Synthesis of macrocycles with anthracene units and amide bonds; Potential building blocks for 1d and 2d constructions

Article abstract of DOI:10.1055/s-0031-1291045

A collection of novel m-terphenyl and mixed m-terphenyl-anthracene building blocks were synthesised on scales between several 100 mg and a few grams. Proper connection of some of these building blocks utilising amide coupling chemistry afforded macrocycles containing two and three anthracene units. These macrocycles were obtained as virtually pure compounds on 14 and 24 mg scales, respectively. Their UV/Vis and fluorescence spectra are reminiscent of the parent anthracene, which renders them potential candidates for various applications including sensing and molecular constructions. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1291045

LETTER
▌1467
lSetyternthesis of Macrocycles with Anthracene Units and Amide Bonds; Potential
Building Blocks for 1D and 2D Constructions
Potential Building Blocks for 1D and 2D Constructions
Animesh Saha, Jeroen van Heijst, Junji Sakamoto,* A. Dieter Schlüter*
ETH Zürich, Department of Materials, Laboratory of Polymer Chemistry, Wolfgang-Pauli Str. 10, HCI J541, 8093 Zürich, Switzerland
Fax +41(44)6331395; E-mail: sakamoto@mat.ethz.ch; E-mail: ads@mat.ethz.ch
Received: 31.01.2012; Accepted after revision: 28.03.2012
Macrocycles have the potential to serve as versatile build-
Abstract: A collection of novel m-terphenyl and mixed m-terphe-
ing blocks in the construction of large supramolecu-
nyl-anthracene building blocks were synthesised on scales between
lar/macromolecular architectures.1 For example, when
several 100 mg and a few grams. Proper connection of some of
these building blocks utilising amide coupling chemistry afforded
stacked on top of each other 1D tubular assemblies result,2
macrocycles containing two and three anthracene units. These mac- but when arranged laterally the same macrocycle can in-
stead form a 2D porous structure.3 In order to promote the
formation of such well-defined supramolecular entities, it
rocycles were obtained as virtually pure compounds on 14 and 24
mg scales, respectively. Their UV/Vis and fluorescence spectra are
reminiscent of the parent anthracene, which renders them potential
is desirable to involve strong (yet reversible) directional
candidates for various applications including sensing and molecular
constructions.
interactions.2–4 In addition, it can be an attractive further
option to covalently fix the obtained supramolecular as-
Key words: macrocycles, anthracene, amides, photochemistry,
sembly by subsequent treatment in order to convert it into
polymers
a non-equilibrium structure.5
In the present study, two new macrocycles were designed
in which three or two sets of m-terphenylene and 1,8-
O
O
O
OH
COOH
COOH
a
3
4
NO2
NO2
NO2
NO2
Br
Br
c
b
OH
OH
HN
OTHP
5
6
7
O
d
NH2
CF3
NH2
NH2
e
OTHP
OTHP
9
8
Scheme 1 Synthetic route used for the preparation of the symmetric (3 and 8) and unsymmetric (4 and 9) building blocks. Reagents and con-
ditions: (a) BnBr, DIPEA, DMF, 40%; (b) [Pd(dppf)Cl2]·CH2Cl2, Na2CO3, benzene–EtOH–H2O, 98%; (c) 3,4-dihydro-2H-pyran, TsOH·H2O,
DMF, 95%; (d) Pd(OH)2/C, H2, CH2Cl2–EtOH, 90%; (e) CF3CO2Et, Et3N, MeOH, 45%.
SYNLETT 2012, 23, 1467–1472
Advanced online publication: 25.05.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0031-1291045; Art ID: ST-2012-D0096-L
© Georg Thieme Verlag Stuttgart · New York

1468
A. Saha et al.
LETTER
anthrylene units6 are alternatively connected to each other that can adopt two extreme conformations, a more or less
through amide bonds (1 and 2, respectively, Figure 1a). flat form and a cylindrical form. The ratio between the
These macrocycles have a semi-rigid molecular structure two forms can be influenced by several measures, which
Figure 1 (a) Chemical structures of macrocycles 1 and 2; flat (left) and cylindrical (right). (b) The conformations may allow the macrocycles
to be used as building blocks for 1D and 2D constructions, respectively.
Synlett 2012, 23, 1467–1472
© Georg Thieme Verlag Stuttgart · New York

LETTER
Potential Building Blocks for 1D and 2D Constructions
1469
can go as far as to favour one conformation completely Scheme 2 (a) describes the random oligomerization be-
over the other. This can be achieved by chemical modifi- tween the symmetric building blocks 3 and 8, Scheme 2
cation,7 temperature,8 pressure,9 solvophobic effects,10,11 (b) shows the sequences used to obtain the more extended
and guest uptake.6,12 Moreover, because of the orientation building blocks 11 and 13, which are required as direct
of the amide bonds and the aromatic planes in 1 and 2, the precursors for 1; Scheme 2 (c) depicts the final assembly
macrocycles may be directed into 1D and 2D assemblies of the target cycle 1 from 11 and 13. In Scheme 1, 1,8-an-
when adopting the flat and the cylindrical conformation, thracene dicarboxylic acid (3), was synthesised in three
respectively (Figure 1b).13
steps from commercially available 1,8-dichloroanthraqui-
none following a published procedure.15 Compound 3 was
obtained on a 25 gram scale. The statistical protection to
generate 4 was performed with benzyl bromide and af-
forded the required intermediate in 40% yield. The ter-
phenylene building block 9 was synthesised starting from
the known dibromide 5,16 which was converted into dini-
troterphenylene 6 by Suzuki–Miyaura cross-coupling
chemistry17 employing 3-nitrobenzene boronic acid. Sim-
ple tetrahydropyran (THP) protection of the alcohol of 6
gave 7, which could be smoothly reduced with H2 over
Pd(OH)2/C. Subsequent statistical protection of one of the
amino functions of 8 with trifluoroacetyl was performed
with ethyl trifluoroacetate to give 9 in a yield of 45%. The
oligomerisation between the bifunctional compounds 3
and 8 afforded, as expected, a rather complex product
mixture containing cyclic and open-chain oligomers of
various molar masses. This mixture was analysed by
MALDI-TOF mass spectrometry using DCTB/Ag+ as a
Photophysical and -chemical properties arising from the
anthracene moieties of our compounds make them attrac-
tive for various applications.14 Once 1D or 2D assemblies
form, these active moieties may arrange themselves with
controlled mutual distances and orientations.11 This may
allow, for example, efficient energy transfer between
them or covalent stabilization of the assembly structure by
subsequent photo-treatment. Furthermore, hydroxymeth-
yl groups are introduced at the periphery of the macrocy-
cle that are protected with tetrahydropyranyl (THP)
groups during the synthesis but can be subsequently mod-
ified with chemical entities of various sorts; this is expect-
ed to lead to the formation of a regular array on the
resultant assembly surface.
We followed two different synthetic strategies to 1 and 2.
For this purpose a collection of small anthracene (3 and 4)
and terphenylene-based building blocks (8 and 9) was
needed; their syntheses are shown in Scheme 1.
f
(a)
(b)
cyclic dimer (2) + cyclic trimer (1) + cyclic tetramer + possibly open-chain oligomers..
+
3
8
NHX
HN
O
O
NH
NHX
g
3 +
9
OTHP
OTHP
10: X = COCF3
11: X = H
h
i
YO
O
O
NH
HN
O
O
OY
+
4
8
OTHP
12: Y = Bn
13: Y = H
j
k
(c)
1
+ possibly open chain oligomers
11
+
13
Scheme 2 Synthetic route used for the preparation of (a) macrocycle 2, (b) extended building blocks for 1, and (c) macrocycle 1. Reagents and
conditions: (f) EDC·HCl, HOBt, DMAP, DIPEA, DMF–CH2Cl2, 2%; (g) EDC·HCl, HOBt, DMAP, DIPEA, DMF–CH2Cl2, 83%; (h) NaOH,
H2O, DMF, 95%; (i) EDC·HCl, HOBt, DMAP, DIPEA, DMF–CH2Cl2, 89%; (j) NaOH, H2O, DMF, 81%; (k) EDC·HCl, HOBt, DMAP,
DIPEA, DMF–CH2Cl2, 5%.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 1467–1472

1470
A. Saha et al.
LETTER
matrix (see the Supporting Information, Figure S23). The carboxylic acid turned out to stick to the silica gel column.
spectrum showed the molecular ions of the dimeric 2, tri- We therefore used it directly for the next reaction without
meric 1, and tetrameric cyclic species; the open-chain chromatographic purification. The obtained crude materi-
oligomers, which were presumably also formed, could not al 13 was then repeatedly washed with water followed by
be detected.18 The product mixture did not dissolve in methanol to remove the formed benzyl alcohol and other
chloroform and methanol but a partial separation could be unwanted components. This procedure was rather suc-
accomplished on Sephadex LH-20 with DMF as an elu- cessful in terms of obtaining pure 13, as the clean NMR
ent. This afforded 2 in a low yield of 2%. Nevertheless, it spectrum provided in the Supporting Information shows.
was obtained on a few mg scale (14 mg) allowing for its
full characterization. Compound 1 and the larger cyclic
species could not be isolated from the complex mixture.
Although repeated chromatography over Sephadex LH-
20 gave fractions enriched in 1, we could not find condi-
tions that would allow its isolation.
Scheme 2 (c) depicts the final cyclization of 11 and 13.
This was performed under moderately high dilution con-
ditions (final concentration 1 mM) starting from 11
(259 mg) and 13 (230 mg). As in the above case, eventu-
ally, open-chain oligomers did not show in the MALDI-
TOF mass spectrum of the product mixture, resulting in a
This was a motivation to start the systematic sequence spectrum that basically contained the molecular ion of 1,
shown in Scheme 2 (b), leading to the immediate cyclisa- however, NMR spectroscopy indicated that there were in
tion precursors 11 and 13. Standard amide coupling reac- fact some open-chain oligomers present. Isolation of 1
tions between 3 and 9 as well as 4 and 8 afforded the key was successful on Sephadex LH-20 with DMF as eluent,
building blocks 10 and 12, respectively, in yields of more followed by reverse-phase chromatography (C18 as sta-
than 80%. These compounds were prepared on a 2.5 gram tionary phase; MeOH–DMF, 9:1) and gave 1 in low yield
scale. Deprotection of 10 was conventional. Whereas de- (24 mg, 5%).19
protection of 12 (NaOH, H2O–DMF) was straightforward,
its purification was found to be laborious in that the free
The UV/Vis and fluorescence spectra of 1, together with
model compound 14, are depicted in Figure 2. It is noted
Figure 2 UV absorption and emission spectra of model compound 14 and monomer 1 together with UV spectrum of the dimer syn-15 in DMSO.
Black, dark-gray, and light-gray lines correspond to the spectra of 1, 14 and 15, respectively. Solid and broken lines are used for the absorption
and emission spectra, respectively. Concentrations: Absorption: 20, 7 and 10 μM for 14, 1, and 15, respectively. Emission: 2 and 0.7 μM for 14
and 1, respectively. As expected, the absorption of the dimer in the range of λ = 350–400 nm is virtually absent, which should allow selective
excitation of the macrocycle.
Synlett 2012, 23, 1467–1472
© Georg Thieme Verlag Stuttgart · New York

LETTER
Potential Building Blocks for 1D and 2D Constructions
1471
(2) Ghadiri, M. R. Adv. Mater. 1995, 7, 675.
(3) Sakamoto, J.; van Heijst, J.; Lukin, O.; Schlüter, A. D.
Angew. Chem. Int. Ed. 2009, 48, 1030.
(4) For examples, see: (a) Barboiu, M.; Vaughan, G.; Graff, R.;
Lehn, J.-M. J. Am. Chem. Soc. 2003, 125, 10257. (b) Bauer,
T.; Zheng, Z.; Renn, A.; Enning, R.; Stemmer, A.;
Sakamoto, J.; Schlüter, A. D. Angew. Chem. Int. Ed. 2011,
50, 7879.
(5) For examples, see: (a) Yamamoto, T.; Fukushima, T.;
Yamamoto, Y.; Kosaka, A.; Jin, W.; Ishii, N.; Aida, T.
J. Am. Chem. Soc. 2006, 128, 14337. (b) Münzenberg, C.;
Rossi, A.; Feldman, K.; Fiolka, R.; Stemmer, A.; Kita-
Tokaczyk, K.; Meier, W.; Sakamoto, J.; Lukin, O.; Schlüter,
A. D. Chem.–Eur. J. 2008, 14, 10797.
(6) Kissel, P.; Schlüter, A. D.; Sakamoto, J. Chem.–Eur. J.
2009, 15, 8955.
(7) Kissel, P.; Erni, R.; Schweizer, W. B.; Rossell, M. D.; King,
B. T.; Bauer, T.; Götzinger, S.; Schlüter, A. D.; Sakamoto, J.
Nat. Chem. 2011, 4, 287.
(8) Moran, J. R.; Ericson, J. L.; Dalcanale, E.; Bryant, J. A.;
Knobler, C. B.; Cram, D. J. J. Am. Chem. Soc. 1991, 113,
5707.
(9) Ariga, K.; Terasaka, Y.; Sakai, D.; Tsuji, H.; Kikuchi, J.
J. Am. Chem. Soc. 2000, 122, 7835.
that the macrocycle shows characteristic signatures of its
three anthracene units, which are completely unaltered as
compared to those of the model compound. This is a clear
sign that they do not form any intramolecular excimers
and that there is no interaction between them and other
parts of the compound either in the ground or the excited
states. Model compound 14 underwent photoinduced
[4+4] cycloaddition dimerisation, which is well known
for anthracenes.14 This supports our view that the macro-
cycles can, in fact, be used for similar reactions involving
anthracene dimerisation, leading to extended covalent
structures. The photochemical dimerisation of model 14
afforded both syn-15 and anti-15 dimers. In contrast to
many other 1,8-disubstituted anthracenes, for which the
anti-dimer is largely favoured,6 in this case, the syn/anti
ratio was 55:45 after standing in DMSO at 21 °C for three
days. The conversion reached 50% with remaining 14 be-
ing unchanged. Preliminary results indicate that this ratio
can be shifted even further towards the syn dimer, which
is considered an indication of possible hydrogen bond in-
volvement in the stereochemistry determining step of the
dimerisation.
(10) Nelson, J. C.; Saven, J. G.; Moore, J. S.; Wolynes, P. G.
Science 1997, 277, 1793.
In conclusion, macrocycles with two and three anthracene
units were obtained through amide coupling chemistry in
virtually pure form (as judged by NMR spectroscopic
analysis). The relatively small scale in which these two
targets were obtained is mainly attributed to the low effi-
ciency of the final cyclisation step. Nevertheless, the cy-
clisations can easily be repeated in order to provide
amounts that are sufficient for subsequent studies. UV/Vis
absorption and fluorescence spectroscopic analyses of the
obtained macrocycles as well as photoreactions of a mod-
el compound indicate that the anthracenes in both macro-
cycles are not only independent from one another but also
do not show signs of interaction with other parts of the
compound. This is a key prerequisite for these macrocy-
cles to be good starting compounds for self-assembly and
subsequent photophysical and -chemical studies. This
self-assembly may be followed at interfaces, in solution or
in bulk.
(11) Kissel, P.; van Heijst, J.; Enning, R.; Stemmer, A.; Schlüter,
A. D.; Sakamoto, J. Org. Lett. 2010, 12, 2778.
(12) Amrheim, P.; Shivanyuk, A.; Johnson, D. W.; Rebek, J. Jr.
J. Am. Chem. Soc. 2002, 124, 10349.
(13) For examples, see: Yang, Y.; Feng, W.; Hu, J.; Zou, S.; Gao,
R.; Yamato, K.; Kline, M.; Cai, Z.; Gao, Y.; Wang, Y.; Li,
Y.; Yang, Y.; Yuan, L.; Zeng, X. C.; Gong, B. J. Am. Chem.
Soc. 2011, 113, 18590.
(14) (a) Becker, H.-D. Chem. Rev. 1993, 93, 145. (b) Bouas-
Laurent, H.; Desvergne, J.-P.; Castellan, A.; Lapouyade, R.
Chem. Soc. Rev. 2000, 29, 43. (c) Bouas-Laurent, H.;
Desvergne, J.-P.; Castellan, A.; Lapouyade, R. Chem. Soc.
Rev. 2001, 30, 248.
(15) Rogers, M. E.; Averill, B. A. J. Org. Chem. 1986, 51, 3308.
(16) Kissel, P.; Breitler, S.; Reinmüller, V.; Lanz, P.; Federer, L.;
Schlüter, A. D.; Sakamoto, J. Eur. J. Org. Chem. 2009, 2953.
(17) For examples, see: (a) Miyaura, N.; Suzuki, A. Chem. Rev.
1995, 95, 2457. (b) Suzuki, A. J. Organomet. Chem. 1999,
576, 147. (c) Miyaura, N. Top. Curr. Chem. 2002, 219, 11.
(18) Open-chain oligomers are likely to be present because the 1H
NMR spectra of crude mixtures showed signals that did not
belong to cycles but absorbed at similar chemical shifts. No
attempts were made to isolate non-cyclic products.
(19) Synthesis of macrocycle 1 from 11 and 13:
Compounds 11 (258.6 mg, 0.26 mmol) and 13 (230.0 mg,
0.26 mmol) was dissolved in a mixture of anhydrous DMF
(500 mL) and anhydrous CH2Cl2 (28 mL). HOBt (356.0 mg,
2.64 mmol), DMAP (3.2 mg, 0.026 mmol), and DIPEA
(853.0 mg, 6.6 mmol) were added successively under N2 and
the mixture was cooled to 0 °C. EDC·HCl (506.0 mg, 2.64
mmol) was added and the mixture was warmed to r.t.
overnight. The reaction was then stirred at r.t. under N2 for
21 d. After the reaction was over, solvent was removed
under reduced pressure. The crude reaction mixture was
purified by using Sephadex LH-20 as packing material and
DMF as the eluent, and finally by reverse-phase chromatog-
raphy (C18 as stationary phase; MeOH–DMF, 9:1) to give 1
(24.0 mg, 5%) as a yellow solid. 1H NMR (500 MHz,
DMSO-d6, 50 °C): δ = 10.54 (s, 6 H, NH), 9.33 (s, 3 H), 8.72
(s, 3 H), 8.21 (d, J = 8.5 Hz, 6 H), 7.96 (s, 6 H), 7.72 (d, J =
Acknowledgment
We thank Dr. X. Zhang and his team at ETH Zurich for mass
measurements, and Ms. A. Grotzky for help in UV/Vis absorption
and fluorescence measurements. Financial support by the ETH
Zurich (TH-05 07-1 and ETH-26 10-2) and the Swiss National Sci-
ence Foundation (200021-129660) is gratefully acknowledged.
J.v.H. thanks the Deutsche Forschungsgemeinschaft for a postdoc-
toral stipend (HE5531/1-1).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
References
(1) For example, see: (a) Moore, J. S. Acc. Chem. Res. 1997, 30,
402. (b) Höger, S. Chem.–Eur. J. 2004, 10, 1320.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 1467–1472

1472
A. Saha et al.
LETTER
139.49, 139.42, 135.0, 131.0, 130.4, 129.0, 128.0, 127.3,
125.8, 125.0, 124.9, 124.0, 122.2, 119.2, 118.4, 97.3, 68.0,
61.3, 30.1, 24.9, 19.0. HRMS (FT-MALDI, DCTB): m/z [M
+ Na]+ calcd for C120H96N6O12: 1835.6978; found:
1835.6990.
6.0 Hz, 6 H), 7.52 (t, J = 7.0 Hz, 6 H), 7.43 (s, 9 H), 7.23–
7.12 (m, 18 H), 4.70–4.65 (m, 6 H, benzyl and THP), 4.47
(d, J = 12.0 Hz, 3 H, benzyl), 3.80–3.77 (m, 3 H, THP), 3.44–
3.42 (m, 3 H, THP), 1.71–1.42 (m, 18 H, THP). 13C NMR
(75 MHz, DMSO-d6, 25 °C): δ = 167.1, 140.7, 140.4, 139.7,
Synlett 2012, 23, 1467–1472
© Georg Thieme Verlag Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.