Synthesis, structure, and electrochemical properties of 1 2,42-dioxo-21,31-diphenyl-7,10,13- trioxa-1,4(3,1)-diquinoxalina-2(2,3),3(3,2)-diindolizinacyclopentadecaphane

Article abstract of DOI:10.1007/s11172-007-0322-7

The oxidative dehydrocyclization of the 3-(indolizin-2′-yl)-2- oxoquinoxaline monopodand performed either electrochemically or under the action of molecular iodine affords new redox-active heterocyclophane consisting of the redox-switchable biindolizine f

Full text of DOI:10.1007/s11172-007-0322-7

Russian Chemical Bulletin, International Edition, Vol. 56, No. 10, pp. 2060—2073, October, 2007
2060
Synthesis, structure, and electrochemical properties of
12,42ꢀdioxoꢀ21,31ꢀdiphenylꢀ7,10,13ꢀtrioxaꢀ1,4(3,1)ꢀdiquinoxalinaꢀ
2(2,3),3(3,2)ꢀdiindolizinacyclopentadecaphane*
V. A. Mamedov,ꢀ A. A. Kalinin, V. V. Yanilkin, N. V. Nastapova, V. I. Morozov, A. A. Balandina,
A. T. Gubaidullin, O. G. Isaikina, A. V. Chernova, Sh. K. Latypov, 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.
Fax: +7 (843 2) 73 2253. Eꢀmail: mamedov@iopc.knc.ru
The oxidative dehydrocyclization of the 3ꢀ(indolizinꢀ2´ꢀyl)ꢀ2ꢀoxoquinoxaline monopodand
performed either electrochemically or under the action of molecular iodine affords new redoxꢀ
active heterocyclophane consisting of the redoxꢀswitchable biindolizine fragment combined
with the polyetherꢀbridged πꢀdeficient quinoxaline systems. The singleꢀcrystal Xꢀray diffracꢀ
tion study showed that the trioxaundecane chain of heterocyclophane adopts an extended
conformation, and one of the phenyl substituents of the molecule closes the pseudocavity
formed by the spacer from one of the sides. The cyclic voltammetric study of heterocyclophane
in MeCN and DMF showed the threeꢀstep oxidation of the indolizine fragments accompanied
by the singleꢀelectron transfer in each step. The first and third steps are reversible, and the
second step is irreversible. The oxidation at potentials of the first peak gives rise to stable radical
cations detected by the ESR method (g = 2.0024, a2N = 0.26 mT).
Key words: 3ꢀ(indolizinꢀ2´ꢀyl)quinoxalinꢀ2ꢀones, 3ꢀacetylquinoxalinꢀ2ꢀone, pyridinium
salts, Ortoleva—King reaction, Chichibabin reaction, monopodands, UV spectra, 1D and
2D NMR spectroscopy, Xꢀray diffraction study, electrochemical oxidation, ESR.
In recent years, the synthesis of macrocyclic comꢀ
cations.10—14 The stability and subsequent transformaꢀ
tions of radical cations are determined primarily by the
presence of hydrogen atoms in the pyrrole ring of the
indolizine system. The radical cations and dications of
3,3´ꢀbiindolizines, in which all hydrogen atoms in the
fiveꢀmembered ring are replaced by alkyl or aryl groups,
are quite stable and can be isolated and characterized as
perchlorates.12 The electrochemical behavior of two diaꢀ
stereomers of macrocyclic biindolizines, in which both
heterofragments are linked at positions 3,3´ and, through
a bridge, at positions 1,1´, is different.13 Thus, the diasteꢀ
reomer having the anti configuration is oxidized to form
stable radical cations and dications, whereas the oxidaꢀ
tion of the diastereomer having the syn configuration is
followed by the intramolecular cyclization with the inꢀ
volvement of the C(5) and C(5´) atoms of the pyridine
rings of the indolizine system having a favorable spatial
arrangement.
pounds, which can reversibly respond to external actions
(thermal, photochemical, electrochemical, pH, etc.) by
changing important properties and characteristics (the
cavity size, the surface shape, the electronic structure, the
complexing ability, etc.) due to the specially introduced
functional groups or fragments, has taken a special place
in supramolecular chemistry.1 Such "sensitive" heteroꢀ
cyclophanes containing redoxꢀactive biindolizine systems
can serve as molecular switches2 and membrane carriers3
and are of great interest in the design of new sensors for
modern technologies based on molecular processes. Unꢀ
like redoxꢀactive compounds (ferrocenes,4,5 tetrathiaꢀ
fulvalenes,6,7 and quaternized 4,4´ꢀbipyridines8,9), biꢀ
indolizines have found little use as active regions, which
make cyclophanes able to respond to external actions, in
spite of the fact that biindolizines are quite stable twoꢀ
step redox systems, whose electrochemical behavior has
been studied in sufficient detail.10—15
In turn, if not all hydrogen atoms in the fiveꢀmemꢀ
bered ring in indolizine molecules are replaced, the oxiꢀ
dation is accompanied by the coupling of the radical catꢀ
ions at the unsubstituted positions.11,14 For example, the
oxidation of 2,2´ꢀdiarylꢀ3,3´ꢀbiindolizines is accompaꢀ
nied by the coupling of the radical cations to form finally
Indolizines are πꢀrich compounds, which are readily
oxidized (~0.2—0.3 V relative to Fc0/+) to form radical
* Dedicated to Professor E. A. Berdnikov on the occasion of his
70th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1991—2003, October, 2007.
1066ꢀ5285/07/5610ꢀ2060 © 2007 Springer Science+Business Media, Inc.

Synthesis and structure of new heterocyclophane
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2061
a polymeric film deposited on the electrode surface.14
The properties of this film depend on the conditions of its
formation. Films, which are prepared at the controlled
potential of the first oxidation step or in the polycycling
mode in the potential range of –0.3 V → +0.8 V →
→ –1.3 V → –0.3 V (relative to Fc0/+), are redoxꢀactive
and can undergo reversible oxidation to form stable paraꢀ
magnetic states detected by the ESR method. The oxidaꢀ
tion under more drastic conditions affords insulating films.
The formation of polymeric films having different
properties is accompanied by oxidation of 2ꢀarylmonoꢀ
indolizines.14 For 2ꢀindolizinylquinoxalines, the nature
of oxidation products depends on the presence or the
absence of substituents at positions 1 and 3 of the fiveꢀ
membered ring of the indolizine system and at the nitroꢀ
gen atom of the quinoxaline ring.14 The behavior of
alkylꢀsubstituted 3ꢀ(indolizinꢀ2ꢀyl)quinoxalinꢀ2ꢀone is
analogous to that of 2ꢀarylindolizines. The oxidation of
3ꢀ(indolizinꢀ2ꢀyl)quinoxalinꢀ2ꢀones containing the free
carbamoyl group N—H affords insulating films regardꢀ
less of the reaction conditions. If the phenyl group is
introduced at position 1 of the indolizine fragment of
3ꢀ(indolizinꢀ2ꢀyl)quinoxalinꢀ2ꢀone, the oxidation does
not give polymeric films regardless of the nature of the
substituent at the nitrogen atom of the quinoxaline ring.14
Two studies were published on cyclophanes conꢀ
taining redoxꢀactive biindolizine fragments, in which
either the polymethylene or polyoxyethylene units15 or,
alternatively, the 1,4ꢀphenylenebis[di(oxyethylene)] or
1,5ꢀnaphthylenebis[di(oxyethylene)] fragments16 serve as
spacers (units that link two indolizine systems at the terꢀ
minal carbon atoms).
hydrogen atom of the N—H group should be replaced by
less mobile groups, 5) to increase the complexing ability
of heterocyclophane, the indolizine fragments should be
linked with the use of benzannelated aromatic heteroꢀ
cyclic systems.21
The designed synthesis of heterocyclophane containꢀ
ing the redoxꢀactive biindolizine systems is based on
monopodand 2b synthesized by the Williamson reaction22
from the corresponding 1,11ꢀdibromoꢀ3,6,9ꢀtrioxaꢀ
undecane and 3ꢀ(3ꢀphenylindolizinꢀ2ꢀyl)quinoxalinꢀ
2(1H )ꢀone (1a) (Scheme 1). Compound 1a was syntheꢀ
sized according to the modified Chichibabin method23
based on the condensation of 3ꢀacetylquinoxalinꢀ2(1H )ꢀ
one with 2ꢀbenzylpyridine in the presence of molecular
iodine20 involving the formation of the pyridinium salt by
the Ortoleva—King reaction24 as the first step.
Scheme 1
The complexing ability of these cyclophanes, particuꢀ
larly with respect to organic molecules, is not too high.15,16
However, according to the terminal group concept,17,18
the addition of heteroaromatic systems, which bear difꢀ
ferent types of atoms, at the ends of the oligo(ethylene
glycol) chain substantially facilitates the complex formaꢀ
tion. In addition, due to a combination of the πꢀsystems
of heteroaromatic rings with electronꢀrich indolizine fragꢀ
ments, the ability of such compounds to serve as active
hosts with respect to guests containing electronꢀdeficient
aromatic moieties is substantially higher.19
R = H (1a), Et (1b); n = 1 (2a), 3 (2b)
i. KOH/DMSO or dioxane.
The analysis of the data published in the literature15,16
and our results20 played the key role in the development
of our strategy for the synthesis of indolizinylquinoxaline
heterocyclophanes. Based on these data, the main reꢀ
quirements for the structure of podands, viz., acyclic preꢀ
cursors, were defined: 1) two indolizinylquinoxaline fragꢀ
ments should be linked by a spacer of a particular length,
2) to perform the oxidative intramolecular cyclization, at
least one of positions 1,3 in both indolizine systems should
be unsubstituted, 3) to avoid polymerization, only one
position of the fiveꢀmembered ring of indolizine should
be unsubstituted, 4) in the quinoxaline fragment, the
Several methods for the oxidative dimerization of
indolizines at unsubstituted position 3 were documented.
However, all these methods have drawbacks. For example,
the use of potassium hexacyanoferrate K3Fe(CN)6 leads
to the formation of byꢀproducts,11 the use of Fe3+ salts
not always gives rise to the desired product,25 and the use
of platinum (Pt/C, 10% Pt) or palladium (Pd/C, 10% Pd)
requires a long reaction time.26 We found that molecular
iodine can serve as an oxidation agent instead of the aboveꢀ
mentioned reagents. Model reactions of compounds 1a
and 1b in chloroform in the presence of molecular I2

2062
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
Mamedov et al.
produce analytically pure biindolizines 3a,b in 30 and
31% yields, respectively, which stimulated us to apply this
method to the oxidation of biindolizinylquinoxaline
monopodand 2b (Scheme 2).
unchanged under the conditions of electrochemical oxiꢀ
dation of compound 2b as well.
The presence of only two types of molecular ion peaks,
MH+ 831 and MH+ 1662, in the MALDI TOF mass
spectra, which were recorded for samples of the crude
products of the chemical and electrochemical oxidation
of compound 2b, is evidence for the formation of impuꢀ
rityꢀfree products 4 and 5, with the former compound
predominating regardless of the oxidation mode, whereas
the latter compound being formed as a byꢀproduct in
trace amounts. The electron impact mass spectrum of a
sample purified by column chromatography shows, along
with a 100% intensity molecular ion peak at m/z 830.2,
molecular ion peaks at m/z 831.2 (61.8%), 832.3 (19.65%),
and 833.2 (4.86%) containing isotopes.
Scheme 2
The structure of the major product, viz., cyclopentaꢀ
decaphane 4, was confirmed by IR, UV, and NMR specꢀ
troscopy and the Xꢀray diffraction study of a single crystal
grown from DMF.
R = H (a), Et (b)
Structural characteristics of
cyclopentadecaphane 4
The treatment of compound 2b with iodine in chloroꢀ
form led to the oxidative dehydrocondensation giving rise
to a mixture of intramolecular (4) and intermolecular
cyclization products (5) in a ratio of 10 : 1, with the former
predominating (two conformations, 4a and 4b, are conꢀ
sidered). The ratio between the products remains virtually
IR spectra. A comparison of the IR spectra of biꢀ
indolizine 3b (see the Experimental section) and macroꢀ
cyclic compound 4 (see Ref. 20) showed no substantial
differences, which could serve as a diagnostic indication
of the formation of cyclophane 4.
UV spectra. The UV spectra of compounds 2b, 4,
and 2a in CHCl3 in the 250—800 nm region show two
intense absorption bands with maxima at ~290 and 350 nm
and a third weak band as an inflection point near 430 nm
(Table 1). Based on the assignments27 for the spectrum of
quinoxaline, two main maxima in the spectra of comꢀ
pounds 2b and 2a can be assigned to πꢀπ* transitions; the
longꢀwavelength maximum, to nꢀπ* transitions. The
πꢀπ* bands of podands 2b and 2a have a vibrational strucꢀ
ture, which is most pronounced in the spectrum of 2a.
The spectra of products 4 prepared by different methods
(chemical and electrochemical) are completely identical.
It should be noted that certain changes are observed in
the spectra of 4 compared to those of podand 2b. Thus,
the band with a maximum at 359 nm is hypsochromically
shifted by 9 nm, the intensities of both πꢀπ* bands are
lower, and their vibrational structure becomes less proꢀ
nounced, which is, apparently, associated with a weakenꢀ
ing of the conjugation in the strained cyclic molecule.
The spectra of precursors 2b and 2a are virtually identical
to the spectrum of indolizinylquinoxalinone 1 regardless
of the spacer length.
NMR spectra. In the NMR spectra of indolizine deꢀ
rivatives, the positions of most signals strongly depend on
the nature of the substituents,11—13,15,16,26 which not alꢀ
ways allows the comparison of the chemical shifts and the
spinꢀspin coupling constants for their structure determiꢀ
Spacer =
, Z =

Synthesis and structure of new heterocyclophane
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2063
Table 1. UV spectra of compounds 1b, 2a, and 2b and heterocyclophane 4, which was synthesized by electrochemical
oxidation (A) and oxidation with iodine (B), in CHCl3
Compound
λmax/nm (logε)
π→π*
n→π*
1b
2a
2b
282 (4.22) sh, 294 (4.31)
281 (4.14), 290 (4.21)
282 (4.37) sh, 295 (4.46)
336 (4.24) sh, 353 (4.33) sh,
368 (4.36), 385 (4.20) sh
323 (4.26) sh, 339 (4.34) sh,
355 (4.43) sh, 370 (4.47), 387 (4.36) sh
337 (4.36) sh, 355 (4.46) sh,
368 (4.47), 385 (4.32) sh
359 (3.91)
359 (3.94)
316 (3.77)
346.5 (3.29)
430 (3.19) sh
432 (3.73) sh
430 (3.46) sh
4 (A)
4 (B)
Quinoxaline27
Indolizine28
298 (4.07)
298 (4.12)
280 (3.41)
294.5 (3.56)
427 (3.08) sh
427 (3.05) sh
339 (2.80)
nation. Hence, it is reasonable to present the assignment
The 1H NMR spectrum (DMFꢀd7) of compound 4 at
333 К consists of wellꢀresolved multiplets at low field
belonging to protons of the aromatic rings and a series of
complex multiplets at δ 4.1—3.3 assigned to the C(1)H2,
C(2)H2, and C(3)H2 methylene groups, in which the
geminal protons are nonequivalent (Fig. 1).
The 13C NMR spectrum of compound 4 at 333 К
shows 20 signals at low field (the relative intensities of two
signals correspond to two carbon atoms each) and four
signals at δ 71—41.
Based on the 2D COSY NMR spectrum (Fig. 2), the
spin systems belonging to the protons of the phenyl rings,
the orthoꢀphenylene fragments of the quinoxaline system,
and the pyridine fragments of the indolizine system, as
well as of three CH2—CH2 groups (as an AA´BB´ spin
system) were identified. Taking into account the
2D HSQC spectrum, the signals for the protonꢀcontainꢀ
ing carbon atoms of these fragments were determined.
The structures of these fragments were completely deꢀ
termined based on the 2D HMBC spectra (Fig. 3). In
the 2D HMBC spectrum, the crossꢀcorrelations beꢀ
tween the H(5) and H(7) atoms (δ 7.29 and 7.49) and
the C(8a) atom (δ 134.06) and between the H(6) and
H(8) atoms (δ 7.20 and 7.50) and the C(4a) atom
(δ 133.52) are observed for the benzo fragment of quinꢀ
oxaline, which allowed us to completely determine the
1
of the signals in the H and 13C NMR spectra of cycloꢀ
pentadecaphane 4 based on 2D NMR methods.29—31
A knowledge of the precise chemical shifts of the signals
and their multiplicities, particularly, for the signals of
the indolizine systems, can be useful for the analysis of
NMR spectra of more complex compounds prepared based
on compound 4.
In the 1H NMR spectrum of compound 4 at 323 К in
DMSOꢀd6, virtually all lines are broadened, particularly,
in the region characteristic of the signals for the protons
of the —OCH2 groups. Moreover, signals were not obꢀ
served in the 13C NMR spectrum at 323 K due to a strong
broadening and a low concentration of the sample. The
observed broadening is most likely associated with the
conformational exchange, whose rate appeared to be inꢀ
termediate on the NMR time scale, although the formaꢀ
tion of intermolecular complexes via πꢀπ interactions beꢀ
tween the aromatic rings of adjacent molecules 4 cannot
be completely excluded solely based on the aboveꢀconꢀ
sidered data.
To avoid complications in the spectra associated with
the conformational exchange, all NMR experiments were
carried out at high temperature, at which the exchange
processes are fast on the NMR time scale and the spectra
are simplified.
C(4)H2
H(8),
H(7)
H(2″),
H(6″)
H(8´),
H(5´)
H(3″), H(5″)
C(3)H2
C(2)H2
H(5)
H(6)
H(6´)
H(4″)
H(7´)
C(1)H2
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
δ
Fig. 1. 1H NMR spectrum of compound 4 in DMFꢀd7 at 333 К (the numbering of the nuclei is given in Fig. 4).

2064
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
Mamedov et al.
H(5)
H(8),
H(7)
C(4)H2
C(3)H2
C(2)H2
C(1)H2
H(6)
H(4″)
H(7´)
H(5´),
H(8´)
H(6´)
δ
C(3)H2/C(3)H2
C(2)H2/C(2)H2
C(4)H2
C(3)H2
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
C(2)H2
C(1)H2
C(1)H2/C(1)H2
H(5´)/H(6´)
H(6´)/H(7´)
H(6´)
H(7´)
H(8´)/H(7´)
H(4″)
H(6)
H(5)
H(6)/H(5)
H(7)/H(6)
H(8), H(7)
H(5´), H(8´)
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
δ
Fig. 2. 2D COSY spectrum of compound 4.
structure of the carbocyclic moiety of the quinoxaline
system (Fig. 4).
C(2)H2 carbon atom (δ 67.62) in the 2D HMBC specꢀ
trum are evidence for the presence of the bond between
the CH2—CH2 fragments of the 3ꢀoxapentane moiety
(see Fig. 4); the crossꢀpeaks between the C(1)H2 protons
(δ 4.01 and 3.82) and the C(8a) (δ 134.06) and C(2)
(δ 154.24) carbon atoms confirm the presence of the bond
between the 3ꢀoxapentane spacer and the quinoxaline
system (see Fig. 4).
The assignment of the signals at δ 147.98 and 125.11
in the 13C NMR spectrum to the C(3) and C(2´) carbon
atoms of the quinoxaline and indolizine systems, respecꢀ
tively, was made based on a comparison of their chemiꢀ
cal shifts with the 13C chemical shifts for compound 2b,20
in the spectrum of which the signals for C(3) and
C(2´) are observed at δ 150.21 and 120.84, respecꢀ
tively. This assignment of the chemical shifts to the
C(3) and C(2´) carbon atoms is in agreement with the
results of calculations of the chemical shifts (GIAO
B3LYP/6ꢀ31G(d)//RHF/6ꢀ31G 32—36) performed for the
simpler model compounds, viz., 2ꢀ(1ꢀmethylꢀ2ꢀoxoꢀ1Hꢀ
pyrazinꢀ3ꢀyl)indolizine (5) and 2,2´ꢀ(1ꢀmethylꢀ2ꢀoxoꢀ
(1H )ꢀpyrazinꢀ3ꢀyl)ꢀ3,3´ꢀbiindolizine (6), according to
In addition, the 2D HMBC spectrum (see Fig. 3)
shows the correlations between the H(5´) and H(7´) proꢀ
tons of the pyridine ring (δ 7.71 and 7.00) and the C(8a´)
atom of the indolizine system (δ 131.42), between the
H(5´) atom of the pyridine ring (δ 7.71) and the C(3´)
atom of the pyrrole ring (δ 115.26), and between the
H(8´) atom of the pyridine ring (δ 7.71) and the C(1´)
atom of the pyrrole ring (δ 115.44), which allowed us to
establish the structure of the indolizine system (see Fig. 4).
The crossꢀpeaks between the H(3″) and H(5″) protons
of the phenyl ring (δ 7.24) and the C(1″) atom (δ 136.01)
and between the H(2″) and H(6″) protons (δ 7.36) and the
C(1´) atom (δ 115.44) in the 2D HMBC spectrum unamꢀ
biguously confirm the presence of the phenyl ring (see
Fig. 3); besides, the presence of the latter crossꢀpeak is
indicative of the bond between the phenyl ring and the
C(1´) atom of the indolizine system.
The crossꢀpeaks between the C(2)H2 protons (δ 3.53
and 3.39) and the C(3)H2 carbon atom (δ 70.70) and
between the C(3)H2 protons (δ 3.48 and 3.42) and the

Synthesis and structure of new heterocyclophane
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2065
H(3″), H(5″)
H(4″)
H(2″), H(6″)
H(5)
H(5´), H(8´)
H(8)
H(6´)
H(7)
H(7´)
H(6)
δ
C(6´)
H(7´)/C(6´)
H(5´),H(8´)/C(6´)
C(8)
C(3´)
C(1´)
114
118
122
126
130
134
138
H(5´)/C(3´)
H(6)/C(8)
H(6´)/C(8´)
H(2″),H(6″)/C(1´)
H(5´),H(8´)/C(7´)
C(8´)
C(7´)
H(7´)/C(5´)
C(6)
H(8),H(7)/C(6)
H(6´)/C(5´)
C(5´)
C(4″)
H(2″),H(6″)/C(4″)
H(8),H(7)/C(5)
C(3″), C(5″)
C(2″), C(6″)
C(7)
H(5´),H(8´)/C(8a´)
C(5)
H(7´)/C(8a´)
C(8a´)
H(5)/C(7)
H(8)/C(4a)
H(7)/C(8a)
C(4a)
C(8a)
H(6)/C(4a)
H(3″),H(5″)/C(1″)
H(5)/C(8a)
C(1″)
7.8
7.6
7.4
7.2
7.0
6.8
6.6
δ
Fig. 3. Fragment of the 2D HMBC spectrum of compound 4.
bound to the latter fragment and the 3,6,9ꢀtrioxaundecane
spacer attached to the quinoxaline system.
Taking into account the MALDIꢀTOF mass spectroꢀ
metric data (for compound 4, MH+ = 831) and the NMR
Fig. 4. Main HMBC correlations for compound 4 (oneꢀhalf of
the molecule is shown).
Table 2. Calculated 1H and 13C chemical shifts for 2ꢀ(1ꢀmethylꢀ
2ꢀoxoꢀ1Hꢀpyrazinꢀ3ꢀyl)indolizine (5) and 2,2´ꢀ(1ꢀmethylꢀ2ꢀ
oxoꢀ1Hꢀpyrazinꢀ3ꢀyl)ꢀ3,3´ꢀbiindolizine (6)
which the chemical shifts of C(3) and C(2´) should be 145
and 121 ppm, respectively. Taking into account that the
13C chemical shifts are underestimated in calculations at
this level of theory,33,34,36 these chemical shifts are in
agreement with the experimental values.
Therefore, based on different homoꢀ (1H—1H) and
heterocorrelation (1H—13C) experiments and quantum
chemical calculations of the 13C chemical shifts, we esꢀ
tablished that the compound under study consists of the
quinoxaline and indolizine fragments with the phenyl ring
Atom
δ
5
6
H(5´)
C(3´)
C(2´)
C(3)
7.51
111.40
120.43
145.00
7.19
109.05
121.51
145.53

2066
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
Mamedov et al.
spectroscopic data, it can be concluded that compound 4
consists of two fragments, and each fragment contains,
along with other atoms, 26 carbon atoms and 21 hydrogen
atoms. Most likely, these fragments are linked by the
3ꢀoxapentane units through the oxygen bridge and through
the C(3´) atoms of the indolizine systems to form the
CH2—O—CH2— and C(3´)—C(3´) bonds.
Qx
Ind
Ind
Ind
O
O
Ph
Ph
Ph
O
1
Ph
This binding mode can be confirmed by the H and
13C chemical shifts. A comparison of the 1H chemical
shifts for product 2b and macrocycle 4 shows that the
signal for the H(5´) proton, which is most closely spaced
to the C(3´)—C(3´) bond of all protons, is observed at
0.61 ppm higher field in the case of the macrocyclic strucꢀ
ture compared to the open structure. This is attributed to
the shielding effect of the indolizine systems in the
macrocycle. For example, the estimation of δ 1H for
the model compounds 5 and 6 predicts the following
effect: the difference in the chemical shifts in going
from pyrazinylindolizine 5 to structure 6 containing the
C(3´)—C(3´) bond is 0.32 ppm. In addition, the experiꢀ
mentally observed difference between the 13C chemical
shifts for C(3´) in the spectra of 2b and 4 (1.77 ppm) is
completely theoretically reproduced both in the order of
magnitude and the sign (2.35 ppm).
O
Qx
Ind
Qx
4a
4b´
Fig. 5. Schematic representation of the structures of isomers of
compound 4 with the anti (4a) and syn orientations (4b´) with
respect to the C(3´)—C(3´) bond in the indolizine fragments.
oxaline and indolizine systems that are fixed after the ring
closure, eight isomers of heterocyclophane 4 can exist.
Since the twisting about the C(3´)—C(3´) bond is imposꢀ
sible due to the steric hindrance caused by the H(5´) and
H(5´) hydrogen atoms of the pyridine rings of the
indolizine system and the quinoxaline fragments, either
two anti* (4a,a´) or two syn orientations* (4b,b´) of the
indolizine fragments can exist, the quinoxaline systems
being arranged so that their carbamoyl groups are directed
in either the same or opposite directions.
The published data on the 1H chemical shifts for analoꢀ
gous compounds having an open or macrocyclic strucꢀ
ture,15,16 viz., biindolizine 7 and cyclophane 8, respecꢀ
tively, is an additional evidence for the C(3´)—C(3´) bond
formation. The presence of anisotropic groups in these
compounds (the pyridine rings of the indolizine systems)
To reveal the details of the isomeric structure (syn or
anti) of compound 4, we calculated the 1H and 13C chemiꢀ
cal shifts for diastereomers 4a and 4b.
1
and their influence on the H chemical shifts are indicaꢀ
tions of the close proximity of the indolizine fragments.
Thus, H(5´) in the ring of compound 8 is also more
shielded (by 0.42 ppm) compared to the analogous proton
in open structure 7.16
Unfortunately, the large size of the macrocycle hinꢀ
ders the use of ab initio methods for the geometry optimiꢀ
zation of possible structural isomers of 4. Hence, we
perfromed the geometry optimization by the MM method,
and this geometry was then used to estimate the chemical
shifts. This approach can be diagnostically valuable.37,38
According to the MM calculations (with the force conꢀ
stants calculated by the MM2 method), the structure with
the syn orientation (4b´) is energetically much more faꢀ
vorable than the structure with the anti orientation.
The main argument in favor of this conclusion is based
on a comparison of the calculated chemical shifts for two
isomers (GIAO B3LYP/6ꢀ31G(d)//MM2) with the exꢀ
perimental data. It can be noted that the chemical shifts
should be substantially different for a number of nuclei
(for example, for H(5), H(5´), H(6´), C(2), C(3), C(1´),
C(2´), C(3´), and C(5´)) in going from one isomer to
another. This can be employed for the spectraꢀstructure
correlations. Taking into account that the chemical shifts
Therefore, based on the results of 2D NMR spectroꢀ
scopy, mass spectrometric data, and the data published in
the literature for model compounds, we established the
structure of macrocyclic compound 4.
Due to three axes of chirality, which coincide with the
newly formed C(3´)—C(3´) bond between two indolizine
systems and two C(3)—C(2´) bonds between the quinꢀ
* For the syn orientation, the dihedral angles between the pyriꢀ
dine rings of the indolizine systems are smaller than 90°; for the
anti orientation, larger than 90°.

Synthesis and structure of new heterocyclophane
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2067
O(64)
C(65)
are underestimated at the B3LYP/6ꢀ31G(d)//MM2 level
of theory, the experimental H chemical shifts correlate
C(63)
1
a
O(62)
O(66)
C(64)
well with the calculated values for the structure with the
syn orientation (R2 = 0.99), whereas the correlation for
the structure with the anti orientation is substantially lower
(R2 = 0.84). Analogously, the 13C chemical shifts are in
good agreement with the experimental data for the
syn isomer (R2 = 0.93) and show much poorer agreement
for the anti isomer (R2 = 0.87).
Hence, the aboveꢀconsidered analysis allowed the conꢀ
clusion that, in solution, compound 4 exists in the
syn configuration (4b´).
C(66)
O(42)
C(62)
C(48)
C(68)
N(11)
C(18)
C(52)
C(61)
C(67)
C(17)
N(41)
C(42)
C(43)
C(56)
O(12)
C(47)
C(58)
C(16)
C(12)
C(13)
C(60)
C(15)
C(46)
C(45)
C(54)
C(22) C(32)
N(14)
C(21)
N(34)
C(31)
To elucidate which configuration, syn or anti, is favorꢀ
able in the crystal, we carried out the Xꢀray diffraction
study of a single crystal of compound 4 grown by recrysꢀ
tallization from DMF.
C(25)
C(26)
C(35)
C(36)
C(38)
C(27)
C(37)
Xꢀray diffraction study. The singleꢀcrystal Xꢀray difꢀ
fraction study of cyclopentadecaphane 4 showed that comꢀ
pound 4 crystallizes with DMF molecules in a ratio of
1 : 2. One DMF molecule is disordered over two positions
with relative occupancies of 0.59 and 0.41. In the crystal
structure, molecules cyclopentadecaphane 4 occupy genꢀ
eral positions. The molecular geometry is shown in Fig. 6.
The quinoxaline and indolizine fragments are planar
within 0.04(2) and 0.05(2) Å, respectively. The dihedral
angle between the planes of two indolizine fragments
linked to each other is 74.5°. The planes of the phenyl
rings are twisted with respect to the planes of the indolizine
fragments bound to these rings by approximately the same
angle (the C(42)—C(43)—C(32)—C(31) torsion angle is
–58.7(4)° and the C(56)—C(55)—C(31)—C(32) torsion
angle is –43.3(5)°), whereas the quinoxaline rings are
twisted with respect to these planes by substantially differꢀ
ent angles (C(12)—C(13)—C(22)—C(21), –95.1(4)°;
C(54)—C(49)—C(21)—C(22), –51.2(4)°). Two quinꢀ
oxaline rings are virtually parallel to each other (the diꢀ
hedral angle between their planes is 17.7°). The trioxaꢀ
undecane chain adopts an extended conformation, and
one of the phenyl substituents closes the pseudocavity
formed by the spacer from one of the sides, thus restrictꢀ
ing the complexing ability of this fragment (see Fig. 6, b).
Intermolecular interactions between the electronic sysꢀ
tems of the aromatic fragments make the greatest contriꢀ
bution to the supramolecular organization of the crystal
structure of compound 4, only the quinoxaline fragments
being involved in πꢀπ interactions. We analyzed this type
of interactions with the use of the Mercury and Platon
programs, in which the following criteria of πꢀπ interacꢀ
tions are included: the distances between the centers of
aromatic rings shorter than 6 Å and the angle β between
the normal to the plane of one ring and the vector linking
the centers of the rings smaller than 60°. These paramꢀ
eters are consistent, for example, with those reported in
the review.39 In addition, the review39 shows that interacꢀ
tions that exist in the case of the mutually perpendicular
C(17)
C(18)
C(18A)
C(16)
C(15)
C(14A)
N(14)
C(13)
b
C(66)
C(65)
O(66)
C(68)
O(64)
C(64)
C(59)
C(67)
C(60)
C(38A)
C(58)
C(31)
C(63)
O(62)
O(12)
C(57)
C(56)
C(53)
O(42)
C(54)
C(22)
C(42)
C(23)
C(43)
C(62)
C(61)
N(41)
N(24)
C(51)
N(44)
C(50)
C(48A)
C(25)
C(26)
C(44A)
C(28)
C(27)
C(48)
C(47)
C(45)
C(46)
Fig. 6. Two projections of compound 4 in the crystal. The hydroꢀ
gen atoms and the DMF molecules are omitted.
arrangement of the aromatic systems (the distances beꢀ
tween the centers of the rings are, on the average, 4.96 Å)
are the most often occurring and energetically favorable
πꢀπ interactions, the interactions between parallel sysꢀ
tems shifted with respect to each other (the interplanar
distances are 3.4—3.6 Å) are the next after the above
interactions, and only a few structures containing comꢀ
pletely overlapping aromatic systems were documented
(this type of interactions is energetically least favorable).
In the crystal of 4 under consideration, each quinoxaline
fragment of the molecule is involved in headꢀtoꢀtail inꢀ
teractions with the corresponding fragments of the adjaꢀ
cent molecules related to the original molecule by centers
of symmetry and the translation 1 along the 0х axis. As a
consequence, the dihedral angles between the aromatic
systems are 0°, and the shortest distances between the
planes of the quinoxaline rings of the adjacent molecules

2068
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
Mamedov et al.
the cavities between the cylindrical structures. In spite of
the presence of the solvent molecules, a high packing
density is not achieved in the crystals of compound 4.
Thus, the packing coefficient calculated with the use of
the PLATON program is 0.66. Apparently, it is possible to
prepare crystal solvates of compound 4 containing larger
molecules.
Therefore, the singleꢀcrystal Xꢀray diffraction study of
cyclopentadecaphane 4 showed that the indolizine fragꢀ
ments in the crystal structure are in the nearly anti orienꢀ
tation with respect to the C(3´)—C(3´) bond, as opposed
to the syn orientation observed in solution. It should be
noted that this mutual arrangement of the indolizine fragꢀ
ments observed in the crystal is unfavorable for their inꢀ
volvement in intramolecular πꢀπ interactions.
Fig. 7. The πꢀπ interactions in the crystal structure of comꢀ
pound 4 (the hydrogen atoms and the DMF molecules are
omitted).
Electrochemical properties of heterocyclophane 4 and
compounds 2a, 2b, and 3b. The cyclic voltammograms of
compounds 2a and 2b are completely identical to the
corresponding curves for indolizinylquinoxaline 1b studꢀ
ied earlier14 under analogous conditions. For all these
compounds, four irreversible oxidation peaks were reꢀ
corded at virtually the same potentials on a glassy carbon
electron in an acetonitrile/0.1 M Et4NClO4 system (Fig. 9,
Table 3). The height of the first peak is larger than the
oneꢀelectron level. The irreversibility of the first peak is
are 3.54 Å for the planes of the ((N(11)—C(18a)) rings
and 3.36 Å for the planes of the (N(41)—C(48a)) rings.
In both cases, the angles β are smaller than 60°. As a
result, infinite cylindrical supramolecular structures are
formed (Fig. 7).
The C—H...O interactions between the hydrogen
atoms of the phenyl substituents and the oxygen atoms of
the carboxy groups (the O...…H distances are in the range
of 2.44—2.55 Å) contribute to this situation.
Since compound 4 and its derivatives hold promise as
selective extractants, we analyzed the crystal packing of
the crystal solvate of 4. On the whole, the cylindrical
supramolecular structures are packed to form a hexagonal
structure (Fig. 8), the solvent molecules being located in
I
2.5 µA
a
5.0 µA
b
5.0 µA
c
0.5
1.0 ϕ/V (rel. to Fc0/+
)
Fig. 9. Cyclic voltammograms of indolizinylquinoxalines 4 (a),
Fig. 8. Fragment of the molecular packing in the crystal of
compound 4. The hydrogen atoms and the solvent molecules are
omitted. The projection along the 0c axis.
2a (b), and 2b (c) (C2a,2b = 5•10–4 mol L–1, C4 = 1•10–4 mol L–1
)
in MeCN/0.1 M Et4NClO4 on a glassy carbon electrode
(υ = 100 mV s–1).

Synthesis and structure of new heterocyclophane
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2069
Table 3. Cyclic voltammetry data for the oxidation of indolꢀ
izines 1b, 2a, 2b, 3b, and 4 on a glassy carbon electrode in
MeCN/0.1 M Et4NClO4*
oxidation of indolizines 2a and 2b. Based on this fact, we
performed the preparative electrooxidation of comꢀ
pound 2b on a platinum electrode in MeCN and obtained
macrocyclic compound 4.
Comꢀ
pound
E1
/V
n1**
E2
E3
E4
p,ox
p,ox
p,ox
p,ox
Heterocyclophane 4 is much less soluble in MeCN
than open precursor 2b, and its limiting concentration at
room temperature is 1•10–4 mol L–1. Three oxidation
peaks are observed in the cyclic voltammograms of comꢀ
pound 4 (see Fig. 9). The shape and characteristics of the
first peak differ from those for compound 2b. First, the
first oxidation peak of 4 is shifted by 40 mV to less positive
potentials with respect to the first oxidation peak of 2b,
which indicates that the macrocyclic compound is more
easily oxidized. This is clear because the oxidation of
biindolizines proceeds more easily than that of monoꢀ
indolizines.14 Second, this peak is reversible, and its height
corresponds to the oneꢀelectron transfer per molecule,
which is evidence for the stability of the radical cation. An
analogous situation is observed in DMF (see Table 3), in
which compound 4 is much more readily soluble (C =
5•10–4 mol L–1) and, correspondingly, the oxidation
peaks are more pronounced (Fig. 10). The electroꢀ
oxidation directly in a resonator of an ESR spectrometer
at potentials of the first peak gives rise to the spectrum of
the radical cation of compound 4 (Fig. 11). The same
spectrum was recorded at room temperature and at lower
temperature (–50 °C). Evidently, this spectrum belongs
to the primary radical cation. The identical spectrum was
V
1b
2a
2b
3b
4
0.30
0.32
0.30
0.29
0.26
0.21
1.3
1.7
1.7
1.0
1.0
1.0
0.58
0.60
0.60
0.49
0.46
0.38
0.76
0.78
0.77
0.98
0.97
0.85
0.96
1.05
1.01
1.31
—
4***
—
* The potentials were measured relative to the standard potenꢀ
tial of the Fc0/+ redox system (the internal standard) with the
use of the Ag/0.01 M AgNO3 reference electrode in MeCN; the
potential scan rate was 100 mV s–1; C1b,2a,2b = 5•10–4 mol L–1
,
C3b = 7•10–4 mol L–1, C4 = 1•10–4 mol L–1
.
** The number of electrons was determined by comparing with
the oneꢀelectron oxidation peak of ferrocene.
*** C4 = 5•10–4 mol L–1 in DMF/0.1 M Et4NClO4.
indicative of the involvement of the radical cations of
indolizinylquinoxalines 1b and 2a,b in subsequent fast
chemical reactions. The potential of the first peak correꢀ
sponds to the oxidation potential of indolizines, and the
resulting radical cation is, apparently, involved in couꢀ
pling reactions, which is typical of radical cations of simple
indolizines.11,14 For compound 1b, the intermolecular
coupling giving rise to dimers is the major process. For
compounds 2a and 2b, both the intramolecular coupling
of two indolizine fragments giving rise to macrocyclic
products and the intermolecular coupling resulting in the
formation of large rings and/or polymers can proceed.
Since biindolizines are more easily oxidized than monoꢀ
indolizines,14 all resulting coupling products are further
oxidized at potentials of the first peak, resulting in an
increase in the current relative to the oneꢀelectron
level (n > 1). The formation of polymeric products is
easily observed by recording polycyclic voltammograms.14
The oxidation of compounds 1b and 2a,b, unlike that of
monoꢀ and biindolizines studied earlier,14 at potentials of
the first peak in the multiple scan mode at a rate of
100 mV s–1 in the potential range of –0.3 → +0.4 →
→ –1.2 → –0.3 does not afford a polymeric film on the
electrode surface, and the cyclic voltammograms remain
virtually unchanged and are wellꢀreproduced. This may
be evidence that the electrolysis of compounds 2a and 2b
at the generation potentials of radical cations under the
particular reaction conditions used is accompanied priꢀ
marily by the formation of lowꢀmolecularꢀweight macroꢀ
cyclic products (monomers, dimers, etc.), which are
soluble in MeCN to a certain extent. These results proꢀ
vide the first voltammetric argument for the possibility of
the preparation of macrocyclic products by the electroꢀ
I
5 µA
0
0.5 ϕ/V (rel. to Fc0/+
)
Fig. 10. Cyclic voltammograms of heterocyclophane 4 (C =
5•10–4 mol L–1) in DMF/0.1 M Et4NClO4 on a glassy carbon
electrode (υ = 100 mV s–1).
0.3 mT
H
Fig. 11. ESR spectrum of the radical cation of heterocyclophane
4 electrochemically generated at the potential Е = +0.4 V in
MeCN/0.1 M Et4NClO4 on a Pt electrode (C = 1•10–4 mol L–1).

2070
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
Mamedov et al.
recorded upon the chemical oxidation of macrocyclic
compound 4 with iodine in CH2Cl2. The spectrum conꢀ
sists of five lines with an approximate intensity ratio beꢀ
tween the lines of 1 : 2 : 3 : 2 : 1, which are associated
with hyperfine couplings with the nuclei of two equivalent
nitrogen atoms of the conjugated indolizine rings, and
has the following characteristics: the g factor is 2.0024,
a2N = 0.26 mT.
Based on the aboveꢀconsidered results, the following
scheme can be proposed for the description of the proꢀ
cesses proceeding at potentials of the first oxidation peak
of compound 2b and giving rise to macrocyclic product 4
(Scheme 3). The first step involves the oneꢀelectron oxiꢀ
dation of each indolizine fragment of molecule 2b to
form the biradical dication followed by the intramolecuꢀ
lar coupling and elimination of two protons to give comꢀ
pound 4.
peak is irreversible) and the appearance of additional oxiꢀ
dation peaks is attributed to the syn diastereomer. Unlike
macrocyclic biindolizines described in the literature,13
the bridge between two indolizine fragments in heteroꢀ
cyclophane 4 contains additionally two quinoxaline fragꢀ
ments. An increase in the length of the bridge leads to an
increase in configurational flexibility, which can impart
new properties, including electrochemical characteristics,
to macrocyclic compounds. Hence, we studied also the
electrochemical oxidation of model compound 3b. The
solubility of this compound in MeCN is substantially
higher than that of macrocyclic product 4; correspondꢀ
ingly, the cyclic voltammograms of the model compound
are of better quality, and the anodic potential range is
broader.
The cyclic voltammograms of compound 3b show two
reduction peaks of the quinoxaline fragments (at –2.08
and –2.32 V) and four oneꢀelectron oxidation peaks of
the biindolizine system (Fig. 12). The first and third oxiꢀ
dation peaks are electrochemically reversible, whereas the
second and fourth peaks are irreversible. The potentials of
the first three peaks are consistent with the potentials of
compound 4. The electrolysis at the potentials of the first
oxidation peak is accompanied by the formation of stable
Scheme 3
radical cations, whose ESR spectrum (g = 2.0024, a2N
=
0.26 mT) is identical to the spectrum of the radical cation
of compound 4. The absence of the fourth oxidation peak
in the cyclic voltammogram of macrocyclic compound 4
is apparently associated with the fact that this peak is
shielded by the discharge current of the supporting elecꢀ
trolyte due to a low concentration of compound 4.
A complete analogy between the cyclic voltammograms
and the ESR spectra at the potentials of the first step for
compounds 3b and 4 indicates that the structures of the
indolizine fragments of both compounds are identical.
Since compound 4 is more easily oxidized than the
starting compound 2b (40 mV), the former compound is
rapidly oxidized to the radical cation. However, the reꢀ
duction peak (Еpred = +0.20 V) of the stable radical cation
of heterocyclophane 4 is not observed in the cyclic
voltammogram of compound 2b (see Fig. 9), which can
be attributed to the homogeneous intermolecular elecꢀ
tron exchange between the radical cation of compound 4
and the starting compound 2b. In other words, macroꢀ
cyclic compound 4 produced in the reaction serves as a
mediator of the electrochemical oxidation of biindolꢀ
izine 2b. The mediator properties combined with low soluꢀ
bility of macrocyclic product 4 result in the fact that the
preparative oxidation of compound 2b is not accompaꢀ
nied by accumulation of the radical cations of 4 in soluꢀ
tion and their electrolysis culminates in the twoꢀelectron
oxidation.
I
5 µA
As mentioned above, the syn and anti diastereomers of
macrocyclic biindolizines differ in the electrochemical
properties.13 The electrochemical behavior of compound 4
corresponds to none of the examples described in the
literature.13 The stability of the radical cations and the
absence of any other paramagnetic species in the course
of the prolonged electrolysis correspond to the anti diaꢀ
stereomer, whereas instability of the dication (the second
–2
–1
0
ϕ/V (rel. to Fc0/+
)
Fig. 12. Cyclic voltammograms of biindolizine 3b (C =
7•10–4 mol L–1) in MeCN/0.1 M Et4NClO4 on a glassy carbon
electrode (υ = 100 mV s–1). The scan begins at –0.45 V.

Synthesis and structure of new heterocyclophane
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2071
data were deposited with the Cambridge Structural Database
(CCDC 609481).
To conclude, we showed that, under the conditions of
electrochemical oxidation or in the presence of molecular
iodine, the oxidative dehydrocyclization of podand 2b
proceeds in an intraꢀ and intermolecular fashion to form
a mixture of heterocyclophanes, with the intramolecular
cyclization product predominating, whereas the intermoꢀ
lecular cyclization product being formed as a byꢀproduct.
The latter was detected only by mass spectrometry. We
showed that cyclopentadecaphane 4 is a reversible redoxꢀ
active system, and its oneꢀelectron oxidation affords the
stable radical cation. The Xꢀray diffraction study of
cyclopentadecaphane 4 demonstrated that in the crystal,
the trioxaundecane chain of heterocyclophane adopts an
extended conformation, and one of the phenyl substituꢀ
ents closes the pseudocavity formed by the spacer from
one of the sides. This is promising for the synthesis of
specific host molecules consisting of the redoxꢀswitchꢀ
able biindolizine fragment combined with the πꢀdeficient
quinoxaline systems linked by a longer polyether bridge.
The cyclic voltammograms were recorded on a PIꢀ50ꢀ1
potentiostat equipped with an H 307/2 XꢀY recorder. A glassyꢀ
carbon disk electrode (∂ = 2 mm) pressed into Teflon served as
the working electrode. Before each measurement, the electrode
was subjected to mechanical polishing. The potential scan rate
υ = 100 mV s–1. The potentials were measured relative to the
standard potential of the ferrocene—ferricinium ion redox sysꢀ
tem (Fc0/+, internal standard) using an Ag/0.01 M AgNO3 silver
reference electrode (0.01 mol L–1) in MeCN. The potentials for
compound 1b are 70 mV more positive that those determined by
the external standard method.14 Dissolved oxygen was removed
by bubbling nitrogen through the solution at 295 K.
Studies by the ESR method (Radiopan SE/Xꢀ2544 specꢀ
trometer) combined with the in situ electrolysis (PIꢀ50ꢀ1
potentiostat) were carried out on an instrument consisting of an
ESR resonator and an electrochemical cell. A platinum plate
served as the working electrode; a platinum wire, as the auxiliary
electrode; a silver wire, as the reference electrode. The solutions
were degassed by three freezing—evacuation—thawing cycles.
The temperatures were 295 and 223 К.
2,2´ꢀDi(2ꢀoxoꢀ1Hꢀquinoxalinꢀ3ꢀyl)ꢀ1,1´ꢀdiphenylꢀ3,3´ꢀbiꢀ
indolizine (3a). A solution of I2 (100 mg, 0.4 mmol) in chloroꢀ
form (3 mL) was added to a solution of compound 1a (100 mg,
0.3 mmol) in chloroform (2 mL). The reaction mixture was
stirred for 3 h and kept for 16 days. The black crystals that
precipitated were filtered off, dried, and washed with a sodium
carbonate solution and water. The residue was dried, refluxed in
EtOH (10 mL) for 5 min, and cooled. The yellow crystals that
formed were filtered off and washed with EtOH. The yield was
30 mg (30%), m.p. > 360 °C. IR, ν/cm–1: 430, 473, 547, 602,
700, 729, 762, 961, 1029, 1098, 1152, 1211, 1236, 1247, 1272,
1344, 1418, 1520, 1563, 1611, 1670, 2500—3220. 1H NMR, δ:
6.77 (ddd, 2 H, H(6´), J = 6.96 Hz, J = 6.64 Hz, J = 1.36 Hz);
6.90 (dd, 2 H, H(8), J = 8.28 Hz, J = 1.32 Hz); 6.94—7.02 (m,
4 H, H(7´), H(6)); 7.12 (dd, 2 H, H (pꢀPh), J = 7.96 Hz, J =
7.32 Hz); 7.15 (d, 2 H, H(5), J = 8.28 Hz); 7.25 (dd, 4 H,
H (mꢀPh), J = 7.96 Hz, J = 7.28 Hz); 7.31—7.38 (m, 2 H,
H(7)); 7.39 (dd, 4 H, H (oꢀPh), J = ~8.3 Hz, J = 1.3 Hz); 7.59
(d, 2 H, H(8´), J = 6.96 Hz); 7.71 (d, 2 H, H(5´), J = 9.28 Hz);
11.78 (br.s, 2 H, NH). Found (%): C, 78.49; H, 4.07; N, 12.63.
C44H28N6O2. Calculated (%): C, 78.56; H, 4.20; N, 12.49.
2,2´ꢀDi(1ꢀethylꢀ2ꢀoxoꢀ1Hꢀquinoxalinꢀ3ꢀyl)ꢀ1,1´ꢀdiphenylꢀ
3,3´ꢀbiindolizine (3b). A solution of I2 (22 mg, 0.09 mmol) in
chloroform (10 mL) was added to a solution of compound 1b
(36 mg, 0.1 mmol) in chloroform (5 mL). The reaction mixture
was stirred for 6 h and kept for 16 days. Chloroform was reꢀ
moved under reduced pressure, and the darkꢀbrown resinous
residue was washed with a sodium thiosulfate solution, a sodium
carbonate solution, and water, dried, and chromatographed on
a silica gel column (Silica gel L 100/160µ, CHCl3 as the eluent).
The yield was 11 mg (31%), m.p. 303—305 °C. IR, ν/cm–1: 700,
741, 1099, 1159, 1218, 1283, 1347, 1461, 1526, 1583, 1602,
1653, 2854, 2924, 2955. 1H NMR, δ: 1.06 (t, 6 H, Me, J =
7.20 Hz); 3.70—3.80 (m, 2 H, CH2); 3.95—4.05 (m, 2 H, CH2);
6.67 (ddd, 2 H, H(6´), J = 7.56 Hz, J = 6.15 Hz, J = 1.26 Hz);
6.86 (ddd, 2 H, H(7´), J = 8.25 Hz, J = 6.54 Hz, J = 1.08 Hz);
6.91 (dd, 2 H, H(6), J = 7.56 Hz, J = 7.32 Hz); 6.96 (d, 2 H,
H(8), J = 8.10 Hz); 7.08 (d, 2 H, H(5), J = 8.40 Hz); 7.12 (dd,
2 H, H(pꢀPh), J = 7.56 Hz, J = 7.32 Hz); 7.22 (dd, 4 H,
Experimental
The melting points were determined on a Boetius hotꢀstage
apparatus. The IR spectra were measured on a Bruker Vectorꢀ22
Fourierꢀtransform spectrometer in KBr pellets. The 1H and
13C NMR spectra were recorded on Bruker AVANCEꢀ600 inꢀ
strument (600.00 MHz for 1H and 150.864 MHz for 13C) for
compound 4 in DMFꢀd7 and on a Bruker MSLꢀ400 instrument
(400.13 MHz) for compounds 3 in DMSOꢀd6 at 333 K. The
residual signal of DMSO (δ 2.54) was used as the internal
H
standard. The electron impact mass spectra (70 eV) were reꢀ
corded on a Finnigan MATꢀ212 instrument. The MALDIꢀTOF
mass spectra were obtained on a Finnigan Dynamo instrument
with the use of 1,8,9ꢀtrihydroxyanthracene as the matrix.
The compounds were named according to the IUPAC phane
nomenclature.40,41
The singleꢀcrystal Xꢀray diffraction study of 4•DMF was
performed on a NONIUS B.V. CADꢀ4 Xꢀray diffractometer.
The crystals, C52H42N6O5•2(C3H7NO), are monoclinic; at
20 °C a = 13.028(5) Å, b = 24.559(5) Å, c = 16.374(4) Å,
β = 103.28(2)°, V = 5099(3) Å3, dcalc = 1.27 g cm–3, Z = 4, space
group P21/n. The unit cell parameters and the intensities of
10601 reflections, of which 5414 reflections were with I > 2σ,
were measured at 20 °C (graphite monochromator, λCuꢀКα,
ω/2θꢀscanning technique, θ < 74.27°). The intensities of three
check reflections showed no decrease in the course of the Xꢀray
data collection. The absorption correction was applied using the
azimuthal scan method (µCu 6.87 cm–1). The structure was
solved by direct methods with the use of the SIR program42 and
refined first isotropically and then anisotropically using the
SHELXL program package.43 The coordinates of the hydrogen
atoms were calculated based on the stereochemical criteria and
refined using a riding model. The final R factors were R = 0.0730,
Rw = 0.1921 based on 5414 independent reflections with F 2 > 4σ.
All calculations were carried out with the use of the MolEN44
and WinGX45 programs. The intermolecular interactions
were analyzed and the figures were drawn with the use of the
Mercury46 and PLATON47 programs. The Xꢀray diffraction

2072
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
Mamedov et al.
H (mꢀPh), J = 7.86 Hz, J = 7.56 Hz); 7.30 (ddd, 2 H, H(7), J =
8.49 Hz, J = 7.02 Hz, J = 1.44 Hz); 7.40 (dd, 4 H, H (oꢀPh), J =
7.56 Hz, J = 1.02 Hz); 7.63—7.73 (m, 4 H, H(5´), H(8´)).
EI MS, m/z (%): 675.4 (4.0), 674.3 (14.0), 673.3 (55.4), 672.3
(100), 671.3 (2.7), 540.3 (1.5), 539.3 (3.35), 538.3 (1.30), 527.3
(1.32), 449.2 (0.4), 337.2 (4.6), 336.7 (7.8), 336.2 (16.8), 335.2
(3.3). Found (%): C, 79.01; H, 4.87; N, 11.63. C48H36N6O2.
Calculated (%): C, 79.10; H, 4.98; N, 11.53.
with water. Compound 4 was isolated and purified on silica gel
as described above. The preparative yield was 40 mg (40%). All
spectroscopic characteristics of compound 4 synthesized elecꢀ
trochemically were completely identical to those of compound 4
prepared by the chemical method.
This study was financially supported by the Russian
Foundation for Basic Research (Project Nos 03ꢀ03ꢀ32865,
04ꢀ03ꢀ32828, 05ꢀ03ꢀ32558, and 05ꢀ03ꢀ33008).
12,42ꢀDioxoꢀ21,31ꢀdiphenylꢀ7,10,13ꢀtrioxaꢀ1,4(3,1)ꢀdiquinꢀ
oxalinaꢀ2(2,3),3(3,2)ꢀdiindolizinacyclopentadecaphane (4). A soꢀ
lution of I2 (300 mg, 1.18 mmol) in chloroform (100 mL) was
added to a solution of compound 2b (360 mg, 0.42 mmol) in
chloroform (200 mL). The reaction mixture was stirred for 3 h,
kept for 2 days, and washed with a sodium carbonate solution, a
sodium thiosulfate solution, and water. Chloroform was removed
under reduced pressure, and the brown resinous residue was
chromatographed on a silica gel column (Silica gel L 100/160µ,
CHCl3 : EtOH, 99 : 1, as the eluent). The yield was 250 mg
(69%), m.p. >330 °C. IR, ν/cm–1: 704, 729, 762, 1103, 1128,
1159, 1251, 1281, 1346, 1366, 1454, 1486, 1524, 1583, 1601,
1649, 2857, 2922. 1H NMR, δ: 3.37—3.45 (m, 8 H, C(4)H2,
1 H C(2)H2, 1 H C(3)H2); 3.48—3.52 (m, 2 H, C(3)H2);
3.52—3.57 (m, 2 H, C(2)H2); 3.99—4.05, 3.80—3.86 (m, 4 H,
C(1)H2); 6.83 (dd, 2 H, H(6´), J = 6.89 Hz, J = 6.67 Hz); 7.02
(dd, 2 H, H(7´), J = 9.42 Hz, J = 6.58 Hz); 7.14 (dd, 2 H,
H (рꢀPh), J = 7.38 Hz, J = 7.00 Hz); 7.20 (ddd, 2 H, H(6), J =
8.00 Hz, J = 5.73 Hz, J = 2.27 Hz); 7.25 (dd, 4 H, (mꢀPh), J =
7.80 Hz, J = 7.58 Hz); 7.30 (d, 2 H, H(5), J = 7.90 Hz); 7.37 (d,
4 H, H (oꢀPh), J = 7.56 Hz); 7.48—7.52 (m, 4 H, H(7), H(8));
7.72 (d, 4 H, H(8´), H(5´), J = 8.67 Hz). 13C NMR, δ: 154.24
(C(2)); 147.98 (C(3)); 133.52 (C(4a)); 129.99 (C(5)); 123.30
(C(6)); 130.52 (C(7)); 114.69 (C(8)); 134.06 (C(8a)); 115.44
(C(1´)); 121.32 (C(2´)); 115.26 (C(3´)); 125.13 (C(5´)); 112.43
(C(6´)); 120.15 (C(7´)); 118.46 (C(8´)); 131.42 (C(8a´)); 136.01
(C(1″)); 129.89 (C(2″)); 128.70 (C(3″)); 126.10 (C(4″)); 42.28
(CH2(1)); 67.62 (CH2(2)); 70.70 (CH2(3)); 70.53 (CH2(4)).
MS of the crude product (MALDI TOF): [MH]+ 831, [MH]+
1662. EI MS, m/z (Irel (%)): 833.2 (4.9), 832.3 (19.7), 831.2
(61.1), 830.2 (100), 415.8 (4.6), 415.3 (13.3), 349.7 (3.4), 349.2
(3.1), 97.3 (5.3), 85.3 (4.1), 83.3 (5.7), 81.3 (6.0). Found (%):
C, 75.25; H, 5.07; N, 10.03. C52H42N6O5. Calculated (%):
C, 75.16; H, 5.09; N, 10.11.
The electrosynthesis of cyclopentadecaphane 4 was perꢀ
formed by the preparative electrochemical oxidation of comꢀ
pound 2b using a PIꢀ50ꢀ1 potentiostat in a diaphragm (celluꢀ
lose) glass electrolytic cell on a platinum cylindrical electrode
(S = 50.8 cm2) in a galvanostatic mode at a controlled potential
of the first oxidation peak (Е < +0.5 V relative to Ag/0.01 mol L–1
AgNO3 in MeCN) in a MeCN/0.1 mol L–1 Et4NClO4 system at
room temperature (22 °C). A platinum wire was used as the
cathode. The working solution (50 mL) was prepared by dissolvꢀ
ing compound 2b (100 mg, 0.12 mmol) in a MeCN/0.1 mol L–1
Et4NClO4 system. The solution was magnetically stirred. The
electrolysis was carried out for 3.88 h (I = 2 mA, τ = 3.22 h; I =
1.5 mA, τ = 0.12 h, I = 1.2 mA, τ = 0.12 h, I = 1.0 mA, τ =
0.42 h). The mass spectrometric study of the reaction mixture
after the electrolysis showed the absence of the starting comꢀ
pound 2b in the solution and the presence of two macrocyclic
products, viz., compound 4 (m/z = 830) and a dimeric macroꢀ
cyclic compound (m/z = 1660). The solvent was evaporated, the
supporting electrolyte was removed, and the residue was washed
References
1. J.ꢀM. Lehn, Supramolecular Chemistry, Concepts and Perꢀ
spectives, VCH, Weinheim, 1995, 271 pp.
2. P. D. Beer, Chem. Soc. Rev., 1989, 18, 409; P. D. Beer, Adv.
Inorg. Chem., 1992, 79.
3. R. A. Bissel, E. Cordova, A. E. Kaifer, and J. F. Stoddart,
Nature, 1994, 369, 133.
4. T. Saji and I. Kinoshita, J. Chem. Soc., Chem. Commun.,
1986, 716.
5. A. M. Allgeier, C. S. Slone, C. A. Mirkin, L. M. Liableꢀ
Sands, G. P. A. Yap, and A. L. Rheingold, J. Am. Chem.
Soc., 1997, 119, 550.
6. Z.ꢀT. Li, P. C. Stein, J. Becher, D. Jensen, P. Mork, and
N. Svenstrup, Chem. Eur. J., 1996, 624.
7. W. Devonport, M. A. Blower, M. R. Bryce, and L. M.
Goldenberg, J. Org. Chem., 1997, 62, 885.
8. E. Cordova, R. A. Bissel, and A. E. Kaifer, J. Org. Chem.,
1995, 60, 1033.
9. M. Asakawa, P. R. Ashton, S. E. Boyd, C. L. Brown, R. E.
Gillard, O. Kocian, F. M. Raymo, J. F. Stoddart, M. S.
Tolley, A. J. P. White, and D. J. Williams, J. Org. Chem.,
1997, 62, 26.
10. S. Hünig, Liebigs Ann. Chem., 1964, 676, 32.
11. S. Hünig and F. Linhart, Liebigs Ann. Chem., 1976, 317.
12. L. Cardellini, P. Carloni, L. Greci, G. Tosi, R. Andruzzi,
G. Marrosu, and A. Trazza, J. Chem. Soc., Perkin Trans. 2,
1990, 2117.
13. M. B. Leitner, T. Kreher, H. Sonnenschein, B. Costisella,
and J. Springer, J. Chem. Soc., Perkin Trans. 2, 1997, 377.
14. V. V. Yanilkin, V. A. Mamedov, A. V. Toropchina, A. A.
Kalinin, N. V. Nastapova, V. I. Morozov, R. P. Shekurov,
and O. G. Isaikina, Elektrokhimiya, 2006, 42, 251 [Russ.
J. Electrochem., 2006, 42 (Engl. Transl.)].
15. H. Sonnenschein, T. Kreher, E. Gründemann, R.ꢀP. Krüger,
A. Kunath, and V. Zabel, J. Org. Chem., 1996, 61, 710.
16. T. Kreher, H. Sonnenschein, B. Costisella, and
M. Schneider, J. Chem. Soc., Perkin Trans. 1, 1997, 3451.
17. F. Vogtle and H. Sieger, Angew. Chem., Int. Ed., 1977,
16, 396.
18. H. Sieger and F. Vogtle, Lieb. Ann. Chem., 1980, 425.
19. A. F. Pozharskii, Teoreticheskie osnovy khimii geterotsiklov
[Theoretical Principles of the Chemistry of Heterocycles],
Khimiya, Moscow, 1985, 280 pp. (in Russian).
20. 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, Izv. Akad. Nauk, Ser. Khim., 2005, 2534
[Russ. Chem. Bull., Int. Ed., 2005, 54, 2616].
21. A. H. Elwahy, Tetrahedron, 2000, 56, 897.

Synthesis and structure of new heterocyclophane
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2073
22. A. W. Williamson, J. Chem. Soc., 1852, 4, 229.
23. A. E. Chichibabin, Chem. Ber., 1927, 60, 1607.
24. J. Hammer and A. Macaluso, Chem. Rev., 1964, 64, 481.
25. R. Andruzzi, L. Cardellini, L. Greci, P. Stipa, M. Poloni,
and A. Trazza, J. Chem. Soc., Perkin Trans. 1, 1988, 3067.
26. H. Sonnenshein, H. Kosslick, and F. Tittelbach, Synthesis,
1998, 1596.
27. Physical Methods in Heterocyclic Chemistry, Ed. A. R.
Katritzky, Acad Press, NewꢀYork—London, 1963,
V.II, 398 p.
37. A. B. Sebag, D. A. Forsyth, and M. A. Plante, J. Org. Chem.,
2001, 66, 7967.
38. A. B. Sebag, R. N. Hanson, D. A. Forsyth, and C. Y. Lee,
Magn. Reson. Chem., 2003, 41, 246.
39. E. A. Meyer, R. K. Castellano, and F. Diederich, Angew.
Chem., Int. Ed., 2003, 42, 1210.
40. F. Cozzi, H. Favre, H. Griinewald, D. Hellwinkel,
K. Hirayama, M. A. C. Kaplan, M. V. Kisakiirek, W. H.
Powell, R. Panico, J. G. Trayaham, and O. Weissbach, Pure
Appl. Chem., 1998, 70, 1513.
28. G. F. Bol´shakov, V. S. Voiago, and F. B. Agrest,
Ul´trafioletovye spektry geteroorganicheskikh soedinenii [Ultraꢀ
violet Spectra of Heteroorganic Compounds], Khimiya,
Leningrad, 1969, p. 499 (in Russian).
41. H. A. Favre, D. Hellwinkel, W. H. Powell, H.A. Smith, Jr.,
and S. S.ꢀC. Tsay, Pure Appl. Chem., 2002, 74, 809.
42. A. Altomare, G. Cascarano, C. Giacovazzo, and D. Viterbo,
Acta Crystallogr. A, 1991, 47, 744.
29. A. E. Derome, Modern NMR Techniques for Chemistry Reꢀ
search, Pergamon, Cambridge, 1988, 280 pp.
30. AttaꢀurꢀRahman, One and Two Dimensional NMR Spectroꢀ
scopy, Elsevier, Amsterdam, 1989.
31. K. Stott, J. Stonehouse, J. Keeler, T. L. Hwang, and A. J.
Shaka, J. Am. Chem. Soc., 1995, 117, 4199.
43. G. M. Sheldrick, SHELXꢀ97. Programs for Crystal Structure
Analysis (Release 97ꢀ2), University of Gottingen, Germany,
1997, 154 p.
44. L. H. Straver and A. J. Schierbeek, MolEN. Structure Deꢀ
termination System, V. 1. Program Description, Delft:
Nonius B.V., 1994, 180 pp.
32. A. De Dios, Progr. Nucl. Magn. Res. Spectroscopy, 1996,
29, 229.
45. L. J. Farrugia, WINGX Main Reference, J. Appl. Cryst., 1999,
32, 837.
33. G. Barone, L. GomezꢀPaloma, D. Duca, A. Silvestri,
R. Riccio, and G. Bifulco, Chem. Eur. J., 2002, 8, 3233.
34. P. Cimino, L. GomezꢀPaloma, D. Duca, R. Riccio, and
G. Bifulco, Magn. Reson. Chem., 2004, 42, 26.
46. Mercury 1.3. User Guide, The Cambridge Crystallographic
Data Centre, 2004, 186 pp.
47. A. L. Spek, PLATON for Windows, Version 98; A. L. Spek,
Acta Crystallogr., 1990, 46, 34.
35. I. Alkorta and J. Elguero, Magn. Reson. Chem., 2004, 42, 955.
36. A. A. Balandina, A. A. Kalinin, V. A. Mamedov, B. Figadere,
and Sh. K. Latypov, Magn. Res. Chem., 2005, 43, 816.
Received July 21, 2006;
in revised form March 30, 2007