Synthesis of azacrown ethers and benzocryptands by macrocyclization of podands at high concentrations of reactants

Article abstract of DOI:10.1007/s11172-011-0075-1

The reactions of 1,2-bis(2-Y-ethoxy)benzenes, N,N-bis(2-Y-ethyl)-N- phenylamines, or 2,6-bis(Y-methyl)pyridines (Y = I, Br, or OTs) with α,ω-polyoxaalkanediamines or diazacrown ethers in the presence or absence of alkali carbonates in a concentrated acetonitrile solution of the reactants afforded the corresponding azacrown ethers or cryptands in high yields.

Full text of DOI:10.1007/s11172-011-0075-1

Russian Chemical Bulletin, International Edition, Vol. 60, No. 3, pp. 478—485, March, 2011
478
Synthesis of azacrown ethers and benzocryptands
by macrocyclization of podands at high concentrations of reactants
M. S. Oshchepkov,a V. P. Perevalov,a L. G. Kuzmina,b A. V. Anisimov,c and O. A. Fedorovaa,c
aD. I. Mendeleev University of Chemical Technology of Russia,
9 pl. Miusskaya, 125047 Moscow, Russian Federation.
Fax: +7 (495) 609 2964. Eꢀmail: fedorova@petrol.chem.msu.ru
bN. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences,
31 Leninsky prosp., 119991 Moscow, Russian Federation
cDepartment of Chemistry, M. V. Lomonosov Moscow State University,
Build. 3, 1 Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (495) 932 8568
The reactions of 1,2ꢀbis(2ꢀYꢀethoxy)benzenes, N,Nꢀbis(2ꢀYꢀethyl)ꢀNꢀphenylamines, or
2,6ꢀbis(Yꢀmethyl)pyridines (Y = I, Br, or OTs) with α,ωꢀpolyoxaalkanediamines or diazacrown
ethers in the presence or absence of alkali carbonates in a concentrated acetonitrile solution of
the reactants afforded the corresponding azacrown ethers or cryptands in high yields.
Key words: macrocyclization of azapolyethers, diamines, alkali carbonates, azacrown ethers,
cryptands, crown compounds.
The replacement of oxygen atoms in macroheterocyꢀ
benzoazacrown compounds by the condensation of acyꢀ
clic precursors under mild conditions. The main differꢀ
ence between this method and the method described earliꢀ
er31 is that the reaction is performed at room temperature
(as opposed to the refluxing of the starting compounds in
acetonitrile) and in a concentrated acetonitrile solution of
the reactants (as opposed to the high dilution technique
used in the method developed earlier31). The formation of
azamacrocyclic compounds can occur even in the absence
of alkali carbonates, which has not been observed earlier
in the syntheses of azacrown ethers. The advantages of the
new method are that the reaction products are formed in
good or high yields and are characterized by higher purity.
We studied the condensation of substituted 1,2ꢀbisꢀ
(2ꢀiodoethoxy)benzenes 1a,b and related dielectrophiles deꢀ
signed on diethylphenylamine 1c,d and 2,6ꢀlutidine 1e,f
with diamines 2a—f and diazacrown ethers 2g,h and 3d in
the presence of alkali carbonates (Scheme 1).
The condensation occurs with linear dielectrophiles
1a—f and dinucleophiles 2a—h or 3d in a concentrated
acetonitrile solution at room temperature within 70—75 h
(in the presence of alkali carbonates) or 250—300 h (in
their absence) with TLC monitoring until the reactants
were completely consumed. To study the substrate depenꢀ
dence, the reactions were carried out under the same conꢀ
ditions (the reaction time, the temperature, and the conꢀ
centrations of the reactants). In particular, the presence of
the formyl group in the starting compound 1b has no subꢀ
stantial effect on the macrocyclization outcome.
clic crown ether compounds by nitrogen atoms affords
complexes capable of being coordinated to different types
of metal cations (alkali, alkaline earth, heavy, and transiꢀ
tion),1—7 due to which this class of ligands has attracted
interest.8—12 Macrocyclic azapolyethers can be derivatized
at the nitrogen atom, with the result that they can be used
as intermediates in the synthesis of ionꢀselective dyes,13—17
biologically active compounds,17—19 bicyclic analogs, and
polymerꢀbound reagents.20,21
There are various methods for the synthesis of azamacꢀ
roheterocyclic compounds.22—30 Nevertheless, the develꢀ
opment of new facile methods for the synthesis of benꢀ
zoazacrown compounds, particularly, of functionalized
derivatives, is an important problem.
Earlier,31 we have developed a method for the syntheꢀ
sis of formyl derivatives of benzodiazacrown ethers and
benzocryptands based on the condensation of 3,4ꢀbis(2ꢀ
iodoethoxy)benzaldehyde with α,ωꢀpolyoxaalkanediamines
and diazacrown ethers in the presence of alkali metal carꢀ
bonates at high dilutions in different organic solvents and
their mixtures with water. However, the reactions of unꢀ
substituted terminal diamines with diazacrown ethers are
accompanied by partial resinification of the starting reacꢀ
tants and, consequently, the purification of the reaction
products presents considerable difficulties.
With the aim of preventing resinification and extendꢀ
ing the range of the reactants, in the present study we
developed a procedure for the synthesis of derivatives of
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 468—475, March, 2011.
1066ꢀ5285/11/6003ꢀ478 © 2011 Springer Science+Business Media, Inc.

Azacrown ethers
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 3, March, 2011
479
Scheme 1
i. M2CO3 or without the salt, MeCN.
M = Na, K
R´ = H (a), CHO (b)
2: X = O (a—c, e, g, h), CH2(NMe)CH2 (d), NH (f);
Y = I (a, b, d), OTs (c, e), Br (f)
R = H (b, c, d, f), Me (a, e);
R—R = CH2(CH2OCH2)2CH2 (g, h); n = 1 (a, b, d, g), 2 (c, e, f, h)
3
R or R—R
R´
X
n
3
R or R—R
Me
R´
X
n
a
b
c
d
e
f
g
h
i
Me
H
Me
H
H
H
H
H
H
H
H
H
CHO
CHO
O
O
O
O
O
O
NH
1
1
2
2
1
2
2
1
1
2
1
2
m
—
O
1
CH2(CH2OCH2)2CH2
CH2(CH2OCH2)2CH2
n
o
p
Me
Me
O
O
O
1
2
2
—
—
—
H
H
Me
Me
1,2ꢀC6H4(OCH2CH2)2
CH2(NMe)CH2
O
O
O
O
j
k
l
CH2(CH2OCH2)2CH2 CHO
CH2(CH2OCH2)2CH2 CHO
The reaction in the absence of the bases occurs slowly
aza podand 5. The final step involves the cyclization of the
aza podand to form macrocycles 3a—l. In the reactions in
the presence of alkali carbonates, the metal cations are
involved in the formation of intermediate template comꢀ
plex 6 (see Ref. 31).
In the absence of carbonates, the starting diamine can
serve as a base. This is confirmed by the fact that diamine
hydroiodide 2a was isolated from the reaction mixture.
Compound 2a was characterized by Xꢀray diffraction
(~280 h), but the yields of the corresponding benzodiazaꢀ
crown compounds vary from good to high (Table 1).
The addition of alkali carbonates makes it possible to reꢀ
duce the reaction time to 75 h. Apparently, the formation
of azacrown compounds 3a—l occurs in several steps
(Scheme 2).
The Nꢀalkylation of compounds 2a—h with 1a,b afꢀ
fords ammonium derivative 4, whose deprotonation gives
Scheme 2

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Russ.Chem.Bull., Int.Ed., Vol. 60, No. 3, March, 2011
Oshchepkov et al.
Table 1. Reaction conditions and yields of crown comꢀ
pounds 3a—p
Crownꢀ
comꢀ
pound
Starting
dinucleoꢀ
phile
Reaction
time/h
Base
Yield
(%)
3a
3b
3c
3d
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1c
1c
1d
1d
1e
1e
1f
280
75
280
75
280
75
280
75
—
K2CO3
—
K2CO3
—
K2CO3
—
Na2CO3
K2CO3
—
—
—
K2CO3
—
K2CO3
—
Na2CO3
K2CO3
—
Na2CO3
—
Na2CO3
—
Na2CO3
—
K2CO3
—
K2CO3
—
K2CO3
—
K2CO3
K2CO3
Na2CO3
74
79
58
76
76
80
56
72
77
63
69
10
28
54
73
73
83
77
71
86
80
26
40
24
78*
77*
Traces
7
Traces
18
Traces
22
53
75
(Fig. 1). Apparently, the cyclization of aza podand 4 to
the macrocycle occurs through the formation of a comꢀ
plex having structure 7, in which a proton is coordinated
to the terminal amino group. On the one hand, the formaꢀ
tion of this complex facilitates the intramolecular cyclizaꢀ
tion as a result of the rearrangement of the podand to the
pseudomacrocycle and the location of the terminal reactꢀ
ing groups in close proximity to each other. On the other
hand, this coordination should hinder the final step of the
reaction, viz., the alkylation of the terminal amino group,
which is manifested in the longer reaction time.
The formation of the azamacrocyclic compound that
occurs with the involvement of the hydrogen bond beꢀ
tween the hydrogen atom of the terminal group and the
nitrogen atom of the podand was documented.32 It was
noted32 that the yield of the macrocyclization product in
the absence of alkali carbonates was higher.
3e
3f
3g
280
280
280
75
280
75
280
75
75
280
75
280
75
280
75
280
75
280
75
280
75
280
75
75
3h
3i
3j
3k
3l
3m
The yields of benzodiazaꢀ15ꢀcrownꢀ5 compounds 3a,b,
benzodiazaꢀ17ꢀcrownꢀ5 compound 3h, and benzodiazaꢀ
18ꢀcrownꢀ6 compounds 3c,d,j are relatively high (see
Table 1). The reaction with tetramine 2f affords the target
product 3g in low yield, which is apparently attributed to
the possible reaction at any of the nitrogen atoms of the
tetramine chain and the formation of a wide range of prodꢀ
ucts (see Table 1).
3n
1f
1f
1f
3o
3p
75
41
* The yield is given based on the azacrown ether.
It was shown by an example of benzocryptands 3k,l
that the reaction performed in the presence of sodium
carbonate gives the product in lower yield compared to the
reaction in the absence of the base (see Table 1). Apparꢀ
ently, the reaction producing cryptands is accompanied
by the strong binding of the alkali metal cation to the
starting diazacrown ether through coordination to the niꢀ
trogen and oxygen atoms. This leads to a reduction of the
nucleophilicity of the nitrogen atoms and a decrease in the
activity in the reactions with dihalides.
C(4)
C(3)
C(1)
C(2)
H(1)
O(1)
N(2)
N(1)
H(2)
C(6)
C(5)
In the case of phenylazacrown ether 3m, the reaction
occurs only with the use of N,Nꢀbis[2ꢀ(pꢀtoluenesulfonylꢀ
oxy)ethyl]ꢀNꢀphenylamine (1c) as the starting compound,
whereas the corresponding diiodide 1d proved to be insufꢀ
ficiently active (see Table 1).
I(1)
Fig. 1. Structure of the asymmetric unit in the crystal structure
of salt 2a.

Azacrown ethers
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 3, March, 2011
481
C(2A)
C(1A)
The condensation of 1,5ꢀbis(methylamino)ꢀ3ꢀoxapenꢀ
tane (2a) with 2,6ꢀpyridinedimethanol ditosylate (1e) or
2,6ꢀbis(bromomethyl)pyridine (1f) was accompanied by
substantial resinification of the reaction mixture, and, conꢀ
sequently, the target product 3n was obtained in low yield.
The reactions with larger diamino compounds 2e and 3d
gave target products 3o,p in higher yields (see Table 1).
Compounds 3a—p were characterized by physicocheꢀ
mical methods. The physicochemical characteristics of formꢀ
yl derivatives 3i—l have been described in our earlier study.31
Compound 2a is diamine hydroiodide (see Fig. 1). Both
nitrogen atoms have a tetrahedral bond configuration, but
one of the nitrogen atoms, N(2), is protonated and bears
a positive charge. Both nitrogen atoms form a N—H...I
hydrogen bond with the iodide anion. The hydrogen bond
with the positively charged nitrogen atom is somewhat
shorter. The I(1)...N(1), I(1)...N(2) and I(1)...H(1),
I(1)...H(2) distances are 3.663(1), 3.602(1) and 2.86(2),
2.78(2) Å, respectively. The angles at the H(1) and H(2)
atoms are 157(2) and 156(2)°, respectively.
C(3A)
C(4A)
O(1A)
H(1A)
N(1A)
C(5A)
H(22B)
C(6B)
N(2A)
H(2A)
C(6A)
I(1A)
H(22A)
I(1B)
N(1B)
C(5B)
N(2B)
H(2B)
H(1B)
O(1B)
C(4B)
C(1B)
C(3B)
C(2B)
Fig. 2. Structure of the dimer formed by N—H...N hydroꢀ
gen bonds.
The central C(1)—C(2)—O(1)—C(3)—C(4) fragment
of the cation is almost planar, and the nitrogen atoms are
located on the same side of the plane. The N(1)—C(1)—
C(2)—O(1) and N(2)—C(4)—C(3)—O(1) torsion angles are
almost equal in magnitude (60.7 and –58.6°, respectively).
These anions are linked into centrosymmetric dimers by
two N—H...N hydrogen bonds with the participation of the
second hydrogen atom at the protonated nitrogen atom.
In the crystal structure, two complexes are linked into
centrosymmetric dimers by the N(2)—H...N(1) hydrogen
bond with the participation of the second proton at
the nitrogen atom N(2) (Fig. 2). The geometric parameꢀ
ters of this bond are as follows: the N(2А)...N(1В) and
H(22А)...N(1В) distances are 2.762(2) and 1.84(3) Å, reꢀ
spectively, the N(2А)—H(22)...N(1В) angle is 172(2)°.
The components of the asymmetric unit in the crystal
structure of Na complex 3´k containing ligand molecule
3k are presented in Fig. 3. The crystal contains the ligand
coordinated to the Na+ cation by all heteroatoms, the
iodide anion disordered over two closely spaced sites I(1)
C(3S)
C(2S)
I(2)
C(1S)
I(1)
C(20)
C(14)
C(15)
C(19)
O(5)
N(2)
C(16)
C(13)
O(4)
C(6)
O(3)
C(1T)
C(18)
C(2T)
C(5)
Na(1)
C(12)
C(17)
C(1)
C(3T)
C(11)
C(4)
O(1)
C(7)
O(2)
C(10)
C(2)
C(3)
C(8)
C(9)
O(6)
C(21)
O(2WA)
Fig. 3. Crystal structure of cryptand complex 3´k.
O(2W)

482
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Oshchepkov et al.
use of Kieselgel 60 (0.0063—0.100 mm), Kieselgel 60
(0.0063—0.200 mm), Aluminium oxide 150 basic (type T)
(0.0063—0.200 mm), Aluminium oxide 90 active, neutral (acꢀ
tivity 1) (0.0063—0.200 mm), and HPTLCꢀAlufolien Cellulose
(Merck).
and I(2), two benzene solvent molecules occupying cenꢀ
ters of symmetry, and a water molecule disordered over
two sites (O(2W) and O(2WA)). Each benzene molecule
is also disordered over two sites.
The Na+ cation is sevenꢀcoordinated and is located in
the cavity of the cryptand. The distances from the cation
to the heteroatoms O(1), O(2), O(3), O(4), O(5), N(1),
and N(2) are 2.460(2), 2.496(2), 2.453(2), 2.458(2),
2.352(2), 2.596(2), and 2.616(2) Å, respectively, and are
in usual ranges. As a result, the sodium cation is somewhat
more distant from the nitrogen atoms.
To sum up, we developed a convenient procedure for
the preparation of azacrown compounds and benzoꢀ
cryptands under mild conditions at room temperature,
suitable for reactants with different oxygen and nitrogen
content. This method holds the most promise for the synꢀ
thesis of azacrown ethers conjugated with complex moleꢀ
cules, since under mild conditions of the condensation,
the moiety of the complex molecule would remain intact.
The method provides an approach to the synthesis of optiꢀ
cal chelating agents, catalytic systems based on organoꢀ
metallic complexes, and extractants for the selective exꢀ
traction of metal salts.
Benzoazacrown compounds 3a—d,g—j,m and benzocryptands
3e,f,k,n—p (general procedure). A. Synthesis in the presence of
K2CO3 (Na2CO3). Compound 2a—h or 3d (0.23 mmol) was addꢀ
ed with stirring to a mixture of dielectrophile 1a—f (0.23 mmol),
K2CO3 (Na2CO3) (1.15 mmol), and MeCN (3 mL). The reacꢀ
tion mixture was then kept without stirring at ~20 °C for 75 h.
The solvent was evaporated in vacuo. The residue was extracted
with dichloromethane (3×20 mL) and washed with water. The
extract was concentrated in vacuo. The product was extracted
with boiling hexane. Cryptands 3k,l were washed off from the
starting compound 1b with benzene and then recrystallized from
an acetonitrile—benzene system. The yields of the compounds
are given in Table 1.
B. Synthesis in the absence of bases. Diamino compound 2a—h
(0.05 mL, 0.25 mmol) was added with stirring to a solution of
dielectrophile 1a—f (0.23 mmol) in MeCN (3 mL). The reaction
mixture was kept without stirring at ~20 °C for 280 h. The solꢀ
vent was evaporated in vacuo. The residue was extracted with
dichloromethane (3×20 mL) and then washed with a 3% K2CO3
solution (20 mL) and water. The extract was concentrated
in vacuo. The product was extracted with boiling hexane.
Cryptands 3k,l were washed off from the starting compound 1b
with benzene and then recrystallized from an acetonitrile—benꢀ
zene system. The yields of the products are given in Table 1.
1,10ꢀDimethylꢀ1,7,13,4,10ꢀbenzotrioxadiazacyclopentadeꢀ
Experimental
Commercial 1,2ꢀbis(2ꢀhydroxyethoxy)benzene, 2,2´ꢀ(ethylꢀ
enedioxy)bis(ethylamine), 4,13ꢀdiazaꢀ18ꢀcrownꢀ6 ether, anhyꢀ
drous acetonitrile, anhydrous sodium and potassium carbonates
(Aldrich), anhydrous sodium iodide (Aldrich), 1,8ꢀbis(methylꢀ
amino)ꢀ3,6ꢀdioxaoctane, 1,5ꢀbis(methylamino)ꢀ3ꢀoxapentane,
and 1,7ꢀdiazaꢀ15ꢀcrownꢀ5 ether (Janssen) were used as purꢀ
chased. 1,2ꢀBis(2ꢀiodoethoxy)benzene (1a), 3,4ꢀbis(2ꢀiodoꢀ
ethoxy)benzaldehyde (1b),31,33 N,Nꢀbis[2ꢀ(pꢀtoluenesulfonylꢀ
oxy)ethyl]ꢀNꢀphenylamine (1c),34 N,Nꢀbis(2ꢀiodoethyl)ꢀNꢀ
phenylamine (1d),35 2,6ꢀpyridinedimethanol ditosylate (1e),36
and 2,6ꢀbis(bromomethyl)pyridine (1f)37 were synthesized acꢀ
cording to known procedures. The reagents and solvents used for
the synthesis were purchased from Fluka, Merck, and Aldrich.
The staring compounds and solvents were not purified before use.
1
cene (3a), yellow oil. H NMR (CDCl3), 25 °C, δ: 2.24 (s, 6 H,
2 NMe); 2.59 (m, 4 H, 2 CH2N); 2.74 (m, 4 H, 2 CH2N); 3.57
(m, 4 H, 2 CH2O); 3.96 (m, 4 H, 2 CH2O); 6.85 (m, 2 H, H(1));
1
6.92 (m, 2 H, H(2)). The H NMR spectrum is consistent with
the published data.24
1,7,13,4,10ꢀBenzotrioxadiazacyclopentadecene (3b) was obꢀ
tained as a powder, m.p. 97—100 °C. 1H NMR (CDCl3), 25 °C,
δ: 2.72 (s, 2 H, 2 NH); 2.87 (t, 4 H, 2 CH2N, J = 5.0 Hz); 3.02
(t, 4 H, 2 CH2N, J = 5.0 Hz); 3.63 (t, 4 H, 2 CH2O, J = 5.0 Hz);
4.11 (t, 4 H, 2 CH2O, J = 5.0 Hz); 6.88 (s, 4 H, Ar). The
physicochemical parameters are consistent with the publishꢀ
ed data.26
4,13ꢀDimethylꢀ1,7,10,16,4,13ꢀbenzotetraoxadiazacyclooctaꢀ
decene (3c), yellow oil. 1H NMR (CDCl3), 25 °C, δ: 2.37 (s, 6 H,
NMe); 2,82 (t, 4 H, CH2N, J = 5.68 Hz); 3.00 (t, 4 H, CH2N,
J = 5.86 Hz); 3.60 (s, CH2O); 3.66 (m, 4 H, CH2O, J = 5.68 Hz);
4.08 (t, 4 H, CH2O, J = 5.86 Hz); 6.87 (m, 4 H, 2 H(1), 2 H(2)).
The 1H NMR spectrum is consistent with the published data.24
1,7,10,16,4,13ꢀBenzotetraoxadiazacyclooctadecene (3d) was
obtained as a powder, m.p. 86—92 °C. 1H NMR (CDCl3), 25 °C,
δ: 2.62 (s, 2 H, 2 NH); 2.87 (t, 4 H, 2 CH2N, J = 4.8 Hz); 3.06
(t, 4 H, 2 CH2N, J = 4.6 Hz); 3.61 (s, 4 H, 2 CH2O); 3.67 (t, 4 H,
2 CH2O, J = 4.8 Hz); 4.13 (t, 4 H, 2 CH2O, J = 4.6 Hz); 6.88
(s, 4 H, Ar). The physicochemical parameters are consistent
with the published data.26
1
The H NMR spectra were recorded on a Bruker DRXꢀ400
spectrometer (operating at 400.13 MHz) using CDCl3, DMSOꢀd6,
and CD3CN as the solvents and the residual protons of the deuꢀ
terated solvent as the internal standard. The chemical shifts and
the spinꢀspin coupling constants were measured with an accuracy
of 0.01 ppm and 0.1 Hz, respectively. The electronꢀimpact massꢀ
spectrometric analysis was performed on a Finnigan MAT 311S
instrument (the ionizing electron energy was 70 eV) equipped
with a quartz capillary column (L = 60 m, d = 0.25 mm) coated
with the DBꢀ1 stationary phase in the temperatureꢀprogrammed
mode; helium was used as the carrier gas. The elemental analysis
was performed at the Laboratory of Microanalysis of the A. N.
Nesmeyanov Institute of Organoelement Compounds of the Rusꢀ
sian Academy of Sciences (Moscow). The melting points (unꢀ
corrected) were measured on a Melꢀtemp II instrument. The
TLC monitoring was carried out on DCꢀAlufolien Kieselgel 60
F254 and DCꢀAlufolien Aluminiumoxid 60 F254 neutral (Tуp E)
plates. The column chromatography was performed with the
8ꢀMethylꢀ1,15,4,8,12ꢀbenzodioxatriazacycloheptadecene
1
(3h), viscous paleꢀyellow oil. H NMR (CDCl3), 25 °C, δ: 1.64
(m, 4 H, CH2); 2.12 (s, 3 H, NMe); 2.30 (t, 4 H, 2 CH2N,
J = 6.06 Hz); 2.81 (t, 4 H, 2 CH2N, J = 6.06 Hz); 3.03 (t, 4 H,
2 CH2N, J = 4.50 Hz); 4.08 (t, 4 H, 2 CH2O, J = 4.50 Hz); 6.88
(m, 4 H, 2 H(1), 2 H(2)). 13C NMR (CDCl3), 25 °C, δ: 26.6,

Azacrown ethers
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 3, March, 2011
483
40.8, 47.3, 48.8, 55.7, 68.9, 113.3, 120.9, 148.7. Electrosprayꢀ
ionization mass spectrum (ESIꢀMS): m/z 308 [MH]+. Found (%):
C, 66.48; H, 9.55. C17H29N3O2. Calculated (%): C, 66.42; H, 9.51.
4,11,17,20,25ꢀPentaoxaꢀ1,14ꢀdiazatricyclo[12.8.5.05,10]ꢀ
heptacosaꢀ5,7,9ꢀtriene (3e) was obtained as a powder, m.p.
Complex of 4,10ꢀdimethylꢀ7ꢀphenylꢀ1ꢀoxaꢀ4,7,10ꢀtriazacyꢀ
clododecane with 4ꢀmethylbenzenesulfonic acid (3m), white crysꢀ
1
tals, m.p. 134—138 °C. H NMR (DMSOꢀd6), 30 °C, δ: 2.29
(s, 3 H, MeTs); 2.60 (s, 1 H, MeN); 3.12 (t, 2 H, Hδ, J = 0.01 Hz);
3.20 (s, 6 H, 2 MeN); 3.46 (m, 2 H, Hβ); 3.56 (m, 2 H, Hβ´); 3.59
(m, 4 H, 2 Hα, 2 Hα´); 3.70 (m, 2 H, Hδ´); 3.75 (m, 2 H, Hγ´);
3.92 (m, 2 H, Hγ); 6.88 (t, 1 H, H(4), J = 7.32 Hz); 7.01 (dd, 2 H,
H(2), H(6), J = 3.8 Hz, J = 8.0 Hz); 7.11 (d, 2 H, CHTs, J = 7.9 Hz,
J = 7.3 Hz); 7.29 (t, 2 H, H(3), H(5), J = 7.9 Hz); 7.48 (d, 2 H,
CHTs, J = 7.9 Hz). ESIꢀMS, m/z: 278 [MH]+. Found (%):
C, 61.49; H, 7.84; N, 9.57. C23H35N3O4S. Calculated (%):
C, 61.44; H, 7.85; N, 9.35.
3,9ꢀDimethylꢀ6ꢀoxaꢀ3,9,15ꢀtriazabicyclo[9.3.1]pentadecaꢀ
1(15),11,13ꢀtriene (3n), viscous paleꢀyellow oil. 1H NMR
(CDCl3), 25 °C, δ: 2.26 (s, 6 H, 2 NMe); 2.62 (m, 4 H, 2 CH2N);
3.54 (m, 4 H, 2 CH2N); 3.65 (s, 4 H, 2 CH2); 7.25 (m, 2 H,
H(3´)); 7.55 (m, 2 H, H(4´)). 13C NMR (CDCl3), 25 °C: 46.3,
57.1, 64.3, 69.3, 121.7, 137.1, 158.7. ESIꢀMS, m/z: 236 [MH]+.
Found (%): C, 66.74; H, 9.09. C13H21N3O. Calculated (%):
C, 66.35; H, 8.99.
1
74—75 °C. H NMR (CD3CN), 25 °C, δ: 2.46—3.06 (m, 12 H,
CH2); 3.44—4.18 (m, 16 H, CH2); 6.90 (s, 4 H, 2 H(1), 2 H(2)).
The physicochemical parameters are consistent with the pubꢀ
lished data.30
4,11,17,20,25,28ꢀHexaoxaꢀ1,14ꢀdiazatricyclo[12.8.8.05,10]ꢀ
triacontaꢀ5,7,9ꢀtriene (3f) was obtained as a yellow oil. 1H NMR
(CDCl3), 25 °C, δ: 2.6—3.1 (m, 12 H, NCH2); 3.3—3.8 (m, 16 H,
OCH2); 4.1 (m, 4 H, ArOCH2); 7.2 (m, 4 H, 2 H(1), 2 H(2)).
The 1H NMR spectrum is consistent with the published data.29
1,16,4,7,10,13ꢀBenzodioxatetraazacyclooctadecene (3g), visꢀ
cous yellow oil. 1H NMR (CDCl3), 25 °C, δ: 2.63—3.01 (m, 16 H,
2 CH2N); 4.05—4.11 (m, 4 H, 2 CH2O); 6.87 (m, 4 H, H(1),
H(2)). 13C NMR (CDCl3), δ: 47.6, 49.1, 55.8, 69.1, 112.3, 120.6,
148.2. ESIꢀMS, m/z: 309 [MH]+. Found (%): C, 62.42; H, 9.10.
C16H28N4O2. Calculated (%): C, 62.31; H, 9.15.
4,10ꢀDimethylꢀ1,7,13,4,10ꢀbenzotrioxadiazacyclopentadeꢀ
ceneꢀ15ꢀcarbaldehyde (3i), yellowish powder, m.p. 70—73 °C
(heptane). 1H NMR (CD3CN), 30 °C, δ: 2.29 (s, 6 H, 2 NMe);
2.64 (t, 4 H, C(5)H2N, C(9)H2N, J = 5.6 Hz); 2.82 (m, 4 H,
C(3)H2N, C(11)H2N); 3.62 (m, 4 H, C(6)H2O, C(8)H2O); 4.08
(m, 2 H, C(12)H2O); 4.11 (m, 2 H, C(2)H2O); 7.06 (d, 1 H,
H(17), J = 8.3 Hz); 7.32 (d, 1 H, H(14), J = 1.7 Hz); 7.49 (dd, 1 H,
H(16), J = 8.3 Hz, J = 1.7 Hz); 9.83 (s, 1 H, CH=O). The
physicochemical parameters are consistent with the published
data.31
3,12ꢀDimethylꢀ6,9ꢀdioxaꢀ3,12,18ꢀtriazabicyclo[12.3.1]ꢀ
octadecaꢀ1(18),14,16ꢀtriene (3o), viscous yellow oil. H NMR
1
(CDCl3), 25 °C, δ: 2.47 (s, 6 H, 2 NMe); 2.62 (t, 4 H, 2 CH2N,
J = 6.06 Hz); 3.49 (s, 4 H, CH2O); 3.61—3.58 (m, 4 H, CH2O);
3.70 (s, 4 H, 2 CH2); 7.17 (d, 2 H, H(3´), J = 7.63 Hz); 7.58 (t, 1 H,
H(4´), J = 7.63 Hz). 13C NMR (CDCl3), 25 °C, δ: 44.9, 55.7,
64.0, 68.3, 70.3, 122.4, 136.3, 158.2. ESIꢀMS, m/z: 280 [MH]+.
Found (%): C, 65.03; H, 8.91. C15H25N3O2. Calculated (%):
C, 64.49; H, 9.02.
4, 11, 17, 20ꢀTetraoxaꢀ1, 14, 29ꢀtriazatetracycloꢀ
[12.8.7.124,28.05,10]nonacosaꢀ5,7,9,24,26,28ꢀhexaene (3p), visꢀ
cous yellow oil. 1H NMR (CDCl3), 25 °C, δ: 3.00 (m, 4 H,
CH2N); 3.15 (m, 4 H, C(3)H2N, C(14)H2N); 3.65—3.80 (m, 12 H,
C(6)H2O, C(11)H2O, C(8)H2O, C(9)H2O, 2 CH2, Py);
3.95—4.05 (m, 4 H, 2 CH2O); 7.00 (m, 4 H, Ar, 2 H(1), 2 H(2));
7.29 (d, 2 H, Py, H(3´), J = 7.60 Hz); 7.77 (t, 1 H, Py, H(4´),
J = 7.60 Hz). 13C NMR (CDCl3), 25 °C, δ: 52.0, 53.3, 59.3,
64.4, 67.0, 69.0, 112.9, 122.3, 122.6, 138.5, 146.8, 158.4. ESIꢀMS,
m/z: 415 [MH]+. Found (%): C, 65.21; H, 6.73. C23H31N3O4.
Calculated (%): C, 66.81; H, 7.56.
4,13ꢀDimethylꢀ1,7,10,16,4,13ꢀbenzotetraoxadiazacyclooctaꢀ
deceneꢀ18ꢀcarbaldehyde (3j), yellow oil. 1H NMR (CD3CN),
25 °C, δ: 2.85 (m, 4 H, C(5)H2N, C(12)H2N); 3.05 (m, 4 H,
C(3)H2N, C(14)H2N); 3.57 (s, 4 H, C(8)H2O, C(9)H2O); 3.59
(m, 4 H, C(6)H2O, C(11)H2O); 4.19, 4.22 (2 m, 4 H, C(2)H2O,
C(15)H2O); 7.13 (d, 1 H, H(20), J = 8.3 Hz); 7.43 (d, 1 H,
H(17), J = 1.9 Hz); 7.43 (dd, 1 H, H(19), J = 8.3 Hz, J = 1.9 Hz);
9.84 (s, 1 H, CH=O). The 1H NMR spectrum is consistent with
the published data.31
4,11,17,20,25ꢀPentaoxaꢀ1,14ꢀdiazatricyclo[12.8.5.05,10]ꢀ
heptacosaꢀ5,7,9ꢀtrieneꢀ7ꢀcarbaldehyde (3k), yellow crystals, m.p.
Crystallographic characteristics and the Xꢀray data collection
and structure refinement statistics for compounds 2a and 3´k.
Single crystals of compounds 2a and 3´k coated with perfluoriꢀ
nated oil were mounted on a Bruker SMART CCD diffractomeꢀ
ter under a cold nitrogen stream at 120 K. The experimental
Xꢀray data were measured using graphiteꢀmonochromated Mo
radiation and the ωꢀscanning technique. The experimental reꢀ
1
255—257 °C (with decomp.). H NMR (DMSOꢀd6), 30 °C, δ:
2.34 (m, 4 H, 2 CH2N); 2.98 (m, 4 H, 2 CH2N); 3.15 (m, 2 H,
CH2N); 3.28 (m, 2 H, CH2N); 3.42 (m, 4 H, 2 CH2O); 3.55 (s, 4 H,
2 CH2O); 3.68 (m, 4 H, 2 CH2O); 4.18 (m, 4 H, 2 CH2OAr);
7.24 (d, 1 H, H(9), J = 8.3 Hz); 7.45 (d, 1 H, H(6), J = 1.7 Hz);
7.62 (dd, 1 H, H(8), J = 8.3 Hz, J = 1.7 Hz); 9.88 (s, 1 H,
CH=O). The physicochemical parameters are consistent with
the published data.31
flections were processed with the use of the Bruker SAINT softꢀ
38
ware
.
Absorption corrections were applied with the use of the
Complex 3k with the Na cation (3´k) was synthesized acꢀ
cording to the method A and was used for the Xꢀray diffracꢀ
tion study.
SADABS program based on the intensities of equivalent reflecꢀ
tions. The structures were solved by direct methods and refined
by the fullꢀmatrix leastꢀsquares method based on F2.
For compound 2a, all hydrogen atoms were located in difꢀ
ference electron density maps. It was found that the N(2) atom
bears two hydrogen atoms, whereas one hydrogen atom is attaꢀ
hced to the N(1) atom. The structure was finally refined by the
leastꢀsquares method with anisotropic displacement parameters
for all nonhydrogen atoms. The hydrogen atoms were refined
isotropically.
4,11,17,20,25,28ꢀHexaoxaꢀ1,14ꢀdiazatricyclo[12.8.8.05,10]ꢀ
triacontaꢀ5,7,9ꢀtrieneꢀ7ꢀcarbaldehyde (3l), yellow powder, m.p.
1
134—138 °C (MeOH—Et2O). H NMR (DMSOꢀd6), 25 °C, δ:
2.55—2.70 (m, 8 H, 4 CH2N); 2.76 (m, 4 H, 2 CH2N); 3.49
(m, 8 H, 4 CH2O); 3.57 (s, 8 H, 4 CH2O); 4.26 (m, 2 H, CH2OAr);
4.30 (m, 2 H, CH2OAr); 7.32 (d, 1 H, H(9), J = 7.9 Hz); 7.51
(s, 1 H, H(6)); 7.60 (d, 1 H, H(8), J = 7.9 Hz); 9.87 (s, 1 H,
CH=O). The physicochemical parameters are consistent with
the published data.31
The structure solution and refinement of 3´k showed that
the iodide anion occupies two closely spaced sites with almost

484
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 3, March, 2011
Oshchepkov et al.
Table 2. Crystallographic characteristics and the Xꢀray data collection and structure refinement statistics for compounds 2a and 3´k
Parameter
2a
3´k
Molecular formula
C6H17IN2O
C27H38IN2 NaO6.2
М
260.12
639.68
Crystal system
Space group
Monoclinic
Triclinic
P21/n
P–1
Z
a/Å
4
2
10.1009(2)
7.9301(16)
b/Å
16.014(3)
11.7577(3)
c/Å
8.5499(17)
13.1584(3)
α/deg
90
99.065(1)
β/deg
103.69(3)
109.0710(1)
95.669(1)
1439.49(6)
γ/deg
90
V/Å3
1054.9(4)
1.638
dcalc/g cm–3
1.476
F(000)
512
2.989
0.40×0.26×0.20
multuꢀscan
0.3811/0.5863
120.0(2)
655
1.170
0.20×0.10×0.04
multuꢀscan
0.6138/1.0000
120.0(2)
μ(MoꢀKα)/mm–1
Crystal dimensions/mm
Absorption correction
Transmission coefficient, min/max
Т/K
Radiation (λ/Å)
θꢀScan mode/range, deg
h,k,l range
Number of measured reflections
Number of independent reflections
Number of reflections with I > 2σ(I)
Number of refined parameters
R factors based on reflections with I > 2σ(I)
R factors based on all reflections
S based on F2
MoꢀKα (0.71073)
ω/2.54—29.98
–10 ≤ h ≤ 11, –22 ≤ k ≤ 21, –11 ≤ l ≤ 12
9470
MoꢀKα (0.71073)
ω/1.78—29.99
–13 ≤ h ≤ 13, –16 ≤ k ≤ 9, –14 ≤ l ≤ 18
10405
2927 [Rint = 0.0237]
2797
7515 [Rint = 0.0254]
6238
160
467
R1 = 0.0198, wR2 = 0.0441
R1 = 0.0211, wR2 = 0.0446
1.122
R1 = 0.0440, wR2 = 0.1012
R1 = 0.0559, wR2 = 0.1064
1.051
Residual electron density
–0.772/0.671
–0.446/1.319
/e•Å–3, ρmin/ρ
max
equal occupancies (0.51 : 0.49). Two benzene solvent molecules
were found. Each molecule occupies a center of symmetry and is
disordered over two sites. The occupancy ratios for the disorꢀ
dered sites occupied by the benzene molecules C(1S)...C(3S)
and C(1T)...C(3T) are 0.80 : 0.20 and 0.51 : 0.49, respectively.
In addition, a water molecule disordered over two sites related
by a center of symmetry was located. The total occupancy of the
water sites is 0.4. The structure was finally refined by the leastꢀ
squares method with anisotropic displacement parameters for all
nonhydrogen atoms, except for the nonhydrogen atoms of the
solvent molecules. The hydrogen atoms were positioned geoꢀ
metrically. In the final steps, the hydrogen atoms of the podand
were refined isotropically. The positional and thermal parameꢀ
ters of the hydrogen atoms of the benzene solvent molecules
were fixed in the leastꢀsquares refinement.
1223ꢀ336ꢀ033; eꢀmail: deposit@ccdc.cam.ac) and can be obꢀ
tained, free of charge.
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 09ꢀ03ꢀ00550).
References
1. J. C. Pedersen, N. J. Salem, M. H. Bromels, Patent US
3.847.949, Patented Nov., 12, 1974.
2. S. J. Leigh, I. O. Sutherland, J. Chem. Soc., Perkin 1,
1979, 1089.
3. Eur. Pat. Application 0, 649 848 A1, 1995, 14.
4. F. Vogtle, E. Weber, Host Guest Complex Chemistry, Macroꢀ
cycles, Synthesis, Structures, Applications, Springer Verlag,
Berlin—Heidelberg—Ney York—Tokyo, 1985.
5. M. Gonza´lezꢀLorenzo, C. PlatasꢀIglesias, F. Avecilla, C. F.
G. C. Geraldes, D. Imbert, J.ꢀC. G. Bunzli, A. de Blas, T. R.
guezꢀBlas, Inorg. Chem., 2003, 42, 6946.
The crystal structures were solved and refined with the use of
the SHELXTLꢀPlus program package.39
The crystallographic characteristics and the Xꢀray data colꢀ
lection and structure refinement statistics for compounds 2a and
3´k are given in Table 2.
The atomic coordinates and other experimental data were
deposited with the Cambridge Crystallographic Data Centre
(CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: (+44)
6. C. Bazzicalupi, A. Bencini, A. Bianchi, V. Fedi, V. Fusi,
C. Giorgi, P. Paoletti, L. Tei, B. Valtancoli, J. Chem. Soc.,
Dalton Trans., 1999, 1101.

Azacrown ethers
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 3, March, 2011
485
7. J.ꢀC. G. Bunzli, N. Andre, M. Elhabiri, G. Muller, C. Piguet,
J. Alloys Compounds, 2000, 303—304, 66.
26. J. Jurczak, T. Stankiewicz, P. Salanski, S. Kasprzyk, P. Lipꢀ
kowski, Tetrahedron, 1993, 49, 1478.
8. B. Ziyadanogullari, G. Topal, S. Erdogan, C. Hamamci,
H. Hosgoren, Talanta, 2001, 53, 1083.
27. G. W. Gokel, D. M. Dishong, R. A. Schultz, V. J. Gatto,
Synthesis, 1982, 12, 997
9. B. Graham, M. J. Grannas, M. T. W. Hearn, Ch. M. Kepert,
L. Spiccia, B. W. Skelton, A. H. White, Inorg. Chem., 2000,
39, 1092.
10. G. Iоnita P. Ionita, J. Inclusion Phenomena Macrocycl. Chem.,
2003, 45, 79.
11. H.ꢀJ. G. Buschmann, L. Mutinack, K. Jansen, J. Inclusion
Phenomena Macrocycl. Chem., 2001, 39, 1.
12. C. de Alwis, J. A. Crayston, T. Cromie, T. Eisenblatter,
R. W. Hay, Ya. D. Lampeka, L. V. Tsymbal, Electrochim.
Acta, 2000, 45, 2061.
28. N. G. Luk´yanenko, Ukr. Khim. Zh. [Ukr. Chem. J.], 1999,
65, No. 9, 17 (in Russian).
29. M. Pietraszkiewicz, P. Salanski, J. Jurczak, Bull. Pol. Acad.
Sci. Chem., 1985, 33, 433.
30. O. A. Gansov, A. R. Kausar, K. B. Triplet, J. Heterocycl.
Chem., 1981, 18, 297.
31. O. A. Fedorova, A. I. Vedernikov, I. E. Baronova, O. V.
Eshcheulova, E. A. Chudinova, S. P. Gromov, Izv. Akad.
Nauk, Ser. Khim., 2004, 381 [Russ. Chem. Bull., Int. Ed.,
2004, 53, 396].
13. L. Cazaux, M. Faher, A. Lopez, C. Picard, P. Tisnes,
J. Photochem. Photobiol. A: Chem., 1994, 77, 217.
14. S. P. Dix, F. Vögtle, Chem. Ber., 1980, 113, 457.
15. J. Bourson, F. Badaoui, B. Valear, J. Fluorescence, 1994,
4, 275.
16. A. P. de Silva, K. R. A. S. Sandanayake, Angew. Chem., Int.
Ed. Engl., 1990, 29, 1173.
17. O. F. Schall, G. W. Gokel, J. Am. Chem. Soc., 1994,
116, 6089.
18. O. Iranzo, T. Elmer, J. P. Richard, J. R. Morrow, Inorg.
Chem., 2003, 42, 7736.
19. L.ꢀN. Ji, X.ꢀH. Zou, J.ꢀG. Liu, Coord. Chem. Rev., 2001,
216, 513.
20. E. Blasius, P. G. Maurer, Makromol. Chem., 1977, 178, 649.
21. R. N. Greene, Pat. US 4,026,851 31 May 1977, Appl. 605,711
13 Aug 1975, 5.
32. S. Chirachanchai, S. Phongtamrug, T. Rungsimanon, Tetraꢀ
hedron Lett., 2008, 49, 3181.
33. O. A. Fedorova, A. I. Vedernikov, O. V. Eshcheulova, P. V.
Tsapenko, Yu. V. Pershina, S. P. Gromov, Izv. Akad. Nauk,
Ser. Khim., 2000, 1881 [Russ. Chem. Bull., Int. Ed., 2000,
49, 1853].
34. Y. Sakurai, M. M. ElꢀMerzabani, Chem. Pharmac. Bull.,
1965, 13, 1363.
35. J. L. Everett, W. S. J. Ross, J. Chem. Soc., 1949, 1972.
36. B. Cabezon, J. Cao, F. M. Raymo, J. F. Stoddart, A. J. P.
White, D. J. Williams, Chem. Eur. J., 2000, 6, 2262.
37. E. Weber, F. Voglte, Angew. Chem., 1980, 92, 1067.
38. SAINT. Version 6.02A, Bruker AXS Inc., Madison Wisconꢀ
sin, USA, 2001.
39. SHELXTLꢀPlus. Release 5.10, Bruker AXS Inc., Madison,
Wisconsin, USA, 1997.
22. J. S. Bradshaw, P. E. Stott, Tetrahedron, 1980, 36, 461.
23. J. Jurczak, R. Ostaszewski, P. Salanski, J. Chem. Soc., Chem.
Commun., 989, 184.
24. J. Jurczak, R. Ostaszewski, P. Salanski, T. Stankiewicz,
Tetrahedron, 1993, 49, 1471.
25. K. E. Krakowiak, J. S. Bradshaw, D. J. ZameckaꢀKrakowiak,
Chem. Rev., 1989, 89, 929.
Received June 4, 2010;
in revised form November 11, 2010