Synthesis and metalation of novel fluorescent conjugated macrocycles

Article abstract of DOI:10.1021/ol0483549

(Chemical Equation Presented) Large shape-persistent conjugated macrocycles with tunable pore diameters in the nanometer regime were prepared by a simple, one-pot procedure. These new self-assembled macrocycles contain rings of 48-66 covalently bonded atoms and can bind multiple metal ions, forming soluble luminescent complexes.

Full text of DOI:10.1021/ol0483549

ORGANIC
LETTERS
2004
Vol. 6, No. 21
3841-3844
Synthesis and Metalation of Novel
Fluorescent Conjugated Macrocycles
Cecily Ma, Andy Lo, Amir Abdolmaleki, and Mark J. MacLachlan*
Department of Chemistry, UniVersity of British Columbia, 2036 Main Mall,
VancouVer, BC, V6T 1Z1, Canada
mmaclach@chem.ubc.ca
Received August 18, 2004
ABSTRACT
Large shape-persistent conjugated macrocycles with tunable pore diameters in the nanometer regime were prepared by a simple, one-pot
procedure. These new self-assembled macrocycles contain rings of 48−66 covalently bonded atoms and can bind multiple metal ions, forming
soluble luminescent complexes.
Shape-persistent, rigid macrocycles are fascinating targets
for creating new materials, including discotic liquid crystals,
chemical sensors, catalysts, and fluorescent substances.1-5
Under certain conditions, conjugated macrocycles may
assemble into nanotubes.6,7 Although many examples of
organic macrocycles have been reported, they remain chal-
lenging to synthesize, often involving a large number of
steps, the use of protecting groups or templates, high dilution
and proceeding in low yields.8,9
Large macrocycles may be formed by the self-assembly
of metal-coordination complexes in solution.10,11 In these
reactions, metals serve to define the structure of the final
macrocyclic product and are in its backbone. The incorpora-
tion of metals into rigid, conjugated covalently bonded
macrocycles may offer opportunities for developing su-
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10.1021/ol0483549 CCC: $27.50
© 2004 American Chemical Society
Published on Web 09/17/2004

pramolecular materials and sensors triggered by ligand
coordination to the metal. Unfortunately, there are few reports
of shape-persistent organic macrocycles that bind multiple
metal centers.12
Scheme 1. Synthesis of Conjugated Macrocycle 6
Schiff-base condensation is a convenient route to small
macrocycles.13 We have previously used this method to
synthesize macrocycle 1, Figure 1.14 This macrocycle has a
The reaction of compound 2 with diamine 5a afforded a red
powder 6 in 68% yield (Scheme 1). The 1H NMR spectrum
of compound 6 revealed the presence of a single imine
(δ 8.58) and a strongly hydrogen-bonded OH resonance
(δ 13.27), consistent with D3h symmetry for the macrocycle.
MALDI-TOF mass spectrometry showed the molecular ion
at m/z ) 1785, supporting the structure of compound 6. A
Raman spectrum of compound 6 showed the CtC stretching
mode at 2208 cm-1. A single imine stretching mode was
observed at 1607 cm-1 in the IR spectrum.
To generalize and test the [3 + 3] Schiff-base condensation
route to giant macrocyclic proligands, we reacted the longer
bis(salicylaldehydes) 3 and 4 with diamines 5b and 5a
(chosen for reasons of solubility), yielding macrocycles 7
and 8, respectively. Remarkably, these macrocycles were
obtained in 62 and 40% yield, respectively.
This one-pot, template-free, selective synthesis of these
expanded macrocycles seems surprising, given the inherent
flexibility of the precursor bis(salicylaldehydes) 2-4. Whereas
in the preparation of macrocycle 1, the diformyldihydroxy-
benzene precursor has a fixed geometry, there is nearly free
rotation around the benzene-alkyne bond in 2-4. The
reaction was not conducted under dilute conditions, with
removal of water, or in the presence of a template. 1H NMR
spectroscopy of the supernatant solution from the preparation
of 6 showed only 6 and a fragment formed by the condensa-
tion of 2 and 5a in 1:2 ratio,16 without formation of
oligomeric or polymeric materials. The reversibility of the
imine condensation reaction allows the reaction to reach the
thermodynamically favored [3 + 3] macrocyclic condensa-
tion product.
Semiempirical calculations of their flat conformations
indicate that macrocycles 6 and 7 have edge lengths (from
the center of the salen pockets) of ca. 13.3 and 15.5 Å,
respectively. Macrocycle 8, a covalently bound ring with 66
atoms, has an interior diameter of >15 Å, and the salen
pockets are arranged in an equilateral triangle separated by
ca. 20.0 Å. The incorporation of phenyleneethynylene spacers
into the backbone of the macrocycles has enabled the facile
preparation of large, flat macrocycles with tunable diameters.
Figure 1. Structures of macrocycle 1 and precursors 2-4.
very small interior pore and, due to its constrained geometry,
is nonplanar even when coordinated to transition metals. As
a step to developing large, flat macrocycles that can be
assembled into nanotubes, we needed access to larger
macrocycles with the metals spaced farther apart. We now
report the remarkably efficient preparation of large macro-
cycles that possess both nanoscopic pores and three N2O2
binding sites that can coordinate transition metals. These
macrocycles represent a new class of giant, soluble, metal-
containing macrocycles.
Compounds 2 and 4 (Figure 1) were synthesized via Pd-
catalyzed Sonogashira-Hagihara cross-coupling of 4-ethyn-
ylsalicylaldehyde with 4-bromosalicylaldehyde and 1,4-di-
iodo-2,5-dimethoxybenzene, respectively.15 Compound 3 was
prepared by oxidative coupling of 4-ethynylsalicylaldehyde.
(12) (a) Henz, O.; Lentz, D.; Scha¨fer, A.; Franke, P.; Schlu¨ter, A. D.
Chem.sEur. J. 2002, 8, 357-365. (b) Li, J.; Ambroise, A.; Yang, S. I.;
Diers, J. R.; Seth, J.; Wack, C. R.; Bocian, D. F.; Holten, D.; Linsey, J. S.
J. Am. Chem. Soc. 1999, 121, 8927-8940. (c) Rucareanu, S.; Mongin, O.;
Schuwey, A.; Hoyler, N.; Gossauer, A.; Amrein, W.; Hediger, H.-U. J.
Org. Chem. 2001, 66, 4973-4988. (d) Campbell, K.; McDonald, R.;
Ferguson, M. J.; Tykwinski, R. R. Organometallics 2003, 22, 1353-1355.
(e) Baxter, P. N. W. Chem.sEur. J. 2003, 9, 5011-5022. (f) Baxter, P. N.
W. Chem.sEur. J. 2003, 9, 2531-2541.
(13) For recent examples of macrocycles containing Schiff-bases, see:
(a) Gawron´ski, J.; Kołbon, H.; Kwit, M.; Katrusiak, A. J. Org. Chem. 2000,
65, 5768-5773. (b) Kuhnert, N.; Rossignolo, G. M.; Lopez-Periago, A.
Org. Biomol. Chem. 2003, 1, 1157-1170. (c) Shimakoshi, H.; Kai, T.;
Aritome, I.; Hisaeda, Y. Tetrahedron Lett. 2002, 43, 8261-8264. (d) Kwit,
M.; Gawron´ski, J. Tetrahedron: Asymmetry 2003, 14, 1303-1308. (e) Gao,
J.; Martell, A. E. Org. Biomol. Chem. 2003, 1, 2795-2800. (f) Zhao, D.;
Moore, J. S. J. Org. Chem. 2002, 67, 3548-3554. (g) Depree, C. V.;
Beckmann, U.; Heslop, K.; Brooker, S. Dalton Trans. 2003, 3071-3081.
(h) Chadim, M.; Budeˇsˇinsky´, M.; Hodacˇova´, J.; Za´vada, J.; Junk, P. C.
Tetrahedron: Asymmetry 2001, 12, 127-133. (i) Sessler, J. L.; Veauthier,
J. M.; Cho, W.-S.; Lynch, V. M. Inorg. Chem. 2004, 43, 1220-1228. (j)
Akine, S.; Taniguchi, T.; Nabeshima, T. Tetrahedron Lett. 2001, 42, 8861-
8864.
(14) Gallant, A. J.; MacLachlan, M. J. Angew. Chem., Int. Ed. 2003, 42,
5307-5310.
(15) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
16, 4467-4470. (b) Hundertmark, T.; Littke, A. F.; Buchwald, S. L.; Fu,
G. C. Org. Lett. 2000, 2, 1729-1731.
(16) 1H NMR (300 MHz, CDCl3): δ 13.24 (s, 2H, OH), 8.53 (s, 2H,
CHdN), 7.35 (d, 2H, CH), 7.16 (d, 2H, CH), 7.10 (dd, 2H, CH), 6.77 (s,
2H, CH), 6.34 (s, 2H, CH), 3.94 (m, 8H, OCH2), 3.85 (s, 4H, NH2), 1.8-
0.8 (m, 60H, C7H15).
3842
Org. Lett., Vol. 6, No. 21, 2004

In addition, the quenching is essentially complete when 3
equiv of Ni(II) are added, giving the stoichiometry of the
final product. On the other hand, upon titration with Zn2+,
macrocycle 6 undergoes a significant increase in fluores-
cence, Figure 3b. This enhanced fluorescence is attributed
to the Zn2+ binding to the salen-type ligands, where it
deprotonates the phenol and rigidifies the macrocycle. The
changes that occurred in the UV-visible spectra arise from
the coordination of Zn2+ ions to the N2O2 binding sites.
When macrocycle 6 was reacted with 3 equiv of
Zn(OAc)2‚2H2O in THF, a new product 9 was obtained,
Scheme 2. MALDI-TOF MS of the red product confirmed
Scheme 2. Synthesis of Metallomacrocycles 9-11
Figure 2. Structures of large macrocycles 7 and 8.
Metalation of the macrocycles was investigated to dem-
onstrate that these macrocycles can coordinate multiple
transition metals in their salen-type pockets. All three metal-
free macrocycles 6-8 are weakly luminescent in THF (Φ
) 0.13-0.15%). When macrocycle 6 was titrated with Ni2+,
the fluorescence intensity decreased, Figure 3a. A large
the incorporation of 3 Zn(II) ions into the complex. In
addition, the Raman spectrum of 9 showed a single CtC
stretching mode at 2196 cm-1. The UV-visible spectrum
of the complex shows a bathochromic shift relative to
macrocycle 6, consistent with enhanced conjugation in the
ligand. Moreover, metallomacrocycle 9 is luminescent in
THF
(Φ ) 0.86%) with peaks at 558 and 596 nm. Macrocycles
7 and 8 were reacted with excess Zn(OAc)2 to produce the
trimetalated macrocycles 10 and 11, respectively. These
macrocycles are also weakly luminescent in solution, Figure
3c. Figure 3d compares the fluorescence of macrocycle 5
upon reaction with 3 equiv of Zn(OAc)2 (i.e., 9) and
Ni(OAc)2.
It is noteworthy that the fluorescence spectra of 9-11 are
nearly identical. This suggests that the luminescence is
localized to the metal complexes and that there is little
electronic coupling of the metal complexes through the
Figure 3. (a) UV-visible and fluorescence spectra of macrocycle
6 upon titration with Ni(OAc)2 (THF). (b) UV-visible and
fluorescence spectra of macrocycle 6 upon titration with Zn(OAc)2
(THF). (c) UV-visible and emission spectra for macrocycles 9-11.
(d) Photograph of fluorescence from macrocycle 6 (i) with no metal,
(ii) with zinc acetate, and (iii) with nickel acetate. Solvent: THF,
5 × 10-5 M; λexc ) 365 nm.
Scheme 3. Synthesis of Model Compound 13
positive deviation from linearity in the Stern-Volmer
analysis indicates that the quenching is static, likely due to
a metal-ligand charge-transfer band near 550 nm that
facilitates energy transfer through a nonradiative pathway.17
(17) Murphy, C. B.; Zhang, Y.; Troxler, T.; Ferry, V.; Martin, J. J.; Jones,
W. E., Jr. J. Phys. Chem. B 2004, 108, 1537-1543.
Org. Lett., Vol. 6, No. 21, 2004
3843

In summary, we report a simple, general approach to
building new, large, shape-persistent conjugated macrocycles
with tunable pore diameters in the nanometer regime. These
macrocycles can bind multiple metals, forming soluble,
luminescent complexes. A space-filling diagram of metal-
lomacrocycle 11 (Figure 4) shows that there is significant
space on the inside of these macrocycles. As well, in the
case of M ) Ni2+, these macrocycles are flat and ready for
supramolecular assembly. We are investigating the supra-
molecular chemistry and coordination chemistry of these and
related macrocycles.
Figure 4. Minimum energy structure of trimetallic macrocycle 11
as determined by semiempirical (PM3) methods using M ) Ni(II)
and with peripheral alkoxy chains and methyl groups omitted.
Acknowledgment. We thank NSERC, CFI, and UBC for
funding and Prof. M. Blades for Raman spectra. C.M. thanks
NSERC for a PGSA scholarship.
organic backbone. Model compound 13 (prepared from
5-(phenylethynyl)salicylaldehyde 12 as shown in Scheme 3)
is also fluorescent, with peaks at 537 and 567 nm (Φ )
0.96%). This represents a blueshift of ca. 20 nm from
metallomacrocycle 9, indicating that the bridging groups do
have some effect on the fluorescence of the macrocycles.
This is also relevant to our studies of conjugated poly-
(salphenyleneethynylenes) since macrocycle 11 is a cyclic
analogue of these polymers.18
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL0483549
(18) Leung, A. C. W.; Chong, J. H.; Patrick, B. O.; MacLachlan, M. J.
Macromolecules 2003, 36, 5051-5054.
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Org. Lett., Vol. 6, No. 21, 2004