Recognition Through Self-Assembly. A Quadruply-Hydrogen-Bonded, Strapped Porphyrin Cleft That Binds Dipyridyl Molecules and A [2]Rotaxane

Article abstract of DOI:10.1021/jo0351872

Quadruply-hydrogen-bonded porphyrin homodimer Zn1·Zn1 has been designed, assembled, and evaluated as a supramolecular cleft-featured receptor for its ability to bind dipyridyl guests in chloroform-d. Monomer Zn1 consists of a 2-ureidopyrimidin-4(1H)-one unit, which was initially reported by Meijer et al., and a zinc porphyrin unit. The zinc porphyrin is strapped with an additional aliphatic chain for controlling the atropisomerization of porphyrin. The 2-ureidopyrimidin-4(1H)-one unit dimerizes exclusively in chloroform even at the dilute concentration of 10-4 M, while the two "strapped" zinc porphyrin units of the homodimer provide additional binding sites for selective guest recognition. ¹H NMR studies indicate that the new homodimer Zn1·Zn1 adopts an S-type conformation due to strong donor-acceptor interaction between the electron-rich porphyrin units and the electron-deficient 2-ureidopyrimidin-4(1H)-one unit. ¹H NMR, UV-vis, and vapor pressure osmometry investigations reveal that Zn1·Zn1 could function as a new generation of assembled supramolecular cleft, to be able to not only efficiently bind linear dipyridyl molecules 14-17, resulting in the formation of stable termolecular complexes, with K_aasoc values ranging from 3.8 × 10⁶ to 8.9 × 10⁷ M ^-1, but also strongly complex a hydrogen-bond-assembled [2]rotaxane, 18, which consists of a rigid fumaramide thread and a pyridine-incorporated tetraamide cyclophane, with K_assoc = 1.2 × 10⁴ M^-1. ¹H NMR competition experiments reveal that complexation to the dipyriyl guests also promotes the stability of the quadruply-hydrogen-bonded dimeric receptor.

Full text of DOI:10.1021/jo0351872

Recogn ition th r ou gh Self-Assem bly. A
Qu a d r u p ly-Hyd r ogen -Bon d ed , Str a p p ed P or p h yr in Cleft Th a t
Bin d s Dip yr id yl Molecu les a n d a [2]Rota xa n e
Xue-Bin Shao,† Xi-Kui J iang,† Xin Zhao,† Cheng-Xue Zhao,‡ Yan Chen,‡ and Zhan-Ting Li*,†
Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China, and Department of Chemistry, Shanghai J iaotong University,
800 Dongchuan Lu, Shanghai 200240, China
ztli@mail.sioc.ac.cn
Received August 12, 2003
Quadruply-hydrogen-bonded porphyrin homodimer Zn 1‚Zn 1 has been designed, assembled, and
evaluated as a supramolecular cleft-featured receptor for its ability to bind dipyridyl guests in
chloroform-d. Monomer Zn 1 consists of a 2-ureidopyrimidin-4(1H)-one unit, which was initially
reported by Meijer et al., and a zinc porphyrin unit. The zinc porphyrin is strapped with an
additional aliphatic chain for controlling the atropisomerization of porphyrin. The 2-ureidopyrimidin-
4(1H)-one unit dimerizes exclusively in chloroform even at the dilute concentration of 10-4 M, while
the two “strapped” zinc porphyrin units of the homodimer provide additional binding sites for
1
selective guest recognition. H NMR studies indicate that the new homodimer Zn 1‚Zn 1 adopts an
S-type conformation due to strong donor-acceptor interaction between the electron-rich porphyrin
1
units and the electron-deficient 2-ureidopyrimidin-4(1H)-one unit. H NMR, UV-vis, and vapor
pressure osmometry investigations reveal that Zn 1‚Zn 1 could function as a new generation of
assembled supramolecular cleft, to be able to not only efficiently bind linear dipyridyl molecules
14-17, resulting in the formation of stable termolecular complexes, with Kaasoc values ranging from
3.8 × 106 to 8.9 × 107 M-1, but also strongly complex a hydrogen-bond-assembled [2]rotaxane, 18,
which consists of a rigid fumaramide thread and a pyridine-incorporated tetraamide cyclophane,
1
with Kaasoc ) 1.2 × 104 M-1. H NMR competition experiments reveal that complexation to the
dipyriyl guests also promotes the stability of the quadruply-hydrogen-bonded dimeric receptor.
In tr od u ction
number of supramolecular capsules have been engineered
and self-assembled by utilizing hydrogen bonds3 or
metal-ligand coordination4 as the driving force. At
present, these new supramolecular species have been
used as novel “tools of physical organic chemistry” 3e for
controllable guest encapsulation and release,5 for recog-
nition sensing,6 and as microreactors.7 Metal-ligand
An ongoing enterprise in supramolecular chemistry is
the design, synthesis, and investigation of unnatural
receptors with convergent recognition functionality.1
Although studies of molecular recognitions based on
unicomponent receptors have always been vigorously
performed,2 in the past decade a significant amount of
multicomponent supramolecular systems have been de-
veloped as a new generation of artificial receptors. A large
(3) (a) Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713. (b)
De Mendoza, J . Chem.sEur. J . 1998, 4, 1373. (c) Rebek, J ., J r. Acc.
Chem. Res. 1999, 32, 278. (d) Hof, F.; Rebek, J ., J r. Proc. Natl. Acad.
Sci. U.S.A. 2002, 99, 4775. (e) Hof, F.; Craig, S. L.; Nuckolls, C.; Rebek,
J ., J r. Angew. Chem., Int. Ed. 2002, 41, 1488.
† Chinese Academy of Sciences.
‡ Shanghai J iaotong University.
(4) (a) MacGillivray, L. R.; Atwood, J . L. Angew. Chem., Int. Ed.
1999, 38, 1018. (b) Fujita, M.; Umemoto, K.; Yoshizawa, M.; Fujita,
N.; Kusukawa, T.; Biradha, K. Chem. Commun. 2001, 509. (c) Seidel,
S. R.; Stang, P. J . Acc. Chem. Res. 2002, 35, 972. (d) Davis, A. V.; Yeh,
R. M.; Raymond, K. N. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4793.
(5) For recent examples, see: (a) Mogck, O.; Pons, M.; Bo¨hmer, V.;
Vogt, W. J . Am. Chem. Soc. 1997, 119, 5706. (b) O’Leary, B. M.;
Grotzfeld, R. M.; Rebek, J ., J r. J . Am. Chem. Soc. 1997, 119, 11701.
(c) Chapman, R. G.; Sherman, J . C. J . Org. Chem. 2000, 65, 513. (d)
Kusukawa, T.; Yoshizawa, M.; Fujita, M. Angew. Chem., Int. Ed. 2001,
40, 1879. (e) Ikeda, A.; Udzu, H.; Zhong, Z.; Shinkai, S. J . Am. Chem.
Soc. 2001, 123, 3872. (f) Caulder, D. L.; Bru¨ckner, C.; Powers, R. E.;
Ko¨nig, S.; Parac, T. N.; Raymond, K. N. J . Am. Chem. Soc. 2001, 123,
8923.
(6) Castellano, R. K.; Rudkevich, D. M.; Rebek, J ., J r. J . Am. Chem.
Soc. 2000, 122, 7876.
(7) For recent examples, see: (a) Kang, J .; Rebek, J ., J r. Nature
1997, 385, 50. (b) Ziegler, M.; Brumaghim, J . L.; Raymond, K. N.
Angew. Chem., Int. Ed. 2000, 39, 4119. (c) Yoshizawa, M.; Takeyama,
Y.; Kusukawa, T.; Fujita, M. Angew. Chem., Int. Ed. 2002, 41, 1347.
(1) (a) Vo¨gtle, F. Supramolecular Chemistry; Wiley & Sons: Chi-
chester, U.K., 1991. (b) Lehn, J .-M. Supramolecular Chemistry; VCH:
Weinheim, Germany, 1995. (c) Atwood, J . L., Davies, J . E. D., Macnicol,
D. D., Vo¨gtle, F., Lehn, J .-M., Eds. Comprehensive Supramolecular
Chemistry; Pergamon: Oxford, 1996; Vols. 1-9. (d) Sauvage, J .-P.,
Dietrich-Buchecker, C., Eds.; Molecular Catenanes, Rotaxanes and
Knots; Wiley-VCH: Weinheim, Germany, 1999. (e) Steed, J . W.,
Atwood, J . L., Eds. Supramolecular Chemistry; Wiley-VCH: Weinheim,
Germany, 1999. (f) Schneider, H.-J .; Yatsimirski, A. Principles and
Methods in Supramolecular Chemistry; Wiley: Somerset, MA, 2000.
(g) Lindoy, L. F.; Atkinson, I. M. Self-assembly in Supramolecular
Systems; Royal Society of Chemistry: London, 2000.
(2) For recent reviews, see (a) Beer, P. D.; Gale, P. A. Angew. Chem.,
Int. Ed. 2001, 40, 486. (b) Lavigne, J . J .; Anslyn, E. V. Angew. Chem.,
Int. Ed. 2001, 40, 3118. (c) Dervan, P. B. Bioorg. Med. Chem. 2001, 9,
2215. (d) Hill, D. J .; Mio, M. J .; Prince, R. B.; Hughes, T.; Moore, J . S.
Chem. Rev. 2001, 101, 3893. (e) Gokel, G. W.; Barbour, L. J .; Ferdani,
R.; Hu, J . Acc. Chem. Res. 2002, 35, 878. (f) Zhao, D.; Moore, J . S.
Chem. Commun. 2003, 807.
10.1021/jo0351872 CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/10/2004
J . Org. Chem. 2004, 69, 899-907
899

Shao et al.
1
coordination-driven supramolecular squares8 and macro-
cyclic ensembles9 and hydrogen-bond-induced rosettes10
and heterodimers11 have also been reported for discrete
guest recognition, transport, or catalysis. Nevertheless,
compared with classic covalent counterparts, investiga-
tion of supramolecular receptors for multimolecular
recognition is still in its infancy. The challenge remains
for the construction of new types of assemblies for
achieving selective recognitions and exploring new bind-
ing modules.
hydrogen-bonded dimeric module17-20 and (2) H NMR,
UV-vis, and vapor pressure osmometry (VPO) studies
of the highly efficient recognition of the new supra-
molecular receptor for dipyridyl molecules 14-17 and
also [2]rotaxane 18, which has been self-assembled by
using Leigh’s hydrogen-bond-templating principle.21,22
Resu lts a n d Discu ssion
The synthesis of compounds H21 and Zn 1 is outlined
in Scheme 1. Acid 2 was first transformed into ester 3
with benzyl chloride. Treatment of 3 with 4 with potas-
sium carbonate as base resulted in the formation of
dialdehyde 5 in high yield. Porphyrin 7 was then pre-
pared in 15% yield from a trifluoroacetic acid-catalyzed
reaction of 5 with 6. Selective deprotection of 7 with
MeSO3H in anisole gave the key intermediate 8 in 85%
yield.23 It was found that this debenzylation reaction
could be achieved by the normal Pd-C-catalyzed hydro-
genation reaction, which led to the formation of insoluble
materials. Another intermediate, 12, was prepared from
the Pd-catalyzed hydrogenation of 11. The latter could
be obtained in good yield from the reaction of 9 and 10
in hot pyridine. Then, treatment of 8 with 12 in CH2Cl2
in the presence of DCC afforded porphyrin H21 in 47%
yield. Porphyrin H21 was then quantitatively trans-
formed into Zn 1 with zinc acetate. The octyl ester and
nonyl groups in H21 and Zn 1 provide them good solubil-
ity in organic solvents such as chloroform, dichloro-
methane, and toluene.
Due to their extraordinary coordination, electronic, and
geometrical properties, porphyrins are ideal building
blocks for constructing artificial receptors. In the past
decade, a large number of covalently bonded porphyrin
receptors have been reported which recognize a variety
of ions and organic molecules.12 Coordination-bond-driven
porphyrin squares have also been extensively investi-
gated.8,13 However, hydrogen-bond-assembled porphyrin
systems for molecular or supramolecular recognition have
been much less investigated; there are yet only a very
few hydrogen-bond-assembled porphyrin rosette recep-
tors in the literature which bind tripyridyl or a sugar
derivative.10
One of the major obstacles for generating self-
assembled porphyrin receptors is atropisomerization of
the attached functional units, which substantially re-
duces or even makes impossible selective guest recogni-
tion.14 To overcome this obstacle, we have developed a
new efficient method to prepare strapped porphyrin
precursors for further incorporation of a specific func-
tional moiety.15,16 The additional strap, which links two
oppositely located phenyl groups, can prevent the
atropisomerization of the corresponding meso-phenyl
groups. It also ensures that any ligand can approach the
porphyrin metal ion only from the strap-free side, con-
sequently facilitating selective self-assembly or molecular
recognition. Moreover, it also raises the chances of
making the two porphyrins arrange in a cofacial orienta-
tion. Here we describe (1) the self-assembly and charac-
terization of the first cleft-featured porphyrin dimeric
receptor Zn 1‚Zn 1 by utilizing Meijer’s versatile quadruply-
Before it was utilized as a bimolecular supramolecular
receptor, Zn 1 had to be proved to exist exclusively as a
homodimer in nonpolar solvents. Therefore, a systematic
1H NMR study was first performed in CDCl3.24 Partial
1H NMR spectra of H21, Zn 1, and 13 (for comparison)
are presented in Figure 1. The large downfield shifts for
the NH signals of 13 as a simple homodimer are well
expected. The AADD binding mode for dimer 13‚13 could
be easily established by comparison with reported sys-
(17) (a) Rebek, J ., J r. Science 1987, 235, 1478. (b) Zimmerman, S.
C.; Wu, W. J . Am. Chem. Soc. 1989, 111, 8054.
(8) (a) Czaplewski, K. F.; Hupp, J . T.; Snurr, R. Q. Adv. Mater. 2001,
13, 1895. (b) Mines, G. A.; Tzeng, B.; Stevenson, K. J .; Li, J .; Hupp, J .
T. Angew. Chem., Int. Ed. 2002, 41, 154.
(9) (a) Sommer, R. D.; Rheingold, A. L.; Goshe, A. J .; Bosnich, B. J .
Am. Chem. Soc. 2001, 123, 3940. (b) Goshe, A. J .; Steele, I. M.;
Ceccarelli, C.; Rheingold, A. L.; Bosnich, B. Proc. Natl. Acad. Sci. U.S.A.
2002, 99, 4823.
(10) (a) Calama, M. C.; Timmerman, P.; Reinhoudt, D. N. Angew.
Chem. 2000, 112, 771; Angew. Chem., Int. Ed. 2000, 39, 755. (b) Ishi-
i, T.; Mateos-Timoneda, M. A.; Timmerman, P.; Crego-Calama, M.;
Reinhoudt, D. N.; Shinkai, S. Angew. Chem., Int. Ed. 2003, 42,
2300.
(11) Mertz, E.; Mattei, S.; Zimmerman, S. C. Org. Lett. 2000, 2, 2931.
(12) For recent examples, see: (a) Sirish, M.; Chertkov, V. A.;
Schneider, H.-J . Chem.sEur. J . 2002, 8, 1181. (b) D’Souza, F.;
Deviprasad, G. R. J . Org. Chem. 2001, 66, 4601. (c) Sanders, J . K. M.
Pure Appl. Chem. 2000, 72, 2265. (d) Sessler, J . L.; Andrievsky, A.
Chem.sEur. J . 1998, 4, 159.
(13) (a) Stang, P. J .; Olenyuk, B. Acc. Chem. Res. 1997, 30, 502. (b)
Dinolfo, P. H.; Hupp, J . T. Chem. Mater. 2001, 13, 3113.
(14) Ogoshi, H. Mizutani, T. Acc. Chem. Res. 1998, 31, 81.
(15) Shao, X.-B.; J iang, X.-K.; Wang, X.-Z.; Li, Z.-T.; Zhu, S.-Z.
Tetrahedron 2003, 59, 4881.
(16) The length of this chain is suitable for the porphyrin unit to
keep its planarity; see: (a) Bag, N.; Grogan, T. M.; Magde, D.;
Slebodnick, C.; J ohnson, M. R.; Ibers, A. J . J . Am. Chem. Soc. 1994,
116, 11833. (b) Osuka, A.; Kabayashi, F.; Maruyama, K. Bull. Chem.
Soc. J pn. 1991, 64, 1213.
(18) Beijer, F. H.; Sijbesma, R. P.; Kooijman, H.; Spek, A. L.; Meijer,
E. W. J . Am. Chem. Soc. 1998, 120, 6761.
(19) For recent reviews concerning this binding module, see: (a)
Brunsveld, L.; Folmer, B. J . B.; Meijer, E. W.; Sijbesma, R. P. Chem.
Rev. 2001, 101, 4071. (b) Schmuck, C.; Wienand, W. Angew. Chem.,
Int. Ed. 2001, 40, 4363.
(20) For recent examples of other types of quadruply-hydrogen-
bonded systems, see: (a) Beijer, F. H.; Sijbesma, R. P.; Kooijman, H.;
Spek, A. L.; Meijer, E. W. J . Am. Chem. Soc. 1998, 120, 6761. (b)
Sessler, J . L.; Wang, R. Angew. Chem., Int. Ed. 1998, 37, 1726. (c)
Lu¨ning, U.; Ku¨hl, C. Tetrahedron Lett. 1998, 38, 5735. (d) Corbin, P.
S.; Zimmerman, S. C. J . Am. Chem. Soc. 1998, 120, 9710. (e) Gong,
B.; Yang, Y.; Zeng, H.; Skrzypczak-J ankunn, E.; Kim, Y. W.; Zhu, J .;
Ickes, H. J . Am. Chem. Soc. 1999, 121, 5607. (f) Corbin, P. S.;
Zimmerman, S. C.; Thiessen, P. A.; Hawryluk, N. A.; Murray, T. J . J .
Am. Chem. Soc. 2001, 123, 10475.
(21) (a) Lane, A. S.; Leigh, D. A.; Murphy, A. J . Am. Chem. Soc.
1997, 119, 11092. (b) Leigh, D. A.; Murphy, A.; Smart, J . P.; Slawin,
A. M. Z. Angew. Chem., Int. Ed. Engl. 1997, 36, 728.
(22) For examples of other types of hydrogen-bonded [2]rotaxanes,
see: (a) Vo¨gtle, F.; Ha¨ndel, M.; Meier, S.; Ottens-Hildebrandt, S.; Ott,
F.; Schmidt, T. Liebigs Ann. 1995, 739. (b) Vo¨gtle, F.; J a¨ger, R.; Ha¨ndel,
M.; Ottens-Hildebrandt, S.; Schmidt, W. Synthesis 1996, 353.
(23) Nakayama, Y.; Senokuchi, K.; Sakaki, K.; Kato, M.; Maruyama,
T.; Miyazaki, T.; Ito, H.; Nakai, H.; Kawamura, M. Bioorg. Med. Chem.
1997, 5, 971.
(24) No useful information could be provided from their 13C NMR
spectra due to important overlaps.
900 J . Org. Chem., Vol. 69, No. 3, 2004

Recognition through Self-Assembly
SCHEME 1a
a
Reagents and conditions: (a) BnCl, KF, DMF, 80 °C, 4 h, 67%, (b) K2CO3, Bu4N+I-, FMD, 80 °C, 3 h, 91%, (c) (i) TFA, CH2Cl2, rt, 2
h, (ii) 4-chloranil, THF, 15%, (d) MeSO3H, PhOMe, rt, 85%, (e) pyridine, 90 °C, 5 h, 71%, (f) HCO2NH4, Pd-C (catalytic), MeOH, reflux,
1.5 h, 84%, (g) 8, DCC, DMAP (cat.), CH2Cl2, rt, 3 days, 47%, (h) Zn(OAc)2, CH2Cl2/MeOH, reflux, 12 h, 100%.
tems18,25 and also from a 2D NOESY study. Unexpectedly,
substantial upfield shifts were exhibited for the NH
protons of both H21 and Zn 1. The very large upfield shifts
of H-1 (-2.93 ppm), H-2 (-2.53 ppm), H-3 (-4.10 ppm),
and H-4 (-2.93 ppm) of Zn 1, relative to those of reference
molecule 13, initially led us to propose a folded conforma-
tion for Zn 1, in which one ureidopyrimidone nitrogen was
coordinated to the central porphyrin zinc ion. However,
molecular modeling revealed that substantial twisting of
the porphyrin skeleton is required for such an intra-
molecular coordination to occur. In addition, VPO experi-
ments gave an average molecular mass of 2850 ( 300 u
in chloroform/toluene (1:1 v/v, 30 °C), which strongly
suggests a dimeric structure (calculated molecular mass
3016 u). The UV-vis spectrum of Zn 1 in CHCl3 between
350 and 650 nm is also very similar to that of the zinc(II)
complex of porphyrin 7 both in shape and intensity,
excluding the existence of significant intra- or inter-
molecular coordination. All the NH signals of Zn 1 and
1
H21 in the H NMR spectra in CDCl3 did not shift upon
dilution (up to 10-5 M) but shifted downfield remarkably
when the temperature was increased. Adding 1.0 equiv
of 13 to the solution of Zn 1 in CDCl3 led to the generation
of a new set of (six) signals for the NH protons (Figure
1d, indicated by the arrows), which could be reasonably
ascribed to the new heterodimer Zn 1‚13, whereas the
signals produced by Zn 1 and 13 themselves were weak-
ened remarkably but did not disappear.26 The new set of
signals were intensified when another 1.0 equiv of 13 was
added (Figure 1e). The chemical shifts of the amide CdO
(25) So¨ntjens, S. H. M.; Sijbesma, R. P.; van Genderen, M. H. P.;
Meijer, E. W. J . Am. Chem. Soc. 2000, 122, 7487.
J . Org. Chem, Vol. 69, No. 3, 2004 901

Shao et al.
F IGURE 2. Proposed S conformation of homodimers 1‚1 and
Zn 1‚Zn 1 in chloroform-d as a result of strong intramolecular
donor-acceptor interaction.
The UV-vis absorption spectra of Zn 1 did not change
in shape over the concentration range of 1.0-0.01 mM.
This observation, together with the above 1H NMR
dilution experiment, suggests a very high binding con-
stant for homodimer Zn 1‚Zn 1 (g107 M-1).25,27,28 These
results well allow homodimer Zn 1‚Zn 1 to be treated as
a single component at [Zn 1] g 0.01 mM.11 Therefore, the
binding behaviors of dimer Zn 1‚Zn 1 to linear dipyridyl
molecules 14-17 were then investigated.
1
F IGURE 1. Partial H NMR spectra (400 MHz) in CDCl3 at
25 °C: (a) H21 (20 mM), (b) Zn 1 (20 mM), (c) 13 (20 mM), (d)
Zn 1 (20 mM) + 13 (1:1), and (e) Zn 1 (20 mM) + 13 (1:2).
carbon and pyrimidin-4(1H)-one CH carbon of Zn 1
(171.17, 103.55 ppm) and H21 (172.39, 104.38 ppm) in
the 13C NMR spectra also notably moved upfield com-
pared to those of 13 (172.92, 105.71 ppm) as a result of
the shielding effect of the porphyrin unit. All these results
indicate that both Zn 1 and H21 exist as stable homo-
dimers Zn 1‚Zn 1 and H21‚H21 in CDCl3. What is different
from dimer 13‚13 is that the hydrogen-bonding moiety
of Zn 1‚Zn 1 and H21‚H21 is shielded by the two periph-
eral porphyrin units. In other words, both dimers Zn 1‚
Zn 1 and H21‚H21 adopt an “S” conformation in CDCl3,
as shown (Figure 2), which may be attributed to the
donor-acceptor interaction between an electron-rich
porphyrin unit and an electron-deficient pyrimidone unit.
The much more stronger shielding effect observed for Zn 1
should reflect the increased electron-donating ability of
the zinc porphyrin unit relative to the metal-free por-
phyrin in 1. The AADD binding pattern of dimer Zn 1‚
Zn 1 in CDCl3 had been established with 2D NOESY
experiments. In principle, an additional group such as
methyl introduced to the carbon of the benzene between
the porphyrin and ester moieties of Zn 1 should prevent
the folding conformation. Nevertheless, it would also
generate potential steric repelling to any guest molecule
in the complexes.
Mixing 14 with 2.0 equiv of Zn 1 in CDCl3 led to the
signals of 14 in the H NMR spectrum to shift upfield
1
substantially, as shown in Figure 3. The large upfield
shift (-6.39 ppm) exhibited by the R-H suggests that the
pyridine unit is fully bonded to the porphyrin zinc.29
Strong binding of the pyridine units to the zinc por-
phyrins also led to weakening of the shielding effect of
the zinc porphyrin unit on the hydrogen-bonding moiety
in dimer Zn 1‚Zn 1. Consequently, the NH signals of Zn 1
shift back greatly to the “normal” downfield positions.18,25
The signals of guest 14 and the signals of the NH protons
of Zn 1 in Figure 3b have been assigned by changing their
ratios and comparing the spectra with those of pure
samples. The 2:1 binding stoichiometry (Zn 1‚Zn 1)‚14 has
1
been proved by a H NMR investigation of J ob’s plot, in
(27) Attempts to determine the Kassoc of dimer Zn 1‚Zn 1 with UV-
vis or the fluorescent dilution method (ref 25) did not succeed, possibly
due to the π π stacking between the porphyrin units and the hydrogen-
binding moiety.
(26) These results were used to support the dimeric structure but
not the possible folded state, since, if it exists, the folded state should
be obviously more stable than the dimeric structure. If 1 equiv of 13
were added to the solution of Zn 1 in CDCl3, such a folded conformation
of Zn 1 would not be broken to the extent as shown in Figure 1d.
However, it is reasonable to assume that the stability of three possible
dimers, Zn 1‚Zn 1, Zn 1‚13, and 13‚13, are comparable and formed in
comparable yields.
(28) A Kdim of 5.7 × 107 M-1 has been determined in chloroform for
similar homodimers; see ref 25.
(29) (a) Ikeda, A.; Ayabe, M.; Shinkai, S.; Sakamoto, S.; Yamaguchi,
K. Org. Lett. 2000, 2, 3707. (b) Hunter, C. A.; Hyde, R. K. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1936.
902 J . Org. Chem., Vol. 69, No. 3, 2004

Recognition through Self-Assembly
F IGURE 5. Absorption spectral change in Zn 1 ([Zn 1] ) 1.0
× 10-4 M) in CHCl3 at 25 °C: [16] ) 1.0 × 10-6 to 7.3 × 10-4
M. Inset: ∆A555 vs [16].
Therefore, UV-vis titration experiments of Zn 1‚Zn 1
with the dipyridine guests were performed in chloroform.
Figure 5 shows the influence of added 16 on the absorb-
ance spectral change of Zn 1. It can be seen that a
pronounced red shift was exhibited for the Q-band of the
porphyrin unit with a clear isosbestic point at 558 nm.29,32
This result indicates that the two pyridine units in guest
16 simultaneously coordinate to Zn(II) in dimer Zn 1‚
Zn 1.29a A plot of the absorbance intensity change of the
porphyrin unit ([Zn 1] ) 1.0 × 10-4 M) at 555 nm vs [16]
(inserted in Figure 5) was then fit to a nonlinear 1:1
binding model,33,34 which afforded an association constant
Kassoc ) (4.7 ( 0.6) × 106 M-1 for the termolecular complex
(Zn 1‚Zn 1)‚16. By using the same principle, Kassoc values
for termolecular complexes (Zn 1‚Zn 1)‚14, (Zn 1‚Zn 1)‚15,
and (Zn 1‚Zn 1)‚17 in chloroform were determined to be
(8.9 ( 1.4) × 107, (9.8 ( 1.4) × 106, and (3.8 ( 0.5) × 106
M-1, respectively. The largest Kassoc exhibited by 14 might
reflect its strongest coordination ability relative to 15-
17. The binding constants are comparable to those of the
covalently bonded diporphyrin receptors for dipyridyl
guests.35
The extremely strong binding affinity exhibited by
homodimer Zn 1‚Zn 1 to the linear pyridine guests sug-
gests that Zn 1‚Zn 1 may recognize more complicated
molecular or even supramolecular species. To explore this
possibility, [2]rotaxane 18, with a neutral cyclic compo-
nent bearing two pyridine units, was designed. The
fumaramide thread 23 was chosen as template, since
previous studies by Vo¨gtle and Leigh et al. had shown
that the rigid fumaramide unit could induce the genera-
tion of the hydrogen-bond-assembled [2]rotaxanes of
similar structures in higher yields,36 whereas the pentyl
groups were introduced to 23 to improve the solubility
of the resulting [2]rotaxane in common organic solvents.
1
F IGURE 3. Partial H NMR spectra (400 MHz) in CDCl3 at
25 °C: (a) 14 (5.0 mM), (b) Zn 1 (10.0 mM) + 14 (2:1), (c) Zn 1
(10.0 mM), (d) Zn 1 (10.0 mM) + 18 (2:1), and (e) 18 (5.0 mM).
F IGURE 4. Proposed structure of termolecular complex (Zn 1‚
Zn 1)‚14.
which the maximum signal change for the R-H of 14 was
observed at the 2:1 mole fraction.30 Therefore, a stable
tercomponent complex is formed, as shown in Figure 4.
Upon mixing Zn 1 with 0.5 equiv of 15, 16, or 17 in
CDCl3, large downfield shifts (-5.65, -6.09, and -6.04
ppm) were also displayed for the pyridine R-H signals,
indicating that strong binding also occurs between dimer-
ic receptor Zn 1‚Zn 1 and these dipyridyl guests, resulting
in the formation of the corresponding tercomponent
complexes similar to (Zn 1‚Zn 1)‚14.31
Quantitative binding studies were first attempted by
using the H NMR dilution or titration method, which
did not afford reliable results due to the lowered resolu-
tion of the pyridine R-H probes at low concentration.
1
(32) Takeuchi, M.; Shioya, T.; Swager, T. M. Angew. Chem., Int. Ed.
2001, 40, 3372.
(33) Assuming a lower limit of Kassoc ) 1.0 × 107 M-1 for dimer Zn 1‚
Zn 1 in chloroform at room temperature, ca. 97.8% of Zn 1 exists as
dimers at [Zn 1] ) 1.0 × 104 M-1
.
(30) J ob, P. Ann. Chim. Ser. 10 1928, 9, 113.
(34) (a) Conners, K. A. Binding Constants: The Measurement of
Molecular Complex Stability; Wiley: New York, 1987. (b) Wilcox, C.
S. In Frontiers in Supramolecular Organic Chemistry and Photochem-
istry; Schneider, H.-J ., Du¨rr, H., Eds.; VCH: New York, 1991; p 123.
(35) Anderson, H. L.; Anderson, S.; Sanders, J . K. M. J . Chem. Soc.,
Perkin Trans. 1 1995, 2231.
(31) Addition of even 10 equiv of pyridine to the solution of Zn 1‚
Zn 1 (5.0 mM) in CDCl3 induced a ca. 1.8 ppm downshifting for the
H-1 signal of Zn 1, indicating that a significant corporative effect exists
for the formation of the complexes between dimeric receptor Zn 1‚Zn 1
and dipyridyl molecules 14-17.
J . Org. Chem, Vol. 69, No. 3, 2004 903

Shao et al.
SCHEME 2a
F IGURE 6. Proposed structure of tetramolecular complex
(Zn 1‚Zn 1)‚18.
compound 25 in the presence of excess 23 led to the
formation of [2]rotaxane 18 in 57% yield.
The [2]rotaxane has a good solubility in nonpolar
solvents such as chloroform and toluene at room tem-
perature, and has been characterized by (2D NOESY) 1H
NMR, ESI-MS, and elemental analysis. Adding 2.0 equiv
of Zn 1 to the solution of [2]rotaxane 18 (5.0 mM) in
CDCl3 caused a significant upfield shift (-0.67 ppm)
(Figure 3d) for the pyridine R-H signal in [2]rotaxane 18,
indicative of significant coordination between the por-
phyrin zinc ion of Zn 1 and the pyridine nitrogen of
1
[2]rotaxane 18. A J ob plot study of the H NMR results,
with the pyridine R-H as a probe, supported a 2:1 binding
stoichiometry. Compared to those of the tercomponent
systems of Zn 1 and 14-17, similar UV-vis absorbance
spectral patterns were also displayed when 18 was added
to the solution of Zn 1 in chloroform. A VPO investigation
afforded an average molecular mass of 3900 ( 400 u in
toluene at 30 °C (calculated value for the species Zn 1/
Zn 1/18, 4368 u).38 All these results support the formation
of the novel tetramolecular complex (Zn 1‚Zn 1)‚18, as
shown in Figure 6. Quantitative binding studies were
then carried out. A 1H NMR dilution investigation15,39 of
the 2:1 solution of Zn 1 and 18 ([18] ) 8.0-0.1 mM) in
CDCl3 afforded a Kassoc of 1.0 × 104 M-1 for (Zn 1‚Zn 1)‚
18. A UV-vis titration study of Zn 1‚Zn 1 ([Zn 1] ) 0.3
mM) at 555 nm with 18 ([18] ) 0.020-5.0 mM) was also
performed, which gave a comparable Kassoc ) (1.2 ( 0.2)
× 104 M-1 for (Zn 1‚Zn 1)‚18. Although the value is
significantly lower than those of the above termolecular
complexes, it is still very impressive considering that
steric hindrance between Zn 1‚Zn 1 and 18 should be
substantially larger than those in the termolecular
systems, and the coordination ability of the pyridines in
18 is expected to be reduced due to the existence of two
electron-withdrawing amide groups at its â-positions.
a
Reagents and conditions: (a) CHOCOOH, H2SO4 (catalytic),
HOAc, 40 °C, 12 h, 68%, (b) NH3(g), DCC, HOBt, CH2Cl2, rt, 12
h, 94%, (c) NaBH4, BF3‚OEt2, THF, reflux, 8 h, 90%, (d) NEt3,
CH2Cl2, rt, 12 h, 78%, (e) NEt3, CHCl3, MeCN, rt, 2 h, 57%.
The synthesis of [2]rotaxane 18 is outlined in Scheme
2. Ether 19 was first converted into acid 20 according to
the condensation method reported by Baarschers.37 20
was then treated with ammonia in the presence of DCC,
to afford amide 21 in high yield. The latter was reduced
with sodium borohydride in the presence of boron tri-
fluoride to amine 22 in good yield. 22 was then treated
with but-2-enedioyl dichloride, to generate the linear
template 23. Treatment of diamine 24 with 1 equiv of
1
A variable-temperature H NMR study reveals signifi-
cant temperature dependence of all the new supra-
molecular complexes. All the pyridine protons of the
guests and the NH protons of Zn 1 shifted upfield
(36) (a) J a¨ger, R.; Baumann, S.; Fischer, M.; Safarowsky, O.; Nieger,
M.; Vo¨gtle, F. Liebigs Ann./ Recl. 1997, 2269. (b) Parham, A. H.;
Windisch, B.; Vo¨gtle, F. Eur. J . Org. Chem. 1999, 1233, 3. (c) Gatti, F.
G.; Leigh, D. A.; Nepogodiev, S. A.; Slawin, A. M. Z.; Teat, S. J . T.;
Wong, J . K. Y. J . Am. Chem. Soc. 2001, 123, 5983.
(37) Baarschers, W. H.; Vukmanich, J . P. Can. J . Chem. 1986, 64,
932.
(38) The VPO investigations for the termolecular species (Zn 1‚Zn 1)‚
14-17 did not provide useful information because of the small change
of their average molecular masses relative to that of dimer Zn 1‚Zn 1.
(39) Corbin, P. S.; Zimmerman, S. C.; Thiessen, P. A.; Hawryluk,
N. A.; Murray, T. J . J . Am. Chem. Soc. 2001, 123, 10475.
904 J . Org. Chem., Vol. 69, No. 3, 2004

Recognition through Self-Assembly
benzyl chloride (8.70 mL, 75.6 mmol) was added in one portion.
The mixture was stirred at 80 °C for 4 h and then cooled to
room temperature. The mixture was triturated with ether
(1000 mL). The organic phase was then washed with water
(100 mL × 3) and saturated brine solution (150 mL) and dried
over Na2SO4. After evaporation of the solvent, the resulting
residue was recrystallized from ethanol, to afford pure com-
pound 3 (10.4 g, 67%) as a white solid. Mp: 106-106.5 °C. 1H
NMR (CDCl3): δ ) 5.34 (s, 2H), 7.01 (d, J ) 9.17 Hz, 1H),
7.35-7.45 (m, 5H), 8.20 (d, J ) 9.16 Hz, 1H), 8.31 (s, 1H),
9.92 (s, 1H), 11.39 (s, 1H). MS (EI): m/z 256 (M+). Anal. Calcd
for C15H12O4: C, 70.30; H, 4.72. Found: C, 70.40; H, 4.74.
2-(10-Ch lor od ecyloxy)ben za ld eh yd e (4). To a stirred
suspension of salicyaldehyde (10.5 mL, 0.10 mol) and K2CO3
(30.0 g, 0.22 mol) in DMF (100 mL) was added 1, 10-
dichlorodecane (32.0 mL, 0.15 mol). The mixture was stirred
at 80 °C for 3 h, and the solvent was evaporated under reduced
pressure. The resulting residue was triturated with ether
(1000 mL), and the organic phase was washed with dilute
NaOH solution (200 mL × 2), water (150 mL), and saturated
brine solution (150 mL) and dried over Na2SO4. After evapora-
tion of the solvent, the residue was purified by column
chromatography (petroleum ether/ethyl acetate, 20:1), to afford
compound 4 (16.2 g, 54%) as an oil. 1H NMR (CDCl3): δ )
1.31-1.49 (m, 12H), 1.71-1.87 (m, 4H), 3.53 (t, J ) 6.8 Hz,
2H), 4.07 (t, J ) 6.3 Hz, 2H), 6.96-7.03 (m, 2H), 7.53 (t, d, J
) 7.7 and 2.1 Hz, 1H), 7.83 (d, d, J ) 7.8 and 2.6 Hz, 1H). MS
(EI): m/z 296 (M+). Anal. Calcd for C17H25ClO2: C, 68.79; H,
8.49. Found: C, 68.77; H, 8.61.
3-F or m yl-4-[10-(2-for m ylp h en oxy)d ecyloxy]b en zoic
Acid Ben zyl Ester (5). To a stirred solution of compounds
3 (5.12 g, 20.0 mmol) and 4 (5.94 g, 20.0 mmol) in dry DMF
(100 mL) were added K2CO3 (5.50 g, 40.0 mmol) and Bu4N+I-
(0.74 g, 2.0 mmol) at room temperature. The mixture was then
stirred at 80 °C for 4 h. The solid was filtered off, and the
solvent was distilled under reduced pressure. The resulting
residue was triturated with dichloromethane (300 mL). The
organic phase was washed with dilute NaOH solution (1 N)
(60 mL × 2), water (60 mL), and saturated brine solution (60
mL) and dried over Na2SO4. After evaporation of the solvent,
the residue was subjected to column chromatography (chloro-
form/ethyl acetate, 80:1). Pure compound 5 (9.36 g) was
obtained as a white solid in 91% yield. Mp: 55-56 °C. 1H NMR
(CDCl3): δ ) 1.35-1.62 (m, 12H), 1.82-1.90 (m, 4H), 4.08 (t,
J ) 6.6 Hz, 2H), 4.15 (t, J ) 6.5 Hz, 2H), 5.35 (s, 2H), 6.96-
7.04 (m, 3H), 7.36-7.53 (m, 6H), 7.83 (d, d, J ) 7.5 Hz, 1.8
Hz, 1H), 8.25 (d, d, J ) 8.7 Hz, 2.4 Hz, 1H), 8.53 (d, J ) 2.4
Hz, 1H), 10.48 (s, 1H), 10.52 (s, 1H). MS (EI): m/z 516 (M+).
Anal. Calcd. for C32H36O6: C, 74.40; H, 7.02. Found: C, 74.03;
H, 6.71.
remarkably with the increase of the temperature, indica-
tive of the weakening of the complexes and decreased
shielding effect at higher temperature. At lowered tem-
perature, these proton signals shifted downfield, and new
sets of signals were generated for the Zn 1 NH protons
of the termolecular complexes. This observation can be
reasonably attributed to the formation of a new type of
more complicated complexes. Unfortunately, quantitative
investigations of the new sets of signals could not be
performed due to the reduced resolution of the spectra
at lower temperature. An attempt to investigate the
influence of the complexation of [2]rotaxane 18 by di-
meric receptor Zn 1‚Zn 1 on the dynamic behavior of the
[2]rotaxane was also proved impossible as a result of the
reduced solubility of the [2]rotaxane at reduced pressure.
Addition of excess 13 (20.0 mM) to the solution of
complex (Zn 1‚Zn 1)‚14 (5.0 mM) caused ca. 30% (based
1
on the H NMR integrating intensity of H-1 of Zn 1) of
the hydrogen-bond-assembled dimer Zn 1‚Zn 1 to dissoci-
ate and induced the formation of the new heterodimer
Zn 1‚13, indicating that the Zn 1‚Zn 1 moiety in complex
(Zn 1‚Zn 1)‚14 is more stable than dimer Zn 1‚Zn 1, which
does not involve a complexing process.
Con clu sion
We have demonstrated that quadruply-hydrogen-
bonded strapped porphyrin homodimer Zn 1‚Zn 1 is a
novel efficient bimolecular receptor for recognizing di-
pyridyl molecules and a supramolecular species. In the
past decade, interlocked systems such as catenanes and
rotaxanes have been important kinds of self-assembling
targets in supramolecular chemistry. The efficient bind-
ing of [2]rotaxane 18 by dimeric receptor Zn 1‚Zn 1, the
first example of its kind, demonstrates that selective
recognition between discrete supramolecular species can
be achieved by rational molecular design. Further study
along this line may lead to development of new supra-
molecular principles for controlling dynamic properties
of specifically designed interlocked assemblies. By intro-
ducing chiral groups to assembled receptors and/or
guests, new chemistries of chiral recognition40 or receptor
amplification41 are also expected. Efforts in these direc-
tions will be reported in due course.
4-[Bis(1H-p yr r ol-2-yl)m eth yl]ben zoic Acid Octyl Ester
(6). A solution of 4-formylbenzoic acid octyl ester43 (8.70 g, 33.2
mmol) and pyrrole (23.0 mL, 0.33 mol) in toluene (250 mL)
was degassed by a stream of nitrogen for 30 min. Then, 1 mL
of saturated tosyl acid in hot toluene solution (at ca. 100°) was
added in one portion. The solution was heated under reflux
for 1.5 h and cooled to room temperature. The solution was
washed with aqueous K2CO3 solution (2 N, 40 mL) and water
(40 mL × 2) and dried over sodium sulfate. Evaporation of
the solvent gave a brown oil, which was subjected to flash
chromatography (CHCl3) and further purified by recrystalli-
zation (chloroform/hexane), to give 8.11 g of pure product 4 in
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are uncorrected. All
reactions were performed under an atmosphere of dry nitrogen.
The 1H NMR spectra were recorded on a 600, 400, or 300 MHz
spectrometer in the indicated solvents. Chemical shifts are
expressed in parts per million (δ) using residual solvent
protons as internal standards. Chloroform (δ 7.26 ppm) was
used as an internal standard for chloroform-d. Elemental
analysis was carried out at the SIOC analytical center. Unless
otherwise indicated, all starting materials were obtained from
commercial suppliers and were used without further purifica-
tion. All solvents were dried before use following standard
procedures.
1
65% yield as a white solid. Mp: 84-85 °C. H NMR (CDCl3):
δ ) 0.89 (t, J ) 6.7 Hz, 3 H), 1.27-1.44 (m, 10 H), 1.71-1.78
(m, 2 H), 4.30 (t, J ) 6.6 Hz, 2 H), 5.53 (s, 1 H), 5.90 (s, 2 H),
6.15-6.18 (m, 2 H), 6.70-6.73 (m, 2 H), 7.24-7.30 (m, 2 H),
7.97 (s, 2 H), 8.00 (s, 2 H). MS (EI): m/z 378 [M]+. Anal. Calcd
for C24H30N2O2: C, 76.16; H, 7.99; N, 7.40. Found: C, 76.25;
H, 7.99; N, 7.29.
3-F or m yl-4-h yd r oxyben zoic Acid Ben zyl Ester (3). A
mixture of compound 242 (10.5 g, 63.0 mmol) and anhydrous
KF (3.70 g, 63.0 mmol) was stirred at 80 °C for 30 min. Then
(40) (a) Huang, X.; Fujioka, N.; Pescitelli, G.; Koehn, F. E.; Will-
iamson, R. T.; Nakanishi, K.; Berova, N. J . Am. Chem. Soc. 2002, 124,
10320. (b) Borovkov, V. V.; Lintuluoto, J . M.; Sugeta, H.; Fujiki, M.;
Arakawa, R.; Inoue, Y. J . Am. Chem. Soc. 2002, 124, 2993.
(41) Prins, L. J .; Reinhoudt, D. N.; Timmerman, P. Angew. Chem.,
Int. Ed. 2001, 40, 2382.
(42) Cheng, C.-C.; Lu, Y.-L. J . Chin. Chem. Soc. 1998, 45, 611.
(43) Barry, J .; Bram, G.; Decodts, G.; Loupy, A.; Orange, C.; Petit,
A.; Sansoulet, J . Synthesis 1985, 40.
J . Org. Chem, Vol. 69, No. 3, 2004 905

Shao et al.
P or p h yr in 7. Compounds 5 (2.07 g, 4.00 mmol) and 6 (1.52
g, 4.00 mmol) were dissolved in dichloromethane (850 mL).
The solution was degassed for 30 min with nitrogen at room
temperature, and then trifluoroacetic acid (1 mL) was added
in one portion. The solution was stirred at room temperature
overnight. Then a solution of 4-chloranil (2.93 g, 12.0 mmol)
in THF (100 mL) was added. The mixture was stirred at room
temperature for another 2 h and then washed with saturated
aqueous NaHCO3 solution (100 mL × 3), water (100 mL), and
saturated brine solution (100 mL) and dried over sodium
sulfate. The solvent was evaporated, and the resulting residue
was subjected to column chromatography (dichloromethane),
to afford the crude product 7, which was unstable in the air
and used directly for the next step.
(1:1). Pure compound 12 was obtained as a white solid (1.37
g, 84%). Mp: 136-138 °C. H NMR (CDCl3): δ ) 0.88 (t, J )
1
6.8 Hz, 3H), 1.31-1.33 (m, 12H), 1.64 (q, J ) 7.7 Hz, 2H), 2.47
(t, J ) 7.7 Hz, 2H), 3.44 (t, J ) 4.5 Hz, 2H), 3.72 (br, 1H),
3.79-3.83 (m, 2H), 5.82 (s, 1H), 10.29 (s, 1H), 11.81 (s, 1H),
13.06 (s, 1H). MS (EI): m/z 293 (M+ - CH3O). Anal. Calcd for
C
16H28N4O3: C, 59.23; H, 8.70; N, 17.27. Found: C, 59.29; H,
8.55; N, 17.01.
P or p h yr in H21. To a stirred solution of compound 8 (0.32
g, 0.28 mmol), compound 12 (0.18 g, 0.56 mmol), and DMAP
(30 mg) in dry dichloromethane (10 mL) was added DCC (0.11
g, 0.56 mmol) at room temperature. The solution was stirred
at room temperature for 3 days and then washed with water
(2 mL × 3) and brine (2 mL) and dried over sodium sulfate.
After evaporation of the solvent, the residue was purified by
column chromatography (dichloromethane/methanol, 40:1), to
give porphyrin H21 as a purple solid (0.19 g, 47%). Mp: 148-
P or p h yr in 8. To a solution of the above compound 7 in
anisole (10 mL) was added methanesulfonic acid (2 mL). The
solution was stirred at room temperature for 2 h. Then
dichloromethane (100 mL) was added. The organic solution
was washed with saturated NaHCO3 solution (30 mL × 3),
water (30 mL), and saturated brine solution (30 mL) and dried
over sodium sulfate. After solvent removal, the resulting
residue was purified by column chromatography (dichloro-
methane/ethyl acetate/triethylamine/methanol, 40:4:4:1), to
afford compound 8 (0.36 g, 7.9% for two steps) as a purple solid.
Mp: 130-132 °C. 1H NMR (CDCl3): δ ) -2.65 (s, 1H), -1.27-
1.22 (m, 2H), -1.02-0.88 (m, 4H), -0.60-0.45 (m, 6H), 0.61-
0.71 (m, 4H), 0.91 (t, J ) 6.8 Hz, 6H), 1.33-1.60 (m, 20H),
1.86-1.96 (m, 4H), 3.69 (t, J ) 5.3 Hz, 2H), 3.84 (t, J ) 4.8
Hz, 2H), 4.50 (t, J ) 6.8 Hz, 4H), 7.24-7.28 (m, 2H), 7.45 (t,
J ) 7.4 Hz, 1H), 7.75 (t, d, J ) 8.0 Hz, 1.7 Hz, 1H), 8.15 (d, J
) 7.8 Hz, 2H), 8.31-8.57 (m, 8H), 8.76-8.85 (m, 8H), 9.10 (d,
J ) 2.1 Hz, 1H). MS (ESI): m/z 1142 (M+). Anal. Calcd for
1
150 °C. H NMR (CDCl3): δ ) -2.71 (s, 2H), -1.13 (br, 4H),
-0.78 (br, 4H), -0.52 (br, 4H), -0.33-0.16 (m, 4H), 0.35-
0.44 (m, 2H), 0.57-1.58 (m, 49H), 1.85-1.95 (m, 4H), 3.58-
3.75 (m, 6H), 4.41-4.51 (m, 5H), 7.14 (d, J ) 8.4 Hz, 1H), 7.28
(br, 1H), 7.44 (t, d, J ) 7.3 Hz, 1H), 7.75 (t, J ) 7.3 Hz, 1H),
8.17 (d, J ) 7.5 Hz, 2H), 8.26-8.52 (m, 8H), 8.71-8.84 (m,
8H), 9.29 (d, J ) 2.4 Hz, 1H), 10.61 (br, 1H), 11.60 (s, 1H),
12.04 (s, 1H). 13C NMR (CDCl3): δ ) 14.12, 14.19, 22.70, 22.67,
24.98, 25.16, 25.77, 26.22, 27.34, 27.54, 27.61, 28.35, 28.57,
28.75, 28.95, 29.05, 29.32, 29.40, 29.78, 30.61, 31.76, 31.91,
38.83, 63.86, 65.55, 69.40, 69.82, 104.38, 111.53, 113.40,
115.37, 116.96, 118.44, 119.93, 121.75, 127.97, 129.89, 130.10,
130.66, 131.35, 131.94, 132.71, 134.50, 134.70, 134.94, 135.36,
146.84, 151.06, 153.79, 156.65, 159.77, 163.43, 166.96, 172.39.
MS (MALDI-TOF): m/z 1448 (M+ + H). Anal. Calcd for
C
73H80N4O8: C, 76.81; H, 7.06; N, 4.91. Found: C, 76.81; H,
C
89H106N8O10: C, 73.83; H, 7.38; N, 7.74. Found: C, 73.73; H,
7.07; N, 4.88.
7.31; N, 7.53.
1-(2-Be n zyloxye t h yl)-3-(6-n on yl-4-oxo-1,4-d ih yd r o-
p yr im id in -2-yl)u r ea (11). To a stirred biphasic mixture of
dichloromethane (280 mL) and saturated aqueous NaHCO3
solution (280 mL) was added BnOCH2CH2NH2‚HCl44 (2.25 g,
14.0 mmol) at room temperature. The mixture was cooled to
0 °C while being stirred for ca. 10 min. Stirring was stopped,
and the layers were allowed to separate. A solution of tri-
phosgene (2.80 g) in dichloromethane (30 mL) was added in a
single portion via syringe to the organic phase. Stirring was
resumed immediately for 0.5 h. The layers were then sepa-
rated, the aqueous phase was extracted with CH2Cl2 (100 mL
× 2), and the combined organic phases were dried over Na2SO4
and concentrated to give crude isocyanate 10. The isocyanate
was dissolved in dry pyridine (50 mL), and then compound
945 (3.32 g, 14.0 mmol) was added. After the solution was
heated under reflux for 4 h, the solvent was removed under
reduced pressure, and the resulting residue was washed
completely with ether and then subjected to column chroma-
tography (dichloromethane/methanol, 30:1), to afford com-
P or p h yr in Zn 1. The free base porphyrin H21 (0.15 g, 0.10
mmol) was dissolved in dichloromethane/methanol (3:1, 60
mL), and zinc acetate (0.12 g, 1.00 mmol) was added with
stirring. The mixture was stirred under reflux overnight. The
solvent was removed in vacuo, and the product was subjected
to column chromatography (dichloromethane/methanol, 40:1),
to afford porphyrin Zn 1 as a purple solid in quantitative yield.
Mp: >260 °C. 1H NMR (CDCl3): δ ) -1.55 (t, J ) 6.2 Hz,
2H), -1.37 (br, 2H), -1.24 (br, 2H), -0.81 (br, 6H), -0.31 (br,
2H), 0.60 (br, 2H), 0.92-1.55 (m, 47H), 1.88-1.93 (m, 4H), 3.03
(s, 2H), 3.36 (s, 2H), 3.53 (s, 1H), 3.67 (s, 2H), 4.48 (br, 4H),
6.58 (s, 1H), 6.80 (d, J ) 8.8 Hz, 1H), 7.26 (br, 1H), 7.41-7.50
(m, 2H), 7.74 (t, J ) 7.5 Hz, 1H), 7.94 (d, J ) 7.5 Hz, 1H),
8.05-8.39 (m, 13H), 8.78-8.86 (m, 4H), 9.45 (s, 1H), 9.91 (s,
1H). 13C NMR (CDCl3): δ ) 14.13, 14.17, 22.71, 2430, 24.92,
26.02, 26.18, 26.89, 27.17, 28.00, 28.38, 28.85, 28.93, 29.28,
29.38, 29.59, 31.38, 31.88, 31.95, 36.53, 59.56, 65.42, 68.80,
69.74, 103.76, 111.30, 113.32, 114.65, 114.70, 117.86, 118.86,
119.85, 121.06, 121.11, 127.50, 127.55, 129.22, 129.67, 130.64,
130.72, 131.55, 131.76, 132.17, 132.41, 132.95, 134.76, 135.06,
147.90, 149.09, 149.63, 149.88, 150.69, 151.12, 151.44, 154.60,
159.47, 163.22, 165.60, 166.84, 171.17. MS (MALDI-TOF): m/z
1509 (M + + H). Anal. Calcd for C89H104N8O10Zn: C, 70.73; H,
6.94; N, 7.41. Found: C, 70.43; H, 6.65; N, 7.50.
1
pound 11 (4.13 g, 71%) as a white solid. Mp: 98 °C. H NMR
(CDCl3): δ ) 0.88 (t, J ) 6.75 Hz, 3H), 1.24-1.32 (m, 12H),
1.64 (p, J ) 7.5 Hz, 2H), 2.46 (t, J ) 7.5 Hz, 2H), 3.49-3.55
(q, J ) 5.6 Hz, 2H), 3.65 (t, J ) 5.6 Hz, 2H), 4.57 (s, 1H), 5.81
(s, 1H), 7.24-7.37 (m, 5H), 10.36 (s, 1H), 11.97 (s, 1H), 13.09
(s, 1H). MS (EI): m/z 414 (M+). Anal. Calcd for C23H34N4O3:
C, 66.64; H, 8.27; N, 13.52. Found: C, 66.61; H, 8.06; N, 13.52.
1-(2-H y d r o x y e t h y l)-3-(6-n o n y l-4-o x o -1,4-d ih y d r o -
p yr im id in -2-yl)u r ea (12). To a mixture of compound 11 (2.07
g, 5.00 mmol) and NH4HCO3 (7.0 g) in methanol (150 mL) was
added 10% Pd-C (0.3 g) at room temperature. The mixture
was then stirred under reflux for 1.5 h and then filtered to
remove the catalyst. The solvent was evaporated, and the
resulting residue was subjected to a flash column. The crude
was then purified by recrystallization from methanol/acetone
[3-(6-Meth yl-4-oxo-1,4-d ih yd r op yr im id in -2-yl)u r eid o]-
a cetic Acid Eth yl Ester (13). A mixture of 2-amino-4-
hydroxy-6-methylpyrimidine (0.50 g, 4.00 mmol) and ethyl
2-isocyanoglycinate (0.50 g, 3.91 mmol) in dried pyridine (20
mL) was stirred under reflux for 3 h. The solvent was removed
under reduced pressure, and the residue was washed with
ether completely and then subjected to flash chromatography
(CH2Cl2/MeOH, 10:1), to give compound 13 as a white solid
(0.77 g, 78%). Mp: 197.5-199 °C. 1H NMR (CDCl3): δ ) 1.25-
1.30 (t, J ) 5.6 Hz, 3H), 2.22 (s, 3H), 3.99 (d, J ) 5.6 Hz, 2H),
4.12-4.25 (m, 2H), 5.82 (s, 1H), 10.76 (s, 1H), 12.13 (s, 1H),
12.87 (s, 1H). 13C NMR (CDCl3): δ ) 13.62, 24.46, 48.21, 60.12,
105.71, 152.22, 154.43, 156.72, 172.92. MS (EI): m/z 254 [M]+.
(44) Hu, X. E.; Cassady, J . M. Synth. Commun. 1995, 25, 907.
(45) Gonza´lez, J . J .; Prados, P.; de Mendoza, J . Angew. Chem., Int.
Ed. 1999, 38, 525.
906 J . Org. Chem., Vol. 69, No. 3, 2004

Recognition through Self-Assembly
Anal. Calcd for C10H14N4O4: C, 47.24; H, 5.55; N, 22.03.
Found: C, 47.17; H, 5.50; N, 22.26.
NMR (CDCl3): δ ) 0.94 (d, J ) 7.2 Hz, 12H), 1.40 (br, 2H),
1.60-1.66 (m, 4H), 1.78-1.87 (m, 2H), 3.23 (d, J ) 7.8 Hz,
2H), 3.86 (t, J ) 7.8 Hz, 1H), 3.94 (t, J ) 6.6 Hz, 4H), 6.83 (d,
J ) 8.7 Hz, 4H), 7.12 (d, J ) 8.7 Hz, 4H). MS (EI): m/z 340
(M+ - CH2NH2). Anal. Calcd for C24H35NO2‚H2O: C, 74.38;
H, 9.62; N, 3.61. Found: C, 74.44; H, 9.48; N, 3.47.
Diison icotin ic Acid 1,4-P h en ylen e Diester (16). To a
stirred suspension of isonicotinoyl chloride hydrochloride (0.77
g, 6.88 mmol) and 1,4-benzenediol (0.18 g, 1.64 mmol) in dry
dichloromethane (15 mL) was added dropwise triethylamine
(1 mL) at room temperature. The clean solution was then
refluxed for 2 h. After workup, the crude product was purified
by column chromatography (dichloromethane/acetone, 8:1), to
give compound 16 (0.39 g, 73%). Mp: 222 °C. 1H NMR
(CDCl3): δ ) 7.33 (s, 4H), 8.03 (d, J ) 5.9 Hz, 4H), 8.89 (d, J
) 5.9 Hz, 4H). MS (EI): m/z 320 (M+). Anal. Calcd for
Bu t -2-en ed ioic Acid Bis({2,2-bis[4-(3-m et h ylb u t oxy)-
p h en yl]eth yl}a m id e) (23). To a solution of 22 (4.70 g, 12.7
mmol) and triethylamine (1.8 mL) in anhydrous dichloro-
methane (150 mL) was added dropwise a solution of fumaryl
chloride (0.70 mL) in anhydrous dichloromethane (20 mL) at
room temperature within 30 min. The mixture was stirred
overnight. After workup, the crude product was subjected to
column chromatography (chloroform/acetone, 25:1), to afford
compound 23 (4.04 g, 78%) as a white solid. Mp: 205-206 °C.
1H NMR (CDCl3): δ ) 0.94 (d, d, J ) 6.2 Hz, 3.5 Hz, 24H),
1.63-1.68 (m, 8H), 1.78-1.87 (m, 4H), 3.87 (d, d, J ) 8.1 Hz,
5.7 Hz, 4H), 3.94 (t, J ) 6.5 Hz, 8H), 4.06 (t, J ) 8.1 Hz, 2H),
5.90 (t, J ) 5.7 Hz, 2H), 6.70 (s, 2H), 6.81 (d, J ) 9.0 Hz, 4H),
7.08 (d, J ) 9.0 Hz, 4H). MS (EI): m/z 818 (M+). Anal. Calcd
for C52H70N2O6: C, 76.25; H, 8.61; N, 3.42. Found: C, 76.39;
H, 8.64; N, 3.16.
C
18H12N2O4: C, 67.50; H, 3.78; N, 8.75. Found: C, 67.36; H,
3.93; N, 8.18.
Diison icotin ic Acid 1,4-Xylylen e Diester (17). This
compound was prepared on the basis of the method described
1
for 16 as a white solid. Mp: 117-118 °C. H NMR (CDCl3): δ
) 5.41 (s, 4H), 7.49 (s, 4H), 7.87 (d, J ) 6.3 Hz, 4H), 8.79 (d,
J ) 6.3 Hz, 4H). MS (EI): m/z 348 (M+). Anal. Calcd for
C
20H16N2O4: C, 68.96; H, 4.63; N, 8.04. Found: C, 68.58; H,
4.65; N, 7.76.
Bis[4-(3-m eth ylbu toxy)p h en yl]a cetic Acid (20). A solu-
tion of glyoxylic acid (5.85 g, 79.0 mmol) and compound 1946
(25.6 g, 0.16 mol) in acetic acid (80 mL) was cooled in an ice
bath. Concentrated sulfuric acid (3 mL) was added dropwise
under stirring. The solution was then stirred at 40 °C
overnight. After most solvent was removed under reduced
pressure, the residue was triturated with dichloromethane
(200 mL). The solution was washed with aqueous sodium
carbonate solution to pH 6, water, and brine and dried over
Na2SO4. After evaporation of the solvent, the residue was
recrystallized from 2-propanol. Compound 20 (16.7 g, 68%) was
[2]Rota xa n e 18. Compound 23 (0.82 g, 1.00 mmol) and
triethylamine (2.1 mL) were dissolved in acetonitrile/chloro-
form (100 mL, 1:9). The mixture was stirred vigorously while
a solution of 24 (1.09 g, 8.00 mmol) in chloroform (45 mL) and
a solution of compound 25 (1.62 g, 8.00 mmol) in chloroform
(45 mL) were added simultaneously over a period of 2 h. The
solution was then stirred for 2 h, and the precipitate was
filtered off. The solution was washed with dilute hydrochloride
solution, dilute sodium carbonate solution, water, and brine
and dried over sodium sulfate. After the solvent was removed,
the residue was subjected to column chromatography (chloro-
form/methanol, 20:1). [2]Rotaxane 18 (0.77 g) was obtained
as a white solid in 57% yield. Mp: >300 °C. 1H NMR (DMSO-
d6): δ ) 0.87-0.91 (m, 12H), 1.60-1.64 (m, 8H), 1.73-1.79
(m, 4H), 3.88-3.92 (m, 12H), 4.10-4.12 (m, 2H), 4.56 (br, 8H),
5.76 (s, 2H), 6.78 (d, J ) 5.4 Hz, 8H), 7.07 (d, J ) 5.4 Hz, 8H),
7.18 (s, 8H), 7.43 (s, 4H), 8.74 (s, 2H), 9.05 (s, 4H), 9.37
(br, 2H). MS (ESI): m/z 1553 [M+ + H]. Anal. Calcd for
1
obtained as a white solid. Mp: 97.5-98 °C. H NMR (CDCl3):
δ ) 0.94 (d, J ) 6.6 Hz, 12H), 1.65 (q, J ) 6.6 Hz, 4H), 1.77-
1.86 (m, 2H), 3.95 (t, J ) 6.6 Hz, 4H), 4.92 (s, 1H), 6.84 (d, J
) 8.9 Hz, 4H), 7.24 (d, J ) 8.9 Hz, 4H). MS (EI): m/z 384
(M+). Anal. Calcd for C24H32O8: C, 74.98; H, 8.39. Found: C,
74.98; H, 8.65.
2,2-Bis[4-(3-m eth ylbu toxy)p h en yl]a ceta m id e (21). To a
stirred suspension of compound 20 (7.70 g, 20.0 mmol) and
HOBt‚H2O (3.10 g, 20.0 mmol) in dichloromethane (50 mL)
was added DCC (5.20 g, 25.0 mmol). The mixture was stirred
at room temperature for 1 h, and then ammonia gas was
bubbled into the solution under stirring for 10 min. The
mixture was stirred overnight under NH3 atmosphere. The
precipitate was filtered off and washed with dichloromethane
(50 mL). The combined organic phase was worked up. After
the solvent was removed, the resulting residue was subjected
to column chromatography (dichloromethane/ethyl acetate, 20:
1). Compound 21 (7.21 g) was obtained as a white solid in 94%
yield. Mp: 124-125 °C. 1H NMR (CDCl3): δ ) 0.93 (d, J )
6.0 Hz, 12H), 1.65 (q, J ) 6.8 Hz, 4H), 1.78-1.87 (m, 2H), 3.95
(t, J ) 6.8 Hz, 4H), 4.92 (s, 2H), 6.84 (d, J ) 9.0 Hz, 4H), 7.21
(d, J ) 9.0 Hz, 4H). MS (EI): m/z 340 (M+ - CONH2). Anal.
Calcd for C24H33NO3: C, 75.14; H, 8.67; N, 3.65. Found: C,
75.11; H, 8.40; N, 3.55.
2,2-Bis[4-(3-m eth ylbu toxy)ph en yl]eth ylam in e (22). Com-
pound 21 (0.38 g, 1.00 mmol) and NaBH4 (0.19 g, 5.00 mmol)
were added to THF (15 mL). To the stirred suspension was
added a solution of BF3‚Et2O (0.82 mL, 6.50 mmol) in THF (5
mL) over a period of 3.5 h. Then the mixture was refluxed for
8 h and then cooled to room temperature. Diluted hydro-
chloride solution was added dropwise until the solid was
dissolved. Most solvent was removed, and diluted sodium
hydroxide solution was added to pH 7. The mixture was
extracted with dichloromethane (100 mL). After normal work-
up, the resulting residue was purified by column chromatog-
raphy (dichloromethane/ethyl acetate, 20:1), to afford com-
pound 22 (0.33 g, 90%) as a white solid. Mp: 57-58 °C. 1H
C
82H96N8O10: C, 72.76; H, 7.15; N, 8.28. Found: C, 72.72; H,
7.50; N, 8.11.
Bin d in g Stu d ies. For UV-vis absorption titration experi-
ments, typically a chloroform solution of Zn 1 was prepared
at a [Zn 1‚Zn 1] of about 1.0 mM. Chloroform solutions of
dipyridyl guests were prepared at concentrations of 10-1000
µM. A 2.5 mL sample of the mixture solution with the fixed
[Zn 1‚Zn 1] and the changing concentration of guests was
placed in a cuvette, and the UV-vis absorption spectra were
sequentially recorded. The values of the absorbance at fixed
wavelengths were used. Origin6.0 software was used to fit the
data to a 1:1 binding isotherm: ∆A ) (∆Amax/[Zn 1‚Zn 1]){0.5[G]
+ 0.5([Zn 1‚Zn 1] + Kd) - 0.5[[G]2 + (2[G](Kd[Zn 1‚Zn 1]) +
(Kd + [Zn 1‚Zn 1])2)1/2]}, where [G] is the dipyridyl guest
concentration and Kd ) (Kassoc)
-1. For the 1H NMR dilution
study, the following equation was used to fit the 1:1 binding
isotherm: ∆δ ) δ - δ0 ) ∆δmax{1 + (0.5/Kassoc[Zn 1‚Zn 1]) -
[(0.5/Kassoc[Zn 1‚Zn 1])2 + 1/Kassoc[Zn 1‚Zn 1]]1/2}, where δ ) the
chemical shift of the probe signal in the monomer/complex
mixture, δ0 ) the chemical shift of the probe signal in the
monomer, and [Zn 1‚Zn 1]) ) [18]. Association constants
reported are the average values of two or three experiments.
Ack n ow led gm en t. This work is financially sup-
ported by the Ministry of Science and Technology (Grant
G2000078101), the National Natural Science Foun-
dation of China (Grant 90206005), the Chinese
Academy of Sciences, and the State Laboratory of
Bio-Organic and Natural Products Chemistry of
China. We thank Prof. J i-Liang Shi and Min Shi for
beneficial discussions.
(46) Chiles, M. S.; J ackson, D. D.; Reeves, P. C. J . Org. Chem. 1980,
45, 2915.
J O0351872
J . Org. Chem, Vol. 69, No. 3, 2004 907