Synthesis and conformational analysis of dicationic N,N′-bridged bis(benzimidazolium) and bis(imidazolium) macrocycles

Article abstract of DOI:10.1002/1099-0690(200108)2001:15<2861::AID-EJOC2861>3.0.CO;2-S

Two-step alkylations of benzimidazole, 2-methylbenzimidazole, and imidazole at their nitrogen atoms with various bifunctional alkylating agents have afforded a series of 16-membered quaternary azacyclophanes. Of these macrocycles, those bearing methyl or

Full text of DOI:10.1002/1099-0690(200108)2001:15<2861::AID-EJOC2861>3.0.CO;2-S

FULL PAPER
Synthesis and Conformational Analysis of Dicationic N,NЈ-Bridged
Bis(benzimidazolium) and Bis(imidazolium) Macrocycles
[a]
[a]
[a]
[a]
[b]
´
´
Istvan Bitter,* Zsolt Török, Viktor Csokai, Alajos Grün, Barbara Balazs,
[b]
[a]
[c]
[e]
´
´
´
´
´ ´
˝
Gabor Toth, György M. Keseru, Zoltan Kovari, and Matyas Czugler
Keywords: Nitrogen heterocycles / Alkylations / Cyclizations / Conformational analysis
Two-step alkylations of benzimidazole, 2-methylbenzimida- or at the aromatic bridges have been found to exist as mix-
zole, and imidazole at their nitrogen atoms with various bi-
tures of conformers. In some cases, the structures of the con-
functional alkylating agents have afforded a series of 16- formers have been determined by NMR methods and X-ray
membered quaternary azacyclophanes. Of these macro- crystallography, and have been correlated with the results of
cycles, those bearing methyl or methoxy groups on the azole
a computer-aided conformational search.
Introduction
Recently, azaaromatic onium macrocycles (cyclophanes)
have attracted much attention due to their supramolecular
structures coupled with their positively charged character.
In
biochemical
hostϪguest
processes
such
as
enzymeϪsubstrate interactions, onium compounds play an
important role in the electrostatic binding of the substrate
to the enzyme.[1] The fast rates and high specificities of en-
zymatic reactions partly originate from the electrostatic sta-
bilization of charged transition states by onium moieties.[2]
Therefore, onium cyclophanes possessing a relatively hydro-
phobic cavity (binding site) and onium residues at defined
positions on the macrocycle (catalytic site) can be used as
artificial enzymes or as receptors to study inclusion electro-
static catalysis.[1]
Although a great number of macrocyclic and linear aza-
aromatic compounds, in which quaternary ammonium units
constitute essential parts of the structure, have been known
for a long time,[1] imidazolium cyclophanes (I) (Figure 1)
have only been reported in the last few years,[3Ϫ8] despite
the fact that imidazole compounds are frequently encoun-
tered in biological systems (quite recently, benztriazolium
cyclophanes have also been described[9]).
Figure 1. General formula of N,NЈ-bridged imidazolium and
bridged 2,2Ј-biimidazolium salts
enes[10] as isolable nucleophilic carbenes derived from imid-
azolium salts by simple deprotonation. By analogy, both I
and II were expected to be potential precursors of macro-
cyclic carbenes or their tetraazafulvalene-type dimers.[11,12]
Generally, bis(azolium) salts (I) have been synthesized by
two-step procedures.[3Ϫ5,7,8,11] A bifunctional alkylating
agent (α,ω-dihaloalkanes, xylenyl bromides) is first con-
densed on the N(1) atom of imidazole or benzimidazole in
the presence of base (NaH, NaOH, KOH/PTC). In the next
step, the linear precursor thus formed is cyclized at the N(2)
atoms with the same or a different alkylating reagent to
afford quaternary salts I (Scheme 1). A similar approach
can be used for the preparation of dibenzimidazolium salts
II, although one-pot cycloalkylations of 2,2Ј-bibenzimid-
azole have also been described.[11]
Another aspect that has aroused interest in bridged bis-
(imidazolium) and dibenzimidazolium salts (Ia and IIb) has
been the recent preparation of N,NЈ-dialkylimidazol-2-ylid-
[a]
Department of Organic Chemical Technology, Budapest
University of Technology and Economics,
P. O. Box 91, 1521 Budapest, Hungary
Fax: (internat.) ϩ 36-1/463-3648
E-mail: bitter.oct@chem.bme.hu
[b]
Technical Analytical Research Group of the Hungarian
Academy of Sciences, Institute for General and Analytical
Chemistry, Budapest University of Technology and Economics,
Scheme 1. Synthetic approach to bis(imidazolium) salts I
´
´
Szent Gellert ter 4, 1111 Budapest, Hungary
[c]
Gedeon Richter Ltd., Computer Assisted Drug Discovery,
P. O. Box 27, 1475 Budapest 10, Hungary
[d]
Some interesting reactions of the bridged dications I and
II have been reported.[11,12] Treatment of the bis(imidazol-
ium) dication Ia [A,B ϭ (CH2)3] with either KH in DMSO
or with NaNH2 in NH3 afforded tetraazafulvalene IIIa (n ϭ
Department of Chemical Information Technologies, Budapest
University of Technology and Economics,
´
´
Szent Gellert ter 4, 1111 Budapest, Hungary
Chemical Research Centre, Hungarian Academy of Sciences,
P. O. Box 17, 1525 Budapest, Hungary
[e]
Eur. J. Org. Chem. 2001, 2861Ϫ2868
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0815Ϫ2861 $ 17.50ϩ.50/0
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I. Bitter et al.
FULL PAPER
3) rather than bis(carbene) IIIaЈ (n ϭ 3). A similar result alkylation of imidazole.[14] Thus, 1-(cyanoethyl)imidazole
was achieved when bis(imidazolium) dication IIa [A,B ϭ was quaternized using the appropriate alkylating agent and
(CH2)3] was reduced with Na in liquid NH3, whereas com- then the cyanoethyl group was removed (Hoffman-type
pound Ia [A,B ϭ (CH2)4] under the same conditions gave β-elimination) by treatment with aqueous NaOH or
the stable bis(carbene) IIIaЈ (n ϭ 4).[12] The corresponding ethanolic NaOEt.
doubly bridged benzimidazolium salts Ib and IIb showed
somewhat different behaviour. Electrolysis of IIb [A,B ϭ
(CH2)3,4] in MeCN at Ϫ1.1 V or treatment of Ib [A,B ϭ
(CH2)3,4] with base (NaH/MeCN, anaerobic conditions)
both led to the air-sensitive IIIb (n ϭ 3,4) and no bis(car-
bene) intermediates could be detected. Upon exposure to
air, compounds IIIb were rapidly oxidized to ureaphanes IV
(n ϭ 3, 4).[11] A further transformation of Ib (A,B ϭ
CH2CH2O) to dibenzotetra(aza)crown-6 (V) has also been
described[13] (Figure 2).
Figure 2. Chemical transformations of azolium salts I and II
It should be emphasized that, with the sole exception of
13,[13] 16-membered onium cyclophanes in which the azaar-
omatic moieties are linked through crown ether and/or ca-
lixarene subunits have not hitherto been reported. In this
paper, we report our results concerning the preparation and
conformational analysis of quaternary macrocycles of this
Scheme 2. Synthesis of the bis(benzimidazole) and bis(imidazole)
precursors
type with a view to the future exploitation of their synthetic
potential for the construction of novel ureaphane and aza-
crown supramolecules.
The cyclizations of compounds 2Ϫ7 and 11, 12 were car-
ried out using various alkylating reagents in boiling acet-
one, MeCN, or MeNO2, depending on the reactivity of the
reactants used. In the case of the more reactive imidazole
derivatives 11, 12, the alkylating agent was added dropwise
to a solution in acetone or MeCN at 60 °C. Although the
bis(benzimidazole)s are weaker nucleophiles, they were also
cyclized in MeCN with the reactive bis(2,6-chloromethyl)-
4-tert-butylphenol and bis(2,6-bromomethyl)anisole deriv-
atives. Bis(2,6-chloromethyl)pyridine and diethylene glycol
ditosylate, which reacted more sluggishly, required the use
of MeNO2 as the solvent for the ring closure. At the end
of the reaction (monitored by TLC, eluting with methanol/
water/aq. NH4Cl, 16:3:1), the products were precipitated
from the solution in moderate yields accompanied by some
minor impurities. The quaternary salts (Figure 3) were
found to be soluble in H2O and/or MeOH, EtOH, hence
the contamination could be removed by recrystallization.
Results and Discussion
Our synthetic approach was based on the two-step
method described by others[3Ϫ5,7,8,11] (Scheme 1). The linear
intermediates used, 2Ϫ7 and 11, 12, are shown in Scheme 2.
The bis(benzimidazole)s 2Ϫ7 were prepared by condensa-
tion of benzimidazole and 2-methylbenzimidazole with
bis(2-chloroethyl) ether, bis(2,6-chloromethyl)pyridine, and
bis(2,6-bromomethyl)anisoles, respectively, in toluene/
DMSO solvent mixtures in the presence of aqueous KOH
and tetrabutylammonium bromide (TBAB) as a phase-
transfer catalyst. This method was first employed by Ecke
et al.[13] for the preparation of compound 2. In contrast,
bis(imidazole)s 11, 12 were obtained using a protectionϪ
deprotection method developed for the selective mono-
2862
Eur. J. Org. Chem. 2001, 2861Ϫ2868

Dicationic N,NЈ-Bridged Bis(benzimidazolium) and Bis(imidazolium) Macrocycles
FULL PAPER
The benzimidazolium salts 13Ϫ15 and imidazolium salt
28, comprising flexible (diethylene)oxy and/or 2,6-(di-
methylene)pyridyl groups, exhibit averaged chemical shifts
for the methylene protons (Table 1). The introduction of
one phenolic moiety into the bridge (21, 22) led to a reduc-
tion in the flexibility of the macrocyclic ring, as manifested
in the ArCH2N proton signals of compounds 21 and 22
appearing at δ ϭ 5.84/5.85 as broad singlets at room tem-
perature that sharpened as the temperature was raised. The
methylene signals of the NCH2CH2O groups are also aver-
aged on the NMR time scale.
1
The H NMR spectra of those compounds (16Ϫ19) in
which the two benzimidazole moieties are linked through
(diethylene)oxy or 2,6-(dimethylene)pyridyl groups and one
2,6-(dimethylene)anisole bridge show a similar signal pat-
tern. The steric proximity of the benzimidazole NϭCH and
anisole MeO protons indicated by the NOESY cross-peaks
for 18 suggests that this molecule exists exclusively in the
cone-like conformation. The rigid conic structure is also
evidenced by the characteristic AB coupling pattern of the
ArCH2N proton signals, as well as by the diastereotopic
appearance of the geminal methylene protons in the
NCH2CH2O group (Figure 4, A). The computed structure
of 18 resembles that shown in Figure 4, B. It is of interest
to note that the conic structure is also preferred by com-
pound 20, which comprises two anisyl bridges.
To compare the flexibilities of the macrocyclic rings, we
studied the effects of a 2-Me substituent on the benzimida-
zole unit (23, 24). Here, in contrast to 21 and 22, the rota-
tion of the benzimidazole moieties is hindered by the 2-Me
groups, resulting in the co-existence of anti and syn con-
formers in a 3:1 ratio. The characteristic differences in the
Me as well as the condensed aromatic proton signals are
of diagnostic value for the determination of conformations
(Figure 5, A). In the anti conformer, the Me group is loc-
ated above the plane of the opposite benzimidazole phenyl
ring (see Figure 5, A) and due to its anisotropic shielding
Figure 3. The synthesized quaternary azolium salts
Structure Determination of the Macrocyclic
Salts
The structures of the macrocycles were determined by 1H effect the Me signal is subjected to a significant upfield shift
NMR measurements (NOESY and ROESY) and, in the and appears at δ ϭ 1.99. In the minor syn conformer, the
case of compound 30, by X-ray crystallography. In some Me groups (δ ϭ 2.92) are unaffected, but the steric proxim-
instances, conformational analyses were carried out by ity of the two benzimidazole rings is reflected in a diamag-
computational methods. The conformational spaces of 18 netic shielding of the aromatic proton signals. Once again,
and of anti- and syn-23 were explored by the particularly computer-aided analysis supported the structures suggested
efficient Low-Mode (LMOD) conformational search proto- by the NMR-spectroscopic data (Figure 5, B).
col[15] as implemented in BatchMin 7.0 (MacroModel
The total energies of the anti and syn conformations of
V7.0).[16] These LMOD calculations were carried out using 23 were calculated to be 54.42 and 52.97 kJ/mol, respect-
the MM2 force field[17] and a distance-dependent dielectric ively; conformational free energies were estimated as
constant (ε ϭ 1.0). 5000 LMOD search steps were applied 954.28 and 955.60 kJ/mol, respectively, by MINTA. Al-
for each molecule and unique conformations within 50 kJ/ though the calculated difference in the total energies sug-
mol of the global minimum after energy minimization were gests a syn preference, the difference in free energies
retained for the MINTA calculation.[18] The MINTA integ- (∆G°)[19] is 1.32 kJ/mol in the present case, which, accord-
rals providing the basis for the binding free-energy calcula- ing to the linear relationship with product distribution,
tion were evaluated as block averages using 52000 inde- corresponds to a calculated anti/syn product ratio of 63:37.
pendent, single-point energy calculations per conformation. The experimental distribution of the two conformers was
Depending on the steric demand of the constituents, the found to be 3:1, which indicates that a reasonable theoret-
azolium macrocycles exist in various conformations, as can ical approximation was achieved. An analogous situation
1
be concluded from analysis of the H NMR measurements was found for 24, where the anti/syn conformer ratio was
obtained in [D6]DMSO (Table 1).
also found to be 3:1.
Eur. J. Org. Chem. 2001, 2861Ϫ2868
2863

I. Bitter et al.
PyCH2N
FULL PAPER
1
Table 1. Selected H NMR spectroscopic data (δ) for the macrocyclic azolium salts
CH2O
4.70 t
4.13 m
4.73 t
4.68 s
CH2N
3.94 t
4.84 m
3.90 t
3.90 s
CH3(O)
ArCH2N
13
14
15
28
21
22
16
5.88 s
5.85 m
5.60 s
5.84 br
5.85 br
5.58 d, 5.93 d
(J ϭ 14.7)
5.58 d, 6.04 d
(J ϭ 14.8)
5.80 s
4.05 s
4.03 s
17
5.72 d, 5.84 d
(J ϭ 15.8)
18
19
20
23
24
29
30
4.72 m
3.90 m
4.07 s
5.61 d, 5.91 d
(J ϭ 14.7)
4.00 s
5.57 d, 6.02 d
(J ϭ 14.8)
5.58 d, 5.82 d
5.59 d, 5.83 d
1.99 s (anti)
2.92 s (syn)
5.75 d, 5.83 d
(J ϭ 15.8)
(J ϭ 14.6)
(J ϭ 14.8)
4.31 s, 4.34 s
3.80, 3.86 m
3.84, 4.00 d
4.53, 4.72 m
4.70 br
4.65, 4.77 d
2.14 s (anti)
2.98 s (syn)
5.68 d, 5.91 d
5.83 m
5.40 d, 5.52 d
(J ϭ 15.2)
5.42 d, 5.51 d
(J ϭ 15.0)
3.91 s
5.18 d, 5.70 d
(J ϭ 14.5)
3.95 s (major)[a]
5.25 d, 5.66 d
(J ϭ 14.5)
3.87 s (minor)[b]
[a]
[b]
8.85 s (NCHN). Ϫ 9.62 s (NCHN).
1
Figure 5. anti/syn conformation of 23 based on H NMR (A) and
computer-aided analysis (B)
We next tried to introduce an anisyl moiety into the mac-
rocyclic ring of 23 and 24 in order to obtain sterically
1
crowded macrocycles 25Ϫ27. The H NMR spectra of the
products were complicated (some impurities could not be
removed despite repeated recrystallization) and we were un-
able to elucidate the conformations of the individual com-
ponents in the mixtures. By comparison of the spectra of
25Ϫ27 with those of 23 and 24, it seems most likely that in
the major conformers the 2-methylbenzimidazole units are
in a syn arrangement on the basis of the chemical shifts of
the Me and the aromatic proton signals: syn-23 (δ ϭ 2.92,
Figure 4. Conformation of 18 established by the steric proximity
of protons (indicated by double arrows) (A) and by computer-aided
conformational analysis (B)
2864
Eur. J. Org. Chem. 2001, 2861Ϫ2868

Dicationic N,NЈ-Bridged Bis(benzimidazolium) and Bis(imidazolium) Macrocycles
FULL PAPER
Figure 7. Perspective view of the final model of the asymmetric
unit of crystal structure 30·2H2O showing atomic and residue num-
bering for non-H atoms; broken lines indicate chemical bonds be-
tween minor disordered atomic sites, four H sites to O1W are also
due to disorder
Figure 6. Conformational equilibrium of 30 determined by
ROESY measurements
7.46, 7.87), 25 (δ ϭ 3.00, 6.78, 6.94, 7.15, 7.50), 27 (δ ϭ
3.00, 6.81, 6.91, 7.13, 7.48), syn-24 (δ ϭ 2.98, 7.29, 7.38),
26 (δ ϭ 2.84, 6.96, 7.08, 7.25). It is noteworthy that the
replacement of one pyridine unit in the imidazolium salt 28
by anisyl so as to afford 29 and 30 diminished the con-
formational motion of the ring and a 3:1 mixture of two
conformers was obtained. ROESY measurements on 30
were indicative of steric proximity of the MeO group and
the imidazole methine protons in both conformers, from
which it was concluded that these three constituents were
in a similar arrangement, but that the direction of the pyr-
idine ring was different (Figure 6).
˚
Table 2. Geometric parameters of the hydrogen bonds (A, °) for
30·2H2O with only meaningful e.s.d. values retained; translation of
symmetry codes to equivalent positions: i: x, 3/2 Ϫ y, 1/2 ϩ z; ii: 1
Ϫ x, 1 Ϫ y, 1 Ϫ z; iii: x, 1/2 Ϫ y, 1/2 ϩ z; iv: x, 1/2 Ϫ y, Ϫ1/2 ϩ z
DϪH···A
DϪH
H···A
D···A
DϪH···A
O1W-H11W···Br2i
O1W-H31W···Br1
O1W-H41W···Br1
O2W-H12W···Br2i
O2W-H22W···Br2ii
C154-H10E···Br2iii
C21-H21···O2W
0.94
1.06
1.06
1.06
1.03
0.97
0.93
0.93
0.97
2.49
2.68
2.28
2.47
2.33
2.83
2.47
2.44
2.91
3.413(6)
3.303(5)
3.303(5)
3.408(7)
3.352(8)
3.771(5)
3.255(9)
3.373(7)
3.557(6)
168
117
162
147
175
164
143
177
125
In the minor component, the significant downfield shift
C52-H52B···O1Wiv
of the signal due to the methine protons (δ ϭ 9.62) proves C61-H61A···Br1
that these protons reside in the plane of the pyridine ring,
resulting in an enhancement of the chemical shift. The same
signal in the major component is upfield shifted to δ ϭ
8.85, which can be rationalized in terms of the methine pro-
tons residing above the plane, in the diamagnetic shielding
region of the pyridine ring. We succeeded in preparing crys-
tals of 30 suitable for X-ray crystallographic analysis. Sur-
prisingly, the structure in the solid state was found to be
that of the minor rather than the major conformer. This
observation underlines the importance of phase-dependent
interactions, which can be decisive in the determination of
the actual structure.
Compound 30 crystallizes as a dihydrate from aqueous
solution and has an almost circular shape (Figure 7). As
indicated in the molecular diagram, the final structure
model comprises a disordered methoxy moiety, together
with its bridgehead carbon atom, with respect to the pyrid-
ine nitrogen atom, and vice versa. The disorder stems from
approximately 75%:25% populated and 180° rotated mo-
same position in the crystal such that the pyridine ring over-
laps with the methoxyphenyl moieties). Apart from this,
there are probable disorders in the hydrogen positions of
one of the water molecules as well. As expected, both water
molecules and both anions are extensively involved in the
hydrogen-bond network of the crystal (Table 2).
Preliminary chemical transformations of compounds 13
and 14 have been carried out. Treatment with NaH in DMF
without protection from air according to ref.[11] afforded
ureaphanes (type IV), whereas hydrolysis with strong aque-
ous base furnished dibenzo(aza)crowns (type V). These re-
sults will be reported in more detail in a forthcoming paper.
Conclusion
A series of 16-membered quaternary azacyclophanes has
lecular positions in the crystal (i.e., on average, every fourth been synthesized by the alkylation of bis(benzimidazole)
molecule is rotated by 180° and resides in essentially the and bis(imidazole) precursors with various dialkylating
Eur. J. Org. Chem. 2001, 2861Ϫ2868
2865

I. Bitter et al.
FULL PAPER
precipitated with NH4OH); Rf ϭ 0.45 (benzene/MeOH, 7:3). Ϫ 1H
NMR (CDCl3): δ ϭ 2.47 (s, 6 H, Me), 3.61 (t, 4 H, CH2N), 4.12
(t, 4 H, CH2O), 7.2 (m, 6 H, ArH), 7.67 (d, J ϭ 7.1, 2 H, ArH).
agents. The flexibility of the macrocyclic ring has been sys-
tematically varied by applying bridging units and azoles
with different steric requirements. Thus, single conformers
or mixtures of conformers were obtained, the structures of
which have been determined. According to the results of
preliminary experiments, the benzimidazolium salts may
provide a facile new access to ureaphane and azacrown sup-
ramolecules.
2,6-Bis[1-(2-methylbenzimidazolyl)methyl]pyridine (6): Reactants:
1b and bis(2,6-chloromethyl)pyridine (10 h); yield: 1.7 g (45%);
m.p. 214Ϫ216 °C (toluene); Rf ϭ 0.58 (benzene/MeOH, 8:2). Ϫ 1H
NMR (CDCl3): δ ϭ 2.57 (s, 6 H, Me), 5.34 (s, 4 H, CH2), 6.74 (d,
J ϭ 7.8 Hz, 2 H, ArH), 7.22 (m, 6 H, ArH), 7.47 (t, 1 H, ArH),
7.73 (d, J ϭ 7.9 Hz, 2 H, ArH).
2,6-Bis[1-(2-methylbenzimidazolyl)methyl]anisole (7): Reactants: 1b
and bis(2,6-bromomethyl)anisole (10 h); yield: 2.0 g (52%); m.p.
250 °C (toluene); Rf ϭ 0.44 (benzene/MeOH, 8:2). Ϫ 1H NMR
(CDCl3): δ ϭ 2.65 (s, 6 H, Me), 3.84 (s, 3 H, MeO), 5.45 (s, 4 H,
CH2), 6.66 (d, J ϭ 7.7, 2 H, ArH), 6.90 (t, 1 H, ArH), 7.26 (m, 6
H, ArH), 7.90 (d, J ϭ 7.8 Hz, 2 H, ArH).
Experimental Section
General Remarks: 1H and 13C NMR spectra were recorded with
samples in [D6]DMSO solution (unless stated otherwise) at 500 and
125 MHz, respectively, with a Bruker Avance DRX-500 spectro-
meter. Chemical shifts are given in δ units. Complete H and 13C
1
2,6-Bis[(1-imidazolyl)methyl]pyridine
(11):
1-(2-Cyanoethyl)-
signal assignments were achieved by utilizing DEPT-135, TOCSY,
HMQC, HMBC [optimized for 7 Hz long-range J(C,H) couplings],
phase-sensitive NOESY, and ROESY (τmixing ϭ 0.5 s) methods. Ϫ
Precoated silica gel plates (Merck 60 F254) were used for analytical
TLC, with benzene/MeOH (8:2 and 7:3) for the linear precursors
and MeOH/water/aq. NH4Cl (16:3:1) for the quaternary salts as
eluent mixtures. Solvents (acetone, MeCN, and MeNO2) were dried
prior to use. Ϫ Imidazole, benzimidazole, 2-methylbenzimidazole,
bis(2-chloroethyl) ether, and diethylene glycol ditosylate were pur-
chased from Fluka. Bis(2,6-chloromethyl)pyridine,[20] bis(2,6-bro-
momethyl)anisole,[21] bis(2,6-bromomethyl)-4-tert-butylanisole,[22]
bis(2,6-chloromethyl)-4-tert-butylphenol,[23] and 1-(2-cyanoethyl)-
imidazole[24] were prepared as described in the literature.
imidazole (5.45 g, 0.045 mol) and bis(2,6-chloromethyl)pyridine
(3.52 g, 0.02 mol) were refluxed in MeCN (50 mL) for 8 h. The
solvent was then removed in vacuo to leave 9 as a sticky solid,
which was redissolved in hot water (30 mL), clarified with charcoal,
and treated with 25% aqueous NaOH (10 mL) at ambient temper-
ature. The deprotection took place in 1 h to afford 11 as white solid
upon cooling of the solution. Yield: 3.0 g (65%); m.p. 118Ϫ120 °C;
Rf ϭ 0.73 (benzene/MeOH, 8:2). Ϫ 1H NMR: δ ϭ 5.64 (s, 4 H,
CH2), 7.55 (d, J ϭ 7.7 Hz, 2 H, ArH), 7.89 (s, 2 H, ArH), 7.96 (t,
1 H, ArH), 8.02 (s, 2 H, ArH), 8.81 (s, 2 H, NCHN).
4-tert-Butyl-2,6-bis[(1-imidazolyl)methyl]anisole (12): 1-(2-Cyano-
ethyl)imidazole (2.66 g, 0.022 mol) and bis(2,6-bromomethyl)-4-tert-
butylanisole (3.50 g, 0.01 mol) were allowed to react in boiling acet-
one (50 mL) for 6 h, which resulted in the formation of 10 as a
sticky solid. After decantation of the solvent, the residue was
treated with 1  NaOEt solution (25 mL) at ambient temperature,
extracted with EtOAc, and washed with water to give 12 as a white
solid. Yield: 2.8 g (85%); m.p. 170Ϫ172 °C; Rf ϭ 0.48 (benzene/
General Procedure for Synthesis of the Linear Precursors 2؊7: A
mixture of benzimidazole (1a) or 2-methylbenzimidazole (1b) (0.02
mol), toluene (20 mL), DMSO (2 mL), the alkylating agent
(0.011 mol), 50% aqueous KOH solution (8 mL), and TBAB cata-
lyst (0.25 g) was agitated at 80 °C for 8Ϫ12 h. In each case, a por-
tion of the product precipitated from the solution, was collected
by filtration and combined with the remainder recovered from the
toluene phase, washed with water, dried, and purified by recrystal-
lization to furnish a white solid.
1
MeOH, 7:3). Ϫ H NMR (CDCl3): δ ϭ 1.18 (s, 9 H, tBu), 3.53 (s,
3 H, MeO), 5.12 (s, 4 H, CH2), 6.90 (s, 2 H, ArH), 7.00 (s, 2 H,
ArH), 7.05 (s, 2 H, ArH), 7.53 (s, 2 H, NCHN).
General Procedure for the Synthesis of Quaternary Macrocycles: To
a solution of the linear precursor (5 mmol) in a dry solvent (acet-
one or MeCN: 40 mL; MeNO2: 15 mL), the appropriate alkylating
reagent (5 mmol) was either added in a single portion and the re-
sulting mixture was refluxed for 8 h (benzimidazolium macrocycles
13؊27) or a solution of the alkylating reagent (5 mmol in 15 mL
of solvent) was slowly added dropwise at 50Ϫ60 °C and the mixture
was heated to reflux for the same period (imidazolium macrocycles
28؊30). After completion of the reaction, the white solid produced
was collected by filtration, thoroughly washed with the same solv-
ent, purified by recrystallization, and dried at 80 °C in vacuo (0.1
Torr).
1,5-Bis(1-benzimidazolyl)-3-oxapentane (2): Reactants: 1a and
bis(2-chloroethyl) ether; yield: 1.8 g (60%); m.p. 104Ϫ106 °C
(EtOH/water) (ref.[13] m.p. 73 °C); Rf ϭ 0.55 (benzene/MeOH, 7:3).
Ϫ
1H NMR (CDCl3): δ ϭ 3.65 (t, 4 H, CH2N), 4.18 (t, 4 H,
CH2O), 7.23 (m, 6 H, ArH), 7.75 (m, 4 H, ArH).
2,6-Bis[(1-benzimidazolyl)methyl]pyridine (3): Reactants: 1a and
bis(2,6-chloromethyl)pyridine (10 h); yield: 3.26 g (93%); m.p.
115Ϫ117 °C (MeOH/water), Rf ϭ 0.58 (benzene/MeOH, 7:3). Ϫ
1H NMR (CDCl3): δ ϭ 5.30 (s, 4 H, CH2), 6.76 (d, J ϭ 7.8, 2 H,
ArH), 7.15 (m, 6 H, ArH), 7.38 (t, 1 H, ArH), 7.73 (d, J ϭ 7.8, 2
H, ArH), 7.92 (s, 2 H, NCHN).
Compound 13: X ϭ TsO; yield: 2.0 g (55%) (MeNO2); m.p.
270Ϫ272 °C (nPrOH) (ref.[13] m.p. 279.5Ϫ280.5 °C); Rf ϭ 0.58. Ϫ
C36H40N4O8S2 (720.87): calcd. C 59.98, H 5.59, N 7.77; found C
2,6-Bis[(1-benzimidazolyl)methyl]-4-tert-butylanisole (4): Reactants:
1a and bis(2,6-bromomethyl)-4-tert-butylanisole (8 h); yield: 2.2 g
(52%); m.p. 178Ϫ180 °C (EtOH); Rf ϭ 0.60 (benzene/MeOH, 8:2).
Ϫ H NMR (CDCl3): δ ϭ 1.08 (s, 9 H, tBu), 3.61 (s, 3 H, MeO),
5.38 (s, 4 H, CH2), 7.05 (s, 2 H, ArH), 7.28 (m, 4 H, ArH), 7.36
(m, 2 H, ArH), 7.82 (m, 2 H, ArH), 7.96 (s, 2 H, NCHN).
1
59.11, H 5.65, N 7.63. Ϫ H NMR: δ ϭ 2.28 (s, 6 H, Me of Ts),
1
3.94 (t, 8 H, CH2N), 4.70 (t, 8 H, CH2O), 7.10 (d, J ϭ 7.9, 4 H,
TsH), 7.51 (d, J ϭ 7.9 Hz, 4 H, TsH), 7.63 (q, 4 H, ArH), 8.05 (q,
4 H, ArH), 9.76 (s, 2 H, NCHN).
1,5-Bis[1-(2-methylbenzimidazolyl)]-3-oxapentane (5): Reactants: 1b
Compound 14: X ϭ Cl; yield: 1.3 g (50%) (MeNO2); m.p. Ͼ 300 °C
and bis(2-chloroethyl) ether (12 h); yield: 1.4 g (42%); m.p. (MeOH); Rf ϭ 0.42. Ϫ C28H24N6Cl2 (515.44): calcd. C 65.25, H
118Ϫ120 °C (dissolved in dilute HCl, clarified with charcoal, and
4.69, N 16.30, Cl 13.76; found C 64.89, H 4.65, N 16.08, Cl 13.58.
2866
Eur. J. Org. Chem. 2001, 2861Ϫ2868

Dicationic N,NЈ-Bridged Bis(benzimidazolium) and Bis(imidazolium) Macrocycles
FULL PAPER
1
Ϫ H NMR: δ ϭ 5.88 (s, 8 H, CH2), 7.34 (m, 8 H, ArH), 7.81 (d,
J ϭ 7.7 Hz, 4 H, ArH), 8.13 (t, 2 H, ArH), 9.80 (s, 2 H, NCHN).
Compound 22: X ϭ Cl; yield: 2.7 g (92%) (MeCN); m.p. 274Ϫ277
°C (MeOH); Rf ϭ 0.60. Ϫ C33H33N5OCl2 (586.56): calcd. C 67.57,
H 5.67, N 11.94, Cl 12.09; found C 66.87, H 5.70, N 11.75, Cl
11.96. Ϫ 1H NMR: δ ϭ 1.36 (s, 9 H, tBu), 5.80 (s, 4 H, CH2), 5.85
(br. signal, 4 H, CH2), 7.48 (t, 2 H, ArH), 7.54 (t, 2 H, ArH), 7.73
(d, 2 H, ArH), 7.86 (d, 2 H, ArH), 7.87 (s, 2 H, ArH), 8.05 (d, 2
H, ArH), 8.06 (t, 1 H, ArH), 9.40 (s, 2 H, NCHN), 10.19 (s, 1
H, OH).
Compound 15: X ϭ Cl; yield: 1.42 g (59%) (MeNO2); m.p. 285 °C
(dec.) (EtOH); Rf ϭ 0.32. Ϫ C25H25N5OCl2 (482.41): calcd. C
62.24, H 5.22, N 14.52, Cl 14.70; found C 61.89, H 5.25, N 14.40,
Cl 14.48. Ϫ 1H NMR: δ ϭ 4.13 (m, 4 H, CH2), 4.84 (m, 4 H, CH2),
5.85 (s, 4 H, CH2), 7.49 (t, 2 H, ArH), 7.56 (t, 2 H, ArH), 7.80 (d,
J ϭ 8.0 Hz, 2 H, ArH), 7.88 (d, J ϭ 8.0 Hz, 2 H, ArH), 8.07 (m,
2 H, ArH), 10.09 (s, 2 H, NCHN).
Compound 23: X ϭ TsO; yield: 1.6 g (42%) (MeNO2); m.p.
267Ϫ269 °C (EtOH); Rf ϭ 0.45. Ϫ C38H44N4O8S2 (744.84): calcd.
C 61.27, H 5.41, N 7.52; found C 60.77, H 5.45, N 7.45. Ϫ 1H
NMR: δ ϭ 1.99 (s, 6 H, Me), 3.80 and 3.86 (m, 2 ϫ 4 H, CH2),
4.53 and 4.72 (m, 2 ϫ 4 H, CH2), 7.64 (br. signal, 4 H, ArH), 8.01
(br. signal, 4 H, ArH). Minor conformer: δ ϭ 2.92 (s, 6 H, Me),
4.70 (br. signal, 16 H, CH2), 7.46 (br. signal, 4 H, ArH), 7.87 (br.
signal, 4 H, ArH).
Compound 16: X ϭ Br; yield: 1.45 g (48%) (MeCN); m.p. 260 °C
(dec.) (water); Rf ϭ 0.52. Ϫ C27H28N4O2Br2 (600.35): calcd. C
54.02, H 4.70, N 9.33, Br 26.62; found C 53.65, H 4.64, N 9.25, Br
1
26.34. Ϫ H NMR: δ ϭ 3.90 (m, 4 H, CH2), 4.05 (s, 3 H, MeO),
4.68 (s, 4 H, CH2), 5.58 (d, J ϭ 14.7, 2 H, CH2), 5.93 (d, J ϭ 14.7,
2 H, CH2), 7.35 (t, 1 H, ArH), 7.56 (m, 4 H, ArH), 7.96 (m, 2 H,
ArH), 8.11 (m, 2 H, ArH), 9.53 (s, 2 H, NCHN).
Compound 24: X ϭ Cl; yield: 1.2 g (48%) (MeNO2); m.p. Ͼ 300 °C
(EtOH); Rf ϭ 0.42. Ϫ C27H29N5OCl2 (510.47): calcd. C 62.53, H
5.73, N 13.72, Cl 13.89; found C 62.07, H 5.68, N 13.61, Cl 13.46.
Compound 17: X ϭ Br; yield: 1.75 g (56%) (MeCN); m.p. 300 °C
(water); Rf ϭ 0.56. Ϫ C30H27N5OBr2 (633.38): calcd. C 56.89, H
4.30, N 11.06, Br 25.23; found C 56.45, H 4.34, N 10.98, Br 25.04.
Ϫ
1H NMR: δ ϭ 2.14 (s, 6 H, Me), 3.84 and 4.00 (d, 2 ϫ 2 H,
1
Ϫ H NMR: δ ϭ 4.03 (s, 3 H, MeO), 5.58 (d, J ϭ 14.8 Hz, 2 H,
CH2), 4.65 and 4.77 (d, 2 ϫ 2 H, CH2), 5.68 and 5.91 (d, J ϭ
16.8 Hz, 2 ϫ 2 H, CH2), 7.64 (t, 4 H, ArH), 7.81 (d, 2 H, ArH),
7.96 (d, 2 H, ArH), 8.05 (t, 1 H, ArH), 8.06 (d, 2 H, ArH). Minor
conformer: δ ϭ 2.98 (s, 6 H, Me), 5.83 (m, 4 H, CH2), 7.29 (t, 2
H, ArH), 7.38 (t, 2 H, ArH), 7.58 (d, 2 H, ArH), 7.79 (d, 2 H,
ArH), 7.90 (d, 2 H, ArH), 8.08 (t, 2 H, ArH).
CH2), 5.72 (d, J ϭ 15.8 Hz, 2 H, CH2), 5.84 (d, J ϭ 15.8 Hz, 2 H,
CH2), 6.04 (d, J ϭ 14.8 Hz, 2 H, CH2), 7.41 (t, 1 H, ArH), 7.46 (t,
2 H, ArH), 7.53 (t, 2 H, ArH), 7.62 (d, J ϭ 8.2 Hz, 2 H, ArH),
7.88 (d, J ϭ 7.8 Hz, 2 H, ArH), 7.99 (d, J ϭ 7.7 Hz, 2 H, ArH),
8.03 (d, J ϭ 8.3 Hz, 2 H, ArH), 8.08 (t, 2 H, ArH), 9.52 (s, 2
H, NCHN).
Compound 25: X ϭ Br; yield: 2.3 g (73%) (MeCN); m.p. Ͼ 300 °C
(EtOH/water); Rf ϭ 0.47. Ϫ C29H32N4O2Br2 (628.41): calcd. C
55.43, H 5.13, N 8.92, Br 25.43; found C 54.07, H 5.18, N 8.69, Br
Compound 18: X ϭ Br; yield: 1.4 g (42%) (MeCN); m.p. 238 °C
(dec.) (water); Rf ϭ 0.40. Ϫ C31H36N4O2Br2 (656.46): calcd. C
56.72, H 5.53, N 8.53, Br 24.34; found C 56.25, H 5.54, N 8.46, Br
24.01. Ϫ 1H NMR: δ ϭ 1.32 (s, 9 H, tBu), 3.90 (m, 4 H, CH2),
4.07 (s, 3 H, MeO), 4.72 (m, 4 H, CH2), 5.61 (d, J ϭ 14.7 Hz, 2 H,
CH2), 5.91 (d, J ϭ 14.7 Hz, 2 H, CH2), 7.56 (m, 4 H, ArH), 7.98
(m, 2 H, ArH), 8.01 (m, 2 H, ArH), 8.19 (d, J ϭ 7.3 Hz, 2 H,
ArH), 9.64 (s, 2 H, NCHN).
1
26.16. Ϫ H NMR (selected data for the major component): δ ϭ
3.00 (s, Me), 6.78, 6.94, 7.15, 7.50 (br. s, ArH).
Compound 26: X ϭ Br; yield: 1.7 g (51%) (MeCN); m.p. 266Ϫ270
°C (EtOH/water); Rf ϭ 0.41. Ϫ C32H31N5OBr2 (661.44): calcd. C
58.11, H 4.72, N 10.59, Br 24.16; found C 57.57, H 4.68, N 10.39,
Br 24.97. Ϫ 1H NMR (selected data for the major component):
δ ϭ 2.84 (s, Me), 6.96, 7.08, 7.25 (br. s, ArH).
Compound 19: X ϭ Br; yield: 1.6 g (46%) (MeCN); m.p. 240 °C
(dec.) (MeOH); Rf ϭ 0.78. Ϫ C34H35N5OBr2 (689.49): calcd. C
59.23, H 5.12, N 10.16, Br 23.18; found C 58.65, H 5.15, N 9.98,
Compound 27: X ϭ Br; yield: 2.2 g (66%) (MeCN); m.p. 266Ϫ268
°C (dec.) (EtOH); Rf ϭ 0.44. Ϫ C32H38N4O2Br2 (670.49): calcd. C
57.32, H 5.71, N 8.36, Br 22.83; found C 56.09, H 5.67, N 8.29, Br
1
Br 22.91. Ϫ H NMR: δ ϭ 1.39 (s, 9 H, tBu), 4.00 (s, 3 H, MeO),
5.58 (d, J ϭ 14.8 Hz, 2 H, CH2), 5.75 (d, J ϭ 15.8, 2 H, CH2), 5.83
(d, J ϭ 15.8 Hz, 2 H, CH2), 6.02 (d, J ϭ 14.7 Hz, 2 H, CH2), 7.46
(t, 2 H, ArH), 7.54 (t, 2 H, ArH), 7.65 (d, J ϭ 8.0 Hz, 2 H, ArH),
7.88 (d, J ϭ 7.4 Hz, 2 H, ArH), 8.08 (m, 5 H, ArH), 9.51 (s, 2
H, NCHN).
1
23.54. Ϫ H NMR (selected data for the major component): δ ϭ
3.00 (s, Me), 6.81, 6.91, 7.13, 7.48 (br. s, ArH).
Compound 28: X ϭ Cl; yield: 0.95 g (46%) (acetone); m.p. Ͼ 300
°C (water); Rf ϭ 0.32. Ϫ C20H20N6Cl2 (415.32): calcd. C 57.84, H
4.85, N 20.23, Cl 17.07; found C 57.32, H 4.90, N 20.11, Cl 16.94.
Compound 20: X ϭ Br; yield: 2.0 g (56%) (MeCN); m.p. Ͼ 300 °C
(MeOH/water); Rf ϭ 0.55. Ϫ C36H38N4O2Br2 (718.53): calcd. C
60.18, H 5.33, N 7.80, Br 22.24; found C 56.65, H 5.37, N 7.68, Br
22.31. Ϫ 1H NMR: δ ϭ 1.26 (s, 9 H, tBu), 4.31 (s, 3 H, MeO), 4.34
(s, 3 H, MeO), 5.58 and 5.82 (d, J ϭ 14.6, 2 ϫ 2 H, CH2), 5.59 and
5.83 (d, J ϭ 14.8, 2 ϫ 2 H, CH2), 7.19 (t, 1 H, ArH), 7.47 (m, 4
H, ArH), 7.95 (d, J ϭ 7.7, 2 H, ArH), 8.00 (s, 2 H, ArH), 8.06
(d, J ϭ 7.6, 2 H, ArH), 8.12 (d, J ϭ 7.6, 2 H, ArH), 9.95 (s, 2
H, NCHN).
1
Ϫ H NMR: δ ϭ 5.60 (s, 8 H, CH2), 7.59 (d, 4 H, ArH), 7.64 (s,
4 H, ArH), 8.00 (t, 2 H, ArH), 9.17 (s, 2 H, NCHN).
Compound 29: X ϭ Br; yield: 1.65 g (56%) (MeCN); m.p. Ͼ 300 °C
(water); Rf ϭ 0.55. Ϫ C26H31N5OBr2 (589.37): calcd. C 52.99, H
5.30, N 11.88, Br 27.11; found C 52.42, H 5.25, N 11.67, Br 26.90.
1
Ϫ H NMR: δ ϭ 1.28 (s, 9 H, tBu), 3.91 (s, 3 H, MeO), 5.18 (d,
J ϭ 14.5 Hz, 2 H, CH2), 5.40 (d, J ϭ 15.2 Hz, 2 H, CH2), 5.52 (d,
J ϭ 15.1 Hz, 2 H, CH2), 5.70 (d, J ϭ 14.5 Hz, 2 H, CH2), 7.44 (d,
J ϭ 12.1 Hz, 4 H, ArH), 7.67 (d, J ϭ 7.7 Hz, 2 H, ArH), 7.75 (s,
2 H, ArH), 8.01 (t, 1 H, ArH), 8.72 (s, 2 H, NCHN).
Compound 21: X ϭ Cl; yield: 2.45 g (86%) (MeCN); m.p. 260Ϫ262
°C (MeOH); Rf ϭ 0.65. Ϫ C31H36N4OCl2 (567.56): calcd. C 65.60,
H 6.39, N 9.87, Cl 12.49; found C 65.05, H 6.37, N 9.68, Cl 12.30. Compound 30: X ϭ Br; yield: 1.1 g (41%) (acetone); m.p. 250 °C
1
Ϫ H NMR: δ ϭ 1.31 (s, 9 H, tBu), 3.90 (t, 4 H, CH2), 4.73 (t, 4
(dec.) (water); Rf ϭ 0.43. Ϫ C22H23N5OBr2 (533.26): calcd. C
H, CH2), 5.84 (br. signal, 4 H, CH2), 7.57 (t, 2 H, ArH), 7.59 (t, 2 49.55, H 4.35, N 13.13, Br 29.97; found C 48.99, H 4.37, N 12.98,
1
H, ArH), 7.81 (s, 2 H, ArH), 7.98 (d, J ϭ 8.0 Hz, 2 H, ArH), 8.16 Br 29.42. Ϫ H NMR: δ ϭ 3.95 (s, 3 H, MeO), 5.25 and 5.66 (d,
(d, J ϭ 7.5 Hz, 2 H, ArH), 9.62 (s, 2 H, NCHN).
Eur. J. Org. Chem. 2001, 2861Ϫ2868
J ϭ 14.5 Hz, 2 ϫ 2 H, CH2), 5.42 and 5.51 (d, J ϭ 15.0 Hz, 2 ϫ 2
2867

I. Bitter et al.
FULL PAPER
H, CH2), 7.34 (t, 1 H, ArH), 7.61 (s, 2 H, ArH), 7.62 (d, 2 H, authors (B. B.) thanks the Hungarian Higher Education and Re-
ArH), 7.74 (d, 2 H, ArH), 7.79 (s, 2 H, ArH), 7.98 (t, 2 H, ArH), search Foundation (Budapest) for a Z. Magyary fellowship.
8.85 (s, 2 H, NCHN). Minor conformer: δ ϭ 3.87 (s, 3 H, MeO),
[1]
7.28 (t, 1 H, ArH), 7.41 (d, 2 H, ArH), 7.49 (d, 2 H, ArH), 7.85
(s, 2 H, ArH), 7.88 (s, 2 H, ArH), 7.98 (t, 2 H, ArH), 9.62 (s, 2
H, NCHN).
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[2]
[3]
X-ray Crystallographic Study: Shiny needle-like crystals of 30·2H2O
were grown by diffusion of acetone vapour into an aqueous solu-
tion of 30 equilibrated at ambient temperature. Crystals suitable
for X-ray diffraction measurements were formed within 48Ϫ72 h.
A selected crystal was sealed in a capillary; it would have decom-
posed in about a minute if exposed to air. Diffraction data were
collected at ambient temperature with an automated four-circle in-
strument[25] [C22H23N5OBr2·2H2O, monoclinic space group P21/c
[4]
[5]
[6]
[7]
[8]
˚
(No. 14), a ϭ 17.439(4), b ϭ 9.191(1), c ϭ 17.781(3) A, β ϭ
3
117.15(1)°, V ϭ 2535.9(8) A , Z ϭ 4, Dcalcd. ϭ 1.491 g/cm3]. Of
˚
5793 collected reflections, 5478 were considered as independent
(Rint ϭ 0.014) and were subsequently corrected for absorption ef-
fects using a semiempirical approach.[26] An initial structure model
was obtained by a direct method procedure (SHELXS-97)[27] as
30·3H2O. This model was easily refined[28] by applying anisotropic
displacement parameters for the non-hydrogen atoms [R1 ϭ 0.0530
for 2492 Fo Ͼ 4σ(Fo) and 0.1486 for all 5490 data]. However, unusu-
ally high ADPs at the methoxy group and at the bridgehead C
atom, the pyridine N atom, and at a putative water site enclosed
in the cavity, together with a significant residual density linking the
[9]
[10]
[11]
[12]
[13]
M. Ecke, M. Mühlstädt, K. Hollmann, J. Prakt. Chem. 1994,
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[14]
[15]
´
A. Horvath, Synthesis 1994, 102Ϫ106.
´
I. Kolossvary, W. C. Guida, J. Am. Chem. Soc. 1996, 118,
5011Ϫ5019.
˚
pyridine N atom to this ‘‘water’’ at a distance of 1.5 A, all pointed
[16]
F. Mohamadi, N. G. J. Richards, W. C. Guida, R. Liskamp,
M. Lipton, C. Caufield, G. Chang, T. Hendrickson, W. C. Still,
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to the existence of a disorder in the structure. Indeed, a highly
symmetrical molecular shape was confirmed by analysis of the non-
crystallographic symmetry [C2v Continuous Symmetry Measure
[17]
[18]
[19]
N. L. Allinger, J. Am. Chem. Soc. 1977, 99, 8127Ϫ8134.
˚
´
I. Kolossvary, J. Phys. Chem. 1997, A101, 9900Ϫ9905.
(CSM): 2.43; average R.M.S. deviation 0.4 A, program PLA-
TON,[29] and references therein]. A subsequent disorder model was
then refined to convergence and adopted as the final structure
model [final residuals: R1 ϭ 0.0545 for 2480 Fo Ͼ 4σ(Fo) and 0.1502
for all 5478 data and 301 parameters]. Some atoms of the disor-
dered parts of the model were treated with isotropic displacement
parameters in order to avoid matrix singularities in the refinement.
The symmetry measures of this model as implemented in PLATON
suggest a fairly symmetrical self-complementary molecular shape
(CSM data for the Cs[x,y,Ϫz] symmetry element in the final model
were: CSM ϭ 0.274, max. diff.: 0.097, RMS ϭ 0.052, tolerance:
0.20).[30] Ϫ Crystallographic data (excluding structure factors) for
the structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary pub-
lication no. CCDC-155924. Copies of the data can be obtained free
of charge on application to the CCDC, 12 Union Road, Cambridge
CB2 1EZ, U.K. [Fax: (internat.) ϩ 44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
´
´
M. Nogradi, Stereoselective Synthesis, VCH, Weinheim, 1987,
pp. 49Ϫ50.
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
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CAD4 Express program package, EnrafϪNonius, Delft, The
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Acknowledgments
This project was supported by the Hungarian Research Fund
(OTKA No. T 030280 and partly No. T 025910) and one of the
Received January 31, 2001
[O01040]
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