Regioselective synthesis of 1,2- vs 1,3-squaraines

Article abstract of DOI:10.1021/ol201093t

Squaraines have been known for many decades as very stable and versatile vis-NIR absorbing dyes. They have found applications for example as sensitizers in organic photovoltaics and photodetectors. The most common squaraine structure is the 1,3-regioisomer. Their 1,2-regioisomers are seldom mentioned and unanimously regarded as side products. A facile direct synthesis of 1,2-squaraines, highlighting the role played by reaction conditions and electronic factors, is described. The first electrochemical characterization of these dyes is also shown.

Full text of DOI:10.1021/ol201093t

ORGANIC
LETTERS
2011
Vol. 13, No. 12
3166–3169
Regioselective Synthesis of
1,2- vs 1,3-Squaraines
Elisabetta Ronchi,† Riccardo Ruffo,† Silvia Rizzato,‡ Alberto Albinati,‡
Luca Beverina,*,† and Giorgio A. Pagani†
Department of Materials Science and INSTM, University of Milano-Bicocca,
Via Cozzi 53, I-20125, Milano, Italy, and Department of Structural Chemistry,
University of Milano, Via Venezian 21, 20133 Milano, Italy
luca.beverina@mater.unimib.it
Received April 26, 2011
ABSTRACT
Squaraines have been known for many decades as very stable and versatile visꢀNIR absorbing dyes. They have found applications for
example as sensitizers in organic photovoltaics and photodetectors. The most common squaraine structure is the 1,3-regioisomer. Their
1,2-regioisomers are seldom mentioned and unanimously regarded as side products. A facile direct synthesis of 1,2-squaraines,
highlighting the role played by reaction conditions and electronic factors, is described. The first electrochemical characterization of
these dyes is also shown.
Squaraines (squarylium dyes) are the condensation pro-
duct of two electron rich derivatives (activated arenes,
anhydrobases) and squaric acid.1 Although alternative synth-
eses are possible,2 symmetric squaraines have almost unan-
imously been prepared by direct condensation of the reactants
under azeotropic removal of the formed water.3 Mostly, the
reaction is regioselective and the major products correspond
to the 1,3-isomers. These products are, from the electronic
point of view, reminiscent of cyanines, with which they share
most of the photophysical properties (i.e., a sharp and intense
absorption band, NIR fluorescence, nonlinear optical
behavior).4 Scheme 1 shows, as a representative example,
the condensation of 2 equiv of the anhydrobase generated in
situ by reaction of 1a with a suitable base (quinoline, imida-
zole, triethylamine) with squaric acid to give the 1,3-squaraine
25 (the major product) and the corresponding 1,2-regioisomer
3 (the side product). Symmetric diarylcyclobutendiones (that
is 1,2-squaraines in the case of a conjugated substituent) have
been selectively prepared by the FriedelꢀKraft reaction of
squaryl chloride and 2 equiv of a suitable arene.6
Nonsymmetric derivatives can be prepared by the se-
quential StilleꢀLiebeskind/Srogl reactions of 3-chloro-4-
arylthiocyclobutene with suitable precursors.7 The direct
(5) Santos, P. F.; Reis, L. V.; Almeida, P.; Serrano, J. P.; Oliveira,
A. S.; Vieira Ferreira, L. F. J. Photochem. Photobiol., A 2004, 163, 267–
269.
(6) Ried, W.; Vogl, M. Liebigs Ann. Chem. 1977, 101–105. The first
1,2-squaraine was prepared by acid hydrolysis of 1,2-diphenyl-3,3,4,4-
tetrafluorocyclobuten by Blomquist (Blomquist, A. T.; La Lancette,
E. A. J. Am. Chem. Soc. 1961, 83, 1387–1391).
† Department of Materials Science and INSTM, University of Milano-
Bicocca.
‡ Department of Structural Chemistry, University of Milano.
(1) Beverina, L.; Salice, P. Eur. J. Org. Chem. 2010, 7, 1207–1225.
(2) Law, K.; Bailey, F. J. Org. Chem. 1992, 57, 3278–3286.
(3) Keil, D.; Hartmann, H. Dyes Pigm. 2001, 49, 161–179.
(4) Sreejith, S.; Carol, P.; Chithra, P.; Ajayaghosh, A. J. Mater.
Chem. 2008, 18, 264–274.
~
(7) Aguilar-Aguilar, A.; Pena-Cabrera, E. Org. Lett. 2007, 9, 4163–
4166.
r
10.1021/ol201093t
Published on Web 05/19/2011
2011 American Chemical Society

reacted ethyl squarate and 1a in ethanol in the presence
of a stoichiometric amount of triethylamine. The reac-
tion gave 6a, along with a strongly red colored
byproduct that was isolated by chromatography
and crystallized by the orthogonal solvents method
to obtain single crystals. The diffraction analysis
confirmed the proposed structure for derivative 3
(see Figure 1).
Scheme 1
This first experiment shows that 1,2-squaraines share
with their 1,3-regioisomers a strong coloration. They
also possess a very remarkable stability and complete
redox reversibility (vide infra). All these properties
make them suitable as sensitizers in organic photovol-
taic and photodetecting devices.14 In particular, 1,2-
squaraines could be highly interesting for green-oper-
ating photodetectors as they show a strong absorption
close to the technologically relevant wavelength of 550
nm.15 The 1,3-squaraines do not efficiently absorb in
this region.
reaction of an activated arene (dimethylaniline) and
butyl squarate in humid BuOH gives the 1,2-squar-
aines only in traces amounts.8 Treibs and Jacobs
obtained 1,2-squaraines by reaction of activated arene
and squaric acid in acetic anhydride. In this case the
squaric acid is readily converted in the corresponding
acetate, which in turn behaves like squaryl chloride.9
The literature does not report any useful direct synth-
esis of 1,2-squaraines from squaric acid or esters.
Moreover no detailed characterization of their proper-
ties with respect to the most common 1,3-derivatives is
available.
Scheme 2
Our interest in this class of compounds was
prompted by the remarkable performances that stan-
dard 1,3-squaraines show as active materials in photo-
conducting devices.10 Also, the lack of complete
condensation regioselectivity in the reaction between
an activated molecule and squaric acid has important
consequences in the synthesis of polysquaraines.11
The formation of the 1,2-regioisomer corresponds
in this case to the formation of 1,2-diketonic defects
that are incorporated in the growing polymer
chain.12 A better understanding of the factors influen-
cing the 1,2- versus 1,3- condensation pathways could
provide guidelines for the synthesis of fully regioregular
polysquaraines.
In this paper, we focus on the improvement of a regio-
selective synthesis of 1,2-squaraines. In order to do this, we
first studied, as a reprehensive case, the syntheses under a
variety of different conditions of two symmetric squar-
aines, the benzothiazole derivative 2 and the dimethylin-
dolenine derivative 8,16 along with their corresponding
1,2-regioisomers (Schemes 1 and 2b).
The first importantobservation tostart withisthat3 was
first obtained while preparing 6a.13 Derivative 3 could be
formed by the reaction of a second equivalent of 1a either
with 6a or with the corresponding emisquaraine 6b
obtained by in situ hydrolysis of 6a. We tested the two
possible reaction pathways by reacting 1a indepen-
dently with 6a in anhydrous ethanol and with the
emisquaraine 6b in absolute ethanol. In the first case
To explore the potentially appealing chemical and
photophysical properties of 1,2-squaraines, we re-
peated the only literature procedure describing (but
without a complete characterization) the direct forma-
tion of 3 as a byproduct in the synthesis of 6a.13 We
(8) Law, K.-Y.; Court Bailey, F. Can. J. Chem. 1986, 64, 2267–2273.
(9) Treibs, A.; Jacob, K. Liebigs Ann. Chem. 1966, 699, 153–167.
(10) (a) Bagnis, D.; Beverina, L.; Huang, H.; Silvestri, F.; Zheng, Y.;
Pagani, G. A.; Marks, T. J.; Facchetti, A. J. Am. Chem. Soc. 2010, 132,
4074–4075. (b) Wei, G.; Wang, S.; Sun, K.; Thompson, M. E.; Forrest,
S. R. Adv. Energy Mater. 2011, 1, 184–187.
(11) Eldo, J.; Ajayaghosh, A. Chem. Mater. 2002, 14, 410–418.
(12) Chenthamarakshan, C. R.; Eldo, J.; Ajayaghosh, A. Macromo-
lecules 1999, 32, 5846–5851.
(13) (a) Sprenger, H. E.; Ziegenbein, W. Angew. Chem., Int. Ed. 1967,
6, 553–4. (b) Sprenger, H. E.; Ziegenbein, W. Angew. Chem., Int. Ed.
1967, 7, 530–535.
(14) Binda, M.; Agostinelli, T.; Caironi, M.; Natali, D.; Sampietro,
M.; Beverina, L.; Ruffo, R.; Silvestri, F. Org. Electron. 2009, 10, 1314–
1319.
(15) Binda, M.; Natali, D.; Sampietro, M.; Agostinelli, T; Beverina,
L. Nucl. Instrum. Meth. A 2010, 624, 443–448.
(16) Treibs, A.; Jacob, K. Liebigs Ann. Chem. 1968, 712, 123–137.
Org. Lett., Vol. 13, No. 12, 2011
3167

we exclusively obtained the 1,2-regioisomer 3. In the
second case we obtained mainly the 1,3-regioisomer 2
with small amounts of 3 (not isolated, only seen on
TLC) (Scheme 3).
squarate mainly gave the corresponding emisquarate
7 along with a little of the 1,3-squaraine 8, exactly the
opposite of what we observed for the benzothiazole
derivatives (Scheme 2b).
Scheme 4
Figure 1. A view of the ORTEP diagram of structure of 3
(disordered THF solvent molecules have been omitted for
clarity). Thermal ellipsoids are drawn at 50% probability.
The anhydrobase of 1a is thus able to react directly with
emisquarate 6a, and this reaction is 1,2-regioselective.
Conversely, the reaction with the emisquaraine follows a
1,3-condensation pathway.
Scheme 4 shows the tentative mechanism for the 1,2
and 1,3 condensation pathways. When 1a reacts with
6a, the first step involves a 1,4-conjugated addition at
the squarate double bond. It follows a 1,5-proton shift
between the benzothiazole methylene and the enolate.
Finally a thermally promoted elimination of ethanol
gives exclusively 2. The attack involves the carbonyl R
to the benzothiazole methylene because the other car-
bonyl is in direct conjugation with benzothiazole
and thus more electron-rich (and less electrophilic)
(Scheme 4a).
Scheme 3
Conversely, when 1a reacts with 6b, the nucleophilic
attack involves the carbonyl β to the benzothiazole
methylene. We speculate that this is the consequence
of the high acidity of squaric acid and emisquaraines.18
6b is partially dissociated in alcoholic solution. The
carbonyl in the R position is conjugated with the
enolate and thus electron-rich. Conversely, the cataly-
tic protonation of the carbonyl in the β position makes
the nucleophilic attack of 6a particularly easy. Ther-
mally driven elimination of water gives exclusively the
1,3-squaraine 3. This mechanism is also supported by
Law’s observation that the reaction of dimethylindole-
nine with butylsquarate is acid catalyzed.8 Therefore,
the formation of a 1,2-squaraine requires a very reac-
tive electron-rich precursor, as in this case there is no
need of catalytic protonation to enhance the reaction
site electrophilicity. This is the reason why we could not
prepare a symmetric 1,2-squaraine out of a dimethy-
lindolenine anhydrobase. 1c is not reactive enough to
aRefluxing pyridine as the solvent. bMicrowave heating (100 °C, 3
bar), the anhydrobase was generated ex situ. cYields are reported in the
Supporting Information.
The presence of small amounts of 3 can be ascribed to
the reaction of 1a with the little 6a formed by in situ
esterification of the emisquaraine 6b with the solvent of
the reaction (Scheme 3).
On going from the very reactive benzothiazole anhy-
drobases17 to the corresponding more stable dimethy-
lindolenine derivatives (1b, 1c), we observed a different
behavior. The reaction of 1 equiv of 1c with ethyl
(17) Denes, V. I.; Farcasan, M.; Ciurdaru, G. Chem. Ber. 1964, 97,
1246–1251 and references therein.
(18) West, R.; Powell, D. L. J. Am. Chem. Soc. 1963, 85, 2577–2579.
Org. Lett., Vol. 13, No. 12, 2011
3168

directly react with 7. The formation of small amounts
of 8 is the consequence of the slow hydrolysis of 7 in
ethanol solution (Scheme 3).
representative derivative 9 in different solvents are
linearly correlated with the corresponding Brooker’s
χ
R values.19
We tested the electrochemical properties of 9. Figure
3 shows its CV plot in a 0.1 M solution of tetrabuty-
lammonium hexafluorophosphate in CH2Cl2. The plot
shows two completely reversible oxidations (V1/2(1) =
0.13 V, E1/2(2) = 0.48 V versus Fcþ/Fc redox couple)
associated with the oxidation of the electron rich
benzothiazole and dimethylindolenine side groups re-
spectively. These data place the HOMO level for 9 at
ꢀ5.3 eV, significantly below that of the 1,3-squaraines
we so far employed in OPV devices.10a This is consid-
ered beneficial for the increase of the open circuit
voltage.
Figure 2. Transition energies of 9 in six solvents plotted against
Brooker’s χR values in the same solvents.
One important consequence of our proposed me-
chanism is that the nonsymmetric 1,2-squaraine 9
bearing both a dimethylindolenine and a benzothiazole
side group could only be prepared by the reaction of 6c
with 1a. In fact, the reaction of 6a with 1b only gave the
starting materials (Scheme 3). In short, the amount of
the 1,2-regioisomer in a 1,3-squaraine synthesis de-
pends on both the reaction conditions and nature of
the reactants. First, only a very reactive species is able
to efficiently react with the emisquarate to give the 1,2-
squaraine. Second, the amount of emisquarate present
in solution depends both on the nature of the alcohol
employed (primary, secondary,..) and on the reaction
time and temperature. Thus, in the case of poorly
reactive arenes and anhydrobases, the amount of 1,2-
regioisomer will be low in any case, while, in the case of
highly reactive electron rich molecules, the condensa-
tion regioselectivity can only be controlled by reducing
the parasite esterification of the emisquaraine inter-
mediate. From the standpoint of the photophysical
properties, we already discussed how 1,3-squaraines
are reminiscent of cyanines. In the case of 1,2-squar-
aines, the allowed canonic representations show a
delocalization of the nitrogen lone pair over the carbo-
nyl of the squarate core, thus giving a merocyanine
structure. This is confirmed by the data shown in
Figure 2 and Table S1 of the Supporting Information.
The transition energies for the absorption spectra of the
Figure 3. Cyclic voltammetry (black) and differential pulse
voltammetry (red) for derivative 9 in 0.1 M TBAMPF6 in
CH2Cl2 with respect to the Fc/Fcþ redox couple. The
working, counter and pseudoreference electrodes were a
Glassy Carbon (GC) disk, a Pt flag, and a Ag/AgCl wire,
respectively.
In conclusion, we identified the main electronic factors
and reaction conditions leading to the formation of 1,2-
squaraines. We proposed a mechanism for the 1,2 vs 1,3
condensation regiochemistry and we successfully exploited
these findings in the facile synthesis of symmetric and
nonsymmetric 1,2-squaraines. We also demonstrated that
such compounds behave like redox reversible merocya-
nines holding promise as new sensitizers in organic photo-
conducting devices.
Acknowledgment. The following funding agencies are
gratefully acknowledged: PRIN 2007 (prot. 2007Y7JM-
4M) and PRISMA 2007 (ISOS).
Supporting Information Available. Synthetic proto-
cols, absorption and emission spectra for 2 and 9,
cyclic voltammetry plot for 2, crystal data and
refinement parameters (Table S3), and crystallo-
graphic information files (CIF) for 3. This material is
available free of charge via the Internet at http://pubs.
acs.org.
(19) The detailed photophysical characterization of the compound
will be published elsewhere.
Org. Lett., Vol. 13, No. 12, 2011
3169