Synthesis and functionalization of double picket fence porphyrins starting from 4,6-disubstituted pyrimidine-5-carbaldehydes

Full text of DOI:10.1021/jo0007938

5882
J . Org. Chem. 2000, 65, 5882-5885
(2,6-dihydroxyphenyl)porphyrin8 and the analogous amino-
substituted tetraarylporphyrins.9 However, in general the
synthesis of these porphyrins is not straightforward. For
instance the condensation of 2,6-dinitrobenzaldehyde
with pyrrole has been reported to give the octanitro
precursor in only in 0.75% yield in the presence of TFA10
while the use of BF3‚Et2O as catalyst gave 2-13% yield.11
Better yields could be achieved using 2,6-dinitro-4-tert-
butyl-benzaldehyde, where the tert-butyl group increased
the solubility of the intermediates.4 However, the latter
aldehyde could only be obtained involving three steps in
an overall yield of 41% starting from 4-tert-butyltoluene.
The reduction toward the ortho,ortho′-amino-substituted
porphyrins could be achieved in 60% yield. Condensation
of 2,6-dimethoxybenzaldehyde with pyrrole yielded the
octamethoxy precursor (12%).12 This porphyrin was then
demethylated using BBr3 giving an overall yield of 9%.8c
Nucleophilic substitution of the chlorine atoms of the
readily available 5,10,15,20-tetrakis(2′,6′-dichlorophenyl)-
porphyrin13 is apparently not feasable. However, func-
tionalization by electrophilic substitution at the meso aryl
position could be achieved using 3- or 4-nitro-substituted
2,6-dichlorobenzaldehyde. The nitro group was reduced
to amine which could then react further with electro-
philes. It should be noted that tailed porphyrins bearing
amido bonds are less stable than those having an ether
linkage.14
Syn th esis a n d F u n ction a liza tion of Dou ble
P ick et F en ce P or p h yr in s Sta r tin g fr om
4,6-Disu bstitu ted
P yr im id in e-5-ca r ba ld eh yd es
S. Smeets, C. V. Asokan, F. Motmans, and W. Dehaen*
Department of Chemistry, Katholieke Universiteit Leuven,
Celestijnenlaan 200F,B-3001 Heverlee, Belgium
wim.dehaen@chem.kuleuven.ac.be
Received May 23, 2000
In tr od u ction
The ortho-substituted and ortho,ortho′-disubstituted
tetraarylporphyrins have been subject of intensive re-
search. In general, sterically encumbered porphyrins
have served as useful models for some aspects of the
chemistry of hemoproteins.1 The “picket fence”,2 “double
picket fence”, and “capped”3 porphyrins have been studied
as models for hemoproteins and as catalysts. Ortho,
ortho′-substituted tetraarylporphyrins or “double picket
fence” porphyrins have been used extensively in second-
generation oxidation catalysts.4 Membranes of picket-
fence cobalt porphyrins have been studied as efficient
oxygen carriers.5 Ferric porphyrins bearing chiral bi-
naphthalene moieties on both faces were used in enan-
tioselective oxidation of sulfides and in asymmetric
epoxidations.6 These “twin coronet” porphyrins have been
further modified to mimic the active center of heme
enzymes such as cytochrome P-450.7 Functionalization
can be achieved with electrophiles on 5,10,15,20-tetrakis-
Resu lts a n d Discu ssion
In this paper we describe the synthesis of several
double picket fence porphyrins using 4,6-disubstituted
pyrimidine-5-carbaldehydes. The 4,6-dichloro-pyrimidine-
5-carbaldehyde 1 can be considered as a heterocyclic
analogue of 2,6-dichlorobenzaldehyde. The chlorine func-
tionalities on the pyrimidine ring are highly activated
toward nucleophilic substitution, allowing us to introduce
substituents at the aldehyde as well as the porphyrin
stage.15
The aldehyde 1 was prepared using the reported
Vilsmeier conditions (DMF/POCl3) for chloroformylation
of 4,6-dihydroxypyrimidine.16 Functionalization of the
two chlorine atoms of aldehyde 1 was carried out with
several substituted phenolates. Typically, the nucleo-
(1) (a) Rose, E.; Quelquejeu, M.; Pandian, R. P.; Lecas-Nawrocka,
A.; Vilar, A.; Ricart, G.; Collman, J . P.; Wang, Z. Straumanis, A.
Polyhedron 2000, 19, 581-586. (b) Rose, E.; Lecas, A.; Quelquejeu,
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1431.
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K. M.; Ibers, J . A. J . Org. Chem. 1996, 61, 3298-3303. (b) Slebodnick,
C.; Fettinger, J . C.; Peterson, H. B.; Ibers, J . A. J . Am. Chem. Soc.
1996, 118, 3216-3224. (c) Slebodnick, C.; Duval, M. L.; Ibers, J . A.
Inorg. Chem. 1996, 35, 3607-3613. (d) Slebodnick, C.; Ibers, J . A. J .
Biol. Inorg. Chem. 1997, 2, 521-525. (e) J ohnson, M. R.; Soek, W. K.;
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Boitrel, B.; Quelquejeu, M.; Kossanyi, A. Tetrahedron Lett. 1993, 34,
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wavran, F.; Bernard N.; Lecas, A J . Am. Chem. Soc. 1996, 118, 1567-
1568.
(5) (a) Suzuki, Y.; Nishide, H.; Tsuchida, E. Macromolecules 2000,
33, 2530-2534. (b) Nishide, H.; Tsukahara, Y.; Tsuchida, E. J . Phys.
Chem. B 1998, 102, 8766-8770. (c) Nishide, H.; Suzuki, T.; Nakagawa,
R.; Tsuchida, E. J . Am. Chem. Soc. 1994, 116, 4503-4504. (d) Tsuchida,
E.; Nishide, H.; Ohyanagi, M.; Okada, O. J . Phys. Chem. 1988, 92,
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(8) (a) Tsuchida, E.; Komatsu, T.; Arai, K.; Nishide, H. J . Chem.
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Komatsu, T.; Nakata, T. Bull. Chem. Soc. J pn. 1991, 64, 888-894. (c)
Komatsu, T.; Hasegawa, E.; Nishide, H.; Tsuchida E. Nakao, K.;
Nishide, H. J . Chem. Soc., Chem. Commun. 1990, 66-68. (d) Tsuchida,
E.; Komatsu, T.; Hasegawa, E.; Nishide, H. J . Chem. Soc., Dalton
Trans. 1990, 2713-2718. (e) Tsuchida, E.; Hasegawa, E.; Komatsu,
T.; Nakao, K.; Nishide, H. Chem. Lett. 1990, 1071-1074.
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Collman, J . P.; Quelquejeu, M.; Straumanis, A. J . Org. Chem. 1998,
63, 2042-2044.
(10) Drain, C. M.; Corden, B. B. Inorg. Chem. 1989, 28, 4374-4376.
(11) Quintana, C. A.; Assink, R. A.; Shellnut, J . A. Inorg. Chem.
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Chem. Soc. 1991, 113, 6865-6872. (b) Naruta, Y.; Tani, F.; Maruyama,
K. Tetrahedron: Asymmetry 1991, 2, 533-542. (c) Naruta, Y.; Ishihara,
N.; Tani, F.; Maruyama, K. Chem. Lett. 1991, 1933-1936.
(7) (a) Matsu-ura, M.; Tani, F.; Nakayama, S.; Nakamura, N.;
Naruta, Y. Angew. Chem., Int. Ed. 2000, 39, 1989-1991. (b) Tani, F.
Nakayama, S. Ichimura, M. Nakamura, N. Naruta, Y. Chem. Lett.
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(16) Klo¨tzer W.; Herberz, M. Monatsh. Chem. 1965, 96, 1567-1572.
10.1021/jo0007938 CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/16/2000

Notes
J . Org. Chem., Vol. 65, No. 18, 2000 5883
Sch em e 1
F igu r e 1.
Ta ble 2. Syn th esis of P or p h yr in s 3a -e
Ta ble 1. Syn th esis of P or p h yr in s 2b-g
crystallization of double picket fence porphyrins 2d (54%)
and 2e (59%) are among the highest ever obtained for a
Rothemund porphyrin synthesis.
It might still be more effective to introduce the sub-
stituents directly at the porphyrin stage by substitution
of the chlorine functions of the meso-(2,6-dichloropyrim-
idyl) substituents. Unfortunately, octachloro porphyrin
2a is not available, as mentioned above. Mixed Rothemund
condensations, as reported by us in a previous com-
munication, give statistical mixtures of several pyrimidyl
porphyrins which are difficult to separate. Therefore, a
5,15-bis(pyrimidyl)porphyrin 3a was prepared by a Mc-
Donald condensation of mesityldipyrromethane18 with
aldehyde 2a . In previous work we reported that the
substitution of 3a with methoxide gave an inseparable
mixture of disubstituted atropoisomers. This reaction was
carried out in THF at reflux for 72 h in the presence of
K2CO3. We now carried out the substitution reaction in
DMF using sodium methoxide. We were able to obtain
the tetramethoxy-substituted porphyrin 3b. Reaction of
porphyrin 3a with several phenols (see Figure 1) in the
presence of potassium carbonate at 60°C in DMF resulted
in the formation of four-picket porphyrins 3d (60%), 3c
(90%), 3e (75%) in high yields (Table 2). In case of
expensive phenol starting materials (e.g., estrone), this
method is clearly superior.
philic substitution of 1a was carried out using 2.2 equiv
of phenol and an excess K2CO3 (5-fold) under reflux in
THF for 5 h. This yielded the 4,6-disubstituted pyrimi-
dine-5-carbaldehydes 1b-g in excellent yields.
These aldehydes were reacted with pyrrole under
Lindsey conditions (Scheme 1).17 The porphyrins 2b-e
were isolated in yields that ranged from good to excellent
(24-59%) (Table 1). On introduction of a nitro group in
ortho-position of phenol (aldehyde 1g) the yield of the
corresponding porphyrin decreased noticeably (6%). This
relatively low yield is not only a consequence of the highly
sterically hindered aldehyde but also of the low solubility
of the corresponding intermediates in the reaction mix-
ture (solvent: dichloromethane).
Con clu sion s
Working under more diluted conditions (3.4 × 10-3
M
instead of 3.4 × 10-2 M) gave an increased yield of 10%.
We were not able to isolate 2a , the heterocyclic analogue
of 5,10,15,20-tetrakis(2′,6′-dichlorophenyl)porphyrin us-
ing either Adler-Longo (refluxing propionic acid) or
Lindsey conditions. Again, this may be a result of low
solubility of the intermediates. On the other hand, the
isolated yields after chromatographic separation and
Double picket fence porphyrins which were highly
sterically crowded could be prepared in high yields either
from pyrimidine or porphyrin starting materials. Sub-
stituents are easily introduced on both faces of the
porphyrins, which leads to three-dimensionally struc-
tured macromolecules. They have been developed as
model compounds for oxygen-binding and oxygen-activat-
(17) Lindsey, J . S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.;
Marguerettaz, A. M. J . Org. Chem. 1987, 52, 827-836.
(18) Lee C.-H., Lindsey, J . S. Tetrahedron 1994, 50, 11427-11440.

5884 J . Org. Chem., Vol. 65, No. 18, 2000
Notes
ing heme proteins,19 octopus porphyrins20 that form
monolayer assemblies, functional dendrimers21 and donor-
acceptor systems22 of potential applications. Enantiose-
lective catalysts can be designed by the introduction of
chiral substituents close to the catalytic center of met-
alloporphyrins.6,23 The three-dimensional architecture of
such molecules would also make them valuable as host
molecules for stereoselective molecular recognition.24
(0.352 g, 2 mmol) and 3,5-di-tert-butylphenol (0.906 g, 4.4 mmol)
gave 1c (0.775 g, 96%): mp 146-148 °C; 1H NMR (400 MHz,
CDCl3) δ 1.35 (s, 36H), 7.01 (d, J ) 1.6 Hz, 4H), 7.36 (s, 2H),
8.42 (s, 1H), 10.69 (s,1H); 13C NMR (100 MHz, CDCl3) δ 31.41,
115.90, 120.16, 151.87, 152.58, 161.18, 170.37, 186.08; IR (KBr),
v ) 2945, 1701, 1569, 1413 cm-1; EI-MS 516 (M+); Anal. Calcd
for C33H44N2O3 C, 76.71; H, 8.58; N, 5.42. Found: C, 76.76; H,
8.70; N, 5.10.
4,6-Bis(4-m et h oxyca r b on ylp h en oxy)p yr im id in e-5-ca r -
ba ld eh yd e (1d ). Reaction of 4,6-dichloropyrimidine-5-carbal-
dehyde (0.352 g, 2 mmol) and methyl 4-hydroxybenzoate (0.669
g, 4.4 mmol) gave 1d (0.718 g, 88%): mp 223-224 °C; 1H NMR
(400 MHz, CDCl3) δ 3.94 (s, 6H), 7.27 (d, J ) 6.8 Hz, 4H), 7.36
Exp er im en ta l Section
Gen er a l. Mass spectra were obtained on a Hewlett-Packard
MS instrument nE 5989A in EI (250 °C), on a Micromass Quatro
II in ESI (infusion of 50 `ıl MeOH/CH2Cl2-NH4OAc (0.1M in
MeOH) with a Harvard pump, model 11), and on a Micromass
Quatro II in APCI (250 µL of MeOH/CH2Cl2 using a Hewlett-
Packard HP 1100 binary pump and infusion of 20-30 µL of
MeOH/CH2Cl2-NH4OAc (0.1M in MeOH) with a Harvard pump
model 11).
(s, 2H), 8.16 (d, J ) 6.8 Hz, 4H), 8.38 (s, 1H), 10.65 (s, 1H); 13
C
NMR (100 MHz, CDCl3) δ 52.25, 103.53, 121.79, 128.26, 131.46,
155.55, 160.67, 166.07, 169.66, 185.02; IR(KBr), 1735, 1702,
1583, 1552, 1441 cm-1; APCI-MS 409 (MH)+. Anal. Calcd for
C
21H16N2O7 C, 61.77; H, 3.95; N; 6.86. Found: C, 61.63; H, 3.95;
N, 6.70.
4,6-Bis[3,5-b is(et h oxyca r b on yl)p h en oxy]p yr im id in e-5-
ca r ba ld eh yd e (1e). Reaction of 4,6-dichloropyrimidine-5-car-
baldehyde (0.352 g, 2 mmol) and diethyl isophthalate (1.05 g,
4.4 mmol) gave 1e (1.115 g, 96%): mp 147-148 °C; 1H NMR
(400 MHz, CDCl3) δ 1.42 (t, J ) 7.2 Hz, 6H), 4.43 (q, J ) 7.2
Hz, 4H), 8.06 (d, J ) 1.48 Hz, 4H), 8.37 (s, 1H), 8.64 (t, J ) 1.48
Hz, 2H), 10.68 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.26,
61.72, 103.43, 127.14, 128.35, 132.72, 151.93, 160.59, 164.73,
Gen er a l P r oced u r e for th e Syn th esis of 4,6-Disu bsti-
tu ted P yr im id in e-5-ca r ba ld eh yd es. To a well-stirred suspen-
sion of anhydrous potassium carbonate (1.52 g, 11 mmol) in THF
(100 mL) the substituted phenol (4.4 mmol) was added, and the
mixture was stirred with refluxing. After 0.5 h, 4,6-dichloropy-
rimidine-5-carbaldehyde 1a (0.352 g, 2 mmol) was added, and
the stirring and refluxing was continued for 5 h. The reaction
mixture was cooled, and solvent was removed under vacuum.
The residue was taken in dichloromethane (100 mL) and washed
with water (3 × 30 mL). The organic layer was dried over
magnesium sulfate and evaporated to give the crude product,
which precipitated on addition of methanol. The resulting
suspension was filtered to give the substituted pyrimidinecar-
baldehydes 1b-g as colorless solids. They were further purified
by recrystallization (methylene chloride/hexane, 1:1).
4,6-Bis[4-(ter t-b u t yl)p h en oxy]p yr im id in e-5-ca r b a ld e-
h yd e (1b). Reaction of 4,6-dichloropyrimidine-5-carbaldehyde
(0.352 g, 2 mmol) and 4-tert-butylphenol (0.660 g, 4.4 mmol) gave
1b (0.735 g, 91%): mp 160-161 °C; 1H NMR (400 MHz, CDCl3)
δ 1.36 (s, 18H), 7.12 (d, J ) 8.7 Hz, 4H), 7.47 (d, J ) 8.7 Hz,
4H), 8.45 (s, 1H), 10.66 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
31.42, 120.95, 126.65, 149.03, 149.77, 160.97, 170.23, 185.73; IR-
(KBr), v ) 2960, 2866, 1701, 1552, 1506, 1420 cm-1; EI-MS 404
(M+); Anal. Calcd for C25H28N2O3: C, 74.23; H, 6.98; N, 6.93.
Found: C, 74.22; H, 7.06; N, 6.85.
169.68, 184.82; IR(KBr) v ) 2976, 1740, 1721, 1700, 1553 cm-1
;
EI-MS 580 (M+). Anal. Calcd for C29H28N2O11 C, 60.00; H, 4.86;
N, 4.83. Found: C, 60.01; H, 4.83; N, 4.66.
4,6-Bis[estr a -17-oxo-1,3,5(10)-tr ien -3-oxy]p yr im id in e-5-
ca r ba ld eh yd e (1f). Reaction of 4,6-dichloropyrimidine-5-car-
baldehyde (0.352 g, 2 mmol) and estrone (1.190 g, 4.4 mmol)
gave 1d (0.953 g, 74%): mp >250 °C; 1H NMR (400 MHz, CDCl3)
δ 0.92 (s, 6H), 1.45-1.66 (m, 12H), 1.96-2.18 (m, 8H), 7.61 (t, J
) 8.0 Hz, 2H), 7.68 (d, J ) 8.0 Hz, 2H), 7.90 (t, J ) 8.0 Hz, 2H),
8.24 (d, J ) 8.0 Hz, 2H), 8.43 (s, 1H), 10.56 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 102.43, 125.46, 125.84, 127.55, 135.82,
141.27, 144.43, 160.46, 168.61, 185.01; IR(KBr), v ) 2928, 2858,
1737, 1700, 1552, 1491 cm-1; CI-MS 645 (MH)+. Anal. Calcd for
C41H44N2O5 C, 76.37; H, 6.88; N, 4.34. Found: C, 76.17; H, 6.81,
N, 4.15.
4,6-Bis(2-n itr op h en oxy)p yr im id in e-5-ca r ba ld eh yd e (1g).
Reaction of 4,6-dichloropyrimidine-5-carbaldehyde (0.352 g, 2
mmol) and 2-nitrophenol (0.612 g, 4.4 mmol) gave 1g (0.642 g,
84%): 1H NMR (400 MHz, CDCl3) δ 7.61 (t, J ) 8.0 Hz, 2H),
7.68 (d, J ) 8.0 Hz, 2H), 7.90 (t, J ) 8.0 Hz, 2H), 8.24 (d, J )
8.0 Hz, 2H), 8.43 (s, 1H), 10.56 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 102.43, 125.46, 125.84, 127.55, 135.82, 141.27, 144.43,
160.46, 168.61, 185.01; IR(KBr), v ) 1703, 1568, 1530, 1506,
1343 cm-1; CI-MS 383 (MH)+. Anal. Calcd for C17H10N4O7 C,
53.41; H, 2.64; N, 14.66. Found: C, 53.48; H, 2.65; N, 14.60.
Gen er a l P r oced u r e for th e Syn th esis of P or p h yr in s 2b -
g. A 0.05 M solution of pyrimidinecarbaldehyde 1b-g and
pyrrole (1 equiv) in dichloromethane was deoxygenated by
purging with argon for 15 min. Boron trifluoride etherate (0.1
equiv) was added by syringe, and the solution was stirred under
argon and protected from light for 2 h at 20 °C. p-Chloranil (1
equiv) was added, and the mixture was refluxed for 1 h. The
solvent was removed, and the residue was chromatographed
(silica gel; CH2Cl2). The obtained product was redissolved in
dichloromethane and precipitated with MeOH yielding 2b-g as
purple solids.
5,10,15,20-Tet r a k is[4,6-b is[4-(ter t-b u t yl)p h en oxy]p yr i-
m id in -5-yl]p or p h yr in (2b) was obtained from aldehyde 1b
(0.650 g, 1.61 mmol) following the general procedure (0.300 g,
40%): 1H NMR (400 MHz, CDCl3) δ -2.45 (s, 2H), 1.12 (72H,
s), 6.93 (d, J ) 8.8 Hz, 16H), 7.16 (d, J ) 8.8 Hz, 16H), 8.91 (s,
4H), 9.15 (s, 8H); UV-vis (CH2Cl2): λmax (log ꢀ) 422.1 (5.5978),
516.4 (4.2845), 549.3 (3.7736), 592.0 (3.8478), 646.9 (3.3078);
APCI-MS 1807.9 (MH+); Anal. Calcd for C116H118N12O8 C, 77.05;
H, 6.58; N, 9.29. Found: C, 76.98; H, 6.65; N, 9.33.
5,10,15,20-Tet r a k is[4,6-b is[3,5-b is(ter t-b u t yl)p h en oxy]-
p yr im id in -5-yl]p or p h yr in (2c) was obtained from aldehyde
1c (0.500 g, 0.97 mmol) following the general procedure (0.135
g, 24%): 1H NMR (400 MHz, CDCl3) δ -2.45 (s, 2H), 1.12 (s,-
144H), 6.80 (d, J ) 1.6 Hz, 16H), 7.07 (d, J ) 1.6 Hz, 16H), 8.88
4,6-Bis[3,5-d i(ter t-b u t yl)p h en oxy]p yr im id in e-5-ca r b a l-
d eh yd e (1c). Reaction of 4,6-dichloropyrimidine-5-carbaldehyde
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Chem. 1990, 55, 3628-3634. (e) Gross, Z.; Galili, N.; Simkhovich, L.
Tetrahedron Lett. 1999, 40, 1571-1574. (f) Gross, Z.; Ini, S. Org. Lett.
1999, 1, 2077-2080. (g) Gross, Z.; Ini, S.; Kapon, M.; Cohen, S.
Tetrahedron Lett. 1996, 37, 7325-7328. (h) Gross, Z.; Ini, S. J . Org.
Chem. 1997, 62, 5514-5521.
(24) (a) Kuroda, Y.; Kato, Y.; Higashioji, T.; Hasegawa, J .; Kawan-
ami, S.; Takahashi, M.; Shiraishi, N.; Tanabe, K.; Ogoshi, H. J . Am.
Chem. Soc. 1995, 117, 10950-10958. (b) Mizutani, T.; Ema, T.; Tomita,
T.; Kuroda, Y.; Ogoshi, H. J . Am. Chem. Soc. 1994, 116, 4240-4250.

Notes
J . Org. Chem., Vol. 65, No. 18, 2000 5885
(s, 4H), 9.21 (s, 8H); UV-vis (CH2Cl2): λmax (log ꢀ) 422.1 (5.5978),
516.4 (4.2845), 549.3 (3.7736), 592.0 (3.8478), 646.9 (3.3078);
APCI-MS 2056.4 (MH+); Anal. Calcd for C148H182N12O8 C, 78.76;
H, 8.13; N, 7.45. Found: C, 78.60; H, 8.00; N, 7.43.
5,10,15,20-Tetr a k is[4,6-bis(4-m eth oxyca r bon ylp h en oxy)-
p yr im id in -5-yl]p or p h yr in (2d ) was obtained from aldehyde
1d (0.500 g, 1.22 mmol) following the general procedure (0.303
g, 54%): 1H NMR (400 MHz, CDCl3) δ -2.37 (s, 2H), 3.83 (s,
24H), 7.04 (d, J ) 8.8 Hz, 16H), 7.89 (d, J ) 8.8 Hz, 16H), 8.87
(s, 4H), 9.16 (s, 8H); UV-vis (CH2Cl2): λmax (log ꢀ) 422.0 (5.6952),
518.1 (4.3272), 547.8 (3.5906), 591.6 (3.7848), 647.03 (2.2552);
APCI-MS 1823.5 (MH+). Anal. Calcd for C100H70N12O24 C, 65.86;
H, 3.87; N, 9.22. Found: C, 65.46; H, 3.97; N, 8.97.
5,10,15,20-Tetr a k is(4,6-bis(3,5-bis(eth oxyca r bon yl)p h e-
n oxy)p yr im id in -5-yl)p or p h yr in (2e) was obtained from al-
dehyde 1e (0.500 g, 0.86 mmol) following the general procedure
(0.320 g, 59%): 1H NMR (400 MHz, CDCl3) δ -2.29 (s, 2H), 1.25
(t, J ) 7.2 Hz, 48H), 4.24 (q, J ) 7.2 Hz, 32H), 7.87 (d, J ) 1.4
Hz, 16H), 8.40 (t, J ) 1.4 Hz, 8H), 8.84 (s, 4H), 9.28 (s, 8H);
UV-vis (CH2Cl2): λmax (log ꢀ) 421.3 (5.6727), 515.1 (4.3407),
545.9 (3.6300), 590.4 (3.8511), 645.0 (3.0256); ES-MS 2511.8
(MH+); Anal. Calcd for C132H118N12O40 C, 63.10; H, 4.73; N, 6.69.
Found: C, 63.02; H, 4.72; N, 6.54.
5,10,15,20-Tetr a k is[4,6-bis[estr a -17-oxo-1,3,5(10)-tr ien -3-
oxy]-p yr im id in -5-yl]p or p h yr in (2f) was obtained from alde-
hyde 1f (0.810 g, 1.26 mmol) following the general procedure
(0.260 g, 30%): 1H NMR (400 MHz, CDCl3) δ -2.54 (s, 2H), 0.68
(s, 24H), 1.05-1.60 (m, 48H), 1.65-2.45 (m, 56H), 2.50-265 (m,
16H), 6.65 (d, J ) 2.3 Hz, 8H), 6.79 (dd, J ) 8.5, 2.3 Hz, 8H),
7.03 (d, J ) 8.4 Hz, 8H), 8.91 (s, 4H), 9.18 (s, 8H); UV-vis (CH2-
Cl2): λmax (log ꢀ) 422.3 (5.8151), 516.8 (4.5928), 547.7 (4.1209),
593.0 (4.1673), 647.2 (3.8322); APCI-MS 2768.4 (MH+). Anal.
Calcd for C180H182N12O16 C, 78.06; H, 6.62; N, 6.07. Found: C,
78.05; H, 6.54; N, 6.19.
organic layer was washed three times with water (3 × 20 mL)
and dried over MgSO4. The solvent was removed and the residue
purified by column chromatography (silica gel; dichloromethane/
hexane 3/1). The obtained product was redissolved in dichlo-
romethane and precipitated with MeOH yielding 3b-d as purple
solids.
5,15-Bis[4,6-d i(4-b r om op h en oxy)p yr im id in -5-yl]-10,20-
bis(2,4,6-tr im eth ylp h en yl]p or p h yr in (3c) was obtained from
4-bromophenol following the general procedure (0.074 g, 90%):
1H NMR (400 MHz, CDCl3) δ -2.43 (s, 2H), 1.86 (s, 12H), 2.64
(s, 6H), 6.87 (d, J ) 8.9 Hz, 8H), 7.31 (s, 4H), 7.32 (d, J ) 8.9
Hz, 8H), 8.78 (d, J ) 4.7 Hz, 4H), 8.81 (s, 2H), 8.94 (d, J ) 4.7
Hz, 4H); UV-vis (CH2Cl2): λmax (log ꢀ) 419.1 (5.7318), 514.5
(4.3567), 548.1 (3.9324), 591.0 (3.8667), 646.6 (3.6673); APCI-
MS 1383.0/1385.0/1387.0/1389.0/1391.0 (MH+). Anal. Calcd for
C70H50Br4N8O4 C, 60.63; H, 3.63; N, 8.08. Found: C, 60.49; H,
3.74; N, 7.80.
5,15-Bis[4,6-b is[4-(ter t-b u t yl)p h en oxy]p yr im id in -5-yl]-
10,20-b is(2,4,6-t r im et h ylp h en yl)p or p h yr in (3d ) was ob-
tained from 4-tert-butylphenol following the general procedure
(0.050 g, 60%): 1H NMR (400 MHz, CDCl3) δ -2.45 (s, 2H), 1.16
(s, 36H), 1.88 (s, 12H), 2.65 (s, 6H), 6.90 (d, J ) 8.8 Hz, 8H),
7.19 (d, J ) 8.8 Hz, 8H), 7.31 (s, 4H), 8.76 (d, J ) 4.7 Hz, 4H),
8.86 (s, 2H), 8.99 (d, J ) 4.7 Hz, 4H); UV-vis (CH2Cl2): λmax
(log ꢀ) 419.2 (5.6847), 514.8 (4.3141), 548.4 (3.8706), 591.2
(3.8047), 646.9 (3.5729); APCI-MS 1295.7 (MH+). Anal. Calcd
for C86H86N8O4: C, 79.72; H, 6.69; N, 8.65. Found: C, 79.60; H,
6.79; N, 8.65.
5,10-Bis[4,6-b is[est r a -17-oxo-1,3,5(10)-t r ien -3-oxy]p yr i-
m idin -5-yl]-10,20- bis(2,4,6-tr im eth ylph en yl)por ph yr in (3e)
was obtained from estrone following the general procedure (0.080
g, 75%): 1H NMR (400 MHz, CDCl3) δ -2.44 (s, 2H), 0.79 (s,
12H), 1.20-1.60 (m, 24H), 1.86 (s, 12H), 1.80-2.20 (m, 20H),
2.22-2.29 (m, 4H), 2.38-2.48 (m, 4H), 2.65 (s, 6H), 2.68-2.76
(m, 8H), 6.67 (d, J ) 2.4 Hz, 4H), 6.79 (dd, J ) 8.6, 2.4 Hz, 4H),
7.12 (d, J ) 8.6 Hz, 4H), 7.31 (s, 4H), 8.77 (d, J ) 4.7 Hz, 4H),
8.86 (s, 2H), 8.99 (d, J ) 4.7 Hz, 4H); UV-vis (CH2Cl2): λmax
(log ꢀ) 419.5 (5.6662), 515.1 (4.3235), 548.2 (3.8699), 591.4
(3.8123), 647.1 (3.5959); APCI-MS 1777.2 (MH+). Anal. Calcd
for C118H118N8O8 C, 79.79; H, 6.70; N, 6.31. Found: C, 79.31; H,
6.70; N, 6.17.
5,15-Bis(4,6-d im eth oxyp yr im id in -5-yl)-10,20-bis(2,4,6-tr i-
m eth ylp h en yl)p or p h yr in (3b). To a well-stirred suspension
of sodium hydride (80%, 0.040 g, 1.3 mmol) in DMF (5 mL) under
argon was added methanol (0.06 mL, 1.48 mmol), and the
mixture was stirred for 15 min at room temperature. A solution
of porphyrin 3a (33.6 mg, 0.04 mmol) in DMF (5 mL) was added,
and the mixture was stirred 60 °C for 40 h. The mixture was
allowed to reach room temperature, water (30 mL) was added,
and the mixture was extracted with dichloromethane (3 × 30
mL). The combined organics were washed with water (3 × 30
mL), dried over anhydrous magnesium sulfate, and evaporated
under vacuum. The residue was chromatographed (silica gel/
dichloromethane) to afford porphyrin 3e which was recrystal-
lized from dichloromethane/methanol (1:1) (0.015 g, 46%): 1H
NMR (400 MHz, CDCl3) δ -2.51 (s, 2H), 1.85 (s, 12H), 2.62 (s,
6H); 3.82(s, 12H); 7.26 (s, 4H), 8.64 (d, J ) 4.7 Hz, 4H), 8.67 (s,
2H), 8.91 (d, J ) 4.7 Hz, 4H); UV-vis (CH2Cl2): λmax (log ꢀ) 417.8
(5.6202), 514.0 (4.2505), 546.8 (3.7227), 590.2 (3.7282), 645.6
(3.4422). APCI-MS 883 (MH+). Anal. Calcd for C50H46N8O4: C,
72.97; H, 5.63; N, 13.62. Found: C, 72.85; H, 5.50; N, 13.60.
5,10,15,20-Tetr a k is[4,6-bis(2-n itr op h en oxy)p yr im id in -5-
yl]p or p h yr in (2g) was obtained from aldehyde 1g (0.500 g, 1.31
mmol) following the general procedure (0.035 g, 6.2%). Modifica-
tion of this procedure using a 5 × 10-3 M solution yielded
porphyrin 2g (0.053 g) in 10% yield; 1H NMR (400 MHz, DMSO)
δ -2.71 (s, 2H), 7.40 (d, J ) 5.8 Hz, 16H), 7.77 (t, J ) 7.4 Hz,
8H), 8.02 (d, J ) 8.0 Hz, 8H), 8.83 (s, 4H), 9.54 (s, 8H); UV-vis
(THF): λmax (log ꢀ) 419.8 (4.4651), 513.2 (4.2741), 540.0 (4.0840),
590.2 (4.0905); ESI-MS 1718.3 (MH+). Anal. Calcd for
C
84H46N20O24: C, 58.68; H, 2.70; N, 16.29. Found: C, 58.61; H,
2.79; N, 16.00.
5,15-Bis(4,6-d ich lor op yr im id in -5-yl)-10,20-bis(2,4,6-tr im -
eth ylp h en yl)p or p h yr in (3a ). A solution of 2,4,6-trimethylphe-
nyldipyrromethane (0.500 g, 1.89 mmol) and 4,6-dichloropyri-
midine-5-carbaldehyde (0.337 g, 1.89 mmol) in dichloromethane
(500 mL) was deoxygenated by purging with argon for 15 min.
Boron trifluoride etherate (0.020 g, 0.19 mmol) was added by
syringe, and the solution was stirred under argon and protected
from light for 1 h at room temperature. p-Chloranil (0.454 g,
1.89 mmol) was added, and the mixture was refluxed for 1 h.
The solvent was removed and the residue chromatographed
(silica gel, dichloromethane) yielding porphyrin 3 as a purple
solid (0.445 g, 53%): 1H NMR (400 MHz, CDCl3) δ -2.50 (s, 2H),
1.86 (s, 12H), 2.63 (s, 6H), 7.29 (s, 4H), 8.59 (d, J ) 4.8 Hz, 4H),
8.76 (d, J ) 4.8 Hz, 4H), 9.26 (s, 2H); 13C NMR (100 MHz, CDCl3)
δ 21.45, 21.75, 108.97, 120.00, 127.96, 129.03, 131.88, 134.72,
137.28, 138.30, 139.35, 158.22, 164.06; UV-vis (CH2Cl2): λmax
(log ꢀ) 419.4 (5.8111), 514.6 (4.4410), 548.1 (3.8030), 591.2
(3.8255), 647.9 (3.5997); ESI-MS 839.2 (MH+). Anal. Calcd for
Ack n ow led gm en t. We thank the Ministerie voor
Wetenschapsbeleid, the FWO-Vlaanderen, and the
Katholieke Universiteit Leuven for their financial sup-
port. C.V.A. and S.S. thank the Research Council of the
KULeuven and the IWT for postdoctoral and predoctoral
fellowships, respectively.
C
43H34N14O8: C, 65.72; H, 4.08; N, 13.33. Found: C, 65.81; H,
4.11; N, 13.36.
Gen er a l P r oced u r e for Syn th esis of P or p h yr in s 3c-e.
To a solution of porphyrin 3a (0.050 g, 0.06 mmol) and
substituted phenol (4.4 equiv) in dry DMF (4 mL) was added
K2CO3 (8.8 equiv). The mixture was stirred for 72 h at 60 °C
under argon atmosphere. The solution was allowed to reach room
temperature, and dichloromethane (20 mL) was added. The
J O0007938