An expedient synthesis of substituted tetraaryltetrabenzoporphyrins

Article abstract of DOI:10.1039/b008816l

A simple route to tetraaryltetrabenzoporphyrins (Ar₄TBPs) is developed; the procedure allows for the introduction of substituents on both benzo- and phenyl-rings and employs readily available, inexpensive components.

Full text of DOI:10.1039/b008816l

An expedient synthesis of substituted tetraaryltetrabenzoporphyrins†
Olga Finikova,a Andrei Cheprakov,*a Irina Beletskayaa and Sergei Vinogradov*b
a Department of Chemistry, Moscow State University, Moscow 119899, Russia. E-mail: avchep@elorg1.chem.msu.ru
b Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA
19104, USA. E-mail: vinograd@mail.med.upenn.edu; Fax: +01-215-573-3787; Phone: +01-215-898-6382
Received (in Corvallis, OR, USA) 31st October 2000, Accepted 22nd December 2000
First published as an Advance Article on the web 23rd January 2001
A simple route to tetraaryltetrabenzoporphyrins (Ar4TBPs)
is developed; the procedure allows for the introduction of
substituents on both benzo- and phenyl-rings and employs
readily available, inexpensive components.
Alder adduct 3 with dimethyl maleate (DMM) is obtained in
85% yield (a). Both products, 3 and 2, are further transformed
into sulfone 4. Compound 3 reacts with PhSCl, which is
followed by oxidation and elimination of HCl (b2); 2 partici-
pates in the similar Diels–Alder reaction (a) with DMM.12
Sulfone 4 reacts with tert-butyl isocyanoacetate (c)13 yielding
cyclohexanopyrrole 5 in 70–95% yield, which is deprotected
and decarboxylated by TFA in CH2Cl2 (d) in 35–40% yield.
Pyrrole 6 obtained in this way is introduced into the Lindsey
condensation (e),14 which produces porphyrins 7a–d in 25–35%
yields. Alternatively, porphyrins 7a–d can be obtained by
directly reacting cyclohexanopyrrole 5 with benzaldehydes
under Alder–Longo conditions (d+e), in which case deprotec-
tion–decarboxylation occurs in situ in the presence of TsOH.
Such simplification of the synthesis is especially practical when
yields of the one-pot procedure (8–12%) are comparable with
yields of the stepwise decarboxylation-condensation (8–14%).
Noteworthy is that in all cases porphyrins 7a–d were isolated as
dications rather than as free-bases (evidenced by UV-VIS
Tetrabenzoporphyrins (TBP’s) and their metal complexes have
rapidly gained popularity as versatile near infra-red dyes. The
spectrum of their applications encompasses PDT (photo-
dynamic therapy),1a non-linear optical absorption,1b optical
limiting1c and dioxygen measurements in vivo by phosphores-
cence quenching.1d Due to solubility considerations the meso-
tetraarylsubstituted TBP’s (Ar4TBP) have proven to be the most
useful, especially those bearing functional groups in benzo and/
or in meso-phenyl rings, which permit their further derivatiza-
tion. However, until very recently all synthetic methods leading
to Ar4TBPs were based on a high temperature condensation
between phthalimide and phenylacetic acids,2a or similar
donors of benzo- and phenyl-groups.2b The harsh conditions of
this process (fusion at 350–400 °C) allowed for only a few inert
substituents, such as alkyl groups or halogens,3 to be introduced
into the TBP macrocycle. In addition, low yields and complex,
virtually inseparable mixtures of products4 made the whole
method quite impractical.
Since the obvious precursor of the Ar4TBP cycle, isoindole,
is highly unstable, the recent search for more convenient
synthetic protocols centered around isoindole-precursors, i.e. c-
annelated pyrroles. These are available via Barton–Zard
isocyanoacetate chemistry and have proven to be useful for the
synthesis of other symmetric extended porphyrins.5 Two
methods of TBP synthesis of this kind were reported to date.
Both methods are based on the Barton–Zard reaction and
involve the initial synthesis of either cycloalkyl6 or bicycloalk-
enyl fused porphyrins.7 These intermediate porphyrins are then
aromatized by either base catalyzed elimination of sulfinate6 or
the thermal retro-Diels–Alder extrusion of ethylene.7 The latter
method affords Ar4TBPs in excellent yields; however, the
synthesis of the isoindole precursors themselves, i.e. bicyclo-
alkenyl fused pyrroles, involves hazardous compounds such as
nitroethyl acetate. Here we report an alternative route to the
Ar4TBP system, which is both simple and general. The
procedure allows for the introduction of substituents in both
benzo- and meso-phenyl rings while employing only inex-
pensive and readily available components.
In our approach, the common precursor of the synthesis is the
inexpensive sulfolene 1‡ (Scheme 1), which is converted to a
tetrahydroisoindole via the Diels–Alder reaction with an
appropriate dienophile,8 followed by the introduction of the
phenylsulfonyl group and subsequent Barton–Zard-type reac-
tion of the resulting vinyl sulfone.9 Tetrahydroisoindoles are
further introduced into Lindsey condensation, giving tetra-
cyclohexanoporphyrins, which are finally aromatized.
Scheme 1 Reagents and conditions: a, DMM, py, 140 °C, pressure tube,
85%; b1, (i) PhSCl. CH2Cl2; (ii) Et3N; (iii) Oxone, MOH, 86% for three
steps; b2, (i) PhSCl, CH2Cl2; (ii) MCPBA; (iii) DBU, 81% for three steps;
The first successful application of this approach to the
synthesis of the substituted Ar4TBPs is shown in Scheme 1.§
Sulfolene 1 is converted to 3-phenylsulfonyl-3-sulfolene10
2
t
c, CNCH2CO2 Bu, tBuOK, THF, Ar, 0 °C, 80–95%; d, TFA–CH2Cl2, Ar, rt,
(b1) using earlier published procedures.11Alternatively, Diels–
35–40%; e, (i) YC6H4CHO, BF3·Et2O, CH2Cl2; (ii) DDQ, 25–35% for two
steps; d + e, YC6H4CHO (X = H), AcOH, TosOH, CH2Cl2, 8–12%; f, (i)
M(OAc)2, MeOH–CHCl3; (ii) DDQ, THF or MeCN, reflux, M = Zn, Cu,
Ni, 98% for two steps.
† Electronic supplementary information (ESI) available: experimental data.
See http://www.rsc.org/suppdata/cc/b0/b008816l/
DOI: 10.1039/b008816l
Chem. Commun., 2001, 261–262
This journal is © The Royal Society of Chemistry 2001
261

to the modified tetrabenzoporphyrin system. Newly synthesized
tetrabenzoporphyrins were found promising basic phosphors
for oxygen measurements by phosphorescence quenching.
S. V. acknowledges support of the grant HL-60100 from the
National Institutes of Health (NIH) of the USA. O. F. and A. C.
acknowledge support of the grant 01-03-33097-A from the
Russian Foundation for Basic Research.
Notes and references
‡ The IUPAC name for sulfolene is 2,5-dihydro-1H-thiophene-1,1-diox-
ide.
§ Newly synthesized porphyrins were characterized by 1H NMR and
MALDI-TOF mass spectrometry. The details of the analysis are given in the
ESI†. The UV-VIS and phosphorescence spectroscopy was performed as
described elsewhere.1d
1 (a) A. Lavi, F. M. Johnson and B. Ehrenberg, Chem. Phys. Lett., 1994,
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therein; (b) M. Brunel, F. Chaput, S. A. Vinogradov, B. Campagne, M.
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2 (a) V. N. Kopranenkov, S. N. Dashkevich and E. A. Luk’yanets, Russ.
J. Gen. Chem. (Engl. Transl.), 1981, 51, 2165; (b) for review see T. D.
Lash, Synthesis of Novel Porphyrinoid Chromophores in Porphyrin
Handbook, ed. K. M. Kadish, K. M. Smith and R. Guilard, Acad. Press,
NY, 2000, Vol. 2, Ch. 10, p. 125.
Fig. 1 (a) Absorption spectra of porphyrin 7a in CH2Cl2 (solid line) and in
pyridine (dashed line); (b) absorption spectrum of Pd-tetrabenzoporphyrin
11a in water (pH 8.0). Insert shows uncorrected emission (phosphores-
cence) spectrum of 11a in deoxygenated solution; (c) excitation spectrum of
11a (corrected for the lamp intensity) related to the emission at 807 nm.
3 V. N. Kopranenkov, E. A. Makarova, S. N. Dashkevich and E. A.
Luk’janets, Russ. Chem. Heterocycl. Comp. (Engl. Transl.), 1988, 24,
630; S. A. Vinogradov and D. F. Wilson, Tetrahedron Lett., 1998, 39,
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4 K. Ichimura, M. Sakuragi, H. Morii, M. Yasuike, M. Fukui and O.
Ohno, Inorg. Chim. Acta, 1990, 176, 31.
5 T. D. Lash and B. H. Novak, Angew. Chem., Int. Ed. Engl., 1995, 34,
683; J. D. Spence and T. D. Lash, J. Org. Chem., 2000, 65, 1530.
6 M. G. H. Vicente, A. C. Tome, A. Walter and J. A. S. Cavaleiro,
Tetrahedron Lett., 1997, 38, 3639.
spectroscopy Fig. 1a). The dications could be fully deprotonated
only in the presence of such bases as Et3N or pyridine, which
suggests that 7a–d exhibit unusually high basicity.15 The
porphyrins 7a–d were converted to their respective metal
complexes and aromatized by refluxing with an excess of DDQ
(f),16 giving the MAr4TBPs (M = Ni, Cu, Zn) 8a–d in nearly
quantitative yields. Interestingly, free-base porphyrins could
not be aromatized under such conditions, most likely due to the
formation of dications, which are apparently not oxidized by
DDQ. The net yield of the entire sequence is 3–8%. Given that
all starting compounds are readily available, this synthesis can
afford gram quantities of substituted Ar4TBPs in a single
preparation.
Zn complexes 8a–c could be quantitatively demetalated by
treatment with TFA in CH2Cl2, to give free-base tetra-
benzoporphyrins 9a–c. The Pd complex of tetraphenylocta-
methoxycarbonyltetrabenzoporphyrin 10a was formed quanti-
tatively upon reacting the free-base porphyrin 9a with PdCl2 in
refluxing benzonitrile. Finally, the methoxycarbonyl groups of
10a were deesterified (NaOH–THF–H2O), giving tetraphenyl-
octacarboxytetrabenzoporphyrin 11a, well soluble in basic
aqueous solutions. The absorption and emission spectra of 11a
are shown in Fig 1b. The near infra-red emission with lmax at
807 nm (phosphorescence) is completely quenched in the
presence of molecular oxygen. In deoxygenated water solutions
this phosphorescence has a lifetime of 107 msec and a quantum
yield of about 10%, which makes metalloporphyrin 11a well
suited for the lifetime oxygen sensing.1d Intriguingly the
phosphorescence of 11a has a significantly higher intensity if
excited at the weaker Q-band, than at the Soret band. The
corrected excitation spectrum of 11a, recorded at a very high
dilution (absorbance at Soret maximum (440 nm) 0.05 OD), is
shown in Fig. 1c. Since no emission was observed directly from
the S2-state, such behavior is most likely due to the existence of
uncommon non-radiative pathways of S2 deactivation.
7 S. Ito, T. Murashima, H. Uno and N. Ono, Chem. Commun., 1998,
1661.
8 It could be advantageous to conserve the sulfolene moiety until the last
stages of the synthesis. However, the attempts to use sulfolenopyrroles
in porphyrin synthesis lead to intractable materials of very low
solubility. The only example of fused tetrasulfoleneporphyrin with
highly sterically encumbered meso-aryl groups has been recently
reported by B. Kräutler, C. S. Sheehan and A. Rieder, Helv. Chim. Acta,
2000, 83, 583.
9 G. Haake, D. Struve and F.-P. Montforts, Tetrahedron Lett., 1994, 35,
9703; Y. Abel, E. Haake, G. Haake, W. Schmidt, D. Struve, A. Walter
and F.-P. Montforts, Helv. Chim. Acta, 1998, 81, 1978.
10 In fact, an isomer mixture consisting of 2 and 4-phenylsulfonyl-
2-sulfolene was obtained; however, in the subsequent reactions this
mixture behaved like pure compound 2.
11 T.-S. Chou and S.-C. Hung, J. Org. Chem., 1988, 53, 3020; P. B.
Hopkins and P. L. Fuchs, J. Org. Chem., 1978, 43, 1208.
12 Interestingly, the Diels–Alder reaction between sulfolene 1 and DMM
leads almost quantitatively to the trans-isomer of 3, while the reaction
of 2 with DMM produces predominantly the cis-isomer of 4. The latter
can also be synthesized from the commercially available cis-tetra-
hydrophthalic anhydride. The trans-isomer, however, affords higher
yields (up to 95%) in the following Barton–Zard condensation with tert-
butyl isocyanoacetate.
13 B. H. Novak and T. D. Lash, J. Org. Chem., 1998, 63, 3998.
14 J. S. Lindsey, I. C. Schreiman, H. C. Hsu, P. C. Kearney and A. M.
Marguerettaz, J. Org. Chem., 1987, 52, 827; J. S. Lindsey, K. A.
Maccrum, J. S. Tyhonas and Y. Y. Chuang, J. Org. Chem., 1994, 59,
579.
15 Similar properties were previously observed for other types of non-
planar-porphyrins: C. J. Medforth, M. D. Berber, K. M. Smith and J. A.
Shelnutt, Tetrahedron Lett., 1990, 31, 3719.
16 This method was used previously for aromatization of tetrahy-
drobenzoporphyrins: T. D. Lash, Energy & Fuels, 1993, 7, 166.
In summary, we have developed a new method of synthesis of
Ar4TBPs, which employs inexpensive, readily available starting
materials. The method allows introduction of functional groups
in both benzo- and phenyl- rings, thus providing a general route
262
Chem. Commun., 2001, 261–262