Porphyrins with exocyclic rings. Part 20: Synthesis and spectroscopic characterization of porphyrins with fused 2,1,3-benzoxadiazole and 2,1,3-benzoselenadiazole moieties

Article abstract of DOI:10.1016/j.tet.2005.09.090

Porphyrins with fused 2,1,3-benzoxadiazole and 2,1,3-benzoselenadiazole units were prepared by the '3+1' MacDonald-type methodology. 4-Nitro-2,1,3-benzoxadiazole, 6-chloro-4-nitro-2,1,3-benzoxadiazole and 4-nitro-2,1,3-benzoselenadiazole condensed with isocyanoacetates in the presence of the non-nucleophilic base DBU to give tricyclic pyrrole derivatives in excellent yields. Further cleavage of the ester moieties and decarboxylation afforded α-unsubstituted pyrroles and these were further condensed with 2 equiv of an acetoxymethylpyrrole tert-butyl ester to give crude preparations of tripyrranes. The tert-butyl ester protective groups were cleaved with TFA and following dilution with dichloromethane, '3+1' condensation with a pyrrole dialdehyde, and oxidation with ferric chloride, the heterocyclic ring fused porphyrins were obtained in moderate yields. The yields were lower than expected because of difficulties in preparing required tripyrranes due to the reduced reactivity of the pyrrolic intermediates. The UV-vis spectra of these new porphyrin systems were highly modified showing broadened split Soret bands. In addition, the nickel(II), copper(II) and zinc complexes gave unusual UV-vis spectra with weakened split Soret bands and strong Q-type absorptions above 600 nm. These modified structures show some potential for applications as photosensitizers in photodynamic therapy.

Full text of DOI:10.1016/j.tet.2005.09.090

Tetrahedron 61 (2005) 11615–11627
Porphyrins with exocyclic rings. Part 20: Synthesis and
spectroscopic characterization of porphyrins with fused
2,1,3-benzoxadiazole and 2,1,3-benzoselenadiazole moieties*
*
Catherine M. Cillo and Timothy D. Lash
Department of Chemistry, Illinois State University, Normal, IL 61790-4160, USA
Received 6 July 2005; revised 19 September 2005; accepted 21 September 2005
Available online 26 October 2005
Abstract—Porphyrins with fused 2,1,3-benzoxadiazole and 2,1,3-benzoselenadiazole units were prepared by the ‘3C1’ MacDonald-type
methodology. 4-Nitro-2,1,3-benzoxadiazole, 6-chloro-4-nitro-2,1,3-benzoxadiazole and 4-nitro-2,1,3-benzoselenadiazole condensed with
isocyanoacetates in the presence of the non-nucleophilic base DBU to give tricyclic pyrrole derivatives in excellent yields. Further cleavage of
the ester moieties and decarboxylation afforded a-unsubstituted pyrroles and these were further condensed with 2 equiv of an acetoxymethylpyrrole
tert-butyl ester to give crude preparations of tripyrranes. The tert-butyl ester protective groups were cleaved with TFA and following dilution with
dichloromethane, ‘3C1’ condensation with a pyrrole dialdehyde, and oxidation with ferric chloride, the heterocyclic ring fused porphyrins were
obtained in moderate yields. The yields were lower than expected because of difficulties in preparing required tripyrranes due to the reduced reactivity
of the pyrrolic intermediates. The UV–vis spectra of these new porphyrin systems were highly modified showing broadened split Soret bands. In
addition, the nickel(II), copper(II) and zinc complexes gave unusual UV–vis spectra with weakened split Soret bands and strong Q-type absorptions
above 600 nm. These modified structures show some potential for applications as photosensitizers in photodynamic therapy.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
for singlet oxygen production.4 Unfortunately, porphyrins
usually only have weak absorptions above 600 nm, and for this
reason modified chromophores are attracting considerable
interest.1,2 However, fusion of many benzenoid aromatic ring
systems to the porphyrin nucleus produces only minor shifts to
the UV–vis absorption spectra. Naphthoporphyrins 1a6,7 and
the related quino- and isoquinoporphyrins 1b and 1c8 produce
shifts of less than 10 nm to the Soret and Q bands, and even
phenanthro-(2a)9 and phenanthrolinoporphyrins (2b)10 give
similar spectroscopic shifts (Chart 1).11 However, acenaphtho-
porphyrins 3 have highly modified spectra with three Soret
absorptions and a relatively strong Q band at 660 nm.12–14 Di-
and tetraacenaphthoporphyrins give even larger shifts, in some
cases showing Soret bands above 600 nm.13,14 Thiadiazolo-
benzoporphyrins 4a also show intriguing UV–vis spectra with
broadened split Soret bands and a highly modified Q band
region.13,15 The related nickel(II), copper(II) and zinc
complexes also show two Soret bands that are atypically
weakened, together with an intense Q-type band near
600 nm.13 Although the absorptions fall short of the desired
wavelength range from 650 to 800 nm, the relatively polar
nature of these porphyrins and the presence of strong
absorption bands at higher wavelengths makes the study of
related chromophores a desirable goal. For this reason we
targeted the synthesis of related porphyrins 4b–d with fused
2,1,3-benzoxadiazole (benzofurazan) and 2,1,3-benzoselena-
diazole units.16
Porphyrins with extended chromophores1,2 have been inves-
tigated for applications that range from material science3 to
medicine.4 Much of this work has concentrated on tetra-
benzoporphyrins,5 but other types of ring fused porphyrin
systems have the potential to produce more diverse physical
and spectroscopic properties.1,2 In some cases, porphyrins with
fused aromatic units show strongly red shifted absorptions,1,2
a
property that could result in the development of superior
photosensitizers for photodynamic therapy (PDT).4 In PDT,
the porphyrin ‘drug’ is excited by visible light and transfers
energy to generate singlet oxygen. As porphyrins commonly
show an affinity for tumor cells over normal tissues, the highly
toxic effects of singlet oxygen are localized to the malignant
tissues. Bodily tissues strongly absorb light through most of the
visible region, but red light in the region of 650–800 nm gives
much better penetration while providing the necessary energy
* For part 19 in the series, see: Lash, T. D.; Lin, Y.; Novak, B. H.; Parikh,
M. D. Tetrahedron 2005, 61, 11601–11614.
Keywords: Pyrroles; 2,1,3-Benzoxadiazoles; 2,1,3-Benzoselenadiazoles;
‘3C1’ Methodology; Modified porphyrin chromophores.
Corresponding author. Tel.: C1 309 438 8554; fax: C1 309 438 5538;
e-mail: tdlash@ilstu.edu
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.090

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C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
Chart 1. Porphyrins with fused aromatic subunits.
Figure 1. (a) Partial 400 MHz proton NMR spectrum of pyrrole ester 8b in
d6-DMSO; (b) 400 MHz Proton NMR spectrum of oxadiazolobenzopyrrole
5b in d6-DMSO.
2. Results and discussion
The synthesis of porphyrins with fused heterocyclic rings
required the availability of pyrrolic tricycles 5 (Scheme 1).
Nitroaromatic compounds with a degree of nitroalkene
character can react with isocyanoacetates in the presence of
a non-nucleophilic base such as DBU to give c-annelated
pyrroles.8–20 This chemistry is in fact a variation on the
Barton–Zard pyrrole condensation which was first reported
in 1985,21 and can be applied to the synthesis of diverse
fused pyrrole and porphyrin products.8–17 In previous work,
4-nitro-2,1,3-benzothiadiazole (6a) was reacted with ethyl
isocyanoacetate (7a) in refluxing THF but only poor yields
(15%) of the required pyrrole ethyl ester 8a was
Scheme 1.
Scheme 2.

C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
11617
Scheme 5.
benzofurazan with concentrated nitric and sulfuric acids at
30 8C gave the nitro-derivative 6b in 90% yield, and this
similarly reacted with 7a and 7b in the presence of DBU in
refluxing THF to give the pyrrole esters 8b and 9b in 65%
Scheme 3.
obtained.13,15 However, under highly diluted conditions,
where 400 mL of THF solvent was used for every 1 g of
nitro compound, a 48% yield of the required tricycle 8a was
obtained, and the related tert-butyl ester 9a was similarly
prepared from 6a and 7b in 47% yield.13,15 It was unclear
why the dilute conditions were beneficial as better results
were usually obtained at higher concentrations for other
nitro compounds, but the low solubility of these hetero-
cycles may be a factor.13 The same approach was used to
prepare the new heterocycles 8b–d and 9b–d. In all cases,
dilute conditions gave superior results. 4-Nitrobenzofurazan
6b (NBD) is not commercially available, and initial
investigations were conducted using the available
7-chloro-derivative NBD chloride (6c). Reaction of 6c
with 7a or 7b gave the ethyl or tert-butyl esters 8c and 9c,
respectively, in 65–72% yield. The very low solubilities of
these products in organic solvents made purification by
chromatography impractical, but impurities could be
removed by heating the crude products with methanol and
this gave the desired pyrroles in pure form. Nitration of
Figure 2. 400 MHz proton NMR spectrum of oxadiazolobenzoporphyrin
4c in TFA–CDCl3.
Scheme 4.

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C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
Figure 3. UV–vis spectra for oxadiazolobenzoporphyrin 4b. (a) Free base in chloroform; (b) Protonated species in 1% TFA–chloroform.
yield. 4-Nitro-2,1,3-benzoselenadiazole (6d) similarly
reacted with DBU and isocyanoacetates 7 in refluxing
DBU to give the related pyrrole esters 8d and 9d in 86–89%
yield. All of these pyrrole esters had very poor solubility
characteristics, but NMR spectra could be obtained in d6-
DMSO. For instance, the proton NMR spectrum of
oxadiazolobenzopyrrole 8b (Fig. 1(a)) confirms the struc-
ture of this heterocycle showing the presence of two
doublets at 7.5 and 8.0 ppm for the central benzo-unit and a
singlet at 8.1 ppm for the pyrrolic CH. The NH is evident as
a broad resonance at 13.4 ppm.
However, when the selenium heterocycle 8d was treated
with KOH under these conditions, complete decomposition
occurred regardless of reaction time (5–30 min) or whether
or not hydrazine was present. Following numerous attempts
to modify these conditions, the best results were obtained in
a two-step procedure. Ethyl ester 8d was saponified under
mild conditions to give the corresponding carboxylic acid.
This underwent decarboxylation in ethylene glycol in the
absence of any base at 180 8C to give the required
a-unsubstituted pyrrole in 85% yield. However, attempts
to convert tert-butyl esters 9 to a-unsubstituted pyrroles by
treatment with TFA were unsuccessful. The NMR spectra
for pyrroles 5 were again generally obtained in d6-DMSO
(e.g., Fig. 1(b)).
Our intent was to prepare the targeted porphyrin systems by
MacDonald-type ‘3C1’ condensations using tripyr-
ranes,22,23 and the unsubstituted pyrroles 5 were required
as precursors to these intermediates. Thiadiazolobenzopyr-
role ethyl ester 8a underwent saponification and decarbox-
ylation with KOH in ethylene glycol under nitrogen at
180 8C for 30 min to give excellent yields of 5a. When the
oxygen analogues 8b and 8c were reacted under these
conditions, very poor yields of the decarboxylation products
were obtained. However, when a small amount of hydrazine
was added to the reaction mixture, the required tricycles 5b
and 5c were isolated in 50–76% yield. The hydrazine
presumably protects the reactants from oxidative degra-
dation due to the presence of trace amounts of oxygen.
The electron impact mass spectra for the new heterocycles
were also investigated. For pyrrole esters with fused
phenanthrene, phenanthroline, quinoline, isoquinoline,
fluoranthene or acenaphthylene rings,8–11,13 the primary
fragmentation pathway was loss of ROH to give species of
type 11 (Scheme 2), although loss of an alkene fragment
was more prominent for the tert-butyl esters resulting in
carboxylic acid radical cations like 12. Similar results were
obtained for thiadiazolopyrrole ester 8a and 9a. The ethyl
ester gave primarily loss of ethanol to give 11 and loss of
alkene was a minor pathway, while both fragmentations

C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
11619
Figure 4. UV–vis spectra for chloro-oxadiazolobenzoporphyrin 4c. (a) Free base in chloroform. (b) Protonated species in 1% TFA–chloroform.
were about equally favored for the tert-butyl ester 9a.13
Apart from the presence of multiple isotope peaks for
selenium, esters 8d and 9d gave similar results. However,
the oxadiazolopyrrole ethyl ester 8b gave loss of EtOH to 11
as a minor fragmentation pathway, and the strongest
fragment ion 13 corresponds to loss of ethylene and CO2.
The tert-butyl ester 9b also gave strong fragment ions for 12
and 13, although it slightly bucks the trend by showing a
small increase in the loss of ROH to give 11. The same types
of fragmentation were observed for the chloro-derivatives
8b and 8c, although the spectra were not of as high a quality.
The unsubstituted tricycle 5a shows loss of HCN as the
main fragmentation pathway.13 As expected, the two
oxadiazolobenzopyrroles 5b and 5c primarily gave loss of
NO. Unfortunately, selenadiazolobenzopyrrole 5d did not
analyze well by EI MS and its behavior in mass
spectrometry could not be determined.
bond forming steps were well removed from the fused
heterocycle during macrocycle formation, thereby necessi-
tating the use of tripyrrane intermediates.10 In the earlier
synthesis of thiadiazolobenzoporphyrin 4a, tricycle 5a was
reacted with 2 equiv of an acetoxymethylpyrrole 14a in
refluxing acetic acid–ethanol23,24 to give a crude preparation
of tripyrrane 15a (Scheme 3).13,15 This intermediate was
taken on without purification and treated with TFA to cleave
the tert-butyl ester groups. In a one pot sequence, the
mixture was diluted with dichloromethane, condensed with
pyrrole dialdehyde 16, and following neutralization with
triethylamine the intermediary species were oxidized
with DDQ to give 4a in up to 40% yield. The same
approach was used to prepare 4b–d. Unfortunately, reaction
of the oxadiazole derivatives 5b or 5c with 14a in refluxing
acetic acid–ethanol afforded virtually no tripyrrane product,
and replacement of the alcohol solvent with 2-propanol gave
no improvement to the yields. Weak acid is used to catalyze
this chemistry but we recognized that protonation of the
heterocycle would further decrease the reactivity of the
pyrrole subunit (Scheme 4). The oxygen-containing
heterocycles appear to have decreased reactivity compared
to 5a, and the major products in the reactions using 5b and
5c were ether derivatives of 14a formed by solvolysis.
Attempts to use other acid catalysts such as p-toluenesul-
fonic acid or Montmorillonite clay gave rise to no tripyrrane
formation. The possibility of avoiding the use of an acid
Now that the heterocyclic building blocks 5 were available,
the synthesis of the heterocyclic ring fused porphyrins could
be investigated. The electron-withdrawing diazole units
decrease the reactivity of the fused pyrrole moieties towards
electrophilic substitution and this can lead to difficulties.
This problem was previously encountered in the synthesis of
phenanthrolinoporphyrins 2b (Chart 1) where the fused
pyridine rings exert a similar disruptive influence.10 The
best results for 2b were obtained when the carbon–carbon

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C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
Figure 5. UV–vis spectra for selenadiazolobenzoporphyrin 4d. (a) Free base in chloroform; (b) Protonated species in 1% TFA–chloroform.
catalyst was also considered using pyridine as a solvent.
The chloromethylpyrrole 14b was reacted with 5b or 5c in
refluxing pyridine. In principle, pyridine would initially
generate a pyridinium salt25 that could readily eliminate and
further react with the pyrrole nucleus. However, only trace
amounts of tripyrrane could be detected under these
conditions as well. The best results for tripyrrane 15b
involved reacting 5b with acetoxymethylpyrrole 14a in
refluxing acetic acid-toluene. However, the product was
heavily contaminated with impurities and as these
tripyrrolic compounds tend to decompose during chroma-
tography this material was taken on through the ‘3C1’
methodology (Scheme 3) in crude form and reacted with
TFA and dialdehyde 16. Subsequent oxidation with DDQ
gave poor yields of the porphyrin product, but much better
results were obtained using an aqueous ferric chloride
solution for the oxidation step,26,27 and following chroma-
tography and recrystallization from chloroform–methanol
the oxadiazolobenzoporphyrin 4b was isolated as a green
powder in 31% yield. The chloro-substituted tricycle 5c
gave the best results when reacted with 14a in refluxing
acetic acid-xylenes. The chloro-group may further decrease
the reactivity of 5c making the use of higher temperatures
beneficial. Even so, the tripyrrane intermediate was
obtained in very crude form. Following deprotection of
the terminal ester groups with TFA, condensation with 16
and oxidation with DDQ, porphyrin 4c was obtained as a
very dark green powder in 17% yield. The selenium
heterocycle 4d was also unreactive toward tripyrrane
formation, but the best solvent in this case was ethyl
acetate. The poor solubility of 5d may also exacerbate the
problems due to diminished reactivity, and even under the
best conditions when 5d was sonicated for 20–30 min with
ethyl acetate prior to the addition of acetic acid to maximize
solubilization, the tripyrrane was generated in very crude
form. This crude material was taken on through the ‘3C1’
route as before, and selenadiazolobenzoporphyrin 4d was
isolated in 9% yield.
During the course of these studies, the use of dipyrrylmethane
intermediates was briefly considered. The tert-butyl esters 9
were condensed with acetoxymethylpyrroles in the presence
of p-toluenesulfonic acidin aceticacid togive moderate yields
of dipyrrylmethanes 17 (Scheme 5). The di-tert-butyl esters
were treated with TFA to cleave the protective groups and
condensed with dipyrrylmethane dialdehyde 18 under
MacDonald ‘2C2’ reaction conditions28–30 but no more
than trace amounts of the desired porphyrin products 19 were
observed. Again, the chemistry appears to be blocked by the
reduced reactivity of the ring fused pyrrole unit.
The free base porphyrins 4b–d were only sparingly soluble
in organic solvents, but high quality NMR spectra were
easily obtained for the protonated forms in TFA–CDCl3.

C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
11621
Figure 6. UV–vis spectra for metal complexes of porphyrin 4b in
chloroform. (a) Ni(II) complex 20b; (b) Cu(II) complex 21b; (c) Zn
complex 22b.
Figure 7. UV–vis spectra for metal complexes of porphyrin 4c in
chloroform. (a) Ni(II) complex 20c; (b) Cu(II) complex 21c; (c) Zn
complex 22c.
The proton NMR spectra showed typical diatropic ring
currents for the porphyrin macrocycles. For instance, 4c
gives four singlets for the meso-protons downfield near
11 ppm, while the internal NHs resonate upfield near
K3 ppm (Fig. 2).
new porphyrins 4b, 4c and 4d are comparatively red shifted
and appear at 591, 595 and 600 nm, respectively. All four
porphyrins also show split Soret bands, with lmax values of
380 and 438 nm for 4a, 374 and 434 nm for 4b, 375 and
436 nm for 4c, and 383 and 451 nm for 4d. For both the
Soret and Q absorptions, the largest shifts are seen for the
selenium system 4d, but the Soret bands are slightly blue
shifted for the oxygen systems 4b and 4c. The presence of a
chloro-substituent in 4c induces small bathochromic shifts
compared to 4b. In TFA–chloroform, the protonated forms
for the oxadiazolobenzoporphyrins 4b and 4c gave a single
Soret band, while the sulfur and selenium containing
The UV–vis spectra for the free base porphyrins 4b–d (Figs.
3–5) were very different from typical porphyrin spectra,
although they were similar to the results previously obtained
for 4a. Porphyrins usually give four Q bands but the longest
wavelength band Q I appears to be very weak or absent in
the spectra for 4a–d and the shortest wavelength band (Q
IV) is relatively weak. Two major Q bands, tentatively
assigned as Q II and Q III, can be seen which are merging in
to one another. The longer wavelength band Q II for 4a
shows up at 588 nm for 4a, but the equivalent bands in the

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C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
showed the largest effects with the longest wavelength band
red shifted compared to the ‘b series’ by 11–14 nm. As is the
case for most porphyrins,31 the absorption bands for all four
series are red shifted going across the period table from
nickel(II) porphyrins 20 to copper(II) porphyrins 21 to zinc
porphyrins 22. Focusing on the zinc complexes 22, the Soret
absorptions were observed at 390 and 442 nm for 22a, 383
and 441 nm for 22b, 385 and 445 nm for 22c and 393 and
458 nm for 22d. The longer wavelength Q band was
observed for this series at 612, 615, 625 and 627 nm,
respectively, for 22a–d. These unusually strong longer
wavelength bands are approaching values that could be
useful for PDT applications, and it is worth noting that the
free base porphyrins 4a–d have all been shown to be
photosensitizers for singlet oxygen generation.32
3. Conclusions
Novel c-annelated pyrroles fused to 2,1,3-benzoxadiazole
or 2,1,3-benzoselenadiazole have been synthesized in
excellent yields by the Barton–Zard methodology. These
pyrroles were taken on to tripyrrane intermediates that
were used in crude form to give moderate yields of
porphyrins with fused heterocyclic subunits. Oxa- and
selenadiazolobenzoporphyrins and their metallo-deriva-
tives have very unusual spectroscopic properties, and
these studies may lead to the development of new
photosensitizers for applications in PDT. The main
limitation in the present study is the diminished
reactivity of the ring fused pyrroles that inhibits
tripyrrane formation. Further studies are in progress to
both improve the yields of porphyrin products and
further increase the bathochromic shifts to the intense Q
bands for the nickel(II), copper(II) and zinc chelates by
extending the fused heterocycles.33
4. Experimental
4.1. General
4-Nitro-2,1,3-benzoselenadiazole (6d), NBD chloride (6c),
TFA, and DBU were purchased from Aldrich or Acros, and
were used without further purification. THF was distilled
from calcium hydride immediately prior to use. Chroma-
tography was performed using Grade III neutral alumina or
70–230 mesh silica gel. Melting points were determined in
open capillary tubes on a Mel-Temp apparatus and are
uncorrected. Due to the small quantities of porphyrin
samples available, high resolution MS data were used in
place of CHN analyses, and purity was established by NMR
spectroscopy and TLC. UV–vis absorption spectra were run
on a Varian Cary Spectrophotometer, and NMR data was
obtained on a Varian Gemini 400 MHz FT NMR
spectrometer. Mass spectral determinations were conducted
at the Mass Spectral Laboratory, School of Chemical
Sciences, University of Illinois at Urbana-Champaign, and
elemental analyses were obtained from the School of
Chemical Sciences Microanalysis Laboratory at the Uni-
versity of Illinois.
Figure 8. UV–vis spectra for metal complexes of porphyrin 4d in
chloroform. (a) Ni(II) complex 20d; (b) Cu(II) complex 21d; (c) Zn
complex 22d.
porphyrins 4a and 4d showed split Soret band regions (Figs.
3–5).
Reaction of porphyrins 4b–d with copper(II), nickel(II) or
zinc acetate in DMF or refluxing chloroform–methanol
afforded the corresponding metalloporphyrins 20–22
(Scheme 3). These all showed very weak Soret bands and
an intense Q band absorption above 600 nm (Figs. 6–8). The
shifts for metallo-derivatives derived from 4a and 4b were
similar, where the longest wavelength band for the ‘b series’
is red shifted by only 1–3 nm. The chloro-derivatives (or ‘c
series’) showed larger bathochromic shifts with the major Q
band having from 8 to 10 nm longer wavelengths than the ‘b
series’. The selenium chelates, or ‘d series’, consistently

C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
11623
4.2. Synthetic procedures
(1.12 g, 83%) as a brown powder, mp 262 8C, dec. An
analytical sample was obtained by sublimation at 0.05 torr
1
and 175 8C as pale yellow crystals, mp 290 8C. H NMR
4.2.1. Ethyl oxadiazolobenzo[4,5-c]pyrrole-1-car-
boxylate (8b). Benzofurazan34 (1.00 g) was taken up in
4.0 mL of concentrated sulfuric acid and the solution cooled
in an ice bath. Concentrated nitric acid (1.5 mL) was added
dropwise, maintaining the temperature !30 8C, and the
resulting mixture stirred at room temperature for a further
20 min. Water was added dropwise, and the resulting
precipitate suction filtered to give 4-nitrobenzofurazan (6b;
1.25 g; 90%) as a pale yellow powder, mp 84–85 8C (lit.
(400 MHz, d6-DMSO): d 1.36 (3H, t, JZ7 Hz), 4.36 (2H, q,
JZ7 Hz), 8.01 (1H, s), 8.13 (1H, s), 13.44 (1H, br s); 13C
NMR (d6-DMSO): d 14.9, 61.4, 106.8, 116.5, 118.1, 122.0,
124.7, 127.8, 145.3, 148.7, 160.4; EI MS (70 eV): m/z (rel.
int.) 267 (23), 265 (60, MC), 237 (3.4, [MCKC2H4]), 230
(7, [MCKCl]), 222 (5), 221 (6), 220 (8), 219 (18, [MCK
EtOH]), 205 (39), 203 (84), 195 (16), 194 (8), 193 (47,
[MCKC2H4–CO2]); HRMS (EI): Calcd for C11H8ClN3O3:
265.0255. Found:265.0254. Anal. CalcdforC11H8ClN3O3:C,
49.73; H, 3.03; N, 15.82. Found: C, 49.51; H, 2.79; N, 15.77.
1
mp35 93 8C); H NMR (400 MHz, CDCl3): d 7.68 (1H, dd,
JZ7.6, 8.8 Hz), 8.32 (1H, d, JZ8.8 Hz), 8.52 (1H, d, JZ
7.6 Hz); 13C NMR (d6-DMSO): d 124.7, 129.9, 130.1,
137.4, 142.8, 150.6. Ethyl isocyanoacetate36 (0.63 g) and
DBU (0.84 g) were dissolved in freshly distilled THF
(300 mL) in a 1000 mL round bottom flask, a solution of 6b
(1.00 g) in THF (200 mL) was added, and the resulting dark
mixture was allowed to stir under reflux overnight. The
solution was diluted with dichloromethane, washed with
water, dried over sodium sulfate, and the solvents
evaporated under reduced pressure. Recrystallization from
methanol gave 8b (0.80 g, 57%) as a pale brown solid, mp
261 8C. An analytical sample was obtained by sublimation
at 0.05 torr and 210 8C as pale yellow crystals, mp 263 8C.
1H NMR (400 MHz, d6-DMSO): d 1.36 (3H, t, JZ7 Hz),
4.36 (2H, q, JZ7 Hz), 7.51 (1H, d, JZ9.6 Hz), 8.05 (1H, d,
JZ10 Hz), 8.14 (1H, s), 13.36 (1H, br s); 1H NMR
(400 MHz, CDCl3, downfield region only): d 7.43 (1H, d,
JZ9.6 Hz), 7.87 (1H, d, JZ3.6 Hz), 8.07 (1H, d, JZ
9.6 Hz), 10.0 (1H, br s); 13C NMR (d6-DMSO): d 15.0, 61.1,
108.0, 112.1, 118.1, 121.5, 125.1, 129.2, 145.3, 149.4,
160.8; EI MS (70 eV): m/z (rel. int.) 232 (14), 231 (100,
MC), 203 (5, [MCKC2H4]), 186 (13), 185 (17, [MCK
EtOH]), 159 (77, [MCKC2H4–CO2]), 158 (13), 157 (22),
156 (3), 155 (15); HRMS (EI): Calcd for C11H9N3O3:
231.0641. Found: 231.0644. Anal. Calcd for C11H9N3O3: C,
57.14; H, 3.92; N, 18.17. Found: C, 57.01; H, 3.79; N, 17.76.
4.2.4. tert-Butyl 7-chloro-oxadiazolobenzo[4,5-c]pyrrole-
1-carboxylate (9c). tert-Butyl isocyanoacetate (0.71 g) and
DBU (0.92 g) in THF (300 mL) were reacted with 6b
(1.00 g) in THF (200 mL) under the conditions described
above. Recrystallization from methanol gave the title
pyrrole (1.18 g, 80%) as a pale brown powder, mp 292 8C,
dec. An analytical sample was obtained by sublimation at
0.05 torr and 210 8C as pale yellow crystals, mp 294 8C. 1H
NMR (400 MHz, CDCl3): d 1.68 (9H, s), 7.83 (1H, s), 8.05
(1H, s), 10.03 (1H, br s); 13C NMR (d6-DMSO): d 28.6,
82.5, 106.6, 116.2, 119.3, 121.5, 124.1, 127.9, 145.3, 148.7,
159.8; EI MS (70 eV): m/z (rel. int.) 295 (6), 293 (18, MC),
239 (34), 238 (11), 237 (100, [MCKC4H8]), 221 (17), 220
(18), 219 (50, [MCKt-BuOH]), 203 (13), 202 (19), 195 (2),
193 (7.6, [MCKC4H8–CO2]), 192 (4), 191 (6.8); HRMS
(EI): Calcd for C13H12ClN3O3: 293.0575. Found: 293.0567.
Anal. Calcd for C13H12ClN3O3$1⁄8 H2O: C, 52.76; H, 4.17;
N, 14.20. Found: C, 52.58; H, 3.88; N, 14.19.
4.2.5. Ethyl selenadiazolobenzo[4,5-c]pyrrole-1-car-
boxylate (8d). Ethyl isocyanoacetate (0.63 g) and DBU
(0.84 g) in THF (300 mL) were reacted with 6d (1.00 g) in
THF (200 mL) under the conditions described above.
Recrystallization from methanol gave the title pyrrole
(1.12 g, 85%) as a brown powder, mp 230 8C. An analytical
sample was obtained by sublimation at 0.05 torr and 210 8C
as pale orange crystals, mp 236 8C. 1H NMR (400 MHz, d6-
DMSO): d 1.36 (3H, t, JZ7 Hz), 4.36 (2H, q, JZ7 Hz),
7.40 (1H, d, JZ9.6 Hz), 7.98 (1H, s), 7.99 (1H, d, JZ
9.6 Hz), 13.12 (1H, br s); 13C NMR (d6-DMSO): d 15.1,
60.9, 116.0, 118.8, 120.8, 122.0, 125.6, 125.9, 155.8, 160.1,
161.2; EI MS (70 eV): m/z (rel. int.) 297 (18), 296 (13), 295
(100, MC), 294 (8), 293 (50), 292 (18), 291 (17), 267 (5.0,
[MCKC2H4]), 265 (2.7), 259 (97.4), 252 (4.7), 251 (17),
250 (19), 249 (86, [MCKEtOH]), 248 (17), 247 (44), 246
(16), 245 (15), 237 (20), 225 (2.2), 224 (2.7), 223 (8.0,
[MCKC2H4–CO2]), 222 (8.1), 221 (15), 203 (41); HRMS
(EI): Calcd for C11H9N3O2Se: 294.9866. Found: 294.9860.
Anal. Calcd for C11H9N3O2Se$1⁄5 H2O: C, 44.37; H, 3.18; N,
14.11. Found: C, 44.19; H, 2.98; N, 14.04.
4.2.2. tert-Butyl oxadiazolobenzo[4,5-c]pyrrole-1-car-
boxylate (9b). tert-Butyl isocyanoacetate9c (0.86 g) and
DBU (0.92 g) in THF (300 mL) were reacted with 6b
(1.00 g) in THF (200 mL) under the conditions described
above. Recrystallization from methanol gave the title
pyrrole (1.12 g, 71%) as a pale brown powder, mp 260 8C,
dec. An analytical sample was obtained by sublimation at
0.05 torr and 210 8C as pale yellow crystals, mp 268–
269 8C, dec. 1H NMR (400 MHz, d6-DMSO): d 1.59 (9H, s),
7.49 (1H, d, JZ9.2 Hz), 8.00 (1H, d, JZ8.8 Hz), 8.10 (1H,
s), 13.18 (1H, br s); 13C NMR (d6-DMSO): d 28.7, 82.3,
107.8, 111.9, 119.4, 121.0, 124.5, 129.3, 145.3, 149.4,
160.2; EI MS (70 eV): m/z (rel. int.) 259 (11, MC), 203 (60,
[MCKC4H8]), 186 (13), 185 (24, [MCKt-BuOH]), 160
(10), 159 (100, [MCKC4H8–CO2]), 158 (13), 157 (22), 156
(3), 155 (15); HRMS (EI): Calcd for C13H13N3O3: 259.0964.
Found: 259.0957. Anal. Calcd for C13H13N3O3: C, 60.22; H,
5.05; N, 16.21. Found: C, 59.97; H, 4.86; N, 16.20.
4.2.6. tert-Butyl selenadiazolobenzo[4,5-c]pyrrole-1-car-
boxylate (9d). tert-Butyl isocyanoacetate (0.64 g) and DBU
(0.87 g) in THF (300 mL) were reacted with 6d (1.00 g) in
THF (200 mL) under the conditions described above.
Recrystallization from methanol gave the title pyrrole
(1.30 g, 92%) as a pale brown powder, mp 210 8C. An
analytical sample was obtained by sublimation at 0.05 torr
4.2.3. Ethyl 7-chloro-oxadiazolobenzo[4,5-c]pyrrole-1-
carboxylate (8c). Ethyl isocyanoacetate (0.56 g) and DBU
(0.76 g) in THF (300 mL) were reacted with 6c (1.00 g) in
THF (200 mL) under the conditions described above.
Recrystallization from methanol gave the title pyrrole
1
and 210 8C as pale orange crystals, mp 212 8C. H NMR

11624
C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
(400 MHz, d6-DMSO): d 1.60 (9H, s), 7.38 (1H, d, JZ
9.6 Hz), 7.95 (1H, s), 7.99 (1H, d, JZ9.6 Hz), 12.94 (1H, br
s); 13C NMR (d6-DMSO): d 28.8, 81.7, 117.2, 118.7, 120.3,
121.8, 125.0, 126.1, 155.9, 160.1 160.7; EI MS (70 eV): m/z
(rel. int.) 325 (5.7), 324 (4.0), 323 (100, MC), 322 (2.1), 321
(13), 320 (4.8), 319 (5.0), 270 (2.4), 269 (20), 268 (11), 267
(100, [MCKC4H8]), 266 (62), 265 (48), 264 (17), 263 (18),
252 (4.6), 251 (17), 250 (19), 249 (86, [MCKt-BuOH]),
248 (9), 247 (45), 246 (17), 245 (17), 224 (2.3), 223 (7.9,
[MCKC4H8–CO2]), 222 (7.0), 221 (10), 220 (4.5), 219
(5.7), 218 (2.4); HRMS (EI): Calcd for C13H13N3O2Se:
323.0182. Found: 323.0172. Anal. Calcd for
C13H13N3O2Se: C, 48.46; H, 4.07; N, 13.04. Found: C,
48.05; H, 3.92; N, 12.82.
deep green precipitate suction filtered and washed well with
water. Following vacuum drying, the carboxylic acid
(0.473 g, 69%) was obtained as a green powder, mp 218–
1
219 8C; H NMR (400 MHz, d6-DMSO): d 7.36 (1H, d,
JZ9.6 Hz), 7.92 (1H, s), 8.03 (1H, d, JZ9.6 Hz), 13.0 (2H,
br); 13C NMR (d6-DMSO): d 116.9, 118.7, 120.2, 121.6,
125.5, 126.3, 155.9, 160.2, 162.6; HRMS (EI): Calcd for
C9H5N3O2Se: 264.9562. Found: 264.9554.
4.2.10. Selenadiazolobenzo[4,5-c]pyrrole (5d). Nitrogen
was bubbled through a mixture of the foregoing carboxylic
acid (1.00 g), and ethylene glycol (48 mL) for 10 min, and
the resulting mixture stirred under nitrogen at 180 8C for
30 min. The mixture was poured into ice water, and the
precipitate suction filtered and dried in vacuo to give the
a-unsubstituted pyrrole (0.51 g, 60%) as a brown powder.
An analytical sample was obtained by sublimation at
0.05 torr and 140 8C as pale orange crystals, mp 180 8C.
1H NMR (400 MHz, d6-DMSO): d 7.03 (1H, d, JZ9.6 Hz),
7.31 (1H, s), 7.55 (1H, d, JZ9.6 Hz), 7.75 (1H, s), 12.07
(1H, br s); 13C NMR (d6-DMSO): d 114.9, 116.2, 117.7,
117.8, 121.8, 127.6, 146.7, 150.3. Anal. Calcd for
C8H5N3Se$1⁄3 H2O: C, 42.12; H, 2.50; N, 18.42. Found: C,
42.28; H, 2.12; N, 18.04.
4.2.7. Oxadiazolobenzo[4,5-c]pyrrole (5b). Nitrogen was
bubbled through a mixture of ethyl ester 8b (1.00 g),
potassium hydroxide (2.35 g) and hydrazine (8 drops) in
ethylene glycol (48 mL) for 10 min, and the resulting
mixture stirred under nitrogen at 180 8C for 30 min. The
mixture was poured into ice water, and the precipitate
suction filtered and dried in vacuo to give the a-unsub-
stituted pyrrole (0.34–0.52 g, 50–76%) as a pale brown
powder, mp 178–179 8C. An analytical sample was obtained
by sublimation at 0.05 torr and 150 8C as pale yellow
crystals, mp 180 8C. 1H NMR (400 MHz, d6-DMSO): d 7.11
(1H, d, JZ9.6 Hz), 7.47 (1H, s), 7.64 (1H, d, JZ9.2 Hz),
7.88 (1H, s), 12.32 (1H, br s); 1H NMR (300 MHz, CDCl3):
d 7.15 (1H, d, JZ9.6 Hz), 7.26 (1H, s), 7.50 (1H, JZ
9.6 Hz), 7.74 (1H, s), 9.0 (1H, br s); 13C NMR (d6-DMSO):
d 106.0, 107.2, 116.9, 117.4, 121.5, 130.6, 146.0, 150.0; EI
MS (70 eV): m/z (rel. int.) 160 (11), 159 (100, MC), 130 (8),
129 (39, [MCKNO]), 128 (4.5); HRMS (EI): Calcd for
C8H5N3O: 159.0434. Found: 159.0433. Anal. Calcd for
C8H5N3O: C, 60.38; H, 3.17; N, 26.40. Found: C, 60.47; H,
3.00; N, 25.69.
4.2.11. tert-Butyl 5-chloromethyl-4-ethyl-3-methylpyr-
role-2-carboxylate (14b). N-Chlorosuccinimide (1.28 g)
was added to a solution of tert-butyl 4-ethyl-3,5-dimethyl-
pyrrole-2-carboxylate37 (2.00 g) in carbon tetrachloride
(200 mL) and the mixture stirred at room temperature
overnight. The solution was washed with water (3!
200 mL) and evaporated under reduced pressure. Recrys-
tallization of the residue from hexanes and subsequent
removal of trace solvent in vacuo afforded the title pyrrole
(1.60 g, 70%) as a pale brown powder, mp 96 8C, dec. Due
to the instability of this compound, it was stored in the
1
freezer. H NMR (CDCl3): d 1.10 (3H, t, JZ7.6 Hz), 1.57
4.2.8. 7-Chloro-oxadiazolobenzo[4,5-c]pyrrole (5c).
Ethyl ester 8c (1.00 g), potassium hydroxide (2.35 g) and
hydrazine (8 drops) in ethylene glycol (48 mL) was reacted
as described for the previous procedure to give 5c (0.38–
0.48 g, 50–65%) as a khaki green powder, mp 274 8C. An
analytical sample was obtained by sublimation at 0.05 torr
(9H, s), 2.24 (3H, s), 2.45 (2H, q, JZ7.6 Hz), 4.59 (2H, s),
8.66 (1H, br s); 13C (CDCl3): d 10.5, 15.7, 17.4, 28.7, 37.0,
81.1, 121.1, 125.7, 126.7, 138.9, 161.2.
4.2.12. tert-Butyl 3(5-benzyloxycarbonyl-3-ethyl-4-
methyl-2-pyrrolylmethyl)oxadiazolobenzo[4,5-c]pyrrole-
1-carboxylate (17). A solution of benzyl 5-acetoxymethyl-
4-ethyl-3-methylpyrrole-2-carboxylate38 (185 mg) in acetic
acid (15 mL) was added via a syringe pump over a 12 h
period to a stirred solution of 9b (150 mg) and p-toluene-
sulfonic acid (40 mg) in acetic acid under a nitrogen
atmosphere. The resulting mixture was stirred for a further
12 h, poured into 200 mL of ice water, and the resulting
precipitate suction filtered and dried in vacuo. The crude
product was chromatographed on grade III alumina eluting
with 5% ethyl acetate–toluene. Once the impurity fractions
had been collected, the eluting solvent system was gradually
increased in polarity to 10% ethyl acetate–toluene. A bright
pink fraction was collected and recrystallized from
methanol to afford the title dipyrrylmethane (140 mg,
48%) as pink crystals, mp 161–161.5 8C; 1H NMR
(400 MHz, d6-DMSO): d 0.65 (3H, t, JZ7.2 Hz), 1.59
(9H, s), 2.10 (3H, s), 2.40 (2H, q, JZ7.2 Hz), 4.37 (2H, s),
5.27 (2H, s), 7.37 (5H, m), 7.47 (1H, d, JZ9.6 Hz), 7.92
(1H, d, JZ9.6 Hz), 11.25 (1H, br s), 12.98 (1H, br s); 13C
NMR (d6-DMSO): d 10.9, 16.1, 17.1, 23.8, 28.7, 65.3, 82.3,
1
and 150 8C as pale yellow crystals, mp 270 8C. H NMR
(400 MHz, d6-DMSO): d 7.48 (1H, s), 7.83 (1H, s), 7.91
(1H, s), 12.51 (1H, br s); 13C NMR (d6-DMSO): d 104.9,
111.2, 117.6, 117.9, 121.2, 129.6, 145.9, 149.2; EI MS
(70 eV): m/z (rel. int.) 196 (3.5), 195 (35), 194 (11), 193
(100, MC), 165 (13), 164 (5.2), 163 (36, [MCKNO]), 162
(3.8); HRMS (EI): Calcd for C8H4ClN3O: 193.0043. Found:
193.0043. Anal. Calcd for C8H4ClN3O$1⁄2 H2O: C, 47.43; H,
2.48; N, 20.74. Found: C, 47.67; H, 2.08; N, 20.22.
4.2.9. Selenadiazolobenzo[4,5-c]pyrrole-1-carboxylic
acid (10). Ethyl ester 8d (0.80 g) was dissolved in DMSO
(20 mL) on a preheated oil bath at 100 8C under a nitrogen
atmosphere. A solution of sodium hydroxide (3.2 g) in water
(10 ml) was added, and the mixture allowed to reflux under
nitrogen for 2 h. The solution was diluted with water
(60 mL) and cooled to 0 8C with the aid of a salt-ice bath.
The solution was neutralized to litmus paper with acetic
acid, maintaining the temperature !5 8C, the resulting
mixture was stirred at room temperature for 20 min, and the

C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
11625
105.7, 112.1, 117.5, 118.5, 124.0, 124.5, 126.5, 128.4,
128.6, 129.1, 129.4, 129.9, 133.3, 137.5, 145.5, 149.6,
160.5, 161.4. Anal. Calcd for C29H30N4O5$H2O: C, 65.40;
H, 6.05; N, 10.52. Found: C, 65.26; H, 5.74; N, 10.71.
and the mixture stirred under reflux in the dark overnight.
The solution was cooled to room temperature, diluted with
chloroform, and washed with water (3!200 mL). The
organic layer was evaporated under reduced pressure and
the residue recrystallized from chloroform–methanol to give
the copper complex (6 mg, 57%) as a deep green powder,
mp O300 8C. UV–vis (1% Et3N–CHCl3): lmax (log103) 380
(4.75), 432 (4.98), 559 (3.93), 608 nm (4.63); HRMS
(FAB): Calcd for C34H32N6OCu: 603.1933. Found:
603.1932.
4.2.13. 8,12,13,17-Tetraethyl-7,18-dimethyloxadiazolo-
benzo[4,5-b]porphyrin (4b). Oxadiazolobenzopyrrole 5b
(100 mg) and acetoxymethylpyrrole 14a39 (352 mg) were
stirred under reflux with acetic acid (0.75 mL) and toluene
(8 mL) under nitrogen for 16 h. The solution was cooled,
diluted with dichloromethane, washed with water and
evaporated to dryness under reduced pressure to give the
crude tripyrrane 15b as a deep burgundy colored solid that
4.2.16. Zinc complex 22b. A saturated solution of zinc(II)
acetate in methanol (10 mL) was added to a solution of
porphyrin 4b (10 mg) in chloroform (10 mL), and the
mixture stirred under reflux in the dark overnight. The
solution was cooled to room temperature, diluted with
chloroform, and washed with water (3!200 mL). The
organic layer was evaporated under reduced pressure and
the residue recrystallized from chloroform–methanol to
give the zinc complex (9.5 mg, 87%) as a green powder,
mpO300 8C. UV–vis (1% Et3N–CHCl3): lmax (log103) 384
(4.71), 443 (4.84), 566 (3.86), 617 nm (4.48); HRMS
(FAB): Calcd for C34H32N6OZn: 604.1929. Found:
604.1929.
1
was used without further purification. H NMR (400 MHz,
d6-DMSO, downfield region only): d 4.13 (2H, s), 4.29 (2H,
s), 7.00 (1H, d, JZ9.6 Hz), 7.49 (1H, d, JZ9.6 Hz), 10.88
(1H, br s), 11.01 (1H, br s), 11.61 (1H, br s). Crude 15b
(100 mg) was dissolved in TFA (2.5 mL) and stirred for
5 min at room temperature under nitrogen. The mixture was
diluted with dichloromethane (40 mL), followed by the
immediate addition of dialdehyde 1623,40 (30 mg) and the
mixture stirred under nitrogen for an additional 2 h. The
dark solution was poured into a separatory funnel and
shaken for 5 min with 0.1% aqueous ferric chloride solution.
The organic layer was separated, the aqueous phase back
extracted with dichloromethane, and the combined organic
phases washed with water, 10% sodium bicarbonate
solution, and water. The solvent was evaporated under
reduced pressure and the residue chromatographed on grade
III alumina eluting with 30% dichloromethane–toluene. A
deep green colored fraction was collected, the solvent
evaporated, and the residue recrystallized from chloroform–
methanol to give porphyrin 4b (29 mg, 31%) as green
crystals, mpO300 8C; UV–vis (1% Et3N–CHCl3): lmax
(log103) 373 (4.83), 393 (4.58), 434 (5.12), 567 (4.42),
592 nm (4.33); UV–vis (1% TFA–CHCl3): lmax (log103)
426 (5.39), 567 (4.06), 591 (3.56), 618 nm (4.30); 1H NMR
(400 MHz, TFA–CDCl3): dK3.37 (4H, br), 1.73–1.88
(12H, m), 3.70 (3H, s), 3.72 (3H, s), 4.17–4.30 (8H, m),
8.74 (1H, d, JZ9.2 Hz), 9.54 (1H, d, JZ9.6 Hz), 10.71 (1H,
s), 10.73 (1H, s), 11.11 (1H, s), 11.62 (1H, s); 13C NMR
(TFA–CDCl3): d 11.9, 16.3, 16.4, 17.2, 20.1, 20.3, 20.5,
99.0, 99.4, 99.9, 101.0, 119.5, 121.3, 126.5, 134.9, 136.4,
137.1, 138.8, 138.9, 142.3, 143.1, 143.5, 144.1, 144.4,
144.8, 145.1, 145.6, 146.3, 150.6; HRMS (ESI): Calcd for
C34H34N6OCH: 543.2872. Found: 543.2859.
4.2.17. 32-Chloro-8,12,13,17-tetraethyl-7,18-dimethylox-
adiazolobenzo[4,5-b]porphyrin (4c). Pyrrole 5c (100 mg)
and acetoxymethylpyrrole 14a (288 mg) were stirred under
reflux with acetic acid (0.75 mL) and xylene (8 mL) under
nitrogen for 16 h. The solution was cooled, diluted with
dichloromethane, washed with water and evaporated to
dryness under reduced pressure to give the crude tripyrrane
15c as a reddish brown solid that was used without further
purification. 1H NMR (400 MHz, d6-DMSO, downfield
region only): d 4.16 (2H, s), 4.26 (2H, s), 7.77 (1H, s), 10.75
(1H, br s), 11.03 (1H, br s), 11.72 (1H, br s). Crude 15c
(100 mg) deprotected with TFA (2.5 mL) and reacted with
dialdehyde 16 (30 mg) under the conditions described for
4b. The crude product was chromatographed on grade III
alumina eluting with 30% dichloromethane–toluene and
recrystallized from chloroform–methanol to give porphyrin
4c (16 mg, 17%) as dark green crystals, mp O300 8C;
UV–vis (1% Et3N–CHCl3): lmax (log103) 374 (4.86), 436
(5.00), 570 (4.36), 596 nm (4.35); UV–vis (1%
TFA–CHCl3): lmax (log103) 427 (5.33), 568 (4.05),
620 nm (4.30); 1H NMR (400 MHz, TFA–CDCl3): dK
2.96 (4H, br), 1.72–1.86 (12H, m), 3.67 (3H, s), 3.68 (3H, s),
4.13–4.26 (8H, m), 9.50 (1H, s), 10.63 (1H, s), 10.65 (1H, s),
10.97 (1H, s), 11.49 (1H, s); 13C NMR (TFA–CDCl3): d
11.7, 16.2, 16.3, 17.2, 20.1, 20.3, 20.4, 99.1, 99.5, 100.1,
100.7, 119.5, 121.2, 125.6, 135.2, 135.9, 136.0, 136.2,
139.4, 139.4, 142.1, 142.2, 143.0, 143.1, 143.6, 144.2,
144.6, 145.3, 145.6, 150.2; HRMS (ESI): Calcd for
C34H33ClN6OCH: 577.2483. Found: 577.2506.
4.2.14. Nickel(II) complex 20b. Porphyrin 4b (12 mg) and
nickel(II) acetate tetrahydrate (42 mg) were stirred with
DMF (10 mL) in the dark under reflux overnight. The
solution was cooled to room temperature, diluted with
chloroform, and washed with water (3!200 mL). The
organic layer was evaporated under reduced pressure and
the residue recrystallized from chloroform–methanol to give
the nickel complex (7.5 mg, 63%) as green sheets, mp
O300 8C. UV–vis (1% Et3N–CHCl3): lmax (log103) 379
(4.66), 428 (4.82), 553 (3.92), 601 nm (4.52); HRMS
(FAB): Calcd for C34H32N6ONi: 598.1991. Found:
598.1992.
4.2.18. Nickel(II) complex 20c. Porphyrin 4c (10 mg) and
nickel(II) acetate tetrahydrate (40 mg) were reacted in DMF
(10 mL) under the conditions described for 20b. Recrys-
tallization from chloroform–methanol gave the nickel
complex (4.8 mg, 32%) as green sheets, mp O300 8C.
UV–vis (1% Et3N–HCl3):lmax (log103) 381 (4.40), 440 (4.39),
610 nm (4.23); HRMS (FAB): Calcd for C34H31ClN6ONi:
632.1601. Found: 632.1603.
4.2.15. Copper(II) complex 21b. A saturated solution of
copper(II) acetate in methanol (10 mL) was added to a
solution of porphyrin 4b (10 mg) in chloroform (10 mL),

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C. M. Cillo, T. D. Lash / Tetrahedron 61 (2005) 11615–11627
4.2.19. Copper(II) complex 21c. Porphyrin 4c (8 mg) and
copper(II) acetate monohydrate (48 mg) were reacted in
DMF (10 mL) under the conditions described for 20b.
Recrystallization from chloroform–methanol gave the
copper complex (6.2 mg, 77%) as a blue-green powder,
mpO300 8C. UV–vis (1% Et3N–CHCl3): lmax (log103) 325
(4.12), 382 (4.61), 442 (4.59), 618 nm (4.39); FD MS: m/z
(rel. int.) 642 (7), 641 (20), 640 (30), 639 (89), 638 (42), 637
(100) (MC).
DMF (10 mL) for 3 h under the conditions described for
20b. Recrystallization from chloroform–methanol gave the
coppercomplex(8 mg, 85%)asagreenpowder, mpO300 8C.
UV–vis (1% Et3N–CHCl3): lmax (log103) 347 (4.00), 392
(4.51), 441 (4.23), 447 (4.22), 620 nm (4.11); HRMS
(FAB): Calcd for C34H32N6SeCu: 667.1150. Found:
667.1151.
4.2.24. Zinc complex 22d. Porphyrin 4d (7 mg) and zinc
acetate dihydrate (50 mg) were reacted in DMF (10 mL) for
3 h under the conditions described for 20b. Recrystalliza-
tion from chloroform–methanol gave the zinc complex
(5.3 mg, 60%) as a green powder, mpO300 8C. UV–vis (1%
Et3N–CHCl3):lmax (log103) 348 (4.22), 393 (4.64), 458 (4.40),
627 nm (4.25); HRMS (FAB): Calc for C34H32N6SeZn:
668.1145. Found: 668.1146.
4.2.20. Zinc complex 22c. Porphyrin 4c (7 mg) and zinc
acetate dihydrate (50 mg) were reacted in DMF (10 mL)
under the conditions described for 20b. Recrystallization
from chloroform–methanol gave the zinc complex (6.3 mg,
86%) as a green powder, mpO300 8C. UV–vis (1%
Et3N–CHCl3): lmax (log103) 387 (4.67), 445 (4.65), 573
(3.83), 627 nm (4.32); FD MS: m/z (rel. int.) 645 (7), 644
(16), 643 (25), 642 (55), 641 (33), 640 (95), 639 (36), 638
(100) (MC).
Acknowledgements
4.2.21. 8,12,13,17-Tetraethyl-7,18-dimethylselenadiazo-
lobenzo[4,5-b]porphyrin (4d). Selenadiazolobenzopyrrole
5d (100 mg) was taken up in ethyl acetate (20 mL) and
sonicated for 20 min. Acetic acid (92 mL) and acetoxy-
methylpyrrole 14a (254 mg) were added, and the resulting
mixture was refluxed with stirring under nitrogen for 16 h.
The solution was cooled, diluted with dichloromethane,
washed with water and sodium bicarbonate solution, and
evaporated to dryness under reduced pressure to give the
crude tripyrrane 15d as a dark red solid that was used
without further purification. Crude 15d (100 mg) depro-
tected with TFA (2.5 mL) and reacted with dialdehyde 16
(29 mg) under the conditions described for 4b. The crude
product was chromatographed on grade III alumina eluting
with 30% dichloromethane–toluene and recrystallized from
chloroform–methanol to give porphyrin 4d (9 mg, 9%) as
green crystals, mp O300 8C; UV–vis (1% Et3N–CHCl3):
lmax (log103) 382 (4.78), 450 (4.69), 574 (4.19), 600 nm
(4.27); UV–vis (1% TFA–CHCl3): lmax (log103) 369 (4.33),
404 (4.70), 427 (5.04), 569 (3.94), 597 (3.44), 621 nm
This material is based upon work supported by the National
Science Foundation under Grant No. CHE-0134472, and the
Petroleum Research Fund, administered by the American
Chemical Society. C.M.C. also acknowledges a summer
fellowship from Abbott laboratories.
References and notes
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1
(4.27); H NMR (400 MHz, TFA–CDCl3): d K3.62 (2H,
br), K2.96 (2H, br), 1.73–1.88 (12H, m), 3.66 (3H, s), 3.69
(3H, s), 4.14–4.29 (8H, m), 8.74 (1H, d, JZ9.2 Hz), 9.57
(1H, d, JZ9.6 Hz), 10.62 (1H, s), 10.64 (1H, s), 11.04 (1H,
s), 12.05 (1H, s); 13C NMR (TFA–CDCl3): d 12.0, 16.6,
16.7, 17.5, 20.2, 20.3, 20.4, 20.5, 98.1, 99.2, 99.5, 102.1,
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