Synthesis and binding behavior of a Zn(II)-porphyrin having calix[5]arene cap

Article abstract of DOI:10.1016/S0040-4039(02)01655-6

The synthesis and binding behavior of a Zn(II)-porphyrin having a calix[5]arene cap are presented. In order to synthesize such a bridged porphyrin, 5,15-bis(7-carboxy-1-naphthyl)-10,20-diphenylporphyrin having the syn arrangement of two naphthalene rings

Full text of DOI:10.1016/S0040-4039(02)01655-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8191–8194
Synthesis and binding behavior of a Zn(II)-porphyrin having
calix[5]arene cap
Hajime Iwamoto, Yoshiko Yukimasa and Yoshimasa Fukazawa*
Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526,
Japan
Received 23 March 2002; revised 3 July 2002; accepted 8 August 2002
Abstract—The synthesis and binding behavior of a Zn(II)–porphyrin having a calix[5]arene cap are presented. In order to
synthesize such a bridged porphyrin, 5,15-bis(7-carboxy-1-naphthyl)-10,20-diphenylporphyrin having the syn arrangement of two
naphthalene rings has been prepared. Amidation of the porphyrin and calix[5]arene having two amino functions and subsequent
treatment of Zn(OAc)2 gave a calix[5]arene capped Zn–porphyrin. Calix[5]arene–Zn–porphyrin was found to bind 4-methylpyri-
dine much stronger than TPP·Zn. © 2002 Elsevier Science Ltd. All rights reserved.
Synthetic metalloporphyrins have received considerable
attention for electron transfer, molecular transport and
oxidation processes.1 These metalloporphyrins were
synthesized in order to understand the important func-
tion of the enzyme having porphyrin. A number of
functionalized porphyrins carrying cyclodextrins,2
crown ethers3 and calixarenes4 have been prepared.
Zn(II)–porphyrin receptors for nitrogen containing
guests were also reported extensively.5 Calix[5]arene is
known as a potential host molecule with binding ability
towards neutral organic guest molecules, such as
fullerenes, alkyl-substituted diketopiperazines and vari-
ous amines.6 It is thus interesting to design a metal-
loporphyrin capped with such a cavity-containing
receptor to understand the cooperative role of the
coordination of the axial ligand and the non-directional
attractive forces such as the CH/p and van der Waals
interactions between the aromatic cavity wall of the
calix[5]arene cap and the axial ligand. In this paper, we
report the synthesis of a calix[5]arene capped Zn–por-
phyrin and its ligand binding properties.
prevented. Thus, the ligand binding space composed of
the calix[5]arene and the porphyrin units is stable in the
designed host molecule. The calix[5]arene can help to
grasp some small organic guest molecules with van der
Waals, CH/p and p–p interactions in organic solvents.
To synthesize the bridged porphyrin, it is necessary to
prepare 5,15-bis(7-carboxyl-1-naphthyl)-10,20-diphenyl-
porphyrin 11 having the syn arrangement of two naph-
thalene rings. In order to synthesize such a syn
arrangement regioselectively, Baldwin’s strategy using
bridged naphthylaldehyde
8 and 5-phenyldipyrro-
methane (9) was employed (Scheme 1).7 Tosylation
of 2-naphthol 2, (p-TsCl, Et3N in THF), followed
by bromination (Br2, Fe in AcOH) gave the
corresponding bromide, whose hydrolysis (NaOH in
Porphyrin having a calix[5]arene cap 1 is designed as an
artificial receptor (Fig. 1). It has two naphthalene moi-
eties as the rigid linker between the calix[5]arene and
porphyrin units. Because of the rigidity of naphthalene
unit, a collapse of the cavity, as can be sometimes seen
in a case of a capped porphyrin with flexible linker, is
Keywords: calix[5]arene; porphyrin; molecular recognition.
* Corresponding author. Tel.: +81-824-24-7427; fax: +81-824-24-0724;
e-mail: fukazawa@sci.hiroshima-u.ac.jp
Figure 1. Compound 1 (M; metal).
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01655-6

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H. Iwamoto et al. / Tetrahedron Letters 43 (2002) 8191–8194
Scheme 1. Synthesis of 5,15-bis(7-carboxy-1-naphthyl)-10,20-diphenylporphyrin.
EtOH and THF) of the toluenesulfonate ester furnished
1-bromo-7-naphthol 3. The trifluoromethanesulfonate
ester 4 was prepared from 3 (Tf2O, 2,4,6-collidine in
CH2Cl2). Chemoselective palladium-catalyzed carbonyl-
ation of aryl triflate 4 (CO, Pd(OAc)2, PPh3, Et3N,
MeOH in DMF, 78%), and subsequent formylation
(CO (45 atm), H2 (45 atm), PdCl2 (dppf), Et3N in
benzene, 62%) provided methyl 1-formyl-7-naphtoate 6.
Acetalization of 6 (ethylene glycol, p-TsOH in CH2Cl2,
98%), followed by deprotection of the methyl ester
(LiOH, MeOH, H2O, THF) gave 7. Esterification of 7
with 1,4-bis-bromomethyl-benzene followed by hydroly-
sis gave 8. Coupling of naphthylaldehyde 8 with 5-
phenyldipyrromethane (9) in CH2Cl2 in the presence of
a catalytic amount of trifluoroacetic acid followed by
oxidation with p-chloranil, afforded free base por-
phyrin 10 in 13% overall yield from 8. Hydrolysis of 10
(6 M NaOH in EtOH), gave 5,15-bis(7-carboxy-1-naph-
thyl)-10,20-diphenylporphyrin 11 in 71% yield.
Capping of the porphyrin with the calix[5]arene was
carried out by the amide formation between 11 and 13
(Scheme 3). Treatment of 11 with carbonyl imidazole
(CDI) in CH2Cl2 followed by coupling of diamino
calix[5]arene 13 gave the porphyrin having the
calix[5]arene cap 1 in 9% overall yield.10
In order to demonstrate the binding ability of 1,
calix[5]arene–Zn–porphyrin was prepared quantita-
tively from the free base porphyrin with excess
Zn(OAc)2 in CH2Cl2. Zn–porphyrins are known to bind
an axial ligand resulting in a five-coordinated com-
plex.11 Binding studies with pyridine derivatives were
performed in CHCl3 using UV titration.12 UV–vis
experiments with 1·Zn in CHCl3 (1.0×10−5 M) showed
two absorption bands at 425 and 551 nm as the Soret
band and the Q-band, respectively. Bathochromic shifts
of the Soret band of 8 nm and the Q-band of 12 nm
The synthesis of the calix[5]arene moiety was performed
as shown in Scheme 2. Diazo coupling of 12,8 followed
by reductive cleavage of the NꢀN double bond fur-
nished diamino calix[5]arene 13 in 68% overall yield.9
Scheme 3. Synthesis of 1.
Scheme 2. Synthesis of diamino calix[5]arene.

H. Iwamoto et al. / Tetrahedron Letters 43 (2002) 8191–8194
8193
Table 1. Binding energies−DG (kJ/mol)a
2. (a) Groves, J. T.; Myers, R. S. J. Am. Chem. Soc. 1983,
105, 5791; (b) O’Malley, S.; Kodadek, T. Tetrahedron Lett.
1991, 32, 2445; (c) Maxwell, J. L.; O’Malley, S.; Brown,
K. C.; Kodadek, T. Organometallics 1992, 11, 645; (d)
O’Malley, S.; Kodadek, T. Organometallics 1992, 11, 2299;
(e) Collman, J. P.; Wang, Z.; Straumanis, A.; Quelquejeu,
M. J. Am. Chem. Soc. 1999, 121, 460.
Guest
1·Zn
10·Zn
TPP·Zn
Pyridine
23.5
25.6
20.4
19.0
19.3
19.4
20.6
20.7
20.4
19.5
19.5
19.7
21.5
21.0
20.2
4-Methylpyridine
4-tert-Butylpyridine
4-Phenylpyridine
3,5-Dimethylpyridine
3. Kuroda, Y.; Sera, T.; Ogoshi, H. J. Am. Chem. Soc. 1991,
113, 2793.
a Measured in CHCl3 at 298 K. Observed 563 nm. Standard deviation
is less than 10%.
4. (a) Groves, J. T.; Viski, P. J. Org. Chem. 1990, 55, 3628;
(b) Collman, J. P.; Herrmann, P. C.; Fu, L.; Eberspacher,
T. A.; Eubanks, M.; Boitrel, B.; Hayoz, P.; Zhang, X.;
Brauman, J. I.; Day, V. W. J. Am. Chem. Soc. 1997, 119,
3481.
5. (a) Rudkevich, M. M.; Verboom, W.; Reinhoudt, D. N.
J. Org. Chem. 1995, 60, 6585; (b) Middel, O.; Verboom,
W.; Reinhoudt, D. N. J. Org. Chem. 2001, 66, 3998; (c)
Elemans, J. A. A. W.; Claase, M. B.; Aarts, P. P. M.;
Rowan, A. E.; Schenning, A. P. H. J.; Nolte, R. J. M. J.
Org. Chem. 1999, 64, 7009.
were observed upon addition of pyridine. A non-linear
regression analysis13 on the UV changes gave an associ-
ation constant of 13.3 0.3×103 M−1, and binding ener-
gies of −23.5 kJ/mol. Binding energies of the other
host–guest complexes were similarly determined and are
summarized in Table 1.
6. (a) Haino, T.; Yanase, M.; Fukazawa, Y. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 259; (b) Haino, T.; Yanase, M.;
Fukazawa, Y. Tetrahedron Lett. 1997, 38, 3739; (c) Haino,
T.; Yanase, M.; Fukazawa, Y. Angew. Chem., Int. Ed.
1998, 37, 997; (d) Yanase, M.; Haino, T.; Fukazawa, Y.
Tetrahedron Lett. 1999, 40, 2781; (e) Yanase, M.; Mat-
suoka, M.; Tatsumi, Y.; Suzuki, M.; Iwamoto, H.; Haino,
T.; Fukazawa, Y. Tetrahedron Lett. 2000, 41, 492; (f)
Haino, T.; Nitta, K.; Saijo, Y.; Matsumura, K.; Hirakata,
M.; Fukazawa, Y. Tetrahedron Lett. 2000, 41, 4139; (g)
Haino, T.; Nitta, K.; Fukazawa, Y. Tetrahedron Lett. 2000,
41, 4139.
In the capped porphyrin case, axial pyridine ligands can
bind from either side of the porphyrin. When we con-
sider the binding energies of 1·Zn, 10·Zn and TPP·Zn
with pyridine itself, it is clear that the ligand bound
from the calix[5]arene side is 1·Zn. It is thus evident
that the attractive interaction between the axial ligand
and the p-wall of calix[5]arene cavity is operative in
1·Zn. The same is true in the case of 4-methylpyridine
and 1·Zn. On the other hand, bulky substituent(s) on
pyridine ring as in the case of 4-tert-butylpyridine,
4-phenylpyridine and 3,5-dimethylpyridine, prevented
the accommodation of the guest into the calix[5]arene
cavity. Therefore, those guests bound to the Zn–por-
phyrin from the opposite side of the calix[5]arene cap.
It is thus clear that the selectivity of the binding of
pyridine derivatives depends on the size of the alkyl
substituent. 4-Methyl pyridine shows the highest
affinity with 1·Zn. The methyl group should give a
good complementarity to the p-basic inner surface of
the calix[5]arene cavity.
7. Baldwin, J. E.; Crossley, M. J.; Klose, T.; O’Tear, A.;
Peters, M. K. Tetrahedron 1982, 38, 27.
8. Haino, T.; Matsumura, K.; Harano, T.; Yamada, K.;
Saijyo, Y.; Fukazawa, Y. Tetrahedron 1998, 54, 12185.
9. (a) Haino, T.; Yanase, M.; Fukazawa, Y. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 259; (b) Yanase, M.; Haino, T.;
Fukazawa, Y. Tetrahedron Lett. 1999, 40, 2781.
10. Compound 1: l 8.78 (d, J=4.5 Hz, 2H), 8.60 (d, J=4.5
Hz, 2H), 8.54 (d, J=4.5 Hz, 2H), 8.37 (d, J=4.5 Hz, 2H),
8.31 (d, J=8.5 Hz, 2H), 8.28 (d, J=8.5 Hz, 2H), 8.12 (d,
J=8.5 Hz, 2H), 8.1 (br, 1H), 8.04 (d, J=7.0 Hz, 2H), 7.96
(d, J=7.0 Hz, 2H), 7.90 (s, 2H), 7.83 (t, J=7.5 Hz, 2H),
7.8 (br, 1H), 7.6 (br, 4H), 7.4 (br, 3H), 7.18 (s, 2H), 6.92
(s, 2H), 6.83 (s, 2H), 6.80 (s, 2H), 6.47 (s, 2H), 6.20 (s, 2H),
3.96 (d, J=14.0 Hz, 1H), 3.86 (d, J=14.0 Hz, 2H), 3.76
(d, J=14.0 Hz, 2H), 3.30 (d, J=14.5 Hz, 3H), 3.016 (d,
J=14.5 Hz, 2H), 2.18 (s, 6H), 1.88 (s, 3H), -2.68 (s, 2H).
IR (CHCl3) cm−1: 3316, 2923, 1665, 1533, 1483, 1347, 1227,
802. UV–vis (CHCl3): umax, 425 nm (m 246 000 mol−1 cd3
cm−1), 551 (11 400), 588 (2 100). HRMS (FAB-MS positive
Mode, NBA) found 1368.5128, calcd 1368.5149
(C92H68N6O7).
Acknowledgements
The measurement of Mass spectroscopy was made
using JEOL SX-102A at the Instrument Center for
Chemical Analysis, Hiroshima University. This work
was supported by Grant-in Aid for Scientific Research
(No. 10304053) from the Ministry of Education, Sci-
ence, Sports and Culture, Japan, which is gratefully
acknowledged.
11. (a) Nappa, M.; Valentine, J. S. J. Am. Chem. Soc. 1978,
100, 5075; (b) Miller, J. R.; Dorough, G. D. J. Am. Chem.
Soc. 1952, 74, 3977; (c) Hambright, P. J. Chem. Soc., Chem.
Commun. 1967, 470.
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1
12. The measurements were performed by H NMR titration
experiments in CDCl3. As host molecule 1·Zn was added
to the solution of 4-methylpyridine in CDCl3, the reso-

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H. Iwamoto et al. / Tetrahedron Letters 43 (2002) 8191–8194
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