1,8-pyrenylene-ethynylene macrocycles

Article abstract of DOI:10.1021/ol200485x

Chemical equations presented. A concise, highly regioselective synthesis of 1,8-dibromo-4,5-dialkoxypyrenes has been developed and exploited in the synthesis of some 1,8-pyrenylene-ethynylene macrocycles. The ¹H NMR data and NICS calculations indicate that there is little or no macrocyclic ring current. Concentration-dependent UV-visible studies indicate no aggregation at low concentration, but 8b forms dimers with voids suitable for intercalation of small molecules in the solid state.

Full text of DOI:10.1021/ol200485x

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2240–2243
1,8-PyrenyleneꢀEthynylene Macrocycles
Gandikota Venkataramana, Prateek Dongare, Louise N. Dawe, David W. Thompson,
Yuming Zhao, and Graham J. Bodwell*
Department of Chemistry, Memorial University, St. John’s, NL, A1B 3X7, Canada
gbodwell@mun.ca
Received February 22, 2011
ABSTRACT
A concise, highly regioselective synthesis of 1,8-dibromo-4,5-dialkoxypyrenes has been developed and exploited in the synthesis of some 1,8-
1
pyrenyleneꢀethynylene macrocycles. The H NMR data and NICS calculations indicate that there is little or no macrocyclic ring current.
Concentration-dependent UVꢀvisible studies indicate no aggregation at low concentration, but 8b forms dimers with voids suitable for
intercalation of small molecules in the solid state.
Aryleneꢀethynylene macrocycles constitute one of the
most important classes of shape-persistent macrocycles.1
Such systems have attracted interest for a variety of
reasons, including their structural, optoelectronic, self-
assembly, and liquid crystalline properties. Among the
many known aryleneꢀethynylene macrocycles, benzene
is by far the most commonly employed aromatic building
block. Other small aromatic and heteroaromatic systems
have also been used quite often, e.g. thiophene, pyridine,
and naphthalene, but larger aromatic systems,2 which have
larger surfaces and more interesting optoelectronic proper-
ties, have been exploited far less often.
Pyrene (1), the smallest peri condensed polynuclear
benzenoid aromatic hydrocarbon, has not previously been
incorporated into an aryleneꢀethynylene macrocycle.
Doing so would require access to synthetically useful
quantities of appropriately disubstituted pyrenes, but this
is nontrivial. For example, electrophilic dihalogenation of
pyrene (1) is not only limited in the disubstitution patterns
it can deliver (1,3-, 1,6-, and 1,8-)3 but also poorly selective
in the ones it provides. Moreover, the resulting isomer
mixtures require painstaking separation. We now report a
short and completely regioselective synthesis of 1,8-dibromo-
4,5-dialkoxypyrenes 5aꢀc and their use as building blocks
for the construction of some 1,8-pyrenyleneꢀethynylene
macrocycles.
The conceptual basis of this work was the premise
that substituents at the 4 and 5 positions of pyrene
(1) would sterically hinder the 3 and 6 positions, there-
by enabling regioselective substitution at the 1 and 8
positions. Alkoxy groups were selected because they
were expected to both activate the pyrene system to-
ward electrophilic substitution and effectively hinder
the 3 and 6 positions.
(1) (a) Zhang, W.; Moore, J. S. Angew. Chem., Int. Ed. 2006, 45,
4416–4439. (b) Zhao, D.; Moore, J. S. Chem. Commun. 2003, 807–818.
(c) Marsden, J. A.; Palmer, G. J.; Haley, M. M. Eur. J. Org. Chem. 2003,
€
2355–2369. (d) Grave, C.; Schluter, A. D. Eur. J. Org. Chem. 2002, 3075–
3098.
(2) Carbazole: (a) Zhao, T.; Liu, Z.; Song, Y.; Xu, W.; Zhang, D.;
Zhu, D. J. Org. Chem. 2006, 71, 7422–7432. Phenanthrene: Morimoto,
M.; Akiyama, S.; Misumi, S.; Nakagawa, M. Bull. Chem. Soc. Jpn. 1962,
35, 857–859. Anthracene: Chen, S.; Yan, Q.; Li, T.; Zhao, D. Org. Lett.
2010, 12, 4784–4787. 1,10-Phenanthroline: Schmittel, M.; Ammon, H.
Synlett 1999, 750–752. [4]Helicene: Nakamura, K.; Okubo, H.;
Yamaguchi, M. Org. Lett. 2001, 3, 1097–1099. 10b,10c-Dimethyl-
10b,10c-dihydropyrene: Kimball, D. B.; Haley, M. M.; Mitchell,
R. H.; Ward, T. R. Org. Lett. 2001, 3, 1709–1711. Triphenylene: Takeda,
T.; Fix, A. G.; Haley, M. M. Org. Lett. 2010, 12, 3824–3827. Porphyrin:
Yu, L.; Lindsey, J. S. J. Org. Chem. 2001, 66, 7402–7419. Dibenzo[e,
€
l]pyrene: Hoger, S.; Cheng, X. H.; Ramminger, A.-D.; Enkelmann, V.;
Rapp, A.; Mondeshki, M.; Schnell, I. Angew. Chem., Int. Ed. 2005, 44,
2801–2805. Dithieno[3,2-a;2,3-c]naphthalene: Chen, T.; Pan, G.-B.;
€
Wettach, H.; Fritzsche, M.; Hoger, S.; Wan, L.-J.; Yang, H.-B.; North-
rop, B. H.; Stang, P. J. J. Am. Chem. Soc. 2010, 132, 1328–1333.
Dibenz[a,j]anthracene: Chan, J. M. W.; Tischler, J. R.; Kooi, S. E.;
Bulovic, V.; Swager, T. M. J. Am. Chem. Soc. 2009, 131, 5659–5666.
BODIPY: Sakida, T.; Yamaguchi, S.; Shinokubo, H. Angew. Chem., Int.
Ed. 2011, 50, 2280–2283. A larger PAH: Liu, W.-J.; Zhou, Y.; Zhou, Q.-
F.; Ma, Y.; Pei, J. Org. Lett. 2008, 10, 2123–2126. Only one reference per
aromatic system is given here. A more complete list appears in the
Supporting Information.
(3) (a) Minabe, M.; Takeshige, S.; Soeda, Y.; Kimura, T.; Tsubota,
M. Bull. Chem. Soc. Jpn. 1994, 67, 172–179. (b) Grimshaw, J.; Trocha-
Grimshaw, J. J. Chem. Soc., Perkin Trans. 1 1972, 1622–1623.
r
10.1021/ol200485x
Published on Web 03/29/2011
2011 American Chemical Society

Scheme 1. Synthesis of 1,8-Dibromopyrenes 5aꢀc
Scheme 3. Synthesis of Macrocycles 8bꢀc
yield. No other cyclic oligomers were isolated. Macro-
cycles 8bꢀc are dark red compounds, which are soluble in
common organic solvents such as hexanes, benzene, di-
chloromethane, ethyl acetate, and acetone.
Functionality at the 4 and 5 positions of pyrene (1) was
introduced selectively by oxidation to dione 2 using a
modifiedversionofarecentprocedure(Scheme1).4 Chang-
ing the solvent from acetonitrile to THF allowed the
reaction time to be reduced to 2.5 h from 16 h without
affecting the yield. Reductive alkylation, which had not
previously been reported for 2 (but had been reported for
related systems such as phenanthrene-9,10-dione5), was
then accomplished using a two-step procedure. Reaction
of 2 with Na2S2O4 afforded 4,5-dihydroxypyrene (3),6
which was immediately di-O-alkylated to afford dialkoxy-
pyrenes 4aꢀc (86ꢀ92% from 2). Dibromination of 4aꢀc
using Br2 (2.2 equiv) was found to occur very readily (<5
min at rt) with complete selectivity for the 1 and 8 positions
to afford dibromides 5aꢀc (95ꢀ96%). The useof 5 equiv of
bromine at room temperature also gave only the 1,8-
disubstituted products. Dibromides 5aꢀc were then con-
verted into the corresponding 1,8-diethynylpyrenes 7aꢀc
using a Sonogashira/deprotecion sequence (Scheme 2) in
83ꢀ86% overall yield.
Scheme 4. Synthesis of Macrocycles 10bꢀc and 11bꢀc
Scheme 2. Synthesis of 1,8-Diethynylpyrenes 7aꢀc
Pyrenyleneꢀethynylene macrocycles with a single ethy-
nylene unit connecting the pyrene units were then targeted
(Scheme 4). Sonogashira coupling of dibromides 5aꢀc
with 2-methylbut-3-yn-2-ol (1.1 equiv) gave ynols 9aꢀc
(65ꢀ68%). An in situ deprotection and self-Sonogashira
reaction7 of 9aꢀc then afforded macrocycles 10bꢀc
(22ꢀ23%) and 11bꢀc (25ꢀ30%). These are also dark
red in color and soluble in a range of common organic
solvents. As with 8a, the methoxy substituted macrocycles
10a and 11a were not isolated.
Diynes 7aꢀc were subjected to oxidative coupling
(Scheme 3).2a For 7a, no cyclicoligomerswereisolated, but
for 7bꢀc, cyclic trimers 8bꢀc were obtained in 26ꢀ28%
(4) Hu, J.; Zhang, D.; Harris, F. W. J. Org. Chem. 2005, 70, 707–708.
(5) Paruch, K.; Katz, T. J.; Incarvito, C.; Lam, K.-C.; Rhatigan, B.;
Rheingold, A. L. J. Org. Chem. 2000, 65, 7602–7608.
(6) 4,5-Dihydroxypyrene (3) has been reported to be very oxygen
sensitive (Tintel, C.; Terheijden, J.; Lugtenburg, J.; Cornelisse, J. Tetra-
hedron Lett. 1987, 28, 2057–2060), but it was found to be reasonably
stable in our hands.
The molecular structures and properties of 8a, 10a, and
11a were calculated at the HF/3-21G//B3LYP/6-31G*
(7) Huynh, C.; Linstrumelle, G. Tetrahedron 1988, 44, 6337–6344.
Org. Lett., Vol. 13, No. 9, 2011
2241

level of theory (see Supporting Information). The opti-
mized structures of the cyclic trimers 8a and 10a are planar
with D3h symmetry, whereas cyclic tetramer 11a was
calculated to have a saddle-shaped D2d-symmetric struc-
ture akin to that of tetrabenzocyclooctatetraene.
Weakly diffracting crystals of 8b suitable for X-ray
crystallographic analysis were obtained from a benzene
solution, and the structure revealed four chemically iden-
tical macrocycles in the asymmetric unit (one is shown in
Figure 1, left). Each unique macrocycle deviates slightly
from planarity, as characterized by the dihedral angles
between pyrene units (3.52(7)° to 16.02(9)°). Ignoring the
difference between the alkoxy substitutents, the experi-
mentally determined structure of 8b was found to be
virtually identical to the calculated structure of 8a (bond
˚
lengths (0.01 A; bond angles (1°). Examination of inter-
molecular interactions shows that dimers with short inter-
˚
centroid distances (3.40 and 3.41 A) form between some
Figure 2. Aromatic regions of the 1H NMR spectra of 7c, 8c,
10c, and 11c.
macrocycles (Figure 1, right). Intercalated solvent benzene
molecules are also present, and dimers associate into a
slipped columnar arrangement (slippage angle of 69.5°)
running parallel to the a-axis (see Supporting Information).
somewhat lower field: (Δδ = 0.08ꢀ0.25 ppm). Similarly,
all aromatic signals for the planar and formally aromatic
cyclic trimer 8c move in the same direction, in this case
substantially toward higher field (Δδ = ꢀ0.68 to ꢀ0.75
ppm). These observations are entirely inconsistent with the
existence of a meaningful macrocyclic ring current. On the
other hand, the large upfield shift of the external protons
(Δδ = ꢀ0.65 to ꢀ0.80 ppm) and the even larger downfield
shift of the internal protons (Δδ = 1.51 ppm) for the
planar and formally antiaromatic trimer 10c are, on the
surface, fully consistent with pronounced antiaromatic
character. However, considering that the external protons
(Hb and Hc) of the two trimeric macrocycles (8c and 10c)
have very similar chemical shifts ((0.08 ppm), a weak-to-
negligible macrocyclic ring current could still be the case if
the low-field chemical shift of the internal protons (Ha) of
10c is anomalous due to other factors.
Figure 1. Left: ORTEP representation of macrocycle 8b with
50% probability displacement ellipsoids; H-atoms omitted for
clarity. Right: A dimer of 8b with associated benzene.
In the calculated structure of 10a (Supporting Informa-
tion), the internuclear distance between Ha on neighboring
˚
0
pyrene systems (HaꢀHa ) is 1.94 A, which is well within the
The inner (30π) and outer (42π) edges of 8aꢀc, as well as
sum of the van der Waals radii (2.4 A).10 Thus, a strong
˚
all other conjugated pathways through the pyrene systems
€
steric deshielding of these nuclei would be expected. By
0
of these macrocycles, correspond to Huckel aromatic π
comparison, the HaꢀHa distances in the calculated struc-
electron counts. In contrast, 10aꢀc (inner: 24π, outer: 36π)
˚
tures of 8a and 11a are 4.45 and 3.47 A, respectively.
€
and 11aꢀc (inner: 32π, outer: 48π) are formally Huckel
Moreover, if 10aꢀc are indeed assemblies of three essen-
tially intact pyrene systems, then each Ha nucleus is
situated not only in the deshielding zone of the pyrene
system to which it is attached but also in those of the other
two pyrene systems, albeit further afield. Since the three
pyrene systems are substantially closer to one another in
10aꢀc than they are in 8aꢀc, any additional deshielding
of Ha from the remote pyrene systems should be strongest
in 10aꢀc.
antiaromatic systems. Based on the large body of prior
work on dehydrobenzannulenes,1 substantial ring currents
in these systems would not be expected, but, at first glance,
1
the H NMR spectra of macrocycles 8c, 10c, and 11c
(Figure 2)8,9 appear to provide conflicting evidence.
In comparison to diyne 7c, the signals for both the
internal and external aromatic protons of nonplanar and
formally antiaromatic cyclic tetramer 11c are observed at
This notion of cooperative deshielding is supported by
NICS calculations (Supporting Information). The NICSzz
value at the centroid of 10a is 17.98. The corresponding
(8) 1,8-Bis(butadiynyl)-4,5-bis(decyloxy)pyrene was also synthe-
sized, and the aromatic region of its H NMR spectrum was virtually
identical to that of 7c.
1
(9) The nature of the side chain (butoxy vs decyloxy) does not
significantly influence the chemical shifts of the pyrene systems, so the
discussion of the NMR spectra is limited to the decyloxy substituted
macrocycles 8c, 10c, and 11c.
(10) Bondi, A. J. Phys. Chem. 1964, 68, 441–451.
Org. Lett., Vol. 13, No. 9, 2011
2242

value for 8a (5.48) is also positive, but smaller. For 10a,
deletion of the alkynes to leave three isolated pyrene
systems11 gave only a modestly diminshed NICSzz value
(14.08). Deletion of the pyrene systems in 10a to leave three
isolated ethyne molecules gave a greatly reduced but still
positive NICSzz value (1.26). Summing the NICSzz values for
the two sets of isolated components of 10a (14.08 þ 1.26 =
15.34) falls short of the value for 10a but leaves little room
for the influence of effects originating from the intact macro-
cycle, such as a paratropic macrocyclic ring current.
The aromatic stabilization energy (ASE) of pyrene has
recently been calculated to be 74.6 kcal/mol,12 so it is not
surprising that little or no evidence can be found tosupport
the existence of a significant macrocyclic ring current in 8
and 10. Macrocyclic delocalization would disrupt the
aromaticity of all three pyrene systems, costing up to 224
kcal/mol. Thus, all of the macrocycles described here are
best viewed as isolated pyrene systems connected by
ethynylene bridges,13 i.e. as pyrenophynes.
Figure 3. Normalized absorption (solid lines) and emission
(broken lines) spectra for 7b, 8b, 10b, and 11b. λexc = 300 nm for
7b; λexc = 400 nm for 8b, 10b, and 11b. Concentrations: [7b] =
2.88 ꢁ 10ꢀ5 M; [8b] = 2.25 ꢁ 10ꢀ6 M; [10b] = 5.45 ꢁ 10ꢀ6 M;
[11b] = 8.20 ꢁ 10ꢀ6 M.
The UVꢀvisand fluorescencespectraof8b, 10b, and 11b
are shown inFigure3.14 Althoughthe lowestenergyS0fS1
transition for an unsubstituted pyrene is symmetry for-
bidden, the absorption spectra of 8b, 10b, and 11b do show
complex absorption bands with appreciable intensity at
longer wavelengths. Clearly, the ethynyl and alkoxyl sub-
stitutents on the pyrene systems break the symmetry and
allow the coupling of the ground- and excited-state wave
functions. TD-DFT calculations (Supporting Information)
predict transitions with mixed orbital parentage at 524 nm
(fosc = 0.002) for 8a and 596 nm (fosc = 0.0001) for 10a, in
good agreement with the onsets of weak absorption bands
observed in their UVꢀvis spectra. The absorption envel-
ope of 11b resembles those of the pyrene monomers,
indicating considerably disrupted electronic communica-
tion as a result of its nonplanarconformation. Optical gaps
were estimated from the onset wavelengths of the low-
energy absorption bands (10b: 2.19 eV, 8b: 2.33 eV, 11b:
2.63 eV), which are in line with their calculated HOMO
ꢀLUMO gaps (10b: 2.56 eV, 8b: 2.88 eV, 11b: 3.06 eV).
The UVꢀvis and MO properties indicate weak electronic
coupling between the pyrene units via the ethynyl linkages
in the ground state, which again points to a small macro-
cyclic ring current.
The emission yields for all of the macrocycles (φem
≈
10ꢀ3) are much smaller than those of the diynes 7aꢀc (φem
≈ 0.13) or the dialkoxypyrenes 4aꢀc (φem ≈ 0.2). Plots of
absorbance vs concentration for the macrocyclic systems
(Supporting Information) are linear in the 10ꢀ6 to 10ꢀ5 M
concentration range, which suggests that there is no sig-
nificant aggregation at these concentrations.
A more detailed investigation of the electronic absorp-
tion and emission spectra of the new 1,8-pyrenyle-
neꢀethynylene macrocycles is underway, as are studies
aimed at the synthesis of other 1,8-pyrenylene-based π
systems.
Acknowledgment. Financial support of this work from
the Natural Sciences and Engineering Research Council
(NSERC) of Canada (G.J.B., D.W.T., Y.Z.), the Canadian
Foundation for Innovation (CFI) (D.W.T.), and the In-
dustrial Research and Innovation Fund (IRIF) (D.W.T.) is
gratefully acknowledged.
Supporting Information Available. Experimental pro-
cedures, characterization data, 1H and 13C NMR spectra
for compounds 2, 4aꢀc, 5aꢀc, 6aꢀc, 7aꢀc, 8bꢀc, 9aꢀc,
10bꢀc, and 11bꢀc. MALDI-TOF mass spectra for 8bꢀc,
10bꢀc, and 11bꢀc. UVꢀvis and fluorescence spectra for
4aꢀc, 7aꢀc, 8bꢀc, 10bꢀc, and 11bꢀc. Detailed structural
description and CIF for 8b. Computational data for
calculated structures of 8a, 10a, and 11a. This material
is available free of charge via the Internet at http://pubs.
acs.org.
(11) Hydrogen atoms were used to replace the akynyl groups.
ꢀ
(12) Wu, J.; Cyranski, M. K.; Dobrowolski, M. A.; Merner, B. L.;
Bodwell, G. J.; Mo, Y.; Schleyer, P. v. R. Mol. Phys. 2009, 107, 1177–
1186.
(13) A 2,4-pyrenyleneꢀvinylene macrocycle was also found to be-
have as an assembly of three pyrene “islands”. Schnorpfeil, C.; Fetten,
M.; Meier, H. J. Prakt. Chem. 2000, 342, 785–790.
(14) Spectra and detailed spectral data for other compounds are
given in the Supporting Information (Figures S4ꢀ1 to S4ꢀ7).
Org. Lett., Vol. 13, No. 9, 2011
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