Complementary Syntheses Giving Access to a Full Suite of Differentially Substituted Phthalocyanine-Porphyrin Hybrids

Article abstract of DOI:10.1002/anie.202016596

Phthalocyanines and porphyrins are often the scaffolds of choice for use in widespread applications. Synthetic advances allow bespoke derivatives to be made, tailoring their properties. The selective synthesis of unsymmetrical systems, particularly phthalocyanines, has remained a significant unmet challenge. Porphyrin-phthalocyanine hybrids offer the potential to combine the favorable features of both parent structures, but again synthetic strategies are poorly developed. Here we demonstrate strategies that give straightforward, controlled access to differentially substituted meso-aryl-tetrabenzotriazaporphyrins by reaction between an aryl-aminoisoindolene (A) initiator and a complementary phthalonitrile (B). The choice of precursors and reaction conditions allows selective preparation of 1:3 Ar-ABBB and, uniquely, 2:2 Ar-ABBA functionalized hybrids.

Full text of DOI:10.1002/anie.202016596

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How to cite: Angew. Chem. Int. Ed. 2021, 60, 7632–7636
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Phthalocyanine Hybrids Very Important Paper
Complementary Syntheses Giving Access to a Full Suite of
Differentially Substituted Phthalocyanine-Porphyrin Hybrids
Faeza Alkorbi, Alejandro Dꢀaz-Moscoso,* Jacob Gretton, Isabelle Chambrier,
Graham J. Tizzard, Simon J. Coles, David L. Hughes, and Andrew N. Cammidge*
Abstract: Phthalocyanines and porphyrins are often the
scaffolds of choice for use in widespread applications.
Synthetic advances allow bespoke derivatives to be made,
tailoring their properties. The selective synthesis of unsym-
metrical systems, particularly phthalocyanines, has remained
a
significant unmet challenge. Porphyrin-phthalocyanine
hybrids offer the potential to combine the favorable features
of both parent structures, but again synthetic strategies are
poorly developed. Here we demonstrate strategies that give
straightforward, controlled access to differentially substituted
meso-aryl-tetrabenzotriazaporphyrins by reaction between an
aryl-aminoisoindolene (A) initiator and a complementary
phthalonitrile (B). The choice of precursors and reaction
conditions allows selective preparation of 1:3 Ar-ABBB and,
uniquely, 2:2 Ar-ABBA functionalized hybrids.
Figure 1. Molecular structures of phthalocyanine (Pc), porphyrin, and
their hybrids.
Dentꢀs original seminal series of papers in the 1930s.[2] The
hybrids possess complementary and superior characteristics
to their parents, bridging the Pc and porphyrin systems and
allowing precise tuning of their properties for specific
applications.[3] However, scarce synthetic availability of
hybrid materials has limited the study of their scope. Synthetic
procedures are mostly derived from the original methods
from the 1930s, employing a carbon-based nucleophile to
initiate reaction with a phthalonitrile (Pn) co-reactant.[3]
These strategies generally have poor yields and selectivity,
leading most investigations to focus on hybrid structures
bearing only simple or no substituents on the macrocycle or
the meso-carbon position. Interest in functional hybrids has
been growing recently. We[4] and others[5] have refined C-
nucleophile procedures, extending studies to include sub-
stituents at the Pn and meso-sites, and controlling product
distribution through stoichiometry and reaction conditions.
Access to the full range of (separable and processable)
hybrids has further revealed their enhanced behavior as
device components.[6] More innovative synthetic inventions
have recently started to redefine the field, charting the first
steps towards controlled synthesis of di-[7] and triaza[8] hybrids.
Our synthesis of meso-aryl tetrabenzotriazaporphyrins
(TBTAPs) provided, for the first time, scalable access to these
hybrid structures functionalized at the meso position.[8] Based
on the proposed mechanism, we recognized that our synthetic
protocol had the potential to introduce different benzo
fragments (A and B) around the macrocycle in a regiospecific
manner, in addition to the meso functionality (Scheme 1).
Such structural control has been long pursued in normal Pc
chemistry with only limited advances.[9] In the hybrid series,
success would deliver materials that are unavailable in
general Pc chemistry, but also offer the opportunity to further
exploit the possibilities provided by the meso-substituent.
P
hthalocyanines (Pc) and porphyrins are among the most
widely studied functional organic materials. Porphyrin deriv-
atives are widespread in nature and perform crucial life-
sustaining functions. Synthetic porphyrins and phthalocya-
nines are diversely used across chemical, biological and other
advanced technology fields. Their popularity stems from
a combination of general molecular properties such as light
absorption and stability (a direct consequence of their
extended aromaticity), and the ability to tune their physico-
chemical properties through a number of complementary
strategies such as metal ion incorporation, perturbation of the
core, and/or introduction of appropriate substituents.[1]
Hybrid structures, intermediate between Pc and porphyr-
ins (Figure 1), were recognized as important scaffolds during
the birth of Pc chemistry, and were discussed in Linsteadꢀs and
[*] Dr. F. Alkorbi, Dr. A. Dꢀaz-Moscoso, J. Gretton, Dr. I. Chambrier,
Dr. D. L. Hughes, Prof. A. N. Cammidge
School of Chemistry, University of East Anglia
Norwich Research Park, Norwich NR4 7TJ (UK)
E-mail: a.diaz.moscoso@csic.es
a.cammidge@uea.ac.uk
Dr. G. J. Tizzard, Prof. S. J. Coles
UK National Crystallography Service
Chemistry University of Southampton
Southampton SO17 1BJ (UK)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202016596.
ꢁ 2021 The Authors. Angewandte Chemie International Edition
published by Wiley-VCH GmbH. This is an open access article under
the terms of the Creative Commons Attribution License, which
permits use, distribution and reproduction in any medium, provided
the original work is properly cited.
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Scheme 1. The synthesis of meso-aryl TBTAPs from reaction between
aminoisoindolene initiator[10] (providing the A ring) and phthalonitrile
(providing the B ring).[8]
Our first attempts to investigate the potential to introduce
substituents onto TBTAP hybrids employed commercially
available 4-tert-butylphthalonitrile,[11] a widely used precursor
in Pc chemistry that imparts good solubility to the final
macrocycles. According to our proposed mechanism for this
reaction, we expected to obtain a 1:3 peripheral substitution
pattern (Scheme 1). However, reaction with our aminoiso-
indolene co-reactant under the conditions optimized for
TBTAP synthesis produced a complex mixture of products.
Therefore, we shifted our strategy to symmetrically disub-
stituted Pns in order to simplify characterization and analysis.
Several examples leading to peripheral substitution were
chosen, avoiding steric clashes with substituents on the new
meso-carbon.[4,8] Initial investigations used the Pn derivative
4, derived from tetramethyl tetralin, synthesized from ben-
zene by Friedel–Crafts alkylation,[12] bromination,[12,13] and
cyanation.[13b,14] An initial test reaction was performed using
Pn 4 alone under the reaction conditions (MgBr2 in diglyme at
reflux) to ensure that Pc formation did not occur directly at
a competitive rate, as already shown for the unsubstituted
phthalonitrile.[8] TBTAP hybrid formation was then
attempted following the previously optimized procedure,
essentially by slowly adding aminoisoindolene “initiator” 6 to
a mixture of Pn 4 (3–5 equiv) and MgBr2 in refluxing diglyme
(Scheme 2).
Scheme 2. Hybrid synthesis from a substituted phthalonitrile, uncover-
ing an alternative pathway leading to Ar-ABBA TBTAP hybrid (Ar=4-
methoxyphenyl); crystal structures of hybrids 7 and 8 (solvent mole-
cules omitted for clarity).
by a retro-Friedel Crafts (de)alkylation under the reaction
conditions. Although unlikely, this possibility was eliminated
in a test experiment whereby Ar-ABBB hybrid 7 was isolated
and subjected to the reaction conditions (MgBr2 in refluxing
diglyme). No reaction took place and it was therefore clear
that the Ar-ABBA hybrid 8 results from an alternative,
dominant reaction sequence.
The most likely mechanism leading to hybrid 8 is shown in
Scheme 3. It has the same first step as the mechanism
proposed in Scheme 1, involving the initial addition of amino-
isoindolene to Pn rendering an AB subunit (like all inter-
mediates in Schemes 1 and 3, this is expected to be complexed
to magnesium ion that is omitted for clarity), but the
pathways then diverge. Addition of this intermediate to
a second Pn eventually leads to the 1:3 ABBB hybrid but this
appears to be a slow step. Self-condensation of two AB
intermediates (through loss of NH3) likely dominates, leading
then to cyclization and aromatization via loss of a benzyl
Macrocycle formation proceeded smoothly but two dis-
tinct hybrid products were isolated. The first product was
characterized as the expected Ar-ABBB (1:3) TBTAP hybrid
7 that likely results from the proposed sequential addition of
aminoisoindolene to 3 Pn units, followed by cyclization and
aromatization (Scheme 1). However, this component was the
minor product. The dominant product was identified as the
unique Ar-ABBA (2:2) TBTAP hybrid 8, produced as a single
regioisomer. It is theoretically possible that this unexpected
product is an artifact produced from the Ar-ABBB hybrid 7
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Scheme 3. Proposed mechanistic pathway leading to Ar-ABBA TBTAP
hybrids.
fragment. Of course, both pathways lead to the same product
if unsubstituted Pn is employed as co-reactant. Further
support for this proposed sequence was provided by the
results observed from changing the reaction stoichiometry
and protocol. Switching to 2:2 aminoisoindolene:Pn stoichi-
ometry and/or increasing the rate of addition (including
reactions where all starting materials are mixed prior to
heating) increased the relative proportion of Ar-ABBA 2:2
TBTAP hybrid in the isolated macrocyclic product mixture.
However, in such reactions the overall yield of both hybrids is
reduced because self-condensation of aminoisoindolene starts
to compete with addition to Pn.
The reaction, therefore, offers potential to produce two
separate classes of TBTAP hybrids, both largely unprece-
dented. Two further series of experiments were carried out to
demonstrate the scope. Firstly, alternative Pn derivatives were
employed. 2,3-Naphthalonitrile 9 is commercially available
and underwent macrocyclization with aminoisoindolene 6
(Scheme 4). Naphthalonitrile 9 appears to be more reactive
than Pn 4 and the reaction is complicated by competing
formation of naphthalocyanine (MgNPc). Nevertheless, Ar-
ABBA TBTAP hybrid 10 was formed and isolated as the
dominant hybrid once again. As expected, p-extended mixed
hybrid (C2v symmetry) shows a split, red-shifted Q-band
absorption at 709 and 681 nm.
The second class of Pn selected were the 4,5-dialkoxy
derivatives 12. In Pc chemistry these Pns are widely
employed.[15] They are known to be relatively easy to prepare
at scale, and within the Pc series the alkoxy substituents
modify the electronic, solubility and self-assembly properties.
The synthesis of the Pns and hybrids is shown in Scheme 4.
Cyanation[14] of dibromobenzene precursors 11 was carefully
controlled to prevent excessive Pc formation under the
reaction conditions. Stopping the reaction before completion
resulted in a mixture of mono- (13) and dinitriles (12), but was
a desirable outcome because we required the bromobenzoni-
trile derivatives for subsequent experiments (vide infra).
Scheme 4. The synthesis of naphthyl (10, top) and tetraalkoxy/phenoxy
(14, bottom) Ar-ABBA TBTAP hybrids.
Dialkoxyphthalonitriles 12a–c were first shown not to
react to form MgPcs in refluxing diglyme in the presence of
MgBr2, allowing our standard reaction conditions to be
employed for hybrid synthesis. Reaction of dimethoxy-Pn
12a with aminoisoindolene, however, failed to produce
significant quantities of macrocycle (hybrid or Pc) and instead
yielded significant quantities of condensation product 15 (plus
unreacted Pn), presumably due to solubility issues. Longer
chain dihexyloxy- and didecyloxy-Pn (12b and 12c, and
diphenoxy-Pn (12d, prepared from 4,5-dichlorophthaloni-
trile), reacted smoothly, however, using the single-operation
procedure whereby a mixture of aminoisoindolene, Pn and
MgBr2 were heated directly in diglyme. Once again, the
dominant macrocyclic product isolated from these reactions
was the Ar-ABBA TBTAP. Separation proved to be challeng-
ing, but the pure Ar-ABBA hybrids 14b–d could be isolated
and characterized.
In all experiments described so far, an identical amino-
isoindolene reactant was employed. Aminoisoindolene 6 has
no substituents on the indolene fragment so delivers unsub-
stituted rings (“A”) into the Ar-ABBA hybrids. Alternative
substitution patterns become available if the indolene frag-
ment is itself functionalized, and in such cases the syntheses
will deliver hybrids with substituents on the rings adjacent to
the meso-Ar. This complementary sequence has been dem-
onstrated using the precursor bromobenzonitriles prepared as
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effectively completes the series and demonstrates that the
full suite of hybrid structures can be accessed at will
(Figure 2).
In conclusion, two pathways are proposed for the syn-
thesis of an important class of functionalized phthalocyanine-
porphyrin hybrids (TBTAPs). The materials are novel in their
own right, but more importantly, the syntheses offer control
and variation over structural and substituent modifications,
a goal not yet achieved even within the extensively inves-
tigated chemistry of the parent phthalocyanines. Differential
substitution can be controlled leading to a full range of
complementary functionality, at the meso-carbon itself (ideal
for attachment of these functional antennae[18] molecules) and
at one or both of the adjacent or opposite benzo sites to the
meso-carbon (controlling molecular electronic character but
also permitting design of super- and supramolecular func-
tional assemblies[19]).
Scheme 5. Complementary synthesis of TBTAP hybrids to introduce
substituents adjacent to the meso-carbon.
part of the earlier Pn synthesis, and is indeed a powerful
approach (Scheme 5).
Bromobenzonitriles 13a–c were converted to the corre-
sponding amidine hydrochloride salts (16a–c) by treatment
with LiHDMS followed by HCl workup.[16] The amidines
were converted to aminoisoindolenes (17a–c) by reaction
with 4-methoxyphenyl acetylene under palladium catalysis.[17]
In accordance with our previous results, reaction of these
substituted aminoisoindolenes with phthalonitrile in a single
operation led to formation of the complementary (meso-
adjacent) Ar-ABBA TBTAP hybrids 18a–c as the dominant
macrocyclic products, alongside traces of the 1:3 Ar-ABBB
TBTAP and phthalocyanine (identified by MALDI-MS). Ar-
ABBA hybrids 18a–c were isolated pure by chromatography
and recrystallization. In the case of the methoxy-substituted
TBTAP 18a, crystals suitable for X-ray diffraction were
obtained and the crystal structure is also shown in Scheme 5.
Unlike the dialkoxy derivatives, aminoisoindolene 19
(prepared from bromobenzonitrile 5 by the same reaction
sequence described for 17) is freely soluble in diglyme
enabling the reaction to be performed by slow addition
(syringe pump) to phthalonitrile and therefore allowing the
sequential addition mechanism to compete more effectively.
Under these conditions the 1:3 TBTAP hybrid 21 could
indeed also be isolated, although it remains a minor compo-
nent compared to the Ar-ABBA 2:2 hybrid 20. This
Figure 2. Suite of TBTAP hybrids that can now be synthesized control-
ling the meso-aryl, adjacent, and opposite benzo-substituents.
Acknowledgements
Support from Najran University, Saudi Arabia (F.A.), UEA
(I.C.), EU (A.D.M.) and EPSRC (the National Crystallog-
raphy and Mass Spectrometry Services) are gratefully
acknowledged.
Conflict of interest
The authors declare no conflict of interest.
Keywords: hybrids · phthalocyanines · porphyrinoids · selectivity
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Manuscript received: December 14, 2020
Accepted manuscript online: January 11, 2021
Version of record online: March 1, 2021
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