Synthesis of calix[4]arene-cyclen conjugates

Article abstract of DOI:10.1016/j.tet.2006.03.083

Novel calix[4]arene derivatives constrained in the cone or 1,3-alternate conformations, bearing one or two cyclen (1,4,7,10-tetraazacyclododecane) moieties directly connected to the upper rim, have been synthesized using Buchwald-Hartwig coupling reaction. The complexation ability and hydrolytic activities of selected Zn(II) complexes of these calixarenes were studied. Although the attempts to hydrolyze activated phosphodiester bonds were unsuccessful, the NMR titration experiments revealed binding affinity for chloride, acetate, and benzoate anions in defined stoichiometry.

Full text of DOI:10.1016/j.tet.2006.03.083

Tetrahedron 62 (2006) 5748–5755
Synthesis of calix[4]arene–cyclen conjugates
a
a,*
a
b,*
V a´ clav Stastny, Pavel Lhot a´ k, Ivan Stibor and Burkhard K o¨ nig
a
Department of Organic Chemistry, Institute of Chemical Technology, Technick a´ 5, 16628 Prague 6, Czech Republic
b
Institut f u¨ r Organische Chemie, Universit a¨ t Regensburg, 93040 Regensburg, Germany
Received 10 January 2006; revised 1 March 2006; accepted 23 March 2006
Available online 27 April 2006
Abstract—Novel calix[4]arene derivatives constrained in the cone or 1,3-alternate conformations, bearing one or two cyclen (1,4,7,10-
tetraazacyclododecane) moieties directly connected to the upper rim, have been synthesized using Buchwald–Hartwig coupling reaction.
The complexation ability and hydrolytic activities of selected Zn(II) complexes of these calixarenes were studied. Although the attempts
to hydrolyze activated phosphodiester bonds were unsuccessful, the NMR titration experiments revealed binding affinity for chloride, acetate,
and benzoate anions in defined stoichiometry.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
1,4,7,10-Tetraazacyclododecane (cyclen) and its metallated
analogues have been widely used in molecular recognition
2.1. Synthesis
1
2
and supramolecular catalysis as artificial metalloenzymes.
The cyclen moiety is known as a good ligand possessing
very high affinity towards transition metals and lanthanide
Based on the previous results on the N-arylation of 1,4,7,10-
1
0
tetraazacyclododecanes, we used the Buchwald–Hartwig
coupling reaction as a synthetic tool for direct N-aryl con-
nection. To the best of our knowledge, this method, based
on the application of recently developed palladium-cata-
3
4
ions. Some metal ions, such as zinc(II), behave as Lewis
acids when coordinated with the ligand and offer free bind-
ing sites (depending on the nature and properties of their
coordination sphere) suitable for reversible coordination of
1
1,12
lyzed N-arylation procedures,
has never been used in
calixarene chemistry so far. The synthesis of tris(Boc)cycl-
enylcalix[4]arenes 8 and 9 in the cone conformation, and
consequently, the formation of their Lewis-acidic Zn(II)
complexes, was accomplished according to Scheme 1.
Starting calix[4]arene 3 was selectively monobrominated
according to a known procedure using 1 equiv of N-bromo-
succinimide in butane-2-one at ambient temperature to
give monobromocalix[4]arene 6 in 55% yield. On the other
hand, dibromocalix[4]arene 7 was obtained in 83% overall
yield by regioselective bromination of dipropoxycalix[4]-
arene 4 using bromine in chloroform at 0 C (intermediate
5 formed in 95% yield) followed by alkylation with propyl
iodide in DMF in the presence of NaH (product 7, 87%
yield) as described by Casnati et al. Both bromocalix[4]-
arenes 6 and 7 were then subjected to the Buchwald–Hartwig
Pd-catalyzed amination reaction with 1,4,7-tris(Boc)cyclen
2. The cyclen 1 was protected before coupling reaction to
avoid the connection of more calixarene molecules on its
skeleton. Since the Boc (tert-butoxycarbonyl) group has
been proven as the most effective protecting group for the
5
the corresponding binding partners (Lewis bases). As the
above metal complexes represent suitable binding sites
for a variety of anionic guest molecules, the attachment
of cyclen moieties to an appropriate rigid scaffold should
lead to highly preorganized artificial receptors with poten-
2
2
6
,7
8,9
tial applications as metalloenzymes. Calix[4]arenes,
due to their unique three-dimensional structures, easy de-
rivatization, and the tunable shape of the molecules, repre-
sent ideal candidates for such a molecular scaffold. While
the connection of calix[4]arene and cyclen moieties via
ꢀ
7
a spacer unit has been published very recently, we as-
sumed that using a rigid connection between the two sub-
units could result in a higher degree of preorganization and
enhanced binding properties. In this paper, we report on the
synthesis of novel calix[4]arene–cyclen conjugates with
the cyclen moiety directly attached to the upper rim of
calix[4]arene.
2
3
1
3
synthesis of cyclic polyamines, we subjected cyclen 1 to
the reaction with 2.75 equiv of Boc O in DCM to form the
protected cyclen 2 in 75% yield. The coupling reaction be-
tween bromocalixarene 6 blocked in the cone conformation
2
1
d
*
0
Corresponding authors. Tel.: +420 220 445 055; fax: +420 220 444 288;
e-mail: lhotakp@vscht.cz
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.083

V. Stastny et al. / Tetrahedron 62 (2006) 5748–5755
5749
H
H
4 (CF COO)-
3
H
N
N+
H
N+
H
N+
H
N
N H
H
H
H
N+
Boc
N
N
O
Pr
O
O
O
R
R
Pr
Pr
Pr
b)
3
Boc
N
N
Boc
f)
g)
8
, 9
N
Br
O
Pr
O
O
O
O
Pr
O
O
O
Pr
Pr
e)
Pr
12 : R=H
13 : R= cyclen-1-yl
Pr
Pr
Pr
1
0 : R=H
O
Pr
11 : R=[4H+]cyclen-1-yl-
O
Pr
O
O
O
O
O
H
O
Pr
tetrakis(trifluoroacetate)
H
Pr
Pr
Pr
Pr
Pr
H
6
8
2 (ClO
)-
4
N
H
H
Boc
Boc
N
N
N
N
N
2+
N
H
N
Zn
N
a)
N
Boc
N
Boc
N
N
N
H
H
Boc
Boc
Boc
N
N
2
N
1
N
Boc
Boc
h)
Br
N
N
Br
1
2
O
Pr
O
O
O
e)
Pr
Pr
Pr
1
4
O
Pr
O
O O
Pr
O
O
O
Pr
O
2 (ClO4)-
H
H
H
N
)-
2 (ClO
H
Pr
Pr
N
4
Pr
Pr
Pr
H
2
+
9
2+
N
N
7
Zn
Zn
N
N
d)
H
N
N
Br
Br
h)
c)
1
3
O
Pr
O
Pr
O
O
O
O
Pr
O
O
O
O
O
O
Pr
H
Pr
H
Pr
H
Pr
H
Pr
1
5
5
4
ꢀ
ꢀ
Scheme 1. (a) 2.75 equiv (Boc)
87%); (e) Pd(OAc) , P(t-Bu)
O 10:1 (v/v) (quant.); (h) Zn(ClO
2
O, CH
2
Cl , rt (75%); (b) 1 equiv NBS, butane-2-one, rt (55%); (c) Br
2
2
, CHCl
Cl
3
, 0 C (95%); (d) PrI, NaH, DMF, ꢁ10 C to rt
ꢀ
Ó
(
H
2
3
, t-BuONa, toluene, 80–90 C (66% for 8, 65% for 9); (f) CF
3
COOH, CH
2
2
, rt (quant.); (g) Ion exchanger III; Merck , CH
3
OH–
2
4
)
2
2 3
$6H O, CH OH, rt (quant.).
and threefold Boc-protected cyclen 2 was carried out in dry
toluene at 80–90 C in the presence of stoichiometric
It is known that the reaction rate of the Pd-catalyzed amina-
tion reaction is determined by the reductive elimination step
ꢀ
amount of base (t-BuONa), a catalytic amount of palladium
acetate, and the corresponding phosphine ligand (see Table
1
4
in the catalytic cycle, which can be considerably influ-
enced by electronic and steric effects of phosphine ligands
used. Indeed, the successful application of more bulky and
electron rich phosphine ligands such as PCy and P(t-Bu)
1
the attempts of N-arylation of Boc-protected cyclen using
). Triphenylphosphine was described as the best ligand in
3
3
1
0
simple aryl halides. However, as shown in Table 1 (run
), the use of Ph P led only to moderate conversion together
in Pd-catalyzed cross-coupling reactions of aryl halides
1
5
1
and secondary amines has precedent in the literature. Con-
sequently, the use of tris(tert-butyl)phosphine led immedi-
ately to the dramatic improvement of both yield and
conversion (run 4). The conversion of the starting bromo-
calix[4]arene 6 increased to 82% and tris(Boc)cyclenyl-
calix[4]arene 8 was isolated in 66% after column
3
with a low yield of the required calix–cyclen conjugate 8 in
our case. Using a large amount of Pd-source, higher temper-
ature, and a longer reaction time did not improve the yield
(run 2). Similar results have been achieved using DPPF as
a chelating ligand (Table 1, run 3).
Table 1. Yields, stoichiometry, and reaction conditions of Buchwald–Hartwig coupling reactions between calix[4]arenes 6, 7, and 16 and protected cyclen 2
ꢀ
a
Yield (%)
Run
Starting materials
Pd-source (mol %)
Ligand (mol %)
Base (equiv)
T ( C)
Time (h)
Product
1.
2.
3.
4.
5.
2 (1.1 equiv)+6
2 (1.1 equiv)+6
2 (1.1 equiv)+6
2 (1.05 equiv)+6
2 (2.1 equiv)+7
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
2
2
(5)
(15)
(7)
(10)
(10)
PPh
PPh
DPPF (7.5)
P(t-Bu)
P(t-Bu)
3
(10)
(10)
NaOt-Bu (1.3)
NaOt-Bu (1.3)
NaOt-Bu (1.3)
NaOt-Bu (1.3)
NaOt-Bu (2.5)
80
90
80
80
80
35
48
70
18
42
8
8
8
8
8
9
21 (42)
17 (32)
19 (31)
66 (81)
18 (18)
65 (65)
3
3
(15)
(10)
3
6.
2 (2.05 equiv)+16
Pd(OAc)
2
(10)
P(t-Bu)
3
(15)
NaOt-Bu (2.3)
80
2
17
1
55 (57)
24 (25)
8
a
Yields in parentheses corrected for recovered starting material.

5750
V. Stastny et al. / Tetrahedron 62 (2006) 5748–5755
Br
O
chromatography. Similarly, the coupling reaction between
dibromocalix[4]arene 7 and threefold Boc-protected cyclen
Br
Br
Br
Pr
Pr
O
O
2
was accomplished under identical conditions, using 2.1–
.5 equiv of protected cyclen 2. Utilization of the already
a)
2
approved P(t-Bu) led to the required bis[tris(Boc)cyclenyl]-
3
O
O
HO
O
Pr
OH
calix[4]arene 9 in high yield, accompanied by a small amount
of mono-conjugate 8 (presumably formed by a b-elimination
during the coupling of the second cyclen unit). The reaction
mixture was easily separated by column chromatography to
yield the conjugates 9 and 8 in 65 and 18% yield, respec-
tively, (see Table 1, run 5). The Boc protective groups were
removed under acidic conditions (TFA–CH Cl , rt, over-
Pr
Pr
Pr
5
16
b)
O
O
O
O
O
O
2
2
N
N
N
N
O
O
night) to yield the corresponding N-protonated cyclenyl
calix[4]arenes 10 and 11 in quantitative yields. These salts
were then basified using strongly basic anion exchanger
O N
O
O
O
O
N
N
N
O
N
N
O
O
N
O
O
N
Ò
+
O
O
O
O
(
Ion exchanger III; Merck ) to form quantitatively cyclenyl-
calix[4]arene 12 and bis(cyclenyl)calix[4]arene 13. The
corresponding metallated derivatives 14 and 15 were then
obtained in quantitative yields (see Scheme 1) by the
reaction of free cyclen conjugates with 1 or 2 equiv of
Zn(ClO ) $6H O (MeOH, rt, overnight). Structures of all
O
O
O
O
4
2
2
the above mentioned compounds were unambiguously
proven by H, C DEPT NMR, and ESIMS spectra.
17
18
1
13
Scheme 2. (a) PrI, (CH
ꢀ
3
)
3
SiOK, THF, rt (75%); (b) 2, Pd(OAc)
2
, P(t-Bu)
3
,
t-BuONa, toluene, 80 C (55% for 17, 24% for 18).
To investigate the influence of the calix[4]arene conforma-
tion on the Pd-catalyzed N-arylation reaction, the dibromo
derivative 16 in the 1,3-alternate conformation was prepared
in the presence of tris(tert-butyl)phosphine and the required
bis[tris(Boc)cyclenyl]calix[4]arene (1,3-alternate) 17 was
obtained in good yield (55%) together with mono-cyclen
conjugate 18 (24%) (see Scheme 2). The presence of by-
product 18 in the reaction mixture represents the evidence
for the b-elimination mechanism as the competitive process
accompanying this N-arylation coupling reaction. On the
other hand, when we applied this coupling reaction to tetra-
(
Scheme 2). The starting dibromo derivative 5 was alkylated
using PrI in anhydrous THF and employing potassium tri-
methylsilyloxide as a base. Surprisingly, under these conditions
the 1,3-alternate conformer 16 was obtained in higher yield
(75%), compared to the commonly used cesium carbonate.
Furthermore, under these conditions, derivative 16 can be iso-
latedbysimpleprecipitationwithoutcolumnchromatography.
1
6
bromocalix[4]arene in the 1,3-alternate conformation 19,
we never obtained the required calix[4]arene substituted
The Buchwald–Hartwig reaction between the dibromo
derivative 16 and protected cyclen 2 gave the best results
with four cyclen units. Using either Ph P, DPPF or P(t-Bu)
3
3
Figure 1. ESIMS (+) of the inseparable reaction mixture after the coupling reaction between tetrabromo-derivative 19 and cyclen 2.

V. Stastny et al. / Tetrahedron 62 (2006) 5748–5755
Boc
Table 2. Complexation constants K
5751
a
c
of conjugate 14 toward selected anions
1
ꢀ
(
H NMR, CD
3
CN, 25 C, 300 MHz)
N
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
NO
3
Boc
O
N
N
Boc
Anion
Cl
1120
AcO
205
BzO
950
H
2
PO
4
HSO
4
Br
ꢁ
1
[mol l]
b
b
c
N
K
c
O
O
Br
O
Br
a
b
c
+
Corresponding TBA salts used.
Precipitate formed during the NMR titration.
Small induced chemical shifts (<10 Hz) observed.
Pd(OAc) , NaOt-Bu
phosphine ligand
Boc
N
O
O
calixarene cavity seems to be blocked even in the case of
the mono Zn(II)cyclenyl derivative 14, which excludes the
efficient binding of the BNPP substrate necessary for the
catalytic activity.
Boc
N
N H
O
Br
Br
O
Br
Br
N
Boc
1
9
20
O
ONa
O
Figure 2. Proposed negative allosteric effect in a 1,3-alternate derivative.
P
O
as phosphine ligands (otherwise under identical conditions
as specified above) we have always obtained only very
complicated (according to H NMR) and inseparable
1
NO2
NO2
reaction mixtures. As shown by ESIMS analysis of such
a mixture, tribromo-tri(Boc)cyclenylcalix[4]arene 20 was
obtained together with the b-elimination products (Fig. 1).
Surprisingly, not more than one cyclen unit could be ap-
pended to the tetrabromocalix[4]arene 19 under the above
mentioned conditions. The explanation could lie in the
increased steric hindrance in the 1,3-alternate system. The
presence of one bulky tri(Boc)cyclen unit at one side of
the calix[4]arene may cause the outstretching of the two
proximal propoxy groups, which implies the slight change
in the conformation (see Fig. 2). As a consequence, the
two bromine atoms on the opposite side of the 1,3-alter-
nate conformer become closer to each other thus making
their substitution impossible. This phenomenon resembles
a complexation-induced negative allosteric effect observed
BNPP
Nevertheless, the rigid connection between both subunits
was found to be effective in the case of coordination of
selected anions. We performed several measurements using
H NMR titration and Job’s plot techniques (acetonitrile-
d3). As follows from Table 2, quite interesting affinity of
ligand 14 towards spherical chloride anion and planar
acetate/benzoate anions was observed. All these anions
formed a complex with ligand 14 with 1:1 stoichiometry
(Fig. 3). On the other hand, the presence of the nitrate anion
in the solution of 14 didn’t cause any changes in the H NMR
spectrum. Meanwhile, the gradual addition of either
1
1
8
1
ꢁ
ꢁ
H PO or HSO4 anions into the CD CN solution of 14
4
2
3
1
7
in some 1,3-alternate calixarenes.
led in both cases to the formation of white precipitates (prob-
ably the corresponding complexes), which were not further
analyzed owing to their total insolubility. Ligand 15 bearing
2
.2. Complexation study
1
two Zn(II)cyclen units was also subjected to H NMR titra-
tion experiments with TBA chloride and TBA benzoate .
+
ꢁ
+
ꢁ
Having developed the synthetic route leading to the calix[4]-
arene–cyclen conjugates in reasonable yields, we have car-
ried out a preliminary study of the hydrolytic activities of
the Zn(II) complexes towards the cleavage of phospho-
diester bonds. These measurements were done in buffered
The addition of these salts to the ligand 15 led in both cases
to considerable shifts in H NMR spectra, however, the titra-
tion curves indicated nontrivial stoichiometry different from
1:1.
1
0
.01 M solution of Tris-base, in a mixture of MeOH–H O
2
9
activated phosphodiester bonds we used sodium bis(p-nitro-
phenyl)phosphate (BNPP). The buffered solution in the UV-
:1 at pH¼8 (I¼0.1 M). As a model compound containing
8
7
6
5
4
3
2
1
0
ꢁ
4
ꢁ1
)
cell containing either ligand 14 or 15 (c¼4ꢂ10 mol l
ꢁ5
ꢁ1
ꢀ
and BNPP (c¼1.6ꢂ10 mol l ) at 30 C was scanned
every 5 min for 9 h in the region between 380 and 420 nm
in the UV spectrophotometer. However, the expected
absorption signal at 400 nm indicating the presence of free
p-nitrophenolate anion in the solution was not observed.
Thus both Zn-complexes were found to be inactive to cleave
the activated phosphodiester bond in BNPP under the condi-
tions used. Neither increasing the pH value to 9, nor increas-
ing the concentration of ligand led to a desired catalytic
activity. These results are in agreement with the previous
7
0
0.2
0.4
0.6
0.8
1
findings of Akkaya and Ozturz. However, the steric hin-
C14/(C14+Cbenzoate
)
drance seems to be even more effective here. This could
be ascribed to a rigid connection between bulky Zn(II)cyclen
and the calix[4]arene moieties. Thus, the entrance to the
+
N benzoate system (300 MHz, CD
ꢁ
Figure 3. Job’s plot for 14/Bu
c
4
3
CN,
ꢁ
1
total¼2 mmol l ).

5752
V. Stastny et al. / Tetrahedron 62 (2006) 5748–5755
3. Conclusions
acetate (10.1 mg, 0.045 mmol, 10 mol %) were added. The
solid materials were suspended in absolute toluene (4 ml).
The tube was sealed, and the mixture was degassed by three
freeze–pump–thaw cycles, then stirred at 80 C for 18 h. The
In summary, we have reported the synthesis of calix[4]-
arene–cyclen conjugates, with direct N-aryl bonds and
constrained calixarene conformations. Optimized conditions
for the palladium-catalyzed N-aryl bond formation to con-
nect protected cyclen with bromocalix[4]arenes were devel-
oped. The cyclen ligands were deprotected and converted
into the bis-zinc(II) complexes. Attempts to use the com-
plexes to hydrolyze activated phosphodiester bonds were
unsuccessful. However, NMR titration experiments revealed
binding affinity of the bis complexes in acetonitrile for
chloride, acetate, and benzoate anions with defined stoichio-
metry.
ꢀ
reaction mixture was cooled to rt, diluted with CH Cl
2
2
(30 ml), filtered through Celite, and concentrated in vacuum.
The crude product was purified by column chromatography
(SiO , PE–EtOAc 10:1–2:1) to give 314 mg (66%) of 8.
2
ꢀ
Mp: 72 C (ethyl acetate). R ¼0.66 (SiO , PE–EtOAc 2:1).
f
2
1
H NMR (CDCl , 250 MHz) d (ppm): 1.04 (m, 12H,
3
–CH –CH ), 1.46 (s, 9H, –C–(CH ) ), 1.47 (s, 18H, –C–
2
3
3 3
(CH ) ), 1.94 (m, 8H, –CH –CH ), 3.08 (d, 2H,
3
3
2
3
J¼12.7 Hz, Ar–CH –Ar, eq.), 3.13 (d, 2H, J¼12.7 Hz, Ar–
2
CH –Ar, eq.), 3.25 (m, 16H, –N–CH –CH –N–), 3.76 (m,
2
2
2
8
H, –O–CH –CH –), 4.43 (d, 2H, J¼13.1 Hz, Ar–CH –
2
2
2
Ar, ax.), 4.44 (d, 2H, J¼13.2 Hz, Ar–CH –Ar, ax.), 6.36
2
4. Experimental
(s, 2H, ArH), 6.39 (m, 6H, ArH), 6.70 (t, 1H, J¼7.1 Hz,
1
3
ArH), 6.88 (d, 2H, J¼7.3 Hz, ArH). C NMR, DEPT
4
.1. General
(135) (CDCl , 63 MHz) d (ppm): 10.1 (+), 10.2 (+), 10.5
3
(
+), 23.0 (ꢁ), 23.1 (ꢁ), 23.4 (ꢁ), 28.5 (+), 28.7 (+), 30.9
All moisture sensitive reactions were carried out under nitro-
gen atmosphere. All dry solvents were prepared according to
standard procedures and stored over molecular sieves. Melt-
ing points are uncorrected and were determined using a
Boetius Block apparatus (Carl Zeiss Jena, Germany).
(ꢁ), 31.3 (ꢁ), 49.4 (ꢁ), 50.6 (ꢁ), 76.7 (ꢁ), 76.8 (ꢁ), 79.4
(C ), 79.7 (C ), 121.9 (+), 127.3 (+), 127.9 (+), 128.5
quat
quat
(+), 134.1 (Cquat), 134.5 (Cquat), 135.9 (Cquat), 136.3 (Cquat),
155.8 (Cquat), 157.1 (Cquat). EA calcd for C H N O : C,
71.16; H, 8.53; N, 5.27. Found: C, 71.09; H, 8.83; N,
63
90 4 10
1
+
NMR spectra were recorded at 250 and 400 MHz ( H) and
5.18. MS (ESI, 70 eV): m/z (rel int.) 1064 [MH] (100).
IR (KBr) cm : 2970, 2927, 1695, 1601, 1462, 1248,
1
3
13
ꢁ1
at 63 and 100 MHz ( C). The multiplicity of the C signals
was determined with the DEPT technique and quoted as: (+)
for CH or CH, (ꢁ) for CH , and (Cquat) for quaternary
ꢁ
1
1167 cm
.
3
2
1
carbons. H NMR titrations were performed with tetrabutyl-
ammonium salts of corresponding anions that were dried
and stored in evacuated desiccator over P O . Elemental
4.3. Synthesis of 5,17-bis[4,7,10-tris(Boc)cyclen-1-yl]-
25,26,27,28-tetrapropoxycalix[4]arene (cone) 9
2
5
analyses were measured on Elementar vario EL (Elementar,
Germany) instruments. All samples were dried in the desic-
The protected cyclen 2 (397 mg, 0.84 mmol), 5,17-dibromo-
25,26,27,28-tetrapropoxycalix[4]arene (cone) 7 (300 mg,
0.4 mmol), and sodium tert-butoxide (96 mg, 1 mmol)
were placed into a Schlenk tube. To this mixture P(t-Bu)3
(8 mg, 0.04 mmol, 10 mol %) and palladium acetate (9 mg,
0.04 mmol, 10 mol %) were added and the solid materials
were suspended in dry toluene (4 ml). The tube was sealed,
degassed by three freeze–pump–thaw cycles, and stirred at
ꢀ
known that the elemental analyses of the calixarene
cator over P O under vacuum (1 Torr) at 80 C for 8 h. It is
2
5
1
9
derivatives are sometimes ambiguous. Mass spectra were
measured using ESI technique on Q-TOF (Micromass)
spectrometer or MALDI-TOF technique on HP G2030A
(
Hewlett Packard) with delayed extraction option. The IR
spectra were measured on an FTIR spectrometer, Nicolet
40 or Bruker IFS66 spectrometers equipped with a heatable
ꢀ
80 C for 42 h. The reaction mixture was then cooled to rt,
diluted with CH Cl (20 ml), filtered through Celite, and
7
2
2
Golden Gate Diamante ATR-Unit (SPECAC) in CHCl and/
3
evaporated in vacuum. The crude product was purified by
column chromatography (SiO , PE–EtOAc 5:1–1:1) to
or in KBr. UV–vis spectra were measured on a JASCO V-530
spectrophotometer. The purity of the substances and the
courses of reactions were monitored by TLC using TLC
alumina sheets with Silica gel 60 F254 (Merck). Preparative
TLC chromatography was carried out on 20ꢂ20 cm glass
2
give 77 mg (18%) of mono-conjugate 8 and 399 mg (65%)
of compound 9 as white solid. Mp: 114 C. R ¼0.21 (SiO ,
ꢀ
PE–EtOAc 2:1). H NMR (CDCl , 250 MHz) d (ppm):
f
2
1
3
0.88 (t, 6H, J¼7.3 Hz, –CH –CH ), 1.10 (t, 6H, J¼7.3 Hz,
2
3
plates covered by Silica gel 60 GF
(Merck) or Al O
–CH –CH ), 1.47 (s, 18H, –C–(CH ) ), 1.49 (s, 36H, –C–
2 3 3 3
2
54
2
3
type G (Fluka). The column chromatography was performed
using Silica gel 60 (Merck).
(CH ) ), 1.80–2.10 (m, 8H, –CH –CH ), 3.02 (d, 4H,
3 3 2 3
J¼13.3 Hz, Ar–CH –Ar, eq.), 3.45 (br s, 32H, –N–CH –
2
2
CH –N–), 3.63 (t, 4H, J¼7.7 Hz, –O–CH –CH –), 3.93 (t,
2
2
2
1
d
20 21 22 23
16
Compounds 2, 3, 4, 6, 7, and 19 were prepared
according to known procedures.
4H, J¼7.1 Hz, –O–CH –CH –), 4.42 (d, 4H, J¼13.1 Hz,
2
2
Ar–CH –Ar, ax.), 6.11 (s, 6H, ArH), 6.53 (s, 4H, ArH).
2
1
3
C NMR, DEPT (135) (CDCl , 63 MHz) d (ppm): 9.9 (+),
3
4
2
.2. Synthesis of 5-[4,7,10-tris(Boc)cyclen-1-yl]-
5,26,27,28-tetrapropoxycalix[4]arene (cone) 8
10.9 (+), 22.9 (ꢁ), 23.6 (ꢁ), 28.5 (+), 28.6 (+), 31.5
(ꢁ), 50.1 (ꢁ), 50.9 (ꢁ), 76.4 (ꢁ), 77.0 (ꢁ), 79.8 (C ),
quat
1
17.8 (+), 121.8 (+), 127.0 (+), 133.2 (C ), 137.5 (Cquat),
quat
The protected cyclen 2 (223 mg, 0.47 mmol), 5-bromo-
2
0
155.1 (Cquat). EA calcd for C H N O : C, 67.34; H,
86 132 8 16
5,26,27,28-tetrapropoxycalix[4]arene (cone) 6 (300 mg,
.447 mmol), and 56 mg of sodium tert-butoxide
0.58 mmol) were placed into a Schlenk tube. To this mixture
8.67; N, 7.30. Found: C, 67.27; H, 8.82; N, 7.19. MS
(ESI, 70 eV): m/z (rel int.) 1535 [MH] (100), 768
+
+
2+
ꢁ1
(
[M+2H ] (60). IR (KBr) cm : 2974, 2933, 1695,
1466, 1250, 1165 cm
ꢁ
1
P(t-Bu) (13.6 mg, 0.067 mmol, 15 mol %) and palladium
3
.

V. Stastny et al. / Tetrahedron 62 (2006) 5748–5755
5753
+
4
2
(
.4. Synthesis of 5-(1,4,7,10-tetrakis[4H ]cyclen-1-yl)-
5,26,27,28-tetrapropoxycalix[4]arene tetrakis-
trifluoroacetate) (cone) 10
solvent mixture and the fractions with basic reaction on
pH-paper were combined, evaporated, and dried under vac-
uum to give 133 mg (95%) of 12 as white solid. Mp: 90–
ꢀ
2 C. H NMR (CDCl , 250 MHz) d (ppm): 1.00 (m, 12H,
3
1
9
Compound 8 (202 mg, 0.19 mmol) was dissolved in CH Cl
2
–CH –CH ), 1.91 (m, 8H, –CH –CH ), 2.63–3.17 (m, 20H,
2
2
2
3
3
(
added. The reaction mixture was stirred for 16 h (until no
starting compound was indicated by TLC (SiO , EtOAc–
2
10 ml) and trifluoroacetic acid (0.43 ml, 5.6 mmol) was
–N–CH –CH –N–, Ar–CH –Ar, eq.), 3.83 (m, 8H, –O–
2 2 2
CH –CH –), 4.43 (d, 2H, J¼13.1 Hz), 4.45 (d, 2H,
2
2
1
3
J¼13.2 Hz), 6.16 (s, 2H, ArH), 6.59 (m, 9H, ArH). C
NMR, DEPT (135) (CDCl , 63 MHz) d (ppm): 10.3 (+),
MeOH 100:1), evaporated, and dried under vacuum to yield
3
2
solid. Mp: 116–117 C. H NMR (CDCl , 250 MHz)
25 mg of title compound 10 (100%) as a brown viscous
ꢀ
10.4 (+), 10.5 (+), 23.2 (ꢁ), 23.3 (ꢁ), 23.4 (ꢁ), 31.0 (ꢁ),
31.3 (ꢁ), 47.0 (ꢁ), 47.4 (ꢁ), 49.2 (ꢁ), 52.8 (ꢁ), 76.7 (ꢁ),
76.8 (ꢁ), 77.3 (ꢁ), 116.7 (+), 121.8 (+), 121.9 (+), 128.0
(+), 135.0 (C ), 144.0 (C ), 150.4 (C ), 156.6 (C ),
1
3
d (ppm): 0.95 (m, 12H, –CH –CH ), 1.98 (m, 8H, –CH –
3
2
2
CH ), 2.71–3.20 (m, 16H, –NCH –CH –N–), 3.10 (d, 4H,
3
2
2
quat
quat
quat
quat
Ar–CH –Ar, eq.), 3.70–3.88 (m, 4H, –O–CH –CH –),
2
156.8 (Cquat). EA calcd for C H N O : C, 75.55; H, 8.72;
48 66 4 4
2
2
3
.93–3.99 (m, 4H, –O–CH –CH –), 4.43 (d, 4H, Ar–CH –
2
N, 7.34. Found: C, 75.30; H, 8.61; N, 7.19. MS (ESI,
70 eV) m/z (rel int.) 763 [MH] (100), 382 [M+2H ]
2
2
3
+
+ 2+
Ar, ax.), 6.23–6.31 (m, 3H, ArH), 6.47 (d, 2H, J¼7.3 Hz,
ꢁ
1
ArH), 6.74–6.93 (m, 6H, ArH), 8.80–10.4 (br s, 4H,
NH(H )). C NMR, DEPT (135) (CDCl , 63 MHz)
(100). IR (KBr) cm : 2962, 2931, 2872, 2362, 1689,
1458, 1199 cm
+
13
ꢁ1
–
.
3
d (ppm): 10.0 (+), 10.5 (+), 10.6 (+), 23.0 (ꢁ), 23.3 (ꢁ),
2
7
2
3.4 (ꢁ), 30.9 (ꢁ), 43.3 (ꢁ), 44.9 (ꢁ), 45.5 (ꢁ), 51.9 (ꢁ),
4.7. Synthesis of 5,17-bis(cyclen-1-yl)-25,26,27,28-tetra-
propoxycalix[4]arene (cone) 13
1
quat (C,F)
6.7 (ꢁ), 77.3 (ꢁ), 77.4 (ꢁ), 116.4 (C , q, J
¼
87.7 Hz), 121.6 (+), 122.3 (+), 123.4 (+), 127.6 (+), 128.3
(
+), 128.9 (+), 134.3 (Cquat), 135.7 (Cquat), 136.3 (Cquat),
40.2 (Cquat), 156.2 (Cquat), 157.0 (Cquat), 161.9 (Cquat, q,
Derivative 11 (536 mg, 0.29 mmol) was dissolved in H O–
2
1
MeOH 1:1 (v/v) mixture (20 ml) and poured onto the col-
umn of strongly basic anion exchanger (Ion exchanger III;
Merck ). The column was then washed with 100 ml of the
2
J(C,F)¼40.2 Hz). MS (ESI, 70 eV) m/z (rel int.) 763
+
2+
ꢁ1
[
3
MH] (50), 382 [M+2H] (100). IR (KBr) cm : 3630–
310, 2965, 2875, 1685, 1461 cm .
Ó
ꢁ
1
same solvent mixture and the fractions with basic reaction
on pH-paper were combined, evaporated, and dried under
vacuum to give 270 mg (99%) of compound 13 as white
+
4
1
(
.5. Synthesis of 5,17-bis(1,4,7,10-tetrakis[4H ]-cyclen-
-yl)-25,26,27,28-tetrapropoxycalix[4]arene octakis-
trifluoroacetate) (cone) 11
ꢀ
1
solid. Mp: 198 C. H NMR (CDCl , 250 MHz) d (ppm):
3
0.86 (t, 6H, J¼7.4 Hz, –CH –CH ), 1.08 (t, 6H, J¼7.4 Hz,
2
3
–CH –CH ), 1.80–2.01 (m, 8H, –CH –CH ), 2.68 (s, 8H,
2 3 2 3
Compound 9 (530 mg, 0.345 mmol) was dissolved in
CH Cl (10 ml) and trifluoroacetic acid (1.6 ml, 20.7 mmol)
–N–CH –CH –N–), 2.85 (s, 16H, –N–CH –CH –N–), 3.32
2 2 2 2
(s, 8H, –N–CH –CH –N–), 3.06 (d, 4H, J¼13.3 Hz, Ar–
2
2
2
2
was added. Reaction mixture was stirred for 16 h (until no
starting compound was indicated by TLC (SiO , EtOAc–
CH –Ar, eq.), 3.63 (t, 4H, J¼6.7 Hz, –O–CH –CH –),
2 2
2
2
2
3.93 (t, 4H, J¼8.2 Hz, –O–CH –CH –), 4.38 (d, 4H,
2
2
MeOH 100:1), evaporated, and dried under vacuum. Com-
pound 11 was obtained in quantitative yield as brown
J¼13.2 Hz, Ar–CH –Ar, ax.), 6.08 (d, 4H, J¼7.4 Hz,
1
3
ArH), 6.21 (t, 2H, J¼6.9 Hz, ArH), 6.77 (s, 4H, ArH).
C
NMR, DEPT (135) (CDCl , 63 MHz) d (ppm): 9.8 (+),
ꢀ
1
viscous solid. Mp: 165–167 C. H NMR (CDCl –CD OD
3
3
3
1
1
–
:1, 400 MHz) d (ppm): 0.9 (t, 6H, J¼7.5 Hz, –CH –CH ),
10.9 (+), 22.9 (ꢁ), 23.5 (ꢁ), 31.2 (ꢁ), 46.1 (ꢁ), 46.4 (ꢁ),
47.6 (ꢁ), 52.5 (ꢁ), 76.4 (ꢁ), 76.8 (ꢁ), 119.9 (+), 122.1
(+), 127.1 (+), 133.1 (C ), 137.1 (C ), 145.0 (C ),
2
3
.3 (t, 6H, J¼7.5 Hz, –CH –CH ), 1.87–2.01 (m, 8H,
2
3
CH –CH ), 3.05–3.42 (m, 36H, –N–CH –CH –N–, Ar–
3
2
2
2
quat
quat
quat
CH –Ar, eq.), 3.66 (t, 4H, J¼6.7 Hz, –O–CH –CH –),
152.3 (Cquat), 155.1 (Cquat). MS (ESI, 70 eV) m/z (rel int.)
933 [MH] (10), 476 [M+2H] (100). EA calcd for
C H N O : C, 72.07; H, 9.07; N, 12.01. Found: C,
2
2
2
+
2+
4
.03 (t, 4H, J¼8.2 Hz, –O–CH –CH –), 4.45 (d, 4H,
2
2
+
J¼13.2 Hz, Ar–CH –Ar, ax.), 4.98 (br s, 8H, –NH(H )),
2
56 84 8 4
ꢁ
1
6
7
.07 (d, 4H, J¼7.6 Hz, ArH), 6.18 (t, 2H, J¼7.5 Hz, ArH),
71.89; H, 9.21; N, 11.91. IR (KBr) cm : 3375–3290,
2929, 2873, 1602, 1456, 1222 cm
1
3
ꢁ1
.11 (s, 4H, ArH). C NMR, DEPT (135) (CDCl –
3
.
CD OD 1:1, 100 MHz) d (ppm): 10.0 (+), 11.1 (+), 23.5
3
(
(
1
ꢁ), 24.0 (ꢁ), 31.4 (ꢁ), 43.1 (ꢁ), 44.3 (ꢁ), 46.0 (ꢁ), 51.4
2
+
4.8. Synthesis of 5-([Zn ]cyclen-1-yl)-25,26,27,28-tetra-
propoxycalix[4]arene bis(perchlorate) (cone) 14
1
quat (C,F)
ꢁ), 77.1 (ꢁ), 77.6 (ꢁ), 117.0 (C , q, J
¼291.0 Hz),
quat
22.6 (+), 124.9 (+), 127.7 (+), 133.3 (Cquat), 139.0 (C ),
1
42.5 (Cquat), 155.8 (Cquat), 156.7 (Cquat), 162.1 (Cquat, q,
Conjugate 12 (325 mg, 0.426 mmol) was dissolved in MeOH
(10 ml) and Zn(ClO ) $6H O (159 mg, 0.426 mmol) was
added. The reaction mixture was stirred at rt for 20 h, and
2
J(C,F)¼35.7 Hz). MS (ESI, 70 eV) m/z (rel int.) 933
+
2+
4 2 2
[
MH] (15), 467 [M+2H] (100).
ꢀ
and the residue was dried under vacuum to give 439 mg
then heated to 50 C for 1 h. The solvent was evaporated
4.6. Synthesis of 5-(cyclen-1-yl)-25,26,27,28-tetra-
propoxycalix[4]arene (cone) 12
ꢀ
decomp.). H NMR (CDCl –CD OD 1:1, 250 MHz)
(quantitative) of 14 as white crystalline solid. Mp: 198 C
(
1
3
3
Derivative 10 (225 mg, 0.19 mmol) was dissolved in H O–
2
d (ppm): 0.91–1.06 (m, 12H, –CH –CH ), 1.84–1.97 (m,
2 3
MeOH 1:1 (v/v) mixture (10 ml) and poured onto the col-
umn of strongly basic anion exchanger (Ion exchanger III;
Merck ). The column was washed with 100 ml of the above
8H, –CH –CH ), 2.49–3.05 (m, 16H, –N–CH –CH –N–),
2 3 2 2
3.13 (d, 2H, J¼13.1 Hz, Ar–CH –Ar, eq.), 3.15 (d, 2H,
2
Ó
J¼13.2 Hz, Ar–CH –Ar, eq.), 3.72 and 3.92 (2m, 8H, –O–
2

5754
V. Stastny et al. / Tetrahedron 62 (2006) 5748–5755
+
CH –CH –), 4.42 (d, 2H, J¼12.9 Hz, Ar–CH –Ar, ax.), 4.43
[M] (100). EA calcd for C H O Br : C, 64.01; H, 6.18;
40 46
2
2
2
4
2
(d, 2H, J¼13.3 Hz, Ar–CH –Ar, ax.), 6.38–6.88 (m, 11H,
ArH).
Br, 21.29. Found: C, 64.05; H, 6.29; Br, 21.18.
2
1
3
C NMR, DEPT (135) (CDCl –CD OD 1:1,
3 3
6
2
4
1
3 MHz) d (ppm): 11.2 (+), 11.6 (+), 11.7 (+), 24.4 (ꢁ),
4.11. Synthesis of 5,17-bis[4,7,10-tris(Boc)cyclen-1-yl]-
25,26,27,28-tetrapropoxycalix[4]arene (1,3-alternate) 17
4.6 (ꢁ), 24.7 (ꢁ), 32.2 (ꢁ), 32.3 (ꢁ), 44.7 (ꢁ), 45.3 (ꢁ),
6.8 (ꢁ), 55.3 (ꢁ), 78.0 (ꢁ), 78.6 (ꢁ), 78.7 (ꢁ), 123.2 (+),
23.8 (+), 124.0 (+), 129.2 (+), 129.8 (+), 130.3 (+), 135.6
The protected azamacrocycle 2 (388 mg, 0.82 mmol), 5,17-
dibromo-25,26,27,28-tetrapropoxycalix[4]arene (1,3-alter-
nate) 16 (300 mg, 0.4 mmol), and sodium tert-butoxide
(88 mg, 0.92 mmol) were placed into a Schlenk tube. To
(
(
Cquat), 136.5 (Cquat), 137.3 (Cquat), 137.4 (Cquat), 142.7
Cquat), 156.2 (Cquat), 157.4 (Cquat), 158.1 (Cquat). MS (ESI,
7
[
0 eV, 1% AcOH in MeOH) m/z (rel int.) 885
M+CH COO] (100),422[M+H O] (40). IR(KBr)cm :
+
2+
ꢁ1
this mixture P(t-Bu) (14 mg, 0.07 mmol) and palladium
3
3
2
ꢁ
1
3
516, 3302, 2960, 2927, 2875, 1460, 1088 cm
.
acetate (10 mg, 0.044 mmol) were added and the solid mate-
rials were suspended in dry toluene (3 ml). The tube was
sealed, and degassed by three freeze–pump–thaw cycles.
2
+
4
.9. Synthesis of 5,17-bis([Zn ]cyclen-1-yl)-25,26,27,28-
ꢀ
tetrapropoxycalix[4]arene tetrakis(perchlorate)
cone) 15
The reaction mixture was stirred at 80 C for 2 h, cooled
to rt, diluted with CH Cl (20 ml), filtered through Celite,
(
2
2
and concentrated in vacuum. The crude product was purified
by column chromatography (SiO , PE–EtOAc 10:1–1:1) to
Conjugate 13 (260 mg, 0.28 mmol) was dissolved in MeOH
10 ml) and Zn(ClO ) $6H O (208 mg, 0.56 mmol) was
added. The reaction mixture was stirred at rt for 20 h, and
2
(
give 366 mg (55%) of the title product 17. Mp: 158–
ꢀ
4
2
2
1
160 C. R ¼0.22 (SiO , PE–EtOAc 2:1). H NMR (CDCl ,
f
2
3
ꢀ
then heated to 50 C for 1 h. The solvent was evaporated
and the residue was dried under vacuum to give 407 mg
250 MHz) d (ppm): 0.67 (t, 6H, J¼7.4 Hz, –CH –CH ),
2 3 3 3
2 3
1.09–1.26 (m, 6H, –CH –CH ), 1.46 (s, 18H, –C–(CH ) ),
1.47 (s, 36H, –C–(CH ) ), 1.50–1.60 (br s, 8H, –CH –
3 3 2
ꢀ
(
(
100%) of 15 as white crystalline solid. Mp: 220 C
decomp.). H NMR (CD CN, 250 MHz) d (ppm): 0.92 (t,
1
CH ), 3.22–3.78 (m, 48H, –N–CH –CH –N–, Ar–CH –Ar,
3 2 2 2
3
6
CH ), 1.81–2.02 (m, 8H, –CH –CH ), 2.77–3.40 (m, 36H,
H, J¼7.4 Hz, –CH –CH ), 1.08 (t, 6H, J¼7.4 Hz, –CH –
–O–CH –CH –), 6.43 (s, 4H, ArH), 6.76 (t, 2H, J¼7.4 Hz,
2
3
2
2
2
1
3
ArH), 6.99 (d, 4H, J¼7.4 Hz, ArH). C NMR, DEPT
3
2
3
–
6
4
N–CH –CH –N–, Ar–CH –Ar, eq.), 3.66 (t, 4H, J¼
(135) (CDCl , 100 MHz) d (ppm): 10.0 (+), 10.2 (+), 22.2
3
2
2
2
.9 Hz, –O–CH –CH –), 3.82 (m, 4H, –N–CH –CH –N–),
2
(ꢁ), 23.2 (ꢁ), 28.5 (+), 28.6 (+), 38.7 (ꢁ), 50.0 (ꢁ), 72.1
2
2
2
.05 (t, 4H, J¼8.2 Hz, –O–CH –CH –), 4.45 (d, 4H,
(ꢁ), 72.3 (ꢁ), 79.4 (C ), 79.6 (C ), 117.7 (+, br),
2
2
quat
quat
J¼13.0 Hz, Ar–CH –Ar, ax.), 6.32 (s, 6H, ArH), 7.17 (s,
121.7 (+), 129.4 (+), 133.8 (Cquat), 134.4 (Cquat), 143.7
2
1
3
4
H, ArH). C NMR, DEPT (135) (CD CN, 63 MHz)
3
(Cquat, br), 150.3 (Cquat, br), 155.5 (Cquat, br), 156.5 (Cquat
br), 156.8 (C ). MS (ESI, 70 eV) m/z (rel int.) 1535
,
d (ppm): 10.2 (+), 11.2 (+), 24.0 (ꢁ), 24.3 (ꢁ), 31.5 (ꢁ),
quat
+
2+
4
1
1
4.2 (ꢁ), 44.5 (ꢁ), 45.9 (ꢁ), 54.7 (ꢁ), 77.5 (ꢁ), 78.2 (ꢁ),
[MH] (100), 768 [M+2H] (15). EA calcd for
C H N O : C, 67.34; H, 8.67; N, 7.30. Found: C,
67.11; H, 8.79; N, 7.22.
23.6 (+), 124.5 (+), 128.7 (+), 133.9 (C ), 139.0 (C ),
quat
quat
86 132 8 16
42.2 (Cquat), 156.4 (Cquat), 156.9 (Cquat). MS (ESI, 70 eV)
+
2+
4+
m/z (rel int.) 1361 [M+3ClO ] (10), 631 (M+2ClO4)
4
3
+
(
80), 415 [M+ClO +2CH CN] (100), 307 [M+4CH CN]
4
The evaporation of first chromatographic fractions yielded
103 mg (24%) of 5-[4,7,10-tris(Boc)cyclen-1-yl]-25,26,
27,28-tetrapropoxy-calix[4]arene (1,3-alternate) 18 Mp:
3
3
ꢁ1
(
1
60). IR (KBr) cm : 3700–3300, 3290, 2962, 2875, 1635,
479 cm
ꢁ1
.
ꢀ
1
7
(CDCl , 250 MHz) d (ppm): 0.82–1.00 (m, 12H, –CH –
6–78 C. R ¼0.50 (SiO , PE–EtOAc 2:1). H NMR
f
2
4.10. Synthesis of 5,17-dibromo-25,26,27,28-tetra-
propoxycalix[4]arene (1,3-alternate) 16
3
2
CH ), 1.48 (s, 9H, –C–(CH ) ), 1.50 (s, 18H, –C–(CH ) ),
3 3 3 3 3
1
.58–1.77 (m, 8H, –CH –CH ), 3.33–3.67 (m, 32H, –N–
2 3
5
4
,17-Dibromo-26,28-dipropoxycalix[4] arene (cone) 5 (3 g,
.5 mmol) and Me SiOK (2.89 g, 22.5 mmol) were dis-
CH –CH –N–, Ar–CH –Ar, –O–CH –CH –), 6.55 (s, 2H,
2 2 2 2 2
ArH), 6.65 (t, 2H, J¼7.4 Hz, ArH), 6.97ꢁ7.01 (m, 7H,
3
ꢀ
2.2 ml, 22.5 mmol) was slowly added. Reaction mixture
13
solved in 50 ml dry THF and cooled to ꢁ5 C. Then PrI
ArH). C NMR, DEPT (135) (CDCl , 63 MHz) d (ppm):
3
(
10.5 (+), 10.55 (+), 10.6 (+), 23.5 (ꢁ), 23.7 (ꢁ), 23.8 (ꢁ),
28.6 (+), 28.7 (+), 36.2 (ꢁ), 36.7 (ꢁ), 48.3–49.9 (ꢁ, br),
73.9 (ꢁ), 74.0 (ꢁ), 74.4 (ꢁ), 79.4 (C ), 79.6 (C ),
was then stirred at rt for 120 h. After this time the reaction
mixture was quenched with 1 M solution of HCl (100 ml)
quat
quat
and extracted three times with CHCl (3ꢂ30 ml). Combined
120.1 (+, br), 121.3 (+), 121.7 (+), 129.7 (+), 130.0 (+),
130.1 (+), 133.3 (Cquat), 133.4 (Cquat), 133.7 (Cquat), 133.9
(Cquat), 143.7 (Cquat), 151.0 (Cquat), 155.5 (Cquat), 156.4
(Cquat), 156.7 (Cquat), 171.1 (Cquat). MS (ESI, 70 eV) m/z
3
organic layers were dried over Na SO and evaporated to
2
4
give crude product. Crystallization from CHCl –MeOH
3
ꢀ
1
yielded 1.63 g (50%) of pure 16. Mp: 235–237 C. H
NMR (CDCl , 250 MHz) d (ppm): 0.89 (t, 6H, J¼7.4 Hz,
+
(rel int.) 1063 [M] (100). EA calcd for C H N O :
63 90 4 10
3
–
1
CH –CH ), 1.03 (t, 6H, J¼7.4 Hz, –CH –CH ), 1.55–
C, 71.16; H, 8.53; N, 5.27. Found: C, 71.07; H, 8.64;
N, 5.28.
2
3
2
3
.74 (m, 8H, –CH –CH ), 3.74 (t, 4H, J¼7.2 Hz, –O–
2
3
CH –CH –), 3.60 (t, 4H, J¼7.2 Hz, –O–CH –CH –), 3.60
2
2
2
2
(
4
s, 8H, Ar–CH –Ar), 6.71 (t, 2H, J¼7.5 Hz, ArH), 6.98 (d,
2
1
3
H, J¼7.5 Hz, ArH), 7.19 (s, 4H, ArH). C NMR
Acknowledgements
(
2
(
1
CDCl , 100 MHz) d (ppm): 10.4 (+), 10.5 (+), 23.4 (ꢁ),
quat
3
3.5 (ꢁ), 36.4 (ꢁ), 73.2 (ꢁ), 73.5 (ꢁ), 114.3 (C ), 121.7
This research was supported by the IQN-MC program of the
University of Regensburg. Authors thank the DAAD for the
financial support.
+), 130.0 (+), 132.4 (+), 133.1 (Cquat), 135.5 (Cquat),
55.6 (Cquat), 156.5 (Cquat). MS (EIMS) m/z (rel int.) 750

V. Stastny et al. / Tetrahedron 62 (2006) 5748–5755
10. K o¨ nig, B.; Subat, M. Synthesis 2001, 12, 1818–1825.
5755
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