Synthesis of symmetrical tetraaryltetranaphtho[2,3]porphyrins

Article abstract of DOI:10.1021/jo047741t

A new method of synthesis of meso-tetraaryltetranaphtho[2,3]porphyrins (Ar₄TNP) has been developed. Ar₄TNPs with peripheral functional groups are obtained by oxidative aromatization of meso-tetraarylporphyrins in which pyrrole units

Full text of DOI:10.1021/jo047741t

Synthesis of Symmetrical Tetraaryltetranaphtho[2,3]porphyrins
Olga S. Finikova,† Sergei E. Aleshchenkov,‡ Raymond P. Brin˜as,† Andrei V. Cheprakov,*,‡
Patrick J. Carroll,§ and Sergei A. Vinogradov*,†
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania
19104, Department of Chemistry, Moscow State University, Moscow 119899, Russia, and Department of
Chemistry, Crystallographic Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania 19104
avchep@elorg.chem.msu.ru; vinograd@mail.med.upenn.ed
Received December 24, 2004
A new method of synthesis of meso-tetraaryltetranaphtho[2,3]porphyrins (Ar4TNP) has been
developed. Ar4TNPs with peripheral functional groups are obtained by oxidative aromatization of
meso-tetraarylporphyrins in which pyrrole units are fused with either octahydro- or dihydronaph-
thalene moieties. These precursor porphyrins are synthesized in four to five steps from readily
available starting materials, such as naphthalene or 1,4-benzoquinone. The pathway originating
in dihydronaphthalene, i.e., the “dialine” route, was found to be superior to the alternative “octaline”
route in that it (1) enables the shortening of the overall reaction sequence, (2) has a broader scope
in terms of the peripheral substitution in Ar4TNPs, and (3) affords higher yields of the target
porphyrins. Pd complexes of the synthesized Ar4TNPs exhibit remarkably strong absorption bands
at 710-720 nm (ꢀ ∼ 200 000 M-1 cm-1) and phosphoresce at room temperature with moderate
quantum yields (φ ) 2-3%, λmax ) 900-1000 nm). The absorption maxima of naphthoporphyrins
substituted with eight methoxy groups (Ar4TNP(OMe)8) were found to be about 15-20 nm red
shifted compared to the corresponding maxima of unsubstituted Ar4TNPs. The X-ray crystallographic
data suggest that these spectral shifts are caused not by the differences in nonplanar distortions
of the macrocycles but by the purely electronic effects of the substituents.
Introduction
suggesting applications in small molecule and ion sens-
ing. Shifting of the absorption bands of porphyrinoids into
the lower energy region can be approached in different
ways, which include expanding the basic tetrapyrrolic
macrocycle by adding extra pyrrolic fragments,6 manipu-
lating porphyrin planarity,7 as well as extending the
porphyrin core by fusing it with external aromatic
fragments.8 The latter approach leads to the so-called “π-
In the past two decades, the interest in tetrapyrrolic
chromophores with enhanced absorption in the far-red
region of the spectrum has been steadily on the rise.
Beginning with singlet oxygen sensitization and tumor
therapy (PDT),1 the usefulness of near-infrared-absorbing
porphyrinoids has been evidenced in biomedical imaging2
and in the development of nonlinear optical materials.3
In addition, these compounds frequently demonstrate
intriguing electrochemical4 and acid-base properties,5
(1) (a) Bonnett, R. Chem. Soc. Rev. 1995, 24, 19. (b) Sessler, J. L.;
Dow, W. C.; O’Connor, D.; Harriman, A.; Hemmi, G.; Mody, T. D.;
Miller, R. A.; Qing, F.; Springs, S.; Woodburn, K.; Young, S. W. J. Alloys
Compd. 1997, 249, 146. (c) Pandey, R. K. In The Porphyrin Handbook;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New
York, 2000; Chapter 43. (d) Brunner, H.; Schellerer, K. M. Monatsh.
Chem. 2002, 133, 679. (e) Moan, J.; Peng, Q. Anticancer Res. 2003,
23, 3591. (f) Nyman, E. S.; Hynninen, P. H. J. Photochem. Photobiol.
B 2004, 73, 1.
* To whom correspondence should be addressed. (S.A.V.) Phone:
(215) 898-6382. Fax: (215) 573-3787.
† Department of Biochemistry, University of Pennsylvania.
‡ Department of Chemistry, Moscow State University.
§ Department of Chemistry, Crystallographic Laboratory, University
of Pennsylvania.
10.1021/jo047741t CCC: $30.25 © 2005 American Chemical Society
Published on Web 05/07/2005
J. Org. Chem. 2005, 70, 4617-4628
4617

Finikova et al.
CHART 1
CHART 2
The extension of all four porphyrin pyrroles by fused
naphthalene fragments leads to a number of isomeric
tetranaphthoporphyrins (Chart 1). Symmetrical tetra-
naphtho[2,3]porphyrins (TNPs)13 stand out in this group
because they possess the highest order of molecular
symmetry and, consequently, exhibit the strongest and
most narrow spectral transitions. The zinc complex of
meso-unsubstituted TNP was originally synthesized by
Lukyanets and co-workers in 1979 by condensing 3-car-
boxymethyl-5,6-benzophthalimidine with zinc acetate at
high temperature.14 Originating from phthalocyanine
chemistry, this approach had been used before in the
synthesis of tetrabenzoporphyrins.15 Later, other naph-
thoporphyrins, such as [1,2]-TNP (Chart 1) and a number
of peripherally substituted TNPs, were synthesized from
the corresponding benzophthalimidines or naphthalenedi-
carboximides16,12b by similar methods.
In terms of practical handling, meso-tetraaryl-substi-
tuted TNPs (Ar4TNP) (Chart 2) offer an important
advantage over their meso-unsubstituted analogues due
to improved solubility. It is known that laterally extended
porphyrins in general and tetranaphthoporphyrins in
particular present considerable solubility problems, which
can be, at least in part, circumvented by introducing
meso-aryl substituents into the porphyrin macrocycle.17
The above-mentioned template condensation approach
has been applied by the same group (Lukyanets and co-
workers) to synthesize Ar4TNPs from [2,3]naphthalene-
dicarboximide and arylacetic acids in the presence of zinc
acetate at 350-400 °C.16a Though it did allow initial
screening of the physical properties of TNPs,12 this
method appeared to be quite impractical due to the
extremely low yields and laborious chromatographic
purifications required for isolation of the final products.
In addition, extremely harsh reaction conditions prohib-
extended porphyrins,” which, though studied relatively
little, have already proven attractive for a variety of
applications. For example, the simplest π-extended por-
phyrins, i.e., tetrabenzoporphyrins (TBP; Chart 1), ap-
pear to be useful in biological oxygen imaging,2b,9 PDT,10
and have shown potential in optical limiting.3a,11 At the
same time, tetranaphthoporphyrins (TNP; Chart 1),
which possess even stronger near-infrared bands, have
been explored only minimally,12 mainly because of their
limited synthetic availability.
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(13) Here and throughout the text we abbreviate tetranaphtho[2,3]-
porphyrins as “TNP”, omitting the numbers [2,3].
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4618 J. Org. Chem., Vol. 70, No. 12, 2005

Synthesis of Symmetrical Tetraaryltetranaphtho[2,3]porphyrins
SCHEME 1
ited the introduction of functional groups into the TNP
macrocycle.
Over the past decade, a different approach to tet-
ranaphthoporphyrins, as well as to the other aromatically
extended porphyrins, has emerged from the works of the
Ono18 and Lash8,17b,19 groups. Their methodology is based
on pyrroles already fused with aromatic rings, from which
the target porphyrins are assembled in standard ways.
Such pyrroles can be prepared from the corresponding
nitroarenes and isocyanoacetates under Barton-Zard
conditions.20 A number of extended porphyrins, including
tetranaphtho[1,2]porphyrins,18 were synthesized using
this method, but naphtho[2,3]porphyrins remained an
inaccessible target, as only [1,2]-naphtho-fused pyrroles
could be produced from either 1-nitro- or 2-nitronaph-
thalene.18,21
In more recent years, Ono and co-workers proposed
another pathway to laterally extended porphyrins based
on the retro-Diels-Alder reaction.22 This approach has
been successfully implemented in the synthesis of both
TNPs and Ar4TNPs (Ar ) Ph).23 According to the Ono’s
method, TNPs are obtained from the precursor porphy-
rins, in which all four pyrroles are fused with bicyclic
fragments, by simply heating these porphyrins under
reduced pressure. Thermal extrusion of ethylene induced
in this manner results in a clean and quantitative
aromatization; however, the synthesis of the precursors
themselves is rather complicated. In addition, the method
is inappropriate for synthesizing porphyrins containing
substituents in the naphtho rings.
In the course of our own work on the synthesis of
π-extended porphyrins, we recently came across a useful
strategy based on the direct oxidative aromatization of
porphyrins annealed with nonaromatic saturated hydro-
carbon rings. This approach enabled us to obtain a
variety of polyfunctionalized tetraaryltetrabenzoporphy-
rins (Ar4TBPs) in good yields from readily available
starting materials.24 The oxidative aromatization method
also proved to be quite applicable to the synthesis of Ar4-
TNPs.25 Herein, we report the optimized synthesis, novel
structural data, and some basic photophysical properties
of two classes of Ar4TNPs with and without substituents
in the naphtho rings.
The routes differ in terms of the types of fused
porphyrins (11 vs 6) which precede the target Ar4TNPs
(12) in Scheme 1. In route 1, further referred to as the
“octaline” route, the starting material is ∆2-octaline 2.
The sequence of transformations leading first to the
octaline-fused porphyrins of type 6 and then to Ar4TNPs
(12) is very similar to our earlier published approach to
Ar4TBPs, in which cyclohexene-fused porphyrins served
as nonaromatized precursor porphyrins.24 Aromatization
of octahydronaphthalene rings in porphyrins 6 required
strong oxidative conditions and was possible only for
copper and palladium complexes of 6.
The alternative route (route 2, Scheme 1) starts with
1,4-dihydronaphthalene derivatives 7a,b and will be
further termed as the “dialine” route. The basic strategy,
i.e., the oxidative aromatization at the last step of the
sequence, remains the same; however, the aromatization
of precursor porphyrins 11 requires the removal of only
8 hydrogens, as opposed to the 32 which must be removed
in the “octaline” route. Accordingly, the aromatization
proceeds much more easily, making the “dialine” route
advantageous in a number of ways. A discussion of both
routes, as well as of the spectroscopic and structural
properties of the obtained Ar4TNPs, is presented below.
Two synthetic routes to Ar4TNPs, both relying on the
oxidative aromatization approach, are shown in Scheme
1.
(18) Ono, N.; Hironaga, H.; Ono, K.; Kaneko, S.; Murashima, T.;
Ueda, T.; Tsukamura, C.; Ogawa, T. J. Chem. Soc., Perkin Trans. 1
1996, 417.
(19) (a) Lash, T. D.; Wijesinghe, C.; Osuma, A. T.; Patel, J. R.
Tetrahedron Lett. 1997, 38, 2031. (b) Lash, T. D.; Novak, B. H.; Lin,
Y. N. Tetrahedron Lett. 1994, 35, 2493. (c) Lash, T. D.; Denny, C. P.
Tetrahedron 1995, 51, 59.
Results and Discussion
The synthesis of Pd complexes of Ar4TNPs (Pd-12a,b)
via the “octaline” route is outlined in Scheme 2.26
cis-∆2-Octaline 2 was prepared from the Diels-Alder
adduct of butadiene and 1,4-benzoquinone 1 using a
published procedure (a1).27 Compound 2 was further
transformed into vinyl sulfone 3 via the sequence of
published reactions (b1, c1).28 Vinyl sulfone 3 was reacted
(20) (a) Barton, D.; Zard, S. J. Chem. Soc., Chem. Commun. 1985,
1098. (b) Barton, D.; Kervagoret, J.; Zard, S. Tetrahedron 1990, 46,
7587.
(21) Lash, T. D.; Thompson, M. L.; Werner, T. M.; Spence, J. D.
Synlett 2000,.
(22) Uno, H.; Ono, N. J. Synth. Org. Chem. Jpn. 2002, 60, 581.
(23) (a) Ito, S.; Murashima, T.; Uno, H.; Ono, N. Chem. Commun.
1998, 1661. (b) Ito, S.; Ochi, N.; Murashima, T.; Uno, H.; Ono, N.
Heterocycles 2000, 52, 399. (c) (a) Ito, S.; Ochi, N.; Uno, H.; Murashima,
T.; Ono, N. Chem. Commun. 2000, 893.
(24) (a) Finikova, O. S.; Cheprakov, A. V.; Beletskaya, I. P.;
Vinogradov, S. A. Chem. Commun. 2001, 261. (b) Finikova, O. S.;
Cheprakov, A. V.; Beletskaya, I. P.; Carroll, P. J.; Vinogradov, S. A. J.
Org. Chem. 2004, 69, 522.
(25) Finikova, O. S.; Cheprakov, A. V.; Carroll, P. J.; Vinogradov,
S. A. J. Org. Chem. 2003, 68, 7517.
(26) The letters above the arrows, followed by the numbers “1” or
“2”, are used in Schemes 2 and 3 to designate similar reactions for the
parallel routes 1 and 2 (Scheme 1), respectively.
(27) Henbest, H. B.; Smith, M.; Thomas, A. J. Chem. Soc. 1958,
3293.
(28) Hopkins, P. B.; Fuchs, P. L. J. Org. Chem. 1978, 43, 1208.
J. Org. Chem, Vol. 70, No. 12, 2005 4619

Finikova et al.
SCHEME 2a
SCHEME 3a
a Key: a2, Me2SO4, K2CO3, acetone, reflux, 36 h (98%); a2′, Na,
EtOH, 3 h (80%); b2, (a) PhSCl, CH2Cl2; (b) m-CPBA (83-90%);
c2, DBU, CH2Cl2, -10 °C-rt, 5 min (60% for 8c); c2′, tBuOK, THF,
t
rt, 2h (90% for 8d); d2, d2′, CNCH2CO2Et, BuOK, THF, reflux
30 min (70-80%); e2, KOH, (CH2OH)2, reflux, 30 min (90-97%);
f2, (1) ArCHO, BF3‚Et2O, CH2Cl2, 1.5 h, rt; g2, DDQ, rt of reflux
30 min (35-49%); h2, PdCl2 or Zn(OAc)2‚2H2O, PhCN/pyridine,
reflux, 1-5 min (80-95%).
a Key: a1, (1) Zn dust, AcOH-H2O, reflux, 30 min, (2)
NH2NH2‚H2O, KOH, ethylene glycol (50%); b1, (1) PhSCl, CH2Cl2;
(2) m-CPBA; c1, DBU, CH2Cl2 (80% for b1 + c1); d1, CNCH2CO2Et,
tBuOK, THF, 0 °C to rt (88%); e1, KOH, (CH2OH)2, reflux, 30 min;
f1, (1) ArCHO, BF3‚Et2O, CH2Cl2, 1.5 h, rt, (2) DDQ (40-45% for
e1 + f1); g1, PdCl2, MeCN-THF, Et3N, reflux, 15 min (95-97%),
or Cu(OAc)2‚2H2O, CH2Cl2-MeOH, reflux, 10 min (99%); h1,
DDQ, toluene, reflux, 5 min (40-46% for Pd-12a,b); or in the
presence of Sc(OTf)3 (20% for Cu-12b).
be obtained at the oxidation step in 60-95% yields, while
the maximal yield achieved in the case of PdAr4TNP 12b
was only 46%. This lower efficiency of the aromatization
is likely to be caused by poor stability of the resulting
metal complexes of Ar4TNPs, which decompose quickly
under strongly oxidative conditions. Indeed, the literature
data point to the fact that the oxidation potentials of
TNPs are quite low.12b,d At the same time, milder
oxidants, such as p-chloranil or o-chloranil, appeared to
be inefficient and failed to induce the aromatization.
The intrinsic limitations of the “octaline” route prompted
us to search for an alternative method of synthesis of Ar4-
TNP. Decreasing the degree of saturation of the fused
rings in the precursor porphyrins seemed like a feasible
way to facilitate the aromatization, avoiding harsh oxida-
tive conditions at the final step of the sequence. Indeed,
replacing the precursor octaline-fused porphyrins 6 with
dihydronaphthalene-fused porphyrins 11 (Scheme 1)
proved to have a pronounced effect on the aromatization
reaction. The details of the corresponding “dialine” route
are shown in Scheme 3.
The key starting material, 1,4-dihydronaphthalene
(1,4-dialine) 7a, can be conveniently prepared in bulk
quantities from naphthalene.32 Similarly, other 1,4-
disubstituted dialines, e.g., 1,4-dialkyl-1,4-dihydronaph-
thalene33 and 1,4-dicarboxy-1,4-dihydronaphthalene,34
which in principle are suitable precursors in this route,
also can be synthesized from naphthalene. Another useful
starting material, 5,8-dihydroxy-1,4-dihydronaphthalene
1a, can be prepared in one step from butadiene and 1,4-
benzoquinone.35 This compound can be readily converted
into a variety of useful derivatives by means of the
Williamson alkylation. In this work, the dimethoxy
derivative 7b was employed.
with ethyl isocyanoacetate in the modified Barton-Zard
synthesis29,30 (d1) to yield pyrrole ester 4, which was
converted into pyrrole 5 upon reflux with KOH in
ethylene glycol (e1). Pyrrole 5 without isolation was
introduced into the Lindsey condensation with aromatic
aldehydes (f1), yielding porphyrins 6a,b. meso-Tetraary-
lated cycloalkene-fused porphyrins possess very high
basicities5e and easily form dications upon treatment with
DDQ. These dications have been shown to be completely
inert in aromatization;23 therefore, octaline-fused por-
phyrins 6 had to be converted into appropriate metal
complexes M-6. The best results were obtained with Pd
derivatives Pd-6a,b, which were oxidized by DDQ (h1)
in refluxing toluene, affording Pd-12a,b in 40-45% yield.
Aromatization of copper complexes appeared to be much
less effective (2-3% yield) but could be improved in the
presence of Sc(OTf)3,31 giving Cu-12b in 20% yield.
Attempts to oxidize nickel complexes of 6 under a variety
of conditions proved unsuccessful as complete decomposi-
tion of porphyrins was observed. In the case of zinc
complexes, aromatization was impeded due to the rapid
demetalation of Zn-6 upon treatment with DDQ, which
resulted in the formation of dications.
The “octaline” synthesis of Ar4TNPs turned out to be
much less efficient than the analogous synthesis of Ar4-
TBPs from cyclohexene-fused porphyrins.24 In the latter,
both copper and palladium complexes of Ar4TBPs could
(29) Abel, Y.; Haake, E.; Haake, G.; Schmidt, W.; Struve, D.; Walter,
A.; Montforts, F. P. Helv. Chim. Acta 1998, 81, 1978.
(30) Arnold, D. P.; Burgess-Dean, L.; Hubbard, J.; Abdur Rahman,
M. Aust. J. Chem. 1994, 47, 969.
(31) The use of Sc(OTf)3 was proposed by Osuka et al. to facilitate
oxidative coupling of porphyrins into conjugated multiporphyrin ar-
rays: Tsuda, A.; Osuka, A. Science 2001, 293, 79.
(32) Hu¨ckel W.; Schlee R. Chem. Ber. 1955, 88, 346.
(33) Rabideau, P. W.; Burkholder, E. G. J. Org. Chem. 1978, 43,
4283.
(34) Lyssy, T. M. J. Org. Chem. 1962, 27, 5.
(35) Rama Rao, A. V.; Yadav, J. S.; Bal Reddy K.; Mehendale, A. R.
Tetrahedron 1984, 40, 4643.
4620 J. Org. Chem., Vol. 70, No. 12, 2005

Synthesis of Symmetrical Tetraaryltetranaphtho[2,3]porphyrins
The transformations following the initial syntheses are
very similar for compounds 7a and 7b. Both 7a and 7b
were first converted (b2) into the corresponding R-chlo-
rosulfones 8a,b using a published procedure.28 The
subsequent synthesis of pyrrole-esters 9a and 9b, how-
ever, required slightly different protocols due to the
differences in the reactivity of the substrates, as well as
to some unforeseen side reactions (vide infra).
affording 9b as a sole product in 77% yield. Apparently,
the potassium derivative of isocyanoacetate, capable of
driving the initial elimination of HCl from 8b, is more
active in the Barton-Zard reaction than in the subtrac-
tion of another proton and the following aromatiza-
tion.
Esters 9a,b were further converted (e2) into pyrroles
10a,b, which reacted with aromatic aldehydes under
Lindsey conditions (f2). In the latter syntheses, the
mixtures were either allowed to stir overnight at room
temperature (12c,d) or refluxed for 30-60 min (12a,b)
following the addition of DDQ. In either case, intermedi-
ate porphyrins of type 11 were not isolated; instead, the
free bases Ar4TNPs 12a,b and Ar4TNP(OMe)8’s 12c,d
were obtained in 35-50% yield. Spectroscopic analysis
of samples taken at different times during the syntheses
of porphyrins 12a,b, however, suggests that under opti-
mized conditions porphyrins 11 can be obtained as
individual compounds. Ar4TNPs 12a,b were further
reacted with zinc acetate or palladium chloride in ap-
propriate solvents, yielding the corresponding metal
complexes M-12.
Pyrrole esters with fused nonaromatic rings, such as
9a,b, are usually synthesized from the corresponding
cyclic R-vinyl sulfones by the modified Barton-Zard
method, in which an R-vinyl sulfone is typically added
to an equimolar mixture of an alkyl isocyanoacetate and
a base (usually tBuOK).24,29 On the other hand, conversion
of the R-chlorosulfone into the R-vinyl sulfone, which
usually precedes the Barton-Zard synthesis, also re-
quires 1 equiv of a base.28 It seemed, therefore, sensible
to combine these two steps into one by simply adding the
R-chlorosulfone to a mixture of 2 equiv of the base and 1
equiv of the isocyanoacetate (d2). In this case, the first
t
equivalent of, e.g., BuOK would be spent to eliminate
HCl, while the second would generate anionic species
from ethyl isocyanoacetate for the Barton-Zard synthe-
sis.
Unexpectedly, naphthoporphyrins 12a,b and 12c,d
exhibit large differences in solubility. Unsubstituted Ar4-
TNPs 12a,b, and their metal complexes are soluble in
most organic solvents (e.g., CH2Cl2, THF). Porphyrins
12c,d (Ar4TNP(OMe)8), on the other hand, are practically
insoluble at room temperature, despite multiple periph-
eral substituents; these porphyrins can, however, be
dissolved to moderate concentrations in hot benzonitrile
and nitrobenzene. The broadening of aromatic resonances
in 1H NMR spectra of both Ar4TNPs and Ar4TNP(OMe)8
suggests that these porphyrins aggregate in solution. It
was possible to improve the resolution of the proton
spectra of metal complexes M-12a-d using polar sol-
vents, such as pyridine-d5, PhNO2-d5, or dmso-d6, and
performing measurements at elevated temperatures.
However, except for Zn-12d, 13C NMR spectra of com-
pounds 12c,d and M-12c,d could not be recorded with
satisfactory resolution. NMR spectra of free base por-
phyrins 12a-d, which are less soluble and more likely
to aggregate than the metal complexes, could not be fully
resolved either, even if measurements were done in polar
solvents at high temperatures (>100 °C). In contrast, the
dications of 12a-d (trifluoroacetates or chlorides) were
found to be easily soluble in CDCl3, although in some
cases aggregation still presented a problem. For example,
As expected, treatment of R-chlorosulfone 8a with a
t
mixture of 2.2 equiv of BuOK and 1.2 equiv of ethyl
isocyanoacetate in THF at 0 °C followed by a 30 min
reflux afforded pyrrole ester 9a in 70% yield (d2).
However, under the same conditions, dimethoxy deriva-
tive 8b gave the target pyrrole ester 9b in about a 1:1
molar ratio with the side product, naphthyl sulfone 8d.
Further, it was found that naphthyl sulfone 8d readily
forms upon treatment of 8b with an excess of a strong
t
base, such as BuOK or DBU, and that the reaction
involves the initial elimination of HCl. For example, the
reaction between R-chlorosulfone 8b and 1 equiv of DBU
(c2) afforded allyl sulfone 8c, and treatment of the latter
t
with an excess of BuOK at rt gave 8d almost quantita-
tively (c2′). It is known that aromatization of cyclohexa-
dienes can be, in principle, incurred by strong bases.36
In this respect, it is interesting that sulfones 8a and 8b
behave so differently under basic conditions: in the case
of unsubstituted sulfone 8a aromatization via the elimi-
nation of the phenylsulfonyl group, leading to the forma-
tion of naphthalene, is the predominant pathway.
Allyl sulfone 8c appeared to be active as a substrate
in the Barton-Zard reaction (d2′), since under basic
conditions it exists in equilibrium with the correspond-
ing vinyl sulfone.37 When reacted with an equimolar
mixture of tBuOK and ethyl isocyanoacetate in refluxing
THF, 8c gave 9b in 80% yield. On the other hand,
avoiding the side reaction (i.e., formation of 8d) and thus
keeping the synthesis of 9b from 8b a one-pot procedure
could be done by simply using 2 M excess of isocyano-
acetate. In this case, R-chlorosulfone 8b had to be added
1
good-quality H and 13C spectra of the dications of Ar4-
TNPs 12a,b were easily recorded for concentrated solu-
tions of trifluoroacetates, while the spectra of Ar4TNP-
(OMe)8 12d could be obtained for chlorides only in very
diluted (∼0.1 mg/mL) solutions.
As shown above, low solubility and strong aggregation
often make handling of naphthoporphyrins very difficult.
Although meso-arylation in many cases improved solubil-
ity, aggregation of both Ar4TNPs and Ar4TNP(OMe)8 still
imposed significant difficulties on the spectroscopic mea-
surements. To overcome this problem, we synthesized
Ar4TNPs in which each meso-aryl ring was substituted
with two butoxycarbonyl groups in the 3,5-positions. The
butyl ester substituents not only improved the solubility
of Ar4TNPs (12e,f) but also considerably prevented their
aggregation. The synthesis of octabutoxycarbonyl-Ar4-
TNPs is shown in Scheme 4.
t
to the mixture of equal amounts of BuOK and ethyl
isocyanoacetate (2.2 mol of each per 1 mol of 8b),
(36) Pines, H.; Stalick, W. M. Base-catalyzed reactions of hydrocar-
bons and related compounds; Academic Press: New York, 1977; p 483.
(37) Allyl sulfones are known to exist in equilibrium with the
corresponding vinyl sulfones in the presence of strong bases, such as
DBU or tBuOK. For examples, see: (a) Savoia, D.; Trombini C.; Umani-
Ronci, A. J. Chem. Soc., Perkin Trans. 1 1977, 123. (b) Inomata, K.;
Hirata, T.; Kinoshita, H.; Kotake H.; Senda, H. Chem. Lett. 1988,
2009.
J. Org. Chem, Vol. 70, No. 12, 2005 4621

Finikova et al.
SCHEME 4a
FIGURE 1. Absorption spectra of ZnTPP (black line), ZnPh4-
TBP (red line), and ZnPh4TNP (green line) in pyridine.
of optical transitions and other photophysical properties
can be assessed systematically. A comparative photo-
physical study as well as some theoretical calculations
have been recently published for Zn and Pd complexes
of symmetrically extended porphyrins.11c,12g One of the
main conclusions made was that the influence of non-
planar distortion on the red shifts of the optical transi-
tions of Ar4TNPs, as compared to Ar4TBPs, is much
smaller than that of the π-conjugation. These results
were based on the analysis of the computationally
obtained structures, since no experimental data on Ar4-
TNPs was available. Herein we present new X-ray data
and some additional photophysical measurements, fur-
ther supporting the above-mentioned conclusion.
Compared to the regular meso-tetraarylporphyrins
(Ar4P), which possess nearly ideally planar structures,
Ar4TNPs exhibit large red shifts of the absorption bands.
For example, in the case of zinc complexes these shifts
reach about 70 nm for the Soret bands and up to 120 nm
for the Q-bands (Figure 1). In addition, relative intensi-
ties of the Q-band maxima increase greatly upon exten-
sion of the macrocycle π-system, e.g., as much as about
15-20 times for Zn complexes.
a Key: i, (CH2OH)2, PhH, p-TosH‚H2O, reflux, 8 h; ii, (1) CO,
BuOH, Pd[(PPh3)4], Et3N, 36 h, 80 °C; iii, HClaq, THF, reflux 40
min (i-iii) 77%); iv, (1) BF3‚Et2O, CH2Cl2, 1.5 h, rt; (2) DDQ, rt
or reflux 30 min (40-45%); v, PdCl2, PhCN, reflux, 20-30 min
(12e, 80%) or PdCl2, PhCN/pyridine, reflux, 3-5 min (12f, 85%).
The precursor aldehyde, dibutyl 5-formylisophthalate
14, was prepared in the total yield of 77% from the
commercially available 3,5-dibromobenzaldehyde 13 in
three steps: (1) protection of the carbonyl group, (2) Pd-
catalyzed butoxycarbonylation, and (3) deprotection. Al-
dehyde 14 reacted with pyrroles 9a,b (Scheme 4) afford-
ing porphyrins 12e,f in 30-40% yields. Palladium
complexes of these porphyrins were prepared by reacting
the free bases with PdCl2 in refluxing PhCN (12e) or in
PhCN-pyridine mixture (12f). Both the free bases and
palladium complexes of octabutoxycarbonyl porphyrins
12e,f are very easily soluble in most organic solvents and
much less prone to aggregation.
Although detailed examination of the photophysical
properties of Ar4TNPs calls for a special investigation,
we performed an initial analysis of their absorption and,
in some cases, their emission characteristics, as well as
some structural studies. The original driving force behind
our work in the area of extended porphyrins is their
potential use as functional elements for biological oxygen
sensors.9,12f In this respect, examining the phosphorescent
characteristics of Pd complexes presents to us a special
interest. On the other hand, there are a number of
questions in the current porphyrin literature associated
with the effects of nonplanar distortion and π-extension
on the spectra of porphyrins.38 Following tetraaryltetra-
benzoporphyrins (Ar4TBP), Ar4TNPs continue the row of
laterally extended porphyrins, in which the influences
of distortion and extended π-conjugation on the red shifts
The Q-bands of Ar4TNPs are significantly red-shifted
in respect to the Q-bands of Ar4TBPs as well, while the
positions the Soret maxima are shifted notably less
(Figure 1). For example, the Q-bands of the homologous
complexes ZnPh4TNP (Zn-12a) and ZnPh4TBP39 differ by
Zn-12a
ZnPh4TBP
65 nm (λQ
) 723 nm vs λQ
) 658 nm). At
the same time, the Soret bands differ by no more than
Zn-12a
ZnPh4TBP
30 nm (λSoret
) 473 nm vs λSoret
) 502 nm)
(Figure 1). The oscillator strengths of the Q-bands of Ar4-
TNPs are about 3-4 times larger than those of the
similar Ar4TBPs. A question arises whether the differ-
ences in these basic photophysical properties of Ar4TNPs
vs Ar4TBPs are caused by stronger nonplanarity of the
former, by the electronic effects of naphtho vs benzo
groups or by a combination of both of these factors.
It has been shown that the classic Gouterman’s four-
orbital model40 cannot adequately explain the absorption
properties of Ar4TNPs.11c In these porphyrins, HOMOs
(38) Haddad, R. E.; Gazeau, S.; Pecaut, J.; Marchon, J. C.; Medforth,
C. J.; Shelnutt, J. A. J. Am. Chem. Soc. 2003, 125, 1253 and references
therein.
(39) Cheng, R. J.; Chen, Y. R.; Chuang, C. E. Heterocycles 1992, 34,
1.
(40) Gouterman, M. J. Mol. Spectrosc. 1961, 6, 138.
4622 J. Org. Chem., Vol. 70, No. 12, 2005

Synthesis of Symmetrical Tetraaryltetranaphtho[2,3]porphyrins
FIGURE 2. X-ray crystal structures of Pd-12b (PdAr4TNP) and Pd-12f (PdAr4TNP(OMe)8). The diagrams on the right depict
the results of the NSD analysis,41 showing only two main out-of-plane (oop; B1u-ruffling and B2u-saddling) and two in-plane (ip;
A1g and A2g) distortion modes. The parameter Doop is a measure of the total distortion of the core tetrapyrrole macrocycle, which
takes into account all out-of-plane distortion modes. The parameter dsad quantifies the B1u saddling distortion only.
are not far enough separated from the other MOs, which
also participate in the configuration interaction defining
the properties of the ground and excited states. Therefore,
the spectra of Ar4TNPs are complicated by extra transi-
tions in the Soret-band region. The lower energy bands
of both Ar4TBPs and Ar4TNPs, however, still can be
formally traced to the transitions involving HOMO-1 (b1)
and the LUMO pair.11c Since HOMO-1 is largely localized
on the R- and â-carbons of the pyrrole rings,40 π-conjuga-
tion, which can be viewed for this purpose as a substitu-
tion of the of â-pyrrole carbons, should affect mostly the
Q-band transitions. This notion manifests itself in larger
red shifts of the Q-bands of Ar4TNP’s vs their Soret bands
(Figure 1).
The recently obtained structural data25 suggest that
the degrees of nonplanarity of MAr4TNPs and MAr4-
TBPs39 are very close, implying that the red shifts of the
absorption bands of Ar4TNPs are caused mainly by the
extended π-conjugation. In this work, we show that the
additional side substitution in naphtho rings, which in
principle could have influenced the Ar4TNP geometry,
has, in fact, no structural effect, but yet causes an extra
red shift of optical transitions. The X-ray crystallographic
structures of Pd complexes of two types of Ar4TNPs, Pd-
12b and Pd-12f, are shown in Figure 2 together with
their NSD (normal-coordinate structural decomposition)
analyses.41 NSD analysis is a very helpful tool for
comparing nonplanar distortions in different types of
porphyrins and for presenting their differences in a
graphical mode.
The analysis of the X-ray data collected from a crystal
of Pd-12f revealed that the side Bu groups and the
cocrystallized solvent (Et2O) molecules were severely
disordered, which lowered the quality of the overall
crystal structure determination (see the Supporting
Information). Nevertheless, the structure of the core
tetrapyrrole macrocycle was determined with adequate
quality, so that only small variations in distortion modes
would be expected should the NSD analysis be performed
on an overall better resolved structure.
The main distortion mode in both Pd-12b (PdAr4TNP)
and Pd-12f (PdAr4TNP(OMe)8) is saddling (B2u), al-
though there are small contributions of ruffling (B1u) and
two in-plane distortions A1g and A2g. The same modes
were found to be dominant in the other reported struc-
tures of extended porphyrins: ZnPh4TBP‚THF,39 H2Ph4-
TBP(CO2Me)8,5e and NiPh4TBP(CO2Me)8.24b Despite eight
methoxy groups in Pd-12f its degree of nonplanarity (Doop
) 2.38Å) is very close to that of Pd-12b (Doop ) 2.57Å),
and in fact, Pd-12f is even slightly less distorted than
Pd-12b. At the same time, for the pair of porphyrins with
the same substituents in the meso-aryl rings (Pd-12e and
Pd-12f), the absorption bands of Pd-12f, which contains
(41) (a) Jentzen, W.; Song, X.-Z.; Shelnutt, J. A. J. Phys. Chem. B
1997, 101, 1684. (b) Jentzen, W.; Ma, J. G.; Shelnutt, J. A. Biophys. J.
1998, 74, 753.
J. Org. Chem, Vol. 70, No. 12, 2005 4623

Finikova et al.
tation at either Q or Soret bands. The phosphorescence
maxima are at about 955 nm and the Stokes shifts
relative to the Q-bands are in the order of 240-250 nm,
which is substantially larger than for PdTPP (166 nm)11c
and PdPh4TBP (172 nm).9b Measuring absolute quantum
efficiencies above 850 nm is intrinsically difficult because
of the rapidly falling sensitivity of detection systems
(PMT) in this wavelength range and the absence of good
reference points for actinometry measurements. Due to
these complications, the reported values should be con-
sidered as only approximate. The phosphorescence quan-
tum yields were found to be 1.8% for Pd-12e and 2.5%
for Pd-12f,45 which is lower than the values obtained for
PdAr4P (φ ) 4.5%) and for PdAr4TBP (φ ) 6.7%) (Ar )
4-MeO2C-C6H4) using the same conditions, i.e., in deoxy-
genated toluene at rt. Consistent with quantum yields,
the phosphorescence lifetimes (τ0 ) 48 µs and τ0 ) 38
µs) are also shorter than those of the reference porphyrins
FIGURE 3. Absorption and phosphorescence (designated as
PHOS) spectra of Pd-12e (black) and Pd-12f (red) in deoxy-
genated toluene solutions.
PdAr4P
PdAr4TBP
(τ0
) 385 µs, τ0
) 205 µs). More rapid
nonemissive deactivation of the triplet states of Ar4TNPs
is most probably caused by their very low energy levels,
which further increase the probability of internal conver-
sion into the ground states common among nonplanar
porphyrins.46 Other spectroscopic features of PdAr4TNPs
are similar to those reported earlier
eight methoxy substituents, are notably red-shifted rela-
tive to those of the unsubstituted Pd-12e: λQPd-12e ) 714
Pd-12f
Pd-12e
nm vs λQ
λSoret
) 721 nm and λSoret
) 458 nm vs
Pd-12f
) 463 nm) (Figure 3).
Phosphorescence of Pd-12f was found to be very
sensitive to oxygen having the Stern-Volmer quenching
constant Kq in DMF of about 20 000 mmHg1-s-1. This
value is more than two times higher than Kq’s of PdAr4P47
or of PdAr4TBP (Ar ) HO2CC6H4), which in DMF at rt
are about 10 000 and 7000 mmHg1-s-1, respectively. Such
high sensitivity to oxygen makes PdAr4TNPs quite potent
as phosphors for in vivo oxygen measurements and also
as PDT agents, despite their moderate emission quantum
yields and lifetimes. In addition, large gaps between the
Q and Soret bands (∆λ > 250 nm) and rather large T0-
T1 extinction coefficients11c place PdAr4TNPs among the
most promising dyes for optical limiting. On the other
hand, for this and other applications, chemical and
photochemical stability of Ar4TNPs will be of crucial
importance. Improving it by a different macrocycle
substitution will be the next synthetic challenge in this
area of porphyrin synthesis.
The red shift, therefore, is most probably caused
exclusively by the electronic effect of eight methoxy
groups in Pd-12f, which are likely to raise the energy of
its HOMO, narrowing the HOMO-LUMO gap. A more
detailed understanding of the effects of peripheral sub-
stitution in extended porphyrins would require spectro-
electrochemical measurements,4 which would help to
track down changes in HOMOs and LUMOs upon sub-
stitution individually.
Ar4TNPs free bases exhibit strong fluorescence (e.g.,
12e: φ ) 0.063, λmax ) 767 nm (DMF); 12f: φ ) 0.132,
λmax ) 769 (DMF); compare to φH2TPP ) 0.11 (C6H6)42),
which is somewhat unexpected considering their high
nonplanarity.43 The observed fluorescence quantum yields
are much higher than those of other saddled porphyrins,
e.g., φH2OETPP ) 0.005 (H2OETPP ) octaethyltetraphen-
ylporphyrin),43 suggesting that the extended π-conjuga-
tion causes a decrease in either the probability of the
internal conversion of 1(π, π*) state or of the intersystem
In conclusion, a method of synthesis of Ar4TNPs based
on oxidative aromatization has been developed. Two
variants of the method, the “dialine” and the “octaline”
routes, have been compared, revealing the former’s
numerous advantages. The “dialine” route employs readily
available 1,4-dihydronaphthalene derivatives as starting
1
crossing from (π, π*) state, or both.
The presence of extremely powerful near infrared
bands in the absorption spectra of Ar4TNPs (ꢀQ ≈ 200 000
M-1 cm-1) automatically draws attention to these por-
phyrins as potential PDT sensitizers and in vivo optical
imaging probes, e.g., for oxygen.9 For these applications,
it is necessary that porphyrins possess stable, long-living
triplet states, which are normally generated via the
intersystem crossing from the first excited singlet states.
The efficiency of intersystem crossing is substantially
increased in the presence of heavy metal ions, e.g., Pt
and Pd,44 and therefore, the corresponding complexes are
especially interesting. It was found that Pd complexes
of Ar4TNPs exhibit relatively strong phosphorescence in
deoxygenated solutions at room temperature upon exci-
(45) In our preliminary communication,25 we reported a different,
probably exaggerated value for the phosphorescence quantum yield of
the compound Pd-12b, i.e., 6.5%. This was probably a result of an
inaccurate calibration curve used for the PMT (Hamamatsu R2685)
correction. Having said that, an error of 5-10% is rather expected for
the measurements in the wavelength range where detector sensitivity
drops by a factor of 10 per each 50 nm. A different detector (photodiode
or an APD) would be required to measure quantum yields of the
naphthoporphyrin’s luminescence more accurately.
(46) (a) Gentemann, S.; Medforth, C. J.; Ema, T.; Nelson, N. Y.;
Smith, K. M.; Fajer, J.; Holten, D. Chem. Phys. Lett. 1995, 245, 441.
(b) Gentemann, S.; Nelson, N. Y.; Jaquinod, L.; Nurco, D. J.; Leung,
S. H.; Medforth, C. J.; Smith, K. M.; Fajer, J.; Holten, D. J. Phys. Chem.
B 1997, 101, 1247. (c) Chirvony, V. S.; van Hoek, A.; Galievsky, V. A.;
Sazanovich, I. V.; Schaafsma, T. J.; Holten, D. J. Phys. Chem. B 2000,
104, 9909.
(42) Seybold, P. G.; Gouterman, M. J. Mol. Spectrosc. 1969, 31, 1.
(43) Gentemann, S.; Medforth, C. J.; Forsyth, T. P.; Nurco, D. J.;
Smith, K. M.; Fajer, J.; Holten, D. J. Am. Chem. Soc. 1994, 116, 7363.
(44) Eastwood, D.; Gouterman, M. J. Mol. Spectrosc. 1970, 35, 359.
(47) (a) Vinogradov, S. A.; Lo, L. W.; Wilson, D. F. Chem. Eur. J.
1999, 5, 1338. (b) Rozhkov, V. V.; Wilson, D. F.; Vinogradov, S. A.
Macromolecules 2002, 35, 1991.
4624 J. Org. Chem., Vol. 70, No. 12, 2005

Synthesis of Symmetrical Tetraaryltetranaphtho[2,3]porphyrins
aq Na2CO3 (100 mL) and finally with 5% aq HCl, after which
it was dried over Na2SO4. The solvent was removed in a
vacuum, and the remaining material was purified on a silica
gel column twice (eluent: CH2Cl2, then CH2Cl2-THF, 10:1).
Each time a bright green band eluting with CH2Cl2-THF was
collected and the solvent was removed in a vacuum. The
remaining green solid was purified by repetitive precipitation
from CH2Cl2 with hexanes-ether mixture (4:1) and dried in a
vacuum. To obtain porphyrins 6a,b as free bases, the CH2Cl2
solutions of the corresponding dications were thoroughly
washed with 10% aq Na2CO3, dried over K2CO3, and evapo-
rated.
6a, as dication dichloride: yield 450 mg, 45%, green powder;
1H NMR (CDCl3-TFA-d) δ 8.3 (br, 8H), 7.8 (br s, 12H), 2.2-
0.0 (m, 56H), -1.6 (br s, 4H); MALDI-TOF m/z 1048.7, calcd
1046.6; UV-vis for dication dichloride, CH2Cl2; λmax nm (ꢀ) 462
(185 000), 610 (92 000), 666 (16 600).
materials and makes it possible to obtain the target
porphyrins in five to six steps, with up to 20% overall
yield. The efficiency and versatility of this method has
been demonstrated by synthesizing a variety of Ar4TNPs
and their metal complexes, including polyfunctional
derivatives with substituents in the fused naphtho rings
and/or in the meso-aryl rings.
Experimental Section
Ethyl isocyanoacetate was prepared from glycine ethyl ester
hydrochloride according to the published method.48 1,4-Dihy-
dronaphthalene 7a,32 5,8,9,10-tetrahydro-1,4-naphthoquinone
1, 5,8-dihydroxy-1,4-dihydronaphthalene 1a, and 5,8-dimethoxy-
1,4-dihydronaphthalene 7b35 were synthesized as described
previously. Octaline 2 was obtained from 1 in 40% yield
according to the published procedure.27 Sulfone 3 was prepared
from 2 in 80% yield following the standard method.28 The
equipment used for analytical characterization of the com-
pounds has been described elsewhere.24,25 Melting points are
uncorrected.
6b, as dication dichloride: yield 485 mg, 40%, green powder;
1H NMR (CDCl3-TFA-d) δ 8.4-8.6 (m, 16H), 4.2 (s, 12H), 2.4-
0.3 (m, 56H), -1.3 (br s, 4H); MALDI-TOF m/z 1280.2, calcd
1279.6; UV-vis for dication dichloride, CH2Cl2, λmax nm (ꢀ) 474
(190 000), 620 (98 200), 677 (18 400).
Pd-Porphyrins (Pd-6a,b). An excess of PdCl2 (20 mg,
0.11 mmol) was added to a solution of porphyrin 6a (90 mg,
0.08 mmol) or 6b (110 mg, 0.08 mmol) in CH3CN-THF (6a:
30 mL, 1:2; 6b: 20 mL, 1:1) or dioxane (30 mL), and the
mixture was refluxed for 10-15 min. Et3N (0.5 mL) was added,
and the mixture was refluxed for an additional 5 min. The
conversion was monitored by UV-vis spectroscopy (solvent
CHCl3-AcOH), and the reaction was stopped when the por-
phyrin-dication band at around 470 nm disappeared. The
mixture was evaporated to dryness, and the remaining mate-
rial was purified on a silica gel column (eluent: CH2Cl2) to
give the product as a red amorphous solid.
Pyrrole Ester 4. Synthesis of 4 followed a general protocol
described earlier.29 A solution of ethyl isocyanoacetate (565 mg,
5.0 mmol) in 15 mL of dry THF was added to a suspension of
90% tBuOK (620 mg, 5.0 mmol) in 25 mL of THF at 0 °C under
Ar. A solution of sulfone 3 (1.1 g, 4.1 mmol) in 30 mL of THF
was added dropwise to the mixture and left to react at rt under
continuous stirring. After 4 h, the volume of the mixture was
reduced to about 10 mL by rotary evaporation. CH2Cl2 (100
mL) was added to the mixture, and the resulting solution was
washed with water and then with brine and dried over Na2-
SO4. After evaporation of the solvent, the residue was dried
in a vacuum to remove the excess isocyanoacetate, and the
product was purified on a silica gel column (eluent: CH2Cl2).
After evaporation of the solvent, the product was crystallized
from CH2Cl2-hexane or ethyl alcohol. 4: yield 890 mg, 88%,
colorless crystals; mp 114-116 °C; TLC, CH2Cl2, Rf ∼ 0.6, dark
1
Pd-6a: yield 87 mg, 95%; H NMR (CDCl3) δ 8.2-7.5 (m,
20H), 2.2-0.7 (m, 56H); MALDI-TOF m/z 1153.6, calcd 1150.5;
UV-vis, CH2Cl2, λmax nm (ꢀ) 424 (200 000), 536 (20 200), 570
(15 300).
1
Pd-6b: yield 107 mg, 97%; 1H NMR (CDCl3) δ 8.5-7.9 (m,
16H), 4.1 (s, 12H), 2.4-0.6 (m, 56H); MALDI-TOF m/z 1382.2,
calcd 1384.0; UV-vis, CH2Cl2, λmax nm (ꢀ) 429 (210 000), 539
(20 600), 576 (16 000).
spot in the UV light; H NMR (CDCl3) δ 8.74 (broad s, 1H),
6.60 (d, 1H, J ) 3 Hz), 4.29 (m, 2H), 3.05 (dd, 1H, J1 ) 17 Hz,
J2 ) 5 Hz), 2.61 (dd, 1H, J1 ) 15 Hz, J2 ) 4 Hz), 2.23 (dd, 1H,
J1 ) 17 Hz, J2 ) 10 Hz), 2.10 (dd, 1H, J1 ) 16 Hz, J2 ) 11
Hz), 1.85 (m, 2H), 1.75 (m, 2H), 1.28-1.35 (ovrlap t + m, 3 +
4H), 1.08 (m, 2H); 13C NMR (CDCl3) δ 161.6, 128.2, 122.2,
118.0, 117.3, 59.8, 39.0, 34.5, 34.4, 30.9, 29.8, 26.6, 26.4, 14.7.
Anal. Calcd for C15H21NO2: C, 72.84; H, 8.56; N, 5.66. Found:
C, 72.59; H, 8.65; N, 5.67.
Cu-Porphyrin (Cu-6b). An excess of Cu(OAc)2‚2H2O (20
mg, 0.11 mmol) was added to a solution of porphyrin 6b (100
mg, 0.074 mmol) in CH2Cl2-MeOH (20 mL, 10:1), and the
mixture was refluxed for 15 min. The conversion was moni-
tored by UV-vis spectroscopy (solvent CHCl3-AcOH). The
reaction was stopped when the Soret absorption of the por-
phyrin dication disappeared. The mixture was evaporated to
dryness, and the remaining material was purified on a silica
gel column (eluent: CH2Cl2) to give the product as red
amorphous solid. Porphyrin Cu-6b: yield 100 mg, 99%;
MALDI-TOF m/z 1307.5, calcd 1307.3; UV-vis CH2Cl2, λmax
nm (ꢀ) 428 (172 000), 559 (14 800).
Pd-Tetranaphthoporphyrins (Pd-12a,b). Pd-6a (80
mg, 0.07 mmol) or Pd-6b (93 mg, 0.067 mmol) was dissolved
in 50 mL of dry toluene under Ar. DDQ (365 mg, 1.61 mmol)
was added, and the mixture was refluxed for 3-5 min. The
color of the solution changed from red to brown and the product
precipitated as a dark green powder. The mixture was allowed
to cool, and the solvent was removed in a vacuum. The
resulting solid was dissolved in CH2Cl2 (several drops of EtOH
were added to dissolve the remaining residue), washed with
10% aq Na2SO3 (2 × 50 mL), 10% aq Na2CO3 (50 mL), water,
and brine, and dried over Na2SO4. The solvent was removed
in a vacuum, and the solid was purified on a silica gel column
(eluent: CH2Cl2, then CH2Cl2-THF, 30:1). The bright green
band was collected. The volume of the solution was reduced
to ∼1 mL by rotary evaporation; it was layered over with
diethyl ether and left in a closed vessel overnight. The product
precipitated as a dark green solid (6a) or dark-green crystals
(6b).
Porphyrins 6a,b. Pyrrole ester 4 (890 mg, 3.60 mmol) was
refluxed under Ar with an excess of NaOH (1.2 g, 30 mmol) or
KOH (1.9 g, 30 mmol) in ethylene glycol (30 mL) for 20 min.
The mixture was rapidly cooled on an ice bath. CH2Cl2
(60 mL) was added, and the mixture was thoroughly washed
with water (2 × 100 mL; brine was added to reduce the
emulsion). The aqueous phase was extracted with CH2Cl2
(3 × 30 mL), the combined organic phase was washed with
brine and dried over Na2SO4, and the solvent was removed in
a vacuum. The resulting material was purified on a short (2
× 10 cm i.d.) silica gel column (eluent: CH2Cl2). The solvent
was removed under vacuum, and the remaining material (560
mg) was dissolved in 320 mL of CH2Cl2. Benzaldehyde (in the
case of 6a: 345 mg, 3.25 mmol) or methyl 4-formylbenzoate
(in the case of 6b: 533 mg, 3.25 mmol) was added, and the
mixture was kept under continuous stirring in the dark under
Ar for 10 min. BF3‚Et2O (90 mg, 0.64 mmol) was added in one
portion, and the mixture was left to react at rt under Ar for
1.5 h. DDQ (900 mg, 4 mmol) was added, and the mixture was
allowed to stir for another 1 h. The resulting green solution
was washed with 10% aq Na2SO3 (2 × 100 mL), then with 10%
(48) Tietze, L. F.; Eicher, T. Reaktionen und Synthesen im organisch-
chemischen Praktikum und Forschungslaboratorium; Georg Thieme
Verlag: New York, 1991.
J. Org. Chem, Vol. 70, No. 12, 2005 4625

Finikova et al.
Pd-12a: yield 31 mg, 40%; 1H NMR (pyridine-d5) δ 8.48-
8.07 (m, 20H), 7.96 (br s, 8H), 7.89 (br, 8H), 7.6 (8H, overlap
with solvent); 13C NMR (pyridine-d5) δ 144.1, 138.9, 136.8,
136.2 (overlap with solvent), 134.7, 131.9, 130.7, 130.2, 129.9,
126.9, 117.8; MALDI-TOF m/z 1120.5, calcd 1119.6; UV-vis,
pyridine, λmax nm (ꢀ) 462 (190 000), 642 (27 600), 706 (204 200).
138.4, 134.2, 129.4, 129.0, 122.2, 121.9, 108.2, 107.9, 64.6, 55.8,
55.7, 52.1, 30.7, 20.3. Anal. Calcd for C18H19ClO4S: C, 58.93;
H, 5.22. Found: C, 58.85; H, 5.29.
Allyl Sulfone 8c. A stirred solution of 8b (1.78 g, 4.85
mmol) in CH2Cl2 (15 mL) was cooled to 0 °C on an ice bath,
and the solution of DBU (0.75 g, 4.95 mmol) in CH2Cl2 (5 mL)
was added dropwise. The ice bath was removed, and the
mixture was stirred at rt for 1-2 h. Diethyl ether (10 mL)
was added to the mixture, and the resulting solution was
washed with 5% aq HCl and then with brine and dried over
Na2SO4. The solvent was removed in a vacuum, and the
resulting material was purified on the silica gel column twice
to give the product as a colorless solid. 8c: yield 0.96 g (60%);
mp 155-156 °C; TLC, CH2Cl2, Rf ∼ 0.5, dark spot in the UV
light; 1H NMR (CDCl3) δ 7.7-7.2 (m, 5H), 6.94 (d, 1H, J ) 10
Hz), 6.56 (d, 1H, J ) 8.5 Hz), 6.43 (d, 1H, J ) 8.5 Hz), 5.99
(dd, 1H, J1 ) J2 ) 10 Hz), 3.91 (m, 1H), 3.75 (s, 3H), 3.65 (dd,
1H, J1 ) 18 Hz, J2 ) 4 Hz), 3.60 (s, 3H), 2.96 (dd, 1H, J1 ) 18
Hz, J2 ) 8 Hz); HR-MS 353.0830 (M+ + Na), calcd 353.0824.
Naphthyl Sulfone 8d. A solution of 8c (430 mg, 1.3 mmol)
or 8b (477 mg, 1.3 mmol) in 25 mL of THF was added dropwise
to stirred solution of 90% tBuOK (500 mg, 4 mmol) in dry THF
(50 mL) at 0 °C. The ice bath was removed, and the mixture
was stirred at room temperature for 2-3 h or until the red
color disappeared. The solvent was removed in a vacuum, and
the resulting material was dissolved in 50 mL of CH2Cl2. The
solution was washed with 10% aq HCl (2 × 50 mL) and then
with brine, dried over Na2SO4, and chromatographed on a
short (2×5 cm i.d.) silica gel column, eluting with CH2Cl2. The
first light-yellow fraction was collected (TLC, CH2Cl2, Rf ∼ 0.8,
fluorescent blue spot in UV light). The product was isolated
as yellow oil upon removal of the solvent. The oil crystallized
upon addition of ethyl alcohol and it was dried in a vacuum.
8d: yield 390 mg (90%), light-yellow solid; mp 156-158 °C;
1H NMR (CDCl3) δ 8.92 (s, 1H), 8.26 (d, 1H, J ) 9 Hz),
7.98+7.44-7.52 (m, 2+3H), 7.86 (d, 1H, J ) 9 Hz), 6.82 (d,
1H, J ) 8.5 Hz), 6.76 (d, 1H, J ) 8.5 Hz), 3.95 (s, 3H), 3.92 (s,
3H); 13C NMR (CDCl3) δ 150.3, 149.3, 142.1, 138.4, 133.2,
129.4, 128.1, 127.9, 125.5, 123.9, 123.8, 122.9, 107.0, 105.1,
56.1, 55.9; HR-MS 351.0656 (M+ + Na), calcd 351.0667.
1
Pd-12b: yield 54 mg, 46%; H NMR (CDCl3-pyridine-d5)
δ: 8.8-8.6 (m, aa′bb′, 16H), 7.7-7.8 (overlap s+m, 8+8H), 6.6
(m, 8H, overlap with solvent), 4.3 (s, 12H); 13C NMR (CDCl3-
pyridine-d5) δ 165.9, 145.6, 137.0, 134.5 (overlap with solvent),
133.4, 130.05, 130.0, 129.9, 128.2, 125.3, 115.1, 51.5; MALDI-
TOF m/z 1351.9, calcd 1351.7; UV-vis, pyridine, λmax nm (ꢀ)
462 (190 000), 647 (25 000), 713 (179 500). Anal. Calcd for
C84H52N4O8Pd: C, 74.64; H, 3.88; N, 4.14. Found: C, 74.30;
H, 3.97; N, 4.11.
Cu-Tetranaphthoporphyrin (Cu-12b). Porphyrin Cu-
6b (30 mg, 0.023 mmol) was dissolved in 30 mL of freshly
distilled dry toluene under Ar. DDQ (120 mg, 0.54 mmol) and
Sc(OTf)3 (100 mg, 0.2 mmol) were added, and the mixture was
refluxed for 20 min. The color of the solution changed from
red to brown-green, and a dark precipitate formed. The
mixture was allowed to cool, and CH2Cl2 (50 mL) was added.
The solution was washed with 10% aq Na2SO3 solution (2 ×
50 mL), water (100 mL), and brine (100 mL) and dried over
Na2SO4. The solvents were removed in a vacuum, and the
remaining solid was purified on a silica gel column (eluent:
CH2Cl2-THF, 30:1). The first green fraction contained a
mixture of porphyrins which were poorly separated and eluted
in the following order: 6b, partially oxidized 6b, Cu-12b.
Cu-12b was collected, the solvent was evaporated in a
vacuum and the remaining green solid was dried in a vacuum.
Cu-12b: yield 6 mg, 20%; MALDI-TOF m/z 1308.9, calcd
1308.1; UV-vis, CH2Cl2, λmax nm (ꢀ) 478 (170 000), 665
(20 400), 731 (154 000). Anal. Calcd for C84H52CuN4O8: C,
77.08; H, 4.00; N, 4.28. Found: C, 77.58; H, 4.68; N, 4.47.
R-Chlorosulfones (8a,b). Synthesis of compounds 8a,b
generally followed the published method.28 To a stirred solu-
tion of PhSCl (50 mmol) in 50 mL of CH2Cl2, prepared as
described in ref 28, was added dropwise a solution of 7a (6.51
g, 50 mmol) or 7b (9.5 g, 50 mmol) in 20-30 mL of dry CH2-
Cl2 at 0 °C under Ar. The mixture was allowed to warm to rt
with stirring and under Ar for 1-2 h. The mixture was kept
in a freezer at -18 °C overnight, and the precipitated succin-
imide was removed by filtration. The remaining solution was
diluted with CH2Cl2 to ∼200 mL total volume and cooled to 0
°C on an ice bath. Solid m-CPBA (77%, 30 g, 125 mmol) was
gradually added to the stirred solution in ∼1-2 g portions.
The ice bath was removed, and the mixture was left to stir at
rt for 1 h. An ice-cold 10% aq Na2SO3 solution (250 mL) was
added, and the resulting mixture was allowed to stir for
another 1 h. Aqueous Na2CO3 solution (10%, 100 mL) was
added to the mixture, and it was transferred into a separatory
funnel. The organic phase was separated, washed with 10%
aq Na2SO3 solution (100 mL) and 10% aq Na2CO3 solution (100
mL), dried over K2CO3, and evaporated to dryness. The
resulting material was recrystallized from ethyl alcohol to give
the product as a colorless solid.
Pyrrole Ester 9a. A solution of ethyl isocyanoacetate (1.4
g, 12.4 mmol) in 10 mL of dry THF was added to a stirred
t
suspension of 90% BuOK (3.1 g, 24.8 mmol) in 30 mL of dry
THF at rt under Ar. A solution of R-chlorosulfone 8a (3.2 g,
10.3 mmol) in 25 mL of THF was quickly added to the mixture,
which was stirred under Ar for 10 min at rt and then refluxed
under Ar for 40 min. The mixture was cooled to rt, and its
volume was reduced to about 15 mL by rotary evaporation.
CH2Cl2 (100 mL) was added to the mixture, and the resulting
solution was washed with water (100 mL) and then with brine
(50 mL) and dried over K2CO3. After evaporation of the solvent,
the residue was recrystallized from hexane and/or ethyl alcohol
to give the ester 9a as pale yellow crystals. 9a: yield 1.6 g,
65%; mp 155-156 °C; TLC, CH2Cl2, Rf ∼ 0.6, dark spot in the
1
UV light; H NMR (CDCl3) δ 9.2 (broad s, 1H), 7.4 (m, 1H),
7.3 (m, 1H), 7.28-7.20 (m, 2H), 6.86 (d, 1H, J ) 2.5 Hz), 4.42
(q, 2H, J ) 7 Hz), 4.23 (s, 2H), 3.95 (s, 2H), 1.46 (t, 3H, J ) 7
Hz); 13C NMR (CDCl3) δ 161.7, 135.3, 135.1, 129.4, 129.1,
126.4., 126.2, 126.1, 120.6, 118.3, 117.6, 60.2, 28.4, 27.1, 14.8.
Anal. Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.81. Found:
C, 74.44; H, 6.27; N, 5.75.
8a: 12.75 g, 83%, colorless crystals; mp 117-118 °C; TLC,
CH2Cl2: moves with solvent front, dark spot in the UV light;
1H NMR (CDCl3) δ 7.92-7.57 (m, 5H), 7.20-7.17 (m, 2H),
7.13-7.09 (m, 2H), 4.83 (m, 1H), 3.73-3.70 (m, 1H), 3.48-
3.44 (dd, 1H, J1 ) 16 Hz, J2 ) 5 Hz), 3.32-3.27 (dd, 1H, J1 )
15 Hz, J2 ) 6.5 Hz), 3.18-3.13 (dd, 1H, J1 ) 6.5 Hz, J2 ) 16
Hz), 3.07-3.06 (dd, 1H, J1 ) 16 Hz, J2 ) 4 Hz); 13C NMR
(CDCl3) δ 138.2, 134.4, 132.8, 132.1, 129.7, 129.1, 128.9, 128.3,
127.4, 127.3, 66.6, 52.8, 37.3, 26.4. Anal. Calcd for C16H15-
ClO2S: C, 62.64; H, 4.93. Found: C, 62.48; H, 4.90.
8b: 16.50 g, 90%, colorless crystals; mp 117-118 °C; TLC,
CH2Cl2, Rf ∼ 0.9, dark spot in the UV light; 1H NMR (CDCl3)
δ: 7.92-7.53 (m, 5H), 6.64 (s, 2H), 4.82 (m, 1H), 3.76 (s, 3H),
3.74-3.70 (s+m, 3H+1H), 3.40-3.33 (dd, 1H, J1 ) 4.5 Hz, J2
) 18 Hz), 3.20-3.17 (m, 3H); 13C NMR (CDCl3) δ 151.2, 150.9,
Pyrrole Ester 9b. Method A. A solution of ethyl isocy-
anoacetate (2.4 g, 21.2 mmol) in 30 mL of dry THF was added
to a stirred suspension of 90% tBuOK (2.4 g, 19.3 mmol) in 50
mL of dry THF at rt under Ar. A solution of R-chlorosulfone
8b (3.5 g, 9.5 mmol) in 40 mL of THF was added dropwise to
the mixture, and the mixture was refluxed under Ar for 1 h.
The mixture was cooled to rt, and the volume of the solvent
was reduced to about 20 mL by rotary evaporation. CH2Cl2
(150 mL) was added to the mixture, and the resulting solution
was washed with water (2 × 100 mL) and brine (100 mL) and
dried over K2CO3. The resulting solution was passed through
4626 J. Org. Chem., Vol. 70, No. 12, 2005

Synthesis of Symmetrical Tetraaryltetranaphtho[2,3]porphyrins
a short (ø2×5 cm) silica gel column, eluting with CH2Cl2-THF
(20:1). After evaporation of the solvents, the residue was
crystallized from ethyl alcohol to give the ester 9b as pale-
yellow crystals. 9b: yield 2.2 g, 77%.
8H), 7.50 (m, 8H), 2.63 (br s, 4H); 13C NMR (as dication
ditrifluoroacetate, CDCl3) δ 140.9, 139.7, 135.6, 132.9, 130.6,
130.2, 129.9, 129.5, 127.5, 125.4, 112.6; MALDI-TOF m/z
1017.2, calcd 1015.2; UV-vis, pyridine, λmax nm (ꢀ) 503
(220 000), 680 (24 000), 731 (104 000). Anal. Calcd for
C76H46N4: C, 89.91; H, 4.57; N, 5.52. Found: C, 88.88; H, 4.23;
N, 5.40.
Pyrrole Ester 9b. Method B. A solution of allyl sulfone
8c (2.74 g, 8.3 mmol) in 10 mL of dry THF was added dropwise
to a stirred mixture of 90% tBuOK (1.20 g, 10 mmol) and ethyl
isocyanoacetate (1.20 g, 10.6 mmol) in 50 mL of dry THF at rt
under Ar. The resulting mixture was refluxed for 1 h, cooled,
and worked up as described above. 9b: yield 1.92 g, 80%; mp
157-158 °C; TLC, CH2Cl2, Rf ∼ 0.4, dark spot in the UV light;
1H NMR (CDCl3) δ 8.92 (broad s, 1H), 6.80 (d, 1H, J ) 2 Hz),
6.69 (s, 2H), 3.36 (q, 2H, J ) 7 Hz), 4.06 (s, 2H), 3.82-3.83
(ovrlapping s+d, 6H+2H), 1.49 (t, 3H, J ) 7 Hz); 13C NMR
(CDCl3) δ 161.4, 151.8, 151.5, 125.3, 124.8, 119.5, 118.2, 117.6,
107.1, 106.9, 59.9, 55.8, 55.7, 22.4, 20.9, 14.6. Anal. Calcd for
C17H19NO4: C, 67.76; H, 6.36; N, 4.65. Found: C, 67.67; H,
6.37; N, 4.56.
12b: yield 45%, bluish green crystals; 1H NMR (as dication
ditrifluoroacetate, CDCl3) δ 8.80-8.64 (m, aa′bb′, 16H), 7.90
(s, 8H), 7.66 (m, 8H), 7.47 (m, 8H), 4.19 (s, 12H), 3.77 (br s,
4H); 13C NMR (as dication ditrifluoroacetate, CDCl3, 40°C) δ
167.1, 143.8, 141.4, 136.3, 133.1, 131.8, 131.2, 129.9, 129.5,
127.5, 125.8, 111.7, 52.8; 1H NMR (as free base, 1,1,2,2-
tetrachloroethane-d2, 90 °C) δ 8.66-8.56 (m, aa′bb′, 8H), 7.70
(s, 8H), 7.67 (m, 8H), 7.46 (m, 8H), 4.41 (s, 12H), 2.27 (br s,
2H); MALDI-TOF: m/z 1246, calcd 1246.4; UV-vis, pyridine,
λmax nm (ꢀ) 500 (207 700), 672 (26 100), 732 (111 000); as
dication ditrifluoroacetate, CH2Cl2, λmax nm (ꢀ) 530 (186 900),
800 (75 300). Anal. Calcd for C84H54N4O8: C, 80.88; H, 4.36;
N, 4.49. Found: C, 88.51; H, 4.24; N, 4.40.
12c: yield 40%, green powder; NMR spectra of 12c could
not be recorded due to its very low solubility and strong
aggregation; MALDI-TOF m/z 1017.2, calcd 1015.2; UV-vis,
pyridine, λmax nm (ꢀ) 509 (200 000), 683 (30 700), 750 (98 400).
Anal. Calcd for C84H62N4O8: C, 80.36; H, 4.98; N, 4.46.
Found: C, 79.90; H, 4.57; N, 4.33.
Pyrroles 10a,b. A stirred mixture of pyrrole ester 9a (2.41
g, 10 mmol) or 9b (3.01 g, 10 mmol) and NaOH (2.0 g, 50 mmol)
was refluxed under Ar in ethylene glycol for 20-30 min. The
resulting solution was rapidly cooled on an ice bath and diluted
with CH2Cl2 (100 mL). The mixture was thoroughly washed
with water (2 × 100 mL; brine was added to reduce the
emulsion), and the aqueous phase was extracted with CH2Cl2
(3×30 mL). The combined organic phases were washed with
brine and dried over Na2SO4. The solvent was removed in a
vacuum, and the resulting material was purified on a short (2
× 10 cm i.d.) silica gel column, eluting with CH2Cl2. The
solvent was evaporated, and the resulting colorless solid was
introduced into the following porphyrin synthesis immediately.
10a: yield 1.7 g, 97%; 1H NMR (CDCl3) δ 7.97 (broad s, 1H),
7.35 (m, 2H), 7.25 (m, ovlpd. w/solv, 2H), 6.67 (d, 2H, J ) 2.5
Hz), 3.99 (s, 4H); 13C NMR (CDCl3) δ 136.7, 129.3, 125.9, 118.7,
112.8, 27.8.
12d: yield 44%, green powder; 1H NMR (as dication
dichloride, CDCl3)49 δ 8.69-8.62 (m, aa′bb′, 16H), 8.32 (s, 8H),
6.64 (m, 8H), 4.16 (s, 12H), 3.78 (s, 12H); MALDI-TOF m/z
1486.5, calcd 1487.5; UV-vis, pyridine, λmax nm (ꢀ) 508
(220 000), 685 (26 100), 754 (135 000). Anal. Calcd for
C92H70N4O16: C, 74.28; H, 4.74; N, 3.77. Found: C, 73.55; H,
4.56; N, 3.97.
1
12e: yield 35%, dark green powder; H NMR (as dication
ditrifluoroacetate, CDCl3) δ 9.52 (s, 8H), 9.38 (s, 4H), 7.85 (s,
8H), 7.70 (m, 8H), 7.51 (m, 8H), 4.42-4.51 (m, 16H), 3.79 (br
s, 4H), 1.82 (m, 16H), 1.41 (m, 16H), 0.88 (t, 24H, J ) 7 Hz);
13C NMR (as dication ditrifluoroacetate, CDCl3) δ 165.6, 141.2,
140.3, 139.9, 133.2, 133.0, 132.4, 129.7, 129.6, 127.9, 125.6,
111.0, 66.1, 30.8, 19.4, 13.8; MALDI-TOF m/z 1818.36, calcd
1816.13; UV-vis, pyridine, λmax nm (ꢀ) 501 (200 000), 685
(24 300), 740 (95 500). Anal. Calcd for C116H110N4O16: C, 76.71;
H, 6.10; N, 3.08. Found: C, 76.45; H, 5.68; N, 3.03.
1
10b: yield 2.06 g, 90%; H NMR (CDCl3) δ 8.06 (broad s,
1H), 6.70 (s, 2H), 6.66 (d, 2H, J ) 2.5 Hz), 3.88 (s, 4H), 3.84
(s, 6H); 13C NMR (CDCl3) δ 151.8, 126.5, 117.5, 113.0, 107.1,
56.0, 21.3.
Tetranaphthoporphyrins (12a-f). Pyrrole 10a,b (2.5
mmol) was dissolved in CH2Cl2 (250 mL), aryl aldehyde (2.5
mmol) was added, and the stirred mixture was kept in the
dark under Ar for 10 min. BF3‚Et2O (71 mg, 0.5 mmol) was
added in one portion, and the mixture was allowed to react at
rt for 1.5 h. DDQ (2.3 g, 10 mmol) was added to the mixture
in one portion, and the mixture was stirred at rt overnight
(12c,d,f) or refluxed for 30-60 min (12a,b,e). The resulting
mixture was washed with 10% aq Na2SO3 (2 × 30 mL) and
with water (2 × 100 mL). The following workup procedures
for the individual porphyrins are described below.
12c,d. The organic phase, containing a fine suspension of
green particles, was evaporated in a vacuum. The remaining
green solid, insoluble in most organic solvents, was repeatedly
washed with water, with THF, and with CH2Cl2-py (10:1) and
recrystallized from hot PhCN. The resulting green precipitate
was washed with CH2Cl2-py (10:1) and dried in a vacuum.
Porphyrins 12c,d are poorly soluble in pyridine and DMF,
moderately soluble in hot benzonitrile and nitrobenzene, and
well soluble in acids (AcOH, TFA).
1
12f: yield 39%, dark green powder; H NMR (as free base,
CDCl3) δ 9.46 (d, 4H, J ) 2 Hz), 9.24 (d, 8H, J ) 1.5 Hz), 8.10
(br, 8H), 6.65 (s, 8H), 4.38 (t, 16H, J ) 7 Hz), 3.86 (s, 12H),
1.69 (m, 16H), 1.34 (m, 16H), 0.82 (t, 24H, J ) 7 Hz); 13C NMR
(as free base, pyridine-d5) δ 166.5, 150.8, 144.6, 139.4, 139.0,
134.1, 132.3, 131.8, 125.5, 119.8, 114.1, 104.7, 66.1, 56.2, 31.2,
19.6, 14.0; MALDI-TOF m/z 2054.8, calcd 2056.3; UV-vis,
pyridine, λmax nm (ꢀ) 505 (225 000), 686 (29 500), 758 (162 900).
Anal. Calcd for C124H126N4O24: C, 72.43; H, 6.18; N, 2.72.
Found: C, 72.10; H, 6.12; N, 2.85.
Tetranaphthoporphyrin (12b) from Cu-12b. Cu-12b
(6 mg, 0.0045 mmol) was dissolved in 5 mL of polyphosphoric
acid and stirred in a closed vessel for 4-5 h at 50 °C, then at
rt overnight. MeOH (10 mL) and H2SO4 (2 mL) were added to
the mixture, and it was left to stir for 24 h. CH2Cl2 (50 mL)
was added, and the organic phase was washed with water,
with 10% aq NaHCO3 solution, and then with brine and dried
over Na2SO4. The solvent was removed in a vacuum, and the
remaining solid was purified on a silica gel column (eluent:
CH2Cl2-THF, 30:1). The green fraction was collected, and the
solvent was evaporated in a vacuum. 7a: yield 4 mg, 72%.
Pd-Tetranaphthoporphyrins (Pd-12) from Free Bases
(12). A solution of porphyrin 12 (0.04 mmol) in PhCN (5-7
mL) was brought to boiling, and an excess of PdCl2 (10 mg,
0.06 mmol) was added to the mixture in one portion. In the
12a,b and 12e,f. The organic layer was dried over K2CO3,
the solvent was evaporated in a vacuum, and the remaining
solid was washed with MeOH (12a) or with CH3CN (12b,e,f),
dried,and purified by chromatography on a silica gel column
(eluent: CH2Cl2, then CH2Cl2-THF 30:1-10:1). The green
band was collected and reduced to a small volume, and the
porphyrin was precipitated by addition of about 20-fold excess
volume of methanol (12a) or CH3CN (12b,e,f). The precipitate
was dried in a vacuum. The trifluoroacetates of dications of
porphyrins 12a,b,e, were prepared by dissolving the free base
porphyrins in TFA and evaporating the solutions in a vacuum.
(49) The NMR sample was obtained by dissolving ∼0.5 mg of 12d
free base in CDCl3 contaminated with traces of HCl, which formed in
CDCl3 upon prolonged storage. The solution of the dication had a deep
purple color.
1
12a: yield 49%, shiny green plates; H NMR (as dication
ditrifluoroacetate, CDCl3) δ 8.63-7.97 (s+m, 8+20H), 7.72 (m,
J. Org. Chem, Vol. 70, No. 12, 2005 4627

Finikova et al.
case of porphyrins 12a,b,e, the mixture was refluxed for 20-
30 min until the conversion was complete (controlled by UV-
vis spectroscopy). For porphyrins 12d,f, the mixture was
refluxed for 3-5 min, after which a few drops of pyridine were
added. The mixtures containing the individual Pd porphyrins
were worked up as described below.
Pd-12a,b,e. PhCN was removed in a vacuum (0.5 mmHg),
and the remaining solid was purified on a silica gel or neutral
alumina column (eluent: CH2Cl2, then CH2Cl2-THF, 30:1).
The bright green band was collected. The solvent was evapo-
rated in a vacuum, and the remaining material was dissolved
in a minimal volume of warm CH2Cl2. The solution was layered
over with an excess (∼10-fold) of acetonitrile (12a,e) or ether
(12b) and left in a closed vessel overnight. The products
precipitated as dark-green crystals.
8H), 8.56-8.11 (m, 20H), 8.82 (br s, 8H); 13C NMR spectra of
Zn-12c could not be recorded due to its very low solubility
and strong aggregation; MALDI-TOF m/z 1320.0, calcd 1318.8;
UV-vis, pyridine, λmax nm (ꢀ) 504 (290 000), 667 (23 600), 730
(171 100). Anal. Calcd for C84H60N4O8Zn: C, 76.50; H, 4.59;
N, 4.25. Found: C, 75.66; H, 4.54; N, 4.31. Zn-12d: 1H NMR
(pyridine-d5) δ 8.97-8.68 (m, aa′bb′, 16H), 8.65 (s, 8H), 6.80
(s, 8H), 4.26 (s, 12H), 3.93 (s, 24H); 13C NMR (pyridine-d5, 50
°C) δ 168.6, 151.3, 144.5, 137.9, 134.9, 131.8, 131.7, 125.3,
119.6, 116.5, 104.1, 56.3, 52.7; MALDI-TOF m/z 1549.4, calcd
1550.9; UV-vis, pyridine, λmax nm (ꢀ), 503 (280 000), 669
(24 700), 732 (166 100). Anal. Calcd for C92H68N4O16Zn: C,
71.25; H, 4.42; N, 3.61. Found: C, 70.91; H, 4.38; N, 3.60.
Dibutyl 5-Formylisophthalate (14). 3,5-dibromobenzal-
dehyde 13 (6.0 g, 22.73 mmol), ethylene glycol (20 mL), and
p-toluenesulfonic acid monohydrate (190 mg, 1 mmol) were
refluxed in benzene (100 mL) with a Dean-Stark refluxing
condenser for 5 h. After cooling, the solution was transferred
into a separatory funnel, washed with 10% aq NaHCO3 (100
mL) and water (100 mL), and dried over Na2SO4. The solvent
was evaporated, and the resulting oil (7.0 g; 1H NMR (CDCl3)
δ 7.54 (d, 1H, J ) 1.5 Hz), 7.44 (d, 2H, J ) 1.5 Hz), 5.64 (s,
1H), 3.89-3.98 (m, 4H)) was placed in a pressure-resistant
vessel for carbonylation. Triethylamine (10 mL), PPh3 (100
mg), and Pd(0)[(PPh3)]4 (100 mg) were added, and the mixture
was heated to 90 °C on an oil bath in CO atmosphere. The
carbonylation was carried out at 90 °C for 48 h under 2 atm
of CO (for details of the carbonylation procedure see refs 47b
and 50]). The mixture was allowed to cool, and the vessel was
opened and left under the fume hood for another 1 h. Et3N‚
HBr, formed as a white precipitate, was removed by filtration,
and the filtrate was dried on a rotary evaporator at 0.5 mmHg.
The remaining oil [8.7 g; 1H NMR (CDCl3) δ 8.66 (s, 1H), 8.30
(d, 2H, J ) 0.5 Hz), 5.88 (s, 1H), 4.34 (t, 4H, J ) 7 Hz), 4.15-
4.04 (m, 4H), 1.76 (m, 4H), 1.47 (m, 4H), 0.97 (t, 6H, J ) 8
Hz)] was dissolved in THF (25 mL), concd HCl (4 mL) and
water (15 mL) were added, and the mixture was refluxed for
1.5 h. CH2Cl2 (150 mL) was added to the mixture, and the
organic phase was washed with 10% aq Na2CO3 (100 mL) and
then with brine (100 mL) and dried over Na2SO4. The solvent
was removed in a vacuum, and the resulting oil was purified
on a neutral alumina column (3 × 20 cm i.d., eluent: CH2-
Cl2-THF, 20:1-10:1). The first fraction (TLC, CH2Cl2-THF,
20:1, Rf ∼ 0.75, dark spot in the UV light) was collected, and
the solvent was evaporated in a vacuum to give the product
Pd-12a: yield 85%; see above. Pd-12b: yield 87%; see
above.
Pd-12e: yield 80%; 1H NMR (pyridine-d5) δ 10.02 (s, 4H),
9.78 (s, 8H), 7.98 (s, 8H), 7.71 (m, 8H), 7.38 (m, 8H), 4.45 (t,
16H, J ) 6.5 Hz), 1.60 (m, 16H), 1.26 (m, 16H), 0.82 (t, 24H,
J ) 7 Hz); 13C NMR (pyridine-d5) δ 166.4, 144.1, 140.1, 138.9,
136.5, 134.2, 132.2, 131.9, 129.9, 127.3, 124.5 (overlap with
solvent), 116.0, 66.5, 31.2, 19.3, 14.1; MALDI-TOF m/z 1921.5,
calcd 1920.5; UV-vis, pyridine, λmax nm (ꢀ) 459 (195 000), 647
(25 500), 715 (195 800). Anal. Calcd for C116H108N4O16Pd: C,
72.54; H, 5.67; N, 2.92. Found: C, 72.40; H, 5.63; N, 2.88.
Pd-12d. The hot mixture (see above) was filtered through
Celite, the solution was diluted with THF, and the precipitate
was collected by centrifugation, repeatedly washed with THF-
pyridine (20:1), and dried in a vacuum. Yield of Pd-12d: 80%,
green powder, insoluble in most organic solvents, moderately
soluble in hot pyridine, PhCN, and hot PhNO2. 1H NMR
(PhNO2-d5/DMSO-d6, 1:1, 80 °C) δ 8.75-8.52 (m, aa′bb′, 16H),
8.20 (s, 8H), 6.77 (s, 8H), 4.25 (s, 12H), 3.87 (s, 24H); MALDI-
TOF m/z 1590.7, calcd 1591.9; UV-vis, pyridine, λmax nm (ꢀ),
465 (170 000), 653 (31 000), 720 (183 000). Anal. Calcd for
C92H68N4O16Pd: C, 69.41; H, 4.31; N, 3.52. Found: C, 67.96;
H, 3.91; N, 3.27.
Pd-12f. The mixture was cooled, PhCN was removed in a
vacuum (0.5 Torr), and the resulting solid was purified on a
neutral alumina column (eluent: CH2Cl2). The bright green
band was collected. The solvent was evaporated, and the
remaining material was dissolved in the minimal volume of
warm CH2Cl2, layered over with an excess volume of ether
(∼10-fold), and left in a closed vessel overnight. The product
precipitated as dark-green crystals. Pd-12f: yield 85%; 1H
NMR (pyridine-d5) δ 10.10 (t, 4H, J ) 1.5 Hz), 9.74 (d, 8H, J
) 2 Hz), 8.61 (s, 8H), 6.73 (s, 8H), 4.44 (t, 16H, J ) 6.5 Hz),
3.93 (s, 12H), 1.59 (m, 16H), 1.26 (m, 16H), 0.71 (t, 24H, J )
7 Hz); 13C NMR (pyridine-d5) δ 166.6, 150.8 (overlap with
solvent), 144.2, 139.2, 138.3, 136.4 (overlap with solvent),
134.4, 132.0, 125.1, 119.3, 115.9, 104.5, 66.2, 56.3, 31.3, 19.7,
14.0; MALDI-TOF m/z 1259.9, calcd 1260.7; UV-vis, pyridine,
λmax nm (ꢀ) 463 (170 000), 654 (31 200), 725 (220 600). Anal.
Calcd for C124H124N4O24Pd: C, 68.93; H, 5.78; N, 2.59. Found:
C, 68.45; H, 5.74; N, 2.55.
Zn-Tetranaphthoporphyrins (Zn-12) from Free Bases
(12). A solution of porphyrin 12 (0.04 mmol) in PhCN (5-7
mL) was brought to boiling, and an excess of Zn(OAc)2‚2H2O
(10 mg, 0.06 mmol) was added to the mixture. In the case of
porphyrins 12a,b, the mixture was refluxed for 15-20 min
until the conversion was complete (controlled by UV-vis
spectroscopy). In the case of porphyrins 12d,f, the mixture was
refluxed for 3-5 min, after which time a few drops of pyridine
were added and the mixture was allowed to cool to rt. The
mixture was diluted with methanol (50-100 mL), and the
green precipitate was collected by centrifugation, repeatedly
washed with methanol-pyridine mixture (50:1), and dried in
a vacuum. Zn-12: yield 85-95%. Zn-12a: as described in
ref 12g. Zn-12c: 1H NMR (pyridine-d5, 70 °C) δ 8.80-8.60 (br,
1
as a light-yellow oil. 14: yield 5.4 g, 77%; H NMR (CDCl3) δ
10.13 (s, 1H), 8.88 (d, 1H, J ) 1.5 Hz), 8.67 (d, 2H, J ) 1.5
Hz), 4.39 (t, 4H, J ) 7 Hz), 1.79 (m, 4H), 1.49 (m, 4H), 0.99 (t,
6H, J ) 8 Hz); 13C NMR (CDCl3) δ 190.6, 164.9, 136.9, 135.8,
134.2, 132.3, 65.8, 30.8, 19.3, 13.8; HR-MS 329.1370 (M+
Na), calcd 329.1365.
+
Acknowledgment. Support from the NIH (Grant
No. EB003663-01), Anteon, Inc. (Contract No. 02-5403-
21-2), the Russian Foundation for Basic Research
(Grant No. RFBR 04-03-32650-a), and a grant from the
Russian Academy of Sciences to A.V.C. is gratefully
acknowledged. We thank Ms. Natalie Kim for proof-
reading the manuscript.
Supporting Information Available: Details of X-ray
structure determination, NSD (Normal-Coordinate Structural
Decomposition), and copies of the NMR spectra of newly
synthesized porphyrins and metalloporphyrins. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO047741T
(50) Vinogradov, S. A.; Wilson, D. F. Tetrahedron Lett. 1998, 39,
8935.
4628 J. Org. Chem., Vol. 70, No. 12, 2005