A new strategy for the synthesis of pendant benzodiazacoronands and their use as components of chromatographic stationary phases

Article abstract of DOI:10.1016/j.tet.2004.05.012

The synthesis of a novel class of functionalized benzophanes in which a (2′-hydroxy)ethoxy pendant arm is attached to the phenyl ring is reported. The reported approach, utilizes simple starting materials, and skillful organization of the synthetic steps

Full text of DOI:10.1016/j.tet.2004.05.012

Tetrahedron 60 (2004) 5769–5776
A new strategy for the synthesis of pendant benzodiazacoronands
and their use as components of chromatographic
stationary phases
Piotr Pia˛tek,a Daniel T. Gryko,b Agnieszka Szumnab and Janusz Jurczaka,b
,
*
aDepartment of Chemistry, Warsaw University, Pasteura 1, 00-273 Warsaw, Poland
bDepartment of Chemistry, Institute of Organic Chemistry of the Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 3 March 2004; revised 13 April 2004; accepted 6 May 2004
Abstract—The synthesis of a novel class of functionalized benzophanes in which a (20-hydroxy)ethoxy pendant arm is attached to the phenyl
ring is reported. The reported approach, utilizes simple starting materials, and skillful organization of the synthetic steps allows for
simultaneous transforms of the macrocyclic ring and the pendant arm. Binding studies of these systems with Pd2þ and Cd2þ cations is
described. A chromatographic stationary phase containing the benzodiazacoronand moiety was also synthesized, and found to interact
specifically with isomeric nitrobenzene derivatives.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
transformation of the original functional groups into
suitable chemical handles. Most of the existing macro-
cyclization methods however are incompatible with our
concept because highly reactive functional groups are
present in both molecules. Thus, we have chosen the
reaction of a a,v-diamines with a esters of a a,v-
dicarboxylic acids leading to the macrocyclic
diamides.10–16
Pendant benzocoronands have received much attention due
to their specific properties, diverse structures and wide
applications. They can serve as intermediates in the
construction of polymer-supported coronands,1 sensors2
and other interesting architectures.3,4 In the field of liquid
chromatography, functionalized benzocoronands have been
used as components of the chromatographic stationary
phases. These phases have been used to separate alkali and
alkaline earth metal ions.5 In contrast, azacoronands have
rarely been applied in chromatography,6 in spite of their
interesting binding properties.7
Our interest in the development of the easily accessible
stationary phases stems from our work in the field of
enantioselective catalysis.17 With the increasing occurrence
of troublesome separations of enantiomers, new highly
selective chiral columns are desirable. In this paper, we
describe the synthesis and binding properties of a series of
benzocoronands functionalized at the 3- as well as the
4-position of the benzene ring. A novel type of the crown-
ether stationary phase was prepared and used as a new
stationary phase in HPLC experiments. The selectivity of
this stationary phase was evaluated by examining the
separation of the positional isomers of chloronitrobenzene.
The most common synthesis of pendant benzocoronands
utilizes a two-step procedure, namely macrocyclization
followed by functionalization of the benzene ring via an
electrophilic aromatic substitution reaction. Because of the
directional effect of the substituents, this strategy leads to
coronands having a 4-substituted benzene ring.8 Only a few
examples of 3-substituted benzocoronands have been
reported in the literature and their synthesis require special
synthetic procedures.9 Our general idea was to reverse the
order of these steps, so as to obtain the appropriate benzene
derivatives and use them in the macrocyclization reaction.
Such a process would be the most efficient means of
constructing this class of compounds since it allows parallel
2. Results and discussion
We have proposed that tripodal esters could be used in a
double-amidation reaction to afford appropriately substi-
tuted diazacoronands in just three steps starting from
commercially available phenols. The crucial issue was
whether such esters would react with diamines to give the
respective diamides leaving one free ester group. Recently,
Keywords: Amides; Chromatography; Macrocyclization; Coronands.
*
Corresponding author. Tel.: þ4822-6323221; fax: þ4822-6316681;
e-mail address: jurczak@icho.edu.pl
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.05.012

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we have shown that trimethyl pyridine-2,4,6-tricarboxylate
reacts at only at 2- and 6-positions leaving a free ester group
at 4-position.16
compounds. One such compound, 13, was isolated and
fully characterized. Interestingly, we proved previously
that, for benzene derivatives, even a large group located
para to the OCH2CO2Me arm did not influence the yield of
macrocyclization.11 Present results, (i.e., ester 4) indicate
that the additional arm diminishes yields of macrocyclic
products. This is most likely because the additional arm
reacts with diamines, giving rise to more non-macrocyclic
products (similar to 13) via intermediates which cannot
cyclize. Decrease of the yield of formation of 9 could also be
explained by the competitive 1,3-macrocyclization. Indeed,
we isolated compound 12, but only in 3% yield. Therefore,
the competitive 1,3-macrocyclization reaction is not the
main factor which decreases the yield of compounds 10 and
11. It is known that tert-butyl esters are unreactive toward
diamines but do react in the presence of DBU or analogous
bases.18,19 tert-Butyl ester 5 proved to be an exception and
we failed to obtain any macrocyclic products from the
reaction of 5 with 6 or 7 even in the presence of DBU.
Thus, using well known conditions, pyrogallol 1 and 1,2,4-
trihydroxybenzene 2 were elongated with methyl bromo-
acetate (Scheme 1). While ester 3 was obtained in almost
quantitative yield (92%), the preparation of the ester 4 was
much less efficient (42%). Therefore, we decided to also
obtain tert-butyl ester 5, hoping that this molecule would be
also suitable for macrocyclization. The Williamson syn-
thesis carried out in DMF gave ester 5 in 81% yield.
The trimethyl esters 2 and 4 reacted with stoichiometric
amounts of a,v-diamines 6 and 7 to afford functionalized
macrocyclic diamides 8-11 in good yields (Scheme 1). The
yields were approximately 30% lower than those of the non-
armed analogs of esters 3 and 4 with the same diamines.11
The presence of the side arm near the reaction centers, as in
compound 3, probably disturbs the closure of the macro-
cyclic ring and favors the formation of open-chain
We were able to obtain crystals suitable for X-ray analysis
Scheme 1.

P. Pia˛tek et al. / Tetrahedron 60 (2004) 5769–5776
5771
for the macrocyclic diamide 9. The 18-membered ring of
diamide 9 is considerably distorted from the typical crown
conformation (Fig. 1). For example, one of the amide groups
is co-planar with the benzene ring and makes a short contact
between amide hydrogen H19 and phenolic oxygen atom
O22. Such a short 1,4 intramolecular contact is typical for
the amide-ether based macrocycles.11 Similarly, the other
amide group makes a contact with the second phenolic
oxygen atom (O7). However, the position of the amide
group, as a whole, is quite different: the group is
perpendicular to the benzene ring. This likely is due to the
steric hindrance caused by the ‘free’ ester arm. Analysis of
the non-bonding contacts implies that a co-planar position-
ing of this amide group would create unusually short
contacts between the methylene group (C8) and the third
phenolic oxygen (O23). Indeed, the unsubstituted ‘arm-free’
analogue of 9 exhibits crown-like conformation,11 we
conclude that the presence of an additional arm in the
ortho position of the macrocyclic ring, albeit external,
causes considerable changes in its conformation.
in binding process than group located at the position 4; (2)
availability of precursor (pyrogallol is drastically cheaper
than 1,2,4-trihydroxybenzene). In order to introduce
different functional groups into the macrocycle we con-
verted diamine 15 into corresponding the N,N0-dibenzoyl
derivative 18 (Scheme 1).
Before entering the next stage of our study, we decided to
perform the preliminary binding studies of selected
compounds with metal cations. Voltamperometric tech-
nique have allowed as to calculate the stability constants,
and to determine the relative complexation dynamics. Our
previous has shown that macrocyclic amides form strong
complexes with Pd2þ and Cd2þ cations.14,19 Therefore, we
decided to test these cations as a probe of the binding
abilities of macrocyclic diamide 9, diamine 15, bis(benza-
mide) 18 and benzo-1,10-diaza-18-crown-6. Diamine 15
displays the highest affinity for both Pd2þ and Cd2þ cations
(Table 1). This binding is higher than that of benzo-1,10-
diaza-18-crown-6 (log b 4.8 and 4.2, respectively) which
indicates participation of the pendant hydroxy group in
binding of cadmium(II). Although diamide 9 has the lowest
affinity for Cd2þ, bis(benzamide) 18 having a hydroxy-
ethylene arm forms complexes of moderate strength.
Voltamperometric studies also reveal that the binding/
release equilibrium is slow for both 9 and 12. In contrast, the
equilibrium of binding between ligand 18 and cadmium(II)
is fast. Therefore, compound 18 appeared to be the most
suitable candidate for use as chromatographic stationary
Reaction of diamides 8-11 with borane–methyl sulfide
complex, followed by acid hydrolysis afforded diamines
14-17 respectively possessing side arms bearing hydroxyl
groups. These compounds were isolated in yields between
47 and 88%. Compound 15 was chosen as substrate for the
synthesis of stationary phase due to the two reasons: (1)
pendant arm located at the position 3 can interact with
macrocyclic ring and thereof play significantly bigger role
Figure 1. X-ray structure of bisamide 9.

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P. Pia˛tek et al. / Tetrahedron 60 (2004) 5769–5776
Table 1. Stability constants (log b) of complexes of Cd2þ and Pb2þ with
benzo-1,10-diaza-18-crown-6 and compounds 9, 15 and 18 in CH3CN
bonded phase showed the loading to be approximately
0.14 mmol (based on carbon) of the macrocyclic selector
per gram of the stationary phase CSP-1. This stationary
phase was slurry-packed into a stainless-steel HPLC column
and the residual silanol groups were endcapped with
trimethylsilane groups to minimize nonspecific retention
of analytes. To evaluate the nonspecific retention of the
silica surface a reference column was packed with
unmodified silica that was also endcapped.
Benzo-1,10-diaza-18-crown-6
9
15
18
Cd2þ
Pb2þ
4.2
Not determined
2.5
4.3
4.8
4.8
3.5
Not determined
phase modifier. Furthermore, the terminal hydroxy group of
18 is perfectly suited for the Pirkle method for binding to
silica gel.20
The chromatographic performance of CSP-1 was tested for
its ability to separate isomers of nitrobenzene derivatives. In
an initial chromatographic experiment, we attempted to
separate the mixture of isomeric chloronitrobenzenes on the
reference column. As shown in Figure 2, only ortho-
chloronitrobenzene was resolved whereas the para and meta
isomers remained unresolved. Next, chromatography was
performed with the CSP-1 column. The retention times of
all three isomers of chloronitrobenzene increased (Fig. 3).
Moreover, the para and meta isomers were separated with
baseline resolution. These results clearly demonstrate that
the benzodiazacoronand moiety interacts specifically with
analytes. Currently, the nature of these interactions remains
unknown. Similar results were obtained in comparative
chromatographic experiments with nitrotoluene isomers
(Fig. 4).
The synthesis of an attachable macrocycle starts from
compound 18. The terminal hydroxy group was alkylated by
allyl bromide in the presence of sodium hydride. Hydro-
silylation of 19 with chlorodimethylsilane followed by
treatment with ethanol led to the benzodiazacoronand
containing ethoxysilane, 20 (Scheme 2).20 This ethoxy
compound was heated with silica gel to form the
benzodiazacoronand-modified chromatographic stationary
phase CSP-1. Elemental analysis of the thoroughly dried
Figure 2.
In conclusion, we have established a convenient method for
the synthesis of 3- as well as 4-pendant benzodiaza-
coronands. The dissymmetrization of simple substrates
and parallel functional groups transformations make it
possible to decrease the amount of steps necessary to
synthesize these targets while maintaining their complex
structure. The functionalized benzodiazacoronand was used
to prepare the chromatographic stationary phase CSP-1. We
have demonstrated that CSP-1 selectively interacts with
nitrobenzene derivatives. The data described herein is both
Scheme 2.

P. Pia˛tek et al. / Tetrahedron 60 (2004) 5769–5776
5773
3. Experimental
3.1. General methods
¨
Melting points were measured with a Kofler type (Boetius)
hot stage apparatus and are uncorrected. H NMR spectra
1
were recorded on a Varian Gemini (200 MHz) spectrometer
in CDCl3, or DMSO-d6. 13C NMR spectra were recorded on
a Varian Gemini (50 MHz) spectrometer. All chemical
shifts are quoted in parts per million relative to tetra-
methylsilane (d 0.00 ppm) and coupling constants (J) are
measured in Hertz. High-resolution mass spectrometry
(HRMS) experiments were performed on an AMD-604
Intectra instrument using the electron impact (EI) or liquid
secondary ion mass spectra (LSIMS) techniques. Column
chromatography was performed on silica gel (Kieselgel-60,
200–400 mesh).
3.2. General procedures for the synthesis of trimethyl
esters
To the solution of trihydroxybenzene (2.52 g, 20 mmol) in
dry acetone, methyl bromoacetate (11.4 g, 75 mmol) and
anhydrous K2CO3 (16.6 g, 120 mmol) were added. The
mixture was stirred vigorously at 60 8C for 72 h. After
cooling, the reaction mixture was filtered and the solvent
was removed under reduced pressure to give a yellow-
brown oil. This oil could be purified by vacuum distillation
or crystallization from MeOH.
Figure 3.
synthetically valuable, and has implications for the design
and development of chiral chromatographic stationary
phases. Their synthesis and chromatographic behavior is
currently being studied in our laboratory.
3.2.1. Triester 3. Colorless solid distilled at 170 8C
1
(0.2 mm Hg) (92%); mp 68–69 8C; H NMR (CDCl3) d
3.78 (s, 6H), 3.80 (s, 3H), 4.71 (s, 4H), 4.76 (s, 2H), 6.56 (d,
J¼8.0 Hz, 2H), 6.94 (dd, J1¼8.0 Hz, J2¼2.7 Hz, 1H); 13C
NMR (CDCl3) d 51.9, 52.1, 66.5, 69.6, 108.8, 123.9, 137.9,
151.5, 169.2, 169.7; HRMS m/z Calcd for C15H18O9 (M)þ
342.0958; found 342.0958. Anal. Calcd for C15H18O9: C,
52.6%; H, 5.3%; found: C, 52.6%; H, 5.3%.
This work was supported by the State Committee for
Scientific Research (Project 3T09A 12715). We wish to
thank the Polish Science Foundation for additional financial
support.
3.2.2. Triester 4. Colorless solid, crystallized from
1
methanol (42%); mp 66–67 8C; H NMR (CDCl3) d 3.79
(s, 3H), 3.80 (s, 3H), 3.81 (s, 3H), 4.56 (s, 2H), 4.67 (s, 2H),
4.70 (s, 2H), 6.45 (dd, J1¼8.8 Hz, J2¼2.9 Hz, 1H), 6.54 (d,
J¼2.9 Hz, 1H), 6.88 (d, J¼8.8 Hz, 1H); 13C NMR (CDCl3)
d 52.3, 52.4, 52.5, 66.0, 66.4, 67.8, 104.1, 106.4, 117.6,
143.0, 149.3, 153.8, 169.3, 169.5, 169.9; HRMS m/z Calcd
for C15H18O9 (M)þ 342.0958; found 342.0942.
3.2.3. Triester 5. To the solution of 1,2,4-trihydroxy-
benzene (1.26 g, 10 mmol) in dry DMF, tert-butyl bromo-
acetate (7.8 g, 40 mmol) and anhydrous K2CO3 (6.2 g,
45 mmol) were added. The reaction mixture was vigorously
stirred and refluxed for 1 h. After cooling, the reaction
mixture was filtered and the solvent was evaporated under
reduced pressure. The brown oil was chromatographed
(silica, hexanes:EtOAc, 3/1) to afford pure 5 as a colorless
oil. 81%; oil; 1H NMR (CDCl3) d 1.47 (s, 9H), 1.48 (s, 18H),
4.43 (s, 2H), 4.54 (s, 2H), 4.56 (s, 2H), 6.38 (dd, J1¼9.2 Hz,
J2¼3.0 Hz, 1H), 6.51 (d, J¼2.9 Hz, 1H), 6.85 (d, J¼8.9 Hz,
1H); 13C NMR (CDCl3) d 28.0, 66.2, 66.6, 68.0, 81.8, 82.1,
82.2, 103.5, 105.9, 117.0, 142.8, 149.1, 152.5, 167.6, 167.9,
168.3; HRMS m/z Calcd for C24H36O9 (M)þ 468.2359;
found 468.2344.
Figure 4.

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P. Pia˛tek et al. / Tetrahedron 60 (2004) 5769–5776
3.3. General procedures for the synthesis of macrocyclic
lactams
4.63 (s, 2H), 4.69 (s, 2H), 4.77 (s, 2H), 6.49–6.60 (m, 4H),
6.91–7.02 (m, 1H), 7.14–7.24 (m, 1H), 7.84 (br s, 1H), 8.14
(br s, 1H); 13C NMR (CDCl3) d 38.5, 38.6, 21.8, 52.0, 52.1,
65.5, 65.6, 68.4, 69.2, 69.6, 69.9, 72.8, 106.9, 107.4, 107.9,
123.8, 124.2, 125.1, 128. 0, 128.8, 137.4, 137.6, 150.7,
151.1, 168.2, 168.6, 168.8, 169.8, 170.3; HRMS m/z Calcd
for C34H44N2O18Na (MþNa)þ 791.2487; found 791.2498.
An equimolar 0.1 M methanolic solution (5 mmol each) of
the a,v-diamine and the triester was left at ambient
temperature for a period of 7 days. Then the solvent was
evaporated and the residue was chromatographed on a silica
gel column using 0.5–10% mixtures of methanol in
chloroform.
3.4. General procedure for the reduction of macrocyclic
lactams
3.3.1. Diamide 8. Colorless solid (46%); mp 254–255 8C;
1H NMR (CDCl3) d 3.66–3.57 (m, 8H), 3.79 (s, 3H), 4.45
(s, 2H), 4.62 (s, 2H), 4.70 (s, 2H), 6.50–6.57 (m, 2H), 7.03
(t, J¼8.4 Hz, 1H), 7.38 (br t, 2H); 13C NMR (CDCl3) d 37.9,
38.2, 52.3, 65.5, 67.1, 68.4, 68.6, 71.6, 106.2, 106.8, 124.5,
135.6, 150.0, 151.6, 166.8, 168.6, 168.7; HRMS m/z Calcd
for C17H22N2O8 (M)þ 382.1376; found 382.1376. Anal.
Calcd for C17H22N2O8: C, 53.4%; H, 5.8%; N, 7.3%; found:
C, 53.0%; H, 5.8%.; N, 7.1%.
Diamide (1 mmol) was dissolved in warm THF and 2 M
solution of the borane–methyl sulfide complex in THF
(9 mmol) was added. The reaction mixture was refluxed for
4 hours and cooled down. Evaporation of the solvent gave
an oily residue that was dissolved in HCl (35%, 2 mL) and
heated to 70 8C for 2 h. After cooling, the reaction mixture
was made basic (pH was set at 13–14 using aqueous NaOH)
and extracted into CH2Cl2. The combined extracts were
dried (Na2SO4), filtered, concentrated and chromatographed
(silica, CHCl3/MeOH, 98:2, then 9:1 up to 1:1).
3.3.2. Diamide 9. Colorless solid (38%); mp 103–107 8C;
1H NMR (CDCl3) d 3.56 (s, 4H), 3.62 (s, 8H); 3.79 (s, 3H),
4.57 (s, 2H), 4.59 (s, 2H), 4.70 (s, 2H), 6.50–6.63 (m, 2H),
7.02 (t, J¼8.4 Hz, 1H), 7.15 (br s, 1H), 7.51 (br s, 1H); 13C
NMR (CDCl3) d 38.8, 38.9, 52.3, 65.5, 68.3, 69.1, 69.5,
70.0, 70.1, 71.8, 107.2, 107.3, 124.6, 136.4, 151.0, 151.4,
167.8, 168.6, 169.0; HRMS m/z Calcd for C19H26N2O9
(M)þ 426.1638; found 426.1637. Anal. Calcd for
C19H26N2O9: C, 53.5%; H, 6.1%; N, 6.6%; found: C,
53.5%; H, 6.3%.; N, 6.6%.
3.4.1. Diamine 14. 47%; oil; 1H NMR (CDCl3) d 2.79–3.00
(m, 8H), 3.45 (br s, 3H), 3.61–3.69 (m, 4H), 3.86 (t,
J¼5.0 Hz, 2H), 4.15–4.02 (m, 6H), 6.50–6.55 (m, 2H),
6.91 (t, J¼8.2 Hz, 1H); 13C NMR (CDCl3) d 46.3, 47.3,
48.9, 49.4, 60.6, 66.9, 67.8, 69.2, 70.8, 72.6, 105.6, 106.9,
123.6, 137.1, 152.3, 152.8.
3.4.2. Diamine 15. 88%; oil; 1H NMR (CDCl3) d 2.79–2.95
(m, 8H), 3.53–3.65 (m, 8H), 3.87 (t, J¼4.0 Hz, 2H), 4.03 (t,
J¼3.9 Hz, 2H), 4.09–4.17 (m, 4H), 6.59 (t, J¼7.0 Hz, 2H),
6.94 (t, J¼8.2 Hz, 2H); 13C NMR (CDCl3) d 47.8, 48.1,
48.4, 49.2, 60.3, 69.3, 69.5, 69.9, 70.1, 70.4, 70.8, 72.8,
107.1, 108.3, 123.5, 138.5, 152.5, 152.8; HRMS m/z Calcd
for C18H31N2O6 (MþH)þ 371.2182; found 371.2172.
3.4.3. Diamine 16. 76%; oil; 1H NMR (CDCl3) d 2.75–2.93
(m, 8H), 3.53–3.60 (m, 4H), 3.76–3.79 (m, 2H), 3.89–4.03
(m, 6H), 6.40 (dd, J¼8.8, 2.6 Hz, 1H), 6.61 (d, J¼2.6 Hz,
1H), 6.81 (d, J¼8.8 Hz, 1H); 13C NMR (CDCl3) d 61.9,
68.5, 69.3, 69.5, 69.9, 71.3, 103.1, 106.2, 115.1, 144.2,
150.7, 155.6; HRMS m/z Calcd for C16H25N2O5 (MþH)þ
326.1841; found 326.1840.
3.3.3. Diamide 10. Colorless solid (33%); mp 220–223 8C;
1H NMR (CDCl3) d 3.62–3.71 (s, 8H), 3.81 (s, 3H); 4.43 (s,
2H), 4.44 (s, 2H), 4.61 (s, 2H), 6.41 (dd, J1¼8.4 Hz,
J2¼2.8 Hz, 1H), 6.57 (t, J¼2.8 Hz, 1H), 6.76 (d, J¼8.8 Hz,
1H), 7.34 (br s, 2H); 13C NMR (CDCl3) d 38.3, 52.3, 65.7,
66.8, 67.3, 68.9, 102.3, 104.9, 112.5, 141.2, 146.8, 152.9,
166.7, 167.2, 169.1; HRMS m/z Calcd for C17H22N2O8
(M)þ 382.1376; found 382.1395.
3.3.4. Diamide 11. Colorless solid (49%); mp 187–189 8C;
1H NMR (CDCl3) d 3.55–3.60 (m, 12H), 3.81 (s, 3H); 4.52
(s, 2H), 4.55 (s, 2H), 4.59 (s, 2H), 6.42 (dd, J1¼8.8 Hz,
J2¼2.9 Hz, 1H), 6.60 (d, J¼2.9 Hz, 1H), 6.79 (d, J¼8.8 Hz,
1H), 7.11 (br s, 2H); 13C NMR (CDCl3) d 38.7, 38.8, 52.4,
65.8, 67.7, 68.3, 69.7, 69.8, 70.2, 102.8, 105.7, 113.8, 141.8,
147.6, 153.2, 167.6, 168.1, 169.2; HRMS m/z Calcd for
C19H26N2O9 (M)þ 426.1638; found 426.1645. Anal. Calcd
for C19H26N2O9: C, 53.5%; H, 6.1%; N, 6.6%; found: C,
53.3%; H, 6.2%.; N, 6.3%.
3.4.4. Diamine 17. 68%; oil; 1H NMR (CDCl3) d 2.80–2.85
(m, 4H), 3.02–3.29 (m, 4H), 3.59–3.64 (m, 8H), 3.81–3.85
(m, 2H), 3.96–4.10 (m, 6H), 6.30 (d, J¼2.8 Hz, 1H), 6.45
(dd, J¼8.8, 2.6 Hz, 1H), 6.86 (d, J¼8.8 Hz, 1H); 13C NMR
(CDCl3) d 61.9, 68.7, 69.2, 70.7, 71.3, 71.4, 72.1, 73.5,
102.9, 105.8, 114.3, 144.2, 150.6, 155.3; HRMS m/z Calcd
for C18H30N2O6 (M)þ 370.2103; found 370.2114.
3.3.5. Diamide 12. Colorless solid (3%); mp 187–189 8C;
1H NMR (CDCl3) d 3.41–3.60 (m, 12H), 3.79 (s, 3H); 4.47
(s, 2H), 4.65 (s, 2H), 4.67 (s, 2H), 6.37 (dd, J1¼8.8 Hz,
J2¼2.8 Hz, 1H), 6.62 (d, J¼2.8 Hz, 1H), 6.83 (d, J¼8.8 Hz,
1H), 6.87 (br t, 1H), 6.92 (br t, 1H); 13C NMR (CDCl3) d
38.5, 39.1, 52.2, 67.3, 67.6, 69.4, 69.5, 69.5, 69.7, 70.3,
70.9, 104.7, 104.8, 116.4, 142.9, 149.3, 153.0, 168.1, 168.7,
169.4; HRMS m/z Calcd for C19H26N2O9 (M)þ 426.1638;
found 426.1649.
3.4.5. Compound 18. To the solution of diazacoronand 15
(1.6 g, 4.4 mmol) in CH2Cl2 (25 mL) the solution of K2CO3
(12 g, 87 mmol) in H2O was added. The reaction mixture
was cooled to 10 8C, followed by addition of benzoyl
chloride (4 mL, 34 mmol). The resulting mixture was stirred
at RT for 30 min, then diluted with CH2Cl2 (80 mL) and the
organic layer was washed with satd. NaHCO3. After
evaporation of the solvent under reduced pressure, the
pale yellow oil was chromatographed (silica, CHCl3, then
CHCl3/MeOH, 96:4), to give compound 18 as a colorless oil
1
3.3.6. Open-chain compound 13. Colorless oil; H NMR
(CDCl3) d 3.53–3.63 (m, 12H), 3.78 (s, 12H); 4.51 (s, 2H),

P. Pia˛tek et al. / Tetrahedron 60 (2004) 5769–5776
5775
(2.086 g) in 82% yield. 1H NMR (CDCl3) d 3.51–3.65 (m,
8H), 3.71–3.82 (m, 6H), 3.95–4.13 (m, 6H), 4.21–4.34 (m,
4H), 6.50–6.63 (m, 2H), 6.93–6.97 (m, 1H), 7.37 (s, 10H);
13C NMR (CDCl3) d 45.6, 46.3, 46.7, 49.5, 50.6, 60.8, 68.0,
69.1, 69.5, 69.7, 78.0, 105.4, 106.2, 123.7, 126.3, 128.2,
128.4, 129.3, 136.2, 152.5, 172.1, 172.5; HRMS m/z Calcd
for C32H38N2O8 (M)þ 578.2628; found 578.2618.
0.31%) indicated that the amount of the diazacoronand was
0.14 mmol per gram of the silica gel.
3.6. Preparation of the chromatographic column
containing CSP-1
A stainless steel column (4.6 mm£10 cm) was filled with
the suspension of CSP-1 in MeOH under pressure of ca.
60 atm. Then column was washed with CH2Cl2 (20 mL) and
solution of hexamethyldisilazane (5 mL) in CH2Cl2
(20 mL) maintaining the flow at 1.0 mL/min. The test
column (containing unmodified silica) was prepared in an
analogous manner.
3.4.6. Compound 19. To a suspension of NaH (20 mg of
60% NaH in mineral oil, 0.6 mmol) in THF, a solution of
compound 18 (290 mg, 0.5 mmol) was added dropwise.
After 15 min of stirring at RT, freshly distilled allyl bromide
(73 mg, 52 mL, 0.6 mmol) was added and the reaction
mixture was refluxed for 6 h. After cooling, the excess of
NaH was destroyed with small amount of water and all
volatile components were evaporated under reduced
pressure. Next, H2O was added to the residue and it was
extracted with CH2Cl2. The organic layer was dried
(Na2SO4) and the solvent was removed. The residue was
chromatographed (silica, acetone/hexanes, 1:1) to afford
3.7. The chromatographic experiments
The chromatographic experiments were undertaken using
LaChrom L7100 pump (Merck) and UV 486 detector
(Waters). The substances were detected by measuring the
absorbance at 254 nm. Both columns were not thermostated
and all experiments were done at RT. The mobile phase was
0.1% isopropanol in hexane; the flow was 1.0 mL/min. The
sample volume was 2 mL.
1
219 mg of compound 19 (71%). H NMR (DMSO-d6) d
3.41–3.74 (m, 8H), 3.91–4.14 (m, 16H), 4.99–5.21 (m,
2H), 5.70–5.88 (m, 1H), 6.53–6.61 (m, 2H), 6.79–6.92 (m,
1H), 7.23–7.34 (m, 10H); 13C NMR (DMSO-d6) d 46.2,
49.2, 49.7, 50.0, 67.1, 67.9, 68.9, 69.6, 70.0, 78.0, 102.3,
105.5, 106.2, 115.1, 122.5, 125.3, 127.1, 127.3, 127.8,
128.0, 135.6, 151.3, 169.7, 169.9; HRMS m/z Calcd for
C35H42N2O8 (M)þ 618.2942; found 618.2934.
3.8. The X-ray structure investigations
The crystal data for the structure were measured on
MACH3 k-diffractometer using Cu Ka radiation and
v–2u scan mode. Structure were solved using direct
methods (SHELXS program) and refined using SHELX97
program. The hydrogen atoms were treated in a mixed way.
Those of N–H, were found from Fourier differential map.
Crystal data for 9: C19H26N2Os, M¼426.42, orthorhombic,
3.4.7. Compound 20. To a solution of 19 (0.946 g,
1.53 mmol) in dry CH2Cl2, dimethylchlorosilane (15 mL)
was added followed by the solution of H2PtCl6 (10 mg) in
dry isopropanol (100 mL). The reaction mixture was
refluxed for 4 h. After cooling, the solvent and excess of
Me2SiHCl were removed under reduced pressure, and the
residue was treated with absolute ethanol (10 mL), dry
diethyl ether (10 mL) and triethylamine (10 mL). The
suspension was stirred for 2 h at RT and the precipitate
was removed by filtration. The supernatant was evaporated
and the crude product was chromatographed (silica, CHCl3,
then CHCl3/MeOH, 97:3) to yield 372 mg of 20 as a light
˚
Pca21, a¼9.694(1), b¼12.9111(5), c¼16.535(1) A,
3
3
21
˚
V¼2069.5(3) A , Z¼4, Dc¼1.369 g/cm , m¼0.929 mm
,
F000¼904, T¼273(2) K, 2umax¼66.388, 1487 reflections
collected, 1487 unique. Final GOF¼1.028, R1¼0.0400,
wR2¼0.1035, R indices based on 1487 unique reflections
(refinement on F 2), 292 parameters, 1 restraint. Crystallo-
graphic data (excluding structure factors) have been
deposited with Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 232678. Copies
of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
þ44-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
1
yellow oil (35%). H NMR (CDCl3) d 0.04 (t, J¼5.4 Hz,
6H), 0.41–0.52 (m, 2H), 1.44–1.59 (m, 3H), 3.51–3.92 (m,
14H), 3.98–4.35 (m, 16H), 6.51–6.61 (m, 2H), 6.82–6.97
(m, 1H), 7.21–7.32 (m, 10H); 13C NMR (CDCl3) d 0.1,
13.9, 23.2, 46.1, 49.6, 49.9, 50.4, 60.6, 67.4, 68.8, 70.4,
73.9, 105.9, 106.9, 123.6, 126.2, 128.0, 128.2, 128.9, 129.1,
136.1, 152.4, 171.7, 171.9.
3.9. The voltammetric studies
Voltammetric measurements were performed on a hanging-
drop mercury electrode (SMDE1, Laboratorni Pristroje,
Praha) using an Autolab electrochemical instrument (Eco
Chemie, The Netherlands). The reference electrode was a
Ag/AgCl electrode filled with 0.1 M solution of tetraethyl-
ammonium chloride in methanol connected to the cell with
an electrolytic bridge containing 0.1 M solution of tetra-
butylammonium perchlorate in acetonitrile. A piece of
platinum foil served as a counter-electrode. In all experi-
ments, 0.1 M solution of tetrabutylammonium perchlorate
(Fluka, electrochem. grade) in acetonitrile (Fluka) was used
as supporting electrolyte. All solutions were deoxygenated
with argon before the measurement. The concentrations of
cadmium and lead ions in the solution in the cell were
typically at the level of 1024 M, obtained by addition of
3.5. The chromatographic stationary phase CSP-1
The silica gel (2.5 g, Kromasil Si 60, 5 mm beads) was dried
for 10 h at 110 8C and 1 mm Hg and then suspended in dry
toluene (10 mL). A solution of compound 20 (350 mg,
0.48 mmol) in toluene (5 mL) was added to this suspension.
Toluene was removed under reduced pressure and the dry
residue was heated at 110 8C and 1 mm Hg for 24 h. Every
2 h, the modified silica gel was mixed ultrasonically for
5 min. After cooling, CSP-1 was washed with CH2Cl2
(50 mL) and MeOH (50 mL). Evaporation of the solvents
indicated that 100 mg of compound 20 remained unbound.
The modified silica gel was then heated for 5 h at 110 8C at
1 mm Hg. Combustion analysis (C, 6.43%; H, 1.11%; N,

5776
P. Pia˛tek et al. / Tetrahedron 60 (2004) 5769–5776
2003, 1002, 63–70. (c) Shi-Lu, D.; Yu-Qi, F.; Hui-Ning, D.;
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small volume of the concentrated stock solutions, CdSO4
(BDH, England) and Pb(ClO4)2 (SERVA, Germany),
respectively, directly to the cell. Concentrations of sodium
and potassium ions were changed from approximately 1024
to approximately 1022 M by addition of concentrated
NaClO4 (Koch-Light, Great Britain) and KPF6 (Fluka)
solutions. For each metal cation, a series of measurements
was made for various metal/ligand concentration ratios. For
each metal/ligand ratio, the voltammograms were measured
at scan rates of 0.05, 0.1, 0.2 and 0.4 V/s. Each
voltammogram was measured twice and averaged. The
conductometric measurements were carried out using CDM
210 conductometer (Radiometer, Denmark) equipped with a
XE 110 probe, in a continuously stirred solution from which
CO2 was removed by bubbling with argon. All measure-
ments were carried out at 20^1 8C. The results obtained
indirectly (Naþ, Kþ) may be influenced by the variation in
the ohmic drop in the solution which shifts the potential
toward positive values and apparently increases b.
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