 0.81 cm–1).
The structure was solved by direct method using the SIR proꢀ
gram22 and refined first isotropically and then anisotropically
using the MolEN program package.23 Subsequently, the hydroꢀ
gen atoms were located from difference electron density maps
and included in the final steps of the refinement with fixed
thermal and positional parameters. The final R factors were
R = 0.059 and Rw = 0.068 based on 1130 reflections with F 2 ≥ 3σ.
The figures were drawn and intermolecular contacts were anaꢀ
lyzed using the PLATON program.24
1
1652. H NMR, δ: 3.37—3.41 (m, 2 H, N(CH2)2OCH2CH2O);
3.45—3.49 (m, 2 H, N(CH2)2OCH2CH2O); 3.71 (t, 2 H,
NCH2CH2O(CH2)2O,
J = 5.50 Hz); 4.41 (t, 2 H,
NCH2CH2O(CH2)2O, J = 5.50 Hz); 6.60 (ddd, 1 H, H(6´), J =
6.81, 6.13, and 0.68 Hz); 6.72 (dd, 1 H, H(7´), J = 6.81, 6.13,
and 0.68 Hz); 7.22—7.28 (m, 3 H, H(5), H(6), Hp); 7.29—7.38
(m, 5 H, H(8´), 2 Ho, 2 Hm); 7.46 (ddd, 1 H, H(7), J = 7.81,
7.80, and 1.41 Hz); 7.55 (d, 1 H, H(8), J = 7.82 Hz); 8.32 (d,
1 H, H(5´), J = 6.80 Hz); 8.52 (s, 1 H, H(3´)). 13C NMR, δ:
41.47 (NCH2CH2OCH2CH2), 66.90 (NCH2CH2OCH2CH2),
69.47 (NCH2CH2OCH2CH2), 69.74 (NCH2CH2OCH2CH2),
113.79 (C(1´)), 114.46 (C(8)), 117.02 (C(3´)), 117.25 (C(8´)),
118.41 (C(7´)), 120.83 (C(2´)), 122.86 (C(6´)), 122.86 (C(6)),
125.17 (Cp), 125.79 (C(5´)), 127.25 (2 Cm), 128.58 (C(5)), 129.15
(C(7)), 129.54 (C(8a´)), 129.92 (2 Co), 135.31 (Ci), 131.90
(C(8a)), 132.01 (C(4a)), 150.20 (C(3)), 153.37 (C(2)).
This study was financially supported by the Russian
Foundation for Basic Research (Project Nos 03ꢀ03ꢀ32865,
04ꢀ03ꢀ32156, and 05ꢀ03ꢀ33008), the US Civilian Research
and Development Foundation (CRDF), and the Minisꢀ
try of Education and Science of the Russian Federation
(Cooperative Grants Program "Basic Research and Higher
Education," BRHE, Grant RECꢀ007).
The yield of compound 12 was 24 mg (2%), m.p. 65—67 °C.
Found (%): C, 62.48; H, 5.15; N, 7.32; Br, 13.73.
C
30H30BrN3O4. Calculated (%): C, 62.66; H, 5.21; N, 7.30;
Br, 13.89. IR, ν/cm–1: 672, 702, 752, 1015, 1184, 1226, 1248,
1288, 1311, 1529, 1581, 1601, 1654. 1H NMR, δ: 3.41—3.44 (m,

3ꢀIndolizinꢀ2ꢀylquinoxalines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2625
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Received June 22, 2005;
in revised form September 5, 2005