Improved syntheses of meso-aryl tetrabenzotriazaporphyrins (TBTAPs)

Article abstract of DOI:10.1016/j.tet.2014.06.086

New tetrabenzotriazaporphyrins are reported that are functionalised at the meso-position. The derivatives functionalised with meso-bromophenyl substituents are synthesised using an improved variation on the traditional reaction between phthalonitriles and Grignard reagents. For all other new derivatives, a modern protocol is employed that gives convenient access to these challenging materials by template co-macrocyclisation between phthalonitriles and aryl-aminoisoindoline derivatives like 15. The newly developed procedure allows design and synthesis of elaborate, functional composites and this is demonstrated by synthesis of meso-pyrenylTBTAP 24, a linked double chromophore in which the two complementary units lie perpendicular to each other and therefore have minimal ground state interaction.

Full text of DOI:10.1016/j.tet.2014.06.086

Tetrahedron 70 (2014) 7370e7379
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Improved syntheses of meso-aryl tetrabenzotriazaporphyrins
(TBTAPs)
Nuha Alharbi a, Alejandro Díaz-Moscoso a, Graham J. Tizzard b, Simon J. Coles b,
,
Michael J. Cook a, Andrew N. Cammidge a
*
a School of Chemistry, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK
b UK National Crystallography Service, School of Chemistry, University of Southampton, Southampton SO17 1BJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 May 2014
Received in revised form 12 June 2014
Accepted 20 June 2014
Available online 26 June 2014
New tetrabenzotriazaporphyrins are reported that are functionalised at the meso-position. The de-
rivatives functionalised with meso-bromophenyl substituents are synthesised using an improved varia-
tion on the traditional reaction between phthalonitriles and Grignard reagents. For all other new
derivatives, a modern protocol is employed that gives convenient access to these challenging materials
by template co-macrocyclisation between phthalonitriles and aryl-aminoisoindoline derivatives like 15.
The newly developed procedure allows design and synthesis of elaborate, functional composites and this
is demonstrated by synthesis of meso-pyrenylTBTAP 24, a linked double chromophore in which the two
complementary units lie perpendicular to each other and therefore have minimal ground state
interaction.
Keywords:
Phthalocyanines
Porphyrins
Heterocycles
Synthesis
Ó 2014 Elsevier Ltd. All rights reserved.
Hybrids
Pyrene
1. Introduction
properties of both Pcs and TBPs they have the potential to offer
advantages over both. This has been nicely illustrated by Borisov
The tetrabenzotriazaporphyrin (TBTAP) ring system is one of
four types of macrocycle Fig. 1 that can be regarded as hybrids of
the much more familiar phthalocyanine (Pc) and tetrabenzopor-
phyrin (TBP) structures. Molecular orbital calculations for all six
molecules,1,2 the most recent of which utilise TD-DFT methods,2
show their close inter-relationships but also predict how system-
atic replacement of the four aza links of the Pc structure by methine
carbon atoms leads to an increase in the HOMOeLUMO energy
differences. Thus each hybrid structure exhibits a visible region
absorption (Q-band) that lies between those of the Pc and TBP
structures: that for TBTAP, the molecular type that is the subject of
this paper, is the least hypsochromically shifted from that of the Pc
ring.
Research into the chemistry, properties, and applications of Pcs
in particular and, to a lesser extent, TBPs have provided the basis of
many thousands of papers and these have been discussed in nu-
merous articles and reviews.3 In contrast, TBTAP compounds, as
well as examples of the other hybrids shown in Fig 1, have received
much less attention. However, by possessing aspects of the
and co-workers.4 Their research into applications of oxygen
quenching of phosphorescence showed that while Pt and Pd met-
allated Pcs, denoted as PtPc and PdPc, possess remarkable chemical,
thermal and photostability they are only weak emitters of phos-
phorescence. At the other extreme Pt and PdTBPs show strong
emission but poor photostability. In contrast, examples of Pt and
PdTBTAPs exhibit both excellent photostability and very satisfac-
tory emission.
As with the Pc and TBP ring system, the TBTAP structure can
provide a diversity of derivatives by varying the ion/metalloid at
the centre of the macrocycle and through the incorporation of
substituents at various points on the macrocycle and, where ap-
propriate, provision of ligands at the metal/metalloid centre.
However, from the synthetic chemistry viewpoint, the more sig-
nificant challenge is the incorporation of the single bridging (meso)
carbon into the central core and exploiting this as a point for added
functionalisation. It is perhaps this issue that has inhibited the
potential of the TBTAP series of macrocycles to be fully realised at
this timedindeed there are fewer than 50 reports on the synthesis
of members of the series.
Unsurprisingly, the majority of reported syntheses have fo-
cussed on intervention into the cyclotetramerisation of a typical Pc
precursor such as phthalonitrile. Pc synthesis is normally
* Corresponding author. Tel.: þ44 (0)1603 592011; fax: þ44 (0)1603 592003;
e-mail address: a.cammidge@uea.ac.uk (A.N. Cammidge).
http://dx.doi.org/10.1016/j.tet.2014.06.086
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

N. Alharbi et al. / Tetrahedron 70 (2014) 7370e7379
7371
Shortly after, Linstead’s group obtained MgTBTAP by reacting
phthalonitrile with either the Grignard reagent MeMgI or methyl
lithium to provide the meso-carbon, following a two-stage pro-
cedure, initially reacting in cold ether solution followed by heating
in a high boiling solvent.8 Acidic conditions removed the magne-
sium to allow other metal ions, eg copper, zinc, lithium, and iron to
be incorporated. Following the same approach several decades
later, Hoffman and co-workers added NiTBTAP to this series9 and
Antunes and Nyokong the dihydroxyphosphorus analogue.10 Dur-
ing the 1960s Solov’ev and co-workers obtained the Mg and Cd
metallated TBTAPs from mixtures of phthalimidineacetic acid and
phthalonitrile or o-cyanobenzamide (in the presence of cadmium
acetate in the latter case) and found that other hybrid molecules
were also formed as conditions were varied.1a,11
Alternative precursors to TBTAPs were published in the late
1980s and early 1990s. Thus nitrophthalimidine as a meso-carbon
provider was described in a Bayer patent12 whilst Kospranenkov
and co-workers13 and Kospranenkov, Luk’yanets and co-workers14
employed adducts from reactions of tert-butyl substituted phtha-
lamide and iminoisoindoline derivatives with malonic acid in the
presence of zinc acetate. Each benzenoid ring was thus substituted
with a t-Bu group. Berezin and co-workers subsequently refined
the purification of the metal-free analogue, (t-Bu)4-H2TBTAP.15
At about the same time, Leznoff and McKeown reinvestigated
the Linstead method, added some refinements to conditions, and
undertook reactions using a range of alkyl Grignard reagents with
phthalonitrile and substituted phthalonitriles.16,17 As an example,
hexadecylmagnesium chloride was reacted with neo-pentylox-
yphthalonitrile to give (neo-PeO)4-meso-n-C15H31eH2TBTAP (after
demetallation) in 13% yield, Scheme 3. The reaction also produced
significant quantities of the corresponding Pc as a by-product along
with trace quantities of the TBDAPs. The use of benzyl magnesium
bromide provided a phenyl group at the meso-position of the TBTAP
ring. Ivanova and co-workers later treated tert-butylphthalonitrile
with MeMgI to form (t-Bu)4-MgTBTAP. They also observed the co-
formation of the Mg metallated Pc analogue.18
Fig. 1. Structures of types of tetrabenzofused 18
p
electron macrocycles. M¼H,H,
a metal ion or metalloid element. Tetrabenzotriazaporphyrin, TBTAP; cis- and trans-
tetrabenzodiazaporphyrins, TBDAPs; tetrabenzomonoazaporphyrin, TBMAP; phthalo-
cyanine and tetrabenzoporphyrin.
undertaken using either strongly basic conditions or by heating in
the presence of a metal ion or metal oxide, which serves to act as
a template and, which also mediates a redox process that ultimately
provides the Pc core. Thus the majority of syntheses of TBTAP de-
rivatives have exploited the use of Pc precursors but with the in-
clusion of a reagent, typically containing a potential ‘nucleophilic’
carbon, to provide the meso-carbon bridge. This is typified in the
first synthesis of a TBTAP derivative by Dent in 1938,5 a paper
published a few months after Helberger6 reported the first example
of a tetrabenzomonoazaporphyrin, TDMAP, and some 4 years after
the first of the pioneering papers on Pcs by Linstead and co-
workers.7 Dent obtained copper metallated TBTAP, i.e., CuTBTAP, by
reacting phthalonitrile with either phthalimidineacetic acid or
methylenephthalimidine as providers of the meso-carbon. The re-
action was carried out in the presence of a copper salt in chlor-
onaphthalene at elevated temperatures (Scheme 1).
Scheme 2. Illustrative use of a long chain Grignard reagent to introduce a long chain
(minus 1 carbon) at the TBTAP meso-site.16
Further reagents that donate the meso-carbon have been re-
ported over the last 10 years or so. Thus Galanin and co-
Scheme 1. The early syntheses of CuTBTAP employing mixed cyclisations between
a phthalonitrile and methylenephthalimidine or its precursor.

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N. Alharbi et al. / Tetrahedron 70 (2014) 7370e7379
TBTAP products were observed when the same conditions were
applied to 4-tert-butylphthalonitrile or 4,5-dihexylphthalonitrile.29
The disparity in reactivities of the isomeric 3,6-
dihexylphthalonitrile and 4,5-dihexylphthalonitrile prompted in-
vestigation into reactivities of dialkyl substituted phthalonitriles
towards Grignard reagents. Reaction of a 4,5-dialkylphthalonitrile
with MeMgBr under modified LeznoffeMcKeown conditions gave
the corresponding TBTAP and the Pc, broadly as expected on the
basis of Leznoff and McKeown’s findings.30 However, application of
these conditions to both 3,6-dihexyl and 3,6-didecylphthalonitriles
gave quite different results.30,31 Both substrates gave mixtures of
hybrids, the composition dependent on the number of equivalents
of MeMgBr that was used. The use of a 1:1 or 2:1 ratio of MeMgBr/
3,6-dialkylphthalonitrile gave the corresponding (np)-octaalkyl-
MgTBTAP as the dominant product alongside the correspondingly
substituted MgTBDAPs and MgTBMAP. Only trace amounts of Pc
were detected. Increasing the ratio further to 4:1 gave the MgTBP
derivative as essentially the only macrocyclic product. Demetalla-
tion of the separated products using acetic acid provided the metal-
free analogues that were re-metallated with other ions.30,32 Co-
lumnar liquid crystal behaviour was examined for various exam-
ples.31 Elsewhere, the synthesis has been repeated and the liquid
crystal behaviour of the TBMAP and TBP compounds investigated.33
Scheme 3. Unexpected formation of an octakis(alkyl) H2TBTAP as a side product of the
cyclotetramerisation of a 1,4-dialkylphthlonitrile in Li/pentanol to form a Pc.
workers19e24 employed the methylene group of carboxylic acids,
RCH2COOH, in mixed cyclisation reactions of these with diiminoi-
soindolines using ZnO or MgO as a template. Their interest was
focussed more on developing access to all the hybrids rather than
specifically targeting TBTAPs, their products containing the R group
(from RCH2COOH) at the meso-position(s). The resulting separable
mixtures contained the TBTAP derivative along with the other hy-
brid compounds and, in some cases, the Pc and the TBP analogues
as well. The synthesis was employed subsequently by Borisov and
A
remaining anomalous result in reactions of 3,6-
dialkylphthalonitriles with Grignard reagents was also un-
covered: the use of long chain Grignard reagents provided the
meso-carbon as expected but bound only to hydrogen.30 The un-
expected CeC cleavage is perhaps related to that which occurs
using Li in alcohols as discussed above.
co-workers, albeit with much lower reported yields of hybrids.4
A
related mixed cyclisation was reported by Bulavka who used
a mixture of potassium phthalimide, the potassium salt of phenyl
acetic acid and urea along with MgO as template.25 Microwave ir-
radiation produced meso-Ph-MgTBTAP in 8% yield but the product
mixture was dominated by MgPc (65%) along with smaller amounts
of the MgTBDAPs, the MgTBMAP and the MgTBP compounds. A
further synthesis of meso-Ph-MgTBTAP reported by Tomilova and
co-workers used phenylacetonitrile as the donor of the meso-car-
bon in reactions with phthalonitrile in the presence of Mg pow-
der.26 They extended the study using substituted phenyl
acetonitriles to obtain a number of meso-aryl-MgTBTAP com-
pounds in 3e10% yield. The group introduced a further innovation
through the reaction of phthalonitrile with quaternary salts of tri-
phenylphosphonium in the presence of Zn powder with gradual
heating from 200 to 300 ꢀC. The product mixture contained the
readily separable ZnPc by-product and meso-Ph-ZnTBTAP, the latter
in 11% yield. Other hybrid compounds were not detected.27 meso-
PheZnTBTAP has recently been exploited as the precursor for the
formation of the first lutetium bis-TBTAP sandwich complex and
the corresponding heterolyptic lutetium TBTAP/Pc sandwich
complex.28
2. Results and discussion
It becomes apparent from the brief review above that the syn-
thetic chemistry of TBTAPs has advanced only modestly since their
discovery. Indeed, although a limited number of TBTAP derivatives
have been prepared, the investigation of functionalised systems or
development of methods for efficient and versatile access to such
hybrids has gone essentially unexplored. We are interested in both
aspectsdfunctional TBTAPs as potential molecular materials and
components of super- and supramolecular structures, and syn-
thetic chemistry development to open the field in a manner parallel
to that enjoyed by the parent phthalocyanines and porphyrins.
In particular we have been interested in novel TBTAPs bearing
aryl substituents at their meso-position and our initial in-
vestigations focused on the known protocol, exemplified in Scheme
2 above, employing Grignard reagents to induce macrocyclisation.
Our first series of functionalised meso-phenyl substituted TBTAPs
were prepared by reaction between phthalonitrile and the isomeric
series of 2-, 3- and 4-bromobenzyl magnesium chlorides, Scheme 4.
Reaction conditions were optimised and in a typical procedure the
Grignard reagent and phthalonitrile were reacted in THF or ether
before changing the reaction solvent to quinoline and heating at
200 ꢀC. The procedure was later improved further by using diglyme
as the only solvent, resulting in a cleaner, more convenient trans-
formation and isolation. It was found that purification of the meso-
aryl TBTAPs, 2, 3 and 4 was relatively straightforward so long as the
magnesium ion was retained in the macrocycle. Acidic conditions
were therefore avoided during workup. Crystals suitable for X-ray
diffraction analysis were grown for TBTAP 2, and the structure is
also shown in the scheme.
The UEA group’s interest in TBTAPs arose from a serendipitous
finding.29 The conventional cyclotetramerisation of 3,6-dihexyl
phthalonitrile into the corresponding non-peripherally (np)
substituted (i.e., 1,4,8,11,15,18,22,25-)octahexylphthalocyanine us-
ing lithium in pentanol as initiator was discovered to give the
TBTAP derivative as
a by-product under specific conditions
(Scheme 3). TBTAP is only formed when lithium metal, in excess, is
added to the alcohol solution of phthalonitrile (Preformed lithium
alkoxide leads to production of the phthalocyanine only.). The use
of 19 equiv of lithium in pentanol gave a 77:23 ratio of Pc/TBTAP,
and the amount of TBTAP formed increased even further when
octanol was used in place of pentanol leading to a 53:47 ratio.
Remarkably, the origin of the meso-carbon was traced to the alcohol
solvent. Thus when octanol labelled with 13C at the
a
-carbon was
It is well known that solubility and processability in macrocycles
such as these can be significantly enhanced by introduction of
solubilising groups such as alkyl chains. Our preliminary work
employed as solvent the isolated TBTAP showed 87% 13C in-
corporation at the meso-site. The mechanism for its incorporation,
the evident CeC cleavage reaction involved, the origin of the 13% of
unlabelled meso-carbon and indeed the mechanism for TBTAP
formation under these conditions remains unclear. Interestingly, no
demonstrated that
bearing a meso-phenyl group could be prepared from benzyl
magnesium chloride and 4,5-dialkylphthalonitrile. The
a peripherally substituted octaalkylTBTAP
a

N. Alharbi et al. / Tetrahedron 70 (2014) 7370e7379
7373
Scheme 4. Synthesis of meso-(bromophenyl)-TBTAPs via the Grignard reagent route, plus the X-ray crystal structure of derivative 4 (ball-and-stick representation).
corresponding functionalised-phenyl derivative was similarly syn-
thesised from reaction between 4,5-bis(2-ethylhexyl)phthalonitrile
5 and 2-bromobenzyl magnesium chloride. This phthalonitrile was
chosen because the branched (chiral) chains, introduced using ra-
cemic 2-ethylhexyl bromide, confer excellent solubility on phtha-
locyanine macrocycles and this behaviour was observed in TBTAP 6
also (solubility >20 mg/ml in chloroform) (Scheme 5).
reaction were examined by mass spectrometry, Fig. 2, and clearly
revealed that the initial steps of the reaction result in formation of
a complex mixture of oligomers. Heating with a template ion leads
to macrocyclisation. However, closer examination of the mass
spectrum indicates that the growing oligomers are themselves
susceptible to attack by Grignard reagent and it is difficult to see
how such intermediates can lead to useful macrocyclic products.
Scheme 5. Synthesis of the peripherally substituted analogue 6.
However, phthalonitrile 5 does have some drawbacks. Its
preparation and purification are tedious, and 1H NMR spectra can
be complicated and broadened due to the formation of mixtures of
diastereomers. We therefore turned our attention to an alternative
4,5-dialkylphthalonitrile, namely 7. Phthalonitrile 7 is relatively
easy to synthesise, has high symmetry yet is heavily branched,
conferring solubility and preventing aggregation. TBTAP formation
was therefore investigated using this derivative as precursor, and
benzyl magnesium chloride and 2-bromobenzyl magnesium chlo-
ride as Grignard reagents. The corresponding meso-aryl TBTAPs, 8
and 9, were isolated, Scheme 6, albeit in relatively low yields, and
characterisation was reasonably straightforward. 1H NMR spec-
troscopy is particularly informative, showing distinct signals for the
protons labelled Ha (ca. 7.0 ppm) that lie in the shielding ring
current of the meso-aryl substituent.
The reaction between phthalonitrile 7 and 2-bromobenzyl
magnesium chloride was given particular attention, and in one
experiment a side product was isolated and identified as phthali-
midine 10. Crystals suitable for X-ray diffraction analysis were
grown and its structure was unambiguously confirmed. Phthali-
midine 10 is a direct analogue of Dent’s original precursor to
TBTAPs, see Scheme 1. However, in our case its origin is likely to be
through hydrolysis of the initial addition product formed between
phthalonitrile 7 and the Grignard reagent.
Unfortunately this cannot be solved by modification of the addition
of Grignard reagent (reduced quantity, slower addition); when only
a low quantity of Grignard reagent initiator is present, the most
favourable cyclisation (and therefore the most abundant product)
would lead to simple phthalocyanine. Although this investigation
revealed fundamental problems with the Grignard initiation route
to TBTAPs, close examination of the mass spectra identified a peak
that most likely corresponds to (protonated) intermediate 12. We
reasoned that this intermediate, if accessed discretely, could initiate
TBTAP formation without the complications described above.
In light of this finding, aminoisoindoline 15, Scheme 8, was se-
lected for investigation as
a new TBTAP precursor. The 4-
methoxyphenyl substituent was chosen to demonstrate in-
troduction of functionality, but also to simplify characterisation by
1H NMR spectroscopy. Synthesis of 15, via 13 and 1434 was
straightforward and followed the method developed by Hellal and
Cuny (Scheme 8).35 Initial reactions to form a TBTAP from amino-
isoindoline 15 and diiminoisoindoline 16 as co-reactant under the
high temperature conditions (220 ꢀC, MgBr2) required for the re-
action demonstrated TBTAP formation but the dominant product
was the simple magnesium phthalocyanine resulting from macro-
cyclisation of diiminoisoindoline alone. Switching the co-reactant
from diiminoisoindoline to phthalonitrile (which does not readily
cyclise to phthalocyanine under these conditions) improved the
reaction outcome considerably. Furthermore, subtle optimisation
led to development of an efficient protocol for formation of meso-
(4-methoxyphenyl)TBTAP 19.36 Specifically, a mixture of amino-
isoindoline 15 and phthalonitrile (1:1) is added slowly to a heated
mixture of phthalonitrile (3 equiv) and MgBr2 in diglyme at 220 ꢀC,
followed by addition of DABCO and more phthalonitrile (1 equiv).
Isolation of phthalimidine 10 stimulated a closer examination of
the reaction course from phthalonitrile and Grignard reagent
through to TBTAP. In order to facilitate analysis of the reaction
mixture by mass spectrometry, the reaction between 4-
methoxybenzyl
magnesium
chloride
and
4,5-dihexyl
phthalonitrile 11 was selected (Scheme 7). Aliquots from the

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N. Alharbi et al. / Tetrahedron 70 (2014) 7370e7379
Scheme 6. TBTAP synthesis employing phthalonitrile 7 and the isolated side product 10 (ball-and-stick representation of the structure obtained by X-ray crystallography).
Scheme 7. Examination of the reaction between phthalonitrile 11 and benzyl Grignard reagents.
Fig. 2. Mass spectra of crude mixtures from the reaction between benzyl Grignard reagents and 4,5-dihexylphthalonitrile.
Adding DABCO to the reaction mixture results in release of
unreacted 15 from its complex with the MgTBTAP product. Com-
plete consumption of starting 15 is then observed with corre-
sponding improvement in the overall yield. Alternative precursor
aminoisoindolines 17 and 18 provided access to the isomeric meso-
(3-methoxyphenyl)TBTAP 20 and meso-(3,5-dimethoxyphenyl)
TBTAP 22, the latter providing crystals suitable for X-ray diffraction;
its structure is also shown in Scheme 8. meso-(3-Methoxyphenyl)
TBTAP was smoothly hydrolysed using BBr3, giving meso-(3-
hydroxyphenyl)TBTAP 21.
The new synthetic route therefore opens the way for design and
synthesis of new families of meso-aryl TBTAPs, and their further
elaboration into complex, functional molecular materials. As in
meso-aryl porphyrins, the meso-aryl moiety on the new TBTAPs lies
essentially perpendicular to the macrocycle plane, minimising
ground state electronic interaction. Intriguing arrays become pos-
sible, where multiple chromophores/fluorophores lie in close
proximity but without interaction. To illustrate the potential of the
new synthetic protocol we selected pyrene as complementary ar-
omatic unit. Thus, 1-ethynylpyrene was reacted with

N. Alharbi et al. / Tetrahedron 70 (2014) 7370e7379
7375
Scheme 8. Improved synthesis protocol for meso-aryl TBTAPs, and the X-ray crystal structure of 22 (ball-and-stick representations).
bromoamidine 14 to give the corresponding aminoisoindoline 23,
Scheme 8. In this case the product 23 was isolated as a mixture of
stereoisomers. Macrocyclisation of the mixture of isomers with
phthalonitrile using our previously developed conditions pro-
ceeded smoothly, leading to isolation of meso-(1-pyrenyl)TBTAP 24.
Crystals suitable for X-ray diffraction were eventually grown and
the structure is shown in Scheme 9.
procedure allows design and synthesis of elaborate, functional
composites and this is demonstrated by synthesis of meso-pyr-
enylTBTAP 24, a linked chromophores dyad in which the two
complementary units lie perpendicular to each other and therefore
have minimal ground state interaction.
4. Experimental
The absorption and fluorescence spectra for meso-(1-pyrenyl)
TBTAP 24 are shown in the Fig. 3. As expected the absorption
spectrum shows no significant perturbation of the individual
chromophoresdthe spectrum is essentially identical to other
members of the MgTBTAP series (19e22) in the TBTAP
(350e700 nm) range, and shows additional absorptions associated
with the pyrene fragment between 250 and 350 nm. Energy
transfer between the two mutually perpendicular chromophores is
expected to be forbidden and weak. Examination of the fluores-
cence spectrum (exciting into the pyrene absorption at 246 nm)
shows that energy transfer from the (excited) pyrene fragment to
the TBTAP is observed but incomplete. Emission occurs from both
the pyrene and TBTAP. This conclusion is further supported by the
excitation spectrum where, recording emission at 674 nm from the
TBTAP only, we see the profile following the absorption of both the
pyrene and TBTAP fragments of the molecule.
4.1. General methods
Reagents and solvents were purchased from commercial sour-
ces and used without further purification. IR spectra were recorded
using a PerkineElmer Spectrum BX FT-IR spectrometer. 1H (and 13
C
NMR) spectra were recorded at 500 (125.7) or 400 (100.6) MHz
using a Bruker AscendÔ 500 or an Ultrashield PlusÔ 400 spec-
trometer. Poor solubility and aggregation prevented acquisition of
useful 13C NMR data for several final compounds. The residual
solvent peaks were used as references. 2D COSY, NOESY, HSQC and
HMBC experiments were used to assist with the NMR spectroscopy
assignments. Thin layer chromatography (TLC) was carried out on
aluminium sheets coated with AlugramÒ Sil G/UV254 (Macherey-
Nagel), with visualisation by UV light and by charring with 0.1%
ninhydrin in EtOH when necessary. Column chromatography was
carried out on silica gel DavisilÒ LC60A 40e63 micron (Grace GmbH
& Co). MALDI-TOF mass spectra were obtained using a Shimadzu
Biotech Axima instrument, and isotopic patterns were compared
with theoretical prediction to confirm sample identity. High-reso-
lution mass spectrometry was performed by the ESPRC UK National
Mass Spectrometry Service Centre at Swansea. UVevis spectra
were recorded in a Hitachi U-3000 spectrophotometer. Melting
points were measured using a Reichert Thermovar microscope with
3. Conclusions
New tetrabenzotriazaporphyrins are reported that are func-
tionalised at the meso-position. In particular, a versatile protocol is
employed that gives convenient access to these challenging mate-
rials by template co-macrocyclisation between phthalonitriles and
aryl-aminoisoindoline derivatives like 15. The newly developed

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N. Alharbi et al. / Tetrahedron 70 (2014) 7370e7379
Scheme 9. Synthesis and crystal structure of meso-pyrenylTBTAP 24 (ball-and-stick representations).
Fig. 3. Absorption, fluorescence and excitation spectra for pyrenylTBTAP 24.
a thermopar based temperature control. Fluorescence excitation
and emission spectra were recorded on a Hitachi F-4500 fluores-
cence spectrometer, using compound concentrations that give 0.1
units of maximum UVevis absorbance. X-ray crystallography data
were collected by the UK National Crystallography Service at Uni-
versity of Southampton.
degassed quinoline was added to the hot vessel via syringe, and the
reaction mixture was heated at 200 ꢀC for 24 h under argon. During
this time the colour of the reaction mixture changed gradually from
dark brown to green. Then, the majority of the quinoline was re-
moved under a stream of argon. The crude product was cooled to
room temperature and MeOH was added to the mixture. After soni-
cation, the resulting suspension was poured onto a column of dry
silica gel. MeOH was initially eluted through the column to remove
the remaining quinoline and other polar by-products, then the eluent
was changed to THF leading to collection of the product as a dark
green fraction. The solvent was removed under reduced pressure and
the resulting green material further purified by column chromatog-
raphy eluting with PE/THF (15:1) to obtain a green (TBTAP) and then
a blue fraction (Pc). Finally, the green material was subjected to
a second chromatographic separation using DCM/PE (1:15).
4.2. General synthetic procedure for the synthesis of
substituted meso-aryl TBTAPs via the Grignard reagent route
using quinoline as solvent
(Substituted) phthalonitrile was dissolved in dry THF and stirred
at room temperature, under an argon atmosphere. A solution of
arylmagnesium halide was added dropwise via a syringe and the
mixture was heated under reflux for 2 h. The reaction mixture un-
derwent a colour change from a yellow solution, to a dark brown
colour. A stream of argon was passed through the reaction flask for
20 min to remove the THF. After removal of the solvent, distilled/
4.2.1. (2,3,9,10,15,16,23,24-Octakis(2-ethylhexyl)-27-(2-
bromophenyl)tetrabenzo-[b,g,l,q][5,10,15]triazaporphinato)

N. Alharbi et al. / Tetrahedron 70 (2014) 7370e7379
7377
magnesium 6. Synthesised following the general procedure de-
scribed above from 4,5-bis(2-ethylhexyl)phthalonitrile 530,36
(200.0 mg, 0.567 mmol, 1 equiv) and 2-bromobenzylmagnesium
bromide (4.54 mL, 0.25 M in Et2O, 1.13 mmol, 2 equiv) in dis-
tilled/degassed quinoline (3.0 mL). The final material was recrys-
tallised from acetone/EtOH (1:1) yielding the title compound as
176.28, 166.35, 160.34, 157.98, 155.83, 154.80, 153.38, 152.27, 151.68,
150.48, 147.92, 146.41, 146.35, 145.95, 144.27, 143.15, 141.08, 140.88,
140.63, 140.14, 139.55, 139.40, 138.13, 133.19, 133.07, 130.15, 129.84,
128.32, 127.38, 125.16, 123.83, 123.80, 123.59; MS (MALDI-TOF) m/z
692 [M]þ (100%); HRMS (ESI) (C39H20BrMgN7) Mþ: calcd: 689.0817;
found: 689.0808.
a green solid (35.0 mg,16%); mp >300 ꢀC; UVevis (THF) lmax/nm (
)
3
685 (3.57ꢁ103), 662 (2.62ꢁ103), 606 (7.14ꢁ102), 450 (4.76ꢁ102),
4.3.3. 20-(4-Bromophenyl)-(tetrabenzo[b,g,q,l][5,10,15]tri-
azaporphyrinato)magnesium 4. Synthesised following the general
procedure described above from phthalonitrile (4.41 mg,
34.45 mmol) and 4-bromobenzylmagnesium bromide (11.98 mL,
2.13 M in Et2O, 25.52 mmol) in diglyme (6.0 mL). The final material
was recrystallised from acetone/EtOH (1:1) yielding the title com-
pound as green crystals with a purple reflex (400 mg, 5%); mp
390 (1.67ꢁ103); nmax/cmꢂ1 (ATR) 2926, 1463, 1376; 1H NMR
(500 MHz, THF-d8, 298 K):
d (ppm) 9.32 (br s, 2H), 9.25 (br s, 4H),
8.28 (d, J¼8.0 Hz, 1H), 8.16 (br s, 1H), 7.99e7.92 (m, 2H), 6.99 (s, 2H),
3.25e3.24 (m, 16H), 2.12 (m, 8H), 1.72e1.59 (m, 64H), 1.03e0.87 (m,
48H); MS (MALDI-TOF) m/z 1589 [M]þ (100%).
4.3. General synthetic procedure for the synthesis of
substituted meso-aryl TBTAPs via the Grignard reagent route
using diglyme as solvent
>300 ꢀC; UVevis (THF) lmax/nm (
3
) 671 (1.75ꢁ103), 648 (1.00ꢁ103),
594 (2.50ꢁ102), 443 (2.14ꢁ102), 394 (6.79ꢁ102); nmax/cmꢂ1 (ATR)
3050, 1463, 1373; 1H NMR (500 MHz, THF-d8, 298 K):
d (ppm) 9.60
(d, J¼7.5 Hz, 2H), 9.52e9.48 (m, 4H), 8.19e8.13 (m, 6H), 8.10 (d,
A suspension of phthalonitrile in dry diglyme was refluxed at
220 ꢀC for 10 min under an argon atmosphere, in a preheated
mantle. A solution of bromobenzylmagnesium bromide was added
dropwise via a syringe. The reaction mixture was heated at 220 ꢀC
under argon for 3 h. A stream of argon was passed through the
reaction vessel in order to remove the solvent. After the reaction
mixture cooled to room temperature, a mixture of DCM/MeOH
(50 ml, 1:1) was added to the reaction mixture and sonicated. After
removal of the solvent under reduced pressure, the crude solid was
loaded on a silica-gel column and eluted with DCM/Et3N/THF
(10:1:4) in order to initially remove the yellow-brown impurities
and then green/blue fractions, which were subjected to a second
column chromatographic separation using PE/THF/MeOH (10:3:1)
as eluent to obtain the pure green product.
J¼7.8 Hz, 2H), 7.91 (t, J¼7.2 Hz, 2H), 7.63 (t, J¼7.5 Hz, 2H), 7.17 (d,
J¼8.1 Hz, 2H); 13C NMR (125.7 MHz, THF-d8, 298 K):
d (ppm) 157.87,
154.69, 153.61, 143.25, 143.17, 141.06, 140.86, 140.68, 140.13, 135.23,
133.26, 130.13, 129.81, 128.28, 127.36, 125.22, 124.15, 123.82, 123.76,
123.57, 121.81, 108.56; MS (MALDI-TOF) m/z 692 [M]þ (100%);
HRMS (ESI) (C39H21BrMgN7) [MþH]þ: calcd: 690.0888; found:
690.0887.
4.4. General synthetic procedure for the synthesis of
aminoisoindolines
Following the reported procedure35 a mixture of amidine 14,
BINAP (0.055 equiv) and PdCl2(MeCN)2 (0.05 equiv) was sealed in
a microwave vessel with a magnetic bar and then purged and
refilled with N2 thrice. Then, a solution of arylethyne (1.2 equiv) and
DBU (2.5 equiv) in dry DMF (12 ml) was added. The mixture was
stirred under N2 for 5 min to give a clear yellow solution with
a white solid. Finally, the mixture was irradiated in a microwave
reactor at 120 ꢀC for 1 h. After cooling, 50 ml of AcOEt was added
and the mixture washed three times with a saturated solution of
NaHCO3 (75 ml). The organic layer was dried (MgSO4), filtered and
concentrated. The residue was finally purified by column chroma-
tography using AcOEt, AcOEt/EtOH/H2O (90:5:3) and finally AcOEt/
EtOH/H2O (45:5:3).
4.3.1. 20-(2-Bromophenyl)-(tetrabenzo[b,g,q,l][5,10,15]tri-
azaporphyrinato)magnesium 2. Synthesised following the general
procedure described above from phthalonitrile (280 mg,
2.19 mmol) and 2-bromobenzylmagnesium bromide (2.92 mL,
0.25 M in Et2O, 0.73 mmol) in diglyme (1.0 mL). The final material
was recrystallised from acetone/EtOH (1:1) yielding the title com-
pound as green crystals with a purple reflex (140 mg, 28%); mp
>300 ꢀC; UVevis (THF) lmax/nm (
3
) 671 (2.12ꢁ103), 650 (1.11ꢁ103),
594 (2.33ꢁ102), 443 (1.55ꢁ102), 396 (5.96ꢁ103); nmax/cmꢂ1 (ATR)
3050, 1462, 1374; 1H NMR (500 MHz, THF-d8, 298 K):
d (ppm) 9.61
(d, J¼7.5 Hz, 2H), 9.53e9.48 (m, 4H), 8.31 (d, J¼8.3 Hz, 1H),
8.18e8.16 (m, 5H), 7.98 (t, J¼7.9 Hz, 1H), 7.93e7.90 (m, 3H), 7.60 (t,
J¼7.5 Hz, 2H), 7.14 (d, J¼8.0 Hz, 2H); 13C NMR (125.7 MHz, THF-d8,
4.4.1. (Z)-1-(3-Methoxybenzylidene)-1H-isoindol-3-amine
17. Synthesised following the general procedure described above
using a solution of 3-ethynylanisole (0.67 g, 5.09 mmol) and DBU
(1.62 g, 10.64 mmol) in dry DMF (12 ml) and adding amidine 14
(1.00 g, 4.25 mmol), BINAP (0.13 g, 0.21 mmol), and PdCl2(MeCN)2
(0.06 g, 0.21 mmol). After purification, the yellow solid was
recrystallised from a DCM/petroleum ether (1:1) to yield the title
compound as yellow needles (440 mg, 41%); mp 183e184 ꢀC;;
298 K):
d
(ppm)¼177.06, 156.67, 153.74, 152.68, 144.36, 142.51,
141.26, 141.03, 140.79, 140.31, 135.27, 134.70, 132.18, 130.15, 129.87,
129.64, 128.59, 127.60, 125.14, 124.71, 123.93, 123.83, 123.74, 108.57,
108.28, 107.83, 102.09, 98.92; MS (MALDI-TOF) m/z 692 [M]þ
(100%); HRMS (ESI) (C39H20BrMgN7) Mþ: calcd: 689.0807; found:
689.0808.
UVevis (DCM) lmax/nm (
3
) 367 (2.93ꢁ103), 292 (9.01ꢁ102); nmax
/
cmꢂ1 (ATR) 3600e3050 (br), 2930, 1593, 1423; 1H NMR (500 MHz,
4.3.2. 20-(3-Bromophenyl)-(tetrabenzo[b,g,q,l][5,10,15]tri-
azaporphyrinato)magnesium 3. Synthesised following the general
procedure described above from phthalonitrile (280 mg,
2.19 mmol) and 3-bromobenzylmagnesium bromide (2.92 mL,
0.25 M in Et2O, 0.73 mmol) in diglyme (1.0 mL). The final material
was recrystallised from acetone/EtOH (1:1) yielding the title com-
pound as green crystals with a purple reflex (120 mg, 24%); mp
CDCl3, 298 K):
d
(ppm) 7.83 (br s, 1H), 7.79 (d, J¼7.6 Hz, 1H), 7.60 (d,
J¼7.6 Hz, 1H), 7.50e7.44 (m, 2H), 7.39 (t, J¼7.4 Hz, 1H), 7.30 (t,
J¼7.9 Hz, 1H), 6.82 (dd, J¼8.2, 2.4 Hz, 1H), 6.73 (s, 1H), 5.74e5.35 (br
s, 2H, NH2), 3.88 (s, 3H); 13C NMR (125.7 MHz, CDCl3, 298 K):
d
(ppm) 165.04, 159.85, 159.84, 159.80, 138.10, 131.11, 129.47, 129.36,
127.40, 126.85, 123.40, 119.97, 119.02, 115.58, 113.64, 55.45; MS
(MALDI-TOF) m/z 251 [M]þ (100%); HRMS (ESI) (C16H15N2O)
[MþH]þ: calcd: 251.1179; found: 251.1180.
>300 ꢀC; UVevis (THF) lmax/nm (
3
) 671 (3.29ꢁ103), 648 (1.91ꢁ103),
593 (4.15ꢁ102), 442 (2.90ꢁ102), 396 (1.09ꢁ103); nmax/cmꢂ1 (ATR)
3050, 1462; 1H NMR (500 MHz, THF-d8, 298 K):
d
(ppm) 9.61 (d,
4.4.2. (Z)-1-(3,5-Dimethoxybenzylidene)-1H-isoindol-3-amine
18. Synthesised following the general procedure described above
using a solution of 1-ethynyl-3,5-dimethoxybenzene (0.83 g,
5.12 mmol) and DBU (1.62 g, 10.64 mmol) in dry DMF (12 ml) and
J¼7.6 Hz, 2H), 9.53e9.47 (m, 4H), 8.37 (s, 1H), 8.25 (d, J¼8.3 Hz, 1H),
8.19e8.15 (m, 5H), 7.94e7.87 (m, 3H), 7.62 (t, J¼7.5 Hz, 2H), 7.15 (d,
J¼8.0 Hz, 2H); 13C NMR (125.7 MHz, THF-d8, 298 K):
d
(ppm)¼

7378
N. Alharbi et al. / Tetrahedron 70 (2014) 7370e7379
adding amidine 14 (1.00 g, 4.25 mmol), BINAP (0.13 g, 0.21 mmol)
and PdCl2(MeCN)2 (0.06 g, 0.21 mmol). After purification, the yel-
low solid was recrystallised from a DCM:petroleum ether (1:1) to
yield the title compound as yellow needles (300 mg, 25%); mp
diglyme (0.5 ml), heating at 220 ꢀC for 10 min under argon and
initially adding aminoisoindoline 17 (100.0 mg, 0.40 mmol) and
phthalonitrile (51.0 mg, 0.40 mmol) in dry diglyme (1.0 ml) over 1 h.
Finally, a solution of phthalonitrile (51.0 mg, 0.40 mmol) and
DABCO (67.0 mg, 0.60 mmol) in dry diglyme (0.5 ml) was added
dropwise over 1 h. The purified product recrystallised from ace-
tone/EtOH (1:1) gave the title compound as green crystals with
167e168 ꢀC;; UVevis (DCM) lmax/nm (
3
) 367 (1.18ꢁ103), 290
(3.36ꢁ102); nmax/cmꢂ1 (ATR) 3600e3050 (br), 1589, 1416; 1H NMR
(500 MHz, CDCl3, 298 K):
d
(ppm) 7.79 (d, J¼7.5 Hz, 1H), 7.51e7.47
(m, 2H), 7.40 (t, J¼7.4 Hz, 1H), 7.30 (d, J¼2.0 Hz, 2H), 6.70 (s, 1H),
purple reflex (50 mg, 20%); mp >300 ꢀC; UVevis (THF) lmax/nm (
)
3
6.42 (t, J¼2.3 Hz, 1H), 3.87 (s, 6H); 13C NMR (125.7 MHz, CDCl3,
670 (7.35ꢁ103), 647 (4.41ꢁ103), 592 (1.03ꢁ102), 442 (1.03ꢁ102),
298 K):
d (ppm) 164.76, 160.91, 159.76, 154.32, 153.83, 152.80,
397 (2.50ꢁ102); nmax/cmꢂ1 (ATR) 2930, 1463, 1379; 1H NMR
138.20, 131.11, 129.80, 128.82, 127.64, 127.30, 120.05, 119.39, 108.49,
100.66, 55.61; MS (MALDI-TOF) m/z 281 [M]þ (100%); HRMS (ESI)
(C17H17N2O2) [MþH]þ: calcd: 281.1285; found: 281.1287.
(500 MHz, THF-d8, 298 K):
d
(ppm) 9.59 (d, J¼7.5 Hz, 2H), 9.53e9.50
(m, 4H), 8.23e8.15 (m, 4H), 7.92 (t, J¼7.1 Hz, 2H), 7.88e7.84 (m, 1H),
7.77e7.68 (m, 2H), 7.63e7.59 (m, 3H), 7.25 (d, J¼8.0 Hz, 2H), 3.98 (s,
3H); 13C NMR (125.7 MHz, THF-d8, 298 K):
d (ppm) 169.56, 161.75,
4.4.3. (Z/E)-1(1-Pyrenylmethylene)-1H-isoindol-3-amine
23. Synthesised following the general procedure described above
using a solution of 1-ethynylpyrene (500 mg, 2.2 mmol) and DBU
(0.7 mL) in dry DMF (10 ml) and adding amidine 14 (435 mg,
1.85 mmol), BINAP (69 mg, 0.11 mmol) and PdCl2(MeCN)2 (24 mg,
0.092 mmol). The crude product was purified by column chroma-
tography using DCM then DCM/MeOH (9:1 to 2:1) as solvent gra-
dient to afford the title compound a bright yellow solid, an
approximate 3:1 mixture of stereoisomers (455 mg, 72%); mp
156.84, 153.81, 152.87, 145.09, 143.05, 141.13, 141.00, 140.90, 140.20,
134.79, 134.51, 133.67, 132.79, 130.86, 130.09, 129.80, 128.24, 127.39,
126.63,125.81,125.69,123.86,123.76,123.64,123.58,122.46,118.90,
115.86, 108.56, 98.90, 56.04; MS (MALDI-TOF) m/z 642 [M]þ (100%);
HRMS (ESI) (C40H23MgN7O) [MþH]þ: calcd: 642.1887; found:
642.1885.
4.5.2. (20-(3,5-Dimethoxyphenyl)-tetrabenzo[b,g,q,l]-5,10,15-
triazaporphyrinato)magnesium 22. Synthesised following the gen-
eral procedure described above using a solution of phthalonitrile
(210 mg, 1.64 mmol) and MgBr2 (148 mg, 0.80 mmol) in dry
diglyme (0.5 ml), heating at 220 ꢀC for 10 min under argon and
initially adding aminoisoindoline 18 (150 mg, 0.54 mmol) and
phthalonitrile (69 mg, 0.54 mmol) in dry diglyme (1.0 ml) over 1 h.
Finally, a solution of phthalonitrile (69 mg, 0.54 mmol) and DABCO
(90 mg, 0.80 mmol) in dry diglyme (0.5 ml) was added dropwise
over 1 h. The purified product recrystallised from acetone/EtOH
(1:1) gave the title compound as green crystals with purple reflex
280e282 ꢀC;; UVevis (DCM) lmax/nm (
3
) 403 (7.64ꢁ103), 238
(1.62ꢁ104); nmax/cmꢂ1 (ATR) 3600e2900 (br), 1652, 1543, 1436; 1H
NMR (500 MHz, CDCl3, 298 K):
d (ppm) major isomer 8.97 (d,
J¼8.1 Hz, 1H), 8.45 (d, J¼9.2 Hz, 1H), 8.22e7.98 (m, 6H), 7.97 (t,
J¼7.6 Hz, 1H),; 7.93 (d, J¼7.6 Hz, 1H), 7.65 (s, 1H, H-a), 7.50 (br td,
J¼7.5, 1.1 Hz, 1H), 7.45 (br dt, J¼7.6, 0.9 Hz, 1H), 7.37 (br td, J¼7.4,
0.9 Hz, 1H), 5.4e4.2 (br s, 2H, NH2); minor isomer 8.23 (d, J¼9.1 Hz,
1H), 8.22e7.98 (m, 8H), 7.69 (s, 1H, H-a), 7.54 (d, J¼7.8 Hz, 1H), 7.22
(br td, J¼7.4, 1.1 Hz, 1H), 7.02 (br td, J¼7.6, 1.0 Hz, 1H), 6.96 (br dt,
J¼7.9 Hz, 0.9, 1H), 5.4e4.2 (br s, 2H, NH2); MS (MALDI-TOF) m/z 344
[M]þ (100%); HRMS (ESI) (C25H17N2) [MþH]þ: calcd: 345.1386;
found: 345.1386.
(30 mg, 8%); mp >300 ꢀC; UVevis (THF) lmax/nm
( ) 670
3
(6.45ꢁ103), 647 (4.23ꢁ103), 594 (1.21ꢁ102), 443 (1.41ꢁ102), 395
(2.82ꢁ103); nmax/cmꢂ1 (ATR) 2934, 1470; 1H NMR (500 MHz, THF-
d8, 298 K):
d
(ppm) 9.59 (d, J¼7.5 Hz, 2H), 9.53e9.50 (m, 4H),
4.5. General synthetic procedure for the synthesis of meso-
aryl TBTAPs via aminoisoindoline intermediates
8.20e8.15 (m, 4H), 7.93 (t, J¼7.6 Hz, 2H), 7.65 (t, J¼8.0 Hz, 2H), 7.45
(d, J¼8.0 Hz, 2H), 7.34 (d, J¼2.3 Hz, 2H), 7.18 (t, J¼2.3 Hz,1H), 3.95 (s,
6H); 13C NMR (125.7 MHz, THF-d8, 298 K):
d (ppm) 162.77, 156.73,
A suspension of phthalonitrile (ca. 150 mg, 3 equiv) and MgBr2
(1.5 equiv) in dry diglyme (0.5 mL) was heated at 220 ꢀC for 10 min
under an argon atmosphere, in a preheated mantle. A solution of
aminoisoindoline (1 equiv) and phthalonitrile (1 equiv) in dry
diglyme (1 ml) was added dropwise over 1 h using a syringe pump.
After finishing the first addition, the reaction mixture was left to
reflux at 220 ꢀC for 30 min. Finally, a solution of phthalonitrile
(1 equiv) and DABCO (1.5 equiv) in dry diglyme (0.5 ml) was added
dropwise over 1 h. The reaction mixture was then refluxed at
220 ꢀC under argon for further 30 min. A stream of argon was
passed through the reaction vessel in order to remove the solvent.
The reaction mixture was cooled to room temperature and a mix-
ture of DCM/MeOH (50 ml, 1:1) was added and the mixture soni-
cated. After removal the solvent under reduced pressure, the
resulting material was purified by two consecutive flash chroma-
tographies. Firstly, the crude was loaded on a silica-gel column and
eluted with DCM/Et3N/THF (10:1:4) in order to remove the yellow-
brown impurities and obtain a green fraction. The green fraction
was then subjected to a second column chromatography using PE/
THF/MeOH (10:3:1) as eluent to obtain the pure green product.
Alternatively, analytically pure material could be obtained by size-
exclusion chromatography over Bio-beads SX-3 using THF eluent.
153.72, 152.83, 145.37, 142.92, 142.14, 141.16, 140.93, 140.21, 130.07,
129.78, 128.35, 127.41, 126.68, 125.97, 123.85, 123.65, 123.54, 111.75,
102.25, 56.14; MS (MALDI-TOF) m/z 672 [M]þ (100%); HRMS (ESI)
(C41H25MgN7O2) [MþH]þ: calcd: 671.1915; found: 671.1923
[MþH]þ.
4 . 5 . 3 . ( 2 0 - ( 1 - P y r e n y l ) - t e t r a b e n z o [ b , g , q , l ] - 5 ,10 ,15 -
triazaporphyrinato)magnesium 24. Synthesised following the gen-
eral procedure described above using a solution of phthalonitrile
(154.0 mg, 1.20 mmol) and MgBr2 (110.0 mg, 0.60 mmol) in dry
diglyme (1.0 ml), heating at 220 ꢀC ꢀC for 10 min under argon and
initially adding aminoisoindoline 23 (138 mg, 0.40 mmol) and
phthalonitrile (51.0 mg, 0.40 mmol) in dry diglyme (1.5 ml) over
30 min. Finally, a solution of phthalonitrile (51.0 mg, 0.40 mmol)
and DABCO (6 mg, 0.60 mmol) in dry diglyme (0.5 ml) was added
dropwise over 30 min and the mixture heated for a further 1.5 h.
The crude product was purified by column chromatography using
AcOEt/PE (1:3) then AcOEt/PE/THF (3:10:1) as eluent gradient.
Recrystallisation from THF and hexane gave 24 as green-purple
crystals (35 mg, 12%); mp >300 ꢀC; UVevis (THF) lmax/nm (
) 670
3
(7.35ꢁ103), 647 (4.41ꢁ103), 592 (1.03ꢁ102), 442 (1.03ꢁ102), 397
(2.50ꢁ102); nmax/cmꢂ1 (ATR) 3054, 1606, 1512, 1481, 1328; 1H NMR
(500 MHz, THF-d8, 298 K):
d (ppm) 9.55e9.50 (m, 6H), 8.79 (d,
4.5.1. (20-(3-Methoxyphenyl)-tetrabenzo[b,g,q,l]-5,10,15-
triazaporphyrinato)magnesium 20. Synthesised following the gen-
eral procedure described above using a solution of phthalonitrile
(154.0 mg, 1.20 mmol) and MgBr2 (110.0 mg, 0.60 mmol) in dry
J¼7.6 Hz, 1H), 8.75 (d, J¼7.6 Hz, 1H), 8.59 (d, J¼9.2 Hz, 1H), 8.46 (d,
J¼9.2 Hz, 1H), 8.42 (dd, J¼7.3, 1.6 Hz, 1H), 8.20e8.17 (m, 4H), 8.09
(dd, J¼7.3, 1.6 Hz, 1H), 8.06 (t, J¼7.3 Hz, 1H), 7.71 (ddd, J¼7.5, 7.0,
0.7 Hz, 2H), 7.61 (d, J¼9.4 Hz, 1H), 7.50 (d, J¼9.4 Hz, 1H), 7.09 (ddd,

N. Alharbi et al. / Tetrahedron 70 (2014) 7370e7379
7379
J¼8.1, 7.0, 1.1 Hz, 2H), 6.23 (br dt, 2H, J¼8.1, 0.7 Hz, 1H).; 13C NMR
Carvalho, C. M. B.; Timothy John Brocksom, T. J.; de Oliveira, K. T. Chem. Soc. Rev.
2013, 42, 3302e3317.
4. Borisov, S. M.; Zenkl, G.; Klimant, I. Appl. Mater. Interfaces 2010, 2, 366e374.
(125.7 MHz, THF-d8, 298 K): d (ppm) 156.7,153.6,153.2,152.6,143.5,
141.1, 140.8, 140.6, 140.1, 138.2, 133.5, 133.3, 133.2, 133.0, 132.1, 131.7,
130.0,129.7, 129.3, 128.8,128.7, 128.1, 127.4, 127.1, 126.6,126.2, 126.1,
126.0, 126.0, 125.9, 125.0, 123.8, 123.6, 123.4; MS (MALDI-TOF) m/z
735.5 [M]þ (100%); HRMS (MALDI) (C49H25N7Mg) [M]þ: calcd:
735.2016; found: 735.2024.
5. Dent, C. E. J. Chem. Soc. 1938, 1e6.
6. Helberger, J. H. Liebigs Ann. 1937, 529, 205e218.
7. Linstead, R. P. J. Chem. Soc. 1934, 1016e1017.
8. Barrett, P. A.; Linstead, R. P.; Tuey, G. A. P.; Robertson, J. M. J. Chem. Soc. 1939,
1809e1820.
9. Godfrey, M. R.; Newcomb, T. P.; Hoffman, B. M.; Ibers, J. A. J. Am. Chem. Soc. 1990,
112, 7260e7269.
10. Antunes, E. M.; Nyokong, T. J. Porphyrins Phthalocyanines 2009, 13, 153e160.
11. Solov’ev, K. N.; Kachura, T. F.; Shkirman, S. F. Zh. Priklad. Spektroskop. 1964, 1,
85e87.
12. Kalleta, B.; Rolf, M.; Wolf, W.; Terrell, D. R. German Patent 39 37 716 A1, 1991.
13. Kopranenkov, V. N.; Makarova, E. A.; Dashkevich, S. N. Khim. Geterotsikl. Soedin.
1985, 10, 1372e1377.
4.5.4. (20-(3-Hydroxyphenyl)-tetrabenzo[b,g,q,l]-5,10,15-tri-
azaporphyrinato)magnesium 21. A solution of TBTAP 20 (40 mg,
0.062 mmol) in distilled DCM (5 mL) was stirred at 0 ꢀC for 5 min
under an argon atmosphere. A solution of BBr3 (1.25 mL, 1.25 mmol,
20 equiv, 1 M in DCM) was added dropwise over 1 h using a syringe
pump. After finishing the addition, the reaction mixture was left to
warm to room temperature and stirred for further 1 h. MeOH (5 ml)
was added and the mixture sonicated for 5 min. The solvents were
removed under reduced pressure and the crude product was pu-
rified by column chromatography on silica gel using DCM/Et3N/THF
(20:1:3) as eluent. Recrystallisation from acetone/EtOH gave the
title compound as green crystals with purple reflex (19 mg, 50%); mp
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>300 ꢀC; UVevis (THF) lmax/nm (
3
) 670 (4.14ꢁ103), 646 (2.26ꢁ103),
592 (5.65ꢁ102), 444 (1.88ꢁ102), 428 (3.77ꢁ102), 383 (1.32ꢁ103);
nmax/cmꢂ1 (ATR) 3600e3100 (br), 1455, 1348; 1H NMR (500 MHz,
THF-d8, 298 K):
d
(ppm) 9.59 (d, J¼7.5 Hz, 2H), 9.53e9.50 (m, 4H),
8.82 (br s, 1H, OH), 8.21e8.15 (m, 4H), 7.92 (t, J¼7.0 Hz, 2H),
7.79e7.74 (m, 1H), 7.66e7.61 (m, 3H), 7.54 (s, 1H), 7.46 (ddd, J¼8.4,
2.4, 0.9 Hz, 1H), 7.36 (d, J¼8.0 Hz, 2H); MS (MALDI-TOF) m/z 628
[M]þ (100%); HRMS (ESI) (C39H21MgN7O) [M]þ: calcd: 627.1653;
found: 627.1654.
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Acknowledgements
We thank the EU (273309) for funding (A.D.-M.) and the EPSRC
National Mass Spectrometry Service Centre, Swansea, for HRMS
data.
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