Social and antisocial [3 + 3] Schiff base macrocycles with isomeric backbones

Article abstract of DOI:10.1021/jo801069g

(Figure Presented) Two new conjugated macrocycles have been prepared in high yield using Schiff base condensation. These are the first Schiff base macrocycles to incorporate phenanthrene, and they contain 66 and 78 atoms, respectively, in their smallest c

Full text of DOI:10.1021/jo801069g

binding sites for further coordination to metals. The size and
shape of the macrocycle obtained from the condensation are
dictatedbythegeometryandlengthofthestartingcomponents.8-10
In our quest to develop highly luminescent Schiff base
macrocycles for sensing applications, we investigated the
incorporation of phenanthrene into a Schiff base macrocycle.
Previously, phenanthrene has been incorporated into luminescent
polymers and materials11,12 but has seldom been studied as a
component of macrocycles.13,14 Herein, we report the synthesis
and characterization of two new macrocycles incorporating
phenanthrene. To the best of our knowledge, the new macrocycle
8 with 78 atoms in the smallest closed ring is the largest
conjugated macrocycle assembled by Schiff base condensation.
This highly efficient synthesis illustrates the utility of Schiff
base condensation for making large molecules. Moreover, one
of these macrocycles aggregates in solution, while the other does
not.
Social and Antisocial [3 + 3] Schiff Base
Macrocycles with Isomeric Backbones
Britta N. Boden, Joseph K.-H. Hui, and
Mark J. MacLachlan*
Department of Chemistry, UniVersity of British Columbia,
2036 Main Mall, VancouVer, BC V6T 1Z1 Canada
mmaclach@chem.ubc.ca
ReceiVed May 22, 2008
We have previously reported the synthesis of compound 1,
which was found to be a useful precursor in the synthesis of
conjugated phenanthrene-containing polymers.12 Coupling of 1
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Two new conjugated macrocycles have been prepared in high
yield using Schiff base condensation. These are the first
Schiff base macrocycles to incorporate phenanthrene, and
they contain 66 and 78 atoms, respectively, in their smallest
closed ring. Although the backbones of the two macrocycles
have nearly the same constitution, one aggregates in chlo-
roform while the other does not. This is rationalized based
on the differential overlap of aromatic components in the
dimers.
(6) (a) Akine, S.; Taniguchi, T.; Nabeshima, T. Tetrahedron Lett. 2001, 42,
8861–8864. (b) Nabeshima, T.; Miyazaki, H.; Iwasaki, A.; Akine, S.; Saiki, T.;
Ikeda, C. Tetrahedron 2007, 63, 3328–3333. (c) Akine, S.; Sunaga, S.; Taniguchi,
T.; Miyazaki, H.; Nabeshima, T. Inorg. Chem. 2007, 46, 2959–2961.
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5307–5310. (b) Ma, C. T.-Z.; MacLachlan, M. J. Angew. Chem., Int. Ed. 2005,
44, 4178–4182. (c) Gallant, A. J.; Hui, J. K.-H.; Zahariev, F. E.; Wang, Y. A.;
MacLachlan, M. J. J. Org. Chem. 2005, 70, 7936–7946. (d) Gallant, A. J.; Yun,
M.; Sauer, M.; Yeung, C. S.; MacLachlan, M. J. Org. Lett. 2005, 7, 4827–4830.
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3841–3844.
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Conjugated, shape-persistent macrocycles are attractive for
studies of supramolecular assembly,1 liquid crystallinity,2 and
nanotube formation.3 Recent studies from our laboratory and
others have shown that imine formation is a synthetically useful
route to assemble conjugated macrocycles.4-7 In particular, we
have been targeting macrocycles that have salphen-type N2O2
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Demus, D., Goodby, J. W., Gray, G. W., Spiess, H. W., Vill, V., Eds.; Wiley
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Chem. Soc. 1994, 116, 2655–2656. (c) Fischer, M.; Lieser, G.; Rapp, A.; Schnell,
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Enkelmann, V.; Bonrad, K.; Tschierske, C. Angew. Chem., Int. Ed. 2000, 39,
2267–2270. (f) Sessler, J. L.; Callaway, W.; Dudek, S. P.; Date, R. W.; Lynch,
V.; Bruce, D. W. Chem. Commun. 2003, 2422–2423. (g) Ho¨ger, S. Chem.sEur.
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J. Chem. 2008, 86, 50–64.
10.1021/jo801069g CCC: $40.75
Published on Web 09/12/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 8069–8072 8069

SCHEME 1. Synthesis of Compound 2
SCHEME 2. Synthesis of Compound 6
FIGURE 1. Absorption (dashed line) and emission (solid line) spectra
of macrocycles 8 (4 × 10-6 M; λexc ) 383 nm) and 9 (3 × 10-6 M;
λexc ) 357 nm) in CH2Cl2 (8 ) black, 9 ) red).
SCHEME 4. Synthesis of Macrocycle 9
SCHEME 3. Synthesis of Macrocycle 8
8 and 9 were consistent with the proposed structures. MALDI-
TOF mass spectra verified that the cycles formed were indeed
[3 + 3] macrocycles, with the molecular ion as the dominant
peak in both cases.
When the alkoxy substituents are ignored, the backbones of
triangular macrocycles 8 and 9 are isomeric with 78 and 66
atoms in the smallest closed ring, respectively. In macrocycle
8, the phenanthrene groups are on the edges with salphen groups
forming the corners of a triangle. In macrocycle 9, the position
of the salphen and phenanthrene moieties is interchanged.
Macrocycle 8 has a conjugated backbone, and there is alternation
of single and double or triple bonds around the ring. In
macrocycle 9, however, the bond alternation is disrupted at each
salicylaldimine since the meta-linkage between alkyne and imine
prevents a path of alternating single and double bonds. We
sought to understand how changing the geometry would affect
the electronic and other properties of the macrocycle.
Figure 1 shows the absorption and emission spectra of
macrocycles 8 and 9. Macrocycle 8 has two large absorption
bands at 300 and 384 nm, while macrocycle 9 absorbs at 309
and 357 nm. The maximum absorbance for macrocycle 9 is 27
nm blue-shifted from that of macrocycle 8, a trend that was
expected due to the decreased conjugation of macrocycle 9.
with 4-ethynylsalicylaldehyde afforded compound 2 in 75%
yield (Scheme 1). Compound 6 was prepared in three steps (39%
overall yield) from dibromodihexyloxyphenanthrene 3 (Scheme
2). Both 2 and 6 have two salicylaldehyde groups bridged by
phenanthrene.
Compounds 2 and 6 were reacted with 1,2-dialkoxy-4,5-
phenylenediamines 7 to form Schiff base macrocycles. Thus,
the reaction of 2 with 7a afforded dark red macrocycle 8 in
71% yield (Scheme 3). 2-Butyloctyl substituents were selected
to ensure the macrocycle was soluble. Similarly, compound 6
was condensed with 7b to form orange microcrystalline mac-
rocycle 9 in 53% yield (Scheme 4). In this case, hexyloxy
substituents were selected on the phenylenediamine since they
were deemed sufficient to render the macrocycles soluble, given
that the phenanthrene groups also have hexyloxy substituents.
The high yields of these macrocycles, which are prepared
without a template, are likely attributed to the strong intramo-
lecular hydrogen bonding within the cycles and the preordained
geometry of precursors 2 and 6. NMR spectra of macrocycles
Both macrocycles are weakly luminescent in solution and in
the solid state. In solution, macrocycle 8 emits with a maximum
at 567 nm (CH2Cl2; ΦF ) 0.4%) and macrocycle 9 emits with
a maximum at 588 nm (CH2Cl2; ΦF ) 1.2%).
8070 J. Org. Chem. Vol. 73, No. 20, 2008

FIGURE 2. (a) Stacked 1H NMR spectra (400 MHz, CDCl3, 1.5 mM)
of macrocycle 9 at various temperatures. (b) Stacked 1H NMR spectra
(400 MHz, CDCl3, RT) of macrocycle 9 at two different concentrations
(/ ) CDCl3).
FIGURE 3. Structures of hypothetical planar dimers of macrocycles
8 (top) and 9 (bottom), with ChemDraw representations on the left
and Spartan models (not energy minimized) on the right.
Polycyclic aromatic hydrocarbons are well-known to stack
as a result of intermolecular π-π interactions.15 Macrocycles
8 and 9 both contain many aromatic units that have potential to
interact, and we probed their aggregation by variable temperature
and variable concentration 1H NMR (VT/VC NMR) spectroscopy.
Initially, solutions of two different concentrations of each
macrocycle were prepared, and 1H NMR spectra were obtained
at four different temperatures, ranging from 25 to 55 °C at 10
°C intervals. Upon changing the temperature of the samples of
macrocycle 8, the only peak that exhibits a change in chemical
shift is the OH resonance, which moves upfield from 13.30 to
13.13 ppm over the 30 °C temperature range. This macrocycle
also showed no concentration dependence in its chemical shifts.
These observations indicate that macrocycle 8 does not ag-
gregate in CDCl3.
On the other hand, VT/VC NMR experiments with
macrocycle 9 gave a different result (Figure 2). Hydroxyl
resonances shift upfield with increasing temperature and
decreasing concentration, while all aromatic resonances shift
downfield. The largest shifts (ca. 0.5 to 1.0 ppm) come from
the imine proton, the aromatic phenylenediimine proton, and
alkoxy OCH2. Additionally, the overlapping imine and the
phenanthrene proton resonances, found near 8.5 ppm, separate
and sharpen with increasing temperature. These initial results
clearly indicate that macrocycle 9 aggregates in solution. The
monomer to aggregate equilibrium is affected by changes in
temperature and concentration.
TABLE 1. Association Constants KE for Dimerization of
Macrocycle 9 in CDCl3
T (°C, K)
KE (imine) (M-1
)
KE (diimine) (M-1
)
5, 278
1600 ( 410
2700 ( 290
1200 ( 380
580 ( 150
290 ( 90
5000 ( 1200
3700 ( 1100
1000 ( 280
420 ( 120
140 ( 60
15, 288
25, 298
35, 308
45, 318
55, 328
280 ( 90
150 ( 60
chemical shift change was less than 1 ppm for all resonances,
this is more consistent with dimer formation than larger
aggregates.16 Data were fit to a model for dimerization (see
Supporting Information) to extract equilibrium constants at each
temperature (Table 1).16 As expected, the association constants
decrease as temperature increases, indicative of weaker ag-
gregation at elevated temperatures. Other imine-containing
macrocycles have values of KE at room temperature in the same
order of magnitude (∼103 M-1) as for macrocycle 9.17
On the basis of the temperature dependence of the data, the
dimerization is clearly enthalpy favored (∆H < 0) and entropy
disfavored (∆S < 0).18 This result is consistent with π-π
interactions being primarily involved in the assembly. The
negative change in entropy is not unexpected, as aggregation
would increase order in solution. Given these results, it is
apparent that, at higher temperatures, the chemical shifts are
nearly independent of concentration, indicating that elevated
temperature effectively deaggregates the macrocycle, and these
spectra are most representative of the free macrocycle. Con-
versely, the most concentrated spectra obtained at the lowest
temperature represent, in effect, the macrocycle in a fully
aggregated environment.
In an effort to quantify the aggregation of macrocycle 9, NMR
data were collected over a range of concentrations (0.045-2.27
mM) and temperatures (5-55 °C); solubility constraints pro-
hibited data collection at low temperature. The resonances
assigned to the imine and phenylenediimine resonances shifted
as a function of concentration and temperature. As the total
(15) (a) Kawano, S.-i.; Tamaru, S.-i.; Fujita, N.; Shinkai, S. Chem.sEur. J.
2004, 10, 343–351. (b) Ranganathan, D.; Haridas, V.; Gilardi, R.; Karle, I. L.
J. Am. Chem. Soc. 1998, 120, 10793–10800. (c) Cockroft, S. L.; Perkins, J.;
Zonta, C.; Adams, H.; Spey, S. E.; Low, C. M. R.; Vinter, J. G.; Lawson, K. R.;
Urch, C. J.; Hunter, C. A. Org. Biomol. Chem. 2007, 5, 1062–1080. (d) Munakata,
M.; Ning, G. L.; Suenaga, Y.; Kuroda-Sowa, T.; Maekawa, M.; Ohta, T. Angew.
Chem., Int. Ed. 2000, 39, 4555–4557.
(16) Martin, R. B. Chem. ReV. 1996, 96, 3043–3064.
(17) Zhao, D.; Moore, J. S. J. Org. Chem. 2002, 67, 3548–3554.
(18) We determined the thermodynamic parameters from a van’t Hoff plot,
but this method does not give accurate parameters unless a broad temperature
range can be accessed.
J. Org. Chem. Vol. 73, No. 20, 2008 8071

mmol) were combined in a Schlenk flask in the glovebox. Degassed
CHCl3 (15 mL) and MeCN (5 mL) were added to the flask, and
the solution was heated to reflux at 90 °C. After heating for 24 h,
the solution was cooled and the solid was precipitated by addition
of MeCN. The solid was recrystallized from CH2Cl2 and MeCN.
Yield: 0.180 g, 0.0584 mmol, 71%. Data for 8: 1H NMR (300 MHz,
CDCl3) δ 13.32 (s, 6H), 8.62 (s, 6H), 8.34 (s, 6H), 7.78 (s, 6H),
7.38 (d, J ) 8.0 Hz, 6H), 7.31 (s, 6H), 7.17 (d, J ) 8.0 Hz, 6H),
6.81 (s, 6H), 4.13 (s, 18H), 4.08 (s, 18H), 3.93 (d, 12H), 2.0-0.80
(m, 138H); 13C NMR (75.5 MHz, CDCl3) δ 161.1, 157. 9, 149.8,
142.4, 135.3, 132.1, 129.0, 128.5, 127.9, 124.4, 122.5, 120.8, 119.7,
114.2, 103.0, 94.5, 88.7, 72.5, 61.4, 56.5, 38.4, 32.2, 31.6, 31.3,
30.0, 29.4, 27.2, 23.3, 23.0, 14.4; MALDI-TOF-MS m/z ) 3084
([M + H]+); IR (KBr) ν ) 3430, 2952, 2932, 2859, 2204, 1606,
Considering that macrocycles 8 and 9 have isomeric back-
bones, it is surprising that they behave differently in solution.
However, Figure 3, which shows hypothetical structures of the
dimers, illustrates a possible reason why 8 does not aggregate
while 9 does. The macrocycles are rotated in the figure because
direct overlap of the aromatic rings would lead to repulsion of
the macrocycles rather than attractive forces necessary for
aggregation. The dimers depicted in Figure 3 would allow
attractive interactions between electron-deficient and electron-
rich rings. Dimers of macrocycle 8 lack overlapping aromatic
rings, greatly reducing its capacity for π stacking and preventing
aggregation. Model dimers of macrocycle 9 have salphen
moieties directly aligned with the phenanthrene groups and the
protons positioned over the aromatic rings, where they would
experience the greatest effects of magnetic anisotropy and
exhibit the greatest change in chemical shift in the VT/VC NMR
spectra. For example, the phenylenediimine proton is positioned
over the center of the phenanthrene rings in the dimer; therefore,
the chemical shifts are considerably upfield at lower tempera-
tures and higher concentrations because of the proximity to the
ring current. Upon deaggregation, the peaks shift downfield
because this proton is no longer in such an electronically
shielded environment, which has been confirmed in previous
studies.19,20
1511, 1457, 1367, 1252, 1207, 1172, 1103, 1015, 813, 696 cm-1
;
UV-vis (CH2Cl2) λmax (ꢀ) ) 300 (1.3 × 105), 384 (2.2 × 105) nm
(L mol-1 cm-1); mp >300 °C. Anal. Calcd for C198H234N6O24
·
2H2O: C, 76.27; H, 7.69; N, 2.70. Found: C, 75.94; H, 7.79; N,
3.11.
Synthesis of Macrocycle 9. To a mixture of compound 6 (0.206
g, 0.309 mmol) and 1,2-dihexyloxy-4,5-diaminobenzene (7b) (0.096
g, 0.311 mmol) was added 10 mL of each CHCl3 and MeCN. The
resulting solution was refluxed at 90 °C for 24 h after which an
orange solid precipitated and was filtered. For additional purifica-
tion, the product was recrystallized in hot CHCl3 and MeCN and
washed with petroleum ether. Yield: 0.156 g, 0.0554 mmol, 53%.
1
Data for 9: H NMR (400 MHz, CDCl3) δ 13.78 (s, 6H), 8.50 (s,
In summary, two giant Schiff base macrocycles with isomeric
backbones containing phenanthrene were synthesized and found
to be weakly luminescent. One macrocycle (9) aggregates in
chloroform, while the other (8) does not. We attribute this
difference to the ability of macrocycle 9 to stack with overlap
of salphen groups with phenanthrene moieties, while in mac-
rocycle 8, fewer π-π interactions are possible. These macro-
cycles illustrate the use of Schiff base chemistry as a route to
well-defined nanoscale macrocycles.
6H), 8.47 (s, 6H), 8.08 (d, J ) 8.5 Hz, 6H), 7.60 (d, J ) 8.5 Hz,
6H), 7.53 (d, J ) 1.3 Hz, 6H), 7.40 (dd, J1 ) 8.6 Hz, J2 ) 1.4 Hz,
6H), 6.98 (d, J ) 8.6 Hz, 6H), 6.36 (s, 6H), 4.15 (t, 12H), 3.81 (t,
12H), 1.87-0.94 (m, 132H); 13C NMR (100.7 MHz, CDCl3) δ
161.8, 159.5, 149.1, 143.8, 136.4, 135.7, 134.8, 129.2, 128.1, 126.3,
122.4, 120.8, 119.6, 118.1, 113.8, 90.2, 88.9, 73.6, 69.3, 32.1, 31.9,
30.8, 29.4, 26.2, 26.0, 23.0, 22.9, 14.4, 14.3; MALDI-TOF-MS m/z
) 2818.9 ([M + H]+); IR (KBr) ν ) 3413, 2958, 2933, 2857,
2204, 1617, 1608, 1503, 1488, 1437, 1352, 1317, 1292, 1263, 1179,
1121, 1062, 828 cm-1; UV-vis (CH2Cl2) λmax (ꢀ) ) 279 (1.9 ×
105), 309 (2.0 × 105), 357 (1.5 × 105) nm (L mol-1 cm-1); mp
>300 °C. Anal. Calcd for C186H210N6O18: C, 79.28; H, 7.51; N,
2.98. Found: C, 79.00; H, 7.67; N, 3.22.
Experimental Section
Synthesis of Macrocycle 8. Compound 2 (0.145 g, 0.247 mmol)
and 1,2-dibutyloctyloxy-4,5-diaminobenzene (7a) (0.118 g, 0.247
Acknowledgment. We thank NSERC for funding.
(19) Hamuro, Y.; Geib, S. J.; Hamilton, A. J. J. Am. Chem. Soc. 1997, 119,
10587–10593.
(20) We cannot eliminate the possibility that the different sizes of the
peripheral alkoxy substituents have a role in the stacking. We have not observed
significant substituent effects with other macrocycles, but they may be involved
here. Efforts are underway to prepare new analogues that will allow better control
of the substituents.
Supporting Information Available: Experimental details,
characterization, and spectra for new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO801069G
8072 J. Org. Chem. Vol. 73, No. 20, 2008