Synthesis and structures of [2n](2,7)naphthalenophanes (n = 2-4)

Article abstract of DOI:10.1139/cjc-2016-0583

Reductive coupling of 2,7-bis(bromomethyl)naphthalene using phenyllithium gave anti-[2₂](2,7)naphthalenophane, [2₃](2,7)naphthalenophane, and [2₄](2,7)naphthalenophane, the distribution of which was dependent on the reaction conditions. The structure of the first compound was established by X-ray crystallographic analysis. On the basis of the similarity between the NMR and UV spectra of [2₃](2,7)naphthalenophane with those reported for syn-[2₂](2,7)naphthalenophane, we conclude that the compound originally assigned to be syn-4 was in fact 6.

Full text of DOI:10.1139/cjc-2016-0583

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Synthesis and Structures of [2n](2,7)Naphthalenophanes (n=2–4)
Kenta Otsuka, Guangke Cai, Kazuya Fujita, Hirokazu Miyoshi, Yoshito Tobe*
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Division of Frontier Materials Science, Graduate School of Engineering Science,
Osaka University, 1-3 Machikaneyama, Toyonaka 560-8531, Japan
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email: tobe@chem.es.osakaꢀu.ac.jp, phone: +81ꢀ6ꢀ6850ꢀ6225, fax: +81ꢀ6ꢀ6850ꢀ6229

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Abstract
Reductive coupling of 2,7ꢀbis(bromomethyl)naphthalene using phenyllithium gave
antiꢀ[22](2,7)naphthalenophane, [23]ꢀ and [24](2,7)naphthalenophanes, the distribution of
which was dependent on the reaction conditions. The structures of the first compound was
established by Xꢀray crystallographic analysis. On the basis of the similarity between the
NMR and UV spectra of [23](2,7)naphthalenophane with those reported for
synꢀ[22](2,7)naphthalenophane, we conclude that the compound originally assigned to be
synꢀ4 was in fact 6.
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Key words
cyclophanes, aromatic compounds, reductive coupling, Xꢀray crystal structure analysis

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Introduction
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[22]Metacyclophane (antiꢀ1 and synꢀ1) among others is one of representative
[22]cyclophane isomers in view of its structural characteristics including conformational
isomerism between anti and syn isomers and chemical shift perturbation due to anisotropic
1
shielding in H NMR and steric compression in 13C NMR spectra, both which are caused by
proximate benzene ring in the molecule.1 Although antiꢀ1 was synthesized easily, synꢀ1 turned
out to be elusive due to facile ring inversion to antiꢀ1. The first derivative of synꢀ1 was
synthesized by Boekelheide by introducing an electronꢀwithdrawing group to one of the
benzene rings of 1, thereby stabilizing the syn isomer by intramolecular chargeꢀtransfer
interaction.2 Parent hydrocarbon synꢀ1 was synthesized for the first time by Mitchell in an
elegant fashion by taking advantage of the electronꢀwithdrawing effect of Cr(CO)3 group
coordinated to one of the benzene rings and it was oxidatively removed at the final stage of
the synthesis.3 Synꢀ1 thus obtained was proven to isomerize to antiꢀ1 quickly with an
activation energy of 18.4 kcal/mol. Because derivatives of [22]metacyclophanediene (2),
undergo ring closure isomerization upon heating or photoꢀirradiation to form the
corresponding bridged [14]annulene framework (i.e. dihydropyrene (3)) and they revert to 2
by photochemical ring opening, these compounds constitute as a photochromic system that
can also be applied to multiꢀstage systems.4 Moreover, the bridged [14]annulenes 3 bearing
internal alkyl groups serve as a tool to evaluate tropicity of a cyclic conjugated system fused

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to the annulene ring by monitoring the chemical shift of the internal methyl groups as a
probe.5 Reg Mitchell has made significant contributions to the rich chemistry of
[22]metacyclophane and its congeners mentioned above.
Insert Chart 1 here.
Cyclophanes bearing condensed aromatic rings are of interest not only in terms of the
conformational and physical properties due to proximate aromatic rings but also as host
molecules with large cavities and precursors of topologically interesting polycyclic aromatic
compounds.6 However, in contrast to extensively investigated [22]metacyclophanes, little has
been studied for the close cousin, [22](2,7)naphthalenophane (4). The first synthesis was
reported as early as 1951 as a precursor of coronene based on the Wurtz coupling of
2,7ꢀbis(bromomethyl)naphthalene (5) with sodium metal.7 This was followed by an improved
synthesis using phenyllithium in the next year.8 In addition to 4, isolation of a small amount of
[23](2,7)naphthalenophane (6) was reported yet with limited spectral information.9 Further
improvement
was
achieved
by
using
Stevens
rearrangement
of
dithia[3.3](2,7)naphthalenophane (8), yielding bis(thiomethyl)naphthalenophane 9 as a
mixture of regioꢀ and stereoisomers (Scheme 1).10 Desulphurization of 9 gave 4 whose
1
structure was assigned anti on the basis of H NMR spectrum. Methylation or oxidation
followed by elimination of 8 gave diene 10, which upon photoꢀirradiation in the presence of
iodine afforded coronene quantitatively.10 It is worth mentioning that dianion and dication of

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tetramethylꢀsubstituted derivative of 10 are predicted theoretically to exhibit
twoꢀelectronꢀfourꢀcenter bonding between the naphthalene cores.11 On the other hand, Sato
and coꢀworkers separated three products of the reductive coupling of 5 from which two were
assigned to antiꢀ4 and synꢀ4 on the basis of mass and NMR spectra.12 In view of the facile
ring inversion of synꢀ1 to antiꢀ1 in the [2.2]metacyclophane system, isolation of synꢀ4 is
worthy of note. Hence, not only because of the inherent interest in antiꢀ4 and synꢀ4 but also as
potential precursors to coroneneꢀrelated aromatic compounds, we reexamined preparation of
antiꢀ4 and synꢀ4 by reaction of 5 with phenyllithium. As a result, we obtained antiꢀ4,
[23](2,7)naphthalenophane (6), and [24](2,7)naphthalenophane (7), while synꢀ4 was not
detected. The structures of antiꢀ4 was established by Xꢀray crystallographic analysis and those
of 6 and 7 were elucidated on the basis of the spectral data. Because of the similarity between
the NMR and UV spectra of 6 with those reported for synꢀ4, we conclude that the compound
originally assigned to be synꢀ4 was in fact 6.
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Insert Chart 2 and Scheme 1 here.
Experimental
Bis(bromomethyl)naphthalene (5) was prepared according to the reported procedures.13
Phenyllithiun solution in hexane was purchased from Aldrich. NMR spectra were measured at
400 MHz for 1H and 100 MHz for 13C in CDCl3 at 30 °C with its residual chloroform peaks at

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7.25 and 77.0 ppm as the references, respectively. More details are described in Supporting
Information.
Reaction of 5 with PhLi (procedure 1): In a 500 mL flameꢀdried threeꢀnecked
roundꢀbottom flask equipped with a stirrer bar, compound 5 (4.00 g, 12.8 mmol) in benzene
(260 mL) was added dropwise over 30 h to a 1.08 M PhLi solution in hexane (30 mL) under
argon. The reaction mixture was heated at 60 °C and stirred for ca. 3 h before the reaction was
quenched by addition of water. The mixture was extracted with CHCl3, the combined extracts
were washed with brine and dried (MgSO4), and the solvent was removed under reduced
pressure. Separation of the products was done by column chromatography (SiO2,
hexane/CHCl3 5:1) followed by GPC to afford antiꢀ4 (428 mg, 1.39 mmol, 22%), 6 (49.6 mg,
0.107 mmol, 2%), and 7 (7.90 mg, 0.0128 mmol, 0.4%).
anti-4: colorless solid, mp 221.0ꢀ221.5 °C; 1H NMR (400 MHz, CDCl3, 30 °C) δ 7.79 (d, J =
8.8 Hz, 4H), 7.27 (dd, J = 8.2, 1.4 Hz, 4H), 5.04 (d, J = 1.6 Hz, 4H), 3.21 (m, 4H), 2.26 (m,
4H); 13C NMR (100MHz, CDCl3, 30 °C) δ 136.1, 133.2, 131.8, 130.9, 127.7, 126.7, 38.9; IR
(KBr, cmꢀ1) 3056, 3036, 3014, 2941, 2921, 2852, 1920, 1907, 1898, 1825, 1781, 1623, 1600,
1509, 1458, 1439, 1353, 1283, 1256, 1180, 1168, 1146, 1119, 989, 962, 947, 921, 863, 832,
686, 658, 636, 491, 461; HRMS (FAB) m/z calcd for C24H20: 308.1565, found 308.1566 (M+).
6: colorless solid, mp 241.5ꢀ242.5 °C.; 1H NMR (400 MHz, CDCl3, 30 °C) δ 7.65 (d, J = 8.4
Hz, 6H ), 7.27 (dd, J = 8.6 , 1.8 Hz, 6H), 6.96 (s, 6H), 3.17 (s, 12 H); 13C NMR (100MHz,

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CDCl3, 30 °C) δ 138.4, 133.7, 130.8, 127.9, 127.13, 127.06, 36.3; IR (KBr, cmꢀ1) 3044, 3012,
2920, 2897, 2854, 1733, 1717, 1685, 1636, 1607, 1509, 1457, 1439, 1354, 1273, 1213, 1183,
1134, 1092, 1038, 920, 909, 832, 764, 658, 607, 477; MS (FAB) m/z 462.2 (M+), HRMS
(FAB) m/z calcd for C36H30: 462.2348, found 462.2346 (M+).
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7: colorless solid, mp 195.0ꢀ196.0 °C.; 1H NMR (400 MHz, CDCl3, 30 °C) δ 7.72 (d, J = 8.4
Hz, 8H ), 7.24 (dd, J = 8.4 , 1.6 Hz, 8H), 6.70 (s, 8H), 3.02 (s, 16 H); 13C NMR (100MHz,
CDCl3, 30 °C) δ 138.7, 133.4, 130.8, 127.6, 127.2, 126.8, 37.6; MS (FAB) m/z 616.3 (M+),
HRMS (FAB) m/z calcd for C48H40: 616.3130, found 616.3132 (M+).
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Reaction of 5 with PhLi (procedure 2): In a 30 mL flameꢀdried threeꢀnecked
roundꢀbottom flask equipped with a stirrer bar, a 1.09 M PhLi solution in hexane (1.49 mL)
was added dropwise over 8 min to a solution of 5 (200 mg, 0.642 mmol) in benzene (260 mL)
under nitrogen. The reaction mixture was heated at 60 °C and stirred for 3.5 h before the
reaction was quenched by the addition of purified water. The crude reaction mixture was
extracted with CHCl3, the combined extracts were washed with brine and dried (MgSO4), and
the solvent was removed under reduced pressure. Separation of the products by column
chromatography (SiO2, hexane/CHCl3 2:1) afforded antiꢀ4 (10.1 mg, 0.0328 mmol, 10%) and
6 (15.3 mg, 0.0331 mmol, 16%).
Results and discussion

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The distribution of products antiꢀ4, 6, and 7 was dependent on the reaction conditions.
Typically addition of a benzene solution of 5 to PhLi gave antiꢀ4 as the major product (22%)
together with small amounts of [23]naphthalenophane 6 and [24]naphthalenophane 7. On the
other hand, the reverse addition gave 6 as the major component (16%) together with antiꢀ4
(10%). The products were separated by chromatography on silica gel and GPC.
The last eluted (the smallest sized) product in GPC was antiꢀ4, which showed identical
spectroscopic data as those reported previously in ref. 12 (given in parentheses for
comparison), including diagnostic upꢀfield shifted signal at 5.04 (5.01) ppm due to the inner
1
naphthalene proton in H NMR spectrum and the downꢀfield shifted signal at 130.9 (130.8)
ppm in 13C NMR spectrum.12 These are attributed to the anisotropic shielding and steric
compression effects due to another naphthalene ring, respectively. The methylene protons
appeared as an AA’BB’ pattern at 2.26 (2.21) ppm as reported. In addition, in UV spectrum
the product exhibit absorption maxima at 226 and 296 nm, which are virtually identical with
those reported as shown in the overlaid spectra (Figure S1). The structure was confirmed by
Xꢀray crystallographic analysis as described below.
The second last eluted product in GPC showed a peak at m/z 462.2 in FAB mass spectrum,
indicating that this is a product of reductive trimerization, i.e. [23](2,7)naphthalenophane (6).
However, the NMR and UV spectral data of this product are very reminiscent with those
1
reported for synꢀ4, which are shown below in parentheses for comparison.12 In H NMR

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spectrum, the aromatic proton signals were observed at 7.65 (7.63), 7.27 (7.22), 6.96 (6.95)
and 3.17 (3.14) ppm. Lowering the temperature down to −70 ºC did not change the spectrum,
indicating the conformational flexibility of the macrocyclic ring. 13C NMR signals were
observed at 138.4 (137.8), 133.7 (133.1), 130.8 (130.3), 127.9 (127.2), 127.13 (126.5), 127.06
(126.5), and 36.3 (35.8) ppm. With the constant shift of 0.5 ppm, the chemical shifts are
virtually identical. In UV spectrum, absorption maxima were observed at 228 and 279 nm,
which resemble well the reported spectrum for syn-4 as shown in the overlaid spectra (Figure
S2). These results indicate that the product assigned as synꢀ4 is not likely a
[22](2,7)naphthalenophane but a [23](2,7)naphthalenophane, i.e. 6. All these spectral
properties are not much different from those of simple naphthalene model such as
2,7ꢀdimethylnaphthalene,12 and do not show any specific feature arising from constraint due
to the [22]cyclophane framework. However, in the literature, the absence of upꢀfield shifted
aromatic proton was ascribed to the geometry of synꢀ4, in which the inner naphthalene proton
is not located in the shielding region of another naphthalene ring. The appearance of the
methylene proton signal as a singlet, in spite of the significant difference in the steric
environment of the germinal hydrogen atoms, was attributed to the conformational mobility
of the ring system. Moreover, the absence of downꢀfield shift of the inner naphthalene carbon
in 13C NMR spectrum was explained in terms of the relative orientation (almost
perpendicular) of the compressed p orbitals in the two naphthalene rings.12 These NMR
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characteristics which puzzled Reg Mitchell1,3b are readily accounted for by 6 with a flexible
macrocyclic ring and little constraint.
The first eluted product was assigned to [24](2,7)naphthalenophane (7) on the basis of the
spectroscopic data. The parent peak in FAB mass spectrum was observed at m/z 616.3. NMR
spectra are indicative of a structure of high symmetry in consistent with the expected
conformational mobility of the macrocyclic ring.
Crystals suitable for Xꢀray analyses of antiꢀ4 was obtained by recrystallization from a
mixture of chloroform/hexane As shown in Figure 1a, antiꢀ4 adopts a conformation in which
the two naphthalene rings orient parallel to each other with a dihedral angle between the two
mean naphthalene planes of 0º. The bridging C(sp3)ꢀC(sp3) bond orients nearly perpendicular
to the mean naphthalene plane with an angle of 82.6º. The naphthalene rings are slightly
deformed from planarity with a dihedral angle between the mean planes of the sixꢀmembered
rings of 13.6º. The inner aromatic hydrogen atom is located at 2.92 Å away from the mean
plane of the facing sixꢀmembered ring, thereby susceptible to anisotropic shielding effect in
1H NMR spectrum as observed.
Insert Figure 1 here.
Theoretically optimized structures of antiꢀ4, synꢀ4, anti,synꢀ6 and syn,synꢀ6 by DFT
calculations at the B3LYP/631G(d) level of theory are shown in Figure 2. Selected structural
parameters are listed in Table 1. The theoretical structure of antiꢀ4 listed agrees reasonably

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with the experimentally observed one. For [22](2,7)naphthalenophane conformers, antiꢀ4 is
estimated to be more stable than synꢀ4 by 46.1 kJ/mol, indicating unlikeliness of the
formation of the syn isomer. In synꢀ4, the naphthalene rings are tilted to each other with a
dihedral angle between the mean naphthalene rings of 36.0º. In this conformation significant
perturbation of the NMR spectra from that of 2,7ꢀdimethylnaphthalene is expected. For
[23]naphthalenophane conformers, anti,synꢀ6 is estimated to be more stable than syn,synꢀ6 by
10.6 kJ/mol. In anti,synꢀ6, one of the naphthalene rings is tilted with respect to the mean plane
of the macrocyclic ring, which contain all the methylene carbons and the naphthalene ring
carbons to which the methylene carbons are attached, by 50.3º, whereas the other two rings
are nearly perpendicularly oriented (dihedral angles: 75.0º and 85.3º), thus avoiding steric
congestion. On the other hand, in syn,synꢀ6 two of the naphthalene rings are tilted by 40.8º
and 49.9º with respect to the macrocyclic ring and only one ring orients nearly perpendicular
to it (dihedral angle: 77.4º), causing steric crowding around one of the faces of the
macrocyclic ring.
Insert Figure 2 and Table 1 here.
Conclusion
We reexamined reductive coupling of 2,7ꢀbis(bromomethyl)naphthalene (5) by with
phenyllithium to obtain antiꢀ[22](2,7)naphthalenophane (antiꢀ4), [23](2,7)naphthalenophane

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(6), and [24](2,7)naphthalenophane (7), but no product previously assigned to synꢀ4 was
obtained. The structure of antiꢀ4 was established by Xꢀray crystallographic analysis and their
structural features were elucidated. On the basis of the similarity between the NMR and UV
spectra of 6 with those reported for synꢀ4, we conclude that the compound originally assigned
to be synꢀ4 was in fact 6.
Supplementary materials
General experimental procedures, Xꢀray crystallographic structure analysis for anti-4, UV
spectra of antiꢀ4 and 6 overlaid to the reported spectra of antiꢀ4 and synꢀ4, respectively,
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copies of H NMR and C NMR spectra of antiꢀ4, 6, and 7, results of DFT calculations and
cif file for Xꢀray crystallographic analysis of antiꢀ4 are available with the article through the
journal Web site at:
Acknowledgement
This work was supported by GrantsꢀinꢀAid for Scientific Research (Nos. 15H02164,
25620032).
References

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10.1021/jo00412a010.
(3) (a) Mitchell, R. H.; Vinod, T. K.; Bushnell, G. W. J. Am. Chem. Soc. 1985, 107, 3340ꢀ3341.
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Figure Captions
Figure 1. ORTEP drawing of anti-4 with thermal ellipsoids of a 50% probability level.
Figure 2. Theoretically optimized structures of anti-4, syn-4, anti,syn-6 and syn,syn-6
Table 1. Selected geometrical parameters for Xꢀray and theoretical structures of anti-4.a
a For carbon numbering see Figure 2.

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Chart 1
80x85mm (300 x 300 DPI)

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Chart 2
97x131mm (300 x 300 DPI)

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Scheme 1
167x55mm (300 x 300 DPI)

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Figure 1. ORTEP drawing of anti-4 with thermal ellipsoids of a 50% probability level.
Figure 1
85x69mm (300 x 300 DPI)

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Figure 2. Theoretically optimized structures of anti-4, syn-4, anti,syn-6 and syn,syn-6.
Figure 2
144x124mm (120 x 120 DPI)

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X-ray analysis DFT calculations
bond lengths / Å
C(1)-C(2)
1.569
1.514
1.575
1.512
C(2)-C(3)
bond angle / º
C(1)-C(2)-C(3)
110.32
120.22
120.27
112.48
121.04
120.18
C(2)-C(3)-C(4)
C(2)-C(3)-C(12)
dihedral angle / º
between two mean six membered rings
bond vs. plane angle / º
C(1)-C(2) vs. mean naphthalene ring (C(3)-C(12))
C(2)-C(3) vs. C(2)-C(4)-C(5)-C(6)-C(11)-C(12)
11.62
13.55
86.46
14.90
82.63
14.87