Convenient synthetic route of versatile 21-monothiatetraphenylporphyrins of the A4 and AB3 type

Article abstract of DOI:10.1016/j.tet.2005.01.037

A novel convenient synthetic route for poly-functional 21- monothiatetraphenylporphyrins of the type A₄ und AB₃ having base labile substituents in meso position was developed. Using this method a series of symmetric and asymmetric 21-thiaporphyrins containing different functional groups at the meso position is reported. The new products were characterized by NMR, UV-Vis and mass spectroscopy.

Full text of DOI:10.1016/j.tet.2005.01.037

Tetrahedron 61 (2005) 2907–2912
Convenient synthetic route of versatile
21-monothiatetraphenylporphyrins of the A4 and AB3 type
*
Silvio Stute, Kerstin Gloe and Karsten Gloe
¨ ¨
Institut fur Anorganische Chemie, Technische Universitat Dresden, 01062 Dresden, Germany
Received 2 December 2004; revised 11 January 2005; accepted 12 January 2005
Abstract—A novel convenient synthetic route for poly-functional 21-monothiatetraphenylporphyrins of the type A4 und AB3 having base
labile substituents in meso position was developed. Using this method a series of symmetric and asymmetric 21-thiaporphyrins containing
different functional groups at the meso position is reported. The new products were characterized by NMR, UV–Vis and mass spectroscopy.
q 2005 Elsevier Ltd. All rights reserved.
Table 1. Yields of thiophene diols
1. Introduction
Compound
Substituent R
Yield [%]
1
2
Core-modified porphyrins show new interesting properties
in metal-complexation, acid–base behaviour, redox-poten-
tials, photochemistry and medicine in comparison with the
well-known N4 porphyrin system that may lead to useful
applications.1–6 21-Monothiatetraphenylporphyrins repre-
sent such a promising type; asymmetric substituted AB2C
and AB3 monothiatetraphenylporphyrins were previously
reported, although the synthesis of reactive functional
groups at the phenyl substituents has been difficult to
achieve.7,8 Groups such as carboxylic, amino, bromo, and
hydroxy are needed as building blocks for the construction
of large porphyrin arrays or for the dendritic encapsulation
of the units. Such large and defined supramolecular
structures and their metal complexes open up new
application possibilities in medicine, optoelectronics and
catalysis.9–12
4-COOMe
40
3,5-OMe
95
substituents is the established reaction sequence (addition
the aldehyde to the dianion) the favoured method. However,
the procedure does not work when base-labile substituents
on the benzaldehyde, for example, phenylcarboxylates, are
used due to side reactions between the carboxylic
substituents and the dianion. In order to avoid more
complex protective groups or longer reaction sequences,
we changed the reaction order at the addition step. The
addition of the thiophene dilithiate to the base-labile
benzaldehyde leads to the wanted substituted diols in
good yields (Table 1). The synthesis of the desired
21-monothiatetraphenylporphyrins from the prepared diols
occurred with the well established Lindsey-conditions,14,15
which obviously gives higher yields in comparison with the
method described by Adler et al.16,17 The porphyrin
condensation resulted in the mixture of three porhyrins
with different core patterns: N4, N3S and N2S2. The
porphyrins were separated by column chromatography, in
which the desired monothiaporphyrins eluted as the second
porphyrin fraction. The ether and ester cleavage was
accomplished by common methods (Table 2) (Scheme 1).
2. Results and discussion
2.1. Modified synthesis of symmetric thiophene diols and
corresponding porphyrins
The preparation of 2,5-bis-phenylhydroxymethyl substi-
tuted thiophene occurs with the classical deprotonation of
the a-hydrogens on the thiophene with n-butyl lithium and
subsequent addition of the benzaldehyde-derivative to
the bislithiated dianion.13 For base-insensitive phenyl
2.2. Modified synthesis of asymmetric thiophene diols
and corresponding porphyrins
We are also interested in synthesizing asymmetric mono-
thiatetraphenylporphyrins of the type AB3. The direct
condensation of thiophene mono-ols to thiaporphyrins
Keywords: Porphyrins; Synthesis; Sulphur; Asymmetry.
* Corresponding author. Tel.: C49 351 463 31479; fax: C49 351 463
31478; e-mail: silvio.stute@chemie.tu-dresden.de
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.037

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S. Stute et al. / Tetrahedron 61 (2005) 2907–2912
Table 2. Yields of symmetric thiaporphyrins
Compound
Substituent R
Yield [%]
8
9
10
4-OMe
19
11
4-COOH
96a
12
3,5-OH
91a
13
4-OH
92a
4-COOMe
22
3,5-OMe
18
a These yields are related to the deprotecting reaction.
Scheme 1. General synthetic scheme of symmetric thiaporphyrins.
Table 3. Yields of asymmetric thiophene diols
Compound
3
4
5
6
7
Substituent R0
Substituent R
Substituent R00
4-Br
OMe
H
4-Br
OAllyl
5-Br
4-Br
OMe
5-Br
3,5-OMe
OAllyl
3-OMe
4-COOMe
OAllyl
H
Yield [%]
36
21
38
18
11
appears due to the lower yields rather unfavourable, thus the
preparation of unsymmetrical thiophene diols is necessary.
This can be effected, such as already described, with a
stepwise procedure8 or like in our case in one concerted
step as described above, with the main difference of using
two differently substituted aldehydes (Table 3). This
reaction yields more side-products, but saves one reaction
step, and is necessary for substituents that are unstable
under the drastic lithiation condition. The chromatographic
separation of the desired diol was achieved without
any problems. Standard porphyrin synthesis resulted
in asymmetric monothiaporphyrins with different core
patterns: N4, N3S and N2S2. The porphyrins were separated
by column chromatography, in which the desired
Table 4. Yields of asymmetric thiaporphyrins
Compound
14
15
16
17
18
4-COOMe
OAllyl
H
7
Substituent R0
Substituent R
Substituent R00
Yield [%]
4-Br
OMe
H
4-Br
OAllyl
5-Br
15
4-Br
OMe
5-Br
9
3,5-OMe
OAllyl
3-OMe
4
3
Scheme 2. General synthetic scheme of asymmetric thiaporphyrins.

S. Stute et al. / Tetrahedron 61 (2005) 2907–2912
2909
Figure 1. 1H NMR spectrum of 15 recorded in CDCl3. Resonance assignments: HT, thiophene H; HP, pyrrole H; HAr, H of the phenyl rings. The showed
spectrum corresponds with the accomplished 2D NMR measurements.
monothiaporphyrins eluted as the second porphyrin fraction
(Table 4) (Scheme 2).
4. Experimental
4.1. General
The displayed NMR (Fig. 1) and absorption (Fig. 2) spectras
of the monothiatetraphenylporhyrin 15 indicate the asym-
metric structure and the typical absorption behaviour.
1H and 13C NMR spectra were obtained on a Bruker DRX-
500 at 500 and 126 MHz, respectively. UV/Vis spectra were
recorded on a Perkin Elmer Lambda 2. The mass spectra
were measured on a Esquire Hewlett & Packard and a
Shimadzu Kratos Kompact MALDI II mass spectrometer.
Column chromatography was carried out with silica gel 60
(0.040–0.063 mm Merck). Fine chemicals were supplied by
Fluka and solvents were dried by standard procedures
before use.
3. Conclusion
We report a modified synthetic method to generate novel
monothiatetraphenylporphyrins having carboxyphenylic
substituents at the meso position. The marginal additional
preparative expense of our method results in better yields
and smaller amounts of side products. We also describe an
alternative way to obtain AB3-type 21-thiaporphyrins with
acceptable yields based on the one step synthesis of the
asymmetrical thiophene diol precursor. The preparation and
characterization of transition metal complexes with these
heteroporphyrins are now underway in our group.
4.2. Data for compounds
The preparation of 5,10,15,20-(4-methoxyphenyl)-21-thia-
porphyrin 10 and 5,10,15,20-(4-bromophenyl)-21-thiapor-
phyrin were described earlier but we used our modified
approach.18
Figure 2. Absorption spectrum of 15 recorded in toluene. The concentrations used were 5!10K6 and 5!10K5 M, respectively. Enlarged Q-Bands are shown
in the inset.

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S. Stute et al. / Tetrahedron 61 (2005) 2907–2912
4.2.1.
2,5-Bis[(4-carboxymethyl)phenyl(hydroxy)-
2.97 ml), n-butyl lithium (38 ml of 1.6 M solution) and
thiophene (9.5 mmol, 750 ml) for the dilithiated thiophene,
which was added at 0 8C to a precooled 1:1 mixture of
4-bromobenzaldehyde (9.5 mmol, 1.76 g) and 2-allyloxy-5-
bromobenzaldeyhde (9.5 mmol, 2.285 g) in dry THF
(30 ml). The crude product was purified by silica gel
column chromatography (ethyl acetate/n-heptane 3:7) and
obtained as yellow solid (1.0 g, 21%).
methyl]-thiophene 1. In a three neck flask equipped
with rubber septum, gas inlet tube and reflux condenser
dry n-hexane (25 ml) was taken. TMEDA (16 mmol,
1.86 ml) and n-butyl lithium (20 ml of a 1.6 M solution)
were added into the stirred solution. Destilled thiophene
(8 mmol, 317 ml) was added and the reaction mixture was
refluxed for 1 h under slow argon purging.
After this time, the dilithiated thiophene mixture was cooled
to 0 8C and transferred into the ice cold solution of methyl
4-formylbenzoate (16 mmol, 2.63 g) in dry THF (30 ml).
The mixture was stirred for 10 min and saturated NH4Cl
added to quench the reaction. The organic layer was
extracted with ethyl acetate and dried over Na2SO4. The
crude product was purified by silica gel column chroma-
tography (ethyl acetate/n-heptane 1:1) and the desired diol 1
was obtained besides small amounts of unreacted aldehyde
and mono-ol as the third fraction (1.32 g, 40%).
1H NMR (CDCl3, d in ppm) 2.3 (bs, 1H, OH); 3.0 (m, 1H,
OH); 4.5 (m, 2H, OCH2); 5.25 (dd, 2H, CH2); 5.9 (dq, 1H,
CH); 5.95 (d, 1H, CH); 6.15 (d, 1H, CH); 6.65 (d, 2H,
b-thiophene); 6.7 (d, 1H, meta-H); 7.3 (d, 2H, ortho-H);
7.35 (dd, 1H, para-H); 7.45 (d, 2H, meta-H); 7.5 (d, 1H,
ortho-H).
4.2.5. 2-[(4-Bromo)phenylhydroxymethyl]-5-[(2-meth-
oxy-5-bromophenyl)hydroxymethyl]-thiophene 5. Com-
pound 5 was prepared following the same method given for
1 by using dry n-hexane (20 ml), TMEDA (10.8 mmol,
1.62 ml), n-butyl lithium (13.5 ml of 1.6 M solution) and
thiophene (5.4 mmol, 430 ml) for the dilithiated thiophene.
The mixture was cooled to 0 8C and transferred into a
precooled 1:1 mixture of 4-bromobenzaldehyde (5.4 mmol,
1.0 g) and 2-methoxy-5-bromobenzaldehyde (5.4 mmol,
1.16 g) in dry THF (30 ml). The crude product was purified
by silica gel column chromatography (ethyl acetate/
n-heptane 3:7). Compound 5 was obtained as a colorless
solid (0.992 g, 38%).
1H NMR (CDCl3, d in ppm) 2.65 (bs, 2H, OH), 3.9 (s, 6H,
OMe), 6.0 (s, 2H, CH), 6.7 (s, 2H, b-thiophene), 7.5 (d, 4H,
meta-H), 8.0 (d, 4H, ortho-H).
4.2.2. 2,5-Bis[(3,5-methoxy)phenyl(hydroxy)methyl]-
thiophene 2. Compound 2 was prepared following the
same method given for 1 by using dry n-hexane (10 ml),
TMEDA (10 mmol, 1.5 ml), n-butyl lithium (6.25 ml of
1.6 M solution) and thiophene (5 mmol, 397 ml) for the
dilithiated thiophene, which was added at 0 8C to a
precooled solution of 3,5-methoxybenzaldehyde
(10 mmol, 1.66 g) in dry THF (10 ml). The crude product
was purified by silica gel column chromatography in ethyl
acetate/n-heptane (4:6). Compound 2 was obtained as a
white solid (1.98 g, 95%).
1H NMR (CDCl3, d in ppm) 2.45 (m, 1H, OH); 3.05 (m, 1H,
OH); 3.75 (d, 3H, OMe); 5.9 (d, 1H, CH); 6.1 (d, 1H, CH);
6.15 (2d, 2H, b-thiophene); 6.25 (dd, 1H, meta-H); 7.3 (d,
2H, ortho-H); 7.35 (dd, 1H, para-H); 7.45 (d, 2H, meta-H);
7.5 (d, 1H, ortho-H).
1H NMR (CDCl3, d in ppm) 2.9 (bs, 2H, OH); 3.75 (s, 12H,
OMe); 5.85 (d, 2H, CH); 6.45 (t, 2H, para-H); 6.6 (d, 4H,
ortho-H); 6.7 (s, 2H, b-thiophene).
4.2.6. 2-[(3,5-Methoxy)phenylhydroxymethyl]-5-[(2-allyl-
oxy-3-methoxyphenyl)hydroxymethyl]-thiophene 6.
Compound 6 was synthesized in the same way as 1 by
using dry n-hexane (25 ml), TMEDA (15.6 mmol, 2.34 ml),
n-butyl lithium (19.5 ml of 1.6 M solution) and thiophene
(7.8 mmol, 660 ml). The mixture of the dilithiated thiophene
was cooled to 0 8C and transferred into a cold solution
of 3,5-dimethoxybenzaldehyde (7.8 mmol, 1.29 g) and
2-allyloxy-3-methoxybenzaldehyde (7.8 mmol, 1.5 g) in
dry THF (30 ml). Purification of the product was done by
silica gel column chromatography (ethyl acetate/n-heptane
1:1). Compound 6 was isolated as a yellow solid (0.61 g,
18%).
4.2.3. 2-[(4-Bromo)phenylhydroxymethyl]-5-[(2-methoxy-
phenyl)hydroxymethyl]-thiophene 3. Compound 3 was
synthesized in the same way as 1 by using dry n-hexane
(25 ml), TMEDA (19 mmol, 2.87 ml), n-butyl lithium
(23.9 ml of 1.6 M solution) and thiophene (9.6 mmol,
766 ml) for the dilithiated thiophene. This mixture was
added at 0 8C to a precooled 1:1 mixture of 4-bromobenz-
aldehyde (9.6 mmol, 1.77 g) and 2-methoxybenzaldehyde
(9.6 mmol, 1.30 g) in dry THF (30 ml). The crude product
was purified by silica gel column chromatography (ethyl
acetate/n-heptane 1:1). 2 was obtained as a yellow solid
(1.39 g, 36%).
1H NMR (CDCl3, d in ppm) 2.3 (bs, 1H, OH); 3.2 (dd, 1H,
OH); 3.75 (s, 6H, OMe); 3.85 (s, 3H, OMe); 4.35 (m, 2H,
OCH2); 5.2 (m, 2H, CH2); 5.85 (m, 1H, CH); 5.9 (d, 1H,
CH); 6.1 (t, 1H, CH); 6.35 (t, 2H, b-thiophene); 6.55 (s, 2H,
ortho-H); 6.65 (t, 1H, para-H); 6.85 (dd, 1H, H-Ar); 7.0 (dt,
1H, H-Ar); 7.05 (dd, 1H, H-Ar).
1H NMR (CDCl3, d in ppm): 2.4 (bs, 1H, OH); 3.25 (bs, 1H,
OH); 3.8 (s, 3H, OMe); 5.9 (s, 1H, CH); 6.1 (s, 1H, CH);
6.7 (m, 2H, thiophene); 6.85 (d, 1H, H-Ar); 6.95 (t, 1H,
H-Ar); 7.3 (t, 2H, ortho-H); 7.35 (d, 1H, H-Ar) 7.4 (d, 2H,
metha-H).
4.2.7. 2-[(4-Carboxymethyl)phenylhydroxymethyl]-5-
[(2-allyloxyphenyl)hydroxymethyl]-thiophene 7. The
synthesis of 7 followed the same manner as given for 1 by
using dry n-hexane (10 ml), TMEDA (26 mmol, 3.9 ml),
n-butyl lithium (32.5 ml of 1.6 M solution) and thiophene
(13 mmol, 1.03 ml). After cooling to 0 8C, the mixture of the
4.2.4. 2-[(4-Bromo)phenylhydroxymethyl]-5-[(2-allyl-
oxy-5-bromophenyl)hydroxymethyl]-thiophene 4. Prepa-
ration of 4 was done following the same method given for 1
by using dry n-hexane (30 ml), TMEDA (19 mmol,

S. Stute et al. / Tetrahedron 61 (2005) 2907–2912
2911
dilithiated thiophene was cooled added to a cold solution of
methyl 4-formylbenzoate (13 mmol, 2.17 g) and 2-allyloxy-
benzaldehyde (13 mmol, 2.14 g) in dry THF (15 ml). After
separating by silica gel column chromatography (ethyl
acetate/n-heptane 1:1), 7 was isolated as a yellow solid
(0.59 g, 11%).
1H NMR (CDCl3, d in ppm) K2.7 (bs, 1H, NH); 4.1 (s, 12H,
OMe); 7.3 (dd, 8H, meta-H); 8.1 (dd, 8H, ortho-H); 8.65
(dd, 4H, b-pyrrole); 8.95 (d, 2H, b-pyrrole); 9.75 (s, 2H,
b-thiophene). MALDI-MS obsd mass 753, calcd mass
751.9.
4.2.11. 5,10,15,20-(4-Carboxy)phenyl-21-thiaporphyrin
11. Compound 8 (0.17 mmol, 150 mg) was dissolved in
THF (20 ml) and water (10 ml) and LiOH (30 mmol,
750 mg) was added. The mixture was refluxed for 5 h,
THF was removed and the pH value was set to 4 (1 N HCl),
so the porphyrin 10 precipitated. After centrifugation the
water was removed and the product was washed with cold
ethyl acetate and water (0.134 g, 96%).
1H NMR (CDCl3, d in ppm) 2.4 (bs, 1H, OH); 3.3 (m, 1H,
OH); 3.9 (s, 3H, OMe); 4.5 (bs, 2H, OCH2); 5.2 (m, 2H,
CH2); 5.9 (dqi, 1H, CH); 6.0 (d, 1H, CH); 6.15 (t, 1H, CH);
6.7 (m, 2H, b-thiophene); 6.85 (d, 1H, H-Ar); 6.95 (t, 1H,
H-Ar); 7.3 (t, 1H, H-Ar); 7.4 (d, 1H, H-Ar); 7.5 (d, 2H,
ortho-H); 8.0 (d, 2H, metha-H).
4.2.8. 5,10,15,20-(4-Carboxymethyl)phenyl-21-thia-
porphyrin 8. Diol
1H NMR (DMSO-d6, d in ppm) K2.8 (s, 1H, NH); 8.37 (d,
8H, ortho-H); 8.39 (d, 8H, metha-H); 8.6 (dd, 4H,
b-pyrrole); 9.0 (d, 2H, b-pyrrole); 9.8 (s, 2H, b-thiophene);
11.1 (bs, 4H, COOH). ESI-MS (C75 V) obsd mass 808,
calcd mass 807.95.
1 (3.2 mmol, 1.32 g), methyl
4-formylbenzoate (6.4 mmol, 1.05 g) and pyrrole
(9.6 mmol, 665 ml) were dissolved in dry CH2Cl2 (350 ml)
under argon purging (degassing) in a one-neck flask.
BF3$OEt2 (0.32 mmol, 40 ml) was added to start the
cyclocondensation and the reaction mixture was stirred for
2 h under argon atmosphere in the dark at room temperature.
DDQ (96 mmol, 2.18 g) was added and the solution was
stirred on air for additional 3 h. The solvent was removed
under reduced pressure and the compound was isolated by
silica gel column chromatography (chloroform/methanol
99:1) as eluent to acquire the purple solid in the second
yellow-brown fraction (0.61 g, 22%).
4.2.12. 5,10,15,20-(3,5-Hydroxy)phenyl-21-thiapor-
phyrin 12. BBr3 (6.02 mmol, 580 ml) was transferred into
a solution of 9 (0.40 g, 0.46 mmol) in 25 ml of dry CH2Cl2
and stirred for 24 h at room temperature under dry
conditions. The reaction was quenched with water, the pH
value was set to 7 (1 N NaOH) and the phases were
separated. The aqueous phase was extracted with ethyl
acetate. The organic layers were dried over Na2SO4 and the
solvent was evaporated. Purification was done by silica gel
column chromatography (ethyl acetate). After removing
solvent the product affords as dark purple solid (0.32 g,
91%).
1H NMR (CDCl3, d in ppm) K2.75 (s, 1H, NH), 4.1 (s, 9H,
COOMe), 8.28 (d, 4H, Haryl), 8.33 (d, 4H, Haryl), 8.45 (d,
4H, Haryl), 8.5 (d, 4H, Haryl), 8.6 (d, 4H, b-pyrrole), 8.9 (s,
2H, b-pyrrole), 9.7 (s, 2H, b-thiophene). ESI-MS (C75 V)
obsd mass 864, calcd mass 863.95.
1H NMR (acetone-d6, d in ppm) K2.7 (s, 1H, NH); 6.9
(t, 4H, para-H); 7.3 (d, 8H, ortho-H); 8.75 (2 s, 8H, OH);
8.8 (d, 4H, b-pyrrole); 9.2 (d, 2H, b-pyrrole); 9.95 (s, 2H,
b-thiophene). ESI-MS (C75 V) obsd mass 760, 821
[MCHAc], calcd mass 759.8.
4.2.9. 5,10,15,20-(3,5-Methoxy)phenyl-21-thiaporphyrin
9. Compound 9 was synthesized in the same procedure like
8, using dry CH2Cl2 (200 ml), diol 2 (2.6 mmol, 1.1 g),
3,5-methoxybenzaldehyde (5.3 mmol, 0.88 g) and pyrrole
(7.9 mmol, 547 ml). BF3$OEt2 (0.3 mmol, 37.5 ml) was
added to start the reaction. After stirring for 1 h, DDQ
(5.3 mmol, 1.2 g) was added. The crude product was
purified by silica gel column chromatography (chloroform)
and isolated as a purple, crystalline solid (0.40 g, 18%).
4.2.13. 5,10,15,20-(4-Hydroxy)phenyl-21-thiaporphyrin
13. Compound 13 was synthesized like porphyrin 11,
dissolving 12a (0.114 mmol, 0.086 g) in CH2Cl2 (8 ml) and
adding BBr3 (1.14 mmol, 110 ml). The product (73 mg,
92%) was isolated by silica gel column chromatography
(ethyl acetate).
1H NMR (CDCl3, d in ppm) K2.75 (bs, 1H, NH); 3.9
(d, 24H, OMe); 6.9 (t, 4H, para-H); 7.4 (dd, 8H, ortho-H);
8.7 (dd, 4H, b-pyrrole); 9.0 (d, 2H, b-pyrrole); 9.8 (s, 2H,
b-thiophene). ESI-MS (C75 V) obsd mass 872, calcd mass
872.02.
1H NMR (acetone-d6, d in ppm) K2.5 (s, 1H, NH); 7.4 (dd,
8H, meta-H); 8.1 (dd, 8H, ortho-H); 8.7 (d, 2H, b-pyrrole);
8.9 (2 s, 4H, OH); 9.1 (s, 2H, b-pyrrole); 9.9 (s, 2H, b-thio-
phene). MALDI-MS obsd mass 697, calcd mass 695.8.
4.2.10. 5,10,15,20-(4-Methoxy)phenyl-21-thiaporphyrin
10. Compound 10 was synthesized in the same manner
like 8, using dry CH2Cl2 (250 ml), 2,5-Bis[(4-methoxy)-
phenyl(hydroxy)methyl]-thiophene (3.9 mmol, 1.4 g),
4-methoxybenzaldehyde (7.8 mmol, 0.95 ml) and pyrrole
(11.8 mmol, 814 ml). BF3$OEt2 (0.4 mmol, 49 ml) was
added to start the reaction. After stirring for 3 h, DDQ
(5.3 mmol, 1.2 g) was added. The crude product was
purified by silica gel column chromatography (chloro-
form/methanol 99:1) and isolated as a purple, crystalline
solid (0.56 g, 19%).
4.2.14. 5-(2-Methoxy)phenyl-10,15,20-(4-bromo)phenyl-
21-thiaporphyrin 14. Compound 14 was prepared follow-
ing the method given for 8, using dry CH2Cl2 (250 ml), 3
(3.5 mmol, 1.35 g), 4-bromobenzaldehyde (7 mmol, 1.29 g)
and pyrrole (10.5 mmol, 724 ml). BF3$OEt2 (0.35 mmol,
44 ml) was added and the mixture was stirred for 3 h before
DDQ (5.2 mmol, 1.19 g) was added. The crude product was
purified by silica gel column chromatography (chloroform)
and isolated as a purple, crystalline solid (100 mg, 3%).
1H NMR (CDCl3, d in ppm) K2.75 (bs, 1H, NH); 3.6 (s, 3H,

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S. Stute et al. / Tetrahedron 61 (2005) 2907–2912
OMe); 7.4 (m, 2H, ortho-H); 7.8–8.1 (m, 14H, H-Ar); 8.6 (2d,
4H, b-pyrrole); 8.9 (s, 2H, b-pyrrole); 9.5 (dd, 2H, b-thiophene).
ESI-MS (C75 V) obsd mass 898, calcd mass 898.52.
(0.13 mmol, 16 ml) and DDQ (2.6 mmol, 0.59 g). The
crude product was purified by two silica gel column
chromatographies (chloroform) and the product afforded
as a orange-purple, crystalline solid (82 mg, 7%).
4.2.15. 5-(2-Allyloxy-5-bromo)phenyl-10,15,20-(4-bro-
mo)phenyl-21-thiaporphyrin 15. Preparation of 15 fol-
lowed the same steps like the preparation of 8, using dry
CH2Cl2 (250 ml), 4 (1.96 mmol, 1 g), 4-bromobenzalde-
hyde (3.92 mmol, 0.72 g) and pyrrole (5.88 mmol, 410 ml).
After BF3$OEt2 (0.2 mmol, 25 ml) was added, the mixture
was stirred for 3 h before DDQ (3.92 mmol, 0.89 g) was
added. The crude product was purified by silica gel column
chromatography (chloroform). After another silica gel
column chromatography (n-heptane/chloroform 1:2) 15
was isolated as a purple, crystalline solid (300 mg, 15%).
1H NMR (CDCl3, d in ppm) K2.75 (bs, 1H, NH); 4.0 (s, 9H,
OMe); 4.4 (s, 2H, OCH2); 4.6 (dd, 2H, CH2); 5.45 (dq, 1H,
CH);7.35(d, 1H, H-Ar);7.4(t, 1H, H-Ar);7.75(dt,1H, H-Ar);
8.0 (d, 1H, H-Ar); 8.3–8.7 (m, 16H, H-Ar, b-pyrrole); 8.9 (s,
2H, b-pyrrole); 9.5 (s, 2H, b-thiophene). ESI-MS (C75 V)
obsd mass 862, 841 [MKallyl], calcd mass 861.98.
References and notes
1H NMR (CDCl3, d in ppm) K2.75 (bs, 1H, NH); 4.4
(m, 2H, OCH2); 4.6 (dd, 2H, CH2); 5.4 (dq, 1H, CH); 7.2
(dd, 1H, H-Ar); 7.8 (dd, 1H, H-Ar); 7.85–8.1 (12H, H-Ar);
8.15 (d, 1H, H-Ar); 8.6 (2 d, 4H, b-pyrrole); 8.9 (s, 2H,
b-pyrrole); 9.65 (dd, 2H, b-thiophene). ESI-MS (C75 V)
obsd mass 1003, 962 [MKallyl], calcd mass 1003.45.
1. Ulman, A.; Manassen, J. J. Am. Chem. Soc. 1975, 97,
6540–6544.
2. Latos-Grazynski, L. In Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; The Porphyrin Handbook; Academic Press: New
York, 2000; Vol. 2, pp 361–416.
3. Broadhurst, M. J.; Grigg, R.; Johnson, A. W. J. Chem. Soc. C
1971, 3681–3690.
4.2.16. 5-(2-Methoxy-5-bromo)phenyl-10,15,20-(4-bro-
mo)phenyl-21-thiaporphyrin 16. Compound 16 was
synthesized using the general procedure (s. 8), with dry
CH2Cl2 (450 ml), diol 5 (3.1 mmol, 1.49 g), 4-bromobenz-
aldehyde (6.2 mmol, 1.14 g), pyrrole (9.2 mmol, 640 ml),
BF3$OEt2 (0.3 mmol, 37 ml) and DDQ (6.2 mmol, 1.396 g).
The purification of the product was done by silica gel
column chromatography (chloroform). After another silica
gel column chromatography (n-heptane/chloroform 1:2) 16
was obtained as a purple, crystalline solid (270 mg, 9%).
4. (a) Ulman, A.; Manassen, J.; Frolow, F.; Rabinovich, D. Inorg.
Chem. 1981, 20, 1987–1990. (b) Pandian, R. P.;
Chandrashekar, T. K. Inorg. Chem. 1994, 33, 3317–3324.
5. (a) Gopinath, C. S.; Pandian, R. P.; Manoharan, P. T. J. Chem.
Soc., Dalton Trans. 1996, 1255–1259. (b) Ulman, A.;
Manassen, J.; Frolow, F.; Rabinovich, D. Tetrahedron Lett.
1978, 167–170. (c) Ulman, A.; Manassen, J.; Frolow, F.;
Rabinovich, D. Tetrahedron Lett. 1978, 1885–1886.
6. Hilmey, D. G.; Abe, M.; Nelen, M. I.; Stilts, C. E.; Baker,
G. A.; Baker, S. N.; Bright, F. V.; Davies, S. R.; Gollnick,
S. O.; Oseroff, A. R.; Gibson, S. L.; Hilf, R.; Detty, M. R.
J. Med. Chem. 2002, 45, 449–461.
1H NMR (CDCl3, d in ppm) K2.75 (bs, 1H, NH); 3.55 (s,
3H, OMe); 7.2 (d, 1H, H-Ar); 7.8–8.1 (m, 14H, H-Ar); 8.55
(dd, 2H, b-pyrrole); 8,6 (dd, 2H, b-pyrrole); 8,9 (d, 2H,
b-pyrrole); 9,6 (dd, 2H, b-thiophene). ESI-MS (C75 V)
obsd mass 977, calcd mass 977.42.
7. Cho, W.-S.; Kim;, H.-J.; Littler, B. J.; Miller, M. A.; Lee,
C.-H.; Lindsey, J. S. J. Org. Chem. 1999, 64, 7890–7901.
8. (a) Agarwal, N.; Hung, C.-H.; Ravikanth, M. Eur. J. Org.
Chem. 2003, 19, 3730–3734. (b) Gupta, I.; Agarwal, N.;
Ravikanth, M. Eur. J. Org. Chem. 2004, 1693–1697.
9. Felber, B.; Calle, C.; Schweiger, A.; Diederich, F. Org.
Biomol. Chem. 2003, 1, 1090–1093.
4.2.17. 5-(2-Allyloxy-3-methoxy)phenyl-10,15,20-(3,5-
methoxy)phenyl-21-thiaporphyrin 17. Compound 17
was prepared in the general procedure (s. 8), with dry
CH2Cl2 (100 ml), 6 (1.4 mmol, 0.61 g), 4-bromobenzalde-
hyde (2.8 mmol, 0.456 g) and pyrrole (4.1 mmol, 290 ml),
BF3$OEt2 (0.14 mmol, 17 ml) and DDQ (2.8 mmol,
0.635 g). After two silica gel column chromatographies
(chloroform) the product was isolated as a orange-purple,
crystalline solid (50 mg, 4%).
10. Finikova, O.; Galkin, A.; Rozhkov, V.; Cordero, M.;
¨ ¨
Hagerhall, C.; Vinogradov, S. J. Am. Chem. Soc. 2003, 125,
4882–4893.
11. Matos, M. S.; Hofkens, J.; Verheijen, W.; De Schryver, F. C.;
Hecht, S.; Pollak, K. W.; Frechet, J. M. J.; Forier, B.; Dehaen,
W. Macromolecules 2000, 33, 2967–2973.
1H NMR (CDCl3, d in ppm) K2.75 (bs, 1H, NH); 4.0 (s,
18H, OMe); 4.1 (s, 3H, OMe); 4.1 (s, 2H, OCH2); 4.3 (dd,
2H, CH2); 4.9 (dq, 1H, CH); 6.9 (d, 6H, ortho-H); 7.4 (m,
8H, H-Ar); 7.65 (dd, 1H, H-Ar); 8.65 (s, 2H, b-pyrrole);
8.7 (d, 1H, b-pyrrole); 8.75 (d, 1H, b-pyrrole); 9.02 (s, 2H,
b-pyrrole); 9.7 (d, 2H, b-thiophene). ESI-MS (C75 V) obsd
mass 898, 857 [MKallyl], calcd mass 898.06.
12. Osuka, A.; Kim, D. Acc. Chem. Res. 2004, 37, 735–745.
13. Ulman, A.; Manassen, J. J. Chem. Soc., Perkin Trans. 1 1979,
4, 1066–1069.
14. Lindsey, J. S.; Schreimann, I. C.; Hsu, H. C.; Kearney, P. C.;
Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827–836.
15. Chmielewski, P.; Grzeszczcuk, M.; Latos-Grazynski, L.;
Lisowski, J. Inorg. Chem. 1989, 28, 3546–3552.
16. Adler, A. D.; Longo, F. R.; Finarelli, J. D.; Goldmacher, J.;
Assour, J.; Korsakoff, L. J. Org. Chem. 1967, 32, 476.
17. Latos-Grazynski, L.; Lisowski, J. J. Am. Chem. Soc. 1987,
109, 4428–4429.
4.2.18.
5-(2-Allyloxy)phenyl-10,15,20-(4-carboxy-
methyl)phenyl-21-thiaporphyrin 18. Preparation of 18
was prepared in analogue to 8, using dry CH2Cl2 (100 ml), 7
(1.3 mmol, 0.534 g), methyl 4-formylbenzoate (2.6 mmol,
0.426 g) and pyrrole (3.9 mmol, 270 ml), BF3$OEt2
18. Srinivasan, A.; Srivedi, B.; Reddy, M. V. R.; Narayanan, S. J.;
Chandrashekar, T. K. Tetrahedron Lett. 1997, 38, 4149–4152.