An efficient synthesis of highly functionalized asymmetric porphyrins with organolithium reagents

Article abstract of DOI:10.1039/b100012h

Functionalized tri- (A₂B-type) and tetra- (A₂BC-type) meso-substituted asymmetric porphyrins bearing highly reactive centers like-NH₂, -OH, -C≡CH, -CHO in substituents at the meso positions were synthesized in good yields via the reaction of 5,15-diphenylporphyrin with corresponding functionalized organolithium reagents. Through further transformation other functional groups like carboxylate, iodophenyl, thiocarboxylate, tertiary amines and quaternary ammonium salts are easily available. Such porphyrins serve as precursors for highly complex tetrapyrrolic systems. As examples, several novel porphyrins with potentially useful chemical and physical properties such as amphiphilicity, water solubility, and electrochemical redox activity were synthesized. In contrast to existing methods such compounds are now accessible regioselectively via one-step or two-step reactions in high yields. In addition, protocols were developed to prepare porphyrins with meso-aryl substituents bearing functional groups at the para, meta, or ortho position. Thus, starting materials for various specifically superstructured tetrapyrroles are available via rational syntheses.

Full text of DOI:10.1039/b100012h

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An efficient synthesis of highly functionalized asymmetric
porphyrins with organolithium reagents
Xiangdong Feng and Mathias O. Senge*
1
Institut für Chemie, Organische Chemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin,
Germany
Received (in Cambridge, UK) 2nd January 2001, Accepted 26th February 2001
First published as an Advance Article on the web 3rd April 2001
Functionalized tri- (A2B-type) and tetra- (A2BC-type) meso-substituted asymmetric porphyrins bearing highly
᎐
reactive centers like -NH , -OH, -C᎐CH, -CHO in substituents at the meso positions were synthesized in good
᎐
2
yields via the reaction of 5,15-diphenylporphyrin with corresponding functionalized organolithium reagents.
Through further transformation other functional groups like carboxylate, iodophenyl, thiocarboxylate, tertiary
amines and quaternary ammonium salts are easily available. Such porphyrins serve as precursors for highly complex
tetrapyrrolic systems. As examples, several novel porphyrins with potentially useful chemical and physical properties
such as amphiphilicity, water solubility, and electrochemical redox activity were synthesized. In contrast to existing
methods such compounds are now accessible regioselectively via one-step or two-step reactions in high yields. In
addition, protocols were developed to prepare porphyrins with meso-aryl substituents bearing functional groups
at the para, meta, or ortho position. Thus, starting materials for various specifically superstructured tetrapyrroles
are available via rational syntheses.
ation reactions.8,9 However, while the latter offers potential
for metal-assisted C–C coupling reactions, many of these
modification reactions require harsh conditions and/or use of
metalloporphyrins, resulting in unsatisfactory yields and low
Introduction
Tetrapyrroles have broad technical applications in the area of
catalysis,1 nonlinear optics,2 molecular recognition,3 photo-
sensitizers,4 and medicinal applications (photodynamic therapy)
tolerance towards functional groups.
– (PDT). Further development of these applications requires
We are involved in a programme aimed at the development of
asymmetric and highly functionalized compounds. For these,
novel and efficient synthetic methods, preferentially via a simple
modification of easily accessible symmetric porphyrins, have
to be developed. Thus, functionalized asymmetric porphyrin
highly efficient methods for the functionalization and modifi-
cation of porphyrins. Two years ago, we found that porphyrins
readily undergo meso substitution reactions with organolithium
reagents10 and since then have developed this reaction to a
precursors like 1 (A = solubility-enhancing groups; B, C =
generally applicable method for the preparative synthesis of
functional groups) are key intermediates for the required
functionalized asymmetric porphyrin precursors.11,12 In order
compounds. Despite many efforts and the theoretical utility of
to show that this method allows the preparation of porphyrins
with complex functional groups suitable for further transform-
porphyrin for both SE and SN reactions, only a few efficient
functionalization reactions have been described.5,6 In particular,
ations, we have now undertaken a study of the reactivity of
the direct, regioselective introduction of functional groups has
5,15-disubstituted porphyrins with more complex reagents
been rather limited up to now.
and report several simple and efficient applications of this
methodology leading to the synthesis of highly functionalized
porphyrins, and demonstrate their active chemical properties in
coupling reactions.
Results and discussion
The overall reaction of RLi with porphyrins is a nucleophilic
substitution like the Ziegler alkylation13 and proceeds via initial
reaction of the organic nucleophile with a meso carbon yielding
an anionic species, which is hydrolyzed to a dihydroporphyrin
or can be used as an in situ nucleophile for the reaction
with alkyl iodides, allowing the introduction of two different
In general, there are several synthetic avenues to functional-
ized, asymmetric porphyrins: a) mixed condensations, followed
by laborious chromatographic separation; b) multi-step total
synthesis by 2 ϩ 2 or 3 ϩ 1 condensation;7 c) direct intro-
duction of functional groups into easily synthesized symmetric
porphyrins to yield the desired target compounds. Due to
the difficult work-up and unsatisfactory yields of a) and the
limited applicability of b),7b route c) offers potential for further
development. Known functionalization reactions include
Vilsmeier formylation, sulfonation, nitration, and halogen-
substituents in a one-pot reaction.11 Subsequent oxidation
with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) yields
meso-substituted porphyrins.12
5,15-Diphenylporphyrin 2 (Scheme 1) is an easily synthesized
symmetric porphyrin14 with two free meso positions, in which
new functionalized substituents from organolithium reagents
and alkyl iodides can be selectively introduced without attack
at β positions.11,15 Alternatively, repetition of the addition–
oxidation sequence of RLi with a tri-meso-substituted por-
phyrin allows the synthesis of bifunctionalized asymmetric
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J. Chem. Soc., Perkin Trans. 1, 2001, 1030–1038
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b100012h

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ester or aldehyde, which are stable only at low temperatures
(<Ϫ50 ЊC),17 could not be employed in this synthesis. Test
experiments recovered only starting material. Lithium
reagents such as o-amino- or o-hydroxyphenyllithium or 2-
pyridyllithium showed no reactivity against 5,15-diphenyl-
porphyrin at various temperatures, while the porphyrin 6
with a m-hydroxyphenyl substituent at the 5-position was
synthesized in yields of only 30%. However, if the functional
groups are protected, e.g., by using o-methoxyphenyllithium as
reagent, the corresponding porphyrins could be prepared in
good yields (for example, porphyrin 7, 83%).
The functional groups introduced are highly reactive and
easily employed in further coupling reactions. For example, it is
known from the literature that amino and hydroxy groups
like those in porphyrins 4 and 5 react as nucleophiles smoothly
with carboxylic acid chloride, anhydride, and its activated ester
[N,NЈ-dicyclohexylcarbodiimide (DCC), hydroxysuccinimide]
as well as with many halogeno compounds.18,19 After deprotec-
tion of the porphyrins 9 and 12 the corresponding aldehydes
can be used as key intermediates for the synthesis of porphyrin
dimers or oligomers undergoing acid-catalyzed condensation
with pyrrole or dipyrromethane as well as with other bifunc-
tional nucleophiles such as Wittig reagents.20–22 Porphyrins 8
and 11 are good intermediates for the synthesis of cationic
derivatives by treatment with iodomethane. Such compounds
are widely used for investigating their interaction with proteins
or used as an entry into water-soluble porphyrins.23 Porphyrins
6 and 7 are very interesting starting materials for the synthesis
of tetrapyrrole systems with modified spatial orientation and
possessing special chelation abilities useful in molecular
recognition and catalysis.24,25 Other potential applications are
the synthesis of ‘picket-fence’ and ‘basket-handle’ porphy-
rins.26,27 In particular, porphyrin 10 will be a candidate for
the rational synthesis of porphyrin-based materials such as
porphyrin arrays or push-pull porphyrins via Glaser or Heck
coupling.28–30 Porphyrins bearing such functional groups have
already found broad applications in the synthesis of super-
structured materials or in the synthesis of phenyl-bridged
porphyrinquinone systems via Dötz reaction.31 However, up to
now the synthesis of such porphyrins was quite laborious and
hampered by the involved chromatographic work-up.29,32
Furthermore, the porphyrins 4–12 still possess a free meso
position, where further functional groups can be inserted either
by another reaction with RLi or other meso-selective reactions
such as iodination with bis(trifluoroacetoxy)iodobenzene
iodine33–35 followed by oxidative coupling to give directly meso-
meso-linked bisporphyrins36 and can therefore be employed in
the synthesis of bifunctionalized porphyrins of the A2BC type
(Scheme 2).
Scheme 1
porphyrins by introducing a second functional group without
formation of regioisomers as is observed in similar reactions
with octaethylporphyrin.10,16 Thus, at first we used 5,15-diphen-
ylporphyrin 2 and its nickel(II) complex 3 for the preparation
of various monofunctionalized porphyrins.
The porphyrins 4–12 were synthesized through the reaction
of organolithium reagents with 5,15-diphenylporphyrin 2 and
its nickel() complex 3 in good yields (≈80%) except for 6. In
order to achieve high yields in the synthesis shown in Scheme 1,
more equivalents (10–15) of organolithium reagents were used
than in our earlier reports on the case of RLi for porphyrin
modification.10–12 Under these reaction conditions no ring-
opened products were observed. The larger excess of organo-
lithium reagent led to a higher concentration of LiOH in the
reaction mixture after hydrolysis with water, thus requiring
more DDQ (10–15 equivalents to porphyrin), which is unstable
in strongly basic media. The excess of hydrolyzed organo-
lithium reagents can be removed either through distillation
under high vacuum at 50–80 ЊC or by chromatographic
separation eluting with an excess of n-hexane. The func-
tionalized target porphyrins are much more polar than
5,15-diphenylporphyrin and thus product and educt can be
separated easily from each other. In general, the reaction of
5,15-diphenylporphyrin 2 with aryllithium reagents requires
a reaction temperature of 0–50 ЊC. Thus, some aryllithium
reagents with highly functional groups like carboxylic acid
For example, porphyrin 13 was prepared via the reaction with
butyllithium and p-aminophenyllithium with an overall yield of
70%. Using 13 as starting material the porphyrins 14 and 15
were prepared in yields of 70 and 92%, respectively. Interest-
ingly, the reaction of 5,15-diphenylporphyrin 2 with an RLi
reagent prepared from p-bromophenylethyne and BuLi yielded
the monoanionic lithiated porphyrin derivative 16 as an
intermediate. This highly active nucleophile can be trapped with
CO2 to yield the porphyrin 17 in 43% yield (not optimized)
and should prove to be useful in trapping reactions with other
functionalized electrophiles such as aldehydes, esters with
highly functional groups37 or in coupling reactions with Pd/Cu
catalysis.38
In order to test the chemical reactivity of the functionalized
porphyrins synthesized, we subjected them to coupling reac-
tions to obtain porphyrins suitable for the applications
described in the Introduction. Porphyrin 4 with a free amino
group at the phenyl substituent reacted smoothly and quan-
titatively with electrophiles like maleic anhydride to afford
porphyrin 20 (95%), while reaction with p-iodobenzoyl chloride
and subsequent introduction of zinc ion gave the porphyrin 19
J. Chem. Soc., Perkin Trans. 1, 2001, 1030–1038
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Scheme 2
in a yield of 86%. Novel tetrapyrrole systems for photochemical
the n-butyl substituent also showed excellent reactivity
studies can be synthesized directly via Heck coupling with the
zinc() porphyrin 19. Other transformations yielded functional
groups like -COOH or -I. Under mild reaction conditions
porphyrin 21 could be obtained by the reaction of porphyrin 4
with (Ϫ)-2,3:4,6-di-O-isopropylidene--gulo-hex-2-ulofurano-
sonic acid in the presence of DCC in 76% yield. In this context
we report here several new porphyrins, which were obtained
from the precursor compounds described above through
reaction of the porphyrin anionic intermediate with alkyl
iodides.11 The results are shown in Scheme 3.
against nucleophilic reagents. For example, the porphyrin 24
was synthesized through the reaction of 23 with potassium
phthalimide in N,N-dimethylformamide (DMF) in a yield of
71%. Porphyrins 22 and 23, like normal alkyl iodides, also
showed good electrophilic properties in their reactions with
secondary and tertiary amines. Thus, porphyrins 25 and 26 were
obtained by substitution with diethylamine and triethylamine
in 53 and 83% yield, respectively while the known compound 27
could be prepared via reaction with KOH. In polar aprotonic,
strong basic media {1,8-diazobicyclo[5.4.0]undec-7-ene (DBU)
in DMF} the iodo group can be substituted by excess of weak
Porphyrins 22 and 2311 with an iodo group at the end of
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Scheme 3
nucleophiles like N-acetyl--cysteine and the porphyrin 28 bear-
fluorescence spectrum of the trisubstituted porphyrin 18
ing an amino acid was synthesized in 55% yield. Compound 29
was prepared by reaction of 22 with potassium thioacetate in
DMF in 91% yield. Porphyrin 30 was obtained by demetalla-
tion of 29 under mild conditions39 with boron tribromide in a
yield of 57%, while several polar, purple fractions were also
detected on TLC. These possibly involve saponification of the
thioester group and ring-opening reactions.
shows an interesting ‘exciton splitting effect’ between the
neighboring porphyrins that indicates a crowded arrange-
ment on the gold surface.42 Porphyrin 24 is a reversible
redox-system,43 while cationic porphyrins such as 26 with
amphiphilic properties can be used in the investigation
of pigment–protein interactions in the biological environ-
ment.23,44
The synthesized porphyrins should be interesting as model
compounds for many studies due to their special chemical and
physical properties. For example, the porphyrins 20 and 21
bearing sugar or carboxy groups should show variable
amphiphilicity in comparison with 14 and 15 with additional
n-butyl substituents. Such compounds and also 27 are often
used in membrane studies due to their special localization
properties.40 Porphyrins 18 and 29 and 30 can be easily bound
to gold particles and layers for surface electrochemical studies.41
In contrast to the easily synthesized tetra-aryl-substituted
porphyrins conventionally used in gold surface studies, the
In conclusion, the present methodology, in conjunction with
established techniques, should allow the synthesis of almost
any desired meso-functionalized-porphyrin and more compli-
cated macrocyclic systems with special chemical and physical
properties in few steps and with high yields.
Experimental
General
All chemicals used were of analytical grade and purified before
J. Chem. Soc., Perkin Trans. 1, 2001, 1030–1038
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use by distillation. The reactions of porphyrins with organo-
lithium compounds were performed under a purified argon
atmosphere by using modified Schlenk techniques and dried
and degassed solvents. Mps are uncorrected and were measured
with a Reichert Thermovar apparatus. Neutral alumina (Alfa)
(usually Brockmann Grade III, i.e. deactivated with 7.5%
water) was used for column chromatography. Analytical thin-
layer chromatography (TLC) was performed on Merck silica gel
or alumina 60 (neutral, fluorescence indicator F254) precoated
plates. Proton NMR spectra were recorded at a frequency of
250 MHz with a Bruker AC 250 instrument. All chemical shifts
are given in ppm and have been converted to the δ-scale and are
referenced against the SiMe4 (TMS) signal as internal standard.
Electronic absorption spectra were recorded with a Specord
S10 (Carl Zeiss) spectrophotometer using dichloromethane as
solvent. Mass spectra were obtained using a Varian MAT 711
mass spectrometer. Calculated mass for Ni complexes refers to
58Ni. Elemental analyses were performed with a Perkin-Elmer
240 analyzer.
J 7.5, HPh †), 7.70–7.80 (6 H, m, HPh), 8.00 (2 H, d, J 7.5, HPh),
8.25 (4 H, m, HPh), 8.85 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 9.05–9.15
(4 H, m, 4 × Hβ-pyrrole), 9.30 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 10.20
(1 H, s, Hmeso); m/z (EI, 80 eV) 553.2261 (Mϩ, 100%. C38H27N5
requires M, 553.2267), 277 (M2ϩ, 11).
5-(p-Hydroxyphenyl)-10,20-diphenylporphyrin 5
n-Butyllithium (4 ml of a 2.5 M solution in n-hexane, 10 mmol)
was added under an argon atmosphere to a 250 ml of Schlenk
flask charged with a solution of p-bromophenol (0.87 g,
5 mmol) in 15 ml of dry diethyl ether at 0 ЊC. After addition of
n-butyllithium the cold bath was removed and stirring was
continued for 16 h at room temperature. The solution slowly
became white opaque. To this vigorously stirred mixture was
added rapidly a solution of 5,15-diphenylporphyrin 2 (200 mg,
0.43 mmol) in 80 ml of dry THF under an argon atmosphere.
The color of the mixture changed from deep purple to brown
within 30 min. The further work-up followed the general
procedure described above. Chromatography and elution with
dichloromethane–n-hexane (3 : 1, v/v) on silica gel yielded 179
mg (75%) of porphyrin 5 as purple crystals (Found: C, 80.85; H,
4.50; N, 9.68. C38H26N4Oؒ0.5H2O requires C, 80.96; H, 4.83; N,
9.95%); mp >300 ЊC (from CH2Cl2–n-hexane); λmax (CH2Cl2)/
nm 413 (log ε/dm3 molϪ1 cmϪ1 5.21), 509 (3.81), 544 (3.12), 584
(3.05), 639 (2.42); δH (250 MHz; CDCl3; SiMe4) Ϫ3.01 (2 H,
s, NH), 6.85 (2 H, d, J 7.5, HPh), 7.75–7.80 (6 H, m, HPh), 8.00
(2 H, d, J 7.5, HPh), 8.25 (4 H, m, HPh), 8.85–9.10 (4 H,
m, 4 × Hβ-pyrrole), 9.15 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 9.40 (2 H,
d, J 5.0, 2 × Hβ-pyrrole), 10.20 (1 H, s, Hmeso); m/z (EI, 80 eV)
554.2152 (Mϩ, 100%. C38H26N4O requires M, 554.2107), 277
(M2ϩ, 37).
General procedure for the reaction of porphyrins with organo-
lithium reagents. A Schlenk flask was charged with 0.4 mmol of
the porphyrin (≈200 mg) dissolved in 80 ml of dry THF under
an argon atmosphere. The porphyrin solution was cooled to
Ϫ40 ЊC and added to a solution of 4–6 mmol organolithium
reagent in a Schlenk flask at 0–40 ЊC. RLi reagents prepared
in situ often form rubber-like precipitates that tend to stick to
the walls of the reaction vessel. Thus, the cooled solution of the
porphyrin was added to the vigorously stirred solution of RLi
and not the other way around. After removal of the cold bath
the reaction mixture was stirred for another 1 hour (TLC
control). The color of the reaction mixture changed from
purple to brown within 30 min (if the color does not change,
slow heating to reflux is necessary), subsequently a mixture of
5 ml of water in 5 ml of tetrahydrofuran (THF) was added
for the hydrolysis. After stirring of the mixture for 20 min, a
solution of 10–15 equivalents of DDQ in dichloromethane
(≈0.06 M) was added and the reaction mixture was stirred for
another 60 min at room temperature. Subsequently, the mixture
was filtered through neutral alumina and the organic solvent
was removed under vacuum. In order to remove residual
bromide or hydrolyzed RLi, the residue was dried under high
vacuum or washed with enough n-hexane during the column
chromatography described below. Final purification was
achieved by column chromatography on neutral alumina
(Alfa) or silica gel (Merck) followed by recrystallization from
CH2Cl2–methanol or CH2Cl2–n-hexane.
5-(m-Hydroxyphenyl)-10,20-diphenylporphyrin 6
n-Butyllithium (4 ml of 2.5 M solution in n-hexane, 10 mmol)
was added under an argon atmosphere to a 250 ml Schlenk
flask charged with a solution of m-bromophenol (0.87 g,
5 mmol) in 15 ml of dry diethyl ether at 0 ЊC. After addition of
n-butyllithium the cold bath was removed and stirring was
continued for 16 h at room temperature. Further steps followed
the general procedure described above. Chromatography and
elution with dichloromethane–n-hexane (3 : 1, v/v) on silica
gel yielded 66 mg (30%) of porphyrin 6 from 5,15-diphenyl-
porphyrin 2 (200 mg, 0.43 mmol) as purple crystals, mp
>300 ЊC (from CH2Cl2–n-hexane); λmax (CH2Cl2)/nm 412 (log
ε/dm3 molϪ1 cmϪ1 5.31), 509 (4.06), 548 (3.42), 580 (3.25);
δH (250 MHz; CDCl3; SiMe4) Ϫ3.00 (2 H, s, NH), 7.25 (1 H, m,
HPh), 7.50–7.60 (1 H, m, HPh), 7.70–7.75 (1 H, m, HPh), 7.70–
7.80 (6 H, m, HPh), 8.00 (1 H, s, HPh), 8.25 (4 H, m, HPh), 8.85
(2 H, d, J 5.0, 2 × Hβ-pyrrole), 8.90 (2 H, d, J 5.0, 2 × Hβ-pyrrole),
9.00 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 9.30 (2 H, d, J 5.0, 2 ×
5-(p-Aminophenyl)-10,20-diphenylporphyrin 4
n-Butyllithium (6 ml of a 2.5 M solution in n-hexane, 15 mmol)
was slowly added (ca. 1 h) under an argon atmosphere to a 250
ml Schlenk flask charged with a solution of p-bromoaniline
(1 g, 5 mmol) in 15 ml of dry diethyl ether at 0 ЊC. After
addition of n-butyllithium the cold bath was removed and the
mixture was stirred for another 1 h at room temperature. The
solution became yellow-brown and at the bottom of the flask
a viscous material was observed. To the vigorously stirred
mixture was added rapidly a solution of 5,15-diphenylpor-
phyrin 2 (200 mg, 0.43 mmol) in 80 ml of dry THF under an
argon atmosphere. The mixture changed from deep purple to
brown within 30 min. Further work-up followed the general
procedure as described above. Chromatography and elution
with dichloromethane–n-hexane (5 : 1, v/v) on silica gel yielded
compound 4 (196 mg, 82%) as purple crystals (Found: C, 80.08;
H, 4.78; N, 11.88. C38H27N5ؒ1H2O requires C, 79.83; H, 5.12;
N, 12.26%), mp >300 ЊC (from CH2Cl2–n-hexane); λmax
(CH2Cl2)/nm 408 (log ε/dm3 molϪ1 cmϪ1 5.21), 514 (4.18), 556
(3.97), 590 (3.82), 646 (3.69); δH (250 MHz; CDCl3: SiMe4)
Ϫ2.85 (2 H, s, 2 × NH), 3.90–4.00 (2 H, s, NH2), 6.96 (2 H, d,
H
β-pyrrole), 10.20 (1 H, s, Hmeso); m/z (EI, 80 eV) 554.2139 (Mϩ,
100%. C38H26N4O requires M, 554.2107), 277 (M2ϩ, 25).
5-(o-Methoxyphenyl)-10,20-diphenylporphyrin 7
n-Butyllithium (2.2 ml of 2.5 M solution in n-hexane, 5.5 mmol)
was added under an argon atmosphere to a 250 ml Schlenk
flask charged with a solution of o-bromoanisole (1 g, 5.4 mmol)
in 15 ml of dry THF at Ϫ78 ЊC. After addition of n-butyl-
lithium the cold bath was removed and the mixture was stirred
for 1 h at room temperature. Further steps followed the general
procedure described above. Chromatography and elution with
dichloromethane–n-hexane (1 : 1, v/v) on silica gel gave 188 mg
(83%) of porphyrin 7 from 5,15-diphenylporphyrin 2 (200 mg,
0.43 mmol) as purple crystals, mp >300 ЊC (from CH2Cl2–n-
hexane); λmax (CH2Cl2)/nm 412 (log ε/dm3 molϪ1 cmϪ1 5.27), 508
(3.97), 547 (3.37), 580 (3.18); δH (250 MHz; CDCl3; SiMe4)
Ϫ2.85 (2 H, s, NH), 3.50 (3 H, s, OCH3), 7.35–7.45 (2 H, m,
† In this paper HPh signifies all types of aromatic protons.
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HPh), 7.70–7.80 (7 H, m, HPh), 8.02 (1 H, d, J 8.1, HPh), 8.25–
8.35 (4 H, m, HPh), 8.80 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 8.90 (2 H,
d, J 5.0, 2 × Hβ-pyrrole), 9.05 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 9.40
(2 H, d, J 5.0, 2 × Hβ-pyrrole), 10.20 (1 H, s, Hmeso); m/z (EI, 80 eV)
568.2229 (Mϩ, 100%. C39H28N4O requires M, 568.2263), 283
(M2ϩ, 6).
porphyrin 2 (200 mg, 0.43 mmol) in 80 ml of dry THF under an
argon atmosphere. The color of the mixture changed from deep
purple to brown within 30 min. Further work-up followed
the general procedure described above. Chromatography and
elution with dichloromethane–n-hexane (1 : 5, v/v) on silica gel
yielded 205 mg (85%) of porphyrin 10 as purple crystals
(Found: C, 84.86; H, 4.90; N, 9.35. C40H26N4ؒ0.35H2O requires,
C, 84.43; H, 4.73; N, 9.85%), mp >300 ЊC (from CH2Cl2–
CH3OH); λmax (CH2Cl2)/nm 413 (log ε/dm3 molϪ1 cmϪ1 5.21),
5-[p-(Dimethylamino)phenyl]-10,20-diphenylporphyrin 8
n-Butyllithium (1 ml of 2.5 M solution in n-hexane, 2.5 mmol)
was slowly added (ca. 1 h) under an argon atmosphere to a
100 ml Schlenk flask charged with a solution of p-(dimethyl-
amino)bromobenzene (0.5 g, 2.5 mmol) in 10 ml of dry diethyl
ether at 0 ЊC. After addition of n-butyllithium the cold bath was
removed and stirring was continued for another 1 h at room
temperature. The solution became bright yellow and opaque.
To the vigorously stirred mixture was added rapidly a solution
of 5,15-diphenylporphyrin 2 (100 mg, 0.22 mmol) in 40 ml of
dry THF under an argon atmosphere. The color changed from
deep purple to brown within 30 min. Further work-up followed
the general procedure described above. Chromatography and
elution with dichloromethane–n-hexane (5 : 1, v/v) on silica gel
yielded 100 mg (78%) of porphyrin 8 as purple crystals (Found:
C, 81.70; H, 5.28; N, 11.53. C40H31N5ؒ0.5H2O requires, C,
81.32; H, 5.46; N, 11.86%), mp >300 ЊC (from CH2Cl2–
CH3OH); λmax (CH2Cl2)/nm 412 (log ε/dm3 molϪ1 cmϪ1 5.22),
513 (4.05), 553 (3.60), 587 (3.45), 643 (3.10); δH (250 MHz;
CDCl3; SiMe4) Ϫ2.95 (2 H, s, 2 × NH), 3.20 (6 H, s, CH3), 7.00
(2 H, d, J 7.5, HPh), 7.75–7.80 (6 H, m, HPh), 8.15 (2 H, d, J 7.5,
HPh), 8.25 (4 H, m, HPh), 8.80 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 9.05–
9.15 (4 H, m, 4 × Hβ-pyrrole), 9.25 (2 H, d, J 5.0, 2 × Hβ-pyrrole),
10.15 (1 H, s, Hmeso); m/z (EI, 80 eV) 581.2547 (Mϩ, 96%.
C40H31N5 requires M, 581.2579), 566 (Mϩ Ϫ CH3, 39), 291
(M2ϩ, 100).
509 (4.01), 544 (3.51), 585 (3.48), 639 (3,16); δH (250 MHz;
᎐
CDCl ; SiMe ) Ϫ3.15 (2 H, s, 2 × NH), 3.40 (1 H, s, HC᎐C),
᎐
3
4
7.75–7.80 (6 H, m, HPh), 7.90 (2 H, d, J 7.4, HPh), 8.20 (2 H, d,
J 7.4, HPh), 8.25–8.35 (4 H, m, HPh), 8.80 (2 H, d, J 5.0, 2 ×
H
β-pyrrole), 8.90 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 9.10 (2 H, d, J 5.0,
2 × Hβ-pyrrole), 9.40 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 10.20 (1 H, s,
Hmeso); m/z (EI, 80 eV) 562.2152 (Mϩ, 100%. C40H26N4 requires
M, 562.2158), 281 (M2ϩ, 8).
5-[3-(Dimethylamino)propyl]-10,20-diphenylporphyrin 11
To a suspension of granular lithium (0.5 g, 0.07 mol) in
dry diethyl ether (40 ml) was added freshly distilled 3-
(dimethylamino)propyl chloride (3.7 g, 0.025 mol) under argon
by means of a dropping funnel. After gentle heating to initiate
the reaction, the reagent was added dropwise, so that reflux
continued. After complete addition, stirring was continued for
1 h. The resulting solution was cooled to room temperature and
used for the reaction following the general procedure described
above. Chromatography and elution with neat dichloromethane
on silica gel yielded 82 mg (75%) of porphyrin 11 as purple
crystals from 5,15-diphenylporphyrin 2 (100 mg, 0.21 mmol),
mp 276 ЊC (from CH2Cl2–n-hexane); λmax (CH2Cl2)/nm 413 (log
ε/dm3 molϪ1 cmϪ1 5.21), 509 (3.86), 545 (3.03), 586 (2.97), 640
(2.02); δH (500 MHz; CDCl3; SiMe4) Ϫ3.05 (2 H, s, NH), 2.35
(6 H, s, CH3N), 2.75 [2 H, t, J 7.5, CH2CH2CH2N(CH3)2],
2.95 [2 H, q, J 7.5, CH2CH2CH2N(CH3)2], 5.10 [2 H, t, J 7.5,
CH2CH2CH2N(CH3)2], 7.70–7.80, 8.15–8.25 (10 H, m, HPh),
8.90–8.95 (4 H, m, 4 × Hβ-pyrrole), 9.25 (2 H, d, J 5.0, 2 ×
5-[p-(1,3-Dioxolan-2-yl)phenyl]-10,20-diphenylporphyrin 9
n-Butyllithium (1 ml of 2.5 M solution in n-hexane, 2.5 mmol)
was slowly added (ca. 1 h) under an argon atmosphere to a
100 ml Schlenk flask charged with a solution of 2-(p-bromo-
phenyl)dioxolane (0.5 g, 2.2 mmol) in 10 ml of dry diethyl
ether at 0 ЊC. After addition of n-butyllithium the cold bath
was removed and the solution was stirred for another 1 h at
room temperature. To this vigorously stirred mixture was
added rapidly a solution of 5,15-diphenylporphyrin 2 (100 mg,
0.22 mmol) in 50 ml of dry THF under an argon atmos-
phere. The color of the mixture changed from deep purple to
brown within 30 min. Further work-up followed the general
procedure described above. Chromatography and elution with
dichloromethane–n-hexane (2 : 1, v/v) on silica gel yielded
116 mg (86%) of porphyrin 9 as purple crystals, mp >300 ЊC
(from CH2Cl2–CH3OH); λmax (CH2Cl2)/nm 411 (log ε/dm3
molϪ1 cmϪ1 5.23), 508 (4.01), 544 (3.60), 584 (3.61), 636 (3.45);
δH (250 MHz; CDCl3; SiMe4) Ϫ3.02 (2 H, s, NH), 4.20, 4.35
(4 H, each m, OCH2CH2O), 6.15 (1 H, s, CHOCH2CH2O),
7.75–7.85 (8 H, m, HPh), 8.25–8.35 (6 H, m, HPh), 8.80–8.90
(4 H, m, 4 × Hβ-pyrrole), 9.05 (2 H, d, J 5.0, 2 × Hβ-pyrrole),
9.40 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 10.20 (1 H, s, Hmeso); m/z
(EI, 80 eV) 610.2329 (Mϩ, 100%. C41H30N4O2 requires M,
610.2369), 566 (Mϩ Ϫ CH2CH2O, 13), 538 [(M ϩ H)ϩ Ϫ
CH(OCH2)2, 16].
H
β-pyrrole), 9.55 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 10.10 (1 H, s, Hmeso);
m/z (EI, 80 eV) 547.2762 (Mϩ, 17%. C37H33N5 requires M,
547.2736), 489 (Mϩ Ϫ C3H8N, 100), 476 [(M ϩ H)ϩ Ϫ C4H10N,
11], 463 [(M ϩ 2H)ϩ Ϫ C5H12N, 27].
{5-[2-(1,3-Dioxan-2-yl)ethyl]-10,20-diphenylporphyrinato}-
nickel(II) 12
A solution of 5 ml (≈2 mmol) of freshly synthesized 2-(1,3-
dioxan-2-yl)ethyllithium45 in THF was added dropwise under
an argon atmosphere to a Schlenk flask charged with a solution
of (5,15-diphenylporphyrinato)nickel() 3 (100 mg, 0.22 mmol)
in 50 ml of THF at Ϫ70 ЊC. Further work-up followed the gen-
eral procedure described above. Chromatography and elution
with dichloromethane–n-hexane (3 : 1 v/v) on silica gel yielded
92 mg (73%) of porphyrin 12 as purple crystals, mp 283 ЊC
(from CH2Cl2–CH3OH); λmax (CH2Cl2)/nm 408 (log ε/dm3
molϪ1 cmϪ1 5.27), 523 (4.22); δH (250 MHz; CDCl3; SiMe4)
2.15–2.40 (2 H, m, OCH2CH2CH2O), 2.75–2.85 [2 H, q, J 7.5,
CH2CH2CH(OCH2CH2CH2O)], 4.20–4.30 (4 H, m, OCH2-
CH2CH2O), 4.55 (1 H, t, J 7.5, CH2CH2CH), 4.75 (2 H, t, J 7.6,
CH2CH2CH), 7.70–7.85, 7.95–8.15 (10 H, m, HPh), 8.80 (2 H, d,
J 5.0, 2 × Hβ-pyrrole), 8.85–8.95 (4 H, m, 4 × Hβ-pyrrole), 9.45 (2 H,
d, J 5.0, 2 × Hβ-pyrrole), 9.50 (1 H, s, Hmeso); m/z (EI, 80 eV)
632.1768 (Mϩ, 100%. C38H30N4O2Ni requires M, 632.1722), 531
(Mϩ Ϫ C5H9O2, 51).
5-(p-Ethynylphenyl)-10,20-diphenylporphyrin 10
n-Butyllithium (4 ml of 2.5 M solution in n-hexane, 10 mmol)
was slowly added (ca. 1 h) under an argon atmosphere to a 100
ml Schlenk flask charged with a solution of p-bromophenyl-
ethyne (0.91 g, 5.0 mmol) in 15 ml of dry diethyl ether at
Ϫ70 ЊC. The reaction mixture was then warmed to Ϫ40 ЊC
and THF was added dropwise until the aryllithium was formed
as a white–bright pink suspension. To this vigorously stirred
mixture was added rapidly a solution of 5,15-diphenyl-
5-(p-Aminophenyl)-15-butyl-10,20-diphenylporphyrin 13
A Schlenk flask was charged with the porphyrin 4 (100 mg,
0.18 mmol) dissolved in 50 ml of dry THF under an argon
atmosphere. Within 15 min the butyllithium (1.5 mmol, 0.6 ml
of a 2.5 M solution in n-hexane) was added dropwise. Further
J. Chem. Soc., Perkin Trans. 1, 2001, 1030–1038
1035

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steps followed the general procedure described above. Chrom-
atography and elution with dichloromethane–n-hexane (3 : 1,
v/v) yielded 97 mg (80%) of porphyrin 13 as purple crystals, mp
272 ЊC (from CH2Cl2–CH3OH); λmax (CH2Cl2)/nm 420 (log
ε/dm3 molϪ1 cmϪ1 5.25), 518 (3.92), 556 (3.71), 594 (3.46), 649
(3.47); δH (250 MHz; CDCl3; SiMe4) Ϫ2.65 (2 H, s, 2 × NH),
1.20 (3 H, t, J 7.5, CH2CH2CH2CH3), 1.80–1.90 (2 H, m,
CH2CH2CH2CH3), 2.45–2.55 (2 H, m, CH2CH2CH2CH3), 3.05
(2 H, s, NH2), 4.95 (2 H, t, J 7.8, CH2CH2CH2CH3), 6.75, 7.90
(4 H, each d, J 8.2, HPh), 7.75–7.85, 8.20–8.30 (10 H, each
m, HPh), 8.75, 8.80, 8.85, 9.45 (8 H, each d, J 4.9, 8 × Hβ-pyrrole);
m/z (EI, 80 eV) 609.2888 (Mϩ, 100%. C42H35N5 requires M,
609.2893), 566 (Mϩ Ϫ CH2CH2CH3, 28), 304 (M2ϩ, 8).
ethyne (0.91 g, 5.0 mmol) in 15 ml of dry diethyl ether at
Ϫ70 ЊC. The reaction mixture was then warmed to Ϫ40 ЊC and
THF was added dropwise until the aryllithium was formed as a
bright pink suspension. To this vigorously stirred mixture was
added rapidly a solution of 5,15-diphenylporphyrin 2 (200 mg,
0.43 mmol) in 80 ml of dry THF under an argon atmosphere.
After removal of the cold bath, the color of the mixture
changed from deep purple to brown within 30 min. The reac-
tion mixture was then cooled again to Ϫ40 ЊC and excess of
solid CO2 was added in portions. Further work-up followed
the general procedure described above. Chromatography and
elution with dichloromethane–methanol (2 : 1, v/v) on silica gel
yielded 112 mg (43%) of porphyrin 17 as purple crystals,
mp >300 ЊC (from CH2Cl2–n-hexane); λmax (CH2Cl2)/nm 413
(log ε/dm3 molϪ1 cmϪ1 5.29), 509 (4.78), 545 (4.75), 582 (4.75),
634 (4.74); δH (250 MHz; DMSO; SiMe4) Ϫ3.20 (2 H, s,
2 × NH), 7.75–7.90 (8 H, m, HPh), 8.15–8.30 (6 H, m, HPh),
8.80–8.90 (4 H, m, 4 × Hβ-pyrrole), 8.95 (2 H, d, J 5.0, 2 ×
5-Butyl-15-{p-[(؊)-2,3:4,6-di-O-isopropylidene-L-gulo-hex-2-
ulofuranosonamido]phenyl}-10,20-diphenylporphyrin 14
DCC 0.1 g (0.48 mmol) was added in portions to a solution of
(Ϫ)-2,3:4,6-di-O-isopropylidene--gulo-hex-2-ulofuranosonic
acid (140 mg, 0.48 mmol) and porphyrin 13 (50 mg, 0.08 mmol)
in CH2Cl2 (50 ml) at room temperature. The reaction mixture
was stirred for 3 h and then washed with distilled water (3 × 100
ml) until the water phase became colorless. The organic phase
was dried with Na2SO4 and evaporated to dryness on a rotary
evaporator. Chromatography and elution with dichloro-
methane–n-hexane (3 : 1, v/v) on silica gel yielded 46 mg (70%)
of porphyrin 14 as bright purple crystals, mp 216 ЊC (from
CH2Cl2–CH3OH); λmax (CH2Cl2)/nm 418 (log ε/dm3 molϪ1 cmϪ1
5.23), 516 (3.82), 552 (3.45), 593 (3.03); δH (250 MHz; CDCl3;
SiMe4) Ϫ2.70 (2 H, s, 2 × NH), 1.20 (3 H, t, J 7.5, CH2CH2-
CH2CH3), 1.45, 1.48, 1.63, 1.80 [12 H, each s, 2 × OC(CH3)2],
1.80–1.90 (2 H, m, CH2CH2CH2CH3), 2.45–2.55 (2 H, m,
CH2CH2CH2CH3), 4.20 (2 H, m, OCH2CHCHOCHOC), 4.30,
4.50, 4.80 (3 H, each s, OCH2CHCHOCHOC), 5.05 (2 H, t,
J 7.8, CH2CH2CH2CH3), 7.70–7.80, 7.95–8.05, 8.20–8.30 (14
H, each m, HPh), 8.85–8.90 (4 H, m, 4 × Hβ-pyrrole), 8.95 (2 H, d,
J 5.0, 2 × Hβ-pyrrole), 9.45 (1 H, s, NHCO), 9.50 (2 H, d, J 5.0,
2 × Hβ-pyrrole); m/z (EI, 80 eV) 865.3854 (Mϩ, 100%. C54H51N5O6
requires M, 865.3839), 850 (Mϩ Ϫ CH3, 6), 822 (Mϩ Ϫ CH2-
CH2CH3, 14), 635 (Mϩ Ϫ C11H18O5, 10), 592 (Mϩ Ϫ CH2CH2-
CH3 Ϫ C11H18O5, 19).
H
β-pyrrole), 9.60 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 10.55 (1 H, s, Hmeso);
m/z FAB (ϩ) 607 (M ϩ Hϩ, 100%. C41H27N4O2 requires m/z,
607), 563 [(M ϩ H)ϩ Ϫ CO2, 52%]; (EI, 80 eV) 562.2198
(Mϩ Ϫ CO2, 100%. C40H26N4 requires m/z, 562.2157).
{5-[p-(p-Iodobenzamido)phenyl]-10,20-diphenylporphyrinato}-
zinc(II) 19
p-Iodobenzoyl chloride (0.2 g, 0.73 mmol) was added in
portions to a solution of porphyrin 4 (100 mg, 0.18 mmol)
in dry THF (50 ml). The reaction mixture was stirred for 30 min
at room temperature and then poured into 100 ml of 0.1 M
NaOH. The porphyrin solution was extracted with CH2Cl2
(3 × 50 ml) until the aqueous phase became colorless. The
combined extracts were dried with Na2SO4 and evaporated to
dryness on a rotary evaporator. The residue was then resolvated
in 50 ml of dry CH2Cl2. Zinc acetate (0.24 g, 1.1 mol) was added
and stirring was continued for 30 min. The reaction mixture
was washed with distilled water (3 × 30 ml), and the organic
phase was dried with Na2SO4 and evaporated to dryness
on a rotary evaporator. Chromatography and elution with
dichloromethane–n-hexane (3 : 1, v/v) on silica gel yielded 130
mg (86%) of porphyrin 19 as bright purple crystals, mp >300 ЊC
(from CH2Cl2–CH3OH) λmax (CH2Cl2)/nm 414 (log ε/dm3 molϪ1
cmϪ1 5.25), 542 (3.82); δH (250 MHz; CDCl3; SiMe4) 7.45–7.55,
7.75–8.05, 8.25–8.35 (18 H, m, HPh), 8.85 (4 H, m, 4 × Hβ-pyrrole),
9.05 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 9.40 (2 H, d, J 5.0, 2 ×
5-Butyl-15-[p-(3-carboxyacrylamido)phenyl]-10,20-diphenyl-
porphyrin 15
H
β-pyrrole), 10.20 (1 H, s, Hmeso); m/z (EI, 80 eV) 845.0615 (Mϩ,
Maleic anhydride (63 mg, 0.64 mmol) was added in portions
to a solution of porphyrin 13 (100 mg, 0.16 mmol) in dry THF
(50 ml). The reaction mixture was stirred for 30 min at room
temperature and then poured into 100 ml of 0.1 M NaOH. The
porphyrin 15 was extracted with CH2Cl2 (3 × 50 ml) until the
water phase became colorless. The combined extracts were
dried with Na2SO4 and evaporated to dryness on a rotary
evaporator. Chromatography and elution with CH2Cl2–MeOH
(3 : 1, v/v) on silica gel yielded 104 mg (92%) of bright purple
crystals; mp >300 ЊC (from CH2Cl2–CH3OH); λmax (CH2Cl2)/
nm 420 (log ε/dm3 molϪ1 cmϪ1 5.25), 517 (3.87), 552 (3.56), 594
(3.08), 648 (2.92); δH (250 MHz; CDCl3; SiMe4) Ϫ2.30 (2 H, s,
2 × NH), 1.20 (3 H, t, J 7.5, CH2CH2CH2CH3), 1.80–1.90 (2 H,
m, CH2CH2CH2CH3), 2.55–2.65 (2 H, m, CH2CH2CH2CH3),
5.05 (2 H, t, J 7.8, CH2CH2CH2CH3), 6.25–6.45 [2 H, m,
NHCO(CH)2COOH], 7.70–7.80, 7.95–8.15, 8.20–8.25, 8.30–
8.35 (14 H, each m, HPh), 8.75–9.90 (6 H, m, 6 × Hβ-pyrrole), 9.40
(2 H, d, J 5.0, 2 × Hβ-pyrrole), 13.90 (1 H, s, COOH); m/z FAB(ϩ)
708 (M ϩ Hϩ, 100%. C46H38N5O3 requires m/z, 708); 609
[(M ϩ H)ϩ Ϫ C4H3O3, 20].
100%. C45H28IN5OZn requires M, 845.0629), 614 (Mϩ Ϫ C7-
H4OI, 11), 231 (C7H4OIϩ, 31).
5-[p-(3-Carboxyacrylamido)phenyl]-10,20-diphenylporphyrin 20
Maleic anhydride (63 mg, 0.64 mmol) was added portionwise
to a solution of porphyrin 4 (100 mg, 0.18 mmol) in dry THF
(50 ml). The reaction mixture was stirred for 30 min at room
temperature and then poured into 100 ml of 0.1 M NaOH.
Porphyrin 20 was extracted with CH2Cl2 (3 × 50 ml) until
the aqueous phase became colorless. The combined extracts
were dried with Na2SO4 and evaporated to dryness on a rotary
evaporator. Chromatography and elution with CH2Cl2–MeOH
(2 : 1, v/v) on silica gel yielded 110 mg (95%) of porphyrin 20
as bright purple crystals, mp >300 ЊC (from CH2Cl2–CH3OH);
λmax (CH2Cl2)/nm 413 (log ε/dm3 molϪ1 cmϪ1 5.28), 509 (3.99),
544 (3.53), 584 (3.46), 637 (3.19); δH (250 MHz; CDCl3; SiMe4)
Ϫ3.02 (2 H, s, NH), 6.40 [2 H, m, NHCO(CH)2COOH], 7.70–
7.80, 8.05–8.15, 8.25–8.35 (14 H, m, HPh), 8.80–8.95 (4 H, m,
4 × Hβ-pyrrole), 9.10 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 9.35 (2 H, d,
J 5.0, 2 × Hβ-pyrrole), 10.20 (1 H, s, Hmeso), 13.60 (1 H, s, COOH);
m/z FAB(ϩ) 652 (M ϩ Hϩ); FAB(Ϫ) 650 (M Ϫ Hϩ).
C42H29N5O3 required M, 651; (EI, 80 eV) 634.2259 (Mϩ Ϫ OH,
11%. C42H28N5O2 requires m/z, 634.2243), 553 (Mϩ Ϫ C4H2O3,
100).
5-[p-(Carboxyethynyl)phenyl]-10,20-diphenylporphyrin 17
n-Butyllithium (4 ml of 2.5 M solution in n-hexane, 10 mmol)
was slowly added (ca. 1 h) under an argon atmosphere to a 100
ml Schlenk flask charged with a solution of p-bromophenyl-
1036
J. Chem. Soc., Perkin Trans. 1, 2001, 1030–1038

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5-{p-[(؊)-2,3:4,6-Di-O-isopropylidene-L-gulo-hex-2-ulofurano-
sonamido]phenyl}-10,20-diphenylporphyrin 21
(Mϩ Ϫ C7H16N, 6), 575 [(M ϩ 2H)ϩ Ϫ C8H18N, 33], 544 (Mϩ Ϫ
C7H16N Ϫ C3H7, 14), 351 (M2ϩ, 7).
DCC 0.11 g (0.54 mmol) was added in portions to a solution of
(Ϫ)-2,3:4,6-di-O-isopropylidene--gulo-hex-2-ulofuranosonic
acid (0.16 g, 0.54 mmol) and porphyrin 4 (50 mg, 0.09 mmol)
in CH2Cl2 (50 ml) at room temperature. The reaction mixture
was stirred for 3 h at room temperature and then washed with
distilled water (3 × 100 ml) until the aqueous phase became
colorless. The organic phase was dried with Na2SO4 and evap-
orated to dryness on a rotary evaporator. Chromatography and
elution with dichloromethane on silica gel yielded 55 mg (76%)
of porphyrin 21 as bright purple crystals, mp >300 ЊC (from
CH2Cl2–CH3OH); λmax (CH2Cl2)/nm 413 (log ε/dm3 molϪ1 cmϪ1
5.26), 509 (4.07), 545 (3.56), 585 (3.54), 639 (3.24); δH (250
MHz; CDCl3; SiMe4) Ϫ3.00 (2 H, s, 2 × NH), 1.45, 1.50, 1.65,
1.70 [12 H, each s, 2 × OC(CH3)2], 4.15 (2 H, m, OCH2CH),
4.20, 4.50, 4.80 (3 H, each s, OCH2CHCHOCHOC), 7.70–7.80,
7.95–8.05, 8.20–8.30 (14 H, each m, HPh), 8.85–8.90 (4 H, m,
4 × Hβ-pyrrole), 9.00 (2 H, d, J 5.0, 2 × Hβ-pyrrole), 9.40 (2 H, d,
J 5.0, 2 × Hβ-pyrrole), 10.20 (1 H, s, Hmeso); m/z FAB (ϩ) 810
(M ϩ Hϩ, 100%), C50H44N5O6 required m/z, 810, 580
[(M ϩ H)ϩ Ϫ C11H18O5, 12]; (EI, 80 eV) 809.3255 (Mϩ, 1%.
C50H43N5O6 requires M, 809.3213), 536 (Mϩ Ϫ C12H19NO6 17),
511 (Mϩ Ϫ C14H20NO6, 100).
{5-Butyl-10,20-diphenyl-15-[4-(triethylammonio)butyl]porphyr-
inato}nickel(II) iodide 26
Triethylamine (1 ml, 7 mmol) was added dropwise to a solution
of
[5-butyl-15-(4-iodobutyl)-10,20-diphenylporphyrinato]-
nickel() 22 (100 mg, 0.13 mmol) in DMF (30 ml). The reaction
mixture was stirred at 60 ЊC for 3 h and then poured into 100 ml
of distilled water. Porphyrin 26 was extracted with CH2Cl2
(3 × 50 ml) until the aqueous phase became colorless. The
combined extracts were dried with Na2SO4 and evaporated to
dryness on a rotary evaporator. Chromatography and elution
with CH2Cl2–MeOH (2 : 1, v/v) on Celite after recrystallization
from aq. MeOH gave 78 mg (83%) purple crystals of 26
(Found: C, 63.62; H, 6.11; N, 8.10. C46H50IN5Niؒ0.5H2O
requires C, 63.72; H, 5.93; N, 8.08%), mp >300 ЊC (from aq.
MeOH); λmax (CH2Cl2)/nm 416 (log ε/dm3 molϪ1 cmϪ1 5.27), 533
(3.99); δH (250 MHz; D6-DMSO; SiMe4) 0.85 (3 H, t, J 7.8
CH3CH2CH2CH2), 1.25 [9 H, t, J 7.5, (CH3CH2)3Nϩ], 1.30–1.45
[2 H, m, CH3CH2CH2CH2], 1.90–2.10 [2 H, m, (CH3CH2)3-
NϩCH2CH2CH2CH2], 2.20–2.30 (2 H, m, CH3CH2CH2CH2),
2.35–2.60 [2 H, m, (CH3CH2)3NϩCH2CH2CH2CH2], 3.20–3.30
[8 H, m, (CH3CH2)3NϩCH2CH2CH2CH2], 4.60–4.75 [4 H, m,
(CH3CH2)3NϩCH2CH2CH2CH2, CH3CH2CH2CH2], 7.75–7.85,
7.95–8.10 (10 H, m, HPh), 8.60 (4 H, m, Hβ-pyrrole), 9.45 (2 H, d,
J 5.0, 2 × Hβ-pyrrole), 9.60 (2 H, d, J 5.0, Hβ-pyrrole); m/z FAB(ϩ)
731 (M ϩ Hϩ, 100%. C46H51N5Ni requires m/z, 731), 629
[Mϩ Ϫ N(CH2CH3)3, 30]; FAB(Ϫ): 127 (IϪ, 100%. I requires
M, 127).
[5,10,15-Triphenyl-20-(4-phthalimidobutyl)porphyrinato]-
nickel(II) 24
Potassium phthalimide (0.1 g, 0.53 mmol) was added portion-
wise to a solution of [5-(4-iodobutyl)-10,15,20-triphenylpor-
phyrinato]nickel() 23 (100 mg, 0.12 mmol) in DMF (50 ml).
The reaction mixture was heated overnight under reflux and
then poured into 100 ml of distilled water. Porphyrin 24 was
extracted with CH2Cl2 (3 × 50 ml) until the aqueous phase
became colorless. The combined extracts were dried with
Na2SO4 and evaporated to dryness on a rotary evaporator.
Chromatography and elution with dichloromethane–n-hexane
(3 : 1, v/v) on silica gel yielded 73 mg (71%) of the title com-
pound as purple crystals, mp 260 ЊC; λmax (CH2Cl2)/nm 415
(log ε/dm3 molϪ1 cmϪ1 5.21), 530 (3.95); δH (250 MHz; CDCl3;
SiMe4) 1.85–2.00 (2 H, m, CH2CH2CH2CH2), 2.25–2.45 (2 H,
m, CH2CH2CH2CH2N), 3.75 (2 H, t, J 7.6, CH2CH2CH2-
CH2N), 4.65 (2 H, t, J 7.8, CH2CH2CH2CH2N), 7.55–7.75,
7.95–8.05 (19 H, each m, HPh), 8.65 (4 H, m, 4 × Hβ-pyrrole), 8.80,
9.35, (4 H, each d, J 4.9, 4 × Hβ-pyrrole); m/z (EI, 80 eV) 795.2184
(Mϩ, 100%. C50H35N5NiO2 requires M, 795.2144), 648 (Mϩ Ϫ
C8H5NO2, 7), 608 [(M ϩ H)ϩ Ϫ C11H10NO2, 60].
[5-Butyl-15-(4-hydroxybutyl)-10,20-diphenylporphyrinato]-
nickel(II) 27
0.4 g KOH in 5 ml H2O was added to a solution of [5-butyl-15-
(4-iodobutyl)-10,20-diphenylporphyrinato]nickel(II) 22 (50 mg,
0.065 mmol) in DMF (30 ml). The reaction mixture was stirred
at 100 ЊC for 4 h and then poured into 100 ml of distilled water.
Porphyrin 27 was extracted with CH2Cl2 (3 × 50 ml) until the
aqueous phase became colourless. The combined extracts were
dried with Na2SO4 and evaporated to dryness under vacuum.
Chromatography and elution with ethyl acetate–n-hexane on
neutral alumina (Alfa) (1:1, v/v) yielded 34 mg (80%) of
porphyrin 27 as purple crystals. The spectroscopic data were
identical with those given in our earlier work.11
{5-[4-(N-Acetyl-L-cystein-5-yl)butyl]-10,15,20-triphenylpor-
phyrinato}nickel(II) 28
5-Butyl-15-{[4-(diethylamino)butyl]-10,20-diphenylporphyr-
DBU (0.5 ml) was added dropwise to a solution of N-acetyl-
-cysteine (0.2 g, 1.3 mmol) and [5-(4-iodobutyl)-10,15,20-
triphenylporphyrinato]nickel() 23 (50 mg, 0.06 mmol) in DMF
(50 ml) at room temperature. The reaction mixture was stirred
for 3 h and then poured into 200 ml of distilled water. Porphy-
rin 28 was extracted with CH2Cl2 (3 × 50 ml) until the aqueous
phase became colorless. The combined extracts were washed
with water (3 × 100 ml), dried with Na2SO4 and evaporated to
dryness on a rotary evaporator. Chromatography and elution
with CH2Cl2–MeOH (5 : 1, v/v) on silica gel yielded 27 mg
(55%) of compound 28 as purple crystals; mp 225 ЊC (from
CH2Cl2–CH3OH); λmax (CH2Cl2)/nm 415 (log ε/dm3 molϪ1 cmϪ1
5.25), 529 (4.22); δH (250 MHz; CDCl3; SiMe4) 1.75–1.85 (2 H,
m, CH2CH2CH2CH2S), 2.10 (3 H, s, HNCOCH3), 2.25–2.40
(2 H, m, CH2CH2CH2CH2S), 2.60 (2 H, m, CH2CH2CH2-
CH2S), 3.10 (2 H, m, NHCHCH2S), 4.40 (1 H, m, NHCH-
CH2S), 4.55 (2 H, t, J 7.8, CH2CH2CH2CHS), 7.55–7.75, 7.85–
7.95 (15 H, each m, HPh), 8.65 (4 H, m, 4 × Hβ-pyrrole), 8.70, 9.35
(4 H, each d, J 4.9, 4 × Hβ-pyrrole); m/z [FAB(ϩ)] 812 (M ϩ Hϩ,
100%. C47H40N5NiO3S requires m/z, 812), 650 [(M ϩ H)ϩ Ϫ
SCH2CHNHCOCH3COOH, 70].
inato}nickel(II) 25
Diethylamine (5 ml, 48 mmol) was added dropwise to a solu-
tion of [5-butyl-15-(4-iodobutyl)-10,20-diphenylporphyrinato]-
nickel() 22 (100 mg, 0.13 mmol) in THF (50 ml). The reaction
mixture was stirred at 50 ЊC for 2 h and then poured into 100 ml
of distilled water. Porphyrin 25 was extracted with CH2Cl2
(3 × 50 ml) until the aqueous phase became colorless. The
combined extracts were dried with Na2SO4 and evaporated to
dryness on a rotary evaporator. Chromatography and elution
with dichloromethane–n-hexane (3 : 1, v/v) on silica gel yielded
the target porphyrin (48 mg, 53%) as purple crystals, mp
>300 ЊC (from aq. MeOH); λmax (CH2Cl2)/nm 416 (log ε/dm3
molϪ1 cmϪ1 5.13), 533 (3.97); δH (250 MHz; CDCl3; SiMe4) 1.05
[9 H, m, CH3CH2CH2CH2, (CH3CH2)2N], 1.45–1.55 (2 H, m,
CH3CH2CH2CH2), 2.20–2.40 [6 H, m, (C2H5)2NCH2CH2-
CH2CH2, CH3CH2CH2CH2], 2.45–2.60 [6 H, m, (CH3CH2)2-
NCH2CH2CH2CH2], 4.50–4.55 [4 H, m, (CH3CH2)2NCH2-
CH2CH2CH2, CH3CH2CH2CH2], 7.65–7.75, 7.95– 8.05 (10 H,
m, HPh), 8.70, 9.35 (8 H, each m, 8 × Hβ-pyrrole); m/z (EI, 80 eV)
701.3073 (Mϩ, 16%. C44H45N5Ni requires M, 701.3028), 587
J. Chem. Soc., Perkin Trans. 1, 2001, 1030–1038
1037

View Online
4 H. Ali and J. E. Lier, Chem. Rev., 1999, 99, 2379.
5 M. G. H. Vicente, I. N. Rezzano and K. M. Smith, Tetrahedron
Lett., 1990, 31, 1365.
{5-[4-(Acetylthio)butyl]-5-butyl-10,20-diphenylporphyrinato}-
nickel(II) 29
Potassium thioacetate (50 mg, 0.4 mmol) was added portion-
wise to a solution of {5-butyl-15-(4-iodobutyl)-10,20-diphenyl-
porphyrinato}nickel() 22 (50 mg, 0.07 mmol) in THF–acetone
(30 ml; 1 : 1, v/v). The reaction mixture was stirred for 12 h at
room temperature and then poured into 100 ml of distilled
water. Porphyrin 29 was extracted with CH2Cl2 (3 × 30 ml) until
the aqueous phase became colorless. The combined extracts
were dried with Na2SO4 and evaporated to dryness on a rotary
evaporator. Chromatography and elution with dichloro-
methane–n-hexane (3 : 1, v/v) on silica gel yielded porphyrin 29
45 mg (91%) as purple crystals, mp 240 ЊC (from CH2Cl2–
n-hexane); λmax (CH2Cl2)/nm 416 (log ε/dm3 molϪ1 cmϪ1 5.15),
532 (4.04); δH (250 MHz; CDCl3; SiMe4) 0.85 (3 H, t,
J 7.8, CH3CH2CH2CH2), 1.45–1.55 (2 H, m, CH3CH2CH2CH2),
1.70–1.80 (2 H, m, SCH2CH2CH2CH2), 2.20–2.30 (7 H, m,
CH3CH2CH2CH2, SCH2CH2CH2CH2, CH3COS), 2.90 (2 H, t,
J 7.8, SCH2CH2CH2CH2), 4.50–4.60 (4 H, m, SCH2CH2-
CH2CH2, CH3CH2CH2CH2), 7.75–7.85, 7.95–8.10 (10 H, m,
HPh), 8.65–8.75 (4 H, m, 4 × Hβ-pyrrole), 9.20–9.30 (4 H, m,
4 × Hβ-pyrrole); m/z (EI, 80 eV) 704.2164 (Mϩ, 100%. C42H38N4-
NiOS requires M, 704.2120), 661 (Mϩ Ϫ CH2CH2CH3, 42),
587 [(M ϩ H)ϩ Ϫ CH2CH2CH3 Ϫ SCOCH3, 72], 544 (Mϩ Ϫ
CH2CH2CH3 Ϫ CH2CH2CH2SCOCH3, 63).
6 M. G. H. Vicente, in The Porphyrin Handbook, ed. K. M. Kadish,
K. M. Smith and R. Guilard, Academic Press, San Diego, 2000;
vol. 1, p. 150.
7 (a) J. S. Lindsey, in The Porphyrin Handbook, ed. K. M. Kadish,
K. M. Smith and R. Guilard, Academic Press, San Diego, 2000,
vol. 1, p. 45; (b) A new paper by Lindsey and co-workers indicates
the possibility to use pyrromethanes for the preparation of
ABCD porphyrins with acid-stable functionalities: P. D. Rao,
S. Dhanalekshmi, B. J. Littler and J. S. Lindsey, J. Org. Chem., 2000,
65, 7323.
8 J. Fuhrhop, in Porphyrins and Metalloporphyrins, ed. K. M. Smith,
Elsevier Scientific, Amsterdam, 1975, p. 625.
9 M. G. H. Vicente, in The Porphyrin Handbook, ed. K. M. Kadish,
K. M. Smith and R. Guilard, Academic Press, San Diego, 2000,
vol. 1, p. 161.
10 W. W. Kalisch and M. O. Senge, Angew. Chem., Int. Ed., 1998, 37,
1107; M. O. Senge, W. W. Kalisch and I. Bischoff, Chem. Eur. J.,
2000, 6, 2721.
11 X. Feng and M. O. Senge, Tetrahedron, 2000, 56, 587.
12 M. O. Senge and X. Feng, J. Chem. Soc., Perkin Trans. 1, 2000, 3615.
13 K. Ziegler and H. Zeiser, Ber. Dtsch. Chem. Ges., 1930, 63, 1847.
14 C. Brückner, J. J. Posakony, C. K. Johnson, R. W. Boyle, B. R. James
and D. Dolphin, J. Porphyrins Phthalocyanines, 1998, 2, 455.
15 M. O. Senge and X. Feng, Tetrahedron Lett., 1999, 40, 4165.
16 M. O. Senge and I. Bischoff, Eur. J. Org. Chem., 2001, in press.
17 W. E. Parham and Y. A. Sayed, J. Org. Chem., 1974, 39, 2051.
18 T. La, R. Richards and G. M. Miskelly, Inorg. Chem., 1994, 33,
3159.
5-[4-(Acetylthio)butyl]-15-butyl-10,20-diphenylporphyrin 30
19 R.-H. Jin, S. Aoki and K. Shima, J. Chem. Soc., Chem. Commun.,
1994, 1557.
A solution of boron tribromide in CH2Cl2 (10 ml; 0.1 M) was
added dropwise to a solution of porphyrin 29 (50 mg, 0.07
mmol) in CH2Cl2 (30 ml) at Ϫ70 ЊC under an argon atmos-
phere. After removal of the cold bath the reaction mixture was
stirred at room temperature for 2 h and then cooled again to
Ϫ70 ЊC. A solution of 1 ml of water in 5 ml of THF was added
dropwise to the vigorously stirred reaction mixture. After the
hydrolysis the solution was stirred for a further 30 min at room
temperature and then poured into 100 ml of 0.1 M NaOH.
Porphyrin 30 was extracted with CH2Cl2 (3 × 30 ml) until the
aqueous phase became colorless. The combined extracts were
dried with Na2SO4 and evaporated to dryness on a rotary evap-
orator. Chromatography and elution with dichloromethane–
n-hexane (1 : 3, v/v) on silica gel gave 32 mg (57%) of porphyrin
30 as purple crystals, mp 234 ЊC (from CH2Cl2–CH3OH); λmax
(CH2Cl2)/nm (log ε/dm3 molϪ1 cmϪ1 5.22), 518 (3.91), 557
(3.68), 594 (3.43), 650 (3.21); δH (250 MHz; CDCl3; SiMe4)
Ϫ2.60 (2 H, s, NH), 1.15 (3 H, t, J 7.8, CH3CH2CH2CH2), 1.80
(2 H, sext, J 7.8, CH3CH2CH2CH2), 2.05 (2 H, quint, J 7.8
SCH2CH2CH2CH2), 2.30 (3 H, s, CH3COS), 2.45–2.75 (4 H, m,
CH3CH2CH2CH2, SCH2CH2CH2CH2), 3.05 (2 H, t, J 7.8,
SCH2CH2CH2CH2), 4.95 (4 H, m, SCH2CH2CH2CH2,
CH3CH2CH2CH2), 7.75–7.85, 8.20–8.30 (10 H, m, HPh), 8.85–
8.95 (4 H, m, 4 × Hβ-pyrrole), 9.35–9.45 (4 H, m, 4 × Hβ-pyrrole);
m/z (EI, 80 eV) 648.2965 (Mϩ, 100%. C42H40N4OS requires M,
648.2923), 605 (Mϩ Ϫ CH3CH2CH2, 30), 574 [(M ϩ H)ϩ Ϫ
SCOCH3, 11], 531 [(M ϩ H)ϩ Ϫ CH3CH2CH2 Ϫ SCOCH3, 36],
517 [(M ϩ H)ϩ Ϫ CH3 Ϫ C5H9SO, 12].
20 O. Wennerstrom, H. Ericsson, I. Raston, S. Svensson and W.
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Acknowledgements
This work was supported by grants from the Deutsche
Forschungsgemeinschaft (Se543/5-1 and Heisenberg fellowship
/3-2) and the Fonds der Chemischen Industrie. We also acknow-
ledge a gift of chemicals from Schering AG (Berlin).
42 G. Li and J.-H. Fuhrhop, unpublished results, Institut für Chemie,
Freie Universität Berlin.
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J. Chem. Soc., Perkin Trans. 1, 2001, 1030–1038