Microwave assisted synthesis of novel annealed porphyrins

Article abstract of DOI:10.1016/j.tetlet.2008.04.094

New pyrrole derivatives (isoindoles) have been readily prepared by the reaction of an α,β-unsaturated sulfone with ethyl isocyanoacetate in the presence of tert-BuOK in good yields. The isoindoles are converted into new porphyrins which undergo retro Diel

Full text of DOI:10.1016/j.tetlet.2008.04.094

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3972–3975
Microwave assisted synthesis of novel annealed porphyrins
Ibrahim Elghamry *, Lutz F. Tietze
Institute of Organic and Biomolecular Chemistry, Georg-August-University Go¨ttingen, Tammannstrasse 2, D-37077 Go¨ttingen, Germany
Received 10 January 2008; revised 28 March 2008; accepted 16 April 2008
Available online 20 April 2008
Abstract
New pyrrole derivatives (isoindoles) have been readily prepared by the reaction of an a,b-unsaturated sulfone with ethyl isocyano-
acetate in the presence of tert-BuOK in good yields. The isoindoles are converted into new porphyrins which undergo retro Diels–Alder
reactions under microwave irradiation at 250 °C for 4 min to give novel annealed porphyrins in quantitative yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Porphyrinoid chromophores possessing a conjugated p-
electron system with a strong absorption in the far-visible/
near-IR region have been the subject of numerous studies
due to their potential applications in multibit molecular-
based information storage arrays,1–3 photodynamic
therapy (PDT),4–7 near-IR dyes, and nonlinear optical
materials.8,9 The extension of the p-electron system has
been achieved by either peripheral changes with different
chromophores at the meso- and b-positions or by addition
of one or more fused aromatic ring systems.10–14 Increased
conjugation usually results in a red shift for a given chro-
mophore, and it is expected that aromatic subunits fused
to the porphyrin nucleus would result in the desired red
shift in the electronic spectra of the chromophores.
Monobenzoporphyrin was first prepared over 30 years
ago and exhibits a slight shift for both the Soret and the
longest wavelength Q-band, (403 and 628 nm, respec-
tively).15 Further extension in mononaphthoporphyrin
leads to a Soret band at 415 nm and a Q-band at
630 nm.16 However, with di- and tetranaphthoporphyrins
these values are only slightly shifted and appear at 424
and 641, and 438 and 672 nm, respectively.17–19 The overall
effects are minimal suggesting that benzenoid ring fusion
does not significantly alter the porphyrin UV–vis absorp-
tion spectra. However, the ability to alter the porphyrin
more profoundly remains an important goal. In this Letter,
we report a microwave assisted synthesis and the UV–vis
spectra of new tetranaphthoporphyrins.
5,8-Dimethoxy-1,4-dihydro-1,4-ethanonaphthalene (1)20
(Scheme 1) was converted into sulfide 2a by reaction with
PhSCl. Subsequent oxidation with m-CPBA followed by
dehydrohalogenation with DBU afforded the a,b-unsatu-
rated sulfone 3 in an overall yield of 90%. Next, the isoin-
dole 2-carboxylate was prepared using the Barton–Zard
reaction.21,22 Thus, treatment of sulfone 3 with ethyl iso-
cyanoacetate in the presence of tert-BuOK23 afforded isoin-
dole 2-carboxylate 4a in 85% yield. Porphyrin 5a was
prepared from 4a following Lindsey condensation24–26
which involves reduction with LiAlH4 followed by tetra-
merization in the presence of TFA and subsequent oxida-
tion with DDQ. Alternatively, deethoxycarboxylation of
isoindole 4a upon heating with KOH in ethylene glycol
at 160–165 °C afforded isoindole 4b in 80% yield, subse-
quent tetramerization in the presence of mesitaldehyde fol-
lowed by oxidation with DDQ produced porphyrin 5b in
30% overall yield.
Retro Diels–Alder reactions often require severe condi-
tions, high temperatures, and sometimes, flash vacuum
thermolysis. Microwave irradiation has been used as an
alternative to these harsh conditions and significant
reductions in reaction times and high yields of the desired
*
Corresponding author. Present address: Misr International University,
Faculty of Pharmacy, Pharmaceutical Chemistry Department, PO Box 1,
Heliopolis, Cairo, Egypt. Tel.: +20 105368228; fax: +20 2 44771566.
E-mail address: ibrahim.ghamry@miuegypt.edu.eg (I. Elghamry).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.094

I. Elghamry, L. F. Tietze / Tetrahedron Letters 49 (2008) 3972–3975
3973
OMe
OMe
SOnPh
Cl
PhSCl
90%
2a n = 0
1
OMe
OMe
m-CPBA
2b n = 2
DBU
90%
OMe
OMe
OMe
R
SO2Ph
CNCH2CO2Et
NH
tert-BuOK/ THF
85%
OMe
MeO
3
OMe
R
i. LiAlH4
ii.TFA
4a R = CO2Et
R
N
iii. DDQ, 28%
KOH/
ethylene
glycol
160-165 ºC
80%
OMe
OMe
OMe
OMe
N
H
N
H
N
i.2,4,6-Me3-C6H2CHO/ TFA
ii. DDQ, 30%
4b R = H
R
R
OMe
MeO
5
a, R = H
b, R = 2,4,6-(CH3)3-C6H2
Scheme 1.
products have been observed.27,28 Porphyrins 5a,b in
DMSO were subjected to microwave irradiation for 4 min
at 250 °C to give a quantitative yield of porphyrins 6a,b
(Scheme 2). 29 It is worth mentioning that, firstly, the prod-
uct annealed porphyrins 6a,b do not need any further puri-
fication (just washing with methanol), and secondly, when
the reaction was performed for a shorter time a mixture of
porphyrins 5a,b and 6a,b was obtained. In order to check
the role of microwave assistance of the reaction a blank
experiment was performed under conventional heating
(sand bath) for the same period of time and at the same
temperature. The annealed porphyrin 6 was obtained but
in a very low yield (25%).29
lene units onto the porphyrin nucleus the absorption
spectra were significantly changed with 6a while those of
6b showed a small change in both the Soret and the longest
wavelength Q bands. Moreover, 6a exhibited a very intense
and strong Soret band at 444 nm and longest wavelength
Q-band at 692 nm. Similar values have been reported for
similar porphyrin ring systems.31 Surprisingly, naphtha-
loporphyrin 6b also exhibited small red shifts (Table 1).
In this case, the steric crowding due to the meso-substitu-
ents most likely leads to severe distortion of the porphyrin
macrocycle, and formation of nonplanar porphyrins, a
factor that is known to cause significant changes in the
absorption spectra.10,31,32
The UV–vis spectra (CHCl3) indicated that porphyrins
5a,b show intensified Soret bands at 410 and 394 nm,
respectively, compared to 396 nm for the related octaethyl-
porphyrin (OEP)10,30 (Table 1). After fusing the naphtha-
In conclusion, novel annealed porphyrins have been pre-
pared using a microwave assisted retro Diels–Alder reac-
tion. The high purity of the products coupled with the
quantitative yields give this method the advantage over

3974
I. Elghamry, L. F. Tietze / Tetrahedron Letters 49 (2008) 3972–3975
MeO
R
OMe
R
MeO
R
OMe
R
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
N
H
N
H
DMSO/MW
250 ºC, 4 min
quant.
N
N
N
N
H
N
H
N
R
R
R
R
OMe
MeO
OMe
MeO
5, 6
a, R = H
b, R = 2,4,6-(CH3)3-C6H2
6
5
Scheme 2.
Table 1
UV–vis (CHCl3) data for [2,3-b]naphthoporphyrins 6a,b and their precursors 5a,b
Naphthaloporphyrin
Soret band
k max (nm) (loge)
Q-bands
5a
5b
6a
6b
410 (5.21)
395 (5.13)
444 (4.89)
372 (4.23)
496 (3.73)
496 (4.35)
568 (4.22)
410 (4.13)
550 (3.96)
527 (4.12)
619 (4.29)
440 (4.10)
589 (3.46)
614 (3.14)
614 (3.76)
692 (4.12)
633 (4.02)
563 (4.05)
645 (4.24)
580 (3.75)
other reported methods31 for constructing similar ring
systems.
7. Raymond, B. J. J. Heterocycl. Chem. 2002, 39, 455 and references
cited therein.
8. Vinogradov, S. A.; Wilson, D. F. J. Chem. Soc., Perkin Trans. 2 1995,
103.
9. Chen, P.; Dvornikov, A. S.; Nakashima, M.; Roach, J. F.; Nabran,
D. M.; Rentzepis, P. M. J. Phys. Chem. 1996, 100, 17507.
10. Elghamry, I.; Tietze, L.-F. J. Heterocycl. Chem. 2005, 42, 503.
11. Ito, S.; Ochi, N.; Uno, H.; Murashima, T.; Ono, N. Chem. Commun.
2000, 893.
12. Lash, T. D.; Chandraseker, P.; Osuma, A. T.; Chany, S. T.; Spence, J.
D. J. Org. Chem. 1998, 63, 8455.
13. Fumoto, Y.; Uno, H.; Murashima, T.; Ono, N. Heterocycles 2001, 54,
705.
Acknowledgments
This work was supported by the Fonds der Chemischen
Industrie. I. Elghamry thanks the Alexander-von-Hum-
boldt foundation for the research fellowship (Long-Term-
Co-operation Program) at the Georg-August-University
in Go¨ttingen, Germany.
14. Ito, S.; Ochi, N.; Uno, H.; Murashima, T.; Ono, N. Chem. Commun.
2000, 893.
Supplementary data
15. Clezy, P. S.; Fookes, C. J. R.; Mirza, A. H. Aust. J. Chem. 1977, 30,
1337.
16. Lash, T. D.; Denny, C. P. Tetrahedron 1995, 51, 59.
17. Lash, T. D.; Roper, T. J. Tetrahedron Lett. 1994, 35, 7715.
18. Ono, N.; Hironaga, H.; Ono, K.; Kaneko, S. J. Chem. Soc., Perkin
Trans. 1 1996, 417.
Supplementary data (spectroscopic data and UV–vis
spectral data) associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.04.094.
References and notes
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I. Elghamry, L. F. Tietze / Tetrahedron Letters 49 (2008) 3972–3975
3975
29. A typical procedure: A mixture of porphyrin 5 (200 mg) and DMSO
(1 mL) was placed in a 5 mL Smith Creator Vial, equipped with a
magnetic stirring bar. The vial was sealed with a Teflon septum and
an alumina crimp top. The vessel was inserted into the cavity of a
Smith Creator microwave reactor, irradiated at 250 °C for 4 min and
subsequently cooled by rapid gas-jet cooling. The vessel was removed
from the cavity and excess pressure released by piercing the Teflon
septum with a needle. The Teflon septum was removed and 3 mL of
methanol was added. The product was collected by filtration and
washed three times with methanol to give porphyrin 6 in quantitative
yield.
2H), 2.42 (br s, 36H), 3.68 (s, 24H), 6.64–6.85 (m, 16H), 8.51 (m, 8H).
Mass (EI) (m/z): 1423.42. Anal. Calcd for C96H86N4O8ÁCH3OH: C,
80.03; H, 6.23; N, 3.85. Found C, 79.87; H, 6.03; N, 3.67.
A blank control experiment: A mixture of porphyrin 5a (200 mg) and
DMSO (1 mL) was placed in a 5 mL Smith Creator Vial and sealed
with a Teflon septum and an alumina crimp top. The vessel was
inserted into a sand bath (preheated and the temperature was kept at
250 2 °C) and heated for 4 min. Following the same workup as
mentioned above, porphyrin 6a was obtained in a low yield (50 mg,
25%).
30. Vicente, M. G. H.; Jaquinod, L.; Khoury, R. G.; Madrona, A. Y.;
Smith, K. M. Tetrahedron Lett. 1999, 40, 8763.
Porphyrin 6a was obtained as dark violet crystals, mp >300 °C. mmax
(KBr)/cmÀ1 3448 (br, NH). 1H NMR (CDCl3, 300 MHz): d À3.41 (s,
2H), 3.72 (s, 24H), 6.63 (d, J = 7.32 Hz, 8H), 8.62 (m, 8H), 10.51 (s,
4H). Mass (EI) (m/z): (M+1) 951.13. Anal. Calcd for C60H46N4O8Á
CH3OH: C, 74.52; H, 5.13; N, 5.70. Found C, 74.38; H, 4.97; N, 5.65.
Porphyrin 6b was obtained as dark violet crystals, mp >300 °C. mmax
(KBr)/cmÀ1 3425 (br, NH). 1H NMR (CDCl3, 300 MHz): d À2.21 (s,
31. Lash, T. D. J. Porphyrins Phthalocyanines 2001, 5, 267.
32. Jentzen, W.; Simpson, M. C.; Hobbs, J. D.; Song, X.; Ema, T.;
Nelson, N. Y.; Medforth, C. D.; Smith, K. M.; Veyrat, M.;
Mazzanati, M.; Ramasseul, R.; Marchon, J. C.; Takeuchi, T.;
Goddard, W. A.; Shelnutt, J. A. J. Am. Chem. Soc. 1995, 117,
11805.