Synthesis of 5,15-diarylporphyrins via orthoesters condensation with aryldipyrromethanes

Article abstract of DOI:10.1016/j.tetlet.2011.04.028

General access to 5,15-diarylporphyrins in two steps is described. Generalization of this approach to tetra-substituted porphyrins allows the reproducible preparation of compounds, in some cases with high yields for porphyrins, which can be used in photodynamic therapy (PDT) in cancer today.

Full text of DOI:10.1016/j.tetlet.2011.04.028

Tetrahedron Letters 52 (2011) 3175–3178
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of 5,15-diarylporphyrins via orthoesters condensation
with aryldipyrromethanes
Zahra Abada a,b, Laurent Ferrié b, Bernardin Akagah a, Anh Tuan Lormier a, Bruno Figadère b,
⇑
a Alpha-Chimica, 5 rue Jean-Baptiste Clément, F-92296 Châtenay-Malabry, France
b UMR CNRS 8076, University Paris-Sud, Laboratoire de Pharmacognosie, UFR de Pharmacie, Châtenay-Malabry F-92296, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 February 2011
Revised 5 April 2011
Accepted 6 April 2011
Available online 12 April 2011
General access to 5,15-diarylporphyrins in two steps is described. Generalization of this approach to
tetra-substituted porphyrins allows the reproducible preparation of compounds, in some cases with high
yields for porphyrins, which can be used in photodynamic therapy (PDT) in cancer today.
Ó 2011 Published by Elsevier Ltd.
Keywords:
Condensation
Symmetry
Acid catalysis
Photosensitizers
Anticancer
The general access to 5,15-diarylporphyrins follows usually the
well known two step procedure,1–3 however giving low yields and
tedious chromatography purifications: namely, preparation of
dipyrromethane4 (an air and moisture sensitive compound5) then
condensation with an aromatic aldehyde followed by DDQ oxida-
tion (Fig. 1).
Recently, Banfi et al. has studied the comparative activity of tet-
ra-arylporphyrins and 5,15-diarylporphyrins in PDT.2,3 The study
has shown that (i) 5,15-diarylporphyrins were more active and
(ii) the crucial importance of hydroxyl groups on the aryl substitu-
ents, both for the solubility concerns and for the photo-toxicity
was observed.3
It is important to note that verteporfin, a 1:1 mixture of photo-
sensitizing porphyrins isomers, has been approved for the treat-
Ar
N
H
1) ArCHO
2)DDQ
HCHO
N
H
N
N
N
H
NH
H
N
Ar
Figure 1. Preparation of 5,15-diarylporphyrins in the literature.
Indeed, in the treatment of cancer, photodynamic therapy (PDT)
has become an attractive alternative approach.6,7 PDT uses a tu-
mor-localizing photosensitizing agent, usually a porphyrin, that
absorbs visible light and in presence of oxygen generates cytotoxic
reactive oxygen species (ROS). It is well admitted that the pro-
duced singlet oxygen (1O2) is responsible for cell death.8
To this date only two compounds have been approved for PDT
cancer treatment: porfimer (photofrin) is derived from hematopor-
phyrin,9 and foscan (m-THPC or 5,10,15,20-terakis(m-hydroxy-
HO
OH
HO
N
N
N
H
O
HN
NH
N
N
H
N
HO
phenyl)chlorin) is
a chlorin, a second generation porphyrin
derivative that shows an interesting photo-toxicity against cancer-
O
ous cell lines (Fig. 2).10
HO
OH
HO
2
O
Foscan
Photofrin
⇑
Corresponding author.
E-mail address: bruno.figadere@u-psud.fr (B. Figadère).
Figure 2. Photofrin and foscan.
0040-4039/$ - see front matter Ó 2011 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2011.04.028

3176
Z. Abada et al. / Tetrahedron Letters 52 (2011) 3175–3178
Table 1
O
O
Preparation of aryldipyrromethanes 2a–i from pyrrole and aldehydes 1a–i
O
HO
O
HO
Entry
Aldehyde
TFA (equiv)
Yield (%)
1
2
3
4
5
6
7
8
9
PhCHO 1a
3-Br-PhCHO 1b
2-Br-PhCHO 1c
2,3,4,5,6-F6-PhCHO 1d
2,6-Cl2-PhCHO 1e
2-NaphthylCHO 1f
3-IndolylCHO 1g
4-NO2-PhCHO 1h
3,4,5-(OMe)3-PhCHO 1i
0.1
0.5
0.5
0.1
0.1
0.1
0.1
0.5
0.5
2a: 89
2b: 80
2c: 74
2d: 62
2e: 70
2f: 72
2g: 75
2h: 70
2i: 71
O
O
N
N
N
+
HN
NH
HN
NH
N
MeO
HO
O
O
HO
MeO
O
O
under nitrogen and with TFA (0.1–0.5 equiv). After work-up, excess
of pyrrole was distilled off and the crude residue purified by flash
column chromatography on silica gel (with 8/2/1 cyclohexane/
EtOAc/NEt3 as eluent), affording the air and moisture stable aryldi-
pyrromethanes 2a–i.
Figure 3. Verteporfin.
R1
Then we studied the condensation of compounds 2a–i with
methyl orthoformate (72 equiv) under acid activation, as re-
ported.11 In our hands the use of an excess of trichloroacetic acid
did not allow us to obtain the desired 5,15-diphenylporphyrin 3a
with the reported yield (14%), albeit in trace amount or around
1% isolated yield, depending on the experiment (Table 2, entry
1). As it was reported,11a preparation of 5,15-diphenylporphyrin
3a was hardly reproducible under these reaction conditions. We
thus decided to study the influence of the acid used (Table 2, en-
tries 2–7) and found that higher yields were obtained in the pres-
ence of trifluoroacetic acid (TFA), better Brønsted acid tested, or
Lewis acids such as magnesium bromide (MgBr2) and trifluorobo-
rate etherate (BF3ÁOEt2). Finally, with 38 equiv of TFA, 5,15-diph-
enylporphyrin 3a was obtained in a moderate but reproducible
36% isolated yield (Table 2, entry 7).13 With lower amounts of
TFA (10 or 23 equiv), yields remain moderate (21% and 27%,
respectively). So far as evidenced by 1H NMR and MS analysis, no
N-confused porphyrin was formed under these reaction conditions.
Indeed, it is worth noting that the remaining mass balance was
mainly due to polymeric material, since besides the expected por-
phyrin a minor product was formed (isolated in 6% yield and sep-
arated by flash chromatography), which corresponds to 10-formyl-
5,15-diphenyl porphyrin 7a.14a
Then 5,15-diarylporphyrins 3b–i were prepared according to
the reaction conditions described above (Table 3), by treatment
of the aryldipyrromethanes 2b–i with methyl orthoformate
(72 equiv) in dichloromethane under nitrogen and in the dark.
TFA (38 equiv) in dichloromethane was added at room tempera-
ture in 30 min. After 4 h of stirring, pyridine was added and stirring
was maintained 17 h, prior bubbling air for 15 min and stirring for
4 h. Solvent was evaporated off under vacuum and the residue was
purified by flash chromatography on silica gel (CH2Cl2/cyclohex-
ane = 70:30 as eluent). Most of the 5,15-diarylporphyrins were ob-
tained with yields ranging from 4% to 9% (Table 3, entries 2, 3, 5–8).
However most of the remaining mass balances were again due to
polymerization, since flash chromatographies on silica gel afforded
RC(OMe)3
then air
ArCHO
N
H
N
H
NH
2a-i
R
R1
N
H
R = H: 3a-i
R = CH3: 4a
R = Ph: 5a
N
N
H
N
R1
R
Figure 4. Our strategy for the synthesis of 5,15-diarylporphyrins 3a-I, 4a, 5a.
ment of abnormal blood vessels in the eyes associated with macu-
lar degeneration (Fig. 3).
It would be interesting to compare the activity of symmetric
5,15-diarylporphyrins (A2 symmetry) with the activity of tetra-
arylporphyrins of several symmetries (A2B2, A2BC, etc.). This re-
quires having a better access to 5,15-diarylporphyrins in term of
yield, purification procedure and access to starting materials.
Our strategy for the preparation of 5,15-diarylporphyrins relies
on the condensation of aryldipyrromethanes with orthoesters, giv-
ing directly the desired porphyrin after air oxidation (Fig. 4). It is
important to note that to our best knowledge, the condensation
of phenyldipyrromethane with methyl orthoformate has been re-
ported once, giving the expected porphyrins in low yields.11 Some
other examples started from dicarboxyl–dipyrromethane and after
in situ decarboxylation, the formation of porphyrin took place with
trimethyl orthoformate.12 These strategies present the advantage
of producing the expected porphyrins directly after condensation
and treatment with air without the drawback of preparing the
unstable dipyrromethane, using DDQ for the oxidation step, or per-
forming tedious chromatography purifications.11
In this letter we report an improved preparation of 5,15-diaryl-
porphyrins in two steps and the preparation of A2B2 tetra-substi-
tuted porphyrins, following the same strategy. Yields were
moderate to good, and a wide variety of porphyrins were thus
obtained.
The aryldipyrromethanes 2a–i were easily prepared through
the well-known Lindsey et al. procedure4 from the corresponding
aromatic aldehydes 1a–i and pyrrole in the presence of a catalytic
amount of trifluoroacetic acid (TFA), in yields ranging from 62% to
89% (Table 1). The reactions were performed in the presence of a
large excess of pyrrole (200 equiv) with 1 equiv of aldehyde 1a–i
Table 2
Preparation of 5,15-diphenylporphyrin 3a from 2a and methyl orthoformate
Entry
Acid
(equiv)
3a (%)
1
2
3
4
5
6
7
CCl3COOH
CH3SO3H
BF3ÁOEt2
MgBr2
CF3COOH
CF3COOH
CF3COOH
(23)
(23)
(23)
(23)
(10)
(23)
(38)
1
9
4
8
21
27
36

Z. Abada et al. / Tetrahedron Letters 52 (2011) 3175–3178
3177
Table 3
ward since the desired porphyrins were easily separated from
polymeric materials and secondary compounds (e.g., 10-formyl-
5,15-diarylporphyrin). Electron-withdrawing substituents on the
phenyl ring of the aryldipyrromethanes (e.g., halogen, nitro group)
gave lower yields as well as indolyl moiety. Extension of this meth-
odology to the condensation of aryldipyrromethanes with methyl
orthoacetate and methyl orthobenzoate allowed us to prepare
the corresponding 5,10,15,20-tetra-substituted porphyrins in
acceptable yields. Finally, double addition of aryllithium reagents
on 5,15-diarylporphyrins gave an easy access to 5,10,15,20-tetra-
arylporphyrines with A4 symmetry in reasonable yields and easy
chromatographic purifications. This study has thus allowed us to
prepare 13 porphyrins (most are new ones) that will be tested in
due course in PDT.
Preparation of 5,15-diarylporphyrins 3a–i and tetra-substituted porphyrins 4a and 5a
Entry
Aryldipyrrromethane (Ar)
Ortho ester
Porphyrin: yield (%)
1
2
3
4
5
6
7
8
9
2a (Ph)
HC(OMe)3
HC(OMe)3
HC(OMe)3
HC(OMe)3
HC(OMe)3
HC(OMe)3
HC(OMe)3
HC(OMe)3
HC(OMe)3
CH3C(OMe)3
3a: 36
3b: 10
3c: 9
3d: 5
3e: 6
3f: 17
3g: 4
3h: traces
3i: 43
4a: 27
5a: 20
2b (3-Br-Ph)
2c (2-Br-Ph)
2d (2,3,4,5,6-F6-Ph)
2e (2,6-Cl2-Ph)
2f (2-naphthyl)
2g (3-indolyl)
2h (4-NO2-Ph)
2i (3,4,5-(OMe)3-Ph)
2a (Ph)
10
11
2a (Ph)
PhC(OMe)
3
easily the expected products. Minor compounds, which were not
the N-confused porphyrins, were sometimes characterized such
as 10-formyl-5,15-bis(3-bromophenyl)porphyrin 7b.14b Higher
yields were however obtained for 5,15-bis-(2-naphthyl)porphyrin
3f (17%, Table 3, entry 6) and for 5,15-bis-(3,4,5-trimethoxy-
phenyl)porphyrin 3i (43%, Table 3, entry 9). Thus the presence of
an electron-withdrawing group, such as 4-nitro or a halogen atom,
seems to have a deleterious effect on the course of the reaction,
whereas electron-donor groups give higher yields. Steric hindrance
(substitution at the 2 and 6 positions of the phenyl group) is also
responsible for lower yields in the expected porphyrins.15
Then, generalization of the reaction was studied by using
methyl orthoacetate and methyl orthobenzoate with phenyldipyr-
romethane 2a. In both cases, the expected A2B2 and A4 tetra-
substituted porphyrins were obtained in moderate but reproduc-
ible yields (27% for 4a16 and 20% for 5a, Table 3 entries 10 and 11).
Finally, with 5,15-diarylporphyrins 3a–i in hands, it is interest-
ing to note that tetra-arylporphyrins could also be obtained in a
four step procedure by addition of 10 equiv of aryllithium and oxi-
dation by DDQ,17,18 followed by a second addition of aryllithium
and DDQ oxidation. For instance, tetra-substituted tetrakis-phenyl
porphyrin 5a was obtained in 47% yield from 6a and 15% overall
yield (from benzaldehyde), through the triarylporphyrine interme-
diate 6a, which was obtained in 97% yield from 3a (Fig. 5).19
In conclusion, this study shows that 5,15-diarylporphyrins can
be prepared from aryldipyrromethanes by condensation with
methyl orthoformate in the presence of trifluoroacetic acid. Yields
were low to moderate, but the purification step was straightfor-
Acknowledgments
Thanks are due to K. Leblanc for her help in chromatography
analyses, and for mass spectrometry analyses. We wish to thank
J. C. Jullian (Châtenay-Malabry) and J. F. Gallard (ICSN, Gif sur Yv-
ette, France) for NMR experiments.
Supplementary data
Supplementary data (1H NMR spectra of compounds 3a–i, 4a,
5a, 6a, 7a,b) associated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2011.04.028.
References and notes
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A. D. Aust. J. Chem. 2004, 57, 1091–1102; (b) Vogeser, M.; Schaffer, M.; Egeler,
E.; Spohrer, U. Clin. Biochem. 2005, 38, 73–78. and references cited therein.
10. (a) Bonnett, R.; White, R. D.; Winfield, U. J.; Berenbaum, M. C. Biochem. J. 1989,
261, 277–280; (b) Bonnett, R.; Charlesworth, P.; Djelal, B. D.; MacGarvey, D. J.;
Truscott, T. G. J. Chem. Soc., Perkin Trans. 2 1999, 325–328; (c) Serra, A. C.;
Pineiro, M.; d’A Rocha Gonsalves, A. M.; Abrantes, M.; Laranjo, M.; Santos, A. C.;
Botelho, M. F. J. Photochem. Photobiol., B-Biol. 2008, 92, 59–65. and references
cited therein.
11. (a) Boyle, W.; Bruckner, C.; Posakony, J.; James, B. R.; Dolphin, D. Org. Synth.
1998, 76, 287–293; (b) Fox, S.; Hudson, R.; Boyle, R. W. Tetrahedron Lett. 2003,
44, 1183–1185.
12. (a) Collman, J. P.; Chong, A. O.; Jameson, G. B.; Oakley, R. T.; Rose, E.; Schmittou,
E. R.; Ibers, J. A. J. Am. Chem. Soc. 1981, 103, 516–533; (b) Lecas, A.; Levisalles, J.;
Renko, Z.; Rose, E. Tetrahedron Lett. 1984, 25, 1563–1566; (c) Boitrel, B.; Lecas,
A.; Renko, Z.; Rose, E. Chem. Commun. 1985, 1820–1821; (d) Boitrel, B.; Lecas,
A.; Renko, Z.; Rose, E. New J. Chem. 1989, 13, 73–99.
N
H
N
H
PhLi
N
N
N
N
then DDQ
97%
H
N
H
N
6a
PhLi
3a
47%
then DDQ
N
H
13. 5,15-Diphenylporphyrin 3a:11 following general procedure from 5-
phenyldipyrromethane (121.5 mg, 0.55 mmol) and trimethyl orthoformate
gave expected porphyrin 3a as purple solid (45.6 mg, 36%), C32H22N4. 1H
(CDCl3, 400 MHz) d À3.11 (br s, 2H, 2NH), 7.81 (m, 6H, m,p-Ph H), 8.29 (m, 4H,
o-Ph H), 9.09 (d, 3J = 4.5 Hz, 4H, b H), 9.40 (d, 3J = 4.5 Hz, 4H, b H), 10.33 (s, 2H,
H-meso). 13C (CDCl3, 100 MHz) d 147.2 (C); 145.2 (C), 141.4 (C), 134.8 (CH),
131.6 (CH), 131.0 (CH), 127.7 (CH), 126.9 (CH), 119. (C), 105.3 (CH meso). UV–
vis (nm): 400, 499, 533, 573. HRMS (ESI): MH+, found 463.1907. C32H22N4
requires 462.1918. Rf (cyclohexane/AcOEt: 7/3) 0.58.
N
N
H
N
5a
Figure 5. Preparation of tetra-substituted porphyrin 5a.

3178
Z. Abada et al. / Tetrahedron Letters 52 (2011) 3175–3178
14. (a) 10-Formyl-5,15-diphenylporphyrin 7a: As
a
purple solid (9.4 mg, 6%),
expected porphyrin 3g as red purple solid (25 mg, 3%), C36H24N6. 1H (CDCl3,
C
31H22N4O. 1H (CDCl3, 400 MHz) d À2.53 (br s, 2H, 2NH), 7.82 (m, 6H, m,p-
300 MHz) d À3.41 (br s, 2H, NH), 7.52 (m, 4H), 7.72 (m, 2H), 7.79 (m,2H), 8.06
(d, J = 2.1 Hz, 1H), 8.88 (brs,1H), 9.27 (d, J = 4.5 Hz, 2H, b H), 9.37 (d, J = 4.5 Hz,
2H, b H), 9.49 (m, 4H, b H), 10.25 (s, 1H), 10.32 (s, 2H, CH meso). 13C (CDCl3,
500 MHz) d 139.1 (C), 131.7 (CH), 131.6 (CH), 131.1 (CH), 131.0 (CH), 128.6
(CH), 122.9 (CH), 120.9 (CH), 120.6, 111.3 (CH), 107.3 (C), 104.5 (CH), 103.4
(CH). UV–vis (nm): 407, 501, 536, 574, 630. HRMS (ESI): MH+ found, 541.1069.
Ph-H), 8.18 (dd, J = 0.9 Hz, J = 7.2 Hz, 4H, o-Ph-H), 8.86 (d, J = 4.5 Hz, 2H, b-Hd),
9.03 (d, J = 5.1 Hz, 2H, b-Hb), 9.22 (d, J = 4.5 Hz, 2H, b-Hc), 10.03 (d, J = 4.5 Hz,
2H, b-Ha), 10.28 (s, 1H, Hmeso), 12.53 (s, 1H, CHO). 13C (CDCl3, 100 MHz) d
195.2 (CHO), 141.2 (C), 134.4 (CH), 131.6 (CH), 131.5 (CH), 128.1 (CH), 126.9
(CH), 122.2 (C), 109.9 (CH), 108.1 (C). UV–vis (nm): 424, 521, 560, 593, 648 in
CHCl3. IR (cmÀ1): 3020, 2165, 1975, 1665, 1215, 1050, 745. LRMS (ESI): 491
(MH+). Rf (cyclohexane/AcOEt: 7/3) 0.49; (b) 10-Formyl-5,15-bis(3-
bromophenyl)porphyrin 7b: As a purple solid (68 mg, 6%), C33H20Br2N4O. 1H
(CDCl3, 400 MHz) d À2.58 (br s, 2H, 2NH), 7.67 (t, J = 7.8 Hz, 2H, Ph-H), 8.00 (d,
J = 8.1 Hz, 2H, Ph-H), 8.13 (d, J = 6.9 Hz, 2H, Ph-H), 8.37 (s, 2H, Ph-H), 8.88 (d,
J = 4.2 Hz, 2H, b-Hd), 9.04 (d, J = 4.8 Hz, 2H, b-Hb), 9.31 (d, J = 4.2 Hz, 2H, b-Hc),
10.09 (d, J = 4.5 Hz, 2H, b-Ha), 10.28 (s, 1H, Hmeso), 12.59 (s, 1H, CHO). 13C
(CDCl3, 75 MHz) d 195.1 (CHO), 174.4, 160.1, 143.2, 136.9, 132.9, 131.4, 128.4,
121.4, 110.1. UV–vis (nm): 424, 521, 560, 593, 648 in CHCl3. LRMS (APCI): 649
(MH+). Rf (cyclohexane/AcOEt: 8/2) 0.56.
C
36H25N6 requires 541.2136. Rf (cyclohexane/AcOEt: 7/3) 0.29; (g) 5,15-
Di(3,4,5-trimethoxyphenyl)-porphyrin 3i:3,20 following general procedure from
5-(3,4,5-trimehtoxypheny) dipyrromethane (300 mg, 0.96 mmol) and
trimethyl orthoformate gave expected porphyrin 3i as dark red purple solid
(133.7 mg, 43%), C38H34N4O6. 1H (CDCl3, 300 MHz) d À3,11 (br s, 2H, NH), 3.99
(s, 12H, m-CH3O), 4.18 (s, 6H, p-CH3O), 7,51 (s, 4H, o-Ph H), 9.16 (d, J = 4.5 Hz,
4H, b H,), 9.38(d, J = 4.5 Hz, 4H, b H,), 10.30 (s, 2H, H meso). 13C (CDCl3, 75 MHz)
d 151.7 (C), 147.1 (C), 145.3 (C), 137.9 (C), 136.9 (C), 131.7 (CH), 131.0 (CH),
118.9 (C), 112.9(CH), 105.4 (CH meso), 61.3 (OMe), 56.4 (OMe). UV–vis (nm):
411, 445, 504, 539, 580, 630. HRMS (ESI): MH+ found, 643.2538. C38H34N4O6
requires 643.2794. Rf (cyclohexane/AcOEt: 7/3) 0.33.
15. (a) 5,15-Bis(3-bromophenyl)porphyrin 3b: Following general procedure from 5-
(3-bromophenyl)dipyrromethane
(1.1 g,
3.59 mmol)
and
trimethyl
16. 5,15-Dimethyl-10,20-diphenylporphyrin 4a: Following general procedure from
5-phenydipyrromethane (100 mg, 0.96 mmol) and trimethyl orthoacetate gave
expected porphyrin as dark purple solid (29.8 mg, 27%), C34H26N4. 1H (CDCl3,
300 MHz) d À2.56 (s, 2H, 2NH), 4.6 (s, 6H, 2CH3), 7.78 (m, 6H, m,p-PhH), 8.20
(m, 4H, o-PhH), 8.85 (d, J = 4.8 Hz,4H, b H), 9.44 (d, J = 4.8 Hz, 4H, b H). 13C
(CDCl3, 75 MHz) d 154.6 (C), 147.0 (C), 129.0 (CH), 128.9 (CH), 128.5 (CH),
128.3 (CH), 101.1 (CH), 29.7 (CH3). 13C (CDCl3, 500 MHz) d 154.6 (C), 147.0 (C),
142.7 (C), 134.5, 131.6, 129.0 (CH), 128.9 (CH), 128.5 (CH), 128.3 (CH), 127.6
(CH), 126.6, 119.2, 116.5, 113.8 (C), 101.1 (CH), 29.7 (CH3). HRMS (ESI): MH+
found, 491.2227. C34H27N4 requires 491.2229. UV–vis (nm): 423, 518, 554, 597,
654. Rf (cyclohexane/AcOEt: 7/3) 0.61.
orthoformate gave expected porphyrin 3b as purple solid (109 mg, 10%),
C
32H20Br2N4. 1H (CDCl3, 300 MHz) d À2.25 (br s, 2H, 2NH), 7.6 (t, J = 7.8 Hz, 2H),
7.83 (ddd, J = 1.9 Hz, J = 2.0 Hz, J = 8.1 Hz, 2H), 8.15 (dd, J = 7.4 Hz, J = 0.9 Hz,
2H, PhH), 8.32 (s, 2H, PhH), 8.88 (d, J = 4.6 Hz, 4H, b H), 9.37 (d, J = 4.7 Hz, 4H, b
H), 10.36 (s, 2H, CH meso). 13C (pyridinD5, 500 MHz) d 137.7, 135.1, 133.8,
132.8, 132.6, 131.4, 131.2, 129.2, 106.4, 103.3, 79.7. UV–vis (nm): 394, 502,
536, 575, 629. HRMS (ESI): MH+ found, 619.0137. C32H21N4Br2 requires
619.0127.
bromophenyl)porphyrin 3c: Following general procedure from 5-(2-
bromophenyl)dipyrromethane (300 mg, 1.00 mmol) and trimethyl
Rf
(cyclohexane/AcOEt:
8/2)
0.71.
(b)
5,15-Bis(2-
orthoformate gave expected porphyrin 3c as purple solid (28.3 mg, 9%),
C
17. Feng, X. D.; Senge, M. O. Tetrahedron 2000, 56, 587–590.
32H20Br2N4.1H (CDCl3, 400 MHz) d À3.11 (br s, 2H, NH), 7.72 (m, 4H, Ph-H),
18. (a) Takanami, T.; Matsumoto, J.; Kumagai, Y.; Sawaizumi, A.; Suda, K.
Tetrahedron Lett. 2009, 50, 68–70; (b) Takanami, T.; Wakita, A.; Sawaizumi,
A.; Iso, K.; Onodera, H.; Suda, K. Org. Lett. 2008, 10, 685–687.
8.07 (m, 2H, Ph-H), 8.19 (dd, J = 2.3 Hz, J = 7.2 Hz, 1H, CH–CBr), 8.23 (dd,
J = 1.9 Hz, J = 7.2 Hz, 1H, Ph-H), 8.90 (d, J = 4.2 Hz, 4H, b H), 9.37 (d, J = 4.2 Hz,
4H, b H), 10.29 (s, 2H, CH meso). 13C (CDCl3, 75 MHz) d 135.4 (CH), 135.3 (CH),
132.2 (CH), 131.8 (CH), 130.5 (C), 130.0 (CH), 127.9 (C), 127.6 (C), 126.0 (CH),
105.4 (CHmeso), 90.1 (C–Br). HRMS (ESI): MH+ found, 619.0125. C32H21N4Br2
requires 619.0127. UV–vis (nm): 407, 503, 532, 575, 630. Rf (cyclohexane/
AcOEt: 7/3) 0.62; (c) 5,15-Bispentafluorphenyl-porphyrin 3d: Following general
procedure from 5-pentafluoro-dipyrromethane (3.25 g, 10,4 mmol) and
trimethyl orthoformate gave expected porphyrin 3d as dark purple solid
(172 mg, 5%), C32H12F10N4. 1H (CDCl3, 300 MHz) d À3.24 (br s, 2H, 2NH), 9.00
(d, J = 4.7 Hz, 4H), 9.49 (d, J = 4.8 Hz, 4H), 10.39 (s, 2H, CH meso). UV–vis (nm):
405, 503, 537, 575, 630. HRMS (ESI): MH+ found, 643.0984. C32H13F10N4
requires 643.0978. Rf (cyclohexane/AcOEt: 7/3) 0.73; (d) 5,15-Bis(2,6-
dichlorophenyl)porphyrin 3e: Following general procedure from 5-bis(2,6-
dichlorophenyl)dipyrromethane (500 mg, 1.72 mmol) and trimethyl
orthoformate gave expected porphyrin 3e as purple solid (63 mg, 8%),
19. (a) 5,10,15-Triphenylporphyrin 6a:18,20,21 In a dry flask, under positive pressure
of nitrogen, containing diphenylporphyrin 3a (15 mg, 0.032 mmol, 1 equiv) in
1.3 mL of dry tetrahydrofurane, PhLi (1.4 mL, 0.24 mmol, 7.5 mmol, 1.8 M in
Bu2O) was added slowly with a syringe at À78 °C. The mixture became black
red and was stirred at À78 °C for 2 h. The bath was removed to allow the
temperature rising. After 1 h at room temperature H2O was added at 0 °C, the
solution was stirred 10 min, DDQ was added and the green mixture became
dark red. Stirring was maintained for 30 min then the reaction mixture was
poured into brine and extracted with dichloromethane. The crude product was
purified by column chromatography (cyclohexane/AcOEt 9/1) to give the
expected triphenylporphyrin 6a as a red purple solid (16.8 mg, 97%), C38H26N4.
1H (CDCl3, 400 MHz) d À2.95 (br s, 2H, NH), 7.81 (m, 9H, m,p-PhH), 8.26 (m, 6H,
o-PhH), 8.91 (m, 4H, b H), 9.04 (d, J = 4.5 Hz, 2H, b H), 9.33 (d, J = 4.5 Hz, 2H, b
H), 10.21 (s, 1H, CH meso). 13C (CDCl3, 100 MHz) d 142.6 (C), 141.8 (C), 134.6
(2CH), 134,5 (CH), 132.4 (CH), 131.5 (CH), 131.4 (CH), 131.3 (CH), 130.7 (CH),
130.0 (CH), 128.3 (CH), 127.7 (2CH), 126.8 (2CH), 126,5 (CH), 120.6 (C), 119.6
(C), 104.8 (CH meso). HRMS (ESI): MH+ found, 539.2208. C38H27N4 requires
539.2230. UV–vis (nm): 414, 440, 509, 543, 583, 640. Rf (cyclohexane/AcOEt: 9/
1) 0.60; (b) Tetrakisphenylporphyrin 5a:22 Following previous procedure above
from triphenylporphyrin 6a the expected tetraphenylporphyrin 5a was
obtained as dark purple solid (46 mg, 47%), C44H30N4. 1H (CDCl3, 300 MHz) d
À2.76 (br s, 2H, NH), 7.75 (m, 12H, m,p-Ph-H), 8.24 (m, 8H, o-Ph-H), 8.84 (s, 8H,
b H). 13C (CDCl3, 75 MHz) d 145.7 (C), 142.2 (C), 134.0 (CH), 130.5 (CH), 127.5
(CH), 126.0 (CH), 119.5 (C). HRMS (ESI): MH+ found, 615.2559. C44H31N4
requires 615.2543. UV–vis (nm): 423, 516, 551, 591, 649. Rf (cyclohexane/
AcOEt: 9/1) 0.63.
C
32H18Cl4N4. 1H (CDCl3, 300 MHz) d À3.10 (br s, 2H, 2NH), 7.83 (m, 6H, Ph
H), 8.87 (d, J = 4.7 Hz, 4H, b H), 9.38 (d, J = 4.8 Hz, 4H, b H), 10.29 (s, 2H, CH
meso). UV–vis (nm): 407, 502, 533, 581, 631. HRMS (ESI): MH+ found,
601.0321. C32H19Cl4N4 requires 600.9726. Rf (cyclohexane/AcOEt: 7/3) 0.58;
(e) 5,15-Bisnaphthylporphyrin 3f: Following general procedure from 5-
naphtyldipyrromethane (300 mg, 1.10 mmol) and trimethyl orthoformate
gave expected porphyrin 3f as purple solid (51.7 mg, 17%),
C
40H26N4. 1H
(CDCl3, 300 MHz) d À3.01 (br s, 2H, NH), 7.76 (m, 4H, CHAR), 8.14 (m, 2H, CHAR),
8.24 (d, J = 8.6 Hz, 2H, CHAR), 8.47 (d, J = 8.4 Hz, 2H, CHAR), 8.74 (s, 2H, CHAR),
9.11 (d, J = 4.6 Hz, 2H, b H), 9.41 (d, J = 4.6 Hz, 2H, b H), 10.34 (s, 2H, CH meso).
13C (CDCl3, 500 MHz) d 147.5, 147.5, 145.4 (4C), 144.9 (4C),139.0 (2C),134.0
(2CH), 132.9, 132.9 (2C), 132.5 (2C), 131.7 (4CH), 131.2 (4CH), 128.5 (2CH),
128.1 (2CH), 126.9 (2CH), 126.9 (2CH), 126.2 (2CH), 119.1 (2C), 118.3 (2C),
105.4 (CH). UV–vis (nm): 410, 506, 541, 578, 633. HRMS (ESI): MH+ found,
563.2226. C40H27N4 requires 563.2230. Rf (cyclohexane/AcOEt: 7/3) 0.63; (f)
5,15-Bis(3-indolyl)porpohyrin 3g: Following general procedure from 5-(3-
indolyl)dipyrromethane (1 g, 3.83 mmol) and trimethyl orthoformate gave
20. Senge, M. O.; Shaker, Y. M.; Pintea, M.; Ryppa, C.; Hatscher, S. S.; Ryan, A.;
Sergeeva, Y. Eur. J. Org. Chem. 2010, 2, 237–258.
21. Senge, M. O. Acc. Chem. Res. 2005, 38, 733–743.
22. Lindsey, J. S.; Hsu, H. C.; Schreiman, I. C. Tetrahedron Lett. 1986, 27, 4969–4970.