Unsymmetrical triangular schiff base macrocycles with cone conformations

Article abstract of DOI:10.1021/ol100028s

chemical Equation presented Two new unsymmetrlcal Schiff base macrocycles with isosceles triangle shapes have been prepared. The macrocycles adopt cone-shaped conformations that rapidly interconvert at high temperature. Dynamic NMR studies show that the m

Full text of DOI:10.1021/ol100028s

ORGANIC
LETTERS
2010
Vol. 12, No. 5
1020-1023
Unsymmetrical Triangular Schiff Base
Macrocycles with Cone Conformations
Jian Jiang and Mark J. MacLachlan*
Department of Chemistry, UniVersity of British Columbia, 2036 Main Mall,
VancouVer, BC, Canada V6T 1Z1
mmaclach@chem.ubc.ca
Received January 6, 2010
ABSTRACT
Two new unsymmetrical Schiff base macrocycles with isosceles triangle shapes have been prepared. The macrocycles adopt cone-shaped
conformations that rapidly interconvert at high temperature. Dynamic NMR studies show that the macrocycle that is tautomerized to the
keto-enamine isomer is slower to flip than is the one in the enol-imine state. These macrocycles are good hosts for binding organic cations
in their interiors.
Elegant control of molecular architectures and their self-
assembly plays a central role in modern chemistry.1,2 The
design and synthesis of discrete macrocyclic polygons and
polyhedra have been under significant development for more
than a decade,3 many assembled by metal coordination
chemistry.4 Using reversible reactions, such as metal binding,
an impressive assortment of high-symmetry structures have
been assembled.5
Schiff base condensation offers a convenient route to self-
assemble large macrocycles6 and polyhedra.7 Triangular
macrocycles, in particular, are easily obtained by the
condensation of a dialdehyde and diamine with the appropri-
ate structure.8 We have been exploring the coordination
chemistry and self-assembly of triangular Schiff base mac-
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7026. (b) Chuang, C.-J.; Li, W.-S.; Lai, C.-C.; Liu, Y.-H.; Peng, S.-M.;
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10.1021/ol100028s  2010 American Chemical Society
Published on Web 02/04/2010

rocycles, but our studies have been limited to cycles with
high symmetry.9 We have found it very difficult to prepare
macrocycles with different components. While the advantage
of this self-assembly method lies in the reversibility of the
imine condensation that enables preparation of thermody-
namically stable macrocycles, reducing the symmetry by
incorporating different components generally leads to a
mixture of inseparable products unless metal templation is
utilized.10 Facile routes to triangular macrocycles where one
side is chemically different than the others may open avenues
to making macrocycles that have different functional groups
on the periphery (e.g., hydrophobic on one side, hydrophilic
on the other). Surprisingly, there are few examples of
macrocycles with isosceles triangular shapes. Only recently
has the development of “isosceles macrocycles”, where two
sides are chemically and geometrically distinct from the third,
been met with success in the case of metal-coordination
macrocycles.11
3. Macrocycle 5 was prepared by the condensation of 3 with
substituted o-phenylenediamine 4. The mass spectrum of the
product clearly showed the [5 + H]+ ion at m/z 1581.3 Da.
At first we were surprised by this result. We expected to
obtain a larger macrocycle or even a polymer since the
macrocycle appears highly strained. However, semiempirical
calculations showed that the macrocycle will adopt a cone
shape analogous to that of a calixarene, Figure 1. In
macrocycle 5, the resorcinol moiety can be regarded as the
base of an isosceles triangle, the two catechol parts are sides,
and the three diamine components are vertices. Thus, the
macrocycle has 3 N2O2 pockets, one flanked by two imines
and the other two by one ketimine and one aldimine.
Scheme 1. Synthesis of Macrocycle 5
Figure 1. Semiempirical (PM3) calculated model of macrocycle
5: (a) space-filling model showing the interior cavity; (b, c) views
of the macrocycle in the cone conformation. Alkoxy chains were
not included in the model.
There has been considerable interest in expanding calix-
arene-based molecules with use of naphthalenes in order to
modify binding and other properties.13 Applying a similar
strategy to that employed in the synthesis of 5, we reacted
diamine 6 (prepared from the condensation of 2 equiv of 4
with 3,6-dibenzoylresorcinol) with naphthalenedialdehyde 7
(7) (a) Mastalerz, M. Chem. Commun. 2008, 4756–4758. (b) Liu, X.;
Liu, Y.; Li, G.; Warmuth, R. Angew. Chem., Int. Ed. 2006, 45, 901–904.
(c) Ic¸li, B.; Christinat, N.; To¨nnemann, J.; Schu¨ttler, C.; Scopelliti, R.;
Severin, K. J. Am. Chem. Soc. 2009, 131, 3154–3155. (d) Sanmart´ın, J.;
Bermejo, M. R.; Garc´ıa-Deibe, A. M.; Rivas, I. M.; Ferna´ndez, A. R.
J. Chem. Soc., Dalton Trans. 2000, 4174–4181. (e) Uribe-Romo, F. J.; Hunt,
J. R.; Furukawa, H.; Klo¨ck, C.; O’Keeffe, M.; Yaghi, O. M. J. Am. Chem.
Soc. 2009, 131, 4570–4571.
Here we report the preparation of novel covalently linked
molecular isosceles triangles using Schiff base chemistry.
The new macrocycles adopt cone-like conformations in
solution that enable them to bind organic cations in their
interiors to form 1:1 host-guest complexes. Scheme 1 shows
the synthetic route to macrocycle 5 with an isosceles shape.
Compound 1 with two ketimine bonds12 was first reacted
with 1,4-diformylcatechol 2 to give dialdehyde compound
(8) For recent examples, see: (a) Akine, S.; Taniguchi, T.; Nabeshima,
T. Tetrahedron Lett. 2001, 42, 8861–8864. (b) Gao, J.; Zingaro, R. A.;
Reibenspies, J. H.; Martell, A. E. Org. Lett. 2004, 6, 2453–2455. (c)
Gawronski, J.; Kwit, M.; Grajewski, J.; Gajewy, J.; Dlugokinska, A.
Tetrahedron: Asymmetry 2007, 18, 2632–2637. (d) Korich, A. L.; Hughes,
T. S. Org. Lett. 2008, 10, 5405–5408. (e) Kwit, M.; Zabicka, B.; Gawronski,
J. Dalton Trans. 2009, 6783–6789.
(9) (a) Shopsowitz, K. E.; Edwards, D.; Gallant, A. J.; MacLachlan,
M. J. Tetrahedron 2009, 65, 8113–8119. (b) Gallant, A. J.; Hui, J. K.-H.;
Zahariev, F. E.; Wang, Y. A.; MacLachlan, M. J. J. Org. Chem. 2005, 70,
7936–7946. (c) Gallant, A. J.; MacLachlan, M. J. Angew. Chem., Int. Ed.
2003, 42, 5307–5310.
(6) (a) Borisova, N. E.; Reshetova, M. D.; Ustynyuk, Y. A. Chem. ReV.
2007, 107, 46–79. (b) Vigato, P. A.; Tamburini, S.; Bertolo, L. Coord. Chem.
ReV. 2007, 251, 1311–1492. (c) MacLachlan, M. J. Pure Appl. Chem. 2006,
78, 873–888. (d) Frischmann, P. D.; Jiang, J.; Hui, J. K.-H.; Grzybowski,
J. J.; MacLachlan, M. J. Org. Lett. 2008, 10, 1255–1258. (e) de Geest,
D. J.; Noble, A.; Moubaraki, B.; Murray, K. S.; Larsena, D. S.; Brooker,
S. Dalton Trans. 2007, 467–475. (f) Hui, J. K.-H.; MacLachlan, M. J. Chem.
Commun. 2006, 2480–2482. (g) Ma, C.; Lo, A.; Abdolmaleki, A.;
MacLachlan, M. J. Org. Lett. 2004, 6, 3841–3844.
(10) Kleij, A. W. Chem.sEur. J. 2008, 14, 10520–10529.
(11) Schmittel, M.; Mahata, K. Inorg. Chem. 2009, 48, 822–824.
(12) Jiang, J.; MacLachlan, M. J. Chem. Commun. 2009, 5695–5697.
(13) Georghiou, P. E.; Li, Z.; Ashram, M.; Chowdhury, S.; Mizyed, S.;
Tran, A. H.; Al-Saraierh, H.; Miller, D. O. Synlett 2005, 879–891.
Org. Lett., Vol. 12, No. 5, 2010
1021

Scheme 2. Synthesis of Macrocycle 9
Figure 3
.
(a) Partial 1H NMR spectrum of macrocycle 5 from 3.7
1
to 4.1 ppm. (b) Partial 2-D H-1H COSY NMR spectrum of 5
from 3.5 to 4.2 ppm (400 MHz, CDCl3, 298 K). (c) Assignments
of the protons of 5 discussed in the text.
1
The H NMR spectrum of 5 showed two distinct reso-
nances for the OCH2 (Hc and Hd in Figure 3c) of the OC12H25
chain. The peaks a and b are located at 3.83 and 3.73 ppm,
1
respectively (shown in Figure 3a). A H-1H COSY NMR
spectrum confirmed that peaks a and b couple with each other
(Figure 3b) and are assigned to these two protons. In 5, these
two protons are therefore diastereotopic, indicating that there
is no plane of symmetry that interchanges them;the
macrocycle is not planar. Upon heating, these peaks coalesce,
indicating that the macrocycle is interconverting between
cone conformations on the NMR time scale (Figure 4). The
observation of a stationary conformation at room temperature
in these Schiff base macrocycles is interesting and potentially
important for generating chiral cycles and other supramo-
lecular structures.
to prepare an isosceles-shaped triangular macrocycle (9) that
incorporates two naphthalenediimines (Scheme 2). In the 1H
NMR spectrum of 9 (Figure 2), the OH resonances (a, b,
and e in Figure 2) appear as two doublets and a singlet.
1H-1H COSY NMR spectroscopy revealed that the doublets
near 15 ppm arise from coupling to the imine protons near
9 ppm.
Figure 2.
1H NMR spectrum of macrocycle 9 (400 MHz, CDCl3,
298 K). The peaks are labeled for reference in the text.
Figure 4.
Stacked 1H NMR spectra of 5 in the region 3.5-4.2 ppm
at the temperatures indicated (400 MHz, 1,1,2,2-tetrachloroethane-
d2).
As this coupling is only observed in the keto-enamine
form and not the enol-imine form of salicylaldimines, we
conclude that macrocycle 9 is predominantly the keto-
enamine form (9-keto). Tautomerization of naphthalenedi-
imines is known,14 and it is also known that tautomerization
of resorcinoldiimines is too high in energy to observe in the
ground state.15 We have previously observed keto-enol
tautomerism in a Schiff base macrocycle.14 Macrocycle 9 is
the first to have both keto-enamine and enol-imine tau-
tomers in the same cycle.
To explore the possibility that the tautomerization of the
macrocycle, as observed in 9, affects the kinetics of cone
inversion, we conducted VT-NMR studies of both 5 and 9
at high temperature. Qualitatively, macrocycle 9 with
naphthalene rings shows a higher barrier to inversion
(coalescence of the methylene OCH2C11H23 protons at 65
°C) than 5 (55 °C). The dynamic NMR line shapes at high
temperature were fit with use of TopSpin 2.1 (see the SI).
From the line shape analysis, we determined that the inversion
barrier for macrocycle 9 is ca. 37 kJ mol-1 higher than that of
macrocycle 5, Table 1. From molecular modeling, we found
(14) Gallant, A. J.; Yun, M.; Sauer, M.; Yeung, C. S.; MacLachlan,
M. J. Org. Lett. 2005, 7, 4827–4830.
(15) Sauer, M.; Yeung, C.; Chong, J. H.; Patrick, B. O.; MacLachlan,
M. J. J. Org. Chem. 2006, 71, 775–788.
1022
Org. Lett., Vol. 12, No. 5, 2010

Table 1. Kinetic Parameters for High-Temperature Cone
Conformation Interconversion from H NMR Spectroscopy
Table 2. Binding Constants (Kassoc) for the Complexes Formed
between Macrocycle 5 or 9 and Guestsa
1
macrocycle Ea, kJ mol-1 ∆Hq, kJ mol-1 ∆Sq, J K-1 mol-1
Kassoc (M-1) for guests 10+-13+
macrocycle
10+
11+
12+
13+
5
9
110 ( 4
147 ( 13
107 ( 4
143 ( 13
119 ( 12
190 ( 40
5
9
19000 ( 6000 2900 ( 200 420 ( 10 50 ( 9
6300 ( 800
b
b
760 ( 70
-
-
a
Determined by H NMR spectroscopy at 300 K in CDCl3. b Binding
1
inversion of macrocycle 9 will change the orientation of the
N-H bond. The intramolecular NsH···OdC hydrogen bond-
ing is expected to reduce the mobility of the naphthalene-
containing rings.
The cone shape adopted by the macrocycles, resembling
calixarenes, suggested that these cycles could bind cationic
guests. Indeed, both macrocycles 5 and 9 are supramolecular
hosts for organic cations, such as pyridinium and ammonium
derivatives. Figure 5 shows a representative NMR spectrum
was too small to determine by NMR spectroscopy.
to form 1:1 complexes, Table 2. Neutral molecules tested
and PPh4Br, which is too large to fit in the macrocycles, do
not bind.
There are a few interesting conclusions to draw from the
binding studies (Table 2). First, the binding constants are
largest for 10+Cl-, which has a pyridyl ring, indicating that
π-π interactions probably play a role in stabilizing the
host-guest complexes. Second, the binding constants for
macrocycle 5 are about four times larger than those for
macrocycle 9, and we could not measure the binding of two
of the guests to 9. Even though 9 has more aromatic rings
to potentially interact with a guest, it has weaker interactions.
We attribute this difference to the keto-enamine tautomer-
ization of the naphthalenediimine moieties, which should
render the carbonyl groups less electronegative than the
hydroxyl groups in 5, and thus yield weaker electrostatic
interactions with a cationic guest.
In summary, we have described a simple synthesis of novel
unsymmetrical, isosceles triangle-shaped Schiff base mac-
rocycles. These macrocycles adopt static cone-shaped con-
formations at low temperature, but can rapidly interconvert
at high temperature. Differences in the inversion rate and
the guest-binding constants of these new macrocycles
indicate that keto-enol tautomerization plays a role in
modifying their properties.
Figure 5.
(a) Partial 1H NMR spectrum of macrocycle 5 from 3.5
to 15 ppm (400 MHz, CD2Cl2, 298 K). (b) Partial 1H NMR spectrum
of a mixture of 10+Cl- and macrocycle 5 (400 MHz, CD2Cl2, 298
1
K, [10+]:[5] ) 3:1). (c) Partial H NMR spectrum of pyridinium
chloride 10+Cl- (400 MHz, CD2Cl2, 298 K).
of the changes observed when cetylpyridinium chloride
(10+Cl-) was added to 5. The formation of a complex formed
by macrocycle 5 and cetylpyridinium chloride (10+⊂5) was
also verified by a 2-D ROESY spectrum, a MALDI-TOF
mass spectrum, and a Job plot, and the UV-vis spectrum
showed small changes (see the SI). Other organic cations
(e.g., cetyltrimethylammonium bromide (11+Br-), tetraeth-
ylammonium bromide (12+Br-), and tetrabutylammonium
bromide (13+Br-)) also bind inside of macrocycles 5 and 9
Acknowledgment. We thank Pete Frischmann (UBC) for
assistance with the dynamic NMR analysis. We are also
grateful to NSERC for funding (Discovery Grant).
Supporting Information Available: Synthetic procedures,
full characterization of new compounds, kinetic data, and
host-guest binding data. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL100028S
Org. Lett., Vol. 12, No. 5, 2010
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