2,2'-Bipyridine lariat calixcrowns: A new class of encapsulating ligands forming highly luminescent Eu3+ and Tb 3+ complexes

Article abstract of DOI:10.1002/(SICI)1521-3765(20000317)6:6<1026::AID-CHEM1026>3.0.CO;2-C

A new class of calix[4]arene crown ethers with one or two bipyridines appended to the polyether ring (lariat calixcrowns) have been designed and synthesized; the luminescence properties of their Eu³⁺ and Tb³⁺ complexes have been studied in acetonitrile. In this solvent, long lifetimes for the metal emitting states and high metal-luminescence intensities obtained upon ligand excitation have been observed in both Eu³⁺ and Tb³⁺ complexes. The association constants in methanol have been determined for some of the complexes studied.

Full text of DOI:10.1002/(SICI)1521-3765(20000317)6:6<1026::AID-CHEM1026>3.0.CO;2-C

FULL PAPER
2,2'-Bipyridine Lariat Calixcrowns: A New Class of Encapsulating Ligands
Forming Highly Luminescent Eu3‡ and Tb3‡ Complexes
Claudia Fischer,[a] Gianluca Sarti,[b] Alessandro Casnati,[a] Barbara Carrettoni,[a]
Ilse Manet,[b] Ruud Schuurman,[a] Massimo Guardigli,[b] Nanda Sabbatini,*[b] and
Rocco Ungaro*[a]
Abstract: A new class of calix[4]arene crown ethers with one or two bipyridines
appended to the polyether ring (lariat calixcrowns) have been designed and
synthesized; the luminescence properties of their Eu3‡ and Tb3‡ complexes have
been studied in acetonitrile. In this solvent, long lifetimes for the metal emitting
states and high metal-luminescence intensities obtained upon ligand excitation have
been observed in both Eu3‡ and Tb3‡ complexes. The association constants in
methanol have been determined for some of the complexes studied.
Keywords: calixarenes ´ conforma-
tion analysis ´ crown compounds ´
lanthanides ´ luminescence
quantum yield upon ligand ex-
Introduction
citation for [Tb ꢀ 1]3‡.[=] How-
Eu3‡ and Tb3‡ complexes of encapsulating ligands are widely
studied because of their potential use as labels in bioaffinity
assays, which is based on time-resolved measurements of the
metal luminescence obtained upon ligand excitation followed
by ligand-to-metal energy transfer.[1±3] The sensitivity of this
type of assay strongly depends on the metal luminescence
intensity, which is determined by the product of the molar
absorption coefficient of the ligand in the complex at the
excitation wavelength and the metal luminescence quantum
yield.[4] Therefore, research in this field aims at obtaining
complexes characterized by high molar absorption coeffi-
cients of the ligands and high metal-luminescence quantum
yields upon ligand excitation. Functionalized calixarenes are
one of the classes of encapsulating ligands able to form Eu3‡
and Tb3‡ complexes that exhibit metal luminescence upon
ligand excitation. The study of the complexes of the calix[4]-
arene tetramide ligand 1[5] with the Eu3‡ and Tb3‡ ions
demonstrated the stability and solubility of these complexes
in water, as well a remarkably high metal-luminescence
ever, for this complex the met-
al luminescence intensity was
rather low because of the low
molar absorption coefficients
of the ligand.
In order to increase the intensity of the metal luminescence,
we introduced two 6-methyl-2,2'-bipyridine or two 2,9-
dimethyl-1,10-phenanthroline chromophores at the lower
rim of the calix[4]arene 1,3-bisamide, which gave a podand-
like structure with two types of chelating chains. Interestingly,
some of the Tb3‡ complexes of these ligands showed intense
metal luminescence upon ligand excitation.[6] The lumines-
cence properties of some Eu3‡ and Tb3‡ complexes of
functionalized calixarenes containing chromophoric units
have also been studied by other authors.[6±9]
More recently, we decided to synthesize a new class of
calix[4]arene receptors incorporating the 2,2'-bipyridine (bpy)
chromophore, in order to examine the effects of the relative
orientations of the chromophore and the calixarene moiety on
the thermodynamic stability and the luminescence properties
of the Eu3‡ and Tb3‡ complexes. Note that in the complexes
studied previously, the bpy chromophore is directly linked to
the calix[4]arene oxygen atom and is nearly perpendicular to
the macrocyclic ring.
[a] Prof. R. Ungaro, Dr. C. Fischer, Prof. A. Casnati, Dr. B. Carrettoni,
Dr. R. Schuurman
Á
Dipartimento di Chimica Organica e Industriale dellꢀUniversita
Parco Area delle Scienze 17/A, 43100 Parma (Italy)
Fax : (‡ 39)0521-905-472
E-mail: ungaro@ipruniv.cce.unipr.it
[b] Prof. N. Sabbatini, Dr. G. Sarti, Dr. I. Manet, Dr. M. Guardigli
Á
Dipartimento di Scienze Farmaceutiche dellꢀUniversita
[=] Following the widely accepted notation (J.-M. Lehn, Struct. Bonding
(Berlin) 1973, 16, 1), we will indicate the formation of the inclusion
complexes of the ligands (L) with different lanthanide ions (Ln3‡) as
Via Belmeloro, 6, 40126 Bologna (Italy)
Fax : (‡ 39)051-343-398
E-mail: mguardig@alma.unibo.it
[Ln ꢀ L]3‡
.
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Chem. Eur. J. 2000, 6, No. 6

1026±1034
A different orientation of the chromophore could, in
principle, give rise to a more efficient ligand ± metal inter-
action, thus increasing the stability of the complexes and the
intensity of the metal luminescence upon ligand excitation. To
this end, we started with a class of ionophores, the calix[4]-
arene crown ethers (calixcrowns), which exhibit exceptional
efficiency in the complexation of metal ions.[10±12] Some of
these ligands have been used for lanthanide complexation, but
their Eu3‡ and Tb3‡ complexes showed poor luminescence
properties.[13] We subsequently designed the new lariat[14]
calixcrowns 2 ± 4 ligands, in which one or two bipyridines
protected hydroxymethyl group on the second carbon atom of
the ethylene chain. Very little is known about the general
synthesis of such oligoethylene glycols and the few examples
reported in literature are fragmentary or incomplete. Ikeda
et al.[15] reported the synthesis of compound 14 by condensa-
tion of the commercially available glycidyl ether and tri-
ethylene glycol. However the reaction is not very regioselec-
tive and the glycol can react with either the primary or the
secondary carbon atom of the epoxy group to afford a mixture
of structural isomers that is very difficult to separate. A more
promising approach has been proposed by Krakowiak
et al.,[16] who reported the use of 1-allyloxy glycerol for the
synthesis of some allyloxymethyl oligoethylene glycols. This
approach also seemed particularly attractive to us because of
the possibility of direct access to one of the two enantiomers
of compound 11, which can be easily prepared from the well-
known and useful chiral synthon (R)- or (S)-2,3-O-isopro-
pylideneglyceraldehyde.[17] Ditosylates 15 and 16 of 2-allyl-
oxymethyl tri- and tetraethylene glycols were prepared
through the reaction sequence depicted in Scheme 1.
are attached to the crown ether units. This ligand structure
would yield a complex with the desired orientation of the
chromophore parallel to the calix[4]arene ring. Moreover, the
conformational flexibility of the chromophore linked to the
crown ether should contribute to optimization of the metal ±
ligand interaction.
In this paper we report the synthesis, the conformational
and binding properties of ligands 2 ± 4, and the luminescence
properties of their complexes with the Eu3‡ and Tb3‡ ions in
acetonitrile.
Scheme 1. Preparation of the ditosylates 15 and 16.
Results and Discussion
First, 1-O-allyl-glycerol [(dl)-11] was protected on the
primary hydroxyl by reaction with trityl chloride and triethyl
amine in dichloromethane.[16] The monotrityl monotosyl
oligoethylene glycols 9 and 10 were prepared by reaction of
trityl chloride in pyridine with a large excess of di- or
triethylene glycols[18,19] followed by the reaction of the
resulting monotrityl ethers (7 and 8) with tosyl chloride in
dichloromethane. The resulting monotrityl monotosyl glycols
9 and 10 were allowed to react with the 1-O-allyl-3-O-trityl
glycerol [(dl)-12] in basic conditions (NaH, DMF); the
products thus formed were deprotected with HCl (36%) to
give glycols 13 and 14 in high yields (75 and 71%, respec-
tively). Compounds 13 and 14 were subsequently tosylated
with tosyl chloride, triethylamine, and a catalytical amount of
dimethylaminopyridine (DMAP) in dichloromethane to yield
15 and 16.
Synthesis of oligoethylene glycols: Synthesis of the racemic
lariat mono-bipyridine calixcrown-4 (2) or calixcrown-5 (3)
requires the use of a tri- or tetraethylene glycol, respectively.
Appropriate glycols such as compounds 13 and 14 bear a
Á
Abstract in Italian: E stata progettata e sintetizzata una nuova
classe di eteri a corona a base calix[4]arenica recanti uno o due
bipiridili legati allꢀanello polietereo, e percio chiamati calix-
Á
crown-lariati. Le proprietà di luminescenza dei corrispondenti
complessi di Eu3‡ e Tb3‡ sono state studiate in acetonitrile. In
questo solvente, sia i complessi di Eu3‡ che quelli di Tb3‡
presentano elevati tempi di vita degli stati emittenti del metallo
e alte intensità di luminescenza per eccitazione nel legante. Per
alcuni dei complessi studiati sono state determinate le costanti
di associazione in metanolo.
In order to prepare a lariat bis-bipyridine calixcrown-5
derivative, we also needed a glycol with two protected
Chem. Eur. J. 2000, 6, No. 6
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R. Ungaro, N. Sabbatini et al.
FULL PAPER
hydroxymethyl groups symmetrically located on the second
and seventh carbon atom of tetraethylene glycol (18). We
synthesized compound 18 by following the reactions reported
in Scheme 2.
Scheme 3. Preparation of enantiomerically pure (R)-11.
use [Pb(OAc)4] because it has been reported to give the best
enantiomeric purity in the synthesis of (R)-2,3-isopropyli-
deneglyceraldehyde.[20] The latter compound was directly
reduced in situ with NaBH4 to afford compound 21, which was
then alkylated with allyl bromide to give compound 22.[21,22]
Deprotection in acidic media to (R)-11 followed by tritylation
gives compound (S)-12 (Scheme 2). Two equivalents of (S)-1-
O-allyl-3-O-trityl glycerol, (S)-12, were treated with diethyl-
ene glycol ditosylate (17); subsequent detritylation in situ
with concentrated HCl gave compound 18c in 76% yield.
Tosylation under the usual conditions (TsCl, Et3N) affords the
ditosylates 19c.
Scheme 2. Synthesis of the tetraethylene glycol 18.
Since compound 18 is formed from two glycerol units and
contains two chiral centers, the synthetic route that starts from
the racemic glycerol (dl)-11 yields a 1:1 mixture of the meso
compound (18a) and the pair of enantiomers (18b); starting
from the enantiomerically pure (R)-11 produces only the R,R-
stereoisomer 18c. This allows us to study the effect of the
stereochemical disposition of the side arms on the binding and
luminescence properties of the lariat bis-bipyridine calix-
crown-5 derivatives. Enantiomerically pure (R)-11 was ob-
tained as depicted in Scheme 3.
Synthesis and conformational properties of the lariat calix-
crowns: The 1,3-dimethoxy-p-tert-butylcalix[4]arene (23) was
allowed to react with the appropriate oligoethylene glycol
ditosylate (15, 16, or 19) and Cs2CO3 as a base in CH3CN
(Scheme 4)Ðthe well-known conditions for high yields of the
calixcrown-5, -6, and -7 derivatives.[11,12] The yields of the
compounds 24, 25, and 26 are quite high (about 70%), which
Among the several methods available for the oxidative
cleavage of mannitol-1,2,5,6-diacetonide (20),[17] we chose to
Scheme 4. Synthesis of the calixcrowns 2 ± 4.
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Chem. Eur. J. 2000, 6, No. 6

Lariat Calixcrowns
1026±1034
indicates that the steric hindrance of the allyloxymethyl side
arm does not affect the cyclization reaction. Interestingly, the
cyclization of the calixcrown-4 (24) proceeds with the same
efficiency as for the calixcrowns-5, -6, and -7.
Subsequent removal of the allyl groups with p-toluenesul-
fonic acid (TsOH) and a catalytic amount of palladium on
charcoal in refluxing ethanol afforded the lariat alcohols 27,
28, and 29 in good yields. Interestingly the calixcrown-4
derivative 27 could be isolated from the reaction mixture as a
1:1 complex with TsOH, which could only be removed from
the organic phase after several washings with basic water. This
indicates that compound 27 is able to form a strong complex
with the hydronium ion. Subsequent reactions of the dialco-
hols 27, 28, or 29 with NaH and 6-bromomethyl-2,2'-bipyr-
idine (30) in dry DMF yielded the calix[4]arene ± bipyridine
lariat ethers 2, 3, 4a, 4b, and 4c. From the reaction that
yielded the meso compound 4a and the mixture of dl
stereoisomers 4b, it was possible to separate 4a from the
mixture 4b by preparative thin-layer chromatography on
Al2O3 with CH2Cl2 as eluent. The assignment of the structure
of compounds 4a and 4b was made on the basis of their NMR
spectra, which were consistent with a compound possessing a
plane of symmetry (4a) and a binary axis (4b), respectively.
The introduction of the bipyridine groups can be easily proven
by analysis of the 1H NMR spectra of compounds 2, 3, and 4;
these always indicate the presence of an AB system for the
diastereotopic methylene groups of the CH2(bpy) moiety and
of the typical absorptions of the bipyridine nuclei between
d ˆ 7.30 and 8.70.
Figure 1. Absorption spectra of a solution (1.1 Â 10 5 m) of ligand 3 in the
presence of increasing amounts of Eu(ClO4)3 in acetonitrile. The europium/
ligand ratio ranges from 0 to 20.
absorbance at 280 and 305 nm versus the metal/ligand ratio
(Figure 2) indicate the formation of a complex with a 1:1
stoichiometry. The association constants in acetonitrile are
Whereas the lariat calixcrown-5 derivatives 3 and 4 are
conformationally mobile, as are most of the 1,3-dimethoxy-
calix[4]arene-crowns-5,[11] calixcrown-4 (2) is present in sol-
ution as a mixture of cone, partial cone, and 1,3-alternate
conformations, which, at room temperature, are in slow
exchange on the 300 MHz NMR timescale. This is clearly
indicated not only by the presence of two singlets at d ˆ 2.91
and 2.81 for the methoxy groups of the inverted anisole nuclei
of the partial cone and 1,3-alternate structure inside the cavity
of the calix[4]arene, but also by the presence of several signals
for the ArCH2Ar carbons in the 13C NMR spectrum (see
Experimental Section). Because of the high asymmetry of the
molecule and the presence of different conformations besides
the cone, the NMR spectrum of the free ligand is not easily
analyzed in terms of the purity of the compound. The sodium
Figure 2. Spectrophotometric titration of ligand 3 with Eu(ClO4)3 in
*
)
acetonitrile at 228C (I ˆ 0.001m Et4NClO4). Absorbances at 280 nm (
~
and 305 nm ( ) are reported in function of the salt/ligand ratio.
too high (logK > 7) to be determined accurately, and there-
fore the same titrations were performed in methanol, in which
the logK values are, as expected,[23a] smaller. In general, the
association constants of the Eu3‡ complexes with ligands 2 and
3 (Table 1) are at least two orders of magnitude higher than
that found with a simple 18-crown-6,[23b] but lower than those
with cryptands.[23c]
1
complex of 2 shows a much simpler H NMR spectrum (see
The photophysical properties of the complexes of ligands
2 ± 4 with Eu3‡ and Tb3 were studied in acetonitrile. The molar
absorption coefficients are quite high and, as expected, the
values for the free ligands and the complexes are proportional
to the number of bipyridine units (Table 2). As in previous
Experimental Section). Here the methoxy groups resonate at
d ˆ 3.99 and 4.03, indicating that the calix is mainly in the cone
conformation.
Complexation and luminescence properties: The complex-
ation of the Eu3‡ and Tb3‡ ions by ligands 2 ± 4 was studied in
methanol and acetonitrile. Spectrophotometric titrations of
the ligands 2, 3, and 4c with salts of the Eu3‡ and Tb3‡ ions
were performed in dry acetonitrile by following the procedure
indicated in the Experimental Section. All the ligands show a
strong bathochromic shift of the absorption maxima upon
complexation of Eu3‡ or Tb3‡. Figure 1 reports the results
obtained for ligand 3. The absorption spectra show two
isosbestic points at ꢁ260 and ꢁ295 nm. The plots of the
Table 1. Association constants (LogK) of perchlorate complexes as
determined by spectrophotometric titration at 228C in methanol (I ˆ
0.001m Et4NClO4).
LogK
[Eu ꢀ 2]3‡
[Tb ꢀ 2]3‡
[Eu ꢀ 3]3‡
[Tb ꢀ 3]3‡
3.68 Æ 0.03
3.87 Æ 0.02
3.76 Æ 0.04
3.74 Æ 0.07
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R. Ungaro, N. Sabbatini et al.
FULL PAPER
Table 2. Absorption and luminescence data.[a]
Conclusion
Absorption
lmax [nm]
e [m 1 cm
Lifetime[b]
Luminescence
quantum
The introduction of one or two bipyridines as pendant arms in
calixcrowns led to the synthesis of new ligands that form
complexes with excellent photophysical properties. Com-
pared with the Eu3‡ and Tb3‡ complexes of more classical 1,3-
dialkoxycalixcrowns, the molar absorption coefficients in-
crease significantly because of the presence of the bipyridines;
the metal-luminescence quantum yields are in addition very
high, not only for the Tb3‡ but also for the Eu3‡ complexes.
The values of the metal-luminescence intensities are among
the highest obtained for Eu3‡ and Tb3‡ complexes with
encapsulating ligands. We are currently studying the possibil-
ity of synthesizing water-soluble lariat calixcrowns in order to
apply these results to the development of efficient labels for
bioaffinity assays.
1
]
t [ms]
yield[c]
F
2
282
305
305
16000
13200
13000
[Eu ꢀ 2]3‡
0.95
1.85
0.18
0.32
[Tb ꢀ 2]3‡
3
282
305
305
18000
14200
13000
[Eu ꢀ 3]3‡
1.38
1.88
0.32
0.35
[Tb ꢀ 3]3‡
4a
282
305
305
25400
22700
23400
[Eu ꢀ 4a]3‡
1.24
1.86
0.23
0.39
[Tb ꢀ 4a]3‡
4b
282
305
305
24000
21000
22700
[Eu ꢀ 4b]3‡
1.29
1.83
0.28
0.37
[Tb ꢀ 4b]3‡
4c
282
305
305
23900
21000
22200
[Eu ꢀ 4c]3‡
1.26
1.93
0.23
0.39
[Tb ꢀ 4c]3‡
[a] In aerated acetonitrile solution at 300 K. [b] Measured in correspond-
7
ence with the most intense metal emission bands (5D0 ! F2 for the Eu3‡ ion
Experimental Section
and D4 ! F6 for the Tb3‡ ion); experimental error ꢂ10%. [c] Excitation
in the ligand absorption; [Ru(bpy)3]2‡ (F ˆ 0.028 in water) and quinine
sulfate (F ˆ 0.546 in 1n H2SO4) were used as standards for the Eu3‡ and
Tb3‡ complexes, respectively; experimental error ꢃ30%.
5
7
General: Most of the solvents and all the reagents were obtained from
commercial suppliers and were used without further purification. DMF was
freshly distilled and stored over molecular sieves (4 Š); the acetonitrile
used for synthesis was also dried over sieves (3 Š). 1H and 13C NMR spectra
were recorded on Bruker AC100, Bruker AC300, or Bruker AMX400
spectrometers. Chemical shifts are reported as d values in ppm from
tetramethylsilane (d ˆ 0.0) as an internal standard. Analytical thin-layer
chromatography was carried out on silica gel plates (SiO2, Merck 60 F254).
Mass spectra were measured with a FINNIGAN MAT SSQ 710 instrument
(CI, CH4). Infrared spectra were recorded with Perkin ± Elmer 298
spectrometer. The optical rotations were measured on a AutopolIII
Rudolph Research Polimeter. Melting points were obtained for compounds
sealed in capillaries under nitrogen on an Electrothermal Apparatus. 25,27-
Dimethoxy-p-tert-butylcalix[4]arene (23) was synthesized according to the
literature method.[25] The UV/Vis absorption spectra were measured with a
Perkin ± Elmer Lambda 6 spectrophotometer. The luminescence spectra
studies,[6,24] complex formation was proven by the red shift of
the ligand absorption bands upon addition of the chloride
salts of Eu3‡ and Tb3‡, and by the analogy between the
absorption spectra and the metal-luminescence excitation
spectra upon ligand excitation. This analogy indicates that
ligand-to-metal energy transfer occurs upon excitation in the
ligand-centered absorption bands and that, in the case of the
complexes of ligands 4a ± c, both bipyridines are involved in
the ligand-to-metal energy transfer.
were obtained with
luminescence decays were acquired on a Perkin ± Elmer LS50 spectro-
fluorimeter and analyzed with least-squares fitting program. The
a Perkin ± Elmer LS50 spectrofluorimeter. The
a
Interestingly, the values of the lifetimes of the metal
emitting states and of the metal-luminescence quantum yields
upon ligand excitation are high for both the Tb3‡ and Eu3‡
complexes. This behavior indicates that the nonradiative
decay processes commonly observed in Tb3‡ and Eu3‡
complexes are not very efficient.[1±3] In particular, in the case
of the Tb3‡ complexes of ligands 2 ± 4, thermally activated
metal-to-ligand back energy transfer may be inhibited be-
cause the energy of the lowest ligand triplet excited state
(obtained from the ligand phosphorescence in the Gd3‡
complexes) is rather high, ranging from 22400 to
luminescence quantum yields were obtained by the method described by
Haas and Stein;[26] standards were [Ru(bpy)3]2‡ (F ˆ 0.028 in aerated
water)[27] for the Eu3‡ complex, and quinine sulphate (F ˆ 0.546 in H2SO4
1n)[28] for the Tb3‡ complex. The solvent used for the photophysical
measurement was CH3CN (Uvasol, Merck).
(S)-1-O-Allyl-2,3-O-isopropylideneglycerol (22):[21] The alcohol 21 (19.2 g,
145.2 mmol) was slowly added to a suspension of NaH (3.83 g, 159.7 mmol)
and allyl bromide (15.1 mL, 174.2 mmol) in dry benzene (80 mL). The
reaction mixture was refluxed for 2 h, cooled, and then quenched
(CAUTION!) with MeOH. Water was added to this mixture, and the
organic phase was separated and dried over MgSO4. The pure allyl ether 22
was obtained after distillation under reduced pressure (20.6 g, 83%). B.p.
25
25
1008C (100 mmHg); [a] ˆ ‡ 19.5 (c ˆ 0.011, CHCl3) (ref. [22]: [a]
ˆ
546
546
1
24000 cm . Most interestingly, in the case of the Eu3‡
‡ 19.7 (c ˆ 0.026, CHCl3)); 1H NMR (300 MHz, CDCl3, 300 K): d ˆ 1.32 (s,
3H; CH3), 1.38 (s, 3H; CH3), 3.38 ± 3.48 (m, 2H; C1HHO or C3HHO),
complexes nonradiative deactivation of the metal-emitting
states by ligand-to-metal charge-transfer states seems to be
negligible. For the Eu3‡ complex of ligand 2, the lower value
of the quantum yield compared with those of the other two
Eu3‡ complexes may be due to a more efficient nonradiative
deactivation by ligand-to-metal charge-transfer states, be-
cause the smaller polyether ring may lead to major involve-
ment of the oxygen atoms of the calix[4]arene in the binding
process. The smaller polyether ring may be also responsible
for a less efficient shielding of the metal ion towards water
molecules present in the lanthanide salts, which, as is
known,[1±3] quench the Eu3‡ and Tb3‡ luminescence.
1
3
ˆ
3.67 ± 3.71 (m, 1H; C HHO or C HHO), 4.00 (m, 3H; OCH2CH CH2,
C HHO or C HHO), 4.22 (m, 1H; C HO), 5.20 (m, 1H; CH CHH), 5.26
(m, 1H; CH CHH), 5.85 (m, 1H; CH CH2); MS (CI, CH4): m/z (%): 172.3
(10) [M] ; C9H16O3 (172.22): calcd C 62.77, H 9.36; found C 62.69, H 9.42.
1
3
2
ˆ
ˆ
ˆ
‡
(R)-3-O-Allylglycerol [(R)-11]:[22] A solution of compound 22 (20.6 g,
119.7 mmol) in a mixture of methanol (140 mL) and HCl (1n, 5 mL) was
refluxed for 1 h. After cooling, the reaction mixture was slowly neutralized
with aqueous NaHCO3 and then evaporated to dryness. The residue was
dried by azeotropic distillation of benzene. The pure deprotected glycerol
(R)-11 was obtained by distillation under reduced pressure (12.3 g, 78%).
25
B.p. 104 ± 1068C (0.1 mmHg); [a] ˆ ‡ 0.6 (c ˆ 0.026, pyridine), (ref. [22]:
589
25
[a] ˆ ‡ 0.6 (c ˆ 0.017, pyridine)); 1H NMR (300 MHz, CDCl3, 300 K):
589
d ˆ 3.40 ± 3.96 (m, 7H; C1H2OH, C2HOH, C3H2O), 4.07 (m, 2H;
1030
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Chem. Eur. J. 2000, 6, No. 6

Lariat Calixcrowns
1026±1034
2
OCH2CH CH2), 5.13 (dd, 3J ˆ 10.5 Hz, J ˆ 1.5 Hz, 1H; CH CHH), 5.21
Ar-H), 7.43 ± 7.47 (m, 6H; Ar-H), 7.80 (d, 3J ˆ 8.4 Hz, 2H; Ar-H); MS (CI,
ˆ
ˆ
3
2
3
3
‡
‡
ˆ
(dd, J ˆ 17.2 Hz, J ˆ 1.5 Hz, 1H; CH CHH), 5.84 (ddt, J ˆ 17.2 Hz, J ˆ
CH4): m/z (%): 502.9 (5) [M] , 243.4 (100) [Tr] ; C30H30O5S (502.63): calcd
3
ˆ
10.5 Hz, J ˆ 5.5 Hz, 1H; CH CH2); C6H12O3 (132.16): calcd C 54.53, H
C 71.69, H 6.02; found C 71.60, H 6.09.
9.15; found C 54.57, H 9.08.
10,10,10-Triphenyl-3,6,9-trioxadecyl-p-toluenesulfonate (10): Pure com-
pound 10 (4.58 g, 80%) was obtained by chromatography (SiO2 gradient
elution: diethyl ether/n-hexane 1:9, 1:1, and then pure diethyl ether). M.p.
(S)-1-O-Trityl-3-O-allyl-glycerol
[(S)-12]:
Tritylchloride
(18.56 g,
66.6 mmol) and triethylamine (9.26 mL, 66.6 mmol) were added to a
solution of (R)-11 (8.8 g, 66.6 mmol) in CH2Cl2 (140 mL). The reaction
mixture was refluxed for 1 h, cooled, and then quenched with diisopropyl
ether (70 mL) and water (70 mL). The organic phase was separated, and
the aqueous one extracted with diisopropyl ether (2 Â 70 mL). After the
combined ethereal extracts had been dried over Na2SO4, the solvent was
distilled off and the residue was chromatographed (SiO2: n-hexane/diethyl
1
75 ± 768C; H NMR (300 MHz, CDCl3, 300 K): d ˆ 2.41 (s, 3H; CH3-Ar),
3
3
3.27 (t, J ˆ 5.1 Hz, 2H; CH2OTr), 3.63 (s, 4H; OCH2CH2O), 3.67 (t, J ˆ
5.1 Hz, 2H; CH2CH2OTr or TsOCH2CH2), 3.73 (t, 3J ˆ 5.1 Hz, 2H;
CH2CH2OTr or TsOCH2CH2), 4.18 (t, 3J ˆ 5.1 Hz, 2H; CH2OTs), 7.23 ±
7.34 (m, 11H; Ar-H), 7.47 ± 7.52 (m, 6H; Ar-H), 7.80 (d, 3J ˆ 8.4 Hz, 2H; Ar-
H); 13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ 21.5 (q, CH3), 63.2, 68.6, 69.2,
70.6, 70.7 (t, OCH2CH2O), 86.4 (s, CPh3), 126.8 (d, Tr-Ar), 127.6 (d, Tr-Ar),
127.8 (d, Ts-Ar), 128.6 (d, Tr-Ar), 129.7 (d, Ts-Ar), 132.9 (s, Ts-Ar), 144.0 (s,
ether, 9:1 to 8:2). The product was crystallized from n-hexane (21.2 g,
85%). M.p. 58 ± 598C (ref. [22]: 588C); [a]
25
ˆ
5 (c ˆ 0.014, CHCl3)
546
25
‡
(ref. [22]: [a]
ˆ
5 (c ˆ 0.013, CHCl3)).
Tr-Ar), 144.6 (s, Ts-Ar); MS (CI, CH4): m/z (%): 546.8 (1) [M] , 243.4 (100)
546
‡
[Tr] ; C32H34O6S (546.68): calcd C 70.31, H 6.27; found C 70.25, H 6.31.
1-O-Trityl-3-O-allyl-glycerol [(dl)-12]: The synthesis was carried out as for
compound (R)-12 by starting from the commercially available alcohol (dl)-
11. M.p. 76 ± 778C (ref. [16]: 758C); 1H NMR (300 MHz, CDCl3, 300 K):
d ˆ 2.50 (d, 3J ˆ 4.7 Hz, 1H; OH), 3.15 ± 3.25 (m, 2H; C1H2O or C3H2O),
General procedure for the synthesis of 2-allyloxymethyl-3,6-dioxa-1,8-
octanediol (13) and 2-allyloxymethyl-3,6,9-trioxa-1,11-undecanediol (14):
NaH (50% in mineral oil, 2.14 g, 44.8 mmol) was added to a stirred solution
of (dl)-12 (13.95 g, 37.3 mmol) in dry DMF (100 mL). After 30 min, the
oligoethylene glycol monotrityl ether monotosylate 9 or 10 (37.3 mmol) was
also added, and the reaction mixture was stirred for 17 h at RT. The solvent
was removed under vacuum, and the residue quenched (CAUTION!) with
water (100 mL). The aqueous phase was subsequently extracted with
CH2Cl2 (2 Â 100 mL), and the combined organic layers were dried over
Na2SO4. The solution was concentrated to about 100 mL, and then
methanol (100 mL) and HCl (36%, 20 mL) were added. The mixture was
stirred at RT for 17 h and then neutralized (CAUTION!) with solid
KHCO3. The solvents were removed under reduced pressure, after which
H2O (200 mL) added to the residue. Methyltrityl ether was filtered off, and
the water was removed from the filtrate under reduced pressure. The
residue was treated with CH2Cl2 (200 mL), and the inorganic salts were
filtered off. The product was obtained as an oil after removal of the solvent
under vacuum.
1
3
ˆ
3.47 ± 3.60 (m, 2H; C H2O or C H2O), 3.92 ± 4.05 (m, 3H; OCH2CH CH2,
C2H), 5.18 (dd, 3J ˆ 10.4 Hz, J ˆ 1.6 Hz, 1H; CH CHH), 5.25 (dd, 3J ˆ
2
ˆ
17.2 Hz, J ˆ 1.8 Hz, 1H; CH CHH), 5.89 (ddt, 3J ˆ 17.1 Hz, 3J ˆ 10.4 Hz,
2
ˆ
3
ˆ
J ˆ 6.7 Hz, 1H; CH CH2), 7.15 ± 7.55 (m, 15H; ArH); MS (CI, CH4): m/z
‡
‡
(%): 374.4 (5) [M] , 243.4 (100) [Tr] ; C25H26O3 (374.48): calcd C 80.18, H
6.99; found C 80.09, H 7.02.
General procedure for the synthesis of oligoethylene glycol monotrityl
ethers 7 and 8: Trityl chloride (50.5 g, 0.18 mol) was added to a solution of
glycol (diethylene glycol 5: 260 mL, 2.7 mol; or triethylene glycol 6:
363 mL, 2.7 mol) and pyridine (22 mL, 0.27 mol), which was then heated at
408C under nitrogen. The reaction mixture was stirred for 16 h and then
extracted with toluene (3 Â 250 mL). The combined organic solution was
washed with H2O (5 Â 100 mL) and dried over Na2SO4. The toluene was
removed under reduced pressure to give a residue which was purified as
described below.
2-Allyloxymethyl-3,6-dioxa-1,8-octanediol (13): The oily residue (6.16 g,
75%) was used directly in the subsequent reaction. 1H NMR (300 MHz,
CDCl3, 300 K): d ˆ 3.35 ± 3.72 (m, 12H; CH2O-allyl, HOCH2CHROCH2-
CH2OCH2CH2OH), 3.72 ± 3.85 (m, 1H; CHCH2O-allyl), 3.86 ± 3.98 (m,
7,7,7-Triphenyl-3,6-dioxaheptanol (7): Pure compound 7 (46.9 g; 75%) was
obtained by crystallization first from CH2Cl2 and then from a mixture of
ethyl acetate and hexane. M.p. 113 ± 1148C (ref. [18]: 112.7 ± 114.58C);
3
1H NMR (300 MHz, CDCl3, 300 K): d ˆ 2.43 (brs, 1H; OH), 3.31 (t, J ˆ
ˆ
ˆ
2H; OCH2CH CH2), 5.05 ± 5.27 (m, 2H; CH CH2), 5.72 ± 5.90 (m, 1H;
5.3 Hz, 2H; CH2OTr), 3.60 ± 3.76 (m, 6H; HOCH2CH2OCH2), 7.15 ± 7.35
(m, 9H; Ar-H), 7.42 ± 7.53 (m, 6H; Ar-H); MS (CI, CH4): m/z (%): 348.6 (4)
‡
ˆ
CH CH2); MS (CI, CH4): m/z (%): 221.4 (100) [M‡H] ; C10H20O5
‡
‡
(220.27): calcd C 54.53, H 9.15; found C 54.46, H 9.20.
[M] , 243.4 (100) [Tr] ; C23H24O3 (348.44): calcd C 79.28, H 6.94; found C
79.23, H 7.00.
2-Allyloxymethyl-3,6,9-trioxa-1,11-undecanediol (14): Pure product 14
(6.98 g, 71%) was obtained after distillation under reduced pressure. B.p.
176 ± 1788C (0.8 mmHg); 1H NMR (300 MHz, CDCl3, 300 K): d ˆ 3.38 ±
3.75 (m, 16H; CH2O-allyl, HOCH2CHRO(CH2CH2O)3H), 3.86 ± 3.97 (m,
10,10,10-Triphenyl-3,6,9-trioxadecanol (8): The product 8 was obtained as a
yellowish oil (58.3 g, 82%) and used without further purification in the
subsequent reaction. Distillation of this oil at 0.3 mmHg brings about
partial decomposition of the product. An analytically pure sample was
therefore obtained by preparative thin-layer chromatography (SiO2:
CHCl3/MeOH, 95:5). 1H NMR (300 MHz, CDCl3, 300 K): d ˆ 1.68 (brs,
1H; OH), 3.26 (t, 3J ˆ 5.1 Hz, 2H; CH2OTr), 3.60 ± 3.74 (m, 10H;
HOCH2CH2OCH2CH2OCH2), 7.18 ± 7.33 (m, 9H; Ar-H), 7.43 ± 7.48 (m,
6H; Ar-H); 13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ 61.3, 63.0 (t, CH2OH;
CH2OTr), 70.1, 70.32, 70.45, 72.30 (t, CH2OCH2CH2OCH2), 86.3 (s, CPh3),
126.6, 127.4, 128.4 (d, Ar), 143.8 (s, Ar); MS (CI, CH4): m/z (%): 392.7 (2)
ˆ
3H; OCH2CH CH2, CHCH2O-allyl), 4.05 (brs, 1H; OH), 4.22 (brs, 1H;
OH), 5.15, 5.24 (m, 2H; CH CH2), 5.86 (m, 1H; CH CH2); 13C NMR
(75.5 MHz, CDCl3, 300 K): d ˆ 61.6, 62.4 (t, CH2OH), 69.5, 69.9, 70.2, 70.5,
ˆ
ˆ
ˆ
70.7, 72.3, 73.2 (t, (OCH2CH2)2OCH2, CHCH2OCH2CH ), 80.5 (d,
CHCH2O-allyl), 117.1 (t, CH CH2), 134.5 (d, CH CH2); MS (CI, CH4):
ˆ
ˆ
‡
m/z (%): 265.5 (100) [M‡H] ; C12H24O6 (264.32): calcd C 54.53, H 9.15;
found C 54.48, H 9.22.
General procedure for the synthesis of 2-allyloxymethyl-1,8-bis(tosyloxy)-
3,6-dioxaoctane (15) and 2-allyloxymethyl-1,11-bis(tosyloxy)-3,6,9-trioxa-
undecane (16): A solution of TsCl (7.8 g, 41 mmol) in dry CH2Cl2 (100 mL)
was added dropwise over a period of 30 min to a stirred solution of
compound 13 or 14 (20.4 mmol), NEt3 (14.2 mL, 102 mmol), and a catalytic
amount of DMAP in dry CH2Cl2 (150 mL) at 08C. After one night of
stirring at RT, the reaction was quenched with H2O (200 mL) and the
organic phase was washed to the point of neutrality. The dichloromethane
solution was dried over Na2SO4, and the solvent was removed under
vacuum.
‡
‡
[M] , 243.4 (100) [Tr] ; C25H28O4 (392.49): calcd C 76.50, H 7.19; found C
76.44, H 7.24.
General procedure for the synthesis of the oligoethylene glycol monotrityl
ether monotosylates 9 and 10: A solution of tosyl chloride (2.10 g,
11.0 mmol) in dry CH2Cl2 (20 mL) was slowly added over 30 min to a
solution of monotrityl glycol (compound 7: 3.66 g, 10.5 mmol; compound 8:
4.12 g, 10.5 mmol) in dry CH2Cl2 (20 mL) and triethylamine (5 mL) at 08C.
The reaction mixture was stirred overnight at RTand then extracted with a
saturated aqueous solution of K2CO3 (2 Â 50 mL) and H2O (2 Â 50 mL).
After the organic phase had been dried over Na2SO4, the dichloromethane
was distilled off, and the residue was purified by column chromatography.
2-Allyloxymethyl-1,8-bis(tosyloxy)-3,6-dioxaoctane (15): Pure compound
15 was obtained (8.86 g, 82%) as a colorless oil after column chromatog-
raphy (SiO2: gradient CH2Cl2 to CH2Cl2/MeOH, 98:2). 1H NMR
(300 MHz, CDCl3, 300 K): d ˆ 2.41 (s, 6H; CH3-Ar), 3.38 ± 3.70 (m, 9H;
OCH2CH2OCH2, CHCH2O-allyl), 3.88 (m, 2H; OCH2CH2OTs), 4.01 (dd,
2J ˆ 10.4 Hz, 3J ˆ 6.1 Hz, 1H; TsOCHHCHCH2O-allyl), 4.11 (dd, 2J ˆ
10.2 Hz, 3J ˆ 6.0 Hz, 1H; TsOCHHCHCH2O-allyl), 4.12 (m, 2H;
7,7,7-Triphenyl-3,6-dioxaheptyl-p-toluenesulfonate (9): After purification
by chromatography (SiO2: n-hexane/diethyl ether, 2:1), compound 9 was
crystallized from diethyl ether (4.12 g, 78%). M.p. 90 ± 918C; 1H NMR
(300 MHz, CDCl3, 300 K): d ˆ 2.41 (s, 3H; CH3-Ar), 3.20 (t, 3J ˆ 5.2 Hz,
3
3
2H; CH2OTr), 3.60 (t, J ˆ 4.7 Hz, 2H; TsOCH2CH2), 3.73 (t, J ˆ 5.2 Hz,
3
ˆ
ˆ
2H; CH2CH2OTr), 4.20 (t, J ˆ 4.7 Hz, 2H; TsOCH2), 7.23 ± 7.31 (m, 11H;
OCH2CH CH2), 5.09 ± 5.21 (m, 2H; CH CH2), 5.71 ± 5.84 (m, 1H;
Chem. Eur. J. 2000, 6, No. 6
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0606-1031 $ 17.50+.50/0
1031

R. Ungaro, N. Sabbatini et al.
FULL PAPER
3
3
ˆ
CH CH2), 7.31 (d, J ˆ 8.3 Hz, 4H; Ar-H), 7.75 (d, J ˆ 8.4 Hz, 2H; Ar-H),
separated and washed with water. After removal of dichloromethane, the
residue was crystallized from MeOH to give compounds 24, 25, 26a,b, or
26c as white solids.
3
‡
7.76 (d, J ˆ 8.3 Hz, 2H; Ar-H); MS (CI, CH4): m/z (%): 529.0 (40) [M] ;
C24H32O9S2 (528.64): calcd C 54.53, H 6.10; found C 54.45, H 6.16.
2-Allyloxymethyl-1,11-bis(tosyloxy)-3,6,9-trioxaundecane (16): Pure com-
pound 16 was obtained (10.18 g, 87%) as a colorless oil after column
chromatography (SiO2: CHCl3). 1H NMR (300 MHz, CDCl3, 300 K): d ˆ
3.30 ± 3.72 (m, 13H; (OCH2CH2)2OCH2, CH(CH2O)allyl), 3.88 (d, 3J ˆ
6 Hz, 2H; TsOCH2), 4.02 (dd, 2J ˆ 10.0 Hz, 3J ˆ 6.0 Hz, 1H; TsOCHHCH-
CH2O-allyl), 4.12 (dd, 2J ˆ 10.0 Hz, 3J ˆ 6.0 Hz, 1H; TsOCHHCHCH2O-
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-(2-allyloxymethyl)-
crown-4 (24): Yield ˆ 1.11 g (68%); m.p. 192 ± 1938C; 1H NMR (300 MHz,
CDCl3, 300 K, mixture of partial cone, 1,3-alternate and cone conformers):
d ˆ 0.81, 0.84, 1.00, 1.03, 1.09, 1.13, 1.28, 1.29, 1.30, 1.31, 1.33, 1.34, 1.37 (s,
9H; C(CH3)3), 2.92, 2.82 (s, 3H; OCH3), 4.05 ± 3.10 (m, 26H; Hax, OCH3,
ˆ
CH2OCH2CH , ArOCH2CHRO(CH2CH2O)2Ar, Heq), 5.10 ± 5.35 (m, 2H;
ˆ
ˆ
allyl), 4.13 (m, 2H; OCH2CH CH2), 5.12 ± 5.20 (m, 2H; CH CH2), 5.72 ±
ˆ
ˆ
CH CH2), 5.80 ± 5.98 (m, 1H; CH CH2), 6.90 ± 7.16 (m, 8H; Ar-H);
13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ 30.4 (t, ArCH2Ar, cone), 30.6,
31.0, 31.1, 31.3, 31.4, 31.5, 31.6 (q, C(CH3)3), 33.7, 34.0 (s, C(CH3)3), 38.3,
38.6, 38.8, 39.7 (t, ArCH2Ar, pc, 1,3-alt), 57.7, 58.1, 58.5 (q, OCH3, pc, 1,3-
alt), 62.2 (q, OCH3; cone), 68.0, 68.7, 69.1, 69.3, 69.5, 70.0, 71.2, 72.1, 72.3,
3
3
ˆ
5.83 (m, 1H; CH CH2), 7.31 (d, J ˆ 8.1 Hz, 4H; Ar-H), 7.75 (d, J ˆ 8.4 Hz,
2H; Ar-H), 7.76 (d, 3J ˆ 8.1 Hz, 2H; Ar-H); 13C NMR (75.5 MHz, CDCl3,
300 K): d ˆ 21.4 (q, CH3Ar), 68.6, 69.2, 69.5, 70.0, 70.5, 70.7, 72.3 (t,
ˆ
CHCH2OCH2CH , CH2CHR(OCH2CH2)3), 76.7 (d, CHCH2O-allyl), 117.1
(t, CH CH2), 127.9, 129.8 (d, Ar), 132.8, 133.0 (s, Ar), 134.3 (d, CH CH2),
144.8 (s, Ar); MS (CI, CH4): m/z (%): 573.1 (10) [M‡H] ; C26H36O10S2
ˆ
ˆ
ˆ
73.0, 75.9 (t, CH2CHRO(CH2CH2O)2, CHCH2OCH2CH ), 79.5 (d,
‡
ˆ
CH2CHRO), 116.3, 116.8 (t, CH CH2), 124.6, 125.3, 125.5, 125.6, 125.9,
(572.69): calcd C 54.53, H 6.34; found C 54.44, H 6.41.
126.0, 126.2, 126.4, 127.2 (d, m-Ar), 133.0, 133.2, 133.4, 133.8 (s, o-Ar), 134.2
ˆ
(d, CH CH2), 144.1, 144.2, 144.5 (s, p-Ar), 154.1, 155.4, 155.5 (s, i-Ar); MS
(CI, CH4): m/z (%): 861.3 (100) [M‡H] ; C56H76O7 (861.22): calcd C 78.10,
Synthesis
of
2,10-bis(allyloxymethyl)-3,6,9-trioxa-1,11-undecanediols
‡
(18a,b): A solution of (dl)-12 (5.42 g, 14.5 mmol) and NaH (50% in
mineral oil, 1.39 g, 30 mmol) in dry DMF (50 mL) was stirred for 30 min at
RT, after which time the ditosylate 17 (3 g, 7.1 mmol) was added. The
mixture was stirred for 48 h and the solvent was then distilled under
reduced pressure. The residue was treated (CAUTION!) with H2O
(50 mL) and CH2Cl2 (50 mL). The organic layer was separated, and the
water phase was extracted with CH2Cl2 (50 mL). After the combined
organic phases had been dried over Na2SO4, the solvent was distilled off.
This crude product was dissolved in a mixture of CH2Cl2/MeOH (1:1,
60 mL), and HCl (36%, 5 mL) was then added. This solution was stirred for
48 h at RTand subsequently neutralized (CAUTION!) with solid KHCO3.
After removal of the solvents under vacuum, the residue was treated with
H2O (50 mL), and the resulting precipitate was filtered off. After the water
had been removed from the aqueous filtrate, and the residue had been
taken up with CH2Cl2 (50 mL), the white precipitate was filtered off. After
removal of dichloromethane from the filtrate, a yellowish oil (1.83 g,
76%) was obtained. 1H NMR (100 MHz, CDCl3, 300 K): d ˆ 3.35 ± 4.11
(m, 24H; HOCH2CHR(OCH2CH2)2OCHRCH2OH; CHCH2O-allyl,
H 8.89; found C 78.01, H 8.96.
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-(2-allyloxymethyl)-
crown-5 (25): Yield ˆ 71%; m.p. 250 ± 2548C (MeOH); 1H NMR
(300 MHz, CDCl3, 300 K): d ˆ 0.86 (s, 9H; C(CH3)3), 0.89 (s, 9H;
2
C(CH3)3), 1.36 (s, 9H; C(CH3)3), 1.37 (s, 9H; C(CH3)3), 3.17, 3.18 (d, J ˆ
ˆ
12.0 Hz, 4H; Heq), 3.45 ± 4.50 (m, 29H; Hax, OCH3, CH2OCH2CH ,
ˆ
ArOCH2CHR(OCH2CH2)3OAr), 5.19, 5.27 (m, 2H; CH CH2), 5.89 (m,
ˆ
1H; CH CH2), 6.53 (s, 2H; Ar-H), 6.58 (s, 2H; Ar-H), 7.13 (s, 2H; Ar-H),
7.15 (s, 2H; Ar-H); 13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ 31.1 (q,
C(CH3)3), 31.5 (t, ArCH2Ar), 31.7 (q, C(CH3)3), 33.5, 34.1 (s, C(CH3)3),
60.8, 61.2 (q, OCH3), 69.2, 69.7, 70.9, 71.1, 71.2, 71.4, 72.4, 72.9, 75.7 (t,
ˆ
CH2CHR(OCH2CH2)3, CHCH2OCH2CH ), 79.1 (d, CH2CHRO), 117.2 (t,
CH ˆ CH2), 124.4, 124.8, 124.9 (d, m-Ar), 132.1, 132.5, 132.6 (s, o-Ar), 134.5
ˆ
(CH CH2), 135.7, 135.9 (s, o-Ar), 144.1, 144.2, 144.6, 144.8 (s, p-Ar), 153.0,
‡
153.4, 156.4, 157.0 (i-Ar); MS (CI, CH4): m/z (%): 905.3 (100) [M‡H] ;
C58H80O8 (905.27): calcd C 76.95, H 8.91; found C 76.85, H 8.88.
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-[2,10-bis(allyloxymethyl)]-
crown-5 (26):
ˆ
ˆ
OCH2CH CH2), 5.00 ± 5.26 (m, 4H; CH CH2), 5.62 ± 6.00 (m, 2H;
‡
ˆ
CH CH2); MS (CI, CH4): m/z (%): 335.3 (100) [M‡H] ; C16H30O7
(334.41): calcd C 57.47, H 9.04; found C 57.40, H 9.12.
(26a,b): Yield ˆ 72%; m.p. 201 ± 2048C (MeOH); 1H NMR (400 MHz,
CDCl3, 300 K): d ˆ 0.85 (s, 18H; C(CH3)3), 1.36, 1.38 (s, 9H; C(CH3)3),
3.12 ± 3.25 (m, 4H; Heq), 3.45 ± 4.18 (m, 28H; OCH3, ArOCH2-
2R-10R-Bis(allyloxymethyl)-3,6,9-trioxa-1,11-undecanediol (18c): The
synthetic route is analogous to that for compounds 18a,b, but starts from
ˆ
alcohol (S)-12. The product 18c shows the same physical and spectroscopic
CHROCH2CH2, CH2OCH2CH ), 3.20 ± 4.51 (m, 4H; Hax), 5.17 ± 5.30 (m,
25
ˆ
ˆ
properties as 18a,b. [a] ˆ ‡ 28.4 (c ˆ 0.0183, CHCl3).
4H; CH CH2), 5.84 ± 5.95 (m, 2H; CH CH2), 6.53 (brs, 4H; CH3OAr-H),
7.12, 7.13, 7.14, 7.15 (s, 2H; Ar-H); 13C NMR (75.5 MHz, CDCl3, 300 K):
d ˆ 31.1 (q, C(CH3)3), 31.6 (t, ArCH2Ar), 31.7 (q, C(CH3)3), 33.5, 34.1 (s,
C(CH3)3), 61.2, 61.4 (q, OCH3), 69.0, 69.1, 69.5, 70.2, 70.5, 71.3, 72.4, 75.7,
589
2,10-Bis(allyloxymethyl)-1,11-bis(tosyloxy)-3,6,9-trioxaundecanes (19a,b):
A solution of TsCl (2.09 g, 10.9 mmol) in CH2Cl2 (30 mL) was added
dropwise over a period of 30 min to a solution of the dialcohol 18a,b
(1.83 g, 5.5 mmol), NEt3 (4.6 mL, 32.8 mmol), and DMAP in dry CH2Cl2
(30 mL) at 08C. The reaction mixture was stirred at RT for 24 h. The
dichloromethane solution was then extracted with water (2 Â 30 mL) and
dried over MgSO4. The solvent was then removed, and pure ditosylate
19a,b (3.10 g, 88%) was obtained after column chromatography (SiO2:
elution gradient CH2Cl2 ± CH2Cl2/MeOH, 99:1). 1H NMR (100 MHz,
CDCl3, 300 K): d ˆ 2.39 (s, 6H; CH3-Ar), 3.31 ± 4.15 (m, 22H; TsOCH2-
ˆ
75.8 (t, CH2CHROCH2CH2, CHCH2OCH2CH ), 78.6, 79.5 (d, CHRO),
117.18, 117.23 (t, CH CH2), 124.5, 124.8, 125.0, 125.1 (d, m-Ar), 132.0,
132.2, 132.5, 132.8 (s, o-Ar), 134.6 (CH CH2), 135.7, 135.9 (s, o-Ar), 144.2,
144.5, 144.8 (p-Ar), 153.5, 156.1, 156.2 (i-Ar); MS (CI, CH4): m/z (%): 974.5
ˆ
ˆ
‡
(100) [M] ; C62H86O9 (975.37): calcd C 76.35, H 8.89; found C 76.28, H 8.95.
25
(26c): Yield ˆ 70%; m.p. 169 ± 1718C (MeOH); [a] ˆ ‡ 12.7 (c ˆ 0.0126,
589
CHCl3); 1H NMR (400 MHz, CDCl3, 300 K): d ˆ 0.83 (s, 18H; C(CH3)3),
1.35 (s, 18H; C(CH3)3), 3.15 (d, 2J ˆ 12.4 Hz, 2H; Heq), 3.17 (d, 2J ˆ 12.5 Hz,
ˆ
CHR(OCH2CH2)2OCHRCH2O, CHCH2O-allyl, OCH2CH CH2), 5.03 ±
5.26 (m, 4H; CH CH2), 5.55 ± 6.95 (m, 2H; CH CH2), 7.30 (d, 3J ˆ
ˆ
ˆ
ˆ
2H; Heq), 3.14 ± 4.50 (m, 28H; OCH2CHROCH2CH2, CHCH2OCH2CH ,
8.0 Hz, 4H; Ar-H), 7.74 (d, 3J ˆ 8.2 Hz, 4H; Ar-H); MS (CI, CH4): m/z
OCH3), 4.33 (d, 2J ˆ 12.4 Hz, 2H; Hax), 4.40 (d, 2J ˆ 12.7 Hz, 2H; Hax), 5.18
‡
‡
3
3
(%): 643.2 (20) [M‡H] , 489 (100) [(M Ts)] ; C30H42O11S2 (642.78):
ˆ
ˆ
(d, J ˆ 10.3 Hz, 2H; CH CHH), 5.25 (d, J ˆ 17.2 Hz, 2H; CH CHH),
5.88 (ddt, 3J ˆ 17.2 Hz, 3J ˆ 10.3 Hz, J ˆ 5.5 Hz, 2H; CH CH2), 6.55 (s,
3
calcd C 56.06, H 6.59; found C 56.11, H 6.53.
ˆ
4H; Ar-H), 7.15 (s, 4H; Ar-H); 13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ
31.0, 31.1, 31.4, 31.6, 31.7 (t, ArCH2Ar, q, C(CH3)3), 33.5, 34.1 (s, C(CH3)3),
61.2, 61.4 (q, OCH3), 69.0, 69.5, 69.6, 69.7, 70.5, 72.4, 75.6
2S-10S-Bis(allyloxymethyl)-1,11-bis(tosyloxy)-3,6,9-trioxaundecane (19c):
The synthesis was carried out in the same way as for ditosylate 19a,b by
starting from the dialcohol 18c. The product shows the same physical and
25
ˆ
(CH2CHROCH2CH2, CHCH2OCH2CH ), 78.6 (d, CHRO), 117.2 (t,
CH CH2), 124.4, 124.5, 124.7, 124.9, 125.1, 125.4 (d, m-Ar), 132.2, 132.5
(s, o-Ar), 134.6 (d, CH CH2), 135.9 (s, o-Ar), 144.2, 144.5 (s, p-Ar), 153.4,
156.2 (s, i-Ar); MS (CI, CH4): m/z (%): 974.5 (100) [M] ; C62H86O9 (975.37):
spectroscopic properties as the racemic 19a,b. [a] ˆ ‡ 6.8 (c ˆ 0.0147,
589
ˆ
CHCl3).
ˆ
General procedure for the synthesis of 25,27-dimethoxy-p-tert-butylca-
lix[4]arene-26,28-allyloxymethyl-crown-4 (24) and -crown-5 (25), (26a,b),
‡
calcd C 76.35, H 8.89; found C 76.30, H 8.93.
(26c):
A solution of dimethoxy-p-tert-butylcalix[4]arene 23 (1.28 g,
1.9 mmol), Cs2CO3 (2.46 g, 7.6 mmol), and ditosylate 15, 16, 19a,b, or 19c
(2.0 mmol) in CH3CN (350 mL) was refluxed for 3 days. The acetonitrile
was then removed under reduced pressure and the residue was taken up in
CH2Cl2 (100 mL) and HCl (10%, 100 mL). The organic phase was
General procedure for the synthesis of 25,27-dimethoxy-p-tert-butylca-
lix[4]arene-26,28-hydroxymethyl-crown-4 (27) and -crown-5 (28), (29a,b),
(29c): A suspension of the appropriate allyloxymethyl derivative 24, 25,
26a,b, or 26c (1.4 mmol), Pd/C (100 mg), and TsOH (240 mg, 1.4 mmol) in
1032
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Chem. Eur. J. 2000, 6, No. 6

Lariat Calixcrowns
1026±1034
a mixture of ethanol/H2O (20:1, 60 mL) was heated to reflux. After 15 ±
18 h, the solvent was removed under reduced pressure.
the reaction mixture was heated at reflux temperature for 12 h. After
removal of the solvent under vacuum, the residue was treated with CH2Cl2
(50 mL) and washed with H2O (2 Â 50 mL). The organic phase was
separated, and the solvent was distilled under vacuum.
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-(2-hydroxymethyl)-
crown-4 (27): The residue was treated with CH2Cl2/MeOH (10:1, 100 mL)
and filtered on celite. The solvents were distilled under vacuum to give a
white solid of the 1:1 complex between compound 27 and TsOH. Yield ˆ
70%; 1H NMR (400 MHz, CDCl3, 300 K): d ˆ 1.06 (s, 18H; C(CH3)3), 1.18,
1.19 (s, 9H; C(CH3)3), 2.04 (brs, 1H; OH), 2.30 (s, 3H; CH3Ar), 3.37 (d,
2J ˆ 12.8 Hz, 1H; Heq), 3.39 (d, 2J ˆ 12.2 Hz, 1H; Heq), 3.41 (d, 2J ˆ 12.7 Hz,
2H; Heq), 3.68 ± 4.70 (m, 17H; ArOCH2CHR(OCH2CH2)OAr, CH2OH;
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-[2-(2,2'-bipyridine-6-
methyl)oxy-methyl]crown-4 (2): Reverse-phase (C18) column chromatog-
raphy (elution gradient CH3OH/H2O, 15:1 ± CH3OH ± CH3OH/CH2Cl2,
20:1). Yield ˆ 66%; m.p. 113 ± 1158C; 1H NMR (CDCl3, 300 MHz, 300 K):
the spectrum was quite complex and demonstrated the presence of a
mixture of conformations. The following signals were assigned: bpy
multiplets at d ˆ 8.67, 8.36, 8.25, 7.77, 7.45, 7.30; OCH2(bpy) at d ˆ 4.77
(brs), 4.71(s); and the two singlets of the OCH3 protons at d ˆ 2.91 and
2.81; 13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ 29.6 (t, ArCH2Ar c), 31.0,
31.2, 31.3, 31.4, 31.5, 31.6 (q, C(CH3)3), 33.8, 34.1 (s, C(CH3)3), 38.4, 38.8 (t,
ArCH2Ar pc, 1,3-alt), 57.7, 58.0, 58.5 (q, OCH3), 62.2 (q, OCH3), 68.2, 68.6,
69.4, 70.0, 70.3, 71.0, 71.2, 72.1, 73.0, 74.3, 74.5, 75.8 (t, CH2CHRO(CH2-
CH2O)2, CHCH2OCH2bpy), 77.4 (d, CHRO), 119.5, 119.7, 120.9 and 121.2
(d, bpy-3, bpy-3'), 123.6, 123.7, 124.7, 125.7, 125.9, 126.1, 126.2, 127.3 (d, m-
Ar, bpy-5, bpy-5'), 133.1, 133.3, 133.4, 133.5, 133.8, 133.9 (s, o-Ar), 136.9,
137.4 (d, bpy4, bpy-4'), 144.1, 144.4, 144.6 (s, p-Ar), 149.1, 149.2 (d, bpy-6'),
154.1, 154.2, 155.3, 155.4, 155.5 (s, i-Ar, bpy-2, bpy-2', bpy-6); MS (CI, CH4):
3
Hax), 6.92 ± 7.25 (m, 10H; Ar-H), 7.81 (d, J ˆ 8.0 Hz, 2H; TsH); 13C NMR
(75.5 MHz, CDCl3, 300 K): d ˆ 21.2 (q, TsCH3), 30.0, 30.3, 30.4, 31.1, 31.3,
31.4 (q, C(CH3)3; t, ArCH2Ar), 34.0, 34.1, 34.2 (s, C(CH3)3), 59.7, 64.0, 64.1
(q, OCH3), 67.8, 70.0, 71.0, 73.7, 76.4 (t, CH2CHR(OCH2CH2)2), 80.0 (d,
CHRO), 125.7, 125.8, 126.1, 126.2 (d, m-Ar), 128.6 (d, Ts) 133.7, 133.8,
134.0, 134.3, 134.4, 134.5 (s, o-Ar), 138.7 (s, Ts), 147.9, 148.1, 148.4 (s, p-Ar),
‡
149.6, 149.7, 155.0 (s, i-Ar); MS (CI, CH4): m/z (%): 821.3 (100) [M‡H] ;
C53H72O7 ´ C7H8O3S (993.35): calcd C 72.55, H 8.12; found C 72.40, H 7.99.
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-(2-hydroxymethyl)-
crown-5 (28): Pure compound 28 was obtained by column chromatography
(SiO2, CHCl3/MeOH, 95:5). Yield ˆ 71%; m.p. 277 ± 2798C; 1H NMR
(300 MHz, CDCl3, 300 K): d ˆ 0.88 (s, 9H; C(CH3)3), 0.92 (s, 9H;
C(CH3)3), 1.25 (s, 9H; C(CH3)3), 1.26 (s, 9H; C(CH3)3), 2.00 (brs, 1H;
‡
m/z (%): 990.2 (100) [M‡H] ; C64H80N2O7 (989.35): calcd C 77.70, H 8.15,
N 2.83; found C 77.83, H 8.25, N 2.76. A simpler 1H NMR spectrum can be
obtained by converting compound 2 into its 1:1 NaSCN complex (mainly in
the cone structure), by stirring a solution of 2 in CDCl3 with solid NaSCN
for 1 night. 2-NaSCN: 1H NMR (300 MHz, CDCl3, 300 K, NaSCN
complex): d ˆ 1.04, 1.13, 1.19, 1.20 (s, 9H; C(CH3)3), 3.35 ± 3.85, 4.15 ± 4.80
(m, 21H; Heq, ArOCH2CHRO(CH2CH2O)2, CHCH2, Hax), 3.99, 4.03 (s,
3H; OCH3), 4.79 (s, 2H; OCH2bpy), 6.98 ± 7.24 (m, 8H; Ar-H), 7.27 (m,
1H; bpy-5'-H), 7.43 (d, 3J ˆ 7.7 Hz, 1H; bpy-5-H), 7.75 (ddd, 3J ˆ 7.5 Hz,
3J ˆ 7.5 Hz, 4J ˆ 1.8 Hz, 1H; bpy-4'-H), 7.85 (dd, 3J ˆ 7.7 Hz, 3J ˆ 7.7 Hz,
1H; bpy-4-H), 8.28 (d, 3J ˆ 7.5 Hz, 1H; bpy-3'-H), 8.37 (d, 3J ˆ 7.7 Hz, 1H;
2
OH), 3.14, 3.17 (d, J ˆ 11.0 Hz, 2H; Heq), 3.53 ± 4.37 (m, 27H; ArOCH2-
CHR(OCH2CH2)3OAr, OCH3, CH2OH; Hax), 6.58 (s, 2H; Ar-H), 6.63 (s,
2H; Ar-H), 7.01 (s, 2H; Ar-H), 7.02 (s, 2H; Ar-H); 13C NMR (75.5 MHz,
CDCl3, 300 K): d ˆ 31.2, 31.7 (q, C(CH3)3; t, ArCH2Ar), 33.6, 34.1 (s,
C(CH3)3), 60.9, 61.3 (q, OCH3), 61.9 (t, CH2OH), 69.4, 71.2, 71.3, 72.9, 75.2
(t, CH2CHRO(CH2CH2O)3), 80.2 (CHRO), 124.7, 125.0 (d, m-Ar), 132.4,
132.9, 135.2 (s, o-Ar), 144.5, 144.7 (s, p-Ar), 153.4, 155.6, 155.8 (s, i-Ar); MS
‡
(CI, CH4): m/z (%): 865.1 (100) [M‡H] ; C55H76O8 (865.21): calcd C 76.35,
H 8.85; found C 76.24, H 8.97.
3
bpy-3-H), 8.65 (d, J ˆ 4.8 Hz, 1H; bpy-6'-H).
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-]2,10-bis(hydroxymethyl)]-
crown-5 (29a,b): Pure compounds 29a,b were obtained by column
chromatography on SiO2 with CHCl3/MeOH (10:1) as eluent. Yield ˆ
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-[2-(2,2'-bipyridine-6-
methyl)oxy-methyl]crown-5 (3): Preparative layer chromatography on
Al2O3 with CH2Cl2 as eluent gave compound 3 in a yield of 71%. An
analytically pure sample can be obtained by crystallization from CH3CN.
M.p. 182 ± 1848C; 1H NMR (300 MHz, CDCl3, 300 K): d ˆ 0.83, 0.86 (s, 9H;
1
64%; m.p. > 3008C; H NMR (400 MHz, CDCl3, 300 K): d ˆ 0.91 (s, 9H;
C(CH3)3), 1.00 (s, 9H; C(CH3)3), 1.22 (s, 9H; C(CH3)3), 1.32, 1.33 (s, 9H;
C(CH3)3), 2.07, 2.28 (brs, 2H; OH), 3.18 ± 3.27 (m, 4H; Heq), 3.59 ± 4.52 (m,
28H; ArCH2CHROCH2CH2, CHCH2OH, OCH3, Hax), 6.59 (brs, 2H;
CH3OAr-H), 6.72 (s, 2H; Ar-H), 6.97, 6.98 (s, 2H; Ar-H), 7.09, 7.10 (s, 2H;
Ar-H); 13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ 31.1, 31.2, 31.6 (q,
C(CH3)3; t, ArCH2Ar), 33.6, 33.7, 34.0, 34.1 (s, C(CH3)3), 61.1, 61.6 (q,
OCH3), 61.5, 62.2 (t, CH2OH), 68.7, 69.7, 70.8, 71.2, 75.0, 75.2 (t,
ArOCH2CHROCH2CH2), 79.9, 80.4 (d, CHRO), 124.7, 124.9, 125.0,
125.2, 125.4 (d, m-Ar), 132.1, 132.8, 133.1, 134.4, 134.5, 135.3 (s, o-Ar),
144.4, 144.5, 144.8 (s, p-Ar), 153.4, 153.5, 155.2, 155.6, 156.1 (s, i-Ar); MS
2
C(CH3)3), 1.33 (s, 18H; C(CH3)3), 3.13 (d, J ˆ 13.2 Hz, 2H; Heq), 3.15 (d,
2J ˆ 13.4 Hz, 2H; Heq), 3.48 ± 4.42 (m, 27H; ArOCH2CHRO(CH2CH2O)3,
2
2
CHCH2, OCH3, Hax), 4.70 (d, J ˆ 13.5 Hz, 1H; OCHHbpy), 4.76 (d, J ˆ
13.5 Hz, 1H; OCHHbpy), 6.50 ± 6.54 (m, 4H; Ar-H), 7.09 (s, 2H; Ar-H),
7.10 (s, 2H; Ar-H), 7.27 (ddd, 3J ˆ 7.5 Hz, 3J ˆ 4.5 Hz, 4J ˆ 1.2 Hz, 1H; bpy-
5'-H), 7.42 (d, 3J ˆ 7.7 Hz, 1H; bpy-5-H), 7.74 (td, 3J ˆ 7.5 Hz, 4J ˆ 1.7 Hz,
1H; bpy-4'-H), 7.80 (dd, 3J ˆ 7.7 Hz, 3J ˆ 7.7 Hz, 1H; bpy-4-H), 8.27 (d, 3J ˆ
7.8 Hz, 1H; bpy-3'-H), 8.37 (d, 3J ˆ 7.8 Hz, 1H; bpy-3-H), 8.66 (d, 3J ˆ
4.5 Hz, 1H; bpy-6'-H); 13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ 31.0 (t,
ArCH2Ar), 31.1, 31.7 (q, C(CH3)3), 33.6, 34.1 (s, C(CH3)3), 60.9, 61.3 (q,
OCH3), 69.8, 70.1, 70.9, 71.1, 71.2, 71.4, 72.9, 74.5, 75.6, 76.6 (t, ArCH2-
CHR(OCH2CH2)3), 77.4 (d, CHRO), 79.2 (t, CH2bpy), 119.7 (d, bpy-3),
121.2 (d, bpy-3'), 123.6, 124.5, 124.9, 125.0 (d, m-Ar, bpy-5, bpy-5'), 132.2,
132.6, 132.7, 132.9, 135.7, 135.8 (s, o-Ar), 136.8 (d, bpy-4'), 137.5 (d, bpy-4),
144.2, 144.3, 144.7 (s, p-Ar), 149.2 (d, bpy-6'), 155.5 (s, bpy-2ꢀ), 156.0, 156.2
(s, i-Ar, bpy-6), 157.9 (s, bpy-2); MS (CI, CH4): m/z (%): 1033.5 (100)
‡
(CI, CH4): m/z (%): 895.6 (100) [M‡H] ; C56H78O9 (895.23): calcd C 75.13,
H 8.78; found C 75.04, H 8.85.
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-[2,10-bis(hydroxymethyl)]-
crown-5 (29c): Pure compound 29c was obtained by column chromatog-
raphy on SiO2 with CHCl3/MeOH (10:1) as eluent. Yield ˆ 65%; m.p. 290 ±
25
2928C; [a]
ˆ
5.0 (c ˆ 0.0140, CHCl3); 1H NMR (300 MHz, CDCl3,
589
300 K): d ˆ 0.96 (s, 18H; C(CH3)3), 1.21 (s, 18H; C(CH3)3), 3.20 (d, 2J ˆ
12.7 Hz, 2H; Heq), 3.23 (d, 2J ˆ 12.7 Hz, 2H; Heq), 4.29 (d, 2J ˆ 13.0 Hz, 2H;
Hax), 4.34 (d, 2J ˆ 13.0, 2H; Hax), 3.61 ± 4.36 (m, 24H; ArOCH2-
CHROCH2CH2, CHCH2OH; OCH3), 6.70 (s, 4H; Ar-H), 6.96 (s, 4H;
Ar-H); 13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ 31.2 and 31.6 (q,
C(CH3)3); t, ArCH2Ar), 33.7, 34.0 (s, C(CH3)3), 61.6, 62.2 (q, OCH3), 68.7,
70.8, 75.0 (OCH2CHROCH2CH2, CHCH2OH), 79.8 (CHRO), 124.9, 125.0,
125.2 (d, m-Ar), 132.8, 133.1, 134.1, 134.4 (s, o-Ar), 144.5, 144.8 (s, p-Ar),
153.5, 155.2 (s, i-Ar); C56H78O9 (895.23): calcd C 75.13, H 8.78; found C
75.01, H 8.71.
‡
[M‡H] ; C66H84N2O8 (1033.40): calcd C 76.71, H 8.19, N 2.71; found C
76.81, H 8.24, N 2.75.
25,27-Dimethoxy-p-tert-butylcalix[4]arene-26,28-[2,10-bis(2,2'-bipyridine-
6-methyl)oxy-methyl]crown-4 (4):
Compounds 4a,b can be obtained from 29a,b in 62% yield after
preparative layer chromatography on Al2O3 with CH2Cl2/MeOH (99:1)
as eluent. The meso compound (4a) (Rf ˆ 0.26) can be separated from the
dl mixture (4b) (Rf ˆ 0.24) by preparative layer chromatography on Al2O3
with CH2Cl2 as eluent.
General procedure for the synthesis of 25,27-dimethoxy-p-tert-butylca-
lix[4]arene-26,28-[(2,2'-bipyridine-6-methyl)oxymethyl]crown-4 (2) and
-crown-5 (3), (4a,b), (4c): NaH (50% in mineral oil, 18 mg, 0.36 mmol
for compounds 27 and 28; or 36 mg, 0.66 mmol for compounds 29a,b and
29c) was added at RT to a stirred solution of calix[4]arene-hydromethyl-
crown 27, 28, 29a,b, or 29c (0.12 mmol) in dry THF (20 mL). After 15 min,
6-bromomethylbipyridine 30 (30.3 mg, 0.12 mmol for compounds 27 and
28; or 61 mg, 0.24 mmol for compounds 29a,b and 29c) was also added, and
meso-4a: 1H NMR (400 MHz, CDCl3, 253 K, cone): d ˆ 0.79 (s, 18H;
2
C(CH3)3), 1.33 (s, 18H; C(CH3)3), 3.13 (d, J ˆ 12.1 Hz, 2H; Heq), 3.16 (d,
2J ˆ 12.0 Hz, 2H; Heq), 3.46 ± 3.78 (m, 16H; ArOCH2CHROCH2CH2,
CHCH2O), 4.02 (s, 3H; OCH3), 4.19 (s, 3H; OCH3), 4.22 ± 4.35 (m, 2H;
CHRO), 4.31 (d, 2J ˆ 11.8 Hz, 2H; Hax), 4.41 (d, 2J ˆ 12.3 Hz, 2H; Hax), 4.69
(d, 2J ˆ 13.8 Hz, 2H; OCHHbpy), 4.83 (d, 2J ˆ 13.8 Hz, 2H; OCHHbpy),
6.46 (s, 2H; Ar-H), 6.47 (s, 2H; Ar-H), 7.14 (s, 2H; Ar-H), 7.15 (s, 2H; Ar-
H), 7.34 (dd, 3J ˆ 8.6 Hz, 3J ˆ 4.7 Hz, 2H; bpy-5'-H), 7.43 (d, 3J ˆ 7.8 Hz,
Chem. Eur. J. 2000, 6, No. 6
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0606-1033 $ 17.50+.50/0
1033

R. Ungaro, N. Sabbatini et al.
FULL PAPER
2H; bpy-5-H), 7.82 (dd, 3J ˆ 8.6 Hz, 3J ˆ 8.0 Hz, 2H; bpy-4'-H), 7.86 (dd,
3J ˆ 7.8 Hz, 3J ˆ 7.8 Hz, 2H; bpy-4-H), 8.21 (d, 3J ˆ 7.8 Hz, 2H; bpy-3-H),
8.32 (d, 3J ˆ 8.0 Hz, 2H; bpy-3'-H), 8.69 (d, 3J ˆ 4.7 Hz, 2H; bpy-6'-H); MS
[3] N. Sabbatini, M. Guardigli, I. Manet, in Advances in Photochemistry
Vol. 23 (Ed.: D. Neckers), Wiley, New York, 1997, p. 213.
[4] B. Alpha, R. Ballardini, V. Balzani, N. Sabbatini, J.-M. Lehn, S.
Perathoner, Photochem. Photobiol. 1990, 52, 299.
[5] N. Sabbatini, M. Guardigli, A. Mecati, V. Balzani, R. Ungaro, E.
Ghidini, A. Casnati, A. Pochini, J. Chem. Soc. Chem. Commun. 1990,
878.
[6] a) N. Sabbatini, M. Guardigli, I. Manet, R. Ungaro, C. Fischer, R.
Ziessel, G. Ulrich, New J. Chem. 1995, 19, 137;b) A. Casnati, C.
Fischer, M. Guardigli, A. Isernia, I. Manet, N. Sabbatini, R. Ungaro, J.
Chem. Soc. Perkin Trans. 2 1996, 395.
[7] a) G. Ulrich, R. Ziessel, I. Manet, M. Guardigli, N. Sabbatini, F.
Fraternali, G. Wipff, Chem. Eur. J. 1997, 3, 1815;b) L. Prodi, S. Pivari,
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[8] N. Sato, S. Shinkai, J. Chem. Soc. Perkin Trans. 2 1993, 621.
[9] F. J. Steemers, W. Verboom, D. N. Reinhoudt, E. B. van der Tol, J.
Verhoeven, J. Am. Chem. Soc. 1995, 117, 9408.
‡
(CI, CH4): m/z (%): 1231.7 (100) [M‡H] ; C78H94N4O9 (1231.63): calcd C
76.07, H 7.69; found C 75.96, H 7.61.
(dl)-4b: 1H NMR (400 MHz, CDCl3, 253 K, cone): d ˆ 0.79 (s, 18H;
C(CH3)3), 1.22, 1.33 (s, 9H; C(CH3)3), 3.15 (d, 2J ˆ 11.8 Hz, 2H; Heq), 3.17
(d, 2J ˆ 11.7 Hz, 2H; Heq), 3.47 ± 4.30 (m, 22H; ArOCH2CHROCH2CH2,
CHCH2O, Hax), 4.10 (s, 6H; OCH3), 4.71 (d, 2J ˆ 13.7 Hz, 2H; OCHHbpy),
4.80 (d, 2J ˆ 13.8 Hz, 2H; OCHHbpy), 6.48 (s, 4H; Ar-H), 7.13, 7.14 (s, 2H;
Ar-H), 7.34 (ddd, 3J ˆ 7.5 Hz, 3J ˆ 4.8 Hz, 4J ˆ 1.0 Hz, 2H; bpy-5'-H), 7.44
(d, 3J ˆ 7.7 Hz, 2H; bpy-5-H), 7.82 (ddd, 3J ˆ 7.8 Hz, 3J ˆ 7.7 Hz, 4J ˆ 1.6 Hz,
2H; bpy-4'-H), 7.85 (dd, 3J ˆ 7.8 Hz, 3J ˆ 7.8 Hz, 2H; bpy-4-H), 8.21 (d, 3J ˆ
7.9 Hz, 2H; bpy-3'-H), 8.33 (d, 3J ˆ 7.9 Hz, 2H; bpy-3-H), 8.69 (d, 3J ˆ
‡
4.7 Hz, 2H; bpy-6'-H); MS (CI, CH4): m/z (%): 1231.7 (100) [M‡H] ;
C78H94N4O9 (1231.63): calcd C 76.07, H 7.69; found C 75.99, H 7.59.
(S,S)-4c: Compound (4c) was prepared from the enantiomerically pure
compound (29c), and was purified by preparative layer chromatography
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Chem. 1997, 69, 1061.
25
(elution gradient CH2Cl2/CH3OH, 100:1 ± CH2Cl2). M.p. 80 ± 828C; [a]
ˆ
589
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‡ 9.04 (c ˆ 0.0188, CHCl3); 13C NMR (75.5 MHz, CDCl3, 300 K): d ˆ 31.1,
31.7 (q, C(CH3)3), 31.9 (t, ArCH2Ar), 33.5, 34.1 (s, C(CH3)3), 61.4 (q,
OCH3), 69.0, 70.3, 70.5, 74.5, 75.5 (t, OCH2CHROCH2CH2, CHCH2O,
OCH2bpy), 78.6 (d, CHRO), 119.7 (d, bpy-3'), 121.2 (d, bpy-3), 123.4 (d,
bpy-5'), 124.5 (d, bpy-5), 124.5, 125.0, 125.1, 125.2 (d, m-Ar), 132.2, 132.5,
135.6, 135.8 (s, o-Ar), 136.8 (d, bpy-4'), 137.5 (d, bpy-4), 144.2, 144.8 (s, p-
Ar), 149.1 (d, bpy-6'), 153.4, 155.4 (s, i-Ar, bpy-2'), 156.0 (s, bpy-6), 157.8 (s,
‡
bpy-2); MS (CI, CH4): m/z (%): 1231.7 (100) [M‡H] ; C78H94N4O9
(1231.63): calcd C 76.07, H 7.69; found C 75.99, H 7.60.
Spectrophotometric titration: Spectrophotometric titrations in dry aceto-
nitrile or methanol (containing ꢁ 5% H2O) were performed on a spec-
trophotometer Kontron 860. Gradually larger amounts of a solution (1 Â
10 3 m) of Tb(ClO4)3 or Eu(ClO4)3 were added to a solution (1 Â 10 5 m,
2.5 mL) of ligands 2, 3, or 4c (containing 5.7 mg of Et4NClO4) in order to
produce a metal-to-ligand ratio in the range from 0.4 to 20. After each
addition the corresponding UV/Vis spectrum was recorded between 240
and 360 nm. These spectra, together with the analytical concentrations of
the ligand and the metal ion, were entered into the program SIRKO[29] for
evaluation of the 1:1 association constants, K, between the ligands and the
lanthanide ions.
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Acknowledgments
This work was partially supported by the C.N.R. (Consiglio Nazionale delle
Ricerche), Progetto ªProdotti e Dispositivi Supramolecolariº, by Human
Capital and Mobility Programme (Contract no. CHRX-CT94 ± 0484) and
by M.U.R.S.T. (Supramolecular Devices Project). We thank the C.I.M.
(Centro Interdipartimentale Misure) dellꢀUniversita di Parma for the
NMR and Mass facilities.
Á
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Neu, Talanta 1994, 41, 2105.
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Chemistry of Rare Earths Vol. 23 (Eds.: K. A. Gschneider, L. Eyring),
Elsevier, Amsterdam, 1996, p. 69.
Received: August 13, 1999 [F1977]
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