Synthesis and spectroscopic properties of porphyrin-(thia)calix[4]arene conjugates

Article abstract of DOI:10.1016/S0040-4020(02)00506-9

Calix[4]arene diacetate and tetraacetate together with their tetrathia-analogs served as starting compounds for the synthesis of novel porphyrin-calixarene conjugates. The introduction of monoaminotetraphenylporphyrin gave corresponding calixarene derivatives, bearing two or four porphyrin units on the lower calixarene rim. These compounds, immobilized in the cone conformation, possess interesting photophysical properties. The absorption and fluorescence emission spectra of the synthesized diporphyrins and tetraporphyrins reveal exciton coupling between the porphyrin units. The flexibility of the amidic bridges accounts for tuning of the degree of porphyrin coupling by the solvent polarity.

Full text of DOI:10.1016/S0040-4020(02)00506-9

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 5475±5482
Synthesis and spectroscopic properties of
porphyrin-(thia)calix[4]arene conjugates
a
Miroslav Dudic, Pavel Lhot a k, Ivan Stibor, Hana Dvor a kov a and Kamil Lang
a,p
a
b
c,p
a
Department of Organic Chemistry, Institute of Chemical Technology, Technicka 5, 16628 Prague 6, Czech Republic
b
NMRDepartment, Institute of Chemical Technology, Technicka 5, 16628 Prague 6, Czech Republic
c
Institute of Inorganic Chemistry, ASCR, 25068 Rez, Czech Republic
Received 8 February2002; revised 22 April 2002; accepted 16 May2002
AbstractÐCalix[4]arene diacetate and tetraacetate together with their tetrathia-analogs served as starting compounds for the synthesis of
novel porphyrin-calixarene conjugates. The introduction of monoaminotetraphenylporphyrin gave corresponding calixarene derivatives,
bearing two or four porphyrin units on the lower calixarene rim. These compounds, immobilized in the cone conformation, possess
interesting photophysical properties. The absorption and ¯uorescence emission spectra of the synthesized diporphyrins and tetraporphyrins
reveal exciton coupling between the porphyrin units. The ¯exibility of the amidic bridges accounts for tuning of the degree of porphyrin
coupling bythe solvent polarit y. q 2002 Elsevier Science Ltd. All rights reserved.
1
. Introduction
(solvent, the presence of cation) to test their abilityto serve
as ¯uorescent receptors for alkali metal ions. The design of
receptors (outlined in Fig. 1) is based on the fact, that the
mutual position of two porphyrin units can be controlled,
e.g. bythe presence/absence of a metal cation or bychang-
ing of the solvent polarity. Under common conditions, the
short-range orbital-overlap dependent interactions of the
porphyrin units (intramolecular dimerisation) and intra-
molecular hydrogen bonding between distal diamides of
Macrocyclic compounds are widely used in supramolecular
chemistryfor the construction of various receptors for
charged or even neutral molecules. Calix[4]arene 1 repre-
sents a unique three-dimensional structure with almost
unlimited derivatisation abilities. Thiacalix[4]arene 2 has
been described as a new member of the calixarene family.
The presence of four sulphur atoms instead of methylene
groups imposes manynew properties on the thiacalix[4]-
arene skeleton when compared with the chemistryof
1
2
6
calix[4]arene bring amidic substituents close to each
other. Such a potential proximityof the porph yr in units
3
,4
7
`
classical' calixarenes. Veryrecentl y, several reactions
leads to exciton coupling in the excited state and, therefore,
unknown in classical calix[4]arene chemistryhave been
described. These features together with easilytuneable
shapes of the molecules make (thia)calix[4]arenes ideal
candidates for building blocks and/or molecular scaffolds
in the design of new sophisticated systems.
to quenching of the ¯uorescence emission intensity. Upon
complexation, the calixarene lower rim can increase the
distance between the porphyrin units and reduce exciton
interactions. These changes can cause the reappearance of
Another important familyof macroc yc lic compounds, the
porphyrins, offers useful photoactive and/or electroactive
5
properties suitable for the construction of arti®cial
molecular devices. Therefore, the combination of (thia)-
calix[4]arene and porphyrin moieties might lead to novel
receptors the function of which is detectable bylumines-
cence spectroscopy. Our purpose was to synthesize new
(thia)calix[4]arene-porphyrin conjugates and to study their
spectroscopic properties depending on the conditions used
Keywords: porphyrin; calix[4]arene; thiacalix[4]arene; synthesis; spectro-
scopic properties.
Corresponding authors. Tel.: 1420-2-2435-4280; fax: 1420-2-2435-
p
4288; e-mail: lhotakp@vscht.cz; Tel.: 1420-2-6617-2193; fax: 1420-
2-2094-1502; e-mail: lang@iic.cas.cz
Figure 1. Design of calix±porphyrin receptors.
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00506-9

5476
M. Dudic et al. / Tetrahedron 58 (2002) 5475±5482
3
11 as a main product. As we have shown recently, chloride
8 reacts in an unexpected manner, never observed in
classical calixarene chemistry. Thiacalix[4]arene diamide
the original ¯uorescence intensityenabling the sensing of
the cations by¯uorescence spectroscopy.
10 was prepared bystirring a dichloromethane solution of
2
. Results and discussion
corresponding diacid 7 with MAP in the presence of DCC
for 2 h at room temperature. This procedure gave the
expected product 10 in high yield (72%) after isolation by
preparative TLC (silica gel). Analogously, diamide 9 was
obtained in 78% yield (Scheme 1).
2
.1. Synthesis of conjugates
The synthesis started from calixarenes 1 and 2 that were
transformed into corresponding diacetates 3 (71% yield)
and 6 (51% yield) by alkylation with an excess of ethyl-
bromoacetate in re¯uxing acetone using 1.05 equiv. of
K CO . These esters were hydrolyzed with NaOH in
aqueous ethanol under re¯ux to yield dicarboxylic acids 4
79% yield) and 7 (98% yield). Diamides 9 and 10 were
prepared bytwo methods: (i) byreacting ac yl chlorides
and 8 with monoaminoderivative of tetraphenylporphyrin
MAP, or (ii) bya direct reaction of carbox yl ic acids 4 and
with MAP using dicyclohexyl carbodiimide as a coupling
agent. The preparation of chlorides was accomplished by
stirring the starting acids with an excess of oxalyl chloride
in CCl under re¯ux. Chloride 5 was obtained in almost
quantitative yield and used as a crude compound in the
next step due to its presumed instability. Subsequent
condensation of 5 with MAP (2.2 equiv., THF, rt) in the
1
The structure of compound 9 was proved using H NMR
spectroscopy. The presence of two doublets of the CH
2
bridging groups (3.71 and 4.51 ppm) with the geminal
coupling constant of 13.2 Hz is a clear evidence of a cone
conformation. Similarly, the spectrum of thiacalixarene
2
3
(
t
5
derivative 10 with two sets of Bu and aromatic singlets
re¯ects the C2v symmetry that is typical for a cone con-
former. The FAB MS spectra show the molecular peaks
[M11] as the most intensive signals (m/z: 1990.0 and
2062.9 for 9 and 10, respectively).
1
7
As diamides 9 and 10 exhibited onlynegligible complexa-
tion abilitytowards alkali metal cations, we attempted to
strengthen the complexation bythe introduction of two
acetate groups. Interestingly, despite the fact that alkylation
of the phenolic OH groups with ethyl bromoacetate is a well
known reaction in the calixarene chemistry, all our attempts
to prepare dialkylated compound 12 have failed. All the
4
presence of base (Et N) gave diamide 9 in 30% yield.
3
Surprisingly, the same procedure using thiacalixarene
derivative 8 does not lead to diamide 10 but to bis-lactone
Scheme 1. (i) BrCH
quant.); (iv) NaOH, EtOH/water, re¯ux (98%); (v) oxalyl chloride/CCl
porphyrin/CH Cl
, rt (4!9, 72%, 7!10, 70%).
2
COOEt/K
2
CO
3
(1.05 equiv.), acetone, re¯ux (3, 71%; 6 51%); (ii) NaOH, EtOH/water, re¯ux (79%); (iii) oxalyl chloride/CCl
4
, re¯ux
(
4
, re¯ux (quant.); (vi) aminoporphyrin/Et N/THF, rt (9, 30%); (vii) DCC/amino-
3
2
2

M. Dudic et al. / Tetrahedron 58 (2002) 5475±5482
5477
Scheme 2. (i) BrCH
2
COOEt/Na CO
2
3
(excess), acetone, re¯ux (14, 32%); (ii) BrCH COOEt/KI/K
2
2
CO
3
(excess), DMF, rt (13, 67%); (iii) BrCH
2
COOEt/NaI/
Na CO (excess), DMF, rt (15, 30% and 16, 43%).
2 3
reaction conditions used (K CO or Na CO /acetone,
2
of the rings bearing porphyrins and between the amide
groups and aromatic protons of the rings bearing acetate
groups (Fig. 2).
3
2
3
K CO or Na CO /DMF, NaH/DMF) led to a verycomplex
3
2
2
3
reaction mixture and onlythe unusual tetraacetate derivative
3 was isolated and fullycharacterized. We found that
compound 9 is transformed to 13 in 67% yield using
1
1
In contrast to 16 in the 1,3-alternate conformation, the H
BrCH COOEt, K CO /DMF system and a catalytic amount
3
NMR spectrum of the cone conformer of 15 revealed a
different signal pattern. The resonances of the aromatic
protons of the rings bearing porphyrins or acetates in
compound 15 differ signi®cantly(7.21, 7.87 ppm), while
the chemical shifts of the corresponding resonances in 16
are almost the same (7.65, 7.68 ppm). This leads us to an
assumption that compound 15 adopts a less symmetrical
pinched cone conformation, where two opposite phenyl
rings face each other in the cavityand two ¯attened rings
are oriented outside the cavity.
2
2
1
of KI. The H NMR spectrum con®rms the C symmetry of
2v
1
2. The presence of the ester groups is supported bytwo
separated methyl signals of these groups (triplets at 1.47 and
.54 ppm) together with three individual singlets of
OCH CO± at 4.62, 4.83 and 4.91 ppm. The FAB MS spec-
1
±
2
1
trum shows the [M1Na] peak at m/z 2357.5 (Scheme 2).
8
The same alkylation reaction of thia-analog 10 resulted in
dialkylated products. Alkylation with ethyl bromoacetate/
Na CO in re¯uxing acetone for ®ve days led to monoester
2
3
1
K CO /DMF/KI system gave a mixture of two main
4 in 32% yield. Using DMF as a solvent in BrCH COOEt/
2
2
3
products 15 and 16. The products were isolated bycolumn
chromatographyon silica gel and identi®ed as diesters.
Generally, the conformational analysis of thiacalix[4]arene
derivatives is not a trivial task. The absence of the CH2
bridges means it is necessaryto applymore complicated
NMR methods. The splitting patterns of diesters 15 and
1
a cone conformation in CDCl . To distinguish between the
1
6 H NMR are similar indicating either a 1,3-alternate or
3
two conformers, a one-dimensional DPFGSE-NOE experi-
ment was carried out. Due to the slow molecular motion of
9
these compounds (molecular weight .2000), we were in the
negative NOE regime and recorded negative NOE enhance-
ments. The strong NOE coupling between the ester and
amide groups and no interaction between the ester groups
and calixarene aromatic rings in 15 indicate the cone confor-
mation. On the other hand, the 1,3-alternate conformation
of 16 was unambiguouslyproven bythe ®nding of NOE
interactions between the ester groups and aromatic protons
1
Figure 2. DPFGSE-NOE spectra of 16 (a) partial H NMR spectrum,
(b) ArH2 irradiated, (c) ArH1 irradiated.

5478
M. Dudic et al. / Tetrahedron 58 (2002) 5475±5482
Figure 3. Proposed preferred structure of compound 15.
To specifythe rings bearing the porphyrin units, a complete
1
3
1
13
assignment based on COSY, C NMR, H± C HMQC and
HMBC experiments was carried out. The keyevidence was
obtained from the HMBC experiment affording H± C two
and three bond correlations. The cross-peaks of the methyl-
ene protons with corresponding carbonyl and C1 carbons
Figure 4. Absorption spectra of (a) TPP, (b) 9, (c) 10, (d) 20 and (e) 24 in
CH Cl per porphyrin unit. Inset: ¯uorescence emission spectra of (f) TPP
and (g) in CH Cl2 excited at 516 nm, matching absorbance
516ˆ0.078^0.002 in 1 cm cell.
1
13
2
2
9
2
A
(
aromatic carbon bearing oxygen atom) determined that
the aromatic rings with less shielded protons (7.87 ppm)
bear the porphyrins and the rings with more shielded
protons (7.21 ppm) bear the acetate groups. These results
indicate that the rings facing each other have the acetate
groups on the lower rim, while the ¯attened rings oriented
outside the cavityare linked to the porph yr in units (Fig. 3).
porphyrin units in the ®rst excited singlet state is close to
that of TPP. However, the Soret bands (Fig. 4) are broader
compared to that of TPP at 418 nm and are split into two
components separated by9 and 17 nm for 9, 10 and 20, 24,
respectively. In addition, the molar absorption coef®cients
per porphyrin at the Soret maxima decrease with the
increasing number of the porphyrin units. A shoulder at
about 400 nm is due to the vibrational B(0,1) transition.
The presence of the methylene or sulphur calixarene bridges
does not affect the absorption spectra indicating that the
observed spectral splitting is caused byintramolecular exci-
ton coupling between the porphyrin units in the second
excited singlet state and that the calixarene moietybehaves
as a bridging unit keeping the porphyrins close enough to
effect short-range exciton coupling. Similarly, the
compound 15 with alkylated free phenolic OH groups
exhibits the same spectral behavior as the parent compound
The synthesis of conjugates bearing four porphyrin units
started from corresponding tetraesters 17 and 21 that were
prepared bythe alk yl ation of 1 and 2 with an excess of
ethyl-bromoacetate/K CO in re¯uxing acetone. These
2
3
esters were hydrolyzed with KOH in aqueous ethanol
under re¯ux to yield tetracarboxylic acids 18 (95% yield)
and 22 (94% yield). Subsequent reaction with oxalyl
chloride in CCl gave corresponding acyl chlorides 19 and
4
2
3 that were used without puri®cation for the next step.
Final condensation of chlorides with MAP (5 equiv.) was
carried out in THF at room temperature in the presence of
base (Et N). Pure tetraamides 20 and 24 were obtained after
7
10. According to the molecular exciton model a spectral
red shift is attributed to a head-to-tail alignment of the inter-
acting chromophores and a blue-shifted band is due to a
face-to-face alignment. The observed split Soret bands are
typical for an oblique alignment of the porphyrin units. Such
3
chromatographic separation on a silica gel column in 45 and
7
1% yields, respectively (Scheme 3).
7
2
.2. Spectroscopic properties
alignment exhibits exciton splitting of 10±20 nm and the
strong dependence of the relative intensities of the respec-
tive bands on the dihedral angle. The compounds 13 and 16
have no splitting of the Soret band indicating veryweak
interaction between the porphyrin units. This can be attrib-
uted to the steric restrictions imposed bytwo N-acetates or
tert-butyls between the arms bearing the interacting
The absorption spectra of 9, 10, 20 and 24 are shown in
Fig. 4. In the region above 500 nm the Q-bands have similar
shape and the molar absorption coef®cients (see Section 3)
are roughlytwice ( 9, 10) and four times (20, 24) as large as
those for 5,10,15,20-tetraphenylporphyrin (TPP). This
additivityindicates that the electronic structure of the
f
Table 1. Emission peaks lmax and the ¯uorescence quantum yields F of
the porphyrins in CH
Cl
2 2
and MeOH
Porphyrin
CH Cl
2
max (nm)
2
MeOH
max (nm)
a
f
a
F
f
l
F
l
b
TPP
9
656, 721
656, 721
656, 721
654, 720
656, 721
657, 723
658, 723
0.11
0.11
0.11
0.11
0.10
0.10
0.11
655, 719
655, 719
656, 720
654, 719
657, 721
661, 724
659, 725
0.10
0.10
0.09
0.09
0.08
0.07
0.02
1
1
1
2
2
0
5
6
0
4
a
Estimated error 10%.
F of TPP taken as a standard.
f
Scheme 3. (i) NaOH, EtOH/water, re¯ux (79%); (ii) oxalyl chloride/CCl
re¯ux (quant.); (iii) MAP/Et N, THF, rt (30%).
3
4
,
b
10

M. Dudic et al. / Tetrahedron 58 (2002) 5475±5482
5479
similar process was not observed till 2908C. The pinched
cone conformation does not support cation complexation.
In conclusion, novel (thia)calixarenes with the porphyrin
units on the lower rim have been prepared. Our results indi-
cate that the porphyrin units attached to the lower rim of the
calixarene cone are ¯exible, however, the steric hindrance
imposed bythe porph yr in units renders the conjugates with
a low tendencyto bind alkali metal cations. On the other
hand, the ¯exibilityof (thia)calixarene±porphyrin conjugates
could be a desired behavior for the design of novel receptors.
The work on more elaborate receptors is underway.
2 2
Figure 5. Absorption spectra in the Soret region of 15 and 16 in CH Cl (a)
and (b) and methanol (c) and (d).
3. Experimental
porphyrins. In CH Cl , the ¯uorescence emission bands do
2
3.1. General
2
not shift and the ¯uorescence quantum yields are the same
for all compounds (Fig. 4, Table 1) in agreement with the
absorption spectra where the Q-bands are unchanged.
Melting points are uncorrected and were determined using a
Boetius Block apparatus. H NMR spectra were recorded on
1
a Varian Gemini 300 and a Bruker AMX3 400 spectro-
meters using tetramethyl silane as an internal standard.
The assignment and NOE experiments were carried out on
The splitting of the Soret bands is stronglysolvent depen-
dent re¯ecting spatial ¯exibilityof the alignment of the
porphyrin units. A broadening of the Soret band (compare,
e.g. Fig. 5(b) and (d) for 16) indicates stronger exciton
coupling in more polar solvents such as methanol or
acetonitrile. More effective exciton coupling in methanol
is also evidenced bythe dramatic decrease of the
1
a Bruker DRX 500 Avance spectrometer. H NMR spectra
were measured with a spectral width 7500 Hz, data size
1
3
32K, the recycle time 3.1 s, and 16 scans. C NMR spectra
were measured with a spectral width 26.5 kHz, data size
32K, the recycle time 2.6 s, and 3000 scans. The spin
¯
uorescence quantum yields (Table 1). Thiacalix[4]arenes
systems were identi®ed by 2D COSY (128 t -increments
1
appear to be more sensitive to the solvent polaritythan
calix[4]arenes.
of 1024 data points,16 scans, spectral width 3000 Hz),
H± C HMQC (128 t increments, spectral widths
1
13
1
1 13
000 Hz in H and 23.7 kHz in C dimensions, respec-
3
tively, 16 scans, the delay for polarization transfer
1
13
2
.3. Complexation study
3
3
.5 ms), H± C HMBC (128 t increments, spectral widths
1
1
13
000 Hz in H and 23.7 kHz in C dimensions, respec-
The complexation behavior of the porphyrin±calixarene
conjugates was studied byUV±VIS and H NMR spectro-
tively, 128 scans, the delay for polarization transfer
1
1
9
60 ms). 1D H DPFGSE-NOE experiment was performed
using selective q3-gaussian-cascade of 79.2 ms, the mixing
time was 2 s. Typical p/2-pulses were 9.5 ms for H, and
scopy. The absorption and ¯uorescence spectra of the conju-
gates do not change upon addition of Li , Na and K as
1
1
1
1
1
studied in CH Cl , methanol and acetonitrile. In H NMR,
13
2
2
12 ms for C. FAB MS were measured on ZAB-EQ VG
no signi®cant changes attributable to the complexation were
observed after addition of alkali metal picrates to the solu-
tion of dihydroxy derivatives 9 and 10 in a CDCl /CD OD
analytical spectrometer. Absorption and ¯uorescence
spectra were measured on a Philips PU 8720 spectro-
photometer and on a Perkin±Elmer LS 50B luminescence
spectrophotometer, respectively. Absorbance titrations were
conducted with concentrated stock solutions of LiClO4,
NaClO and KClO in methanol. The salts were dried in a
3
3
1
4
:1 v/v mixture. It is well-known that calix[4]arene tetra-
esters or tetraamides have a pre-organized cavityon the
lower rim that considerablyincreases the af®nityfor cations.
Surprisingly, both tetraamides 20 and 24 appear to be very
poor complexation agents towards alkali metal cations. The
4
4
vacuum oven before the preparation of the solutions. All
emission spectra were corrected for the characteristics of
the detection monochromator and photomultiplier. The
1
11
broadening of the H NMR signals excluded determination
of the complexation constants. Evidently, the steric restric-
tions imposed byfour bulkyporph yr in units on the lower
rim hinder the pre-organization needed (C symmetry). A
absorbances were adjusted to the same value (,0.08/
1 cm) at the excitation wavelength at the Q (1,0) absorption
y
4
band (516 nm). Then, the ¯uorescence quantum yields Ff
were obtained bycomparison of the integrated area under
dynamic NMR study of tetraamide 24 (CD Cl ) revealed the
2
2
1
0
broadening of the signals at low temperatures which indi-
cates an additional dynamic process. This can be ascribed to
the emission spectra of the compounds and TPP in CH Cl
2 2
1
2
(F ˆ0.11) using refractive index correction.
f
the C ±C
v
0
interconversion between the two pinched cone
conformations. While the aromatic region of the spectrum
remains verybroad at the lowest accessible temperature
2
2v
1
3
14
15
8
Compounds 3, 6, 17 and 21 were prepared according
to procedures known bythe reaction of 1 and 2 with ethyl
bromoacetate in boiling acetone in the presence of Na CO
(
2808C), the signal of the tert butyl groups is clearly sepa-
2
3
rated into two singlets ꢀDn ù 200 Hz† with a coalescence
temperature approx. 2608C. This temperature is much
higher than that of corresponding tetraacetate 21 where a
or K CO . Corresponding diacid 4 and tetraacid 18 were
2 3
prepared by the hydrolysis of starting esters using NaOH
in boiling aqueous ethanol, while the thiacalix[4]arene
1
6

5480
M. Dudic et al. / Tetrahedron 58 (2002) 5475±5482
1
4
derivatives 7 and 22 were obtained bythe same procedure
using KOH.
OCH CO), 7.74 (m, 20H, CH por.), 7.78 (s, 4H, H-arom),
2
7.86 (s, 4H, H-arom), 8.20 (m, 10H, CH por.), 8.34 (s, 8H,
CH por.), 8.84 (s, 8H, CH por.), 8.94 (d, Jˆ4.8 Hz, 4H, CH
por.), 9.28 (d, Jˆ4.8 Hz, 4H, CH por.), 9.51 (s, 2H, ArOH),
N O S : C,
132 110 10 6 4
3
.1.1. Synthesis of derivative 9. Method A. A mixture of
1
6
22
diacid 4 (17 mg; 2.24£10 mmol) and (COCl) (39 ml;
11.13 (s, 2H, NHCO). EA calcd for C
H
2
0
.44 mmol) in 5 ml of anhydrous CH Cl was stirred under
2
76.94; H, 5.38; N, 6.80; Found: C, 77.39; H, 5.71; N,
7.13. FAB MS m/z (rel. int.) 2062.9 [M11] (100).
2
1
re¯ux for 3 h. The solvent was distilled off, the residue was
dissolved in anhydrous CH Cl (5 ml) and the solvent was
2
1
21
UV±VIS (CH Cl ) l (nm), 1 (mM cm ): 417 (620),
max
2
2
2
2
again evaporated under reduced pressure. This procedure
was repeated twice to remove all traces of oxalyl chloride.
The resulting solid (acyl chloride 5) was then dried in a high
vacuum for 1 h. The solid was dissolved in 5 ml of dryTHF
and this solution was added dropwise at room temperature
516 (31.3), 551 (14.5), 591 (9.1), 647 (7.3).
3.1.3. Synthesis of derivative 13. A mixture of 9 (100 mg,
2
2
5.03£10 mmol) and K CO (70 mg, 0.503 mmol) in
2
3
anhydrous DMF (10 ml) was stirred for 30 min. Thereafter
ethyl bromoacetate (56 ml, 0.51 mmol) and a catalytic
amount of KI were added and the reaction mixture was
stirred for 4 days at room temperature. DMF was removed
in vacuo and the residue was stirred overnight in a CHCl3/
water mixture (30 ml/30 ml). The organic layer was dried
1
7
22
to a stirred solution of MAP (30 mg; 4.76£10 ) and Et N
3
(
31 ml; 0.22 mmol) in 5 ml of dryTHF. The reaction
mixture was stirred for 1 h and the solvent was removed
in a reduced pressure. The residue was dissolved in CHCl3
(
20 ml) and washed with water (20 ml). The separated
organic layer was dried over MgSO . After the evaporation
over MgSO and evaporated under a reduced pressure. The
4
4
of solvent, the crude product was puri®ed bycolumn chro-
matographyon silica gel using CHCl /petroleum ether (5:1)
residue was puri®ed bycolumn chromatographyusing
CHCl /acetone (2:1) mixture with 2% Et N as an eluent to
give the pure product as purple micro crystals (72 mg, 67%).
3
3
3
as an eluent to give the product 9 as a purple powder (13 mg,
3
1
0%). Mp .3508C (ethyl acetate). H NMR (CDCl ): d
1
Mp 263±2658C (CHCl /ethanol). H NMR (300 MHz,
3
3
t
2.81 (s, 4H, NH por.), 1.20 (s, 18H, Bu ), 1.34 (s, 18H,
t
CDCl ) d: 22.78 (s, 4H, NH por.), 1.16 (s, 18H, Bu ),
2
3
t
t
Bu ), 3.71 (d, Jˆ13.2 Hz, 4H, ArCH Ar eq.), 4.51 (d,
1.20 (s 18H, Bu ), 1.47 (t, Jˆ7.3 Hz, 6H, OCH CH ), 1.54
2
2
3
Jˆ13.2 Hz, 4H, ArCH Ar ax.), 4.96 (s, 4H, OCH CO),
(t, Jˆ7.3 Hz, 6H, OCH CH ), 3.50 (d, Jˆ11.7 Hz, 4H,
2
2
2
3
7
.16 (s, 4H, H-arom), 7.24 (s, 4H, H-arom), 7.71 (m, 20H,
ArCH Ar), 4.43 (q, Jˆ7.0 Hz, 4H, OCH CH ), 4.50 (d,
2 2
2
2
3
CH por.), 8.17 (m, 10H, CH por.), 8.30 (m, 8H, CH por.),
.80 (s, 8H, CH por.), 8.84 (s, 2H, ArOH), 8.88 (d,
Jˆ11.7 Hz, 4H, ArCH Ar), 4.62 (s, 4H, CH CO), 4.67 (q,
2 3 2
8
Jˆ7.0 Hz, 4H, OCH CH ), 4.83 (s, 4H, CH CO), 4.91 (s,
Jˆ4.8 Hz, 4H, CH por.), 9.17 (d, Jˆ4.8 Hz, 4H, CH por.),
4H, CH CO), 7.19 (s, 8H, H-arom), 7.78 (m, 16H, H-arom),
2
1
1.11 (s, 2H, NHCO). C NMR (100 MHz, CDCl ): d
3
1
3
1
1
1
7.89 (d, Jˆ8.1 Hz, 4H, H-arom), 4.52 (d, Jˆ5.9 Hz, 8H,
H-arom), 8.34 (d, Jˆ7.7 Hz, 4H, H-arom), 8.79 (d,
Jˆ7.7 Hz, 4H, H-arom), 8.86 (brs, 16H, H-arom), 8.94
3
1.09, 31.63, 32.70, 34.06, 34.36, 75.11, 117.67, 119.82,
19.87, 120.03, 126.03, 126.57, 126.71, 127.29, 127.54,
32.57, 134.48, 135.03, 137.71, 138.46, 142.24, 142.28,
43.89, 148.55, 149.17, 149.49, 165.95. IR (CHCl ) n
1
3
(m, 2H, H-arom). C NMR (100 MHz, CDCl ) d: 14.46,
3
29.69, 30.11, 31.32, 34.22, 36.94, 51.85, 61.83, 61.97,
73.52, 74.45, 117.79, 120.45, 120.74, 125.83, 125.98,
126.16, 126.49, 126.73, 127.83, 134.57, 136.36, 139.97,
3
max
2
1
(cm ): 1689 (CvO), 3320 (OH, NH). EA calcd for
C136H118N O : C, 82.15; H, 5.98; N, 7.04. Found: C,
10
6
8
2.58; H, 6.24; N, 7.34. FAB MS m/z (rel. int.) 1990
1
142.03, 148.37, 150.09, 150.56, 169.17, 170.40, 171.24.
IR (CHCl ) n
EA calcd for C152H142N O : C, 78.26; H, 6.14; N, 6.00;
10 14
1
21
(cm ): 1749, 1676 (CvO), 3322 (NH).
max
[
(
(
M11]
(100). UV±VIS (CH Cl ) lmax (nm),
2
2
3
2
1
21
mM cm ): 417 (730), 516 (37.9), 551 (17.9), 591
11.5), 646 (8.6).
Found: C, 78.51; H, 6.47; N, 6.33. FAB MS m/z (rel. int.)
(nm), 1
max
1
357.5 [M1Na] (100). UV±VIS (CH Cl ) l
(mM cm ): 419 (650), 516 (25.3), 550 (11.8), 590 (7.7),
645 (5.5).
2
2
2
2
1
21
Method B. A solution of 4 (130 mg; 0.17 mmol) and
dicyclohexyl carbodiimide (141 mg; 6.82 mmol) in
CH Cl (10 ml) was stirred for 10 min and then MAP
2
2
(
215 mg; 0.34 mmol) was added. The reaction mixture
3.1.4. Synthesis of derivative 14. Na CO3 (32 mg;
2
was then stirred for 2 h at room temperature. The solvent
was removed in vacuo, the residue was dissolved in CHCl3
0.302 mmol) and BrCH COOEt (34 ml; 0.306 mmol) were
2
2
2
added to a solution of 10 (63 mg; 3.06£10 mmol) in
anhydrous acetone and the reaction mixture was re¯uxed
for 5 days. The solvent was removed in vacuo. The residue
(
was dried over MgSO . The crude product was puri®ed by
50 ml) and washed with water (30 ml). The organic layer
4
column chromatographyon silica gel using CHCl 3/
petroleum ether (5:1) mixture as an eluent to yield the
product 9, identical with the above-obtained sample
was dissolved in CHCl (15 ml) and washed with water
3
(20 ml). The organic layer was dried over MgSO and
4
evaporated to dryness. The crude product was puri®ed by
preparative TLC using CH Cl /ethyl acetate/petroleum
ether mixture (1:1:12) as an eluent to give 22 mg of the
(
264 mg, 78%).
2
2
3
.1.2. Synthesis of derivative 10. Analogouslyto the
synthesis of 9 (Method B) starting from 7 (150 mg;
.18 mmol) and DCC (141 mg; 0.682 mmol) product 10
title compound (32%) as a purple powder. Mp 236±2398C
(CHCl /MeOH). H NMR (300 MHz CDCl ) d: 22.87 (s,
1
3
3
0
4H, NH por.), 1.00 (t, Jˆ7.3 Hz, 3H, OCH CH ), 1.15 (s,
2
3
t
t
18H, Bu ), 1.18 (s, 9H, Bu ), 1.31 (s, 9H, Bu ), 4.43 (q,
t
was obtained as a purple powder after column chromato-
graphyon silica gel using CHCl /petroleum ether (4:1)
Jˆ7.3 Hz, 2H, OCH CH ), 5.00 (d, Jˆ15.4 Hz, 2H,
OCH CONH), 5.05 (s, 2H, OCH COOEt), 5.45 (d,
2 2
3
2
3
mixture as an eluent (270 mg, 72%). Mp .3508C (CHCl /
3
1
hexane). H NMR (300 MHz, CDCl ) d: 22.74 (s, 4H, NH
Jˆ15.4 Hz, 2H, OCH CONH), 7.4 (brs, 8H, H-arom),
3
2
t
por.), 1.28 (s, 18H, Bu ), 1.37 (s, 18H, Bu ), 5.11 (s, 4H,
t
7.48 (m, 8H, H-arom), 7.68 (s, 2H, H-arom), 7.75 (m, 8H,

M. Dudic et al. / Tetrahedron 58 (2002) 5475±5482
5481
H-arom), 7.84 (d, Jˆ7.0 Hz, 4H, H-arom), 8.23 (m, 16H,
H-arom), 8.52 (d, Jˆ4.8 Hz, 4H, H-arom), 8.68 (d,
Jˆ4.0 Hz, 4H, H-arom), 8.79 (m, 4H, H-arom), 8.87 (m,
74.88; H, 5.27; N, 5.95. FAB MS m/z (rel. int.) 2233.0
[M1H]
(mM cm ) in parentheses: 419 (690), 516 (30.4), 551
(16.2), 591 (9.3), 647 (7.0).
1
(100). UV±VIS (CH Cl ) lmax (nm), 1
2 2
2
1
21
4
H, H-arom), 10.51 (s, 1H, CONH). FAB MS m/z (rel.
1
int.) 2147.7 [M1H] (100).
1
6
3
.1.6. Synthesis of derivative 20. A solution of 18
2
2
3
1
.1.5. Synthesis of derivative 15 and 16. To a solution of
(30 mg, 3.4£10 mmol) and (COCl) (0.3 ml, 3.4 mmol)
2
2
2
0 (150 mg; 7.28£10 mmol) in anhydrous DMF (20 ml),
in anhydrous CCl (5 ml) was re¯uxed for 4 h. The solvent
4
BrCH COOEt (81 ml, 0.73 mmol), Na CO (78 mg,
2
0
the reaction mixture was stirred for 7 days at room tempera-
ture. DMF was removed under reduced pressure, the residue
was dissolved in CHCl /H O (50 ml/100 ml) mixture and
was removed in vacuum and the residue was dissolved in
anhydrous CH Cl (5 ml). The CH Cl was distilled off
2
3
2
2
.73 mmol) and NaI (10 mg, 6.67£10 ) were added and
2
2
2
2
again. This procedure was repeated twice. The resulting
acyl chloride 19 was then dried in high vacuo for 1 h. The
crude product was dissolved in 5 ml of anhydrous THF and
this solution was added dropwise to a mixture of MAP
3
2
stirred overnight. The organic layer was separated, dried
over MgSO4 and evaporated. The crude product was
puri®ed bycolumn chromatographyon silica gel using
CH Cl /Et N (100:1) to give two conformations of the
(107 mg, 0.17 mmol) and Et N (38 ml, 0.27 mmol) in
3
anhydrous THF (5 ml). The reaction mixture was stirred
for 2 h at room temperature. The solvent was removed in
vacuo, the residue was dissolved in CHCl (30 ml) and
2
2
3
product: 1,3 alternate 16 (70 mg, 43%) and cone 15
48 mg, 30%).
3
(
washed with water (20 ml). The separated organic layer
was dried over MgSO . The crude product was puri®ed by
4
1
Compound 15. Mp 271±2758C (CHCl /MeOH). H NMR
column chromatographyon silica gel using CHCl 3/
petroleum ether (3:1) mixture containing 2% of Et N as
3
(
500 MHz, CDCl ) d: 22.75 (s, 4H, NH por.), 1.06 (s, 18H,
3
3
t
t
Bu ), 1.09 (t, Jˆ7.1 Hz, 6H, OCH CH ), 1.42 (s, 18H, Bu ),
an eluent to yield the product as a purple powder (50 mg,
45%). Mp .3508C. H NMR (300 MHz, CDCl ) d: 22.91
2
3
1
4
OCH COOEt), 5.70 (s, 4H, OCH CONH), 7.21 (s, 4H,
.17 (q, Jˆ7.1 Hz, 4H, OCH CH ), 5.00 (s, 4H,
2
3
3
t
(s, 8H, NH por.), 1.27 (s, 36H, Bu ), 3.64 (d, Jˆ13.19 Hz,
2
2
H-arom), 7.64 (t, Jˆ7.4 Hz, 8H, CH por.), 7.71 (t,
4H, CH eq.), 5.05 (d, Jˆ13.19 Hz, 4H, CH ax.), 5.13 (s,
2
2
Jˆ7.4 Hz, 4H, CH por.), 7.79 (m, 6H, CH por.), 7.87 (s,
8H, CH CO), 7.08 (brs, 16H, CH por.), 7.23 (s, 8H,
2
4
H, H-arom), 8.09 (d, Jˆ7.1 Hz, 8H, CH por.), 8.25 (d,
H-arom), 7.63 (brs, 8H, CH por.), 7.75 (s, 24H, CH por.),
8.19 (d, Jˆ4.03 Hz, 16H, H por.), 8.29 (brs, 8H, H por.),
8.62 (brs, 8H, H por.), 8.71 (brs, 8H, H por.), 8.76 (d,
Jˆ6.6 Hz, 4H, CH por.), 8.28 (d, Jˆ8.2 Hz, 4H, CH por.),
.39 (d, Jˆ8.2 Hz, 4H, CH por.), 8.77 (d, Jˆ4.4 Hz, 4H, CH
por.), 8.81 (d, Jˆ4.4 Hz, 4H, CH por.), 8.85 (d, Jˆ4.3 Hz,
H, CH por.), 8.94 (d, Jˆ4.3 Hz, 4H, CH por.), 11.15 (s, 2H,
8
1
3
Jˆ4.03 Hz, 16H, H por.), 10.00 (s, 4H, NHCO). C NMR
4
(100 MHz, CDCl ) d: 31.46, 34.27, 73.55, 119.134, 119.84,
3
1
3
NHCO). C NMR (100 MHz, CDCl ) d: 14.01, 29.70,
126.06, 126.60, 127.08, 127.58, 132.82, 134.02, 134.47,
135.32, 136.72, 137.21, 141.61, 142.16, 146.20, 168.32.
3
3
1
1
1
1
0.99, 31.35, 34.22, 34.41, 72.61, 74.72, 119.86, 119.96,
20.01, 120.06, 126.52, 126.65, 127.54, 127.64, 128.20,
28.26, 133.22, 134.44, 134.55, 135.06, 136.73, 137.80,
38.42, 142.07, 142.21, 147.11, 147.63, 156.46, 159.25,
2
1
IR (CHCl ) n
3
(cm ): 1681 (CvO), 3321 (NH). EA
max
calcd for C228H180N O : C, 82.29; H, 5.45; N, 8.42;
20
8
Found: C, 81.81; H, 5.17; N, 8.11. FAB MS m/z (rel. int.)
(nm), 1
max
2
1
1
3326.6 [M11] (100). UV±VIS (CH Cl ) l
68.16, 168.99. IR (CHCl ) n
3
(cm ): 1751, 1679
max
2
2
2
1
21
(
CvO), 3295 (NH). EA calcd for C140H122N O S : C,
10
(mM cm ): 419 (990), 517 (63.7), 552 (30.9), 591
(19.5), 648 (16.4).
10 4
7
5
5.31; H, 5.51; N, 6.27; Found: C, 74.81; H, 5.47; N,
.91. FAB MS m/z (rel. int.) 2233.0 [M11] (100).
1
2
1
21
UV±VIS (CH Cl ) l (nm), 1 (mM cm ): 418 (670),
max
3.1.7. Synthesis of derivative 24. A solution of 22 (30 mg,
2
2
2
2
5
16 (30.7), 550 (13.3), 591 (9.1), 646 (6.8).
3.15£10 mmol) and oxalyl chloride (0.3 ml, 3.4 mmol) in
anhydrous CCl (5 ml) was re¯uxed for 4 h. The solvent was
4
1
Compound 16. Mp 243±2458C (CHCl /MeOH). H NMR
distilled off, the residue was dissolved in anhydrous CH Cl
2
3
2
(
500 MHz, CDCl ) d: 22.69 (s, 4H, NH por.), 1.26 (s, 18H,
3
(5 ml) and the solvent was distilled off again. After drying in
high vacuo for 1 h the acyl chloride 23 was dissolved in 5 ml
of absolute THF and the resulting solution was added to a
t
t
Bu ), 1.27 (t, Jˆ7.1 Hz, 6H, OCH CH ) 1.36 (s, 18H, Bu ),
2
3
4
OCH COOEt), 5.08 (s, 4H, OCH CONH), 6.76 (brs, 4H,
.27 (q, Jˆ7.1 Hz, 2H, OCH CH ), 4.74 (s, 4H,
2
3
solution of MAP (100 mg, 0.16 mmol) and Et N (38 ml,
3
2
2
CH por.), 6.98 (brs, 8H, CH por.), 7.65 (s, 4H, H-arom),
.68 (s, 4H, H-arom), 7.78 (m, 6H, CH por), 7.81 (d,
Jˆ8.0 Hz, 4H, CH por.), 7.92 (d, Jˆ7.3 Hz, 8H, CH por.),
.11 (d, Jˆ8.0 Hz, 4H, CH por.), 8.22 (d, Jˆ6.6 Hz, 4H, CH
por.), 8.68 (d, Jˆ4.0 Hz, 4H, CH por.), 8.75 (d, Jˆ4.2 Hz,
H, CH por.), 8.81 (d, Jˆ4.2 Hz, 4H, CH por.), 8.85 (d,
0.27 mmol) in anhydrous THF (5 ml). The reaction mixture
was stirred for 2 h at room temperature. THF was removed
in vacuo, the residue was dissolved in CHCl (30 ml) and
7
3
8
washed with water (20 ml). The organic layer was dried
over MgSO . The crude reaction mixture was puri®ed by
4
4
column chromatographyon silica gel using petroleum ether/
CHCl /ethyl acetate (4:1:1) with 2% Et N as an eluent to
yield the product as a purple powder (65 mg, 71%). Mp
1
3
Jˆ4.3 Hz, 4H, CH por.), 9.17 (brs, 2H, NHCO). C NMR
3
3
(
100 MHz, CDCl ) d: 14.19, 29.70, 30.97, 31.35, 34.54,
3
1
6
1
1
1
1
0.71, 65.93, 117.97, 119.49, 120.06, 126.05, 126.63,
27.02, 127.66, 128.41, 128.76, 132.87, 133.99, 134.53,
34.89, 137.36, 138.51, 141.85, 142.21, 147.54, 147.92,
.3508C. H NMR (300 MHz, CDCl ) d: 22.89 (s, 8H,
3
t
NH por.), 1.31 (s, 36H, Bu ), 5.69 (s, 8H, CH CO), 7.09
2
(t, Jˆ6.96 Hz, 8H, H-arom), 7.21 (t, Jˆ6.22 Hz, 4H,
H-arom), 7.70 (m, 44H, H-arom), 8.18 (d, Jˆ5.13 Hz, 8H,
H-arom), 8.26 (d, Jˆ8.42 Hz, 8H, H-arom), 8.36 (d,
Jˆ4.40 Hz, 8H, H-arom), 8.49 (d, Jˆ8.42 Hz, 8H,
2
1
55.81, 156.66, 166.74, 167.62. IR (CHCl ) n
3
(cm ):
max
770, 1685 (CvO), 3286 (NH). EA calcd for
C140H122N O S : C, 75.31; H, 5.51; N, 6.27; Found: C,
10 10 4

5482
M. Dudic et al. / Tetrahedron 58 (2002) 5475±5482
H-arom), 8.65 (d, Jˆ4.76 Hz, 8H, H-arom), 8.76 (d,
Jˆ4.76 Hz, 8H, H-arom), 8.82 (d, Jˆ4.76 Hz, 8H,
5. Sessler, J. L.; Wang, B.; Springs, S. L.; Brown, C. T.
Comprehensive Supramolecular Chemistry; Murakami, Y.,
Ed.; Elsevier Science: Oxford, 1996; Vol. 4, pp. 311±336.
6. Stibor, I.; Ruzickov a , M.; Kr a tk y , R.; Vindys, M.; Havl Âõ cek,
J.; Pinkhassik, E.; Lhot a k, P.; Musta®na, A. R.; Morozova,
Y. E.; Kazakova, E. K.; Gubskaya, V. P. Collect. Czech.
Chem. Commun. 2001, 66, 641±662.
1
H-arom), 10.36 (s, 4H, NHCO). C NMR (100 MHz,
3
CDCl ): d 31.26, 34.55, 75.83, 118.80, 119.51, 119.79,
3
1
1
1
3
5
19.88, 126.08, 126.61, 127.08, 127.58, 127.93, 134.10,
34.51, 135.39, 137.32, 138.83, 141.74, 142.27, 148.21,
2
1
58.15, 167.28. IR (CHCl ) n
3
(cm ): 1690 (CvO),
max
320 (NH). EA calcd for C224H172N O S : C, 79.13; H,
20
7. Kasha, M.; Rawls, H. R.; El-Bayoumi, M. A. Pure Appl.
Chem. 1965, 11, 371±392. (b) Hunter, C. A.; Sanders,
J. K. M.; Stone, A. J. Chem. Phys. 1989, 133, 395±404.
(c) Stomphorst, R. G.; Koehorst, R. B. M.; Van Der Zwan,
G.; Benthem, B.; Schaafsma, T. J. J. Porph. Phthal. 1999, 3,
8 4
.10; N, 8.24; Found: C, 78.81; H, 5.17; N, 8.01. UV±VIS
2
1
21
(
CH Cl ) l
2
(nm), 1 (mM cm ): 419 (1 020), 517
max
2
(
62.2), 552 (29.9), 592 (19.0), 648 (15.7).
346±354. (d) Osuka, A.; Maruyama, K. J. Am. Chem. Soc.
1988, 110, 4454±4456.
Acknowledgements
8
. Lhot a k, P.; Stastn y , V.; Zlatu sÏ kov a , P.; Stibor, I.; Michlov a ,
V.; Tkadlecov a , M.; Havl Âõ cek, J.; S y kora, J. Collect. Czech.
Chem. Commun. 2000, 65, 757±771.
We thank the Grant Agencyof the Czech Republic for
®
nancial support (No. 104/00/1722 and 203/99/1163).
9
. Stott, K.; Stonehouse, J.; Keeler, J.; Hwang, T. L.; Shaka, A. J.
J. Am. Chem. Soc. 1995, 117, 4199±4200.
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