Synthesis of a Hexagonal Nanosized Macrocyclic Fluorophore with Integrated Endotopic Terpyridine Metal-Chelation Sites

Article abstract of DOI:10.1002/chem.200304786

A rigid nanosized hexagonal phenylethynyl cyclophane 5 has been prepared, which incorporates two 2,2′:6′,2″-terpyridines as integral structural units, for the purpose of binding metal ions. Macrocycle 5 was obtained by a 14-step synthesis in an overall yield of 11%, and was characterised by spectroscopic techniques. The efficiency and ease of all transformations, and the relatively enhanced yield of the final macrocyclisation suggests that the entire synthetic pathway should be amenable to scale-up. Cyclophane 5 possesses four bulky triisopropylsilyl(TIPS) -protected ethyne substituents which serve a dual role. Firstly, they solubilise the structure thereby facilitating purification and subsequent handling. Secondly, they enable post-synthetic modification in which additional functionality may be attached to the periphery of the ring. Significantly, 5 was found to be a fluorescent chromophore, and may therefore potentially function as a new sensory platform for the detection of metal ions and H-bond donating biological substrates. The structurally well-defined nanosized morphology of 5, coupled with its interesting spectroscopic properties, supports the expectation that 5 and related architectures will attain a wealth of future applications within the developing fields of nanochemistry and nanoscience.

Full text of DOI:10.1002/chem.200304786

FULL PAPER
Synthesis of a Hexagonal Nanosized Macrocyclic Fluorophore with Integrated
Endotopic Terpyridine Metal-Chelation Sites
[a, b]
Paul N.W.Baxter*
Abstract: A rigid nanosized hexagonal
phenylethynyl cyclophane 5 has been
prepared, which incorporates two
2,2':6',2''-terpyridines as integral struc-
tural units, for the purpose of binding
metal ions. Macrocycle 5 was obtained
by a 14-step synthesis in an overall yield
of 11%, and was characterised by spec-
troscopic techniques. The efficiency and
ease of all transformations, and the
relatively enhanced yield of the final
macrocyclisation suggests that the entire
synthetic pathway should be amenable
to scale-up. Cyclophane 5 possesses four
bulky triisopropylsilyl(TIPS)-protected
ethyne substituents which serve a dual
role. Firstly, they solubilise the structure
thereby facilitating purification and sub-
sequent handling. Secondly, they enable
post-synthetic modification in which
additional functionality may be attached
to the periphery of the ring. Significant-
ly, 5 was found to be a fluorescent
chromophore, and may therefore poten-
tially function as a new sensory platform
for the detection of metal ions and
H-bond donating biological substrates.
The structurally well-defined nanosized
morphology of 5, coupled with its inter-
esting spectroscopic properties, supports
the expectation that 5 and related archi-
tectures will attain a wealth of future
applications within the developing fields
of nanochemistry and nanoscience.
Keywords: alkynes ¥ cyclooligomer-
isation ¥ cyclophanes ¥ macrocyclic
ligands ¥ nanostructures
collapse of the desired superstructure. In recent years,
phenylethynyl precursor units have been demonstrated to
serve as particularly effective rigidifying building blocks for
Introduction
Over the past two decades, synthetic organic chemistry has
witnessed a gradual paradigm shift, from that of the discovery
of new reactions and the synthesis of novel small molecules, to
the property-targeted generation of new materials with
c]
the conservation of nanomolecular shape.[3a The latter
approach has thus far enabled the creation of a structurally
diverse variety of organic phenylethynyl-nanoarchitectures,
d]
d]
specific functions.[1a Nowhere has the quest for organic
such as hyperbranched and dendritic macromolecules,[4a
f]
molecules with new properties been more intense than in the
developing fields of nanoscience and nanochemistry. Nano-
sized organic molecules may exhibit novel physicochemical
properties not expressed by their component parts, and in this
respect constitute a reservoir of structurally and functionally
complex modules from which the forthcoming generation of
catenanes,[5] linear oligomers and nanowires,[6a folded spi-
ral[7a e] and double helical structures,[8a,b] cages[9a,b] and macro-
cycles.[10a With respect to phenylethynyl nanoarchitecture
n]
generation, large macrocyclic structures have attracted a
considerable proportion of interest, due primarily to their
ready synthetic access. The latter class of organic materials are
particularly attractive candidates for nanochemical applica-
tions as they display useful functional properties, such as for
21st century smart materials may be expected to emerge.[2a
h]
The relationship between morphology and function be-
comes especially significant when the size of a molecule enters
into the nanoscopic domain. However, the preservation of
molecular shape necessitates the employment of relatively
rigid structural units that can collectively resist opposing
external forces that would otherwise lead to solvophobic
d]
c]
example, host guest inclusion,[11a liquid crystallinity,[12a
solid-state porosity.[13a,b]
To expand and diversify the potential range of utilisable
properties of nanosized phenylethynyl macrocycles, an espe-
cially intriguing avenue of investigation would be to endow
such scaffolds with the ability to bind metal ions and
complexes, either internally or externally on the outer surface
[a] Dr. P. N. W. Baxter
l]
of the ring.[14a As well as the above-mentioned properties,
¬
Laboratoire de Chimie Supramoleculaire
¬
Institut Le Bel, Universite Louis Pasteur
rigid molecular edifices of this type may be envisioned to
exhibit electrochemical, photochemical, magnetic, optical,
4rue Blaise Pascal, 67000 Strasbourg (France)
E-mail: pbaxter@chimie.u-strasbg.fr
f]
catalytic, mechanical and sensory abilities for example.[15a
[b] Dr. P. N. W. Baxter
In relation to the latter considerations, earlier work focused
upon the syntheses of ortho-conjugated phenylethynyl macro-
cycles of the tetrabenzodehydroannulene-type, which incor-
Current address: Institut Charles Sadron, 6 Rue Boussingault, 67083
Strasbourg (France)
E-mail: pbaxter@ics.u-strasbg.fr
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DOI: 10.1002/chem.200304786
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P. N. W. Baxter
FULL PAPER
porated 2,2'-bipyridine 1 3,[14f,h] and pyridine 4,[14a] moieties
for the purpose of metal ion coordination. It was anticipated
that interaction of the pyridine nitrogen atoms with metal ions
would initiate electron density perturbations within the
the presence of for example, nanosized hydrogen bond donor
biomolecular guests as well as cations.
Nanophane 5 (see Scheme 3) is an example of an organic
molecule that embodies the latter structural requirements.
The cyclophane comprises two endotopic oligopyridine
2,2':6',2''-terpyridine units incorporated into a conjugated
hexagonal phenylethynyl macrocyclic scaffold of nanoscopic
dimensions. Towards the goal of creating nanosized sensory
materials, the following account describes the successful
synthesis of 5, and its characterisation by spectroscopic
methods.
Results and Discussion
Nanophane 5 was constructed by using a synthetic strategy
that involved three main stages. In the first stage, the
phenylethynyl vertex precursor 13 was prepared from the
commercially available 6 in five steps (Scheme 1). The second
stage required the synthesis of the metal ion binding module
24 in seven steps starting from the commercially available 14
(Scheme 2). Finally, 13 and 24 were combined to provide the
macrocycle half unit 25, which was subsequently deprotected
and cyclised to give 5 (Scheme 3).
Synthesis of vertex precursor 13: During initial attempts to
prepare 13, it was anticipated that the required unsymmetrical
1,3,5-R,R',R''-phenyl substitution pattern could be achieved
by using sequential Sonogashira coupling reactions directly
upon 6 (Scheme 1). However, the 1:1 stoichiometric reaction
between trimethylsilylacetylene (TMSA) in the presence of
CuI and [PdCl2(PPh3)2] catalysts and in Et3N/toluene solu-
tions over a range of temperatures yielded only statistical
mixtures of unreacted 6, 8, di- and tri-ethynylated products
which were difficultly separable by column chromatography
on a large scale. Pure 8 was therefore obtained by way of 7.
The reaction between 7[16] and TMSA in Et3N with CuI and
[PdCl2(PPh3)2] catalysts proceeded very selectively at ambient
temperature to afford 8[17a, b] in 93% yield after work-up.
Treatment of 8 with one equivalent of nBuLi in Et2O at low
conjugated macrocyclic framework, which would in turn be
accompanied by a change in properties such as redox
potentials and fluorescence emission energies and intensities.
The ligands would thus function as cation sensors, affording
for example visual spectroscopic signal outputs characteristic
of specific metals. Detailed ion-binding studies revealed that
1
4 did in fact function as fluorescence ion sensors, with 1
giving a chromogenic response specific to Zn2‡ ions, 2 and 3
undergoing fluorescence quenching with Cu2‡ and 4 display-
ing fluorescence quenching spe-
cific to Hg2‡ and PdCl2. It was
concluded from the latter studies
that subtle structural changes in
the macrocyclic framework re-
sulted in dramatic changes in
ion-binding selectivity and sen-
sory signal output. Prior to the
above investigations, it was an-
ticipated that a rigidified, nano-
sized macrocycle with endotopic
metal ion binding sites of in-
creased denticity, may display
particularly efficient guest inclu-
sion and therefore sensory prop-
erties, due to the inherent pre-
Scheme 1. Synthesis of phenylethynyl vertex precursor 13. i) a) 1 equiv nBuLi, À788C, Et2O, 3 h, b) I2/Et2O
(84%); ii) [PdCl2(PPh3)2], CuI cat., TMSA, Et3N, 20 8C, 4d (93%); iii) a) 1 equiv n-BuLi, À788C, Et2O, 2 h,
b) ICH2CH2I/Et2O (95%); iv) [PdCl2(PPh3)2], CuI cat., TIPSA, Et3N, 20 8C, 4.5 days (99%); v) as in (iv), (97%);
organisation of the ring. Signifi-
cantly, a sensory platform of this
type may be expected to signal vi) as in (i), (71%); vii) as in (ii), (72%); viii) as in (iii), (93%).
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Nanosized Macrocyclic Fluorophores
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temperature, followed by quenching the phenyllithium inter-
mediate with 1,2-diiodoethane provided 9 in 95% yield after
chromatographic purification. The oil 9 was then coupled with
triisopropylsilylacetylene (TIPSA) in Et3N with CuI and
[PdCl2(PPh3)2] catalysts, to give 10 as a colourless, very viscous
oil in near quantitative yield after work-up.
at ambient temperature, to give 17 in 85% yield after
c]
chromatography and recrystallisation.[21a Bromoethyne 17
was then found to undergo a selective halogen lithium
exchange at the ethynyl-bromine with one equivalent of
nBuLi in Et2O at À788C. Subsequent quenching of the
reaction with ClSiMe3 at low temperature, provided 18 in
88% yield after work-up.
In parallel to the above synthesis, an alternative preparative
pathway to 10 was also investigated, in which the TIPSA
group was introduced prior to the TMSA. Thus coupling of 7
with TIPSA under conditions similar to that used for the
generation of 8, afforded 11[18] in 97% yield after chromatog-
raphy. Selective monolithiation of 11 followed by addition of
iodine to the intermediate phenyllithium, employing condi-
tions identical those used for the generation of 7, gave 12 in
71% yield. The reaction of 12 with TMSA in Et3N in the
presence of CuI and [PdCl2(PPh3)2] catalysts furnished 10 in
72% isolated yield. The syntheses of 12 and its subsequent
conversion to 10 proceeded in significantly lower yields
compared to the previously described route using 9. The
inferior yields of 12 were partly attributable to a side reaction
in which proteo-debromination of the phenyl ring was
occurring. Both the production of 12 and its reaction with
TMSA involved considerably less clean transformations than
those encountered during the syntheses of 9 and its conversion
to 10. Laborious and repeated column chromatographic
purifications of 12, and the 10 prepared from 12, were thus
required to obtain products that were clean by 1H NMR
spectroscopy. These latter findings demonstrated that the
optimal preparative route to 10 required the introduction of
the TIPSA group in the final synthetic step.
At this point it was envisioned that the tri-n-butylstannyl-
pyridine 19 would also serve as a useful synthon in the
preparation of ethynyl-oligopyridine molecular scaffolds.[22a, b]
Accordingly, the latter stannylpyridine was synthesised by
treatment of a solution of 18 in THF at À788C with one
equivalent of nBuLi, followed by quenching of the pyridyl-
lithum intermediate with ClSn(nBu)3, affording 19 in 68%
isolated yield. Scaling-up the lithiation stannylation reaction
to quantities of 18 of greater than 2 g did however result in the
isolation of significantly reduced yields of 19. With both
oligopyridine building blocks 18 and 19 in hand, exploratory
investigations could then be undertaken in order to determine
the optimal conditions for the generation of 23.
To assess the potential utility of 19 for the construction of
oligopyridine units, initial approaches to the synthesis of
terpyridine 23 focused upon the palladium catalysed Stille
reaction between 19 and 2,6-dibromopyridine 20.[23] Thus the
reaction between 19 and 20 in the presence of Pd(PPh3)4
catalyst and LiCl in toluene yielded 59% of 23. However,
reduced yields of 23 resulted when the reaction was carried
out using ꢀ0.5 g of 19.
Distannylpyridines have been described in the literature as
serving as ideal substrates for the rapid and convergent
e]
It was anticipated that later in the reaction sequence, the
utilisation of iodophenyl 13, rather than 10, would afford bis-
coupling product 25 in higher yield and greater purity.[19]
Bromophenyl 10 was therefore
construction of oligopyridines.[23, 24a It was originally antici-
pated therefore that the use of distannylpyridines 21[25] and
22[24c, 26a, b] may provide the most convergent and economic
lithiated and iodinated at low
temperature in Et2O, to furnish
13 in 93% yield after work-up.
Synthesis of terpyridine precur-
sor 24: The terpyridine precur-
sor 24 was synthesised by way of
a seven-step pathway starting
from 14 (Scheme 2). Thus 14
was converted to 15[20a,b] and
the latter compound subjected
to a Corey Fuchs reaction, in
which a CH2Cl2 solution of CBr4
was added to a mixture of 15,
PPh3 and excess Et3N in CH2Cl2
at À788C. The dibromovinylpyr-
idine 16 was subsequently ob-
tained in 93% yield after work-
up. The reaction was found to be
very exothermic when conduct-
ed at ambient temperature, af-
Scheme 2. Synthesis of 5,5''-diethynyl-terpyridine precursor 24. i) a) 1 equiv nBuLi, À788C, Et2O, 1.75 h, b) DMF
(80%); ii) a) PPh3, Et3N, CH2Cl2, b) CBr4/CH2Cl2, À708C, 1 h (93%); iii) NaOMe/MeOH, 208C, 48 h (85%); iv)
a) 1 equiv nBuLi, À788C, Et2O, 2.5 h, b) ClSiMe3 (88%); v) a) 1 equiv nBuLi, À788C, THF, 1 h, b) ClSn(nBu)3
(68%); vi) [Pd(PPh3)4] cat., LiCl, toluene, 1208C, 24h (59%); vii) as in (vi), (35%); viii) as in (vi), (53%); ix)
TBAF/THF, THF/distilled H2O, 20 8C, 6 h (93%).
fording considerably reduced
yields of 16. Dibromovinylpyri-
dine 16 was dehydrobrominated
with NaOMe in MeOH solution
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P. N. W. Baxter
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method of access to 23. However, reaction of a 2:1 stoichio-
metric ratio of 18:21 under conditions identical to those used
for the preparation of 23 from 19 and 20, resulted in the
formation of 23 in a much reduced isolated yield of 35%.
Reaction scale-up caused further reductions in the yield of 23.
When the coupling was performed using 22 in place of 21, an
enhancement in the isolated yield of 23 to 53% occurred, and
the reaction was also found to be amenable to scale-up.
The above results therefore suggest that the syntheses of
terpyridine 23 from 19 ‡ 20, and 18 ‡ 21, are limited
primarily to small-scale preparations. The most reliable
approach to 23, using the pyridine building blocks described
above is thus the reaction between 18 and 22.
inferior purity was obtained, which required repeated chro-
matography to remove the contaminants. As a result, a
slightly lower yield of 59% 23 was isolated from the reaction
catalysed by [PdCl2(dppf)] ¥ CH2Cl2.
Preferential deprotection of trimethylsilylethynes in the
presence of triisopropylsilylethynes has been reported to be
achievable with aqueous hydroxide.[29] Surprisingly, when a
solution of 25 in THF at 08C was treated with two equivalents
of aqueous KOH in MeOH, and the reaction stirred at
ambient temperature for 24h, the deprotection occurred
unselectively with the formation of a statistical distribution of
four desilylated products as judged by TLC analysis. The
desired terpyridine 26 was subsequently isolated from the
reaction in a disappointing 53% yield. An alternative
selective deprotection methodology was therefore attempted,
which involved the use of K2CO3 in MeOH.[30] Thus, the
reaction between a 1:1 stoichiometric mixture of 25 and
powdered K2CO3 in 2:1 Et2O/MeOH at ambient temperature
resulted in the clean formation of 26, which was isolated in
97% yield. Having successfully obtained the precursor
diethynyl-terpyridine 26 in sufficient quantities, its macro-
cyclisation reaction to 5 could finally be undertaken.[31]
Treatment of an aqueous THF solution of 23 with TBAF,
resulted in smooth desilylation to afford the deprotected
diethynyl-terpyridine precursor 24, in 93% yield.[27]
Synthesis of cyclophane 5: The third and final stage in the
construction of 5 comprised the combination of the central
metal ion-binding terpyridine unit 24 with 13 to give the
macrocycle precursor half-unit 25 (Scheme 3). Selective
deprotection of 25 followed by a metal-mediated oxidative
dimerisation was then expected to result in the formation of 5.
Thus the ambient temperature reaction between a 2:1
stoichiometric combination of 13 and 24, in the presence of
[PdCl2(PPh3)2] and CuI catalysts and Et3N in pyridine,[28]
afforded 25 in 62% yield. When the reaction was performed
with [PdCl2(dppf)] ¥ CH2Cl2 (dppf ˆ 1,1'-bis(diphenylphos-
phino)ferrocene) in place of [PdCl2(PPh3)2], a product of
Previous ethyne-coupling macrocyclisations to give 1
3
suggested that cyclisation yields were strongly influenced by
the coordination of the precursor bipyridine subunits to the
CuCl catalyst, and/or other copper species generated there-
from.[14f,h] For example, macrocyclisations performed under
similar conditions afforded a much lower yield of 2 (9 13%),
compared to that of 1 (34%). The yield disparity between 1
and 2 was consistent with the
presence of ion-templating phe-
nomena.[32]
In the light of the aforemen-
tioned observations, it was
therefore decided to explore
the effectiveness of the Eglin-
ton/Galbraith ethyne coupling
protocol in the cyclisation of 26,
which uses [Cu2(OAc)4] in
place
of
CuCl.[31]
The
[Cu2(OAc)4] would be expected
to exhibit a significantly lower
ambient temperature coordina-
tion affinity towards 26 com-
pared to that of CuCl, and CuI/II
species generated from the lat-
ter. The relatively high concen-
tration of [Cu2(OAc)4] com-
pared to 26 would also disfa-
vour
the
generation
of
[Cu(26)2]I/II type complexes.
Rewardingly, the cyclisation
of 26 under medium/high dilu-
tion conditions in degassed pyr-
idine with an excess of
[Cu2(OAc)4], proceeded with-
out problem, affording a re-
spectable 39% yield of 5 after
Scheme 3. Synthesis of macrocycle 5 from precursors 13 and 24. i) [PdCl2(PPh3)2], CuI cat., pyridine, 208C, 7d
(62%); ii) K2CO3, MeOH/Et2O, 20 8C, 14h (97%); iii) a) excess [Cu 2(OAc)4], pyridine, 208C, 8 h addition, then
b) seven days, 208C (39%).
work-up.
A
1H NMR and
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Nanosized Macrocyclic Fluorophores
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MALDI TOF mass spectral analysis of the toluene extract of
the crude reaction product prior to chromatographic purifi-
cation, showed that 5 was formed in >50% yield. The
MALDI TOF mass spectrum also exhibited three small
higher mass peaks assignable to the presence of a small
quantity of tetrameric, pentameric and hexameric cyclic or
linear oligomers.[33]
a single compound and not a mixture of species. Peaks
originating from the protons of terminal ethynes were
completely absent in the H NMR spectrum of the coupling
product, lending further support for the macrocyclic identity
of this compound.
Spectral assignments of 5 were made on the basis of
integrations, coupling constants and comparisons with the
spectra of 23 26.[34]
1
Characterisation of nanophane 5: The structure of the product
isolated from the [Cu2(OAc)4]-mediated coupling of 26 was
established to be that of the macrocyclic architecture 5
(Scheme 3) on the basis of mass spectrometric, infrared, H
and 13C NMR spectroscopic studies.
Spectroscopic properties of 5, and precursors 23 26: The UV/
Vis spectra of CHCl3 solutions of 23 26 all comprised four
absorption envelopes. In the case of 25 and 26 (Figure 2), the
1
The FAB mass spectrum of the coupling product recorded
in 10 20% CF3COOH/CHCl3 displayed a single isotope
cluster peak centred at m/z 1681, in the m/z range of 350
‡
2040, corresponding exactly to that calculated for the [M ‡
H] isotopic envelope of macrocycle 5. This structural assign-
ment was further substantiated by a high-resolution FAB
‡
mass spectrometric measurement of the [M ‡ H] isotopic
envelope, which confirmed the exact elemental composition
of the product to be C114H115N6Si4 in accordance with the
macrocyclic structure 5 plus one hydrogen. The 13C NMR
spectrum of the coupling product of 26 comprised 22 peaks,
consistent with the above macrocyclic structural assignment.
The chemical shifts of the six peaks at d ˆ 105.0 75.2 ppm
correspond to the chemically and magnetically inequivalent
carbon atoms of three unsymmetrically substituted alkyne
groups. The remaining 14downfield peaks at d ˆ 155.6
119.7 ppm, and the two upfield peaks at d ˆ 18.7 11.6 ppm,
correspond to the aromatic ring and isopropyl carbon atoms,
respectively.
Figure 2. UV/Vis spectra of 5 and 23 26 in CHCl3 solution at 208C.
1
The H NMR spectrum of the coupling product of 26, was
also consistent with the macrocyclic structure 5, displaying
two lowest energy absorptions were shifted approximately 20
to 30 nm to lower energy indicating an increased degree of
conjugation within these molecules. The UV/Vis spectrum of
5 on the other hand was particularly distinctive, comprising six
absorption envelopes from 261 to 348 nm (Figure 2). The
absorption maxima of 5 exhibited a linear relationship
between concentration and absorbance, and zero change in
energies at [5] ꢁ1.1 Â 10À5 mol dmÀ3, demonstrating that
kinetically fast aggregation phenomena were either negligible
or absent in dilute solution.
eight resonances with the expected splitting patterns between
1
d ˆ 9.0 and 7.5 ppm, due to aromatic protons (Figure 1). H
1H COSY and ROESY measurements also verified that it was
Interestingly, CHCl3 solutions of macrocycle 5, and terpyr-
idine precursors 23 26 all emitted a strong purple-blue
coloured fluorescence when irradiated with a UV lamp
operating at 365 nm. The emission energies and intensities
of all compounds remained unchanged in the presence and
absence of air, showing that the excited states of 23 26 and 5
were insensitive to quenching by oxygen. The emission bands
of the terpyridine ligands decreased in energy in the following
order, 24 > 23 ꢂ 25 ꢃ 26 > 5 (Figure 3). The effect of the
electron donating Me3Si substituents in 23 were therefore to
lower the emission energy of the conjugated terpyridine
chromophore. The even greater relative decrease in the
emission energy of 25, 26 and 5 evidenced the extension of the
chromophore conjugation into the peripheral phenyl rings.
The fluorescence emission spectra of 25 and 26 were however,
virtually identical, exemplifying the structural similarity of the
excited states of these two molecules. Dilution studies
1
Figure 1. 500 MHz H NMR of 5 recorded in CDCl2CDCl2 at 808C.
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P. N. W. Baxter
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isolation of a respectable 39% yield of 5. Furthermore, all
reaction products were readily purified by conventional
column chromatographic techniques. These factors collec-
tively suggest that the entire synthetic sequence should be
amenable to scale-up in order to provide gram quantities of
5.[37]
Molecular modelling studies confirmed that 5 was a nano-
sized macrocyclic structure possessing a large central cavity,
and with a calculated intra-terpyridyl distance of 15 ä (Fig-
ure 4).[38] Cyclophane 5 should therefore be expected to bind
to a wide spectrum of guest species either by hydrogen-
bonding to the terpyridyl nitrogen atoms,[39a, b] or through
coordination interactions when the terpyridines are bound to
metal ions. Of especial note is the fact that 5 is fluorescent
when exposed to UV light. This latter physical property,
coupled with potential guest inclusion abilities suggests that 5
and related structures may possibly function for example, as a
Figure 3. Normalised fluorescence emission spectra of 5 and 23 25 in
CHCl3 solution at 208C (300 nm excitation).
f]
new class of nanosensory materials.[40a
performed with CHCl3 solutions
of 23 26, revealed that the
emission energies remained con-
stant with change in concentra-
tion below 2 Â 10À5 mol dmÀ3,
showing that excited-state ag-
gregation of these systems was
absent in dilute solution. In the
case of 5, similar dilution studies
demonstrated that the macrocy-
cle was not undergoing excited-
state aggregation at [5] ꢁ 2.9 Â
10À6 mol dmÀ3.[35] However, the
emission spectrum of a thin film
of 5 comprised a broad band
(lmax ˆ 454 nm) at a significantly
lower energy than that of 5 in
solution and
Figure 4. Energy-minimised structures of the all-planar conformation of the macrocyclic ring of 5, without the
TIPSA substituents; plan view through cavity: space-filling representation (left), stick representation (right). The
minimisations were obtained by AM1 semi-empirical calculations, using SPARTAN 02 Linux/Unix, Wave-
function, Irvine CA (USA).
(lmax ˆ 358
375 nm), indicating that excit-
ed-state aggregation of the mac-
rocycle was existent in the solid
state.
A design feature of particular significance is that 5 has been
constructed with four outwardly projecting triisopropylsilyle-
thynyl subunits. The latter functionality endows 5 with two
important structural assets; 1) enhanced solubility in lip-
ophilic solvents, which facilitates purification, characterisa-
Conclusion
tion and processing and reduces problems originating from
self-aggregation phenomena, and 2) the possibility of post-
synthetic-modification. In the latter case, partial or complete
deprotection of the TIPS groups should enable further
Sonogashira alkynyl couplings to be performed upon 5,
thereby allowing the introduction of a plethora of additional
functionality, and the possibility for incorporation into larger
superstructures.[41]
The synthetic approach to 5 detailed above should thus
enable the creation of a palate of hybrid organic/inorganic
scaffolds currently conceivable on the nanostructural hyper-
surface. Nanophane 5 and related structures may also be
expected to contribute to the development of novel materials
The above work discloses a successful preparative strategy for
the construction of a large nanosized ethynyl cyclophane, or
nanophane 5, which incorporates oligopyridine subunits for
the purpose of metal ion coordination.[36] The synthesis
comprised a convergent approach in which the appropriately
functionalised phenylethynyl vertex 13, and metal ion binding
terpyridine 24 were independently assembled, then subse-
quently connected to give the macrocycle half-unit 25.
Selective deprotection of 25 to give 26, followed by cyclisation
afforded 5, in a total of 14steps from 6, 14 and 22, and in an
overall yield of 11%. Eleven of the steps proceeded in ꢀ80%
yield, and the employment of the Eglinton/Galbraith ethyne
coupling protocol for the final cyclisation resulted in the
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5011 5022
‡
(s), 670 (s), 654cm À1 (m); EIMS (CHCl3): m/z (%): 380 (44) [M ], 365
with complex functional properties, within the realm of
nanoscience and nanotechnology.
‡
‡
(100) [M À {CH3}]; HRMS (EI, CHCl3, [M ]) calcd for C11H12BrISi:
377.8936; found: 377.8932.
1-Bromo-3-[2-(1-triisopropylsilylethynyl)]-5-[2-(1-trimethylsilylethynyl)]-
benzene (10), (from 9): Et3N (30 mL), which had been bubbled with argon,
was added by syringe to a mixture of 9 (4.239 g, 1.12 Â 10À2 mol) and
[PdCl2(PPh3)2] (0.060 g, 8.55 Â 10À5 mol) under an atmosphere of argon.
After the mixture had been stirred for a few minutes, TIPSA (2.087 g,
1.14 Â 10À2 mol) and a solution of CuI (0.060g, 3.15 Â 10À4 mol) in degassed
Et3N (10 mL) were added consecutively by syringe. The mixture was stirred
at ambient temperature for 4.5 days in the absence of light, during which
time a copious cream precipitate formed. All solvent was subsequently
removed under reduced pressure on a water bath and the residue worked-
up and purified as described for 8 above. After flash chromatography on
silica with hexane eluant, the product was dried under dynamic vacuum to
yield 10 (4.778 g, 99%) as a colourless odourless oil.
Experimental Section
General: Starting materials 6 and 14, 20, TMSA, TIPSA,[42] CuI, and
[Cu2(OAc)4] were purchased from Aldrich and used as received. The
catalysts [Pd(PPh3)4],[43] [PdCl2(PPh3)2],[44] [PdCl2(dppf)] ¥ CH2Cl2,[45] were
prepared according to literature procedures. Standard inert atmosphere
and Schlenk techniques were employed for reactions conducted under
argon. The Et3N, toluene and pyridine solvents used in the preparation of
respectively 8, 10, 11, 23 and 25, were deoxygenated by bubbling with argon
for 0.5 h directly prior to use. The THF and Et2O used in the preparation of
7, 9, 12, 13, 15, 18 and 19 were freshly distilled off Na/benzophenone under
argon. The CH2Cl2 solvent used in the preparation of 16 was freshly
distilled off P4O10 under argon. The silica used for all flash chromatography
was purchased from Merck (Geduran, Silica gel Si 60, 40 60 mm). The
alumina (neutral, standard activity) used in the chromatographic purifica-
tion of 19 and 24 was purchased from Merck. Unless otherwise stated, all
1H NMR spectra were recorded at 500 MHz and 13C NMR spectra at
125.8 MHz in CDCl3 at 258C. The 1H and 13C NMR spectra recorded in
CDCl3 were referenced to the solvent peaks at d ˆ 7.26 and 77.0 ppm,
respectively. The 1H and 13C spectra of 5 recorded in CDCl2CDCl2 were
referenced to the solvent peaks at d ˆ 6.00 and 74.0 ppm, respectively.
Intramolecular proton connectivities were determined by 1H 1H COSY,
NOESY and ROESY NMR measurements. The fluorescence emission
spectra were recorded at 20 258C on a Aminco, Bowman Series 2
luminescence spectrophotometer (SLM Instruments, Inc.). All fluores-
cence emission spectra recorded in CHCl3 solution were corrected for the
instrumental response. The infrared spectrum of 25 was recorded as a
CHCl3 evaporated thin film on a KBr disc, and that of 5 as nujol and
polychlorotrifluoroethylene mulls. All the other infrared spectra were
recorded as liquid thin films or KBr discs. Melting point measurements
were performed on an Electrothermal Digital Melting Point apparatus
calibrated with standards of known melting points. Elemental analyses
were performed by the Service de Microanalyse, Institut de Chimie,
1H NMR: d ˆ 7.539 (d, 2H; H2/6), 7.482 (t, 1H; H4), 1.120 (s, 21H;
CH(CH3)2), 0.244 ppm (s, 9H; Si(CH3)3); 13C NMR: d ˆ 134.6, 134.4, 133.9,
ꢄ
ꢄ
ꢄ
ꢄ
125.4, 125.0, 121.6, 104.4 (-C ), 102.5 (-C ), 96.6 (-C ), 93.2 (-C ), 18.6
(CH(CH3)2), 11.2 (CH(CH3)2), À0.2 ppm (Si(CH3)3); IR: nÄ ˆ 2958 (s), 2943
ꢄ
ꢄ
(s), 2892 (s), 2865 (s), 2156 (m) (C C), 2063 (w) (C C), 1550 (s), 1250 (s),
975 (s), 882 (s), 860 (s), 843 (s), 676 cmÀ1 (s); EIMS (CHCl3): m/z (%): 434
‡
‡
‡
(5) [M ], 419 (5) [M À CH3], 391 (100) [M À {CH(CH3)2}], 363 (22)
‡
‡
[M À {CH(CH3)2} À 2{CH2}], 349 (25) [M À {CH(CH3)2} À 3{CH2}], 335
‡
‡
(49) [M À {CH(CH3)2} À 4{CH2}], 321 (63) [M À {CH(CH3)2} À 5{CH2}];
‡
HRMS (EI, CHCl3, [M ]) calcd for C22H33BrSi2: 432.1304; found: 432.1301.
(3,5-Dibromophenylethynyl)triisopropylsilane (11): Et3N (25mL), which
had been bubbled with argon, was added by syringe to a mixture of 7
(4.170 g, 1.15 Â 10À2 mol), TIPSA (2.103 g, 1.15 Â 10À2 mol) and
[PdCl2(PPh3)2] (0.093 g, 1.32 Â 10À4 mol) under an atmosphere of argon.
A solution of CuI (0.083 g, 4.36 Â 10À4 mol) in degassed Et3N (4mL) was
then added by syringe and the mixture stirred at ambient temperature for
four days in the absence of light. All solvent was subsequently removed
under reduced pressure on a water bath and the residue worked-up and
purified as described for 8 above. After flash chromatography on silica with
hexane eluant, the product was dried under dynamic vacuum to yield 11
(4.681 g, 97%) as a colourless oil.
1H NMR (CDCl3, 500 MHz, 218C): d ˆ 7.608 (t, 4J(4,2;4,6) ˆ 1.8 Hz, 1H;
¬
Universite Louis Pasteur.
H4), 7.531 (d, 2H; H2/6), 1.117 ppm (s, 21H; CH(CH3)2); 13C NMR: d ˆ
(3-Bromo-5-iodophenylethynyl)trimethylsilane (9): A dried 500 mL two-
necked round-bottomed flask charged with 8 (4.208 g, 1.27 Â 10À2 mol), was
equipped with a vacuum/argon inlet adaptor, alcohol thermometer, rubber
septum and a magnetic stirrer ovoid. The flask was then evacuated and
back-filled with argon four times in succession and Et2O (125 mL), which
had been freshly distilled off Na/benzophenone under argon, was added by
syringe. The stirred solution was subsequently cooled to an internal
temperature of À788C using a CO2/acetone bath. A 1.6m solution of nBuLi
in hexanes (8 mL, 1.28 Â 10À2 mol) was added dropwise by syringe at a rate
which maintained the reaction temperature between À78 and À708C.
During addition, the reaction solution initially became pink in colour, then
changed to pale yellow and finally became almost colourless when all the
nBuLi had been added. The reaction solution was then stirred at À788C for
2 h. Et2O (25 mL) was syringed into a dried, argon-filled schlenk flask
containing diiodoethane (5 g, 1.77 Â 10À2 mol), and the mixture stirred until
all the diiodoethane had dissolved. The diiodoethane solution was then
added dropwise by syringe to the phenyllithium reaction mixture at a rate
which maintained the internal temperature between À78 and À708C. The
reaction mixture was stirred at À788C for a further 1 h, and was then
allowed to warm to ambient temperature with continued stirring overnight.
The reaction solution was extracted with distilled water (3 Â 60 mL), and
the organic layer separated, dried (anhydrous MgSO4), filtered, and the
Et2O removed by distillation at ambient pressure on a water bath. The
remaining oil was flash chromatographed three times on columns of silica,
eluting with hexane. The product thus obtained was finally dried under
dynamic vacuum (0.01 mmHg) to yield 9 (4.556g, 95%) as an odourless,
colourless oil.
ꢄ
ꢄ
134.0, 133.4, 126.8, 122.5, 103.6 (-C ), 94.3 (-C ), 18.6 (CH(CH3)2),
11.2 ppm (CH(CH3)2); IR: nÄ ˆ 2958 (s), 2942 (s), 2890 (s), 2864 (s), 2163
ꢄ
(m) (C C), 1578 (s), 1540 (s), 1462 (s), 1418 (s), 1400 (s), 996 (s), 896 (s), 882
(s), 855 (s), 748 (s), 680 (s), 670 (s), 651 cmÀ1 (s); EIMS (CHCl3): m/z (%):
‡
‡
‡
416 (22) [M ], 373 (100) [M -{CH(CH3)2}], 345 (22) [M À {CH(CH3)2} À
‡
‡
2{CH2}], 331 (21) [M À {CH(CH3)2} À 3{CH2}], 317 (37) [M À
‡
{CH(CH3)2} À 4{CH2}], 303 (43) [M À {CH(CH3)2} À 5{CH2}]; HRMS
‡
(EI, CHCl3, [M ]) calcd for C17H24Br2Si: 414.0014; found: 414.0008.
(3-Bromo-5-iodophenylethynyl)triisopropylsilane (12): The preparation of
12 was performed in a similar way to that of 9 described above. Thus Et2O
(25 mL, freshly distilled from Na/benzophenone under argon) was syringed
into a dried argon filled flask containing 11 (1.730 g, 4.16 Â 10À3 mol), and
the stirred solution cooled to À788C. A 1.6 m solution of nBuLi in hexanes
(2.6 mL, 4.16 Â 10À3 mol) was added dropwise by syringe at a rate which
maintained the reaction temperature between À78 and À708C. The
resulting pale brown solution was then stirred at À788C for 2 h. A solution
of iodine (1.06 g, 8.35 Â 10À3 mol) in Et2O (10 mL, freshly distilled from Na/
benzophenone under argon) was prepared in a dried argon filled schlenk,
and subsequently added dropwise by syringe to the lithiophenyl solution at
a rate which maintained the reaction temperature at À708C. The reaction
was then stirred at À788C for 2 h, and allowed to warm to ambient
temperature overnight with continued stirring. Work-up, purification and
drying as described for 9 above, yielded 12 (1.358 g, 71%) as a colourless
oil.
4
4
1H NMR: d ˆ 7.797 (t, J(4,2;4,6) ˆ 1.7 Hz, 1H; H4), 7.723 (t, J(6,2;6,4) ˆ
1.3 Hz, 1H; H6), 7.558 (t, 4J(2,4;2,6) ˆ 1.6 Hz, 1H; H2), 1.116 ppm (m,
21H; CH(CH3)2); 13C NMR: d ˆ 139.5, 139.1, 134.0, 126.9, 122.4, 103.5, 94.2
4
4
1H NMR: d ˆ 7.797 (t, J(4,2;4,6) ˆ 1.6 Hz, 1H; H4), 7.731 (t, J(6,2;6,4) ˆ
4
ꢄ ꢄ
(-C ), 93.7 (-C ), 18.6 (CH(CH3)2), 11.2 ppm (CH(CH3)2); IR: nÄ ˆ 2955 (s),
1.3 Hz, 1H; H6), 7.560 (t, J(2,4;2,6) ˆ 1.5 Hz, 1H; H2), 0.237 ppm (s, 9H;
Si(CH3)3); 13C NMR: d ˆ 139.7, 139.1, 133.9, 126.6, 122.4, 101.5, 97.6 (-C ),
2941 (s), 2923 (s), 2890 (s), 2864 (s), 2161 (m) (C C), 2063 (w) (C C), 1573
(s), 1533 (s), 1462 (s), 1414 (s), 1397 (s), 884 (s), 855 (s), 730 (s), 678 (s),
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
93.6 (-C ), À0.3 ppm (Si(CH3)3); IR: nÄ ˆ 2958 (s), 2165 (s) (C C), 1572 (s),
‡
‡
1533 (s), 1414 (s), 1397 (s), 1249 (s), 1104 (m), 893 (s), 844 (s), 760 (s), 730
670 cmÀ1 (s); EIMS (CHCl3): m/z (%): 464 (10) [M ], 421 (100) [M À
Chem. Eur. J. 2003, 9, 5011 5022
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5017

P. N. W. Baxter
FULL PAPER
‡
‡
‡
‡
{CH(CH3)2}], 393 (23) [M À {CH(CH3)2} À 2{CH2}], 379 (20) [M À
127.8, 93.3 ppm; EIMS (CHCl3): m/z (%): 341 (100) [M ], 262 (42) [M À
‡
‡
‡
{CH(CH3)2} À 3{CH2}], 365 (37) [M À {CH(CH3)2} À 4{CH2}], 351 (48)
Br], 181 (75) [M À 2Br]; HRMS (FAB, [M ‡ H]) calcd for C7H5Br3N:
‡
‡
[M À {CH(CH3)2} À 5{CH2}]; HRMS (EI, CHCl3, [M ]) calcd for
339.7972; found: 339.7965.
C17H24BrISi: 461.9875; found: 461.9865.
2-Bromo-5-[2-(1-bromoethynyl)]pyridine (17): Sodium metal (0.914g,
3.97 Â 10À2 mol) was cut into strips and added in portions to absolute
MeOH (60 mL) over 2 h. During addition, the vigorous exothermic
reaction was periodically moderated by immersion of the reaction flask
in an ice bath when necessary. When the addition was complete, the
mixture was stirred until all the sodium had reacted, and the resulting
solution allowed to cool to ambient temperature. The latter NaOMe
solution was then added dropwise to a solution of 16 (13.47 g, 3.94 Â
10À2 mol) in MeOH (250 mL), and the mixture stirred at ambient temper-
ature for 48 h. During stirring, a copious white suspension slowly formed.
The progress of the reaction could be monitored by TLC (Silica plate/
CH2Cl2 eluant). The solvent was then removed by distillation under
reduced pressure on a water bath at 458C, and the residue partitioned
between distilled water (200 mL) and CH2Cl2 (200 mL), and the aqueous
phase extracted with further CH2Cl2 (3 Â 50 mL). The combined organic
extracts were dried (anhydrous MgSO4), filtered and the solvent removed
by distillation under ambient pressure on a water bath. The crude product
was then twice flash chromatographed on columns of silica, eluting with
CH2Cl2. The last quarter of the 17 co-eluted with a contaminant, which
could however be removed upon two successive recrystallisations from
MeOH. The combined yield was further dried under dynamic vacuum to
furnish 17 (8.741g, 85%) as cream coloured crystals. The product could also
be additionally purified by sublimation under vacuum (808C/0.01 mmHg)
to give a white crystalline solid. M.p. 132.8 133.58C.
1-Bromo-3-[2-(1-triisopropylsilylethynyl)]-5-[2-(1-trimethylsilylethynyl)]-
benzene (10), (from 12): Et3N (15mL), which had been bubbled with argon,
was added by syringe to a mixture of 12 (1.356 g, 2.93 Â 10À3 mol),
[PdCl2(PPh3)2] (0.030 g, 4.27 Â 10À5 mol) and CuI (0.031 g, 1.63 Â
10À4 mol) under an atmosphere of argon. The mixture was stirred for a
few minutes, then a solution of TMSA (0.321g, 3.27 Â 10À3 mol) in degassed
Et3N (4mL) was added by syringe. The mixture was subsequently stirred at
ambient temperature for four days in the absence of light. The reaction was
worked up as described for 8 above. The crude product was purified by
twice flash chromatographing on silica with hexane as eluant, followed by
drying under dynamic vacuum to yield 10 (0.909 g, 72%) as a colourless
viscous oil.
1-Iodo-3-[2-(1-triisopropylsilylethynyl)]-5-[2-(1-trimethylsilylethynyl)]-
benzene (13): The preparation of 13 was performed in an identical way to
that of 9 described above. Thus a 1.6m solution of nBuLi in hexanes
(7.0 mL, 1.12 Â 10À2 mol) was added dropwise by syringe to a stirred
solution of 10 (4.587 g, 1.06 Â 10À2 mol) in Et2O (140 mL), which had been
previously cooled to À788C. The addition was conducted at a rate which
maintained the reaction temperature below À708C. The pale yellow
lithiophenyl solution was stirred at À788C for 2 h, then a solution of
diiodoethane (6.00 g, 2.13 Â 10À2 mol) in Et2O (50 mL) added by syringe at
a rate which ensured the reaction temperature remained between À78 and
À708C. The reaction solution was stirred at À788C for 1.5 h, then allowed
to warm to ambient temperature with continued stirring, and worked up as
described for 9 above. The crude product was twice flash chromatographed
on silica with hexane as eluant, and the isolated 13 dried under dynamic
vacuum (0.01 mmHg) first at 708C to remove any excess diiodoethane, then
at ambient temperature, to give 13 (4.710 g, 93%) as a pale yellow viscous
oil.
1H NMR: d ˆ 8.436 (d, 4J(6,4) ˆ 2.3 Hz, 1H; H6), 7.570 (dd, 3J(4,3) ˆ
8.2 Hz, 4J(4,6) ˆ 2.4 Hz, 1H; H4), 7.450 ppm (d, 3J(3,4) ˆ 8.3 Hz, 1H;
13
ꢄ
H3); C NMR: d ˆ 152.9, 141.5, 140.9, 127.7, 119.2, 75.8 (-C ), 55.3 ppm
ꢄ
ꢄ
(-C ); IR: nÄ ˆ 2199 (s) (C C), 1543 (s), 1459 (s), 1447 (s), 1354 (s), 1091 (s),
1022 (s), 832 cmÀ1 (s); EIMS: m/z (%): 261 (100) [M ], 180 (54) [M À Br],
‡
‡
‡
‡
101 (27) [M À 2Br]; HRMS (FAB, [M ‡ H]) calcd for C7H4Br2N:
259.8710; found: 259.8714.
1H NMR: d ˆ {(7.741 (t, 4J ˆ 1.5 Hz, 1H), 7.732 (t, 4J ˆ 1.6 Hz, 1H)); H2/6},
7.509 (t, 4J(4,2;4,6) ˆ 1.4Hz, 1H; H4), 1.113 (s, 21H; CH(CH 3)2), 0.237 ppm
(s, 9H; Si(CH3)3); 13C NMR: d ˆ 140.3, 140.1, 134.4, 125.3, 125.0, 104.2,
2-Bromo-5-[2-(1-trimethylsilylethynyl)]pyridine (18): Compound 18 was
prepared by a halogen/lithium exchange reaction in an identical way to that
described above for the preparation of 9. Thus a 1.6m solution of nBuLi in
hexanes (30 mL, 4.80 Â 10À2 mol) was added dropwise by syringe to a
stirred suspension of 17 (12.15 g, 4.66 Â 10À2 mol) in Et2O (400 mL), which
had been previously cooled to À788C. The addition was conducted at a rate
which maintained the reaction temperature below À708C. After the
addition was complete, the resulting orange solution was stirred at À788C
for 2.5 h, during which time a suspended solid re-precipitated. Chloro-
trimethylsilane (8.56g, 7.88 Â 10À2 mol) was then added by syringe at a rate
which ensured that the reaction temperature remained below À708C. The
stirred mixture was maintained at À788C for 1 h, allowed to warm to
À358C and held at this temperature for 1 h, then left to warm to ambient
temperature overnight. The mixture was subsequently extracted with
distilled water (3 Â 70 mL), and the ether layer dried (anhydrous MgSO4),
filtered, and the solvent removed by distillation on a water bath at ambient
pressure. The remaining yellow solid was flash chromatographed on silica,
eluting with 10% Et2O/hexane. The product co-eluted with a contaminant
which could, however, be removed upon successive extraction of the eluate
with 5m aqueous HCl (2 Â 100 mL) and distilled water (100 mL). The
organic phase was then dried (anhydrous MgSO4), filtered and the solvent
removed by distillation under reduced pressure on a water bath. The
product was finally dried under dynamic vacuum to yield 18 (10.36 g, 88%)
as a pungent smelling soft white crystalline solid. M.p. 71.0 71.98C.
ꢄ
ꢄ
ꢄ
ꢄ
102.3 (-C ), 96.6 (-C ), 93.1 (-C ), 92.9 (-C ), 18.6 (CH(CH3)2), 11.2
(CH(CH3)2), À0.2 ppm (Si(CH3)3); IR: nÄ ˆ 2958 (s), 2942 (s), 2865 (s), 2155
ꢄ
ꢄ
(m) (C C), 2062 (w) (C C), 1542 (s), 1250 (s), 973 (s), 857 (s), 843 (s), 816
(s), 678 cmÀ1 (s); EIMS (CHCl3): m/z (%): 480 (6) [M ], 465 (4) [M À
‡
‡
‡
‡
CH3], 437 (100) [M À {CH(CH3)2}], 409 (21) [M À {CH(CH3)2} À
‡
‡
2{CH2}], 395 (25) [M À {CH(CH3)2} À 3{CH2}], 381 (42) [M À
‡
{CH(CH3)2} À 4{CH2}], 367 (60) [M À {CH(CH3)2} À 5{CH2}]; HRMS
‡
(EI, CHCl3, [M ]) calcd for C22H33ISi2: 480.1166; found: 480.1157.
2-Bromo-5-(2,2-dibromovinyl)pyridine (16): A dried 500 mL two-necked
round-bottomed flask charged with 15 (8.00 g, 4.30 Â 10À2 mol) and PPh3
(23.00g, 8.77 Â 10À2 mol) was equipped with a vacuum/argon inlet adaptor,
alcohol thermometer, rubber septum and a magnetic stirrer ovoid. The
flask was then evacuated and back-filled with argon four times in
succession and CH2Cl2 (200 mL), which had been freshly distilled off
P4O10 under argon, was added by syringe. The stirred solution was
subsequently cooled to an internal temperature of À788C using a CO2/
acetone bath, and Et3N (6mL) added by syringe. During cooling, the 15 re-
precipitated from solution. CH2Cl2 (40 mL) was syringed into a dried,
argon-filled schlenk flask containing CBr4 (29.00 g, 8.74 Â 10À2 mol), and
the mixture stirred until all solids had dissolved. The CBr4 solution was then
added dropwise by syringe to the suspension of 15 at a rate which
maintained the internal temperature between À78 and À708C. The cream
coloured mixture was stirred at À708C for a further 1 h, and was then
allowed to warm to 108C with continued stirring over 4h. All solvent was
removed by distillation on a water bath at ambient pressure, and the
remaining honey coloured syrup twice flash chromatographed on silica,
eluting with CH2Cl2. The product thus obtained was dried under dynamic
vacuum to yield 16 (13.70 g, 93%) as a hard cream coloured solid. The solid
could be further purified by sublimation under vacuum at 808C/0.01 mmHg
whereby it formed jagged platy needles resembling shards of broken glass.
M.p. 67.7 69.48C.
1H NMR: d ˆ 8.425 (dd, 4J(6,4) ˆ 2.4Hz, 5J(6,3) ˆ 0.8 Hz, 1H; H6), 7.572
3
4
3
(dd, J(4,3) ˆ 8.2 Hz, J(4,6) ˆ 2.4 Hz, 1H; H4), 7.427 (dd, J(3,4) ˆ 8.2 Hz,
5J(3,6) ˆ 0.8 Hz, 1H; H3), 0.254ppm (s, 9H; Si(CH 3)3); 13C NMR: d ˆ
ꢄ
ꢄ
152.8, 141.2, 140.9, 127.5, 119.5, 100.0 (-C ), 99.9 (-C ), -0.2 ppm
ꢄ
(Si(CH3)3); IR: nÄ ˆ 2162 (C C) (s), 1569 (s), 1449 (s), 1362 (s), 1251 (s),
À1
1225 (s), 1084(s), 1016 (s), 862 (s), 841 (s), 826 (s), 759 (s), 679 cm
(s);
‡
‡
EIMS: m/z (%): 255 (25) [M ], 240 (100) [M À CH3]; HRMS (FAB,
‡
[M ‡ H]) calcd for C10H13BrNSi: 254.0001; found: 254.0003.
2-(Tri-n-butylstannyl)-5-[2-(1-trimethylsilylethynyl)]pyridine (19): A 1.6m
solution of nBuLi in hexanes (5.2 mL, 8.32 Â 10À3 mol) was added dropwise
by syringe to a stirred solution of 18 (2.008g, 7.90 Â 10À3 mol) in THF
(40 mL), which had been previously cooled to À858C (liq. N2/hexane bath).
1H NMR: d ˆ 8.439 (dd, 4J(6,4) ˆ 2.6 Hz, 1H; H6), 7.829 (dd, 3J(4,3) ˆ
8.4Hz, 4J(4,6) ˆ 2.5 Hz, 1H; H4), 7.498 (d, 3J(3,4) ˆ 8.5 Hz, 1H; H3),
7.403 ppm (s, 1H; CH CBr2); 13C NMR: d ˆ 149.9, 141.6, 137.2, 132.3, 130.7,
ˆ
5018
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 5011 5022

Nanosized Macrocyclic Fluorophores
5011 5022
The addition was conducted at a rate which maintained the reaction
temperature below À788C. After the addition was complete, the resulting
orange-brown solution was stirred at À788C for 1 h, then ClSn(nBu)3
(4.20 g, 1.29 Â 10À2 mol) added by syringe at a rate which maintained the
reaction temperature below À708C. The resulting pale yellow-orange solu-
tion was stirred at À788C for 1 h, and allowed to warm to ambient
temperature overnight with continued stirring. Most of the THF was removed
by distillation under reduced pressure on a water bath and the residue
partitioned between distilled water and Et2O, and extracted with distilled
water (2 Â 60 mL). The organic phase was dried (anhydrous MgSO4),
filtered, the solvent removed by distillation on a water bath at ambient
pressure, and the remaining oil chromatographed on a short column of
alumina, eluting with 5% Et2O/hexane. The product thus obtained was
dried under dynamic vacuum to yield 19 (2.504g, 68%) as a colourless oil.
water bath at atmospheric pressure. The remaining solid was chromato-
graphed on alumina, eluting with CH2Cl2. The solid thus obtained was
briefly ultrasonicated in MeOH (3 mL), filtered under vacuum, washed
with MeOH (2 mL) and finally air dried to yield 24 (0.245 g, 93%) as a
white fibrous solid. M.p. 182.0 182.88C.
1H NMR: d ˆ 8.793 (dd, 4J(6,4;6'',4'') ˆ 2.1 Hz, 5J(6,3;6'',3'') ˆ 0.7 Hz, 2H;
H6/6''), 8.580 (dd, 3J(3,4;3'',4'') ˆ 8.2 Hz, 5J(3,6;3'',6'') ˆ 0.8Hz, 2H; H3/3''),
3
8.466 (d, J(3',4';5',4') ˆ 7.7 Hz, 2H; H3'/5'), 7.970 (t, 3J(4',3';4',5') ˆ 7.9 Hz,
3
4
1H; H4'), 7.936 (dd, J(4,3;4'',3'') ˆ 8.2 Hz, J(4,6;4'',6'') ˆ 2.1 Hz, 2H; H4/
4''), 3.314ppm (s, 2H; H-C C); 13C NMR: d ˆ 155.3, 154.6, 152.2, 139.9,
ꢄ
ꢄ
ꢄ
ꢄ
138.0, 121.7, 120.3, 119.2, 81.4(-C ), 80.7 ppm (-C ); IR: nÄ ˆ 3242 (H-C )
ꢄ
(s), 2107 (C C) (w), 1587 (s), 1544 (s), 1478 (s), 1444 (s), 1369 (s), 1024 (s),
865 (s), 815 (s), 750 cmÀ1 (s); UV/Vis (CHCl3): lmax (e) ˆ 263 (31675), 292sh
(31894), 305 (37953), 313 nm (37090 mÀ1cmÀ1); fluorescence emission
([24] ˆ 2.8  10À6 mol dmÀ3 in CHCl3, 300 nm excitation): lmax ˆ 338,
1H NMR: d ˆ 8.776 (dd, 4J(6,4) ˆ 2.1 Hz, 5J(6,3) ˆ 0.8 Hz, 1H; H6), 7.527
4
‡
(dd, 3J(4,3) ˆ 7.6 Hz, J(4,6) ˆ 2.1 Hz, 1H; H4), 7.346 (dd, 3J(3,4) ˆ 7.7 Hz,
349 nm; EIMS: m/z (%): 281 (100) [M ], 253 (33); elemental analysis
5J(3,6) ˆ 0.9 Hz, 1H; H3), 1.536 (pentet, 3J(2,1/2,3) ˆ 7.8 Hz, 6H;
calcd (%) for C19H11N3: C 81.12, H 3.94, N 14.94; found: C 81.23, H 3.68, N
14.81.
CH2CH2CH2CH3),
1.310
(sextet,
3J(3,2/3,4) ˆ 7.4Hz,
6H;
3
CH2CH2CH2CH3), 1.111 (t, J(1,2) ˆ 8.1 Hz, 6H; CH2CH2CH2CH3), 0.866
2,2':6',2''-terpyridine-5,5''-diylbis-[1-(2,1-ethynediyl)-3-(2-(1-triisopropylsi-
lylethynyl))-5-(2-(1-trimethylsilylethynyl))benzene] (25): Argon bubbled
pyridine (15 mL) was added by syringe to a mixture of 13 (0.904g, 1.88 Â
10À3 mol), 24 (0.245g, 8.71 Â 10À4 mol) and [PdCl2(PPh3)2] (0.042g, 5.98 Â
10À5 mol) under argon. After stirring the mixture for 0.1 h, a solution of CuI
(0.030 g, 1.58 Â 10À4 mol) in Et3N (2 mL) was added by syringe, and the
reaction stirred in the absence of light at ambient temperature for seven
days. All solvent was then removed under reduced pressure, the residue
extracted with hot hexane (4 Â 35 mL), and the combined extracts filtered
under vacuum through a G4frit. The hexane was removed under reduced
pressure and the residue flash chromatographed on silica, eluting with
CH2Cl2. The product thus obtained was finally dried under vacuum
(0.01 mmHg/24h), to yield 25 (0.531g, 62%) as a cream coloured opaque
glass.
(t, 3J(4,3) ˆ 7.3 Hz, 9H; CH2CH2CH2CH3), 0.252 ppm (s, 9H; Si(CH3)3);
13
ꢄ
ꢄ
C NMR: d ˆ 174.4, 152.6, 135.6, 131.2, 118.2, 102.3 (-C ), 97.6 (-C ), 29.0,
27.3, 13.7, 9.9, À0.1 ppm (Si(CH3)3); IR: nÄ ˆ 2956 (s), 2925 (s), 2871 (s), 2851
ꢄ
(s), 2160 (s) (C C), 1464 (s), 1446 (s), 1250 (s), 1022 (s), 866 (s), 843 (s),
760 cmÀ1 (s); HRMS (FAB, [M ‡ H]) calcd for C22H40NSiSn: 462.1947;
‡
found: 462.1945.
5,5''-bis-[2-(1-trimethylsilylethynyl)]-2,2':6',2''-terpyridine (23), (From
18‡22): Toluene (24mL), which had been bubbled with argon, was added
by syringe to a mixture of 18 (1.816g, 7.14 Â 10À3 mol), [Pd(PPh3)4] (0.090 g,
7.79 Â 10À5 mol) and anhydrous LiCl (1.820 g, 4.29 Â 10À2 mol) under an
atmosphere of argon. 2,6-bis(trimethylstannyl)pyridine 22 (1.331g, 3.29 Â
10À3 mol) was then added by syringe, and the mixture stirred in a bath at
1188C for 28 h. All solvent was removed under reduced pressure on a water
bath and the residue flash chromatographed on a column of silica, eluting
first with CH2Cl2. The product 23 could be visualised on the column as a
purple-blue fluorescent band upon irradiation with a UV lamp operating at
365 nm. When the 23 had descended halfway down the column, the silica
above the product was removed, and the 23 eluted from the column with
1% MeOH/CH2Cl2. If the latter procedure is not adhered to, then the
impurities and 23 co-elute. The product thus obtained was briefly ultra-
sonicated in ice-cold MeCN (3 mL), filtered under vacuum, washed with
ice-cold MeCN (2 mL), and air-dried to yield 23 (0.742 g, 53%) as a white
powder. M.p. 226.9 228.68C.
1H NMR: d ˆ 8.823 (dd, 4J(6,4;6'',4'') ˆ 2.1 Hz, 5J(6,3;6'',3'') ˆ 0.8 Hz, 2H;
pyridine H6/6''), 8.632 (dd, 3J(3,4;3'',4'') ˆ 8.2 Hz, 5J(3,6;3'',6'') ˆ 0.8 Hz,
3
2H; pyridine H3/3''), 8.491 (d, J(3',4';5',4') ˆ 7.8 Hz, 2H; pyridine H3'/5'),
7.990 (t, 3J(4',3';4',5') ˆ 7.8 Hz, 1H; pyridine H4'), 7.961 (dd, 3J(4,3;4'',3'') ˆ
8.2 Hz, 4J(4,6;4'',6'') ˆ 2.1 Hz, 2H; pyridine H4/4''), 7.623 (m, 4H; phenyl
H2/6), 7.559 (t, 4J(4,2;4,6) ˆ 1.5 Hz, 2H; phenyl H4), 1.137 (s, 42H;
CH(CH3)2), 0.261 (s, 18H; Si(CH3)3); 13C NMR: d ˆ 155.0, 154.7, 151.7,
139.4, 138.0, 135.3, 134.7, 134.6, 124.3, 123.9, 123.1, 121.6, 120.5, 119.9, 105.0
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
(-C ), 103.0 (-C ), 96.0 (-C ), 92.5 (-C ), 91.9 (-C ), 87.4(-C ), 18.6
(CH(CH3)2), 11.2 (CH(CH3)2), À0.2 ppm (Si(CH3)3); IR: nÄ ˆ 2957 (s), 2942
1H NMR: d ˆ 8.751 (d, 4J(6,4;6'',4'') ˆ 1.4Hz, 2H; H6/6 ''), 8.551 (d,
3J(3,4;3'',4'' ˆ 8.2 Hz, 2H; H3/3''), 8.452 (d, 3J(3',4';5',4') ˆ 7.9 Hz, 2 H ;
H3'/5'), 7.953 (t, 3J(4',3';4',5') ˆ 7.8 Hz, 1H; H4'), 7.896 (dd, 3J(4,3;4'',3'') ˆ
(s), 2924(s), 2865 (s), 2157 (C C) (m), 1578 (s), 1446 (s), 1250 (s), 982 (s),
ꢄ
881 (s), 855 (s), 843 (s), 818 (s), 761 (s), 679 cmÀ1 (s); UV/Vis (CHCl3): lmax
(e) ˆ 257 (79995), 269 (96148), 333 (75333), 345 nm (70154mÀ1cmÀ1);
fluorescence emission ([25] ˆ 1.3  10À6 moldmÀ3 in CHCl3, 300 nm exci-
tation): lmax ˆ 357, 373 nm; FABMS: (1% CF3COOH/NBA): m/z (%): 987
8.2 Hz, 4J(4,6;4'',6'') ˆ 2.0 Hz, 2H; H4/4''), 0.297 (s, 18H; Si(CH3)3);
13
ꢄ
C NMR: d ˆ 154.9, 154.7, 152.1, 139.7, 138.0, 121.6, 120.2, 101.8 (-C ),
‡
‡
ꢄ
ꢄ
99.2 (-C ), À0.2 ppm (Si(CH3)3); IR: nÄ ˆ 2957 (s), 2160 (C C) (s), 1584(s),
1543 (s), 1445 (s), 1250 (s), 1022 (s), 865 (s), 843 (s), 818 (s), 757 (s), 660 (s),
645 cmÀ1 (s); UV/Vis (CHCl3): lmax (e) ˆ 274(30778), 298sh (35746), 312
(43496), 318 nm (43653 MÀ1cmÀ1); fluorescence emission ([23] ˆ 2.3 Â
10À6 mol dmÀ3 in CHCl3, 300 nm excitation): lmax ˆ 343, 353 nm; EIMS:
(100) [M ‡ H]; HRMS (FAB, [M ‡ H]) calcd for C63H76N3Si4: 986.5116;
found: 986.5130.
2,2':6',2''-terpyridine-5,5''-diylbis-[1-(2,1-ethynediyl)-3-(ethynyl)-5-(2-(1-
triisopropylsilylethynyl))benzene] (26): Powdered K2CO3 (0.080 g, 5.79 Â
10À4 mol) was added to a solution of 25 (0.571 g, 5.79 Â 10À4 mol) in 2:1
Et2O/MeOH (20 mL) and the mixture stirred at ambient temperature in
the absence of light for 14h. A copious white suspension formed, during
the first hour of stirring. All solvent was removed by distillation under
reduced pressure on a water bath at ambient temperature, and the residue
dissolved in CH2Cl2 and extracted with distilled water (3 Â 25 mL). The
organic phase was dried (anhydrous MgSO4), filtered, and the solvent
removed by distillation on a water bath at atmospheric pressure. The
remaining solid was suspended in MeOH (15 mL) and homogenised by
brief ultrasonication, filtered under vacuum, washed with excess MeOH
and air dried to yield 26 (0.472g, 97%) as a dusty white powder. M.p.
235.0 237.28C upon heating from 233.08C, and >3258C upon slow heating
from ꢁ2268C.
‡
‡
m/z (%): 425 (76) [M ], 410 (100) [M À CH3]; elemental analysis calcd
(%) for C25H27N3Si2: C 70.54, H 6.39, N 9.87; found: C 70.50, H 6.37, N
10.03.
5,5''-Bis-[2-(1-trimethylsilylethynyl)]-2,2':6',2''-terpyridine (23), (From
19‡20): Compound 23 was prepared and purified using a procedure
identical to that described above. Thus from the reaction between 19
(0.505 g, 1.09 Â 10À3 mol), 20 (0.107 g, 4.52 Â 10À4 mol), [Pd(PPh3)4]
(0.017 g, 1.47 Â 10À5 mol) and anhydrous LiCl (0.153 g, 3.61 Â 10À3 mol),
stirred and heated at 1208C in toluene (5 mL) for 24h, was isolated 23
(0.114g, 59%).
5,5''-Diethynyl-2,2':6',2''-terpyridine (24): TBAF (2 mL, 1.0m solution in
THF, 2 Â 10À3 mol) was added to a stirred solution of 23 (0.400 g, 9.40 Â
10À4 mol) in THF (20 mL) and distilled water (0.5 mL). The solution was
then stirred at ambient temperature in the absence of light for 6 h. All
solvent was removed under reduced pressure at ambient temperature and
the residue partitioned between distilled water (40 mL) and Et2O (60 mL)
and extracted with further distilled water (4 Â 20 mL). The organic phase
was then dried (anhydrous MgSO4), filtered, and the solvent removed on a
1H NMR: d ˆ 8.827 (d, 4J(6,4;6'',4'') ˆ 2.1 Hz, 2H; pyridine H6/6''), 8.634
(d, 3J(3,4;3'',4'') ˆ 8.3 Hz, 2H; pyridine H3/3''), 8.495 (d, 3J(3',4';5',4') ˆ
7.8 Hz, 2H; pyridine H3'/5'), 7.988 (t, 3J(4',3';4',5') ˆ 7.9 Hz, 1H; pyridine
H4'), 7.967 (dd, 3J(4,3:4'',3'') ˆ 7.9 Hz, 4J(4,6;4'',6'') ˆ 2.3 Hz, 2H; pyridine
H4/4''), 7.660 (t, 4J(2,4;2,6) ˆ 1.5 Hz, 2H; phenyl H2), 7.635 (t, 4J(6,2;6,4) ˆ
1.6 Hz, 2H; phenyl H6), 7.584(t, 4J(4,2;4,6) ˆ 1.5 Hz, 2H; phenyl H4),
Chem. Eur. J. 2003, 9, 5011 5022
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5019

P. N. W. Baxter
FULL PAPER
3.126 (s, 2H; H-C C)), 1.141 ppm (s, 42H; CH(CH3)2); 13C NMR: d ˆ
[2] For the property-targeted synthesis of nanosized organic molecules,
see for example: a) N. C. Seeman, A. M. Belcher, Proc. Nat. Acad. Sci.
2002, 99, 6451; b) M. D. Watson, A. Fechtenkˆtter, K. M¸llen, Chem.
Rev. 2001, 101, 1267; c) Top. Curr. Chem. 2001, 212, whole volume;
d) Top. Curr. Chem. 2000, 210, whole volume; e) V. Balzani, A. Credi,
F. M. Raymo, J. F. Stoddart, Angew. Chem. 2000, 112, 3484; Angew.
Chem. Int. Ed. 2000, 39, 3348; f) Top. Curr. Chem. 1998, 197, whole
volume; g) Electronic Materials: The Oligomer Approach (Eds.: K.
M¸llen, G. Wegner), Wiley-VCH, Weinheim, 1998; h) N. C. Seeman,
Angew. Chem. 1998, 110, 3408; Angew. Chem. Int. Ed. 1998, 37,
3220.
ꢄ
155.1, 154.7, 151.7, 139.4, 138.0, 135.5, 135.1, 134.6, 124.4, 123.2, 122.9, 121.7,
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
120.4, 119.8, 104.8 (-C ), 92.8 (-C ), 91.7 (-C ), 87.6 (-C ), 81.8 (-C ), 78.5
ꢄ
ꢄ
(-C ), 18.7 (CH(CH3)2), 11.2 ppm (CH(CH3)2); IR: nÄ ˆ 3303 (H-C ) (m),
ꢄ
2942 (s), 2864 (s), 2156 (C C) (s), 1578 (s), 1446 (s), 881 (s), 817 (s), 753 (s)
680 cmÀ1 (s); UV/vis (CHCl3): lmax (e) ˆ 256 (76991), 270 (78223), 332
(84956), 345 nm (78382 mÀ1cmÀ1); fluorescence emission ([26] ˆ 1.3 Â
10À6 mol dmÀ3 in CHCl3, 300 nm excitation): lmax ˆ 356, 373 nm; FABMS:
‡
(1% CF3COOH/NBA): m/z (%): 842 (100) [M ‡ H]; HRMS (FAB,
‡
[M ‡ H]) calcd for C57H60N3Si2: 842.4326; found: 842.4334.
Cyclophane 5: In a well-ventilated hood, [Cu2(OAc)4] (2.40g, 1.32 Â
10À2 mol) was dissolved in hot pyridine (600 mL), and the solution left to
cool to ambient temperature, then bubbled with argon for 2 h. A solution of
26 (0.200 g, 2.37 Â 10À4 mol) in degassed pyridine (20 mL) was subsequent-
ly added dropwise to the [Cu2(OAc)4] solution over 8 h with continued
stirring and argon bubbling. A white suspended solid slowly formed during
the addition. After all the 26 had been added, the blue mixture was stirred
under a static atmosphere of argon at ambient temperature in the absence
of light for seven days. All solvent was then removed under reduced
pressure on a water bath, and distilled water (200 mL) added along with
excess ice, followed by the dropwise addition of concentrated aqueous
KCN (10 mL). The mixture was stirred for 0.2 h, filtered under vacuum,
and the collected solid washed with excess distilled water and air-dried. The
product was then boiled in toluene (250 mL), gravity filtered, and the
filtrate left to cool to ambient temperature. The solid which formed was
isolated by filtration under vacuum, washed with toluene (4mL), air-dried
and dissolved in boiling CHCl3 (500 mL). The hot solution was then
successively flash chromatographed three times on silica, eluting each
column first with CHCl3 followed by 2% MeCN/CHCl3. The progress of
the chromatographic purification was best monitored using a UV lamp
operating at 365 nm. Upon irradiation of the columns, the product and
impurities appeared as purple fluorescent bands. The product thus obtained
was suspended in acetone (4mL), filtered under vacuum, washed with
acetone and finally air dried to yield 5 (0.077 g, 39%) as a white solid. M.p.
>3208C.
[3] a) J. S. Moore, Acc. Chem. Res. 1997, 30, 402; b) J. K. M. Sanders in
Comprehensive Supramolecular Chemistry (Eds.: J. L. Atwood,
J. E. D. Davies, D. D. McNicol, F. Vˆgtle), Vol. 9, Templating, Self-
Assembly, and Self-Organisation (Vol. Eds.: J.-P. Sauvage, M. W.
Hosseini), Pergamon, Oxford, 1996. Chapter 4, p 131; c) S. Anderson,
H. L. Anderson, J. K. M. Sanders, Acc. Chem. Res. 1993, 26, 469.
[4] a) J. S. Melinger, Y. Pan, V. D. Kleiman, Z. Peng, B. L. Davis, D.
McMorrow, M. Lu, J. Am. Chem. Soc. 2002, 124, 12002; b) J. Wang, M.
Lu, Y. Pan, Z. Peng, J. Org. Chem. 2002, 67, 7781; c) V. J. Pugh, Q.-S.
Hu, L. Pu, Angew. Chem. 2000, 112, 3784; Angew. Chem. Int. Ed. 2000,
39, 3638; for a review of earlier literature with related structures, see:
¬
d) S. M. Grayson, J. M. J. Frechet, Chem. Rev. 2001, 101, 3819.
[5] ÷. ‹nsal, A. Godt, Chem. Eur. J. 1999, 5, 1728.
[6] For recent examples of nanosized ethynyl rods and wires with
aromatic bridging units, see for example: a) J. G. RodrÌguez, J. L.
Tejedor, J. Org. Chem. 2002, 67, 7631; b) S. H. Lee, T. Nakamura, T.
Tsutsui, Org. Lett. 2001, 3, 2005; c) A. Khatyr, R. Ziessel, J. Org.
Chem. 2000, 65, 3126. For reviews, see: d) U. H. F. Bunz, Chem. Rev.
2000, 100, 1605; e) P. F. H. Schwab, M. D. Levin, J. Michl, Chem. Rev.
1999, 99, 1863; f) J. M. Tour, Chem. Rev. 1996, 96, 537.
[7] a) A. Tanatani, T. S. Hughes, J. S. Moore, Angew. Chem. 2002, 114,
335; Angew. Chem. Int. Ed. 2002, 41, 325; b) T. Nishinaga, A. Tanatani,
K. Oh, J. S. Moore, J. Am. Chem. Soc. 2002, 124, 5934; c) R. B. Prince,
S. A. Barnes, J. S. Moore, J. Am. Chem. Soc. 2000, 122, 2758; d) R. B.
Prince, J. G. Saven, P. G. Wolynes, J. S. Moore, J. Am. Chem. Soc. 1999,
121, 3114; e) J. C. Nelson, J. G. Saven, J. S. Moore, P. G. Wolynes,
Science, 1997, 277, 1793.
[8] a) D. L. An, T. Nakano, A. Orita, J. Otera, Angew. Chem. Int. Ed.
2002, 41, 171; b) A. Orita, D. L. An, T. Nakano, J. Yaruva, N. Ma, J.
Otera, Chem. Eur. J. 2002, 8, 2005.
[9] a) Z. Wu, J. S. Moore, Angew. Chem. 1996, 108, 320; Angew. Chem.
Int. Ed. 1996, 35, 297; b) Z. Wu, S. Lee, J. S, Moore, J. Am. Chem. Soc.
1992, 114, 8730.
1H NMR (CDCl2CDCl2, 500 MHz, 808C): d ˆ 8.871 (d, 4J(6,4;6'',4'') ˆ
3
1.7 Hz, 4H; pyridine H6/6''), 8.680 (d, J(3,4;3'',4'') ˆ 8.3 Hz, 4H; pyridine
H3/3''), 8.541 (d, 3J(3',4';5',4') ˆ 7.8 Hz, 4H; pyridine H3'/5'), 8.033 (dd,
3J(4,3;4'',3'') ˆ 8.2 Hz, 4J(4,6;4'',6'') ˆ 2.1 Hz, 4H; pyridine H4/4 ''), 8.003 (t,
4
3J(4',3';4',5') ˆ 7.9 Hz, 2H; pyridine H4'), 7.749 (t, J(2,4;2,6) ˆ 1.4Hz, 4H;
phenyl H2), 7.696 (t, 4J(6,2;6,4) ˆ 1.5 Hz, 4H; phenyl H6), 7.636 (t,
4J(4,2;4,6) ˆ 1.5 Hz, 4H; phenyl H4), 1.231 ppm (s, 84H; CH(CH 3)2);
13C NMR (CDCl2CDCl2, 125.8 MHz, 1108C): d ˆ 155.6, 155.0, 151.6 (C6/6'',
py), 139.6 (C4/4'', py), 137.8 (C4', py), 135.7 (C2, ph), 135.3 (C4, ph), 135.0
(C6, ph), 125.0, 123.9, 122.6, 121.8 (C3'/5', py), 120.5 (C3/3'', py), 119.7, 105.0
[10] For a selection of recent reports on the synthesis and properties of
nanosized ethynylphenyl macrocyclic structures, see: a) S. Hˆger, S.
Rosselli, A.-D. Ramminger, V. Enkelmann, Org. Lett. 2002, 4, 4269;
b) S. Hˆger, D. L. Morrison, V. Enkelmann, J. Am. Chem. Soc. 2002,
124, 6734; c) Y. Yamaguchi, S. Kobayashi, N. Amita, T. Wakamiya, Y.
Matsubara, K. Sugimoto, Z. Yoshida, Tetrahedron Lett. 2002, 43, 3277;
d) Y. Tobe, N. Utsumi, K. Kawabata, A. Nagano, K. Adachi, S. Araki,
M. Sonoda, K. Hirose, K. Naemura, J. Am. Chem. Soc. 2002, 124,
5350; e) Y. Tobe, N. Utsumi, A. Nagano, M. Sonoda, K. Naemura,
Tetrahedron, 2001, 57, 8075; f) K. Nakamura, H. Okubo, M. Yama-
guchi, Org. Lett. 2001, 3, 1097; g) S. Hˆger, K. Bonrad, A. Mourran, U.
Beginn, M. Mˆller, J. Am. Chem. Soc. 2001, 123, 5651; h) P. H. Ge, W.
Fu, W. A. Herrmann, E. Herdtweck, C. Campana, R. D. Adams,
U. H. F. Bunz, Angew. Chem. 2000, 112, 3753; Angew. Chem. Int. Ed.
2000, 39, 3607; for reports of macrocyclic phenylethynyl belts, see: i) T.
Kawase, N. Ueda, K. Tanaka, Y. Seirai, M. Oda, Tetrahedron Lett.
2001, 42, 5509; j) M. Ohkita, K. Ando, T. Tsuji, Chem. Commun. 2001,
2570; k) M. Ohkita, K. Ando, T. Suzuki, T. Tsuji, J. Org. Chem. 2000,
65, 4385; for the synthesis and STM visualisation of nanosized
ethynylterthiophene macrocycles, see: l) E. Mena-Osteritz, P. B‰uerle,
Adv. Mater. 2001, 13, 243, and references therein; for reviews of the
field up to 1999, see: m) Top. Curr. Chem. 1999, 201, whole volume;
n) S. Hˆger, J. Polym. Sci., Part A: Polym. Chem. 1999, 37, 2685.
[11] a) Y. Hosokawa, T. Kawase, M. Oda, Chem. Commun. 2001, 1948;
b) Y. Tobe, N. Utsumi, A. Nagano, K. Naemura, Angew. Chem. 1998,
110, 1347; Angew. Chem. Int. Ed. 1998, 37, 1285; c) D. L. Morrison, S.
Hˆger, Chem. Commun. 1996, 2313; d) U. Neidlein, F. Diederich,
Chem. Commun. 1996, 1493.
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
ꢄ
(-C ), 93.9 (-C ), 91.7 (-C ), 88.3 (-C ), 80.7 (-C ), 75.2 (-C ), 18.7
ꢄ
(CH(CH3)2), 11.6 ppm (CH(CH3)2); IR: nÄ ˆ 2942 (s), 2865 (s), 2154 (C C)
(m), 1577 (s), 1447 (s), 876 (s), 813 (s), 676 cmÀ1 (s); UV/Vis (CHCl3): lmax
(e) ˆ 261 (117543), 274 (129708), 298 (141700), 317 (238469), 338
(261379), 348 sh nm (175827mÀ1cmÀ1); fluorescence emission ([5] ˆ 2.9 Â
10À7 moldmÀ3 in CHCl3, 300 nm excitation): lmax ˆ 358, 375 nm; MALDI
‡
MS (1, 8, 9-anthracenetriol matrix): m/z (%): 1681 (100) [M ‡ H]; HRMS
‡
(FAB, 10% CF3COOH/CHCl3, [M ‡ H]) calcd for C114H115N6Si4:
1679.8260; found: 1679.8313.
Acknowledgement
¡
The College de France is acknowledged for financial support and Roland
Graff for the H 1H NMR COSY, NOESY, ROESY and H 13C HSQC
experiments. Prof. Alexandre Varnek is also thanked for the molecular
modelling studies.
1
1
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Chem. Int. Ed. 1990, 29, 1320, and references therein.
5020
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Nanosized Macrocyclic Fluorophores
5011 5022
[12] a) A. Godt, S. Duda, ÷. ‹nsal, J. Thiel, A. H‰rter, M. Roos, C.
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conformationally flexible nanosized ethynyl macrocycles without
aromatic bridging units have also been recently demonstrated to
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[22] For the use of Stille-coupling methodology in the construction of
ethynylpyridyl scaffolds, see: a) reference [14h]; b) P. N. W. Baxter, J.
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[23] For a pioneering investigation into the construction of oligopyridines
using Sille-coupling methodology, see: Y. Yamamoto, Y. Azuma, H.
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[24] The use of distannylpyridines for the palladium-catalysed synthesis of
oligopyridines has been recently revived; a) M. Heller, U. S. Schubert,
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1999, 5, 854.
[14] In particular, the construction of ethynyl macrocycles incorporating
pyridine and pyridine-type units is currently the focus of rapidly
growing interest. For examples of conjugated ethynyl macrocycles
incorporating pyridine units, see a) P. N. W. Baxter, Chem. Eur. J.
2003, 9, 2531; b) K. Campbell, R. McDonald, N. R. Branda, R. R.
Tykwinski, Org. Lett. 2001, 3, 1045; c) S.-S. Sun, A. J. Lees, Organo-
metallics, 2001, 20, 2353; d) Y. Tobe, A. Nagano, K. Kawabata, M.
Sonoda, K. Naemura, Org. Lett. 2000, 2, 3265; e) Y. Tobe, H.
Nakanishi, M. Sonoda, T. Wakabayashi, Y. Achiba, Chem. Commun.
1999, 1625; for examples of conjugated ethynyl macrocycles incorpo-
rating bipyridine units, see f) P. N. W. Baxter, Chem. Eur. J. 2002, 8,
5250; g) O. Henze, D. Lentz, A. Sch‰fer, P. Franke, A. D. Schl¸ter,
Chem. Eur. J. 2002, 8, 357; h) P. N. W. Baxter, J. Org. Chem. 2001, 66,
4170; i) O. Henze, D. Lentz, A. D. Schl¸ter, Chem. Eur. J. 2000, 6,
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Eng. 1999, 80, 165; for an example of a conjugated phenylethynyl
macrocycle incorporating phenanthroline units, see: l) M. Schmittel,
H. Ammon, Synlett 1999, 750.
¡
[25] G. S. Hanan, U. S. Schubert, D. Volkmer, E. Riviere, J.-M. Lehn, N.
Kyritsakas, J. Fischer, Can. J. Chem. 1997, 75, 169.
¬
[26] a) E. F. Corsico, R. A. Rossi, Synlett, 2000, 227; b) Y. Yamamoto, A.
Yanagi, Chem. Pharm. Bull. 1982, 30, 1731.
[27] During manuscript preparation, a publication appeared, outlining a
synthesis involving 23 and 24. See: J. Otsuki, H. Kameda, S. Tomihira,
H. Sakaguchi, T. Takido, Chem. Lett. 2002, 610. However, information
concerning the preparation, yields, purification and characterisation
of 23 and 24, were not reported in the latter communication. This data
is therefore provided above.
[28] It was initially anticipated that the relatively strongly chelating
terpyridine unit 24, may possibly interfere with its coupling to 13, by
selective coordination and concomitant deactivation of the palladium
and copper catalysts. The Sonogashira coupling between 13 and 24 was
therefore conducted in pyridine in order to suppress any possible
coordination of 24 to the catalysts and intermediate species derived
therefrom.
[29] O. Lavastre, L. Ollivier, P. H. Dixneuf, S. Sibandhit, Tetrahedron, 1996,
52, 5495.
[30] M. L. Bell, R. C. Chiechi, C. A. Johnson, D. B. Kimball, A. J. Matzger,
W. Brad Wan, T. J. R. Weakley, M. M. Haley, Tetrahedron. 2001, 57,
3507.
[15] For examples of ethynyl macrocycles functioning as ligands in
characterised coordination and organometallic complexes see; a) ref-
erence [14g]; b) reference [13a]; c) R. Gibe, J. R. Green, Chem.
Commun. 2002, 1550; d) M. Laskoski, W. Steffen, J. G. M. Morton,
M. D. Smith, U. H, F. Bunz, Angew. Chem. 2002, 114, 2484; Angew.
Chem. Int. Ed. 2002, 41, 2378; e) reference [14b]; f) W. J. Youngs,
C. A. Tessier, J. D. Bradshaw, Chem. Rev. 1999, 99, 3153.
[31] The copper-mediated oxidative cyclisation of terminal diethynes has
provided a versatile and widely exploited method for the preparation
of medio- and macrocyclic ring systems. The methodology is broad in
scope and tolerant to wide range of functional groups. The cyclisations
are normally performed at medium to high dilution in a basic solvent
such as pyridine, but reaction parameters such as co-solvents, temper-
ature and the nature of the copper oxidant have been subject to a
range of modifications. Of particular significance, is the fact that there
appears to be no predictable relationship between the yield of
macrocyclisation and the structure of the starting terminal diethyne.
The optimal reaction parameters must be determined independently
for each type of substrate. For a discussion of copper mediated ethyne
coupling protocols in macrocyclisation reactions, see for example: L.
Rossa, F. Vˆgtle, Top. Curr. Chem. 1983, 113, 72 75.
[16] P. Lustenberger, F. Diederich, Helv. Chim. Acta, 2000, 83, 2865. The
3,5-dibromoiodobenzene
7 was prepared by a slightly modified
version of the above literature procedure. Thus, after the addition of
1.6 m nBuLi at À788C, the reaction solution was allowed to warm to
À208C for 1.5 h, then recooled to À788C and excess iodine in Et2O
solution added slowly at between À788C and À708C. After work-up,
the crude product was recrystallised from abs. EtOH (two crops of
crystals were obtained) to afford 7 in 84% yield (compared to the
reported 56%).
[17] a) J. S. Moore, Z. Xu, Macromolecules, 1991, 24, 5893; b) A. M.
McDonagh, M. G. Humphrey, M. Samoc, B. Luther-Davies, Organo-
metallics, 1999, 18, 5195.
[18] K. Onitsuka, M. Fujimoto, N. Ohshiro, S. Takahashi, Angew. Chem.
1999, 111, 737; Angew. Chem. Int. Ed. 1999, 38, 689. Information
concerning the preparation, purification and characterisation of
11, was however not reported. This data is therefore described
above.
[19] For a recent report of an improved procedure for the coupling of
terminal alkynes with aryl bromides, see: S. Thorand, N. Krause, J.
Org. Chem. 1998, 63, 8551.
[20] a) T. Iida, T. Wada, K. Tomimoto, T. Mase, Tetrahedron Lett. 2001, 42,
4841; b) B. H. Lipshutz, S. S. Pfeiffer, W. Chrisman, Tetrahedron Lett.
1999, 40, 7889.
[21] For the Corey Fuchs transformation of heterocyclic aldehydes to the
corresponding 2,2-dibromovinyl analogues, and subsequent NaOMe-
mediated dehydrobromination of the latter groups to bromoethynes,
see: a) V. Bakthavachalam, M. d'Alarcao, N. J. Leonard, J. Org. Chem.
1984, 49, 289; b) M. d'Alarcao, N. J. Leonard, J. Am. Chem. Soc. 1983,
105, 5958. Interestingly, the direct conversion of 5-(2,2-dibromovinyl)-
2,2'-bipyridine to 5-ethynyl-2,2'-bipyridine with nBuLi, followed by an
aqueous quench, failed to proceed in high yield; c) J. Polin, E.
Schmohel, V. Balzani, Synthesis, 1998, 321.
[32] In the case of 1, molecular modelling studies showed that coordination
of two precursor ligands to CuI/II would juxtaposition the ethyne
groups into a favourable orientation for cyclisation. Ion coordination
would therefore be expected to result in an enhancement in the yield
of 1. On the other hand, the chelation of two 26 molecules to CuI/II
would position the ethynes of each ligand at distances out of range for
intra-complex cyclisation, favouring the formation of polymeric and
possibly catenated products. For a discussion of guest templating
effects in the formation of ethynyl-porphyrin macrocycles, see:
references [3b, c].
[33] MALDI TOF mass spectrometry has been successfully used for the
characterisation of nanosized ethynylphenyl macrocycles and also
their gas phase aggregation behaviour; S. Hˆger, J. Spickermann,
D. L. Morrison, P. Dziezok, H. J. R‰der, Macromolecules, 1997, 30,
3110.
[34] The aromatic resonances were assigned as follows: The doublet at d ˆ
8.871 ppm was the furthest downfield resonance in the 1H NMR
spectrum of 5, and was therefore assigned to the pyridyl H6/6'' protons
of the outer two pyridine rings due to their proximity to the electron-
withdrawing nitrogen atoms. The doublet of doublets at d ˆ 8.033 ppm
exhibited a crosspeak with the doublet at d ˆ 8.871 ppm in the 1H 1H
COSY spectrum of 5, and was therefore assigned to the H4/4'' protons
of the outer pyridine rings. A crosspeak in the 1H 1H COSY spectrum
Chem. Eur. J. 2003, 9, 5011 5022
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5021

P. N. W. Baxter
FULL PAPER
of 5, between the triplet at d ˆ 8.003 ppm due to the H4' proton of the
central pyridine, and the doublet at d ˆ 8.541 ppm indicated that the
latter resonance originated from the central pyridine H3'/H5' protons.
The remaining pyridyl doublet at d ˆ 8.680 ppm was therefore
assigned to the H3/3'' protons of the outer pyridines. This conclusion
was unambiguously verified by the presence of a crosspeak in the 1H
1H COSY spectrum, between the latter resonance and that at d ˆ
8.033 ppm originating from the H4/4'' protons. The three triplets at
d ˆ 7.749, 7.696 and 7.636 ppm were assigned to the phenyl H2, H6 and
H4protons, respectively, by comparison with the spectra of 25 and 26
and on the basis of expected electronic effects translated through the
adjacent ethynes. The furthest downfield phenyl resonance at d ˆ
7.749 ppm was thus assigned to the H2 phenyl proton, directed
towards the interior of the macrocyclic cavity. The latter proton would
be expected to experience the greatest downfield shifting due to its
situation between the ethynes with the most electron-withdrawing
substituents. The most upfield triplet at d ˆ 7.636 ppm was assigned to
the H4proton which is positioned between the ethyne bearing the
relatively electron-donating triisopropylsilyl group, and the ethyne
with lesser of the two electron withdrawing substituents, that is, the
butadiyne group. Finally, in the case of 5, a 1H 13C HSQC experiment
enabled the assignation of the proton-connected aromatic carbon
atoms (see characterisation data for 5 above).
sessing bulky substituents, may offer a more widely applicable route to
synthetically useful quantities of nanosized ethynyl macrocycles
incorporating pyridine-type metal ion binding units.
[37] These factors are of crucial importance if structures such as 5 are to be
considered as realistic candidates for nanomaterials research. It may
also be noted that the described synthetic sequence involves the
generation of a range of phenylethynyl and pyridyl synthons. These
may serve as useful building blocks in their own right, for example as
pivotal construction units for incorporation into alternative organic
scaffolds and nanostructures.
[38] That is, the distance between the van der Waals surfaces of the
terpyridine nitrogens that point towards the interior of the cavity. It
may be noted that the molecular modelling studies revealed additional
conformational energy minima in which the ring of 5 was non-planar.
This finding suggests that 5 may be semi-flexible in solution and the
gas phase, and able to oscillate through
a series of puckered
conformations while retaining its overall hexagonal geometry.
[39] For examples of terpyridine-organic molecule H-bonding interactions,
see: a) C.-Y. Huang, V. Lynch, E. V. Anslyn, Angew. Chem. 1992, 104,
1259; Angew. Chem. Int. Ed. 1992, 31, 1244; b) M. Inouye, T. Miyake,
M. Furusyo, H. Nakazumi, J. Am. Chem. Soc. 1995, 117, 12416.
[40] Literature reports of the utilisation of terpyridine chromophores for
the luminescence detection of metal ions are sparse. See for example;
a) W. Goodall, J. A. G. Williams, Chem. Commun. 2001, 2514; b) R.
Ziessel, J. Incl. Phenomena Macrocycl. Chem. 1999, 35, 369; c) M.
Kimura, T. Horai, K. Hanabusa, H. Shirai, Adv. Mater. 1998, 10, 459;
d) F. Barigelletti, L. Flamigni, G. Calogero, L. Hammarstrˆm, J.-P.
Sauvage, J.-P. Collin, Chem. Commun. 1998, 2333; e) A. P. de Silva,
H. Q. N. Gunaratne, T. E. Rice, S. Stewart, Chem. Commun. 1997,
1891. For an example of a terpyridine-based electrochemical anion
sensor, see: f) B. Fabre, U. Lehmann, A. D. Schl¸ter, Electrochim.
Acta, 2001, 46, 2855.
[41] The TIPS-protected ethynyl substituents should enable further
synthetic addition of conjugated structures to the periphery of 5. In
this way, the global conjugation of 5 could be increased and the
spectroscopic properties controllably adapted to specific applications.
[42] T. K. Jones, S. E. Denmark, Helv. Chim. Acta, 1983, 66, 2397.
[43] D. R. Coulson, L. C. Satek, S. O. Grim, Inorg. Synth. 1990, 28, 107.
[44] J. S. Brumbaugh, A. Sen, J. Am. Chem. Soc. 1988, 110, 803.
[35] It may be noted that the emission spectral energies of 23 26 recorded
at ꢁ2 Â 10À7 mol dmÀ3
,
and of
5
at ꢁ3 Â 10À8 mol dmÀ3 were
particularly sensitive to the presence of trace amounts of adventitious
transition metal contaminants, possibly originating from the solvent
and/or the walls of the glass volumetric and measuring equipment.
Repeatable results were however obtained when the dilution studies
of all ligand solutions were carried out in the presence of 1 Â
10À3 moldmÀ3 NaCN (introduced as a 1:1 H2O/MeOH solution, and
4% of the total volume of each volumetric solution). The cyanide
would be expected to preferentially complex any transition metal
impurities, if present. The above observation supports the expectation
that 5 and related structures may function as efficient fluorescence
sensors for metal ions.
[36] During completion of the manuscript, an excellent review on nano-
sized ethynyl macrocycles appeared, which also reported work in
progress on systems related to 5, and undertaken concurrently with
the synthesis of 5 described above; see: C. Grave, A. D. Schl¸ter, Eur.
J. Org. Chem. 2002, 3075; see also reference [14k] for work connascent
with that described herein. However, the reported yields were
significantly lower than that obtained for 5. It appears therefore that
the Eglinton/Galbraith ethyne macrocyclisation of precursors pos-
¡
[45] B. Corain, B. Longato, G. Favero, D. Ajo, G. Pilloni, U. Russo, F. R.
Kreissl, Inorg. Chim. Acta. 1989, 157, 259.
Received: January 29, 2003
Revised: May 16, 2003 [F4786]
5022
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www.chemeurj.org
Chem. Eur. J. 2003, 9, 5011 5022