Syntheses and properties of functionalized oxacalix[4]arene porphyrins

Article abstract of DOI:10.1016/j.tet.2007.03.005

Six new functionalized oxacalix[4]arene porphyrins have been synthesized via a high-yielding '3+1' condensation between meso-(3,5-dihydroxyphenyl)triphenylporphyrin and readily available new fluorodinitrobenzene-containing trimers. The X-ray structure of

Full text of DOI:10.1016/j.tet.2007.03.005

Tetrahedron 63 (2007) 4011–4017
Syntheses and properties of functionalized
oxacalix[4]arene porphyrins
*
Lijuan Jiao, Erhong Hao, Frank R. Fronczek, Kevin M. Smith and M. Grac¸a H. Vicente
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
Received 6 November 2006; revised 16 February 2007; accepted 1 March 2007
Available online 6 March 2007
Abstract—Six new functionalized oxacalix[4]arene porphyrins have been synthesized via a high-yielding ‘3+1’ condensation between
meso-(3,5-dihydroxyphenyl)triphenylporphyrin and readily available new fluorodinitrobenzene-containing trimers. The X-ray structure of
one linear trimer is presented. The synthesis of a porphyrin containing two oxacalix[4]arene moieties is also reported using a similar strategy.
1H NMR data and computer calculations using the AM1 semiempirical method incorporated into the Spartan program indicate that the
oxacalix[4]arene porphyrins adopt 1,3-alternating conformations. The photophysical properties of the oxacalix[4]arene porphyrins were
investigated.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
routes currently available and the lack of susceptibility to
modular modifications of the target systems.14
The mechanisms of proton-coupled electron transfer
(PCET) processes, which occur in many natural systems,1–3
have been the subject of several investigations using model
porphyrin-based compounds.4,5 Such studies indicate that
either a face-to-face or side-to-side arrangement of the
acid–base and redox sites are crucial for efficient proton
and electron transfers.6 On the other hand, the recognition
that the hydrogen-bond framework in heme model systems
is a determinant of heme structure and function has resulted
in the targeted synthesis of model systems containing one or
more hydrogen-bond functionalities.7–10 Some such porphy-
rins were found to have interesting structural and electronic
properties, particularly the so-called ‘hangman’ porphyrins,
which are potential model systems for investigations of both
hydrogen-bond frameworks and energy transfer agents in
natural systems.6,11–19 Hangman porphyrins bearing hy-
drogen synthons with different pKa values have been re-
ported6,13–19 and the acidity of these systems was found to
influence both the speed and the stability of the catalyst in
proton-coupled O–O activation reactions.6,15c These types
of porphyrins are attractive PCET model systems since
they allow the control of both the proton and electron trans-
fers while providing the opportunity to introduce a hydro-
gen-bond active group with specific proton-donating
ability and arrangement relative to the metalloporphyrin re-
dox site.6 However, the synthesis of such models presents
several challenges due to very long and tedious synthetic
Calixarenes have been extensively studied in recent years
because of their interesting chemical and physical proper-
ties.20–32 However, heterocalixarenes are far less prevalent
in the chemical literature. Among those, oxacalixarenes
are especially scarce, despite the fact that their modest yield
synthesis was first reported in 1966.26 Although this flexible
route based on a nucleophilic aromatic substitution can be
used to efficiently synthesize highly functionalized oxaca-
lixarenes, it requires high temperature with extended reac-
tion time. Recently, Katz et al.30 made a significant
improvement in oxacalixarene synthesis by choosing selec-
tive bases and solvents to let the reaction proceed at room
temperature and in high yields. We have recently reported
the synthesis of calixarene-locked bisporphyrins via the
nucleophilic aromatic substitution reaction of 1,5-difluoro-
2,4-dinitrobenzene with a 3,5-dihydroxyphenyl-containing
porphyrin.33 Synthetic routes to the unsymmetric hetero-
calixarenes are few, especially for oxacalixarenes, although
Wang and Yang24 recently developed a fragment-coupling
synthesis of O- and N-bridged calixarenes using triazine;
the reaction in general needs a long time to go to completion.
Herein we report the first efficient preparation and properties
of functionalized unsymmetrical oxacalixarene porphyrins
via a ‘3+1’ condensation of readily available aryl trimers
with meso-(3,5-dihydroxyphenyl)porphyrins. Due to the
unique discrete 1,3-alternating conformations of oxacalix-
[4]arenes,20–33 we envisioned the design and synthesis of
porphyrin-oxacalix[4]arene systems containing hydrogen
* Corresponding author. Tel.: +1 225 578 7405; fax: +1 225 578 3458;
e-mail: vicente@lsu.edu
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.005

4012
L. Jiao et al. / Tetrahedron 63 (2007) 4011–4017
synthons in a face-to-face arrangement relative to the por-
phyrin macrocycle, for application as heme model systems.
Our synthetic strategy involves the preparation of a series of
novel unsymmetrical oxacalix[4]arenes by nucleophilic
aromatic substitution of functionalized meta-dihydroxyben-
zenes with 1,5-difluoro-2,4-dinitrobenzene.
2. Results and discussion
The synthesis of functionalized oxacalix[4]arene porphyrins
1a–c from readily available dihydroxybenzenes 2a–c is
shown in Scheme 1. The linear aryl trimers 3a–c were read-
ily prepared on a multi-gram scale in 75–85% yield, by
reacting 2a–c with 3 equiv of 1,5-difluoro-2,4-dinitrobenz-
ene and 4 equiv of finely ground K2CO3 (<80 mm) in
acetone at room temperature for 1–2 h. The amount of sym-
metrical oxacalix[4]arene byproducts resulting from this re-
action was minimized by using acetone as the solvent and
3 equiv (rather than two) of 1,5-difluoro-2,4-dinitrobenzene.
The linear trimers 3a–c shared characteristic 1H NMR spec-
tra, showing two downfield singlets (around 8.9 ppm) for the
protons next to the carbons bearing the NO2 groups, and two
upfield singlets (around 6.9 ppm) for the protons next to the
carbons bearing the fluorines. The structure of trimer 3c was
further confirmed by crystallography at T¼150 K (see
Fig. 1). The crystals were destroyed by cooling to tempera-
tures lower than 150 K, apparently as a result of a phase
Figure 1. Molecular structure of trimer 3c.
disappearance of the starting materials as monitored by
TLC). These fragment-coupling reactions are very efficient
and no higher analogs were detected compared with other
fragment-coupling reactions reported in the literature.20–25
The porphyrin-containing trimer 3d was also prepared in
80% yield from the reaction of porphyrin 2d with an excess
of 1,5-difluoro-2,4-dinitrobenzene in acetone at room tem-
perature. A side product in this reaction was the symmetric
oxacalix[4]arene bisporphyrin 1d. Using DMSO as the sol-
vent in place of acetone resulted in a lower yield of the trimer
product and increased the yield of bisporphyrin 1d. How-
ever, the coupling of porphyrin-containing trimer 3d with
2a–c and 2e in DMSO, in the presence of finely ground
K2CO3, resulted in low yields (10–25%) of the correspond-
ing oxacalix[4]arene porphyrins 1a–c and 1e. The major
product from these reactions was invariably the symmetric
oxacalix[4]arene bisporphyrin 1d,33 obtained from scram-
bling of trimer 3d under the reaction conditions. The thermo-
dynamic reversibility of oxacalixarene formation during
nucleophilic substitution has been studied and confirmed
˚
change. The C–F distances are 1.331(2) and 1.334(2) A.
The reaction of meso-(dihydroxyphenyl)triphenylporphyrin
2d (obtained by a mixed aldehyde condensation followed
by demethylation using BBr3 according to the literature)35
and trimers 3a–c produced the target functionalized oxa-
calix[4]arene porphyrins in 80–86% yields (Scheme 1);
4 equiv of finely ground K2CO3 in DMSO were required,
at room temperature, for 30 min to 3 h (until complete
O2N
NO2
F
O N
2
NO
F
2
OH
OH
O
2a-d
F
R
R
DMSO, K2CO3
CH3COCH3
K2CO3
O
F
O2N
NO2
2a-e
3a-d
1a: R = CHO
O2N
NO2
Ph
O
N
O
1b: R =
O
O
NH
N
Ph
R
1c: R = CO2Et
N
HN
Ph
O
O
NH
N
Ph
O2N
NO2
Ph
1d: R =
N
HN
Ph
1e: R = OH
1f : R = CO2H
Scheme 1. Synthesis of functionalized oxacalix[4]arene porphyrins.

L. Jiao et al. / Tetrahedron 63 (2007) 4011–4017
4013
Table 1. 1H NMR shifts for the interior protons on the NO2-bearing benzene
rings of porphyrins 1a–c,e,f and 4
recently by Katz et al.;30 their results are also in agreement
with studies reported for thiocalixarenes34 and with our
own observations. Hydrolysis of the ester functionality in
1c, upon refluxing in THF/4 M aqueous HCl (v/v¼1/2) for
3 days, provided 1f in 95% yield. The functionalized
oxacalix[4]arenoporphyrins 1a–c and 1e,f were character-
Porphyrin
1a
6.77
1b
6.70
1c
6.43
1e
6.87
1f
6.70
4
6.49
1H NMR shift (ppm)
1
ized by HRMS, UV–vis, fluorescence, and by H NMR
spectroscopy.
suggest that our functionalized oxacalix[4]arene porphyrins
also adopt 1,3-alternating conformations in solution, in
agreement with results reported for symmetrical oxaca-
lix[4]arenes.26–33 Furthermore, computer calculations using
the AM1 theoretical model incorporated into the Spartan
program were performed to determine the minimum energy
conformations for oxacalix[4]arene porphyrins 1a–f. Such
calculations have been found reliable for the determination
of geometrical parameters in porphyrin arrays.37–40 Similar
optimized geometries were found for all oxacalix[4]arene
porphyrins (see Fig. 2) and the calculated structure obtained
for bisporphyrin 1d was in agreement with the crystal data.33
These results suggest, as seen in Figure 2, favorable 1,3-
alternating conformations for all oxacalix[4]arene porphy-
rins, with the hydrogen-bond synthons hanging over an
adjacent pyrrole ring. Such a conformation would provide
a face-to-face structural arrangement for the porphyrin mac-
rocycles and hydrogen-bond synthons, therefore making
these compounds suitable as model systems for PCET and
hydrogen-bond investigations.
In order to prepare bis(oxacalix[4]areno)porphyrin 4, 5,15-
di(3,5-hydroxyphenyl)porphyrin 5 (prepared by mixed alde-
hyde condensation under Lindsey conditions36 followed by
demethylation with BBr3) was used in the coupling reaction
along with 2 equiv of trimer 3c (Scheme 2). The presence of
the four tert-butyl groups in porphyrin 4 induced high solu-
bility in organic solvents; an analog of porphyrin 4 without
the tert-butyl groups was also prepared separately (as con-
firmed by MALDI-MS) but it was poorly soluble and diffi-
cult to purify and characterize. Porphyrin 4 was isolated
in 84% yield and its structure was confirmed by HRMS (a
molecular ion peak was observed at 1923.5460), UV–vis,
fluorescence, and 1H NMR spectroscopy.
Based on the characteristic upfield chemical shifts observed
in the 1H NMR spectra of oxacalix[4]arenes for the interior
protons on the electrophilic (NO2-bearing) aromatic rings,28
it is believed that these compounds adopt 1,3-alternating
structures in solution.20–33 Recent X-ray structures26–33
have confirmed this conformation of oxacalix[4]arenes in
The photophysical properties of porphyrins 1a–c,e,f and 4
are summarized in Table 2. The long wavelength absorption
and fluorescence emission bands for all porphyrins except 1f
were observed between 646–652 and 652–658 nm,
1
the solid state. Table 1 shows the H NMR shifts observed
for these protons on porphyrins 1a–c,e,f and 4. These results
tBu
tBu
OH
HO
HO
NH
N
N
HN
OH
tBu
tBu
tBu
5
3c
DMSO, K2CO3
tBu
O2N
O
NO2
O
O2N
NO2
O
O
NH
N
EtO2C
CO2Et
N
HN
O
O
O
O
O2N
NO2
O2N
NO2
tBu
tBu
4
Scheme 2. Synthesis of a bis(oxacalix[4]arene)porphyrin.

4014
L. Jiao et al. / Tetrahedron 63 (2007) 4011–4017
spectra were measured on a Perkin Elmer Lambda 35 UV–
vis spectrophotometer in the 300–800 nm wavelength region
with 0.1 nm accuracy. Fluorescence spectra were measured
on a Perkin Elmer LS55 spectrometer in the 500–800 nm
wavelength region with 1 nm accuracy. The fluorescence
quantum yields were measured using the standard method
and 5,10,15,20-tetraphenylporphyrin as the standard
(quantum yield is 0.11), according to the literature.41 Mass
spectra were obtained on Applied Biosystems QSTAR XL.
High-resolution mass spectra were obtained on a Q-TOF2
eletrospray at the mass spectrometry facility of Ohio State
University. All solvents were obtained from Fisher Scientific
(HPLC grade, Houston, TX) and used without further puri-
fication unless indicated. Acetone (reagent plus, phenol
free, ꢀ99.5%) and DMSO (Biotech grade solvent, 99.8%)
were purchased from Sigma–Aldrich and used without fur-
ther purification. K2CO3 was ground and dried at 140 ꢁC.
Compounds 2b42 and 2d35 were synthesized according to
literature procedures. Solvents were dried according to
literature procedures.43 The computational simulations
used the AM1 semiempirical Hamiltonian method44 incor-
porated into the quantum mechanical Spartan program.45
The coordinates used to build the porphyrins in this study
were based on the X-ray crystal structure of 1d.33
Figure 2. Optimized geometry for porphyrin 1f calculated using the AM1
semiempirical method.
Table 2. Spectral properties of porphyrins 1a–c,e,f and 4 in degassed
CH2Cl2 at room temperature
Porphyrin
Absorption lmax (nm)
Emissiona
lmax (nm)
Fluorescenceb
quantum yield
1a
1b
1c
1e
1f
4
418, 514, 548, 591, 647
418, 515, 550, 591, 652
418, 513, 548, 591, 649
417, 513, 548, 591, 646
418, 514, 548
652
658
652
655
600, 646
656
0.13
0.15
0.13
0.17
0.03
0.22
4.1.1. Aryl trimer 3a. 3,5-Dihydroxybenzaldehyde (1a)
(276.7 mg, 2.0 mmol) was mixed with 1,5-difluoro-2,4-dini-
trobenzene (816.5 mg, 4.0 mmol) and K2CO3 (561.4 mg,
4 mmol) in 10 mL of acetone at room temperature under
air. When the reaction was complete, acetone was removed
under vacuum. The resulting residue was purified by silica
gel column chromatography using CH2Cl2/ethyl acetate
(v/v¼20/1) for elution. After removal of the solvent under
vacuum and washing with hexane (2ꢂ10 mL), pure trimer
3a was obtained as a white solid in 85% yield (860.0 mg).
1H NMR (300 MHz, CDCl3) d 10.03 (s, 1H), 8.98 (s, 1H),
8.95 (s, 1H), 7.58 (d, 2H, J¼2.25 Hz), 7.30 (s, 1H), 7.06
(s, 1H), 7.02 (s, 1H). ESI-MS calcd for C19H8F2N4O11 m/z
506.3, found: 506.5.
422, 518, 553, 592, 650
a
Excitation at 415 nm.
Calculated using 5,10,15,20-tetraphenylporphyrin as the standard.
b
respectively. The carboxyl group in porphyrin 1f is probably
involved in intermolecular hydrogen-bonding, resulting on
its distinct absorbance and emission spectra compared
with the other porphyrins, as well as its reduced fluorescence
quantum yield (0.03). All other oxacalix[4]arene porphyrins
showed quantum yields between 0.13 and 0.22.
3. Conclusions
4.1.2. Aryl trimer 3b. Compound 2b (510.4 mg, 2 mmol)
was mixed with 1,5-difluoro-2,4-dinitrobenzene (1.63 g,
8.0 mmol) and K2CO3 (2.21 g, 16 mmol) in 20 mL of ace-
tone at room temperature under air. When the reaction was
complete, acetone was removed under vacuum. The result-
ing residue was purified by silica gel column chromato-
graphy using CH2Cl2 to CH2Cl2/ethyl acetate (v/v¼20/1)
for elution. After removal of the solvent under vacuum and
washing with hexane (2ꢂ10 mL), trimer 3b was obtained
as a white solid in 75% yield (935.0 mg). 1H NMR
(300 MHz, acetone-d6) d 8.93 (d, 2H, J¼7.67 Hz), 7.93
(m, 4H), 7.69 (s, 1H), 7.65 (s, 1H), 7.60 (d, 2H, J¼
2.21 Hz), 7.48 (s, 1H). ESI-MS calcd for C26H11F2N5O12
m/z 623.4, found: 623.8.
An efficient and convenient stepwise fragment-coupling
approach to the synthesis of unsymmetrical architectures
composed of porphyrins and hydrogen-bond functionalities
anchored to an oxacalix[4]arene spacer is reported. Spectro-
scopic data and computer calculations indicate that these
oxacalix[4]areneporphyrins adopt1,3-alternatingconforma-
tions. These novel, high-yield syntheses of unsymmetrical
oxacalix[4]arenes will find applications in supramolecular
chemistry and molecular design.
4. Experimental
4.1. General
4.1.3. Aryl trimer 3c. Ethyl 3,5-dihydroxybenzoate (2c)
(182.0 mg, 1 mmol) was mixed with 1,5-difluoro-2,4-dini-
trobenzene (408.0 mg, 2 mmol) and K2CO3 (560.0 mg,
4 mmol) in 10 mL of acetone at room temperature under
air. When the reaction was complete, acetone was removed
under vacuum. The resulting residue was purified by silica
gel column chromatography using CH2Cl2 for elution. After
removal of the solvent and washing with hexane (2ꢂ10 mL),
Silica gel (32–63 mm) was used for flash column chromato-
graphy. All reactions were monitored by TLC using
0.25 mm silica gel plates with or without UV indicator
(60F-254). 1H and 13C NMR spectra were obtained on either
a DPX-250 or a ARX-300 Bruker spectrometer. Chemical
shifts (d) are given in ppm relative to CDCl3, acetone-d6,
DMSO-d6 or THF-d8 as indicated. Electronic absorption

L. Jiao et al. / Tetrahedron 63 (2007) 4011–4017
4015
trimer 3c was obtained as a white solid in 82% yield
(451.0 mg). H NMR (300 MHz, CDCl3) d 8.94 (s, 1H),
1230.2700. UV–vis (CH2Cl2) lmax (log 3) 418 (5.57), 515
(4.20), 550 (3.79), 591 (3.49), 652 (3.43) nm.
1
8.91 (s, 1H), 7.74 (d, 2H, J¼2.34 Hz), 7.19 (s, 1H), 6.96
(s, 1H), 6.92 (s, 1H), 4.39 (q, 2H), 1.38 (t, 3H). Anal. Calcd
for C21H12F2N4O12: C, 45.83; H, 2.20; N, 10.18. Found: C,
45.79; H, 2.26; N, 9.98. ESI-MS calcd for C21H12F2N4O12
m/z 550.3, found: 549.8.
4.1.7. Porphyrin 1c. Trimer 3c (55.0 mg, 0.1 mmol) was
mixed with 2d (64.6 mg, 0.1 mmol) and K2CO3 (56.0 mg,
0.44 mmol) in 20 mL of DMSO at room temperature under
air (the reaction was considered complete after TLC showed
the complete disappearance of the starting material). HCl
(0.1 M, 40 mL) was used to quench the reaction. The water
layer was extracted with 100 mL of ethyl acetate, and the or-
ganic layer was washed once with water and dried over an-
hydrous Na2SO4. The resulting residue was purified by silica
gel column chromatography using CH2Cl2 for elution. Pure
porphyrin 1c was obtained as a purple solid in 86% yield
4.1.4. Aryl trimer 3d. 5-(3,5-Dihydroxyphenyl)triphenyl-
porphyrin (2d) (32.8 mg, 0.05 mmol) was mixed with
1,5-difluoro-2,4-dinitrobenzene (81.6 mg, 0.2 mmol) and
K2CO3 (56.0 mg, 0.4 mmol) in 20 mL of acetone at room
temperature under air. After the reaction was complete, ace-
tone was removed under vacuum. The resulting residue was
purified by silica gel column chromatography using CH2Cl2/
hexane (v/v¼10/1) for elution. Pure trimer 3d was isolated
in 80% yield (40.6 mg) after recrystallization from hexane
1
(100.1 mg) after recrystallization from CH2Cl2/hexane. H
NMR (250 MHz, CDCl3) d 8.93 (s, 2H), 8.82 (m, 6H),
8.41 (s, 4H), 8.16 (m, 6H), 8.04 (d, 2H, J¼2.22 Hz), 7.99
(d, 2H, J¼2.22 Hz), 7.71 (m, 9H), 6.43 (s, 2H), 4.01 (q,
2H), 1.11 (m, 3H), ꢃ2.88 (s, 2H). MALDI-TOF calcd for
C65H40N8O14 m/z 1157.058, found: 1159.198. HRMS
(MALDI-TOF) calcd for [M+H]+ C65H41N8O14 m/z
1157.2742, found: 1157.2787. HRMS (ESI) calcd for
[M+H]+ C65H41N8O14 m/z 1157.2742, found: 1157.2799.
UV–vis (CH2Cl2) lmax (log 3) 418 (5.89), 513 (4.51), 548
(4.09), 591 (3.88), 649 (3.76) nm.
1
and CH2Cl2. H NMR (250 MHz, CDCl3) d 8.84 (m, 6H),
8.68 (d, 2H, J¼2.37 Hz), 8.19 (m, 8H), 7.73 (m, 11H),
7.05 (m, 1H), 6.80 (m, 2H), ꢃ3.03 (s, 2H). HRMS (MALDI-
TOF) calcd for [M+H]+ C56H33F2N8O10 m/z 1015.2288,
found: 1015.2265. UV–vis (CH2Cl2) lmax (log 3) 417
(5.84), 513 (4.47), 548 (4.03), 590 (3.85), 646 (3.58) nm.
4.1.5. Porphyrin 1a. Trimer 3a (50.1 mg, 0.1 mmol) was
mixed with 2d (64.1 mg, 0.1 mmol) and K2CO3 (60.3 mg,
0.44 mmol) in 20 mL of DMSO at room temperature under
air for 1 h (until TLC showed the complete disappearance of
starting material). HCl (0.1 M, 40 mL) was used to quench
the reaction. The water layer was extracted with 100 mL
of ethyl acetate, and the organic layer was washed once
with water and dried over anhydrous Na2SO4. The resulting
residue was purified by silica gel column chromatography
using CH2Cl2 for elution. Pure porphyrin 1a was obtained
as a purple solid in 83% yield (92.1 mg) after recrystalliza-
4.1.8. Bisporphyrin 1d. This compound was synthesized
and characterized as previously reported.33
4.1.9. Porphyrin 1e. Trimer 3d (20.3 mg, 0.02 mmol) was
mixed with 2e (2.5 mg, 0.02 mmol) and K2CO3 (11.0 mg,
0.08 mmol) in 5 mL of DMSO at room temperature under
air for 40 min. HCl (0.1 M, 20 mL) was used to quench
the reaction. The water layer was extracted with 50 mL of
ethyl acetate, and the organic layer was washed once with
water and dried over anhydrous Na2SO4. The resulting resi-
due was purified by silica gel column chromatography using
THF/hexane for elution. Porphyrin 1e was obtained in 20%
1
tion from CH2Cl2/hexane. H NMR (250 MHz, THF-d8)
d 10.07 (s, 1H), 8.98 (s, 2H), 8.84 (m, 6H), 8.66 (s, 2H),
8.20–8.21 (m, 6H), 8.13 (d, 2H, J¼2.10 Hz), 8.00 (d, 2H,
J¼2.16 Hz), 7.81–7.82 (m, 9H), 7.64 (s, 1H), 7.52 (s, 1H),
6.77 (s, 2H), ꢃ2.76 (s, 2H). MALDI-TOF-MS calcd for
[M+H]+ C63H37N8O13 m/z 1114.0, found: 1114.0. HRMS
(ESI) calcd for [M+H]+ C63H37N8O13 m/z 1113.2480, found:
1113.2501. UV–vis (CH2Cl2) lmax (log 3) 418 (5.88), 514
(4.50), 548 (4.11), 591 (3.93), 647 (3.72) nm.
1
yield (4.5 mg). H NMR (300 MHz, THF-d8) d 9.95 (br s,
1H), 9.06 (d, 2H, J¼3.90 Hz), 8.93 (s, 2H), 8.84 (s, 4H),
8.71 (d, 2H, J¼2.0 Hz), 8.20–8.28 (m, 6H), 8.13 (d, 2H,
J¼4.58 Hz), 7.79–7.81 (m, 9H), 7.61 (s, 1H), 6.86 (s, 2H),
6.75 (s, 1H), 6.70 (d, 2H, J¼6.93 Hz), ꢃ2.75 (s, 2H).
MALDI-TOF calcd for [M+H]+ C62H36N8O13 m/z 1102.0,
found: 1103.3. HRMS (ESI) calcd for [M+H]+
C62H37N8O13 m/z 1101.2480, found: 1101.2545. UV–vis
(CH2Cl2) lmax (log 3) 417 (5.75), 513 (4.37), 548 (3.92),
591 (3.71), 646 (3.43) nm.
4.1.6. Porphyrin 1b. Trimer 3b (63.3 mg, 0.1 mmol) was
mixed with 2d (65.7 mg, 0.1 mmol) and K2CO3 (60.0 mg,
0.43 mmol) in 10 mL of DMSO at room temperature under
air for 3 h (until TLC showed the complete disappearance of
starting material). HCl (0.1 M, 40 mL) was used to quench
the reaction. The water layer was extracted with 100 mL
of ethyl acetate, and the organic layer was washed once
with water and dried over anhydrous Na2SO4. The resulting
residue was purified by silica gel column chromatography
using CH2Cl2 for elution. Pure porphyrin 1b was obtained
as a purple solid in 83% yield (102.0 mg) after recrystalliza-
4.1.10. Porphyrin 1f. Hydrolysis of 1c was achieved by dis-
solving 1c (24.6 mg, 0.02 mmol) in 10 mL of THF, followed
by addition of 4 M HCl (20 mL). The reaction mixture was
refluxed at 60 ꢁC in an oil bath for 3 days. After completion
of the reaction, the mixture was extracted with ethyl acetate
and the organic layer washed with brine. The resulting resi-
due was purified by silica gel column chromatography using
CH2Cl2/ethyl acetate (v/v¼20/1) for elution. Pure porphyrin
1f was obtained in 95% yield (21.5 mg) after recrystalliza-
1
tion from CH2Cl2/hexane. H NMR (300 MHz, THF-d8)
d 8.98 (s, 2H), 8.90 (br s, 2H), 8.82 (br s, 4H), 8.20 (br s,
4H), 8.17 (s, 3H), 8.14 (s, 3H), 7.79–7.81 (m, 9H), 7.63 (s,
2H), 7.56 (s, 1H), 7.35 (s, 1H), 6.95 (d, 4H, J¼2.55 Hz),
6.70 (s, 2H), ꢃ2.84 (s, 2H). MALDI-TOF calcd for
[M+H]+ C70H40N9O14 m/z 1230.3, found: 1230.8. HRMS
(ESI) calcd for [M+H]+ C70H40N9O14 m/z 1230.2694, found:
1
tion from CH2Cl2/hexane. H NMR (300 MHz, THF-d8)
d 8.97 (s, 1H), 8.93 (d, 2H, J¼4.40 Hz), 8.83 (s, 6H), 8.77
(s, 2H), 8.21 (m, 6H), 8.14 (d, 2H, J¼1.98 Hz), 8.03 (d,
2H, J¼2.06 Hz), 7.79 (d, 9H), 7.53 (s, 1H), 7.49 (s, 1H),
6.87 (s, 2H), ꢃ2.74 (s, 2H). MALDI-TOF calcd for

4016
L. Jiao et al. / Tetrahedron 63 (2007) 4011–4017
[M+H]+ C63H37N8O14 m/z 1129.2, found: 1130.2. HRMS
(ESI) calcd for [M+H]+ C63H37N8O14 m/z 1129.2429, found:
1129.2405. UV–vis (CH2Cl2) lmax (log 3) 418 (5.43), 514
(3.90), 548 (3.32) nm.
4.1.13. Molecular structures. The crystal structure of tri-
mer 3c was determined using data collected at T¼150 K to
q¼31.5ꢁ with Mo Ka radiation on a Nonius KappaCCD dif-
fractometer. The X-ray crystallographic data for 3c can be
found in supplementary publication CCDC-626294 avail-
able from the Cambridge Crystallographic Data Centre.
4.1.11. 5,15-Di(3,5-dihydroxyphenyl)-10,20-di(3,5-di-
tert-butylphenyl)porphyrin (5). 3,5-Dimethylbenzalde-
hyde (0.83 g, 5.0 mmol), 3,5-di-tert-butylbenzaldehyde
(1.09 g, 5.0 mmol), and pyrrole (0.70 mL, 10 mmol) were
mixed in a 2 L flask. Dry CH2Cl2 (1000 mL) was added
and the solution was stirred for 10 min under argon before
0.4 mL of 2.5 M BF3$OEt in CH2Cl2 was added. The reac-
tion mixture was stirred under argon and in the dark for
2 h. DDQ (1.64 g) was added and the mixture stirred for
45 min. The reaction mixture was concentrated to give a resi-
due that was purified by silica gel column chromatography
using a mixture of hexane and CH2Cl2 for elution. The third
eluted purple fraction contained 5,15-di(3,5-dimethoxy-
Acknowledgements
The work described was supported by the National Science
Foundation, grant number CHE-304833.
References and notes
1. Dismukes, G. C. Science 2001, 292, 447–448.
2. Tommos, C.; Babcock, G. T. Acc. Chem. Res. 1998, 31, 18–25.
3. Yocum, C. F.; Pecoraro, V. L. Curr. Opin. Chem. Biol. 1999, 3,
182–187.
4. (a) Dawson, J. H. Science 1988, 240, 433–439; (b) Sono, M.;
Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem. Rev. 1996,
96, 2841–2887.
5. Ozaki, S.-I.; Roach, M. P.; Matsui, T.; Watanbe, Y. Acc. Chem.
Res. 2001, 34, 818–825.
6. Chang, C. J.; Chng, L. L.; Nocera, D. G. J. Am. Chem. Soc.
2003, 125, 1866–1876.
7. Mims, M. P.; Porras, A. G.; Olson, J. S.; Noble, R. W.; Peterson,
J. A. J. Biol. Chem. 1983, 258, 14219–14232.
8. Rohlfs, R. J.; Mathaws, A. J.; Carver, T. E.; Olson, J. S.;
Springer, B. A.; Egeberg, K. D.; Sligar, S. G. J. Biol. Chem.
1990, 265, 3168–3176.
9. Momenteau, M.; Reed, C. A. Chem. Rev. 1994, 94, 659–698.
10. Chang, C. K.; Kondylis, M. P. J. Chem. Soc., Chem. Commun.
1986, 316–318.
11. Chang, C. J.; Brown, J. D. K.; Chang, M. C. Y.; Baker, E. A.;
Nocera, D. G. Electron Transfer in Chemistry; Balzani, V., Ed.;
Wiley-VCH: Weinheim, Germany, 2001; Vol. 3.2.4, pp 409–461.
12. (a) Deng, Y.; Roberts, J. A.; Peng, S.-M.; Chang, C. K.; Nocera,
D. G. Angew. Chem., Int. Ed. 1997, 36, 2124–2127; (b) Cukier,
R. I.; Nocera, D. G. Annu. Rev. Phys. Chem. 1998, 49, 337–369.
13. Chang, C. K.; Liang, Y.; Aviles, G. J. Am. Chem. Soc. 1995,
117, 4191–4192.
phenyl)-10,20-di(3,5-di-tert-butylphenyl)porphyrin.
The
solvent was removed under vacuum to give 192 mg (7.9%
yield) of this porphyrin as a purple powder. MALDI-TOF-
MS calcd for [M+H]+ C64H71N4O4 m/z 960.25, found:
1
960.17. H NMR (CDCl3) d 9.07 (d, 4H, J¼4.70 Hz), 9.01
(d, 4H, J¼4.70 Hz), 8.20 (d, 4H, J¼1.68 Hz), 7.91–7.90
(m, 2H), 7.53 (d, 4H, J¼2.24 Hz), 6.97–6.99 (m, 2H), 1.63
(s, 36H), ꢃ2.63 (s, 2H). To a solution of 5,15-di(3,5-
dimethoxyphenyl)-10,20-di(3,5-di-tert-butylphenyl)porphyrin
(0.096 g, 0.1 mmol) in dry CH2Cl2 (20 mL) at ꢃ20 ꢁC was
added dropwise a solution of BBr3 (0.3 mL, 3.1 mmol) in
CH2Cl2 (1 mL) with vigorous stirring under argon over a pe-
riod of 30 min. The reaction mixture was stirred at room
temperature for 24 h and then poured into water and ex-
tracted with ethyl acetate (3ꢂ50 mL). The combined organic
layers were washed successively with brine and aqueous
NaHCO3 solutions. The organic solution was dried over
Na2SO4 and evaporated to dryness, giving the title porphyrin
(82.7 mg, 0. 092 mmol) as purple crystals in 91.6% yield.
MALDI-TOF-MS calcd for [M+H]+ C60H63N4O4 m/z
904.14, found: 904.21. 1H NMR (CD2Cl2) d 9.04 (d, 4H, J¼
4.80 Hz), 8.90 (d, 4H, J¼4.75 Hz), 8.70 (s, 4H), 8.15 (d, 4H,
J¼1.81 Hz), 7.96–7.94 (m, 2H), 7.26 (d, 4H, J¼2.18 Hz),
6.84–6.82 (m, 2H), 1.56 (s, 36H), ꢃ2.75 (s, 2H).
4.1.12. Porphyrin 4. 5,15-Di(3,5-dihydroxyphenyl)-10,20-
di(3,5-di-tert-butylphenyl)porphyrin 5 (36.1 mg, 0.04 mmol)
was mixed with trimer 3c (44.0 mg, 0.08 mmol) and
K2CO3 (33.6 mg, 0.24 mmol) in 10 mL of DMSO at room
temperature under air for 3 h. Dilute HCl (0.1 Mꢂ40 mL)
was used to quench the reaction and ethyl acetate
(2ꢂ25 mL) was used to extract the water layer. The resulting
organic phase was dried over anhydrous Na2SO4 and
purified by alumina column chromatography using
CH2Cl2/ethyl acetate (v/v¼100/1) for elution. Porphyrin 4
14. Liu, S. Y.; Nocera, D. G. J. Am. Chem. Soc. 2005, 127, 5278–
5279.
15. (a) Yeh, C. Y.; Chang, C. J.; Nocera, D. G. J. Am. Chem. Soc.
2001, 123, 1513–1514; (b) Chang, C. J.; Yeh, C. Y.; Nocera,
D. G. J. Org. Chem. 2002, 67, 1403–1406; (c) Chng, L. L.;
Chang, C. J.; Nocera, D. G. Org. Lett. 2003, 5, 2421–2424.
16. Zhang, X. X.; Lippard, S. J. J. Org. Chem. 2000, 65, 5298–
5305.
17. Liang, Y.; Chang, C. K. Tetrahedron Lett. 1995, 36, 3817–
3820.
18. Chang, C. K.; Bag, N.; Guo, B. M.; Peng, S. M. Inorg. Chim.
Acta 2003, 351, 261–268.
1
was obtained in 84% yield (64.7 mg). H NMR (250 MHz,
CDCl3) d 8.95 (br s, 8H), 8.46 (br s, 4H), 8.09 (s, 4H),
8.05 (d, J¼1.86 Hz, 4H), 8.02 (d, J¼1.82 Hz, 4H), 7.92
(s, 2H), 7.25 (br s, 4H), 6.49 (s, 4H), 3.98–4.06 (m, 4H),
1.56 (s, 36H), 1.27 (t, 6H). MALDI-TOF-MS calcd
for [M+H]+ C102H83N12O28 m/z 1923.5, found: 1923.1.
HRMS (ESI) calcd for [M+H]+ C102H83N12O28 m/z
1923.5440, found: 1923.5460. UV–vis (CH2Cl2) lmax
(log 3) 422 (5.79), 518 (4.40), 553 (4.08), 592 (3.87), 650
(3.85) nm.
19. Arimura, T.; Brown, C. T.; Springs, S. L.; Sessler, J. L. Chem.
Commun. 1996, 2293–2294.
€
20. Konig, B.; Fonseca, M. H. Eur. J. Inorg. Chem. 2000, 2303–
2310.
ꢀ
21. Lhotak, P. Eur. J. Org. Chem. 2004, 1675–1692.
22. Chambers, R. D.; Hoskin, P. R.; Kenwright, A. R.; Khalil, A.;
Richmond, P.; Sandford, G.; Yufit, D. S.; Howard, J. A. K. Org.
Biomol. Chem. 2003, 1, 2137–2147.

L. Jiao et al. / Tetrahedron 63 (2007) 4011–4017
4017
23. Li, X.; Upton, T. G.; Gibb, C. L. D.; Gibb, B. C. J. Am. Chem.
Soc. 2003, 125, 650–651.
Enkelmann, V.; Gherghel, L.; Reuter, R.; M€ullen, K. Eur. J.
Org. Chem. 1998, 63, 555–564.
24. (a) Wang, M.-X.; Yang, H.-B. J. Am. Chem. Soc. 2004, 126,
15412–15422; (b) Wang, M.-X.; Zhang, X.-H.; Zheng, Q.-Y.
Angew. Chem., Int. Ed. 2004, 43, 838–842.
25. Yang, F.; Yan, L.; Ma, K.; Yang, L.; Li, J.; Chen, L.; You, J. Eur.
J. Org. Chem. 2006, 1109–1112.
26. Sommer, N.; Staab, H. A. Tetrahedron Lett. 1966, 25, 2837–
2841.
27. Lehmann, F. P. A. Tetrahedron 1974, 30, 727–733.
28. Gilbert, E. E. J. Heterocycl. Chem. 1974, 11, 899–904.
29. Bottino, F.; Foti, S.; Pappalardo, S. Tetrahedron 1976, 32,
2567–2570.
30. (a) Katz, J. L.; Feldman, M. B.; Conry, R. R. Org. Lett. 2005, 7,
91–94; (b) Katz, J. L.; Geller, B. J.; Conry, R. R. Org. Lett.
2006, 8, 2755–2758; (c) Katz, J. L.; Selby, K. J.; Conry,
R. R. Org. Lett. 2005, 7, 3505–3507.
31. Maes, W.; Rossom, W. V.; Hecke, K. V.; Meervelt, L. V.;
Dehaen, W. Org. Lett. 2006, 8, 4161–4164.
32. Konishi, H.; Tanaka, K.; Teshima, Y.; Mita, T.; Morikawa, O.;
Kobayashi, K. Tetrahedron Lett. 2006, 47, 4041–4044.
33. Hao, E.; Fronczek, F. R.; Vicente, M. G. H. J. Org. Chem. 2006,
71, 1233–1236.
34. For reversibility in thiocalixarene formation by nucleophilic
€
substitution, see: Freund, T.; Kubel, C.; Baumgarten, M.;
35. Tanaka, T.; Endo, K.; Aoyama, Y. Bull. Chem. Soc. Jpn. 2001,
74, 907–916.
36. Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.;
Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827–836.
37. Jollife, K. A.; Langford, S. J.; Oliver, A. M.; Shephard, M. J.;
Paddon-Row, M. N. Chem.—Eur. J. 1999, 5, 2518–2530.
38. Parusel, A. J. Mol. Model. 1998, 4, 366–378.
39. Hermann, D. T.; Schindler, A. C.; Polborn, K.; Gompper, G.;
Stark, S.; Parusel, A.; Grabner, G.; Kohler, G. Chem.—Eur. J.
1999, 5, 3208–3220.
40. Odobel, F.; Suresh, S.; Blart, E.; Nichlas, Y.; Quintard, J.-P.;
Janvier, P.; Questel, J.-Y.; Illien, B.; Rondeau, D.; Richomme, P.;
Haupl, T.; Wallin, S.; Hammarstrom, L. Chem.—Eur. J. 2002,
8, 3027–3046.
41. Fery-Forgues, S.; Lavabre, D. J. Chem. Educ. 1999, 76, 1260–
1264.
42. Thorn, M. A.; Denny, G. H.; Babson, R. D. J. Org. Chem. 1975,
40, 1556–1558.
43. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon: Oxford, 1988.
44. Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P.
J. Am. Chem. Soc. 1985, 107, 3902–3909.
45. Spartan, version 2.0; Wavefunction: Irvine, CA, 2001.