Synthesis and characterization of 2,7-di(tertbutyl) pyreno[4,5-c:9,10- c′]difuran and derived pyrenophanes

Article abstract of DOI:10.1021/jo901482y

(Chemical Equation Presented) Isobenzofurans (IBF)s have seen widespread use in the synthesis of both natural products and polycyclic aromatic hydrocarbons. There are few examples that have two IBF entities linked in a fused aromatic ring system. Here we present the synthesis and characterization of a bis(IBF), 2,7-di(tert-butyl)pyreno[4,5-c:9,10-c0]difuran.Reactionwith bis(maleimide) dienophiles gives pyrenophanes. The solidstate structures of the bis(IBF) and two cyclophanes are discussed. 2009 American Chemical Society.

Full text of DOI:10.1021/jo901482y

pubs.acs.org/joc
synthesis of medicinal natural products,6-9 polycyclic aro-
Synthesis and Characterization of 2,7-Di(tert-
butyl)pyreno[4,5-c:9,10-c0]difuran and Derived
Pyrenophanes
matic hydrocarbons,10-14 and fullerene derivatives.15,16
There are only three previously known examples of bis(IBF)s
in which the two furan entities are part of a common aromatic
ring system: benzodifuran 2 and naphthodifuran 3, both pre-
pared by Wege,17 and isomeric naphthodifuran 4.18,19 A syn-
thetic equivalent to bis(IBF) 5, for which no stable classical
valence bond structure can be drawn, was developed by Hart.20
Collectively, these and related examples are very useful and
have been used to prepare π-molecular switches,21,22 linear
acenes,20,23 and cyclophanes.19,23 We now report the synthesis
of 2,7-di(tert-butyl)pyreno[4,5-c:9,10-c0]difuran, 6, an example
in which the furans are fused to opposite faces of a pyrene ring
system. Note that this molecule is an expanded analogue of 5 in
which the additional rings enable one to draw a classical valence
bond structure. As examples of the utility of 6, two novel
pyrenophanes have been prepared by its reaction with tethered
bis(maleimide) dienophiles.
ꢀ
David Franz, Steven J. Robbins, Rene T. Boere, and
ꢀ
Peter W. Dibble*
Department of Chemistry and Biochemistry, University of
Lethbridge, 4401 University Drive, Lethbridge,
Alberta T1K 3M4, Canada
dibble@uleth.ca
Received July 13, 2009
Isobenzofurans (IBF)s have seen widespread use in the
synthesis of both natural products and polycyclic aromatic
hydrocarbons. There are few examples that have two IBF
entities linked in a fused aromatic ring system. Here we
present the synthesis and characterization of a bis(IBF),
2,7-di(tert-butyl)pyreno[4,5-c:9,10-c0]difuran. Reaction with
bis(maleimide) dienophiles gives pyrenophanes. The solid-
state structures of the bis(IBF) and two cyclophanes are
discussed.
FIGURE 1. Examples of isobenzofuran and bis(isobenzofuran)s.
The synthesis of 6 (Scheme 1) started with the addition of
tert-butyl groups24 to positions 2 and 7 of pyrene; these
groups direct subsequent bromination25 to give the tetra-
bromide 7. Reaction with n-BuLi forms arynes sequentially
that were trapped with furan to produce bis(epoxide) 8, as a
mixture of syn and anti isomers. Reaction with dipyridylte-
trazine (dipytet)26 gave difuran 6. The relative reactivities of
IBFs are easily predicted using the structure count ratio
method developed by Herndon27 and applied to IBFs by
Wege.28 On this basis, we expected 6 to be almost 300 times
less reactive than 1 and probably isolable, whereas 1 is not.
Isobenzofuran (IBF, 1, Figure 1) and its related com-
pounds1-5 are highly reactive dienes in the Diels-Alder
reaction and have proven to be useful intermediates in the
(1) Friedrichsen, W. Adv. Heterocycl. Chem. 1980, 26, 135–241.
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7544 J. Org. Chem. 2009, 74, 7544–7547
Published on Web 08/28/2009
DOI: 10.1021/jo901482y
r
2009 American Chemical Society

Franz et al.
JOCNote
TABLE 1. Comparison of Bond Lengthsa of 6 and Related Structures
bond
6b
9
10
11
12
C1-C2
C1-O1
C2-C3
C2-C9
C10-C100
C5-C6
C9-C10
C6-C7
C7-C11
a
1.373
1.372
1.431
1.454
1.471
1.391
1.412
1.392
1.532
1.322
1.369
1.425
1.373
1.368
1.434
1.426
1.434
1.345
1.434
1.417
1.390
1.415
1.392
1.531
1.493
1.390
1.396
1.387
1.349
Selected bond lengths in angstroms of 6 and reference structures:
furan,30 9; biphenyl,31 10; 2,7-di(tert-butyl)pyrene,32 11; and 1,3-diphe-
nylisobenzofuran,33 12, using the atom numbering introduced in
Figure 2.
b Due to disorder in one of the unique molecules in the crystal structure,
bond lengths used are from “molecule 1”; see Supporting Information.
SCHEME 1. Synthesis of Bis(IBF) 6 and Cyclophanes 13 and 14
FIGURE 2. Solid-state structure of 6 showing the crystallographic
inversion symmetry. Only one of the two independent molecules in
the unit cell is shown. Ellipsoids drawn to 50% probability level,
and hydrogens are drawn with arbitrary reduced radii using
X-Seed (1999).
In the event, while chromatography of crude material led to
substantial loss, it was possible to obtain large diffracting
crystals of 6 from toluene in 2% yield.
ꢀ
From inspection of the Kekule structure, one might expect the
solid-state structure of 629 (Figure 2) to resemble that of biphenyl
with two bridging furans. Comparisons to related molecules
(Table 1) show, however, that the bond lengths of the furan rings
most closely resemble those of diphenylisobenzofuran and the
bond lengths of the benzenoid rings in 6 are closer to those of
pyrene than those of biphenyl. Furthermore the single bond
(C2-C9) is shorter than a typical single bond, which when
combined with the lengthening of the “interior aromatic bonds”
(C2-C3 and C9-C10) suggests that π electrons are shared
around the entire ring rather than in four separate moieties.
Cyclophanes 13 and 14 (Scheme 1) were prepared using
bis(maleimide) dienophiles with methylene tethers 3 and 5
carbons in length. Reactions were carried out by stirring the
bis(dienophile) with either 6 or with 6 generated in situ.
Yields are poor (6% and 2%, respectively) but represent
isolated yields of X-ray quality material and are not opti-
mized. The proton NMR spectra of 13 and 14 exhibit signals
upfield of TMS that are characteristic of these compounds.
Both compounds exhibit apparent C2v symmetry in solution.
In 13, the central methylene is highly shielded by the pyrene π
electrons and appears at -2.4 ppm. This cyclophane is
closely comparable to naphthalenophane 1519,34 in which
the central methylene appears at -1.4 ppm. Cyclophane 14,
with the longer tether, exhibits two upfield signals: the
central methylene appears at -2.1 ppm, and the adjacent
methylenes (β to N) appear at -0.5 ppm.
Solid-state structures of 1335 and 1436 were obtained. The
structure of 13 provides a useful comparison to that of
naphthalenophane 15.34,37 Both exhibit an antistaggered
(29) CCDC 738425 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(30) Fourme, R. Acta Crystallogr., Sect. B: Struct. Sci 1972, B28, 2984–
2991.
(31) Charbonneau, G. P.; Delugeard, Y. Acta Crystallogr., Sect. B:
Struct. Sci 1977, 33, 1586–1588.
(32) Nather, C.; Jess, I.; Havlas, Z.; Bolte, M.; Nagel, N.; Nick, S. Solid
State Sci. 2002, 4, 859–871.
ꢀ
(34) Robbins, S. J.; Thibault, M. E.; Masuda, J. D.; Ward, D. R.; Boere,
R. T.; Dibble, P. W. J. Org. Chem. 2009, 74, 5192–5198.
(35) CCDC 738426 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(36) CCDC 738427 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(37) Thibault, M. E.; Parvez, M.; Dibble, P. W. Acta Crystallogr. 2008,
E64, o1837.
ꢀ
(33) Boere, R. T.; Dibble, P. W.; Fischer, K. E. Acta Crystallogr. Sect. E:
Struct. Rep. Online 2008, 64, O686–U1126.
J. Org. Chem. Vol. 74, No. 19, 2009 7545

Franz et al.
JOCNote
FIGURE 4. Structure of 14 as found in the crystal. tert-Butyl groups
are omitted for clarity. Ellipsoids drawn to 50% probability level, and
hydrogens are drawn with arbitrary reduced radii using X-Seed (1999).
of gauche interactions between the methylenes. Torsional
angles along the chain are not optimally staggered: 61.8(3)°,
78.3(3)°, 94.0(3)°, and 71.8(3)°. Geminal angles fall in a
narrow range (111.8(2)-114.1(2)°). Surprisingly, the central
methylene adopts a position similar to the other examples
˚
(pointing into the aromatic ring) and its carbon lies 3.26 A
away from the centroid of the C15-C16 bond, slightly closer
than in 13 and 15.
For cyclophanes 13 and 15, complexity in the proton
NMR methylene signals are consistent with a solution-state
structure that is conformationally rigid. In contrast, the
tether signals of 14 suggest that there is significant confor-
mational averaging in solution. Nevertheless, the high up-
field shift of the central methylene and the results of a
conformational search38 suggest that the conformation
adopted by 14 in the solid state is also important in solution.
The most surprising feature in the solid-state structure of 14
is the distortion in the pyrene backbone. It is warped inward
with the carbon atoms bearing the tert-butyl groups (C2 and
FIGURE 3. Structures of 13 and 15 as found in the crystals; 13 is
located on a crystallographic mirror plane that bisects C(7)-C(10)
and C(18). tert-Butyl groups are omitted for clarity. Ellipsoids
drawn to 50% probability level, and hydrogens are drawn with
arbitrary reduced radii using X-Seed (1999).
chain between the two N atoms. Distances between the N
˚
atoms in 13 and 15 are very similar: 4.83 and 4.89 A,
respectively. The distances from the central methylene car-
bons to the centroids of the carbon-carbon bonds below
(C8-C9 in 13, C9-C14 in 15) are nearly identical: 3.37
˚
C9) lying 0.4 A out of the plane defined by the central 10 carbon
atoms. The ring exhibits an overall bend angle39 of 18.5°. We
were tempted to attribute this to the tether forcing the N atoms
apart since in physical models this induces the observed warp.
Analysis of the crystal packing, computational modeling, and
the similarity of the UV spectrum to that of pyrene indicates
that this distortion is due to intermolecular interactions in the
solid state (see Supporting Information).
˚
versus 3.35 A. There is a marked difference in the geminal
angles found in the different methylene tethers. In 15, the
geminal angles along the tether are 108°-115°-108°. On the
basis of this and other structural data, our conclusion was that
the geminal angle about the central methylene of 15 was
widened because it was being pushed out by the π electrons
and not because the tether was being stretched between the two
N atoms. In contrast, the geminal angles along the tether of 13
are similar to each other and closer to normal angles: 110.4(2)°,
112.6(2)°, 110.4(2)°. There is clear evidence that in 13 there is
some strain associated with the N atoms being tugged together.
Although the pyrene ring is still planar, all four bridgehead
In summary, we have developed the synthesis of a novel
bis(IBF) based on pyrene and have characterized two cyclo-
phane derivatives. In addition to being a cyclophane pre-
cursor, we believe that 6 can be applied to the synthesis of an
aromatic molecular belt or cyclacene,40,41 and we are explor-
ing those possibilities. Other potential applications are to
˚
carbons (such as C14) are pulled approximately 0.4 A out of the
(38) Random torsion variation conformational search using Hyperchem
Release 7.52 for Windows.
(39) Bodwell, G. J.; Bridson, J. N.; Cyranski, M. K.; Kennedy, J. W. J.;
Krygowski, T. M.; Mannion, M. R.; Miller, D. O. J. Org. Chem. 2003, 68,
2089–2098.
pyrene plane. In addition, the geminal angles about the bridge-
head carbons (such as C13-C14-C15) are slightly narrower
(107.3(1)-107.5(1)°) than in 15 (108-111°).
Pyrenophane 14 has a tether that is too long to easily adopt
an antistaggered conformation between the N atoms. In this
structure (Figure 4) the N atoms are much further apart (6.09
(40) Cory, R. M.; McPhail, C. L.; Dikmans, A. J.; Vittal, J. J. Tetrahedron
Lett. 1996, 37, 1983–1986.
(41) Cory, R. M.; McPhail, C. L. In Advances in Theoretically Interesting
Molecules; Thummel, R. P., Ed.; JAI Press: Greenwich, CT, 1998; Vol. 4, pp
53-80.
˚
A). The “slack” in the tether is taken up with a series
7546 J. Org. Chem. Vol. 74, No. 19, 2009

Franz et al.
JOCNote
the preparation of graphitic materials,42 Diels-Alder poly-
chromatography eluting with ethyl acetate/hexanes. Crystals (27
mg, 0.042 mmol, 5.8%) were obtained from CHCl3: mp
mers,43,44 and polyacene ribbon polymers.45,46
1
340 °C (dec); IR (ATR, neat) 874, 1218, 1698 cm-1; H NMR
(CDCl3, 300 MHz) δ -2.46 (m, 2H), 1.64(s,18H), 2.23 (m,4H),
3.91 (m,4H), 6.57 (m,4H), 8.25 (s,4H) ppm;13C NMR (CDCl3, 75
MHz) δ 24.2, 31.8 34.1, 35.5, 48.36, 80.5, 121.0, 123.7, 124.9,
138.0, 150.0, 172.2 ppm; UV-vis (CH2Cl2) λmax (nm) [log ε
(mol-1 cm-1 L)] 246 (4.71), 254 (4.74), 280 (4.48), 293 (4.64), 330
(4.00), 346 (4.32), 363 (4.51); HRMS calcd for C39H36N2O6Naþ
651.24656, found m/z 651.24693.
Experimental Section
syn- and anti-2,9-Di(tert-butyl)-4,7,11,14-diepoxy-4,7,11,14-
tetrahydrodibenzo[e,l ]pyrene (8). To a solution of 7 (4.87 g,
7.73 mmol) and furan (20 mL, 0.28 mol) cooled to -70 °C were
added two aliquots of 1.6 M n-BuLi (5 mL, 8.0 mmol) 1 h apart.
The solution was cooled for an additional 1 h and left overnight.
The solution was quenched with water, extracted with CHCl3,
dried (MgSO4), and concentrated. It was used in the next step
6,14-Di(tert-butyl)-4,16:8,12-diepoxy-3a,4,8,8a,11a,12,16,16a-
octahydro-2,10-pentanopyreno[4,5-f:9,10-f 0]diisoindole-1,3,9,11-
tetrone (14). To a solution of crude 8 (1.0 mmol) in CHCl3 were
added dipyridyltetrazine (0.51 g, 2.2 mmol) and N,N0-1,5-bis-
(maleimido)pentane (0.27 g, 1.0 mmol), and the mixture was
refluxed overnight. The solution was washed with 1 M HCl and
dried (MgSO4). The solvent was removed, and the residue was
subjected to flash chromatography eluting with ethyl acetate/
hexanes. Crystals (11.3 mg, 0.0172 mmol, 1.65%) were formed
from a mixture of CHCl3 and hexanes: mp = 340 °C (dec); IR
(ATR, neat) 752, 853, 1393, 1692 cm-1; 1H NMR (CDCl3, 300
MHz) δ -2.1 (m,2), -0.46 (p, J=5.9 Hz, 4H), 1.63 (s,18H), 2.61
(t, J=6.2 Hz, 4H), 4.06 (d, J=3.6 Hz, 4H), 6.48 (d, J = 2.9 Hz,
4H), 8.27 (s,4H); 13C NMR (CDCl3, 75 MHz) δ 17.6, 24.6, 31.8,
35.6, 37.3, 48.5, 80.3, 120.1, 123.3, 125.0, 139.0, 149.9, 173.9 ppm;
UV-vis (CH2Cl2) λmax (nm) [log ε (mol-1 cm-1 L)] 246
(4.93), 254 (4.99), 280 (4.68), 292 (4.90), 330 (4.26), 345 (4.59),
1
without further purification. H NMR (CDCl3, 300 MHz) δ
1.63 (s, 18H), 6.57 (s, 4H) 7.36 and 7.40 (s,4H), 8.20 (s,4H) ppm;
13C NMR (CDCl3, 75 MHz) δ 32.0, 35.4, 82.2, 116.9, 119.75,
119.78, 126.69, 126.76, 144.21, 144.25, 148.22, 148.27 ppm.
2,7-Di(tert-butyl)pyreno[4,5-c:9,10-c0]difuran (6). A solution
of crude 8 (∼3.9 mmol) in CHCl3 was charged with dipyridyl-
tetrazine (1.97 g, 8.35 mmol) and refluxed for 18.5 h. The
solution was then washed with 1 M HCl and dried (MgSO4).
Crystals (116.7 mg, 0.2958 mmol, 2.0%) were found after an
extended period in toluene: mp = 240 °C (dec); IR (ATR, neat)
647, 770, 1043, 1547, 1608 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 1.51 (s, 18H), 8.02 (s, 4H) 8.36 (s, 4H) ppm; 13C NMR (CDCl3,
75 MHz) δ 31.5, 34.9, 119.2, 121.7, 122.5, 125.7, 136.4, 149.8
ppm; UV-vis (CH2Cl2) λmax (nm) [log ε (mol-1 cm-1 L)] 255
(4.65), 299 (4.35), 273 (4.61), 312 (4.27), 327 (4.18); HRMS calcd
for C28H26N2O2þ 394.19273, found m/z 394.19294.
6,14-Di(tert-butyl)-4,16:8,12-diepoxy-3a,4,8,8a,11a,12,16,16a-
octahydro-2,10-propanopyreno[4,5-f:9,10-f 0]diisoindole-1,3,9,11-
tetrone (13). To a solution of crude 8 (0.73 mmol) in CHCl3 was
added dipyridyltetrazine (0.36 g, 1.5 mmol), and the solution was
refluxed overnight. N,N0-1,5-bis(maleimido)propane (0.18 g,
0.75 mmol) was added, and the solution stirred for 1 h. The
solution was washed with 1 M HCl and dried (MgSO4). The
solvent was removed, and the residue was subjected to flash
þ
363 (4.81); HRMS calcd for C41H40N2O6 656.28809, found
m/z 656.28847.
Acknowledgment. We gratefully acknowledge the support
of the University of Lethbridge, the Natural Sciences and
Engineering Research Council of Canada, Dr. Matthew
Piggott and the University of Western Australia, and the
Keith and Faith Hope Memorial Fund (Robbins).
Supporting Information Available: Compound character-
ization data, including copies of 1H and 13C NMR spectra of 6,
8, 13 and 14, details of our preparation of 7, and both crystal-
lization information files (CIF format) and UV-vis spectra of
compounds 6, 13, and 14. This material is available free of
charge via the Internet at http://pubs.acs.org.
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