Hydrogen-bonded aryl amide macrocycles: Synthesis, single-crystal structures, and stacking interactions with fullerenes and coronene

Article abstract of DOI:10.1021/jo702046f

(Figure Presented) Six hydrogen-bonded shape-persistent aryl amide macrocycles have been prepared by using one-step and (for some) step-by-step approaches. From the one-step reactions, 3 + 3, 2 + 2, or even 1 + 1 macrocycles were obtained in modest to goo

Full text of DOI:10.1021/jo702046f

Hydrogen-Bonded Aryl Amide Macrocycles: Synthesis,
Single-Crystal Structures, and Stacking Interactions with Fullerenes
and Coronene
Yuan-Yuan Zhu, Chuang Li, Guang-Yu Li, Xi-Kui Jiang, and Zhan-Ting Li*
State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
ztli@mail.sioc.ac.cn
ReceiVed September 18, 2007
Six hydrogen-bonded shape-persistent aryl amide macrocycles have been prepared by using one-step
and (for some) step-by-step approaches. From the one-step reactions, 3 + 3, 2 + 2, or even 1 + 1
macrocycles were obtained in modest to good yields. The reaction selectivity was highly dependent on
the structures of the precursors. The X-ray structural analysis of two methoxyl-bearing macrocycles revealed
intramolecular hydrogen bonding and weak intermolecular stacking interaction; no column-styled stacking
1
structures were observed. The H (DOSY) NMR, UV-vis, and fluorescent experiments indicated that
the new rigidified macrocycles complex fullerenes or coronene in chloroform through intermolecular
π-stacking interaction. The association constants of the corresponding 1:1 complexes have been determined
if the stacking was able to cause important fluorescent quenching of the macrocycles or coronene.
Introduction
of the intermediates, which are stabilized by successive in-
tramolecular hydrogen bonding. In addition, some of the
macrocycles have been revealed to be capable of binding
guanidinium ions or DNA G-quadruplex through intermolecular
hydrogen bonding or stacking interaction.4b,5a
Shape-persistent macrocycles have received considerable
attention for their unique structures, properties, and applications
in supramolecular and materials chemistry.1,2 Many of these
rigidified molecules are developed based on the oligomeric
m-aryleneethynylene skeletons,3 which are usually prepared by
transition metal-catalyzed multistep coupling reactions. More
recently, one-step preparation of shape-persistent aryl amide or
urea macrocycles has been reported from hydrogen bonding-
mediated monomers.4,5 The high efficiency of such an approach
is greatly attributed to the preorganized folded conformations
(3) (a) Zhao, D.; Moore, J. S. J. Org. Chem. 2002, 67, 3548. (b) Grave,
C.; Lentz, D.; Schaefer, A.; Samori, P.; Rabe, J. P.; Franke, P.; Schlu¨ter,
A. D. J. Am. Chem. Soc. 2003, 125, 6907. (c) Odermatt, S.; Alonso-Gomez,
J. L.; Seiler, P.; Cid, M. M.; Diederich, F. Angew. Chem., Int. Ed. 2005,
44, 5074. (d) Campbell, K.; Ooms, K. J.; Wasylishen, R. E.; Tykwinski, R.
R. Org. Lett. 2005, 7, 3397. (e) Zhang, W.; Brombosz, S. M.; Mendoza, J.
L.; Moore, J. S. J. Org. Chem. 2005, 70, 10198. (f) Venturi, M.; Marchioni,
F.; Ribera, B. F.; Balzani, V.; Opris, D. M.; Schlu¨ter, A. D. ChemPhysChem
2006, 7, 229. (g) Seo, S. H.; Jones, T. V.; Seyler, H.; Peters, J. O.; Kim, T.
H.; Chang, J. Y.; Tew, G. N. J. Am. Chem. Soc. 2006, 128, 9264. (h) Shu,
L.; Mayor, M. Chem. Commun. 2006, 4134.
(4) (a) Jiang, H.; Le´ger, J.-M.; Guionneau, P.; Huc, I. Org. Lett. 2004,
6, 2985. (b) Shirude, P. S.; Gillies, E. R.; Ladame, S.; Godde, F.; Shin-ya,
K.; Huc, I.; Balasubramanian, S. J. Am. Chem. Soc. 2007, 129, 11890.
(5) (a) Yuan, L.; Feng, W.; Yamato, K.; Sanford, A. R.; Xu, D.; Guo,
H.; Gong, B. J. Am. Chem. Soc. 2004, 126, 11120. (b) Sanford, A. R.;
Yuan, L.; Feng, W.; Yamato, K.; Flowers, R. A.; Gong, B. Chem. Commun.
2005, 4720. (c) Zhang, A.; Han, Y.; Yamato, K.; Zeng, X. C.; Gong, B.
Org. Lett. 2006, 8, 803.
(1) (a) Moore, J. S. Acc. Chem. Res. 1997, 30, 402. (b) Grave, C.;
Schlu¨ter, A. D. Eur. J. Org. Chem. 2002, 3075. (c) Zhao, D. H.; Moore, J.
S. Chem. Commun. 2003, 807. (d) Yamaguchi, Y.; Yoshida, Z.-i. Chem.
Eur. J. 2003, 9, 5430. (e) Ho¨ger, S. Chem. Eur. J. 2004, 10, 1320. (f) Ho¨ger,
S. Angew. Chem., Int. Ed. 2005, 44, 3806. (g) Zhang, W.; Moore, J. S.
Angew. Chem., Int. Ed. 2006, 45, 4416.
(2) (a) Chong, Y. S.; Shimizu, K. D. Synthesis 2002, 1239. (b)
MacLachlan, M. J. Pure Appl. Chem. 2006, 78, 873. (c) He, L.; An, Y.;
Yuan, L.; Feng, W.; Li, M.; Zhang, D.; Yamato, K.; Zheng, C.; Zeng, X.
C.; Gong, B. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 10850.
10.1021/jo702046f CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/31/2008
J. Org. Chem. 2008, 73, 1745-1751
1745

Zhu et al.
CHART 1
We recently demonstrated that hydrogen bonding-induced aryl
Results and Discussion
amide or hydrazide foldamers could function as new synthetic
receptors for binding neutral and ionic species or preorganized
scaffolds for assembling well-defined architectures.6,7 We also
found that several folded structures resembled the extended
conjugated systems, such as porphyrins, phthalocyanines, or
rigidified phenylene-acetylene macrocycle,8,9 to stack with
fullerenes in both the solution and solid state.10 In search of
new compact synthetic receptors,11 we became interested in
preparing new hydrogen bonding-mediated aryl amide macro-
cycles. We herein describe the synthesis of six new aryl amide
macrocycles and their stacking behaviors with fullerenes and
conorene.
We have previously established the intramolecular five- and
six-membered F‚‚‚H-N hydrogen-bonding motif and utilized
it to direct folded or helical conformation of aryl amide
oligomers.7d,10,12 Different from the MeO‚‚‚H-N hydrogen-
bonded folded structures,6a,7e,i in which the inwardly located
methyl groups were deviated from the rigidified backbones due
to the steric hindrance and intrinsic angular requirement of the
ether bonds, the F‚‚‚H-N hydrogen-bonded foldamers possessed
more planar extended skeletons. To compare the efficiency of
discrete hydrogen-bonding motifs in directing macrocyclization
and also to explore their possible influence on the structures of
the resulting macrocycles, we used the one-step method to pre-
pare macrocycles from the reactions of the corresponding diacyl
chlorides and diamines.4,5 To our surprise, macrocycles 1-4
with a changing number of segments were obtained (Chart 1).
Mixing the identical molar equiv of compounds 57e and 613
(38 mM) in THF in the presence of triethylamine at room
temperature led to the formation of 3 + 3 macrocycle 1 in 40%
yield as the sole isolated product (Scheme 1).14 In contrast, under
the identical conditions, the reaction of 5 with 7 (1:1, 38 mM)
afforded three macrocyclic products 2a, 2b, and 2c in 10%,
40%, and 30% yields, respectively. The formation of the smaller
1 + 1 and 2 + 2 products should reflect the shrunk shape of
pyridine relative to that of benzene.4,12b The reaction of diamine
8 with 9 (1:1, 38 mM) gave rise to the expected 3 + 3 product
(6) For reviews on aryl amide foldamers, see: (a) Gong, B. Chem. Eur.
J. 2001, 7, 4336. (b) Huc, I. Eur. J. Org. Chem. 2004, 17. (c) Sanford, A.;
Yamato, K.; Yang, X. W.; Yuan, L. H.; Han, Y. H.; Gong, B. Eur. J.
Biochem. 2004, 271, 1416. (d) Lockman, J. W.; Paul, N. M.; Parquette, J.
R. Prog. Polym. Sci. 2005, 30, 423. (e) Li, Z.-T.; Hou, J.-L.; Li, C.; Yi,
H.-P. Chem. Asian J. 2006, 1, 766.
(7) (a) Hou, J.-L.; Shao, X.-B.; Chen, G.-J.; Zhou, Y.-X.; Jiang, X.-K.;
Li, Z.-T. J. Am. Chem. Soc. 2004, 126, 12386. (b) Wu, Z.-Q.; Jiang, X.-K.;
Zhu, S.-Z.; Li, Z.-T. Org. Lett. 2004, 6, 229. (c) Zhu, J.; Wang, X.-Z.;
Chen, Y.-Q.; Jiang, X.-K.; Chen, X.-Z.; Li, Z.-T. J. Org. Chem. 2004, 69,
6221. (d) Li, C.; Ren, S.-F.; Hou, J.-L.; Yi, H.-P.; Zhu, S.-Z.; Jiang, X.-K.;
Li, Z.-T. Angew. Chem., Int. Ed. 2005, 44, 5725. (e) Yi, H.-P.; Chuang Li,
C.; Hou, J.-L.; Jiang, X.-K.; Li, Z.-T. Tetrahedron 2005, 61, 7974. (f) Zhu,
J.; Lin, J.-B.; Xu, Y.-X.; Shao, X.-B.; Jiang, X.-K.; Li, Z.-T. J. Am. Chem.
Soc. 2006, 128, 12307. (g) (i) Yi, H.-P.; Wu, J.; Ding, K.-L.; Jiang, X.-K.;
Li, Z.-T. J. Org. Chem. 2007, 72, 870. (h) Li, C.; Wang, G.-T.; Yi, H.-P.;
Jiang, X.-K.; Li, Z.-T.; Wang, R.-X. Org. Lett. 2007, 9, 1797.
(8) (a) Konishi, T.; Ikeda, A.; Shinkai, S. Tetrahedron 2005, 61, 4881.
(b) Boyd, P. D. W.; Reed, C. A. Acc. Chem. Res. 2006, 38, 235. (c) Kawase,
T.; Kurata, H. Chem. ReV. 2006, 106, 5250. (d) Tashiro, K.; Aida, T. Chem.
Soc. ReV. 2007, 36, 189.
(9) Pan, G.-B.; Cheng, X.-H.; Ho¨ger, S.; Freyland, W. J. Am. Chem.
Soc. 2006, 128, 4218.
(10) Li, C.; Zhu, Y.-Y.; Yi, H.-P.; Li, C.-Z.; Jiang, X.-K.; Li, Z.-T.; Yu,
Y.-H. Chem. Eur. J. 2007, 13, 9990.
(11) An intramolecular hydrogen-bonding, free aryl amide-based mac-
rocyclic receptor for anions has been reported: Choi, K.; Hamilton, A. D.
J. Am. Chem. Soc. 2003, 125, 10241.
(12) (a) Zhao, X.; Wang, X.-Z.; Jiang, X.-K.; Chen, Y.-Q.; Li, Z.-T.;
Chen, G.-J. J. Am. Chem. Soc. 2003, 125, 15128. (b) Zhu, Y.-Y.; Wu, J.;
Li, C.; Zhu, J.; Hou, J.-L.; Li, C.-Z.; Jiang, X.-K.; Li, Z.-T. Cryst. Growth
Des. 2007, 7, 1490.
(13) Doxsee, K. M.; Feigel, M.; Stewart, K. D.; Canary, J. W.; Knobler,
C. B.; Cram, D. J. J. Am. Chem. Soc. 1987, 109, 3098.
(14) Under the identical conditions, a similar 3 + 3 macrocyclic product
was also generated from the reaction of 5 with isophthaloyl dichloride, as
evidenced by MALDI-TOF. The attempt of separating this product did not
succeed. We thank one of the reviewers for critical comments on this issue.
1746 J. Org. Chem., Vol. 73, No. 5, 2008

Hydrogen-Bonded Aryl Amide Macrocycles
SCHEME 1
SCHEME 2
3 in 45% yield. However, its reaction with pyridine derivative
7 of the same concentration (38 mM) afforded 2 + 2 compound
4 as the sole macrocycle. The introduction of the N,N-di-n-
octylamide groups rendered compounds 1 and 2 good solubility
in organic solvents. It is noteworthy that, with less polar
dichloromethane or chloroform as solvent,4,5 the macrocycles
could also be prepared. Nevertheless, the yields of the products,
usually 10-15%, were pronouncedly decreased. When the
reactions were conducted at lower concentrations, the yields of
the macrocycles were increased modestly. For example, com-
pound 1 was obtained in 45-52% yields when the concentra-
tions of 5 and 6 were reduced to the range of 20 to 3.5 mM.
hydrogen bonding. Diluting the solution of the macrocycles in
chloroform-d from 5.0 to 0.2 mM did not cause salient change
of their chemical shifts, indicating that there was no significant
intermolecular hydrogen bonding or aromatic stacking. The NH
signals of 2a, 2b, and 2c appeared at 9.99, 10.55, and 9.61 ppm,
Compounds 2a, 2b, and 2c were separated by careful column
1
chromatography. Due to their structural symmetry, their H
1
respectively, in the H NMR spectra (5 mM). The fact that 2b
NMR spectra in CDCl3 all exhibited four signals in the
downfield area. The signal of the amide protons appeared at
9.99, 10.55, and 9.61 ppm, respectively. CPK (Corey-Pauling-
Koltun) modeling showed that the amide units of 2a take the
trans conformation as a result of the small size of the backbone
and no intramolecular hydrogen bonds are formed. No similar
products were obtained from the reactions of 6 or 9. Therefore,
its formation should be attributed to the small spatial hindrance
and shrunk conformation of the pyridine unit.
displayed a substantially large chemical shift suggested that this
macrocycle had a low intramolecular tension and consequently
strong hydrogen bonds, which is also consistent with its high
yield relative to those of 2a and 2c.
After numerous attempts to crystallize the macrocycles, single
crystals of 3 and 4 suitable for X-ray analysis were grown by
slow evaporation of their chloroform-ethyl acetate solution.
Their solid state structures are provided in Figures 1 and 2. As
expected, the amide protons of both compounds are involved
in intramolecular three-center hydrogen bonding. No column-
styled stacking was observed in the solid state structures,15
possibly because the methyl groups prevented intermolecular
face-to-face stacking. For macrocycle 3, four adjacent methyl
groups were located on one side of the backbone, while another
two pointed to the other side. One of the diamidobenzene units
stacked with the identical unit of another molecule, giving rise
to an extended slip-styled array structure (Figure 1). In the solid
state of 4 (Figure 2), the two interior methyl groups pointed to
both sides of the backbone, respectively. The two pyridine rings
were orientated in one plane and the two benzene rings deviated
from the plane considerably. As a result, a chair-styled
To explore the influence of the different hydrogen-bonding
motifs on the macrocyclization, compounds 1 and 2c were also
prepared by using the step-by-step approach. The synthetic
routes are provided in Schemes 2 and 3, respectively. As
expected, the yields of the cyclization reactions were higher
than those of the above one-step reactions, because only two
amide bonds were formed in these reactions. The yields of the
macrocyclization reactions are also quite close, implying that
the F‚‚‚H-N and N‚‚‚H-N hydrogen-bonding motifs in the
precursors have comparable capacity in directing the macrocy-
clization.
Macrocycles 1-4 have been characterized by the 1H and 13
C
NMR spectroscopy and (high resolution) mass spectrometry or
X-ray single crystal analysis. Due to the high structural
(15) (a) Shimizu, L. S.; Hughes, A. D.; Smith, M. D.; Davis, M. J.; Zhang,
B. P.; Zur Loye, H.-C.; Shimizu, K. D. J. Am. Chem. Soc. 2003, 125, 14972.
(b) Gibson, S. E.; Lecci, C. Angew. Chem., Int. Ed. 2006, 45, 1364. (c)
Pasini, D.; Ricci, M. Curr. Org. Synth. 2007, 4, 59.
1
symmetry, the H NMR spectra of all the macromolecules in
CDCl3 displayed one signal for the amide protons at the down-
field area, supporting that they were involved in intramolecular
J. Org. Chem, Vol. 73, No. 5, 2008 1747

Zhu et al.
SCHEME 3
FIGURE 2. The solid state of 2 + 2 macrocycle 4.
FIGURE 3. The solid state of compound 15.
conformation was produced. Extended array structures were
formed by intermolecular pyridine-pyridine stacking, but no
aromatic stacking was observed for the diamidobenzene units,
which may be attributed to the steric effect of the inwardly
located methyl groups. The fact that no two- or six-residue
macrocycle was produced from the reaction of 7 with 8 indicated
that (1) the shrunk shape of the 2,6-disubstituted pyridine unit
was favorable for the formation the 2 + 2 product and (2) the
larger methoxyl group in 8 suppressed the formation of the even
smaller 1 + 1 macrocycle similar to 2a, which were in
accordance with the above result. These observations clearly
revealed the great influence of the size of the hydrogen-bonded
groups on the distribution of the products. The solid state
structure of intermediate 15 is provided in Figure 3. The
hydrogen-bonded N‚‚‚H distance is 2.249 Å, which is very close
to the value of 2.254 Å for that of macrocycle 4. Since no
intramolecular spatial repulsion was observed for 15, this
observation also implied that no large skeleton tension existed
in 4 and the 2,6-diaminopyridine derivatives preferred to form
more compact folded or macrocyclic structures.16
It is well-established that rigidified macrocycles are able to
stack intermolecularly.17 Our recent study also revealed that
some of the hydrogen bonding-induced foldamers have a great
tendency to stack with fullerenes in both the solution and solid
states.10 The possibility of a similar interaction between the new
rigidified macrocycles and fullerenes was therefore explored
1
with the H NMR experiments. Adding 1 equiv of C60 to the
solution of 1 (5 mM) in CS2-CDCl3 (1:2 v/v) caused small
but distinct downfield shifting for the NH signal (Figure 4).18,19
Similar shifting was also observed for the mixture of 1 and C70.
The chemical shifts for the signals in the downfield region in
the absence and presence of fullerenes are listed in Table 1 (vide
infra). These observations were consistent with those revealed
(16) Hamuro, Y.; Geib, S. J.; Hamilton, A. D. J. Am. Chem. Soc. 1996,
118, 7529.
(17) (a) Diederich, F.; Go´mez-Lo´pez, M. Chem. Soc. ReV. 1999, 28, 263.
(b) Haino, T.; Yanase, M.; Fukazawa, Y. Angew. Chem., Int. Ed. 1998, 37,
997. (c) Ikeda, A.; Yoshimura, M.; Udzu, H.; Fukuhara, C.; Shinkai, S. J.
Am. Chem. Soc. 1999, 121, 4296. (d) Atwood, J. L.; Barbour, L. J.; Heaven,
M. W.; Raston, C. L. Angew. Chem., Int. Ed. 2003, 42, 3254.
(18) CS2 was used for improving the solubility of fullerenes.
FIGURE 1. The solid state of 3 + 3 macrocycle 3.
1748 J. Org. Chem., Vol. 73, No. 5, 2008

Hydrogen-Bonded Aryl Amide Macrocycles
2b, 2c, and 4, implying that their interactions with these
cyclophanes were much weaker.
Adding C60 or C70 to the solution of 1 or 3 in chloroform
also caused significant decrease of the absorption bands of the
macrocycles (see the Supporting Information), which represents
additional evidence for the formation of the stacking complexes.
In addition, the emissions of both macrocycles could be
quenched remarkably by fullerenes. On the base of the
fluorescent titrations (Figure 6), we determined the association
constants (Kassoc) of complexes 1‚C60, 1‚C70, 3‚C60, and 3‚C70
in chloroform to be ca. 5.9 × 104, 9.1 × 104, 2.5 × 104, and
4.1 × 104 M-1, respectively, by using the Benesi-Hildebrand
(BH) plot.22 The values of C70 are notably larger than those of
C60, implying that its stacking with the macrocycles mainly took
place at its extended equatorial region.8
Because fullerenes are electron deficient,23 it is reasonable
to consider that their stacking with fluorine-bearing 1 was not
driven by the electrostatic interaction. Since pyridine-incorpo-
rated 2c did not exhibit similar capacity of strongly interacting
with fullerenes, we propose that the stacking between 1 and
fullerenes most likely resulted from a combination of the
extended fluoroarene-π24 and solvophobic interactions. The fact
that the values of 3 were smaller than those of 1 may be simply
ascribed to the steric hindrance of the six methyl groups at its
central area.
The stacking behavior of the macrocycles with planar
coronene (18) was also investigated.25 The 1H NMR spectra of
their 1:1 solutions in CDCl3 (5 mM) displayed small shifting
for their signals in the downfield area. The largest change was
observed for the NH signal of 1 (∆δ ) -0.023 ppm). The
emission of coronene were remarkably quenched by 2c, 3, and
4 (see the Supporting Information). Also on the base of the
fluorescent titrations, we estimated the Kassoc values of com-
plexes 2c‚18, 3‚18, and 4‚18 in chloroform to be 1.2 × 103,
1.8 × 103, and 9.1 × 103 M-1, respectively. The value of 3‚18
is significantly lower than that of 3‚C60. Surprisingly, the binding
affinity of smaller 4 is considerably greater than that of 2c and
3, which may reflect that its four aryl units could match well
for interacting with coronene as a result of the reduced size.
Unexpectedly, adding 1 to the solution of coronene did not lead
to similar quenching for the emission of the latter. Considering
the great capacity of 1 to interact with fullerenes, this result
should not be used as evidence to exclude stacking interaction
between 1 and coronene. We consider this may just reflect that
there was no efficient intermolecular electron or energy transfer
between them.
FIGURE 4. The downfield region of the 1H NMR spectra (500 MHz)
of the solutions of 1 + C60, 1, and 1 + C70 in CDCl3 at 25 °C (5 mM).
TABLE 1. Diffusion Coefficients of 1 and 3 in the Absence and
Presence of Fullerenes (1:1, 5 mM), Probed with Their Downfield
Signals in CDCl3 and CS2 (1:1, v/v)
1
1 + C60
1 + C70
δ
D
δ
D
δ
D
proton (ppm) (10-9 m2/s) (ppm) (10-9 m2/s) (ppm) (10-9 m2/s)
H-1
H-2
H-3
H-4
8.962
8.173
8.057
7.271
10.66
10.97
11.23
11.58
8.965
8.171
8.057
7.272
8.57
8.88
8.88
8.95
8.966
8.170
8.058
7.275
9.72
10.02
10.12
10.27
3
3 + C60
3 + C70
δ
D
δ
D
δ
D
proton (ppm) (10-9 m2/s) (ppm) (10-9 m2/s) (ppm) (10-9 m2/s)
H-1
H-2
H-3
H-4
9.404
8.295
8.177
7.463
11.88
12.32
12.57
11.98
9.400
8.295
8.175
7.462
6.98
7.43
7.37
7.30
9.404
8.292
8.176
7.463
7.08
7.16
7.22
7.00
for F‚‚‚H-N hydrogen-bonded foldamers and fullerenes and
supported intermolecular interactions also existed between the
macrocycle and the fullerenes.10 Under the identical conditions,
smaller or no shifting was observed for the signals of 2-4 in
the presence of C60 or C70.
More solid evidence came from the diffusion-ordered spec-
troscopic (DOSY) experiments in CDCl3 and CS2 (1:1, v/v).20,21
The diffusion coefficients (D) obtained for macrocycles 1 and
3 in the absence and presence of C60 or C70 are presented in
Table 1. It can be found that the presence of C60 or C70 led to
significant and consistent decrease of the D values of the
macrocycles probed with all their four signals at the downfield
area. Moreover, the values of the same systems obtained with
different probes displayed a similar changing tendency. All these
observations supported that close proximity took place for the
two species (Figure 5), leading to an increase of the apparent
size or molecular weight of the macrocycles. Under the identical
conditions, the addition of fullerenes could only produce
remarkably smaller change for the diffusion coefficients of 2a,
Conclusions
We have prepared six amide-derived macrocycles that are
rigidified by intramolecular hydrogen bonding. The shape or
(22) The Benesi-Hildebrand (BH) plots were used to evaluate the
association constants, which yielded a 1:1 stoichiometry for all the
complexing systems. Applying the titrating data to a 1:2 or 2:1 stoichiometry
gave rise to poor results. For the establishment of the 1:1 complexing
stoichiometry, see: (a) Benesi, A. H.; Hildebrand, J. H. J. Am. Chem. Soc.
1949, 71, 2703. (b) Abou-Zied, O. K. Spectrochim. Acta A 2005, 62, 245.
(23) (a) Martin, N.; Sanchez, L.; Illescas, B.; Perez, I. Chem. ReV. 1998,
98, 2527. (b) Guldi, D. M. Chem. Commun. 2000, 321.
(24) (a) Prasanna, M. D.; Row, T. N. G. Cryst. Eng. 2000, 3, 135. (b)
Babudri, F.; Farinola, G. M.; Naso, F.; Ragni, R. Chem. Commun. 2007,
1003.
(25) (a) Ermer, O.; Neudorft, J. HelV. Chim. Acta 2001, 84, 1268. (b)
Yoshizawa, M.; Nakagawa, J.; Kumazawa, K.; Nagao, M.; Kawano, M.;
Ozeki, T.; Fujita, M. Angew. Chem., Int. Ed. 2005, 44, 1810.
(19) It has been reported that fullerenes usually cause small or imper-
ceptible shifting of the signals of macrocyclic receptors in the 1H NMR
spectra even in the case of strong complexation, see ref 10 and also: (a)
Wang, M.-X.; Zhang, X.-H.; Zheng, Q.-Y. Angew. Chem., Int. Ed. 2004,
43, 838. (b) Gong, H.-Y.; Zhang, X.-H.; Wang, D.-X.; Ma, H.-W.; Zheng,
Q.-Y.; Wang, M.-X. Chem. Eur. J. 2006, 12, 9262. (c) Pe´rez, E. M.; Sierra,
M.; Sa´nchez, L.; Torres, M. R.; Viruela, R.; Viruela, P. M.; Ort´ı, E.; Mart´ın,
N. Angew. Chem., Int. Ed. 2007, 46, 1847.
(20) (a) Gafni, A.; Cohen, Y. J. Org. Chem. 1997, 62, 120. (b) Gafni,
A.; Cohen, Y. J. Org. Chem. 2002, 67, 2639. (c) Zhao, T.; Beckham, H.
W.; Gibson, H. W. Macromolecules 2003, 36, 4833.
(21) Wu, J.; Hou, J.-L.; Li, C.; Wu, Z.-Q.; Jiang, X.-K.; Li, Z.-T.; Yu,
Y.-H. J. Org. Chem. 2007, 72, 2897.
J. Org. Chem, Vol. 73, No. 5, 2008 1749

Zhu et al.
FIGURE 5. Stacking interaction between macrocycles 1 and 3 and C60.
pressure to give crude product 6 as a pale yellow solid. The material
was again dissolved in THF (30 mL). The solution and a solution
of 7a (0.30 g, 0.76 mmol) in THF (30 mL) were then simultaneously
added dropwise to a solution of triethylamine (0.5 mL) in THF
(30 mL) at 0 °C. The mixture was stirred at room temperature for
1 h. The precipitate formed was filtered off and the filtrate
concentrated under a reduced pressure. The resulting residue was
triturated with chloroform (60 mL) and the organic phase washed
with diluted hydrochloric acid (1 N, 20 mL), water (20 mL × 2),
and brine (20 mL) and dried over sodium sulfate. After the solvent
was removed, the crude product was purified by column chroma-
tography (CHCl3/AcOEt 1:1) to afford 1 as a white solid (0.17 g,
40%). Mp 222-224 °C. 1H NMR (CDCl3) δ 8.95 (s, 6 H), 8.32 (s,
6 H), 8.11(t, J ) 6.0 Hz, 6 H), 7.34 (t, J ) 7.8 Hz), 3.30 (s, 6 H),
3.20 (s, 6.0 H), 1.28-1.17 (m, 72 H), 0.86 (s, 9 H), 0.79 (s, 9 H).
13C NMR (CDCl3) δ 170.1, 161.1, 158.6, 156.1, 145.0, 142.6, 136.1,
133.5, 126.0, 125.6, 122.5, 122.3, 116.9, 49.3, 44.9, 31.9, 31.8,
29.7, 29.4, 29.2, 29.1, 28.6, 27.4, 27.1, 26.7, 22.6, 22.6, 14.1. 19F
NMR (CDCl3) δ -115.0 (s, 3 F), -142.6 (s, 3 F). MS (MALDI-
TOF) m/z 1648.6 [M + Na]+, 1664.5 [M + K]+. HRMS (MALDI-
TOF) calcd for C93H124N9O9F6 [M]+ 1624.9421, found 1624.9465.
Macrocycle 2a: White solid. Mp 290-292 °C. 1H NMR (CDCl3)
δ 9.99 (s, 2 H), 8.40 (d, J ) 7.7 Hz, 2 H), 8.08 (t, J ) 7.8 Hz, 1
H), 7.99 (s, 2 H), 3.36 (br s, 2 H), 3.26 (br s, 2 H), 1.57 (br s, 4 H),
1.34-1.18 (m, 20 H), 0.85 (s, 3 H), 0.78 (s, 3 H). 13C NMR (CDCl3)
δ 169.6, 161.0, 148.4, 139.6, 133.6, 125.9, 125.7, 125.6, 117.4,
49.6, 45.3, 31.8, 29.7, 29.2, 28.8, 27.6, 27.4, 27.1, 26.7, 22.6, 14.0.
19F NMR (CDCl3) δ -137.3 (s). MS (MALDI-TOF) m/z 524.1
[M + H]+. HRMS (MALDI-FT) calcd for C30H42N4O3F [M]+
525.3236, found 525.3223.
FIGURE 6. Fluorescent titration spectra of 1 (3.6 × 10-5 M) with
C60 in chloroform at 25 °C (excitation wavelength ) 309 nm). Inset:
The Benesi-Hildebrand (BH) plot (variation of the fluorescence
intensity of 1 with the addition of C60).
geometry of the precursors remarkably affects the structures of
the products. As a result, macrocycles with 1 + 1, 2 + 2, and
3 + 3 segments can be prepared by simply changing the
precursors. The stacking interaction revealed between the new
macrocycles and fullerenes and coronene represents the first
example of its kind observed for unconjugated aromatic amides,
while the strong complexing affinity reflects the cooperativity
of the aromatic units of the macrocycles in strengthening the
stacking. The results provide a new avenue for self-assembling
architectures and materials. We are currently trying to introduce
amino or aldehyde groups to the aryl rings and expect that three-
dimensional column systems will be developed by using the
dynamic covalent approach.26
Macrocycle 2b: White solid. Mp 208-210 °C. 1H NMR (CDCl3)
δ 10.55 (s, 4 H), 8.43 (d, J ) 7.7 Hz, 4 H), 8.22 (t, J ) 7.7 Hz, 2
H), 8.17 (t, J ) 2.8 Hz, 4 H), 3.46 (br s, 4 H), 3.25 (br s, 4 H),
1.69-1.62 (m, 8 H), 1.37-1.16 (m, 40 H), 0.92 (s, 6 H), 0.76 (s,
6 H). 13C NMR (CDCl3) δ 169.7, 160.3, 148.6, 142.9, 141.6, 140.6,
135.0, 126.3, 125.5, 112.4, 49.4, 45.3, 31.8, 29.4, 29.3, 29.0, 28.7,
27.6, 27.2, 26.6, 22.7, 22.5, 14.0. 19F NMR (CDCl3) δ -144.69.
MS (MALDI-TOF) m/z 1071.6 [M + Na]+, 1049.6 [M + H]+.
HRMS (MALDI-FT) calcd for C60H83N8O6F2 [M]+ 1049.6398,
found 1049.6398.
Experimental Section
Macrocycle 2c: White solid. Mp 118-120 °C. 1H NMR (CDCl3)
δ 9.61 (s, 6 H), 8.46 (d, J ) 7.5 Hz, 6 H), 8.15 (t, J ) 7.8 Hz, 3
H), 7.98 (d, J ) 6.9 Hz, 6 H), 3.42-3.31 (m, 12 H), 1.65 (s, 12
H), 1.30-1.21 (m, 60 H), 0.86-0.81 (m, 12 H). 13C NMR (CDCl3)
δ 169.8, 162.1, 148.8, 139.5, 133.4, 126.2, 125.5, 120.0, 49.6, 45.1,
31.8, 29.2, 28.6, 27.5, 27.0, 26.7, 22.6, 14.1. 19F NMR (CDCl3) δ
-139.4 (s, 3 F). MS (MALDI-TOF) m/z 1612 [M + Na]+, 1596.9
[M]+. HRMS (MALDI-TOF) calcd for C90H124N12O9F3 [M]+
1573.9561, found 1573.9575.
General Procedures. See the Supporting Information.
Typical Procedure for the One-Step Synthesis of Macrocycles
1-4. Compound 1: To a solution of 2-fluoroisophthalic acid (0.14
g, 0.76 mmol) in THF (20 mL) was added oxalyl dichloride (1.6
mL, 19.8 mmol) and DMF (0.05 mL). The solution was stirred at
room temperature for 0.5 h and then concentrated under reduced
(26) Corbett, P. T.; Leclaire, J.; Vial, L.; West, K. R.; Wietor, J.-L.;
Sanders, J. K. M.; Otto, S. Chem. ReV. 2006, 106, 3652.
1750 J. Org. Chem., Vol. 73, No. 5, 2008

Hydrogen-Bonded Aryl Amide Macrocycles
Macrocycle 3: White solid. Mp >300 °C dec. 1H NMR (CDCl3)
δ 9.49 (s, 6 H), 8.32 (d, J ) 7.8 Hz, 6 H), 8.22 (s, 6 H), 7.50 (t,
J ) 7.8 Hz, 3 H), 4.06 (s, 9 H), 3.94 (s, 9 H), 2.45 (s, 9 H). 13C
NMR (CDCl3) δ 162.7, 155.2, 136.7, 136.0, 135.8, 130.8, 128.1,
126.2, 118.0, 64.6, 61.5, 21.9. MS (MALDI-TOF) m/z 959.4 [M
+ Na]+. HRMS (MALDI-FT) calcd for C51H48N6O12Na [M]+
959.3222, found 959.3259.
19F NMR (CDCl3) δ -111.3 (s, 2 F), -147.2 (s, 1 F). MS (ESI)
m/z 726.3 [M + H]+. Anal. Calcd for C39H46F3N3O7‚0.5H2O: C,
63.75; H, 6.45; N, 5.72. Found: C, 63.77; H, 6.25; N, 5.55.
1
Compound 16: H NMR (CDCl3) δ 10.40 (s, 2 H), 8.35 (d, J
) 7.8 Hz, 2 H), 8.21 (d, J ) 7.2 Hz, 2 H), 8.03-7.96 (m, 4 H),
3.57 (t, J ) 6.0 Hz, 2 H), 3.28 (t, J ) 4.5 Hz, 2 H), 1.65-1.64 (m,
4 H), 1.30-1.10 (m, 24 H), 0.85-0.75 (m, 6 H). 13C NMR (CDCl3)
δ 169.3, 165.2, 162.1, 162.0, 148.8, 147.1, 145.4, 140.8, 133.6,
128.1, 126.1, 118.9, 48.9, 44.8, 31.7, 29.0, 28.5, 27.5, 26.9, 26.3,
22.5, 14.3. 19F NMR (CDCl3) δ -137.0 (s, 1 F). MS (ESI) m/z
692 [M + H]+. HRMS (ESI) calcd for C37H47N5O7F [M]+
692.3454, found 692.3455. Anal. Calcd for C37H46FN5O7‚H2O: C,
62.61; H, 6.82; N, 9.87. Found: C, 62.25; H, 7.02; N, 9.73.
Macrocycle 4: White solid. Mp >300 °C dec. 1H NMR (CDCl3)
δ 10.79 (s, 4 H), 8.46 (d, J ) 7.5 Hz, 4 H), 8.23 (t, J ) 7.5 Hz, 2
H), 8.00 (s, 4 H), 3.65 (s, 6 H), 2.45 (s, 6 H). 13C NMR (CDCl3)
δ 160.6, 149.2, 140.4, 137.0, 136.0, 130.9, 125.1, 114.3, 61.5, 22.0.
MS (MALDI-TOF) m/z 567 [M + H]+. HRMS (MALDI-FT) calcd
for C30H27N6O6 [M]+ 567.1987, found 567.1985.
Compound 11: To a solution of 2-fluoro-3-(methoxycarbonyl)-
benzoic acid27 (1.00 g, 5.52 mmol) in THF (20 mL) were added
oxalyl dichloride (2.0 mL, 25 mmol) and DMF (0.1 mL). The
solution was stirred at room temperature for 0.5 h and then
concentrated in vacuo. The resulting pale yellow solid 10 was
dissolved in THF (30 mL). This solution was then added dropwise
to a stirred solution of 5 (1.09 g, 2.77 mmol) and triethylamine (4
mL) in THF (30 mL), which was cooled in an ice-bath. Stirring
was continued for 1 h and the solution concentrated under reduced
pressure. The resulting residue was triturated with chloroform (30
mL). After workup, the crude product was purified by column
chromatography (hexane/AcOEt 2:1 to 3:2) to afford 11 as a white
Compound 13: To a solution of 12 (0.65 g, 0.89 mmol) in THF
(20 mL) were added oxalyl dichloride (1.0 mL, 12 mmol) and DMF
(0.1 mL). The solution was stirred at room temperature for 0.5 h
and then concentrated. The resulting pale yellow solid was dissolved
in THF (30 mL) and the solution added slowly to a stirred solution
of 5a (1.65 g, 2.67 mmol) and triethylamine (2 mL) in THF (30
mL) at °C. The solution was stirred for 1 h and concentrated under
reduced pressure. The resulting residue was triturated with chlo-
roform (30 mL). After workup, the crude product was purified by
column chromatography (n-hexane/AcOEt 3:2) to afford 13 as a
pale yellow solid (0.80 g, 60%). 1H NMR (CDCl3) δ 9.15 (d, J )
4.5 Hz, 2 H), 8.85 (d, J ) 10.2 Hz, 2 H), 8.25 (d, J ) 4.8 Hz, 2
H), 8.15-8.10 (m, 4 H), 7.67 (s, 2 H), 7.37 (t, J ) 6.9 Hz, 2 H),
6.59 (d, J ) 5.4 Hz, 2 H), 3.43-3.22 (m, 12 H), 1.04-1.00 (m, 72
H), 0.89 (s, 9 H), 0.82 (s, 9 H). 13C NMR (CDCl3) δ 170.9, 170.1,
161.3, 160.9, 159.5, 156.1, 144.0, 140.8, 135.1, 134.9, 133.5, 133.3,
126.2, 126.1, 125.9, 125.7, 125.1, 123.1, 123.0, 122.8, 116.5, 111.3,
109.8, 60.4, 49.5, 49.2, 45.3, 45.0, 31.8, 31.7, 29.7, 29.4, 29.3, 29.1,
28.6, 27.4, 27.1, 26.6, 22.7, 22.6, 21.0, 14.1. 19F NMR (CDCl3) δ
-114.2 (s, 2 F), -142.7 (s, 1 F), -150.1 (s, 2 F). MS (MALDI-
TOF) m/z 1499.0 [M + Na]+. HRMS (MALDI-TOF) calcd for
C85H123N9O7F5 [M]+ 1476.9460, found 1476.9483.
By using a similar procedure, compound 17 was prepared from
16 and 5 (4 equiv) as a white solid in 60% yield. 1H NMR (CDCl3)
δ 10.00 (s, 2 H), 9.79 (s, 2 H), 8.46 (d, J ) 7.2 Hz, 2 H), 8.41 (d,
J ) 8.1 Hz, 4 H), 8.08 (t, J ) 7.8 Hz, 2 H), 7.71 (d, J ) 5.4 Hz,
2 H), 6.43 (d, J ) 7.2 Hz, 2 H), 3.79 (s, 4 H), 3.34 (s, 6 H), 3.19
(s, 6 H), 1.65-1.50 (m, 12 H), 1.42-1.21 (m, 36 H), 1.18-1.01
(m, 18 H). 13C NMR (CDCl3) δ 175.1, 171.2, 170.0, 161.0, 160.9,
148.9, 148.3, 143.6, 140.5, 139.7, 135.8, 135.7, 134.0, 133.6, 125.9,
125.7, 125.5, 125.3, 114.9, 111.9, 107.9, 49.4, 45.3, 45.1, 31.9,
31.8, 30.7, 29.7, 29.6, 29.5, 29.3, 29.1, 28.7, 27.7, 27.2, 26.7, 22.7,
22.6, 17.7, 14.1. 19F NMR (CDCl3) δ -148.7 (s, 1 F), -153.8 (t,
J ) 33.0 Hz, 2 F). MS (MALDI-FT) m/z 1443.5 [M + H]+. HRMS
(MALDI-TOF) calcd for C83H123N11O7F3 [M]+ 1442.9535, found
1442.9547.
1
solid (1.45 g, 70%). H NMR (CDCl3) δ 8.83 (d, J ) 16.2 Hz, 2
H), 8.33 (t, J ) 7.5 Hz, 2 H), 8.26 (d, J ) 6.6 Hz, 2 H), 8.13 (t,
J ) 7.2 Hz, 2 H), 3.99 (t, J ) 0.9 Hz, 6 H), 3.44 (s, 2 H), 3.24 (s,
2 H), 1.34-1.18 (m, 20 H), 0.88 (s, 3 H), 0.79 (s, 3 H). 13C NMR
(CDCl3) δ 169.9, 164.0, 164.0, 161.2, 160.7, 157.7, 136.7, 136.2,
133.9, 133.8, 126.1, 125.9, 124.8, 124.7, 122.4, 122.2, 119.8, 119.7,
116.3, 53.0, 52.8, 52.5, 49.4, 45.3, 31.8, 31.7, 31.6, 29.4, 29.3, 29.1,
28.7, 27.5, 27.2, 26.7, 22.7, 22.6, 14.1, 14.0. 19F NMR (CDCl3)
δ -112.1 (d, t, J1 ) 16.8 Hz, J2 ) 6 Hz, 2 F), -144.2 (s, 1 F).
MS (MALDI-TOF) m/z 754.5 [M + H]+. Anal. Calcd for
C41H50F3N3O7: C, 65.32; H, 6.69; N, 5.57. Found: C, 65.55; H,
6.79; N, 5.46.
By using a similar procedure, compound 15 was prepared in 65%
yield as white solid from 5a and 14.28 1H NMR (CDCl3) δ 10.36
(s, 2 H), 8.47 (d, J ) 8.1 Hz, 2 H), 8.36-8.30 (m, 4 H), 8.10 (t,
J ) 7.8 Hz, 2 H), 4.07 (s, 6 H), 3.48 (t, J ) 7.8 Hz, 2 H), 3.27 (t,
J ) 7.8 Hz, 2 H), 1.67-1.59 (m, 4 H), 1.37-1.12 (m, 20 H), 0.88
(t, J ) 6.6 Hz, 6 H). 13C NMR (CDCl3) δ 170.0, 164.7, 161.3,
149.5, 146.8, 145.6, 142.3, 139.0, 134.1, 134.0, 127.8, 126.1, 126.0,
125.6, 115.4, 53.1, 49.4, 45.3, 31.8, 29.4, 29.3, 29.1, 28.7, 27.6,
27.2, 26.7, 22.7, 14.1, 1.0. 19F NMR (CDCl3) δ -144.1 (s, 1 F).
MS (ESI) m/z 720.3 [M + H]+. Anal. Calcd for C39H50FN5O7: C,
65.07; H, 7.00; N, 9.73. Found: C, 65.05; H, 7.02; N, 9.63.
Compound 12: A solution of 11 (1.25 g, 1.66 mmol) and lithium
hydroxide (0.24 g, 10.0 mmol) in water (50 mL) and THF (10 mL)
was stirred at room temperature for 2 h. Hydrochloric acid (2 N)
was added dropwise to pH 5 and then the mixture was concentrated
under reduced pressure. The resulting residue was suspended in
water (5 mL). The precipitate formed was filtered, washed with
water, and recrystallized from ethanol to give 12 as a white solid
Acknowledgment. This work was financially supported by
the National Natural Science Foundation (Nos. 20732007,
20425208, 20572126, 20621062, 20672137) and the National
Basic Research Program (2007CB808000) of China.
1
(1.14 g, 95%). H NMR (CDCl3) δ 8.94 (d, J ) 20.4 Hz, 2 H),
8.47-8.42 (m, 4 H), 8.24 (t, J ) 7.5 Hz, 2 H), 7.40 (t, J ) 7.5 Hz,
2 H), 3.49 (s, 2 H), 3.27 (s, 2 H), 1.38-1.19 (m, 24 H), 0.92 (s, 3
H), 0.78 (s, 3 H). 13C NMR (DMSO-d6) δ 168.9, 164.6, 162.6,
159.1, 157.0, 134.1, 132.7, 128.9, 128.2, 125.9, 125.4, 124.4, 120.2,
119.0, 48.6, 44.4, 31.2, 28.6, 28.5, 28.1, 27.0, 26.4, 25.9, 22.0, 13.9.
Supporting Information Available: General experimental
procedures, UV-vis and fluorescent spectra of partial complexes,
the simulated diffusion decay curves of 1, 1 + C60, and 1 + C70,
1H NMR spectra of new compounds, and CIF files of 3, 4, and 15.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(27) Wang, Q.-C.; Qu, D.-H.; Ren, J.; Chen, K.; Tian, H. Angew. Chem.,
Int. Ed. 2004, 43, 2661.
(28) Wang, X.-B.; Dacres, J. E.; Yang, X.; Broadus, K. M.; Lis, L.; Wang,
L.-S.; Kass, S. R. J. Am. Chem. Soc. 2003, 125, 296.
JO702046F
J. Org. Chem, Vol. 73, No. 5, 2008 1751