Synthesis and Aggregation Studies of Functional Binaphthyl-Bridged Chiral Phthalocyanines

Article abstract of DOI:10.1021/acs.orglett.9b02718

We describe the preparation of a battery of chiral Zn(II) phthalocyanines with an AABB substitution pattern through cross-condensation of different chiral, binaphthyloxy-linked bisphthalonitriles and (non)functionalized single phthalonitriles. All the compounds are endowed with reactive groups (halogen and/or ethynyl moieties) that will allow us to prepare customized amphiphilic phthalocyanines. Preliminary self-assembly studies in solution have been performed by UV-vis and circular dichroism experiments.

Full text of DOI:10.1021/acs.orglett.9b02718

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Synthesis and Aggregation Studies of Functional Binaphthyl-
Bridged Chiral Phthalocyanines
†
,†,‡,§
́
́
Miguel A. Revuelta-Maza, Tomas Torres,*
and Gema de la Torre*,†,‡
†
́
́
Universidad Autonoma de Madrid, c/Francisco Tomas y Valiente 7, 28049 Madrid, Spain
‡
́
Institute for Advanced Research in Chemical Sciences (IAdChem), Universidad Autonoma de Madrid, 28049 Madrid, Spain
§Instituto Madrilen
o de Estudios Avanzados (IMDEA)-Nanociencia, c/Faraday 9, Cantoblanco, 28049 Madrid, Spain
̃
S
* Supporting Information
ABSTRACT: We describe the preparation of a battery of
chiral Zn(II) phthalocyanines with an AABB substitution
pattern through cross-condensation of different chiral,
binaphthyloxy-linked bisphthalonitriles and (non)-
functionalized single phthalonitriles. All the compounds are
endowed with reactive groups (halogen and/or ethynyl
moieties) that will allow us to prepare customized amphiphilic
phthalocyanines. Preliminary self-assembly studies in solution
have been performed by UV−vis and circular dichroism
experiments.
ecause of their excellent optical and electronic properties,
active AABB Pcs and related derivatives functionalized with
Bphthalocyanines (Pcs) are appealing functional chromo- solubilizing akyl or alkoxy moieties at the B isoindoles,18−21
but there are no reports on the synthesis and characterization
of chiral C2v-type AABB Pcs with an amphiphilic character
imparted by the proper substitution at either the binaphthyl
rings or the A isoindoles, or at both sites.22 Self-assembling
amphiphile systems, specially π-conjugated23 and chromo-
phoric24 building blocks, is an efficient route to construct a
large variety of useful nanostructures.25 Therefore, a
customized functionalization of optically active AABB Pcs
could convert them in amphiphiles prone to self-assemble in a
chiral fashion through an interplay of π−π interactions and
solvent-induced effects.
In recent years, we have reported several examples of
“oppositely” substituted-Pcs (ABAB, D2h type),26 which have
been successfully employed either for building unprecedented
donor-π-acceptor chromophores for photovoltaic cells27 or as
potential photosensitizers for photodynamic therapy when
appropriately functionalized with hydrophilic groups.28 Now,
we are focusing our attention on the synthesis of binaphthyl-
containing AABB Pcs as platforms for the preparation of
differently functionalized C2v systems provided with amphi-
philic character and self-assembly abilities that can give rise to
outstanding chiral nanostructures. To this aim, we have
explored the preparation of a battery of optically active, low
symmetrical AABB Pcs (1−6, Scheme 1) from AA
bisphthalonitriles (7a−d) and (non)functionalized single
phthalonitriles (8a−d). The final goal is to prepare AABB
phores with applications in different fields that span from
materials science to nanomedicine.1 In particular, helical
supramolecular architectures fabricated from optically active
Pc compounds have attracted widespread attention in relation
with their potential applications in chiral sensing, catalysis, and
chiroptical devices.2−4 Among the different strategies to induce
chirality in Pcs,3−7 the introduction of optically active
binaphthyl conformers as substituents deserves special
mention. Binaphthyl-containing Pcs were formerly described
by Kobayashi and co-workers,8 who demonstrated that the
optical purity of the binaphthyloxy-phthalonitrile precursor
was preserved under the harsh conditions of the Pc core
formation. From then on, several Pcs and related compounds
endowed with optically pure binaphtyl cores have been
prepared,9−13 some of them (i.e., symmetrically substituted
derivatives) showing self-assembly abilities that lead to chiral
supramolecular structures.14−17
Within this family of compounds, particularly interesting are
the low-symmetry, optically active “adjacent” type Pcs with C2v
symmetry (Scheme 1), which can be envisioned as central
cores for the development of amphiphilic Pcs after proper
functionalization at the different positions of the macrocycle.
This type of compounds was previously synthesized by mixed
condensation between a (non)functionalized phthalonitrile
(B) and a geometrically constrained binaphthyloxy-bridged
bisphthalonitrile (AA). This approach substantially reduced
the number of possible Pcs formed in the statistical cross-
condensation from six to three, namely AAAA, AABB, and
BBBB Pcs. Several groups have reported a number of optically
Received: August 2, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02718
Org. Lett. XXXX, XXX, XXX−XXX

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Organic Letters
Letter
a
together with the corresponding symmetrical (B)4 and (AA)2
ZnPcs. It is worth mentioning that, in the previous reports on
binaphthyl AABB Pcs, AA phthalonitriles had to be converted
into their more reactive isoindoline forms, and then reacted
with another 1,3-diiminoisoindoline derivative, followed by a
metalation step.18,21 In our case, using the above-mentioned
conditions, we could skip the activation of both precursors and
the subsequent metalation, while still obtaining our ZnPcs 1−6
in similar, or even higher yields, than those previously
reported.
Scheme 1. Synthesis of AABB ZnPcs
From all the possible combinations of bisphthalonitriles 7a−
d and phthalonitriles 8a−d, we selected those in which (i)
halogens are installed in only one of the components, AA or B
(i.e., ZnPcs 1 and 4), which would permit further coupling
reactions with, for instance, hydrophilic moieties; (ii) one of
the components is endowed with hydrophobic alkyl chains and
the other holds halogen atom(s) (i.e., ZnPcs 2, 3 and 5); and
(iii) the ethynyl-containing bisphthalonitrile 7d is reacted with
halogen-containing phthalonitriles, affording the possibility of
orthogonal functionalization of both components through
cross-coupling methodologies. First, cross condensation
between nonfunctionalized bisphthalonitrile 7a and iodo-
containing phthalonitriles 8a and 8b was tackled. Isolation of
the target AABB ZnPc 1 proved difficult, but it was finally
obtained in 11% yield. However, the condensation of 7a with
8b gave rise to mixtures from which the target AABB
compound could not be isolated. Bisphthalonitrile 7b,
functionalized with two octyl chains, reacted successfully
with both iodo-containing phthalonitriles 8a and 8b, leading to
ZnPcs 2 and 3 in 17% and 33% yields, respectively, which can
be considered from moderate to good considering the
statistical nature of the process. However, the opposite
approach that implies the reaction of the hydrophobic
phthalonitrile 8d with the bromo-containing bisphthalonitrile
7c led to the corresponding AABB ZnPc 5 in the lowest yield
of the series (6%). 7c was also reacted with the non-
functionalized phthalonitrile 8c to give ZnPc 4 in 21% yield.
Finally, ethynyl-containing bisphthalonitrile 7d was reacted
with 8a and 8b, but only ZnPc 6 endowed with two iodine
atoms could be obtained in moderate 13% yield. Attending to
their interesting functionalization pattern, which can also lead
to interesting nanostructures upon appropriate derivatization,
the symmetrical tetrabromo- ((AA)2-c) and tetraethynyl-
((AA)2-d) ZnPcs were isolated from the reaction mixtures
and properly characterized (see the Supporting Information).
1H NMR spectra of ZnPcs 1−6 were registered in
coordinative solvents such as THF-d8 or DMSO-d6 to avoid
aggregation, but in most of the cases, heating at 50 °C (in
THF) or 90 °C (in DMSO) was also necessary to further
break the aggregation that most of the compounds show at
NMR concentrations (i.e., 10−3 M) (see the Supporting
Information). In Figure 1, the well-resolved spectrum of AABB
ZnPc 5 is compared with those of its B4 and (AA)2
counterparts.
a
(i): o-DCB/DMF, 2:1, Zn(OAc)2 160°C, overnight.
Pcs in reasonable yields, and containing reactive groups
(halogen and/or ethynyl moieties) that can give rise to further
chemical transformations directed toward the introduction of
hydrophilic residues. On the other hand, in order to enhance
the solubility and enlarge the hydrophobic part of the final Pc,
some of the AA and B precursors have been decorated with
alkyl chains. In such a way, the prepared Pc building blocks can
give rise to a variety of customized compounds with
amphiphilic features that will allow us to modulate their
properties in terms of solubility and supramolecular organ-
ization.
Key AA-bisphthalonitriles 7a−d were prepared from the
chiral (R)-1,1′-bi-2-naphthol (BINOL) (see the Supporting
Information). The synthesis of 7a18,29 and 7b14,30,31 had been
previously described. In the case of 7c, we have also prepared
the (S)-enantiomer in order to check if the chirality of the
binaphthyl unit is preserved under the conditions that we apply
for the preparation of Pcs. Therefore, 7c was prepared through
a double ipso-substitution of 3-nitrophthalonitrile with either
(S)- or (R)-6,6′-dibromo-1,1′-bi-2-naphthol 9 (Scheme S1 at
the Supporting Information), which were previously obtained
by bromination of the corresponding enantiomer of BINOL.30
Finally, (R)-9 was subjected to Sonogashira coupling with
tBuMe2Si-acetylene,32 yielding a BINOL derivative function-
alized with protected ethynyl moieties (10) that led to the
latter bisphthalonitrile 7d (Scheme S1).
To confirm the optical stability of the binaphthyl unit under
the reaction conditions, and therefore the optical purity of the
final ZnPcs, we have recorded the circular dichroism (CD)
spectra in THF of ZnPcs 4 prepared from the two different
enantiomers of 7c (Figure 2). The presence of the optically
active binaphthyl moieties induces the appearance of CD
signals in both the Soret and Q band regions,9 although the
latter is much less intense than the Soret contribution. The
spectra recorded with identical concentrations of the R and S
With the bisphthalonitriles 7a−d in hand, we proceeded to
carry out the mixed condensation with single phthalonitriles,
8a−d (Scheme 1), which are either commercially available or
prepared following reported procedures (see the Supporting
Information). The cross condensation was performed by
heating a 1:2 mixture of the corresponding AA-bisphthaloni-
triles and the single phthlonitriles B, respectively, in the
presence of Zn(OAc)2 in o-DCB/DMF 2:1 at 160 °C. In these
conditions, the target AABB derivatives 1−6 were formed,
B
DOI: 10.1021/acs.orglett.9b02718
Org. Lett. XXXX, XXX, XXX−XXX

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Organic Letters
Letter
ing broad blue-shifted bands compatible with the formation of
H-aggregates (see the spectra for ZnPc 3 in Figure 2). ZnPc 3
is the compound that seems to form more stable aggregates
(please compare Figure 3 and Figures S20 and S47 in the
Figure 1. 1H NMR of B4-d, ZnPc 5 and (AA)2-c in DMSO-d6 (*) at
90 °C. For full assignation, see the Supporting Information.
Figure 3. CD and absorption spectra for ZnPc 3: temperature
dependence of the CD signals (top) and the absorption bands
(bottom) in toluene (A) and MCH (B). Concentration: ∼10−4 M. *:
Spectra recorded after cooling down from 353 K.
Supporting Information), which could be rationalized on the
basis of (i) it largest polarization, due to the presence of four
iodine atoms (instead of the two installed in 2 and 6) and/or
(ii) a better organization of the Pcs in the assembly, as ZnPc 3
is composed of a single regioisomer, while 2 and 6 are, indeed,
a mixture of three positional isomers. Therefore, further
aggregation experiments for this compound are detailed below,
while studies on 2 and 6 are detailed in the Supporting
Information.
Therefore, to check the stability of the aggregates formed in
noncoordinative solvents, we heated the toluene and MCH
solutions of ZnPc 3 up to 80 °C (Figure 3). For the former,
the absorption spectrum of the monomeric species was
recovered, but for MCH, the monomer/aggregate band ratio
remained similar. Similarly, addition of THF to the solutions of
ZnPc 3 in toluene at room temperature led to the recovery of
the monomeric species (with only 1% of THF), but in MCH,
full disaggregation was only achieved at 40% of THF.
Turning to CD experiments, and comparing the spectra in
THF with those in toluene and MCH (Figure 2), we can
observe a change in the dichroic behavior of the monomeric
species and the aggregates. In THF, a weak Cotton effect was
observed in the Q band transition, with a negative and a
positive sign at 696 and 627 nm, respectively, and a very strong
positive signal at 352 nm for the B band transition. In toluene,
a change of sign for the CD signals in the Q band region is
observed (i.e. positive signal at 743 nm and negative at 637
nm), together with the raising of a new small positive signal at
565 nm, while the B band region remains similar. The
spectrum recorded in MCH exhibits similar signals to those in
toluene for the Q band transitions, whereas the intensity of the
signal at 352 nm decreases. According to the UV−vis
experiments, heating the toluene solution at 80 °C (Figure
Figure 2. (A) CD of ZnPcs (S)-4 and (R)-4 (top) together with the
electronic absorption spectrum in THF (bottom); (B) CD of ZnPc
(R)-3 in THF, toluene and MCH, together with the corresponding
electronic absorption spectra.
enantiomers show transitions that are mirror images, thus
confirming that racemization does not occur during the
formation of the Pc. Importantly, as observed in similar,
previously reported, (R)-binaphthyloxy-bridged AABB Pcs,18
the spectra for ZnPcs 1−6 in THF solution, where they are
molecularly dissolved, show mainly positive CD envelopes
corresponding to the main Soret and Q bands (see Figure 2
and the Supporting Information).
Following with the optical characterization of ZnPcs 1−6,
we registered their absorption in different solvents. For all the
compounds, UV−vis spectra in THF at concentration ca. 10−6
M showed a single, narrow Q band typical for metallic
monomeric Pcs, which is also compatible with their C2v
symmetry. Turning to toluene solutions, ZnPcs 1, 4, and 5
do not aggregate either in this solvent (see the Supporting
Information), but the compounds holding alkyl chains or
alkylsilyl-protected ethynyl moieties at the binaphthyl unit (2,
3, 6) show evidence of aggregation in their spectra (Figure 2
and Supporting Information), probably as a consequence of
their most pronounced amphiphilic character imparted by both
the presence of hydrocarbon chains and the polarization of the
aromatic core induced by the halogen atoms. For the three
derivatives we recorded the absorption spectra in a more
nonpolar solvent, namely methylcyclohexane (MCH), discern-
C
DOI: 10.1021/acs.orglett.9b02718
Org. Lett. XXXX, XXX, XXX−XXX

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Organic Letters
Letter
(6) Rai, R.; Saxena, A.; Ohira, A.; Fujiki, M. Langmuir 2005, 21,
3957−3962.
3) leads to a disassembly of the aggregate (please compare the
spectrum at 353 K in toluene in Figure 3A and the spectrum in
THF in Figure 2B), but in the case of MCH solutions, the CD
signals remain similar and only an increase in intensity is
observed. This behavior matches that observed in the UV−vis
experiments, both indicating that robust H-aggregates of ZnPc
3 are formed in MCH.
As a conclusion, we have successfully prepared a battery of
chiral, binaphthyl-functionalized AABB ZnPcs, which are
endowed with halogen and/or ethynyl moieties that can be
further transformed to obtain a variety of customized
compounds with amphiphilic features, in the search for chiral
supramolecular nanostructures. Some of the ZnPcs show
aggregation behavior in nonpolar solvents, and, in particular,
ZnPc 3 with a well-defined C2v geometry forms robust, chiral
nanostructures in solution. This feature, together with its
functionalization with both alkyl chains and iodine atoms, turn
this derivative into a model synthon for further preparation of
amphiphilic ZnPcs able to self-assemble in polar media. More
profound studies on the self-assembly of these compounds and
their derivatives to discern the chiral nature of the
nanostructures formed in solution and/or on surfaces will be
undertaken.
́
(7) Berrocal, J. A.; Torres, T.; Gonzalez-Rodríguez, D.; García-
Iglesias, M. Chem. Commun. 2016, 52, 10870−10873.
(8) Kobayashi, N.; Kobayashi, Y.; Osa, T. J. Am. Chem. Soc. 1993,
115, 10994−10995.
(9) Kobayashi, N.; Higashi, R.; Titeca, B. C.; Lamote, F.;
Ceulemans, A. J. Am. Chem. Soc. 1999, 121, 12018−12028.
(10) Liu, H.; Liu, Y.; Liu, M.; Chen, C.; Xi, F. Tetrahedron Lett.
2001, 42, 7083−7086.
(11) Zhao, L.; Wang, K.; Furuyama, T.; Jiang, J.; Kobayashi, N.
Chem. Commun. 2014, 50, 7663−7665.
(12) Zhou, H.; Wang, K.; Qi, D.; Jiang. J. Dalton Trans. 2014, 43,
1699−1705.
(13) Zhao, L.; Wang, K.; Shang, H.; Jiang, J. Dyes Pigm. 2015, 120,
52−56.
(14) Lv, W.; Zhang, X.; Lu, J.; Zhang, Y.; Li, X.; Jiang, J. Eur. J. Inorg.
Chem. 2008, 2008, 4255−4261.
(15) Wu, L.; Wang, Q.; Lu, J.; Bian, Y.; Jiang, J.; Zhang, X. Langmuir
2010, 26, 7489−7497.
(16) Wang, K.; Qi, D.; Wang, H.; Cao, W.; Li, W.; Jiang, J. Chem. -
Eur. J. 2012, 18, 15948−15952.
(17) Zhang, C.; Jing, L.; Lin, S.; Hao, Z.; Tian, J.; Zhang, X.; Zhu, P.
ChemPhysChem 2013, 14, 3827−3833.
(18) Kobayashi, N. Chem. Commun. 1998, 487−488.
(19) Kobayashi, N.; Miwa, H.; Isago, H.; Tomura, T. Inorg. Chem.
1999, 38, 479−485.
ASSOCIATED CONTENT
* Supporting Information
■
(20) Kobayashi, N.; Miwa, H.; Nemykin, V. N. J. Am. Chem. Soc.
2002, 124, 8007−8020.
S
(21) (a) Seotsanyana-Mokhosi, I.; Nyokong, T. J. J. Porphyrins
Phthalocyanines 2004, 8, 1214−1221. (b) Seotsanyana-Mokhosi, I.;
Chenb, J.-Y.; Nyokong, T. J. Porphyrins Phthalocyanines 2005, 9, 316−
325.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02718.
Experimental procedures and spectral data for all the
new compounds (PDF)
(22) Non-chiral ZnPcs but with an amphiphilic character and C2v
geometry have been described: Ongarora, B. G.; Hu, X.; Li, H.;
Fronczek, F. R.; Vicente, M. G. MedChemComm 2012, 3, 179−194.
(23) (a) Hill, J. P.; Jin, W.; Kosaka, A.; Fukushima, T.; Ichihara, H.;
Shimomura, T.; Ito, K.; Hashizume, T.; Ishii, N.; Aida, T. Science
2004, 304, 1481−1483. (b) Jin, W.; Yamamoto, Y.; Fukushima, T.;
Ishii, N.; Kim, J.; Kato, K.; Takata, M.; Aida, T. J. Am. Chem. Soc.
2008, 130, 9434−9440.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: tomas.torres@uam.es.
*E-mail: gema.delatorre@uam.es.
(24) (a) Chen, Z.; Liu, Y.; Wagner, W.; Stepanenko, V.; Ren, X.;
ORCID
Ogi, S.; Wu
̈
rthner, F. Angew. Chem., Int. Ed. 2017, 56, 5729−5733.
̈
̈
(b) Wurthner, F.; Saha-Moller, C. R.; Fimmel, B.; Ogi, S.;
́
Tomas Torres: 0000-0001-9335-6935
Notes
Leowanawat, P.; Schmidt, D. Chem. Rev. 2016, 116, 962−1052.
(25) (a) Wang, C.; Wang, Z.; Zhang, X. Acc. Chem. Res. 2012, 45,
608−618. (b) Ramanathan, M.; Shrestha, L. K.; Mori, T.; Ji, Q.; Hill,
J. P.; Ariga, K. Phys. Chem. Chem. Phys. 2013, 15, 10580−10611.
(c) Barclay, T. G.; Constantopoulos, K.; Matisons, J. Chem. Rev. 2014,
114, 10217−10291.
(26) Fazio, E.; Jaramillo-García, J.; de la Torre, G.; Torres, T. Org.
Lett. 2014, 16, 4706−4709.
(27) (a) Fazio, E.; Nazeerudin, M. K.; de la Torre, G.; Medel, M.;
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work has been supported by MINECO (CTQ2017-
85393-P) and ERA-NET/MINECO EuroNanoMed2017-191/
PCIN-2017-042.
̈
Gratzel, M.; Jaramillo-García, J.; Urbani, M.; Torres, T. Chemis-
́
tryOpen 2017, 6, 121−127. (b) Fazio, E.; Winterfeld, K. A.; Lopez-
REFERENCES
■
́
Perez, A.; Torres, T.; Guldi, D. M.; de la Torre, G. Nanoscale 2018,
(1) (a) McKeown, N. B. Phthalocyanine Materials Synthesis, Structure
and Function, Cambridge; University Press: Cambridge, 1998. (b) de
la Torre, G.; Bottari, G.; Torres, T. Adv. Energy Mater. 2017, 7,
1601700. (c) Almeida-Marrero, V.; van de Winckel, E.; Anaya-Plaza,
E.; Torres, T.; de la Escosura, A. Chem. Soc. Rev. 2018, 47, 7369−
7400.
10, 22400−22408.
(28) (a) Revuelta-Maza, M. A.; Hally, C.; Nonell, S.; de la Torre, G.;
Torres, T. ChemPlusChem 2019, 84, 673−679. (b) Revuelta-Maza, M.
A.; Nonell, S.; de la Torre, G.; Torres, T. Org. Biomol. Chem. 2019, 17,
7448.
(29) Leznoff, C. C.; Marcuccio, S. M.; Greenberg, S.; Lever, A. B. P.;
Tomer, K. B. Can. J. Chem. 1985, 63, 623−631.
(30) Sogah, G. D. Y.; Cram, D. J. J. Am. Chem. Soc. 1979, 101,
3035−3042.
(2) Kobayashi, N. Coord. Chem. Rev. 2001, 219−221, 99−123.
(3) Thordarson, P.; Nolte, R. J. M.; Rowan, A. E. In Porphyrin
Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic
Press: 2003; Vol 18, pp 281−301.
(4) Jiang, Y.; Liu, C.; Wang, X.; Wang, T.; Jiang, J. Langmuir 2017,
33, 7239−7247.
(5) Engelkamp, H.; Middelbeek, S.; Nolte, R. J. M. Science 1999,
284, 785−788.
(31) Hu, Q.-S.; Zheng, X.-F.; Pu, L. J. Org. Chem. 1996, 61, 5200−
5201.
(32) Sasai, H.; Tokunaga, T.; Watanabe, S.; Suzuki, T.; Itoh, N.;
Shibasaki, M. J. Org. Chem. 1995, 60, 7388−7389.
D
DOI: 10.1021/acs.orglett.9b02718
Org. Lett. XXXX, XXX, XXX−XXX