Novel and rapid synthetic routes to A3B- and AB3-type 21-thiaporphyrins and their use in the construction of unsymmetrical covalent and non-covalent porphyrin arrays

Article abstract of DOI:10.1002/ejoc.200300764

Novel and very simple methods were developed for the synthesis of 21-thiaporphyrins having both one functional group (A₃B) and three functional groups (AB₃). These A₃B- and AB ₃-type 21-thiaporphyrin building bl

Full text of DOI:10.1002/ejoc.200300764

SHORT COMMUNICATION
Novel and Rapid Synthetic Routes to A3B- and AB3-Type 21-Thiaporphyrins
and Their Use in the Construction of Unsymmetrical Covalent and Non-
Covalent Porphyrin Arrays
Iti Gupta,[a] Neeraj Agarwal,[a] and Mangalampalli Ravikanth*[a]
Keywords: Porphyrins / Synthesis design / Macrocycles / Sulfur
Novel and very simple methods were developed for the syn-
thesis of 21-thiaporphyrins having both one functional group
(A3B) and three functional groups (AB3). These A3B- and
AB3-type 21-thiaporphyrin building blocks were used to syn-
thesize both covalently and non-covalently linked unsym-
metrical porphyrin arrays containing N3S and N4 porphyrin
cores.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
that a thiophene mono-ol can be used as a precursor for
the synthesis of N3S porphyrins. Using this method, any
desired 21-thiaporphyrin can be synthesized in reasonable
quantity in one step. It is applicable to the synthesis of 21-
thiaporphyrins having various functional groups, which can
be used further to synthesize complex 21-thiaporphyrin-
based systems. We have also developed an alternative high-
yielding method, using the previously unreported unsym-
metrical thiophene diols 10؊17 for the synthesis of the
A3B-type 21-thiaporphyrins 18؊25. We also report the use
of A3B- and AB3-type 21-thiaporphyrin building blocks in
the synthesis of covalent and non-covalent unsymmetrical
porphyrin arrays containing two different porphyrin cores.
21-Thiaporphyrins (with an N3S core) resulting from the
replacement of one of the pyrrole nitrogen atoms of regular
porphyrins (with an N4 core) exhibit unique properties both
in terms of aromatic character and their ability to stabilize
metals in unusual oxidation states.[1] These porphyrins can
be synthesized by following a well-established synthetic
strategy (shown in Scheme 1), in which 2,5-bis(α-aryl-α-
hydroxymethyl)thiophene, a symmetrical thiophene diol, is
the key precursor. According to this method, the conden-
sation of one equivalent of thiophene diol with two equiva-
lents of aldehyde and three equivalents of pyrrole under
mild acid conditions followed by oxidation with DDQ re-
sulted in the formation of an N3S porphyrin. However, only
the cis-A2B2 and A4 types of N3S porphyrins can be synthe-
sized by this method.[1,2]
Results and Discussion
The desired thiophene mono-ols were prepared by treat-
ing thiophene with 1.2 equivalents of nBuLi, followed by
1.2 equivalents of the appropriate aldehyde in THF at 0 °C.
TLC analysis of the reaction mixture showed the formation
of the mono-ol along with small amounts of unchanged
aldehyde and thiophene. The crude mixture was subjected
to silica gel column chromatography, to give the pure thio-
phene mono-ols as brownish-white solids in 65Ϫ70% yield.
The A3B- and AB3-type N3S porphyrins 1؊9 were syn-
thesized by condensing two equivalents of the appropriate
thiophene mono-ol with two equivalents of aldehyde and
three equivalents of pyrrole in propionic acid (Scheme 2).
We anticipated the formation of 21-thiacorrole in this reac-
tion, but none was observed.[5] We also varied the number
of equivalents of thiophene mono-ol, keeping the amounts
of aldehyde and pyrrole constant. When only one equiva-
lent (rather than two equivalents) of thiophene mono-ol
was used, we observed the formation of only the N4 por-
phyrin. No corrole was formed even when more than two
The chemistry of N3S porphyrins is currently in its in-
fancy, due to the lack of availability of suitable 21-thiapor-
phyrin building blocks. Porphyrins with one functional
group are potential building blocks for the development of
novel porphyrin systems.[3] However, synthesizing porphy-
rins with one functional group involves multi-step synthesis
and tedious purification procedures.[4] To the best of our
knowledge, there is no one-step method available for the
synthesis of A3B and AB3 type 21-thiaporphyrins. In this
communication, we report for the first time the synthesis of
A3B- and AB3-type 21-thiaporphyrins 1؊9 by using 2-(α-
aryl-α-hydroxymethyl)thiophene(thiophene mono-ol) in place
of a symmetrical thiophene diol. This method is simple; fur-
thermore, there have been no reports so far that have shown
[a]
Department of Chemistry, Indian Institute of Technology,
Powai, Mumbai 400076, India
E-mail: ravikanth@chem.iitb.ac.in
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2004, 1693Ϫ1697
DOI: 10.1002/ejoc.200300764
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1693

I. Gupta, N. Agarwal, M. Ravikanth
SHORT COMMUNICATION
Scheme 1. A general literature procedure for the synthesis of 21-thiaporphyrins
equivalents of thiophene mono-ol was used, but the yields phene mono-ols can be synthesized in multigram quantity,
of N3S porphyrins were reduced drastically. and the chromatographic separation of the N3S from the N4
Therefore, we used two equivalents of thiophene mono- porphyrins is simple and straightforward. Characterization
ol to prepare the A3B- and AB3-type N3S porphyrins 1؊9. data (NMR, mass, UV/vis and fluorescence spectra) for the
The crude mixtures were purified by double silica gel col- A3B- and AB3-type N3S porphyrins 1؊9 is given in the
umn chromatography, to afford the desired products in Supporting Information.
yields of 2Ϫ7%. Although the yields of porphyrin are low,
A3B-type 21-thiaporphyrins were also synthesized from
this method presents the first facile preparation of mono- the unsymmetrical thiophene diols 10؊17 (Scheme 3).
and tri-functionalized N3S porphyrins from one precursor. These novel diols were prepared by treating 2-[α-hydroxy-
The desired N3S porphyrin can be prepared easily on a 100- α-phenyl]methylthiophene (26) with two equivalents of
mg scale in a one-pot reaction, since the precursor thio- nBuLi, followed by 1.2 equivalents of the desired aromatic
Scheme 2. Synthesis of A3B- and AB3-type 21-thiaporphyrins from thiophene mono-ols
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Eur. J. Org. Chem. 2004, 1693Ϫ1697

Novel and Rapid Synthetic Routes to A3B- and AB3-Type 21-Thiaporphyrins
SHORT COMMUNICATION
Scheme 3. Synthesis of A3B-type 21-thiaporphyrins from unsymmetric thiophene diols
Scheme 4. Synthesis of the unsymmetrical covalently linked dimer 27
Eur. J. Org. Chem. 2004, 1693Ϫ1697
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I. Gupta, N. Agarwal, M. Ravikanth
SHORT COMMUNICATION
aldehyde in THF at 0 °C. TLC analysis of the crude reac- nylporphyrin (H2TPP), the desired A3B-type 21-thiapor-
tion mixture indicated the formation of the diol, along with phyrin and a mixture of cis- and trans-A2B2-type 21,23-
unchanged aldehyde and the thiophene mono-ol 26. Purifi- dithiaporphyrins. The crude mixture was purified by silica
cation of the crude reaction mixture by silica gel column gel column chromatography; the desired 21-thiaporphyrin
chromatography afforded the pure unsymmetrical diols always eluted as the second chromatographic band, and the
10؊17 in 26Ϫ45% yield.
21,23-dithiaporphyrins eluted together in the last band. The
To optimize the reaction conditions for the synthesis of 21-thiaporphyrins (with small impurities of the other por-
unsymmetrical thiophene diols, we varied the number of phyrins) were subjected to a second silica gel column chro-
equivalents of nBuLi; the best diol yields were obtained matography, to afford the pure 21-thiaporphyrins 18Ϫ25 in
with two equivalents of nBuLi. Diol yields were much lower 2Ϫ15% yield (Scheme 3). No attempts were made to separ-
with one equivalent of nBuLi, and were not much improved ate the cis- and trans-21,23-dithiaporphyrins. The identities
when we used more than two equivalents of nBuLi. It seems of the 21-thiaporphyrins 18؊25 were confirmed by spec-
likely that at least two equivalents of nBuLi are needed for troscopy (see Supporting Information).
this reaction because the hydroxyl group of thiophene
We sought to broaden the scope of A3B- and AB3-type
mono-ol gets lithiated during the reaction. Although the N3S porphyrin building blocks by constructing covalent
yields of diols are moderate, the preparation of large quan- and non-covalent unsymmetrical porphyrin arrays contain-
tities of unsymmetrical diols is simple by this method. Fur- ing two different porphyrin cores. Such unsymmetrical por-
thermore, the desired mono-functional group of N3S por- phyrin arrays are suitable models for mimicking the energy-
phyrins can be incorporated easily at the thiophene diol transfer and electron-transfer processes of photosynthesis,
stage.
because of the feasibility of selective excitation of one por-
To synthesize the 21-thiaporphyrins, one equivalent of phyrin unit and energy transfer to another porphyrin unit.
the appropriate unsymmetrical diol was condensed with Recently, several unsymmetrical porphyrin dimers (such as
two equivalents of an aromatic aldehyde and three equiva- porphyrinϪchlorin and porphyrinϪ corrole) have been syn-
lents of pyrrole under standard porphyrin-forming con- thesized in order to obtain long-lived charge-transfer
ditions (Scheme 3). The condensation resulted in the forma- states.[6] Interestingly, there is only one report on unsym-
tion of a mixture of four porphyrins; 5,10,15,20-tetraphe- metrical arrays containing N3S and N4 porphyrin cores.[7]
Scheme 5. Synthesis of the unsymmetrical non-covalently linked tetramer 28
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Eur. J. Org. Chem. 2004, 1693Ϫ1697

Novel and Rapid Synthetic Routes to A3B- and AB3-Type 21-Thiaporphyrins
SHORT COMMUNICATION
Therefore, we decided to synthesize the covalently linked shown that mono- and tri-functionalized N3S porphyrin
diarylethyne-bridged unsymmetrical porphyrin dimer 27 building blocks can be used to construct covalent and non-
containing one N3S and one N4 porphyrin core. Coupling covalent unsymmetrical porphyrin arrays containing both
of the deprotected (terminal alkyne) form of 1 with the zin- N3S and N4 porphyrin units. Preliminary investigations
c() complex of 5,10,15-tri(mesityl)-20-(4-iodophenyl)por- indicate that A3B- and AB3-type N3O porphyrins can also
phyrin in toluene/triethylamine at 35 °C in the presence of be synthesized using the mono-ol or unsymmetrical diol
Pd2(dba)3 and AsPh3, followed by column chromatography, methods reported in this paper.
gave 27 in 67% yield (Scheme 4) (see Supporting Infor-
mation for spectroscopic data).
To demonstrate energy transfer in the porphyrin dimer
Acknowledgments
M. R. thanks the Department of Atomic Energy (Government of
27, we recorded the emission spectrum at an excitation India) for funding the project.
wavelength of 550 nm (where the Zn derivative of the N4
[1]
porphyrin unit absorbs strongly). The emission spectrum of
27 showed bands due mainly to the N3S unit. The emission
bands of the Zn derivative of the N4 unit in 27 were
quenched to great extent, indicating that there was an ef-
ficient energy transfer from the Zn derivative of N4 unit to
the N3S unit. Similar observations have been made for
ethyne-bridged porphyrin arrays.[8]
To demonstrate the use of AB3-type N3S porphyrins, the
non-covalently[9] linked unsymmetrical porphyrin tetramer
28 containing one N3S unit and three N4 units was synthe-
sized (Scheme 5). The N3S porphyrin 8 was treated with
3.2 equivalents of RuTPP(CO)(EtOH) in toluene at reflux
overnight, to give the porphyrin tetramer 28 in 17% yield,
after silica gel column chromatography and size exclusion
chromatography.
L. Latos-Grazynski, in The Porphyrin Handbook (Eds.: K. M.
Kadish, K. M. Smith, R. Guilard), Academic Press, New York,
2000, Vol 2, p. 361Ϫ416, and references cited therein.
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Conclusion
The method reported in this communication gives access
for the first time to A3B- and AB3-type N3S porphyrin
building blocks containing functional groups at the meso
carbon atoms. A3B-type 21-thiaporphyrins were also syn-
thesized in improved yield by using unsymmetrical thio-
phene diols. The methods reported are simple, versatile and
applicable to all N3S porphyrins with either one or three
functional groups at the meso positions. We have also
[7]
R. P. Pandian, T. K. Chandrashekar, Inorg. Chem. 1994, 33,
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Received December 6, 2003
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