Organic Letters
Letter
Abundant literature exists on the synthesis of species similar
to 4.15 Treatment of 4 with 3,5-dibromobenzaldehyde in 4:1
EtOH/H2O and excess NaHSO3 under reflux for 2 days
affords 3 in 70% yield (>2.5 g, Scheme 1). Suzuki−Miyaura
conformer is maintained in solution, as indicated from the
chemical shift of i′′ (>5.5 ppm, independent of the solvent
system used).16 Following a similar analysis, under C4
symmetry we expect 10 aromatic resonances for tubularene 1
(Figure 1c). Indeed, all resonances are observed and assigned
1
based on comparisons to 3, DFT-calculated H NMR (Table
Scheme 1. Syntheses of Tubular[4,12,0,8]arene (1) and
Tubular[4,16,0,12]arene (2)
S4), and their splitting pattern, for example, a and b. Whereas
the 1H NMR of 2 is more complex relative to 1, the long-range
4
coupling J observed in 2 helped us deduce the resonances
Also, the MALDI-TOF MS for 1−3 display a single ion in each
case across a wide range of m/z (Figure 2e). Upon close
inspection, the observed mass spectra match the simulated [M
+ H]+ isotopic distribution patterns for 1−3, as indicated in
Figure 2e1−e3.
Tubularene’s rigidity is particularly relevant to maintain the
radial orientation of the π-system, and it also creates a
permanent cavity. Octabromo species 3 maintains its tubular
shape thanks to its belt of hydrogen bonds (Figure 2e, inset).
Closely related cavitands are known to flip between open
(kite) and closed (vase) conformers depending on the guest or
temperature,17 and in some, the closed conformer has been
enforced by intramolecular hydrogen bonding.14b,18 Octabro-
mo species 3 has eight hydrogen bonds formed between N and
O atoms at an average distance of 2.77(1) Å (Figure S1),
which is relatively short and likely provides a significant
energetic stabilization to the tubular form of 3.19 In the
absence of the hydrogen bond donor−acceptor interaction,
compound 3 lacks any significant solubility, presumably
forming aggregates without an internal cavity. This is not the
case in 1 and 2, where covalent bonding rigidifies the overall
structure creating pores along the walls (Figure S22) and
permanent internal void spaces (Figure 2e, inset). The
and S24), respectively. These are remarkably larger than those
of initially reported porous organic cages20 and on par with
those of state-of-the-art organic moisture-stable porphyrin box
cages with permanent porosity.21 The calculated internal
S24), respectively, and were obtained in a similar way to
tubular[4,8,8,8]arene.13 Tubularene’s internal cavity and
rigidity make them ideal candidates for novel porous organic
solids.22
Radially bending the aromatic π-system in 1 and 2
inherently builds strain. DFT calculations employing the
homodesmotic reactions described in Figure S25, at different
levels of theory, provide average strain energies (SEs) for 1 and
2 of 42.2 and 61.9 kcal/mol (Table S6),23 respectively. These
are significantly lower in comparison with the average SEs of
tubular[4,8,8,8]arene and tubular[4,8,8,12]arene at 89 and 81
kcal/mol, respectively, and substantially higher than those
reported for [n]CMPs10 (≤23 kcal/mol) and [n]cyclo-2,7-
naphthylenes24 ([n]CNAP ≤ 19 kcal/mol). The obtained SEs
are counterintuitive, because in a first approximation, one
would expect 2 to have less strain than 1 based on its larger
diameter.25 In fact, whereas the top nanoring in 1 resembles a
radial [n]CMP,11 the analogous nanoring in 2 with its 2,7-
naphthylene moieties can be devised as a partial [n]cyclacene26
because it has conjugated edge-sharing benzene rings, a feature
extensively investigated27 and, until very recently, unprece-
dented8,28 in the literature.
cross-coupling reaction of 3 with 1,3-phenyldiboronic acid
bis(pinacol) ester in 10:1:1 THF/H2O/EtOH at 70 °C, with
excess K2CO3 and using Pd(PPh3)4 as a catalyst, affords 1 in a
3.3% yield. Under similar reaction conditions, the cross-
coupling of 3 with 2,7-naphthalenediboronic acid bis(pinacol)
ester provides 2 in 2.5% yield. Unassigned 1H NMR
resonances in 1 and 2 may indicate the trapping of molecules
in their cavities. Analogous tubularene wall structures 5a and
5b (Scheme 1) were synthesized to gain more insight into the
effects of rigidifying the overall architecture while maintaining
the radially oriented π-system
Compounds 1−3 have poor solubility in standard organic
solvents, but upon the addition of a small alcohol, for example,
MeOH or EtOH, these species readily go into solution. Vapor
diffusion of Et2O into a solution of 3 in MeOH/DCM formed
colorless block-shaped crystals. The molecular crystal structure
of 3, shown in Figure 2a, confirms our hypothesis in which a
belt of hydrogen bonds is formed by the benzimidazole
fragments and an external hydrogen bond donor−acceptor.
Crystals of two different adducts have been obtained: 3·2H2O·
2MeOH (Figure 2a) and 3·H2O·3MeOH (Figure S1). Density
functional theory (DFT) optimized structures of tubularenes 1
and 2 at the MN15/6-31G*+PCM(CH2Cl2) level of theory
are shown in Figure 2b,c, respectively. Attempts to grow
crystals of 1 and 2 have only produced microcrystals with
extremely weak X-ray diffraction. The structural information
suggests that compounds 1−3 should be C4-symmetric in
solution. Indeed, 1H NMR indicates a symmetric environment
in all three cases (Figure 2d). From compound 3, we expect six
unique chemical aromatic environments, all integrating for one
hydrogen atom, except one, e′′, which is expected to integrate
for two hydrogen atoms. The single resonance for e′′ at 7.82
ppm demonstrates that at room temperature there is no steric
hindrance for free rotation of the 1,3-dibromophenyl fragment,
as shown in Figure 2d. Note, however, that the tubular
Tubularene 2 can be regarded as an intermediate between a
fully fused zigzag nanoring, [n]cyclacene, and a nonfused
B
Org. Lett. XXXX, XXX, XXX−XXX
Castro, Edison
