Extreme Projection of a Proton into the π-Cloud of an Aromatic Ring: Record Shielding of an Aromatic Proton in trans-10b-Methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene

Article abstract of DOI:10.1021/ja038380m

A synthetic sequence involving dithiametacyclophane → metacyclophanediene → dihydropyrene was employed to prepare trans-10b-methyl-10c-(2-naphthyl)- and trans-10b-methyl-10c-(1-naphthyl)-10b, 10c-dihydropyrene 5 and 6, respectively. Both exhibit a strong

Full text of DOI:10.1021/ja038380m

Published on Web 12/31/2003
Extreme Projection of a Proton into the π-Cloud of an
Aromatic Ring: Record Shielding of an Aromatic Proton in
trans-10b-Methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene
Yuhua Ting and Yee-Hing Lai*
Contribution from the Department of Chemistry, National UniVersity of Singapore,
3 Science DriVe 3, Singapore 117543
Received September 7, 2003; E-mail: chmlaiyh@nus.edu.sg
Abstract: A synthetic sequence involving dithiametacyclophane f metacyclophanediene f dihydropyrene
was employed to prepare trans-10b-methyl-10c-(2-naphthyl)- and trans-10b-methyl-10c-(1-naphthyl)-
10b,10c-dihydropyrene 5 and 6, respectively. Both exhibit a strong diamagnetic ring current despite the
introduction of an internal bulky substituent within the π-electron cloud. Their electronic spectra suggest
interaction between the two near-perpendicular naphthyl and dihydropyrenyl π systems, resulting in red
shift and band broadening. All naphthyl protons are well resolved in their 1H NMR spectra due to a strong
shielding effect of the dihydropyrene ring. The most shielded protons in 5 and 6 are H1′ and H2′ at δ 2.47
and 1.42, respectively, being 5.25 and 5.95 ppm shifted from those of reference protons. There is evidence
for free rotation on the NMR time scale of the 2-naphthyl ring in 5 with a preference for a particular conformer,
whereas the 1-naphthyl ring in 6 is conformationally rigid with its H2′ projecting deeply into the π-cloud,
thus accounting for the most shielded aromatic proton (H2′ in 6) reported to date.
Introduction
whether there is a limit to the proximity of a proton projecting
into an aromatic π-cloud. We report the synthesis of the two
One of the strongest shielding effects of a benzene ring was
observed on the methine proton (δ -4.03)1 of metacyclophane
1 exhibiting a 6 ppm upfield shift from the methine resonance
(δ 1.87)2 in adamantane. Placing a methine proton within the
π-cloud of the dihydropyrene 2 (δHi ) -5.49)3 results in an
even more significant shielding effect. The conformationally
rigid naphthalenophane 3 has its aromatic Hi located directly
above the shielding zone of one of its naphthalene rings. Its
chemical shift (δHi ) 3.95)4 is 4 ppm upfield compared to that
of H2 (δ 6.95)2 of m-xylene. Again a more substantial shift
was observed going from H2,6 (δ 7.40)2 of tert-butylbenzene
to the H2′,6′ in 4 (δHi ) 2.55)5 where the phenyl ring, despite
the fact that it is likely to be freely rotating, is enclosed within
the ring current of the dihyropyrene unit.
naphthyldihydropyrenes 5 and 6 and a study of their diatropicity
and shielding effect. The H2′ in 6 was in fact found to be shifted
6 ppm upfieldsa record shielding of an aromatic protonsusing
the corresponding proton in 1,5-di-tert-butyl-naphthalene as a
reference.
The 14π aromatic system in 10b,10c-dihydropyrene has been
shown to be strongly diatropic, and the ring current is sensitive
to geometric changes, annelation, and conjugation effect.6
Replacing the phenyl ring in 4 with a sterically more demanding
aromatic substituent was expected to restrict its conformational
mobility, thus compelling one or more aromatic protons of the
internal substituent to intrude more deeply into the π-cloud of
the dihydropyrene moiety. An interesting question remains
Results and Discussion
Synthetic Routes to 10b-Methyl-10c-naphthyl-10b,10c-
dihydropyrenes. The organonickel-catalyzed7 coupling reac-
tions of the Grignard reagent of 2-bromo-m-xylene with
2-bromonaphthalene and 1-bromonaphthalene yielded 7a and
7b, respectively. Compound 7a was obtained as a colorless oil,
whereas 7b was isolated as colorless crystals. Separate free
radical bromination reactions of 7a and 7b with 2 equiv of NBS
gave dibromides 8a and 8b, respectively, in about 40% yield.
(1) Pascal, R. A., Jr.; Grossman, R. B.; Van Engen, D. J. Am. Chem. Soc.
1987, 109, 6878.
(2) ACD/Labs software: Aldrich FT-NMR Library Pro 4.5; Advanced Chem-
istry Development, Inc.: Toronto, c1994-2000.
(3) Mitchell, R. H.; Boekelheide, V. J. Am. Chem. Soc. 1974, 96, 1547.
(4) Lai, Y.-H.; Lim, T.-H. J. Org. Chem. 1989, 54, 5991.
(5) Mitchell, R. H.; Anker, W. Tetrahedron Lett. 1981, 22, 5139.
(6) (a) Mitchell, R. H. Chem. ReV. 2001, 101, 1301. (b) Mitchell, R. H. AdV.
Theor. Interesting Mol. 1989, 1, 135.
(7) Clough, R. L.; Mison, P.; Roberts, J. D. J. Org. Chem. 1976, 41, 2252.
9
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J. AM. CHEM. SOC. 2004, 126, 909-914
909

A R T I C L E S
Ting and Lai
1
The H NMR spectrum of 8a shows an AB system at δ 4.26
protons. The methyl protons of anti-10b appear at δ 1.61, being
strongly shielded by the opposite benzene ring while those of
syn-10b were observed within the expected range at δ 2.62.
and 4.21 for the two pairs of bromomethyl protons. The
corresponding AB quartet for 8b appears at δ 4.18 and 3.94.
The above observation was consistent with restricted rotation
of the benzene ring in each case, with the methylene protons in
each bromomethyl group being diastereotopic and thus magneti-
cally nonequivalent. These AB systems remained invariant at
temperatures up to 150 °C, indicating high rotational energy
barriers.8 Treatment of dibromides 8a and 8b in separate
reactions with thiourea in refluxing THF followed by hydrolysis
in refluxing aqueous KOH solution afforded quantitatively the
dithiols 9a and 9b, respectively, as colorless oils.
The coupling reaction of 9a with 2,6-bis(bromomethyl)-
toluene3 under high dilution conditions3 in refluxing ethanol in
the presence of KOH yielded 68% of dithiacyclophane 10a as
a mixture of anti and syn isomers in a 3:1 ratio. All attempts to
separate these isomers failed, but a satisfactory elemental
analysis was obtained for a mixture of anti- and syn-10a. In
the 1H NMR spectrum of the mixture the internal methyl protons
of anti-10a are significantly shielded by the opposite aryl ring
at δ 1.59 similar to related examples reported earlier.3,5 On the
contrary the internal methyl protons of syn-10a appear at δ 2.52,
being slightly deshielded by the opposite naphthyl ring compared
to those in reported examples.3,5
Separate Wittig rearrangements11 of 10a and 10b occurred
smoothly when they were treated with n-BuLi. Quenching with
MeI yielded 11a and 11b, respectively, each as a mixture of
isomers in near quantitative yield.12 The general structures of
11a and 11b were supported on the basis of their respective
1
mass and H NMR spectra. In each case a molecular ion was
observed at m/z 440, and singlets at δ 0.8-0.9 and δ 2.1-2.2
characteristic of the methylthio and anti methyl protons were
present.12 Treatment of compounds 11a and 11b separately with
13
(CH3)3CHBF4 afforded the corresponding bissulfonium salts
12a and 12b, respectively. Hofmann elimination11 of the salt
12a in the presence of t-BuOK at room temperature gave a
mixture of the dihydropyrene 5 and the diene 13a in a total
yield of ca. 20%.14 The observed ratio of 5 to 13a in freshly
isolated mixtures, based on integrations of the respective methyl
signals, ranged from 1:1 to 2:1. Diene 13a was found to undergo
valence isomerization readily to 5 and thus could not be
separated pure by chromatography. A pure sample of 5 could
be obtained on prolonged standing of a solution of the mixture
of 5 and 13a. A similar elimination reaction of the salt 12b at
room temperature, however, did not result in the formation of
either 6 or 13b. Carrying out the reaction in THF at reflux gave,
after chromatography, only the dihydropyrene 6 in 10% yield.
Diene 13b, the valence isomer of 6, was not observed,
presumably because the severe steric interaction caused by the
1-naphthyl group accelerated the isomerization of the initially
formed diene 13b to dihydropyrene 6. The relatively more
sterically demanding 1-naphthyl group in 13b may then explain
why the Hofmann elimination of 12b to form 13b was slower
than that of 12a to 13a but the subsequent valence isomerization
of 13b to 6 is faster than that of 13a to 5. Carrying out the
Hofmann elimination of salt 12a in refluxing THF also resulted
in direct isolation of only 5 without the presence of 13a in the
product. Thermally, 5 was found to be relatively more stable
than 6. In fact, 6 readily decomposed, particularly in solution,
on prolonged standing.
A similar coupling reaction between either 2,6-bis-(mercap-
tomethyl)toluene3 with dibromide 8b or dimercaptan 9b with
2,6-bis(bromomethyl)toluene failed to give either isomer of
dithiacyclophane 10b. This could be attributed to unfavorable
steric interaction caused by the 1-naphthyl group in the
cyclization step. Cesium carbonate has been employed in the
successful synthesis of many thia- and dithiacyclophanes that
are otherwise difficultly accessible.9 By employing the cesium
effect10 we could successfully prepare 10b. It was, however,
only obtained in about 10% optimum yield as a mixture of anti
and syn isomers (5:1) by carrying out the coupling reaction in
DMF in the presence of cesium carbonate at 70 °C. The
decreased syn:anti ratio in going from 10a to 10b is also
consistent with an increase in unfavorable steric interaction
going from a 2-naphthyl to a 1-naphthyl moiety. Recrystalli-
zation and chromatography failed to yield pure samples of either
anti or syn isomer of 10b. Satisfactory elemental analysis was,
however, obtained for the mixture of 10b. Assignment of the
stereochemistry of each isomer in the mixture could again be
readily made on the basis of the chemical shift of the methyl
The spatial demand of the 2-naphthyl group in 13a was
expected to restrict rotation about the aryl-aryl bond similar
to that observed for the phenyl analogue reported earlier.5 Two
of its possible conformations are illustrated in 13a-A and 13a-
(11) Mitchell, R. H.; Otsubo, T.; Boekelheide, V. Tetrahedron Lett. 1975, 16,
319.
(12) A syn-to-anti isomerization is known to occur in such Wittig rearrangements
although the extent of isomerization may vary from one system to another.
Signals of methyl protons of the corresponding syn isomers, if present,
would be masked by those of the SCH3 protons.
(8) (a) Clough, R. L.; Roberts, J. D. J. Am. Chem. Soc. 1976, 98, 1018. (b)
Wolf, C.; Mei, X. J. Am. Chem. Soc. 2003, 125, 10651.
(9) Rossa, L.; Vo¨gtle, F. Top. Curr. Chem. 1983, 113, 12.
(13) Borch, R. F. J. Org. Chem. 1969, 32, 627.
(10) (a) Buter, J.; Kellogg, R. M. J. Org. Chem. 1982, 46, 4481. (b) Vo¨gtle, F.;
Klieser, B. Synthesis 1982, 249. (c) Klieser, B.; Vo¨gtle, F. Angew. Chem.
Suppl. 1982, 1392. (d) Kato, N.; Matsunaga, H.; Oeda, S.; Fukazawa, Y.;
Ito, S. Tetrahedron Lett. 1979, 20, 2419.
(14) Mixture of the bissulfonium salts might contain the corresponding syn
isomers of anti 12. There was, however, no indication of the presence of
syn-cyclophandiene or cis-dihydropyrene in the product mixture after
Hofmann elimination.
9
910 J. AM. CHEM. SOC. VOL. 126, NO. 3, 2004

Shielding of an Aromatic Proton
A R T I C L E S
Table 1. Shielding Effect on Selected Aromatic Protons of 4-6 in
Comparison to Reference Protons in 15-17
B. The appreciable shielding of H4′ (δ 7.46) compared to
chemical shifts of other protons on the naphthyl ring indicates
a preference for conformer 13a-A. Conformer 13a-B is also
expected to be sterically unfavorable with the naphthyl ring in
close proximity to the opposite phenyl ring. The upfield shift
of H4,6 (δ 6.14) and H5 (δ 6.22) in 13a-A no doubt derives
from shielding by the naphthyl ring.
a
b
c
ortho-H
meta-H
para-H
compd
δ
|∆δ|
δ
|∆δ|
δ
|∆δ|
4
15
5
2.55
7.40
2.47
3.62
7.72
7.55
1.42
7.37
5.6
7.29
6.50
6.0
4.85
1.69
1.16
7.16
5.25
3.93
1.25
16
7.75
6
17
5.80
7.22
6.82
8.27
5.95
1.42
1.45
a H2′,6′ of 4; H1′ and H3′ of 5, respectively; H2′ of 6; H2,6 of 15; H1
and H3 of 16, respectively; H2,6 of 17. b H3′,5′ of 4; H4′ of 5; H3′ of 6;
H3,5 of 15; H4 of 16; H3,7 of 17. c H4′ of 4; H4′ of 6; H4 of 15; H4,8 of
17.
Diatropicity and Spectral Properties. The internal methyl
protons of 5 and 6 appear at δ -4.25 and -4.32, respectively,
indicating that their ring currents are very similar to that of the
parent dihydropyrene 14 (δCH3 -4.25).3 Although the spatially
more demanding 1-naphthyl group may result in certain degree
of geometric deviation from planarity of the peripheral ring in
6 (see later discussion), the seemingly identical ring currents
of 6 and 14 suggests that such deformation, if any, does not
of 5-6 ppm due to the extensive shielding effect of the
dihydropyrene ring (Figures 1 and 2). The most shielded proton
in 5 is H1′ appearing at δ 2.47. There is no reported series of
reference compounds with similar steric, conformational, and/
or strain effects found in 4, 5, and 6, although such effects could
affect proton chemical shift. In comparison to the strong
shielding effect in 4-6, the steric, strain, and/or conformational
effect, if any, will, however, be expected to be relatively small.
For example, from the optimized structures of 5 and 6 derived
from B3LYP/6-31G* (DFT) method (refer to Figures 5a and
7a), the distances between H1′ (in 5) or H2′ (in 6) and the
peripheral carbons C10b, C1, and C2 are between 2.6 and 2.9
Å. These are only slightly smaller than the sum of their van
der Waals radii (2.9 Å),16 and thus the steric effect is not
expected to induce very significant changes in the proton
chemical shift of H1′ or H2′. The series of compounds 15, 16,
and 17 may not approximate the steric, conformational, and/or
strain effects found in 4, 5, and 6, respectively, but their
structural features are consistent in the series for a reasonable
comparative study. Using tert-butylbenzene 152 and 2,6-di-tert-
butylnaphthalene 1617 as the corresponding reference com-
pounds, the shielding of H1′ in 5 is similar (ca. 5 ppm) to that5
observed for the H2′,6′ in 4 (Table 1). Going from 5 to 6 leads
to a more shielded aromatic proton in H2′ of 6, being shifted
upfield to δ 1.42sa shielding of about 6 ppm compared to the
chemical shift of H2,6 of the reference 1,5-di-tert-butylnaph-
thalene 17.18 This appears to be one of the largest shieldings of
an aromatic proton and may, in fact, be a record. The above
observation may suggest a conformationally rigid naphthyl ring
in 6 with its H2′ projecting deeply toward the center of its
diamagnetic ring current (see later discussion on conformational
studies).
1
affect significantly the diatropicity of the macro ring. The H
NMR spectra of 5 and 6 are shown in Figure 1 and Figure 2,
respectively. Proton assignments of 5 and 6 were made on the
1
basis of their H NMR, 2D COSY, and HMBC spectra and a
series of NOE experiments.
Interestingly, all the ring protons in the dihyropyrene unit in
5 and 6 have essentially identical coupling constants (7.7-7.8
Hz). This clearly suggests that there is little bond alternation in
the 14π peripheral ring consistent with the strong diatropicity
observed in 5 and 6.15 In fact, their aromatic protons of the
internal naphthyl ring were well resolved within a wide range
Figure 1. 1H NMR (300 MHz) spectrum of the aromatic protons in
dihydropyrene 5.
Close promixity between the π orbitals in the benzenoid and
the dihydropyrene in 4-6 held near-perpendicular to each other
(15) (a) Cremer, D.; Gu¨nther, H. Liebigs Ann. Chem. 1972, 763, 87. (b) Lai,
Y.-H.; Chen, P.; Dingle, T. W. J. Org. Chem. 1997, 62, 916. (c) Mitchell,
R. H.; Chen, Y. S.; Khalifa, N. J. Am. Chem. Soc. 1998, 120, 1785. (d)
Andres, W.; Gu¨nther, H.; Gu¨nther, M.-E.; Hausmann, H.; Gu¨nther, J.; von
Puttkamer, H.; Schmickler, H.; Niu-Schwarz, J.; Schwarz, W. H. E. HelV.
Chim. Acta 2001, 84, 1737.
Figure 2. 1H NMR (300 MHz) spectrum of the aromatic protons in
dihydropyrene 6.
(16) Bondi, A. J. Phys. Chem. 1964, 68, 441.
9
J. AM. CHEM. SOC. VOL. 126, NO. 3, 2004 911

A R T I C L E S
Ting and Lai
Figure 4. Possible conformations for naphthyldihydropyrene 5.
Figure 3. Electronic spectra of aryldihydropyrenes 4 (s), 5 (-- -) and 6
(- ‚ - ‚ -).
represents a unique type of π-π interaction. Although this effect
was not clearly evident in the study of 4,5 such interaction
between two aromatic rings is expected to lead to a splitting of
the molecular orbitals in the excited-state, thus resulting in a
red shift and/or broadening of the absorption bands in their
electronic spectra.19 The electronic spectra of 4,5 5, and 6 are
illustrated in Figure 3. It is interesting to note that the spectrum
of 5 in the range of 300-600 nm is similar to that of 4 but the
Figure 5. Optimized structures of (a) 5A and (b) 5E derived from B3LYP/
6-31G* (DFT) method.
conformers 5A, 5D, and 5E are energy minima, and their relative
Gibb’s free energy at 298 K was found to be 0:9.3:3.0 kJ mol-1
.
The optimized structures of 5A and 5E are shown in Figure 5.
The dihydropyrene moiety remains essentially planar in 5A and
5E with a relatively larger deviation observed for C7 in 5E.
Conformer 5C was a random point on the potential energy
surface, and full optimization of 5C led to conformer 5D. A
full optimization of 5C with the transition search keyword,
however, resulted in conformer 5B. Optimization of a structure
whose starting geometry is very similar to that of 5B led to
5D. The above observation indicates that 5B is a transition state,
and its Gibb’s free energy at 298 K was estimated to be 18.2
kJ mol-1 at 298 K. The differences in relative free energy of
5A, 5B, 5D, and 5E are reasonably low to suggest possible
rotation of the naphthyl ring about the C10b-C2′ bond. A piece
of evidence came from the following NOE experiments.
Irradiation of either H1′ or H3′ of 5 resulted in enhancement of
signals of all the peripheral ring protons H1-H10. Thus, it is
likely that the naphthyl ring in 5 undergoes rotation with 5A
being the major conformer, and hence there is a significant
difference in the shielding of H1′ and H3′. This is similar to a
related phenomenon in the conformational study of 9-H-9-ethyl-
10-methyl-anthracenium ion.22 A dynamic 1H NMR study of 5
ranging from -80 to 80 °C indicated a significant change (∆δ
) 0.6 ppm) in the chemical shift of H1′. This was expected
since the chemical shift of H1′ should be most sensitive to a
change in the relative population of rapidly interconverting
conformers as the temperature was varied. A much smaller
change was observed for H3′, and the chemical shifts of the
other protons remained practically invariant within the temper-
ature range studied.
λ
max are red-shifted. The spectrum of 6 in the same wavelength
range, however, exhibits significant broadening of the absorption
bands in addition to a small red shift. This again supports a
relatively rigid conformation of the 1-naphthyl ring in 6, thus
maximizing the novel through-space interaction between the two
near-perpendicular aromatic π systems.
Conformational Studies. A conformational study of 4 did
not confirm whether the phenyl ring in it undergoes free rotation
on the NMR time scale.5 It is interesting to note that the
shielding of the two “ortho” protons H-1′ and H3′ of 5 is
significantly different by >1 ppm (Table 1). This may suggest
that the 2-naphthyl ring in 5 is not freely rotating on the NMR
time scale or it favors a certain conformation at equilibrium.
Observation from appropriate molecular models suggests several
possible conformations as indicated in Figure 4. Geometries of
these conformers of 5 were optimized using the B3LYP/6-31G*
(DFT) method with the Gaussian 98 suite of programs.20 Such
programs have been employed successfully in optimizing
structural geometries of macrocyclic annulenes that correlated
satisfactorily with their experimentally observed physical prop-
erties.21 Results derived from our calculations showed that
(17) (a) Koch, K.-H.; Mu¨llen, K. Chem. Ber. 1991, 124, 2091. (b) Smith, K.;
Roberts, S. D. Catal. Today 2000, 60, 227.
(18) Van Bekkum, H.; Nieuwstad, Th. J.; Van Barneveld, J.; Klapwijk, P.;
Wepster, B. M. Recueil 1969, 88, 1028.
(19) (a) Katoh, T.; Ogawa, K.; Inagaki, Y.; Okazaki, R. Bull. Chem. Soc. Jpn.
1997, 70, 1109-1114. (b) Jiang, J.; Lai, Y.-H. J. Am. Chem. Soc. 2003,
14296.
(20) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M.
A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann,
R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin,
K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi,
R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.;
Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.;
Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz,
J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.;
Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.;
Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian
98, revision A.7; Gaussian, Inc.: Pittsburgh, PA, 1998.
In the 14π system of 10b,10c-dihydropyrene the shielding
effect is expected to be the most significant along the central
z-axis given a distance d from the molecular plane.23 In 6, H8′
(21) Kimball, D. B.; Haley, M. M.; Mitchell, R. H.; Ward, T. R.; Bandyo-
padhyay, S.; Williams, R. V.; Armantroat, J. R. J. Org. Chem. 2002, 67,
8798. (b) Boydston, A. J.; Haley, M. M.; Williams, R. V.; Armantroat, J.
R. J. Org. Chem. 2002, 67, 8812.
(22) Brouwer, D. M.; Van Doorn, J. A. Recl. TraV. Chim. Pays-Bas 1970, 89,
88.
(23) Lai, Y.-H.; Zhou, Z.-L. J. Org. Chem. 1997, 62, 925.
9
912 J. AM. CHEM. SOC. VOL. 126, NO. 3, 2004

Shielding of an Aromatic Proton
A R T I C L E S
as the solvent. Chemical shifts are reported in ppm relative to TMS.
Elemental analysis was performed at the Chemical and Molecular
Analysis Center, Department of Chemistry, National University of
Singapore. Mass spectra were determined by electron impact ionization.
Relative intensities are given in parentheses.
2-(2-Naphthyl)-m-xylene, 7a. A solution of 2-bromo-m-xylene (5.0
g, 27 mmol) in THF (20 mL) was added dropwise to a suspension of
magnesium (0.65 g, 27 mmol) in THF (5 mL). The reaction was
initiated by addition of 1,2-dibromoethane, and the mixture was
maintained at gentle reflux until all magnesium reacted. The solution
was transferred to a dropping funnel and added slowly to a solution of
2-bromonaphthalene (3.11 g, 15 mmol) and Ni(acac)2 (30 mg, 3.24
mmol) at room temperature. The mixture was warmed to 40 °C and
maintained at that temperature for 16 h. Water was added, and the
mixture was extracted with CH2Cl2 (150 mL), washed, dried, and
evaporated. The residue was preadsorbed on silica gel and chromato-
graphed on silica gel with petroleum ether (40-60 °C) to give 7a (66%)
Figure 6. Possible conformations for naphthyldihydropyrene 6.
1
as colorless oil. H NMR δ 7.90 (d, J ) 8.4 Hz, 1H), 7.80-7.91 (m,
2H), 7.62 (br s, 1H), 7.47-7.52 (m, 2H), 7.29 (dd, J ) 1.6 Hz, J )
8.4 Hz, 1H), 7.12-7.23 (m, 3H), 2.04 (s, 6H). MS m/z 232 (100, M+),
217 (80), 202 (20). Anal. Calcd for C18H16: C, 93.06; H, 6.94. Found:
C, 92.82; H, 7.14.
Figure 7. Optimized structures for (a) 6A and (b) 6E derived from B3LYP/
6-31G* (DFT) method.
appears at δ 5.63, while H2′ is significantly more shielded at δ
1.41. This suggests a preference for a conformation where H2′
is located along the central axis of the dihydropyrene ring and
projecting deeply into the center of the π-electron cloud such
as 6A or 6B (Figure 6). Geometries of conformers of 6 (Figure
6) were also optimized using the B3LYP/6-31G* (DFT) method
with the Gaussian 98 suite of programs.20 Results from these
calculations only indicated conformers 6A and 6E as energy
minima, and their optimized structures are shown in Figure 7.
It is apparent that the dihydropyrene moiety in 6A and 6E is
significantly deviated from planarity compared to that in 5A
and 5E (Figure 5) due to a larger steric demand of the 1-naphthyl
substituent. Conformers 6B, 6C, and 6D are random points on
the potential energy surface. A transition state 6C′ was, however,
found to have a structure similar to that of 6C with a relatively
larger dihedral angle of 42° for its C2′-C1′-C10c-C10d (that
of 6C is 30°). The relative Gibb’s free energy of 6A:6C′:6E
was calculated to be 0:42.7:16.4 kJ mol-1 at 298 K.
2-(1-Naphthyl)-m-xylene, 7b. This was prepared by a procedure
similar to that described for 7a. Compound 7b was isolated as colorless
1
crystals (60%): mp 67-68 °C. H NMR δ 7.90 (d, J ) 8.2 Hz, 1H),
7.86 (d, J ) 8.2 Hz, 1H), 7.56 (d, J ) 7.0 Hz, 1H), 7.53 (d, J ) 7.0
Hz, 1H), 7.16-7.46 (m, 6H), 1.90 (s, 6H). MS m/z 232 (100, M+),
217 (90), 202 (30). Anal. Calcd for C18H16: C, 93.06; H, 6.94. Found:
C, 93.12; H, 6.94.
1,3-Bis(bromomethyl)-2-(2-naphthyl)benzene, 8a. NBS (3.38 g,
19.0 mmol) was added to a solution of 7a (2.20 g, 9.48 mmol) in CCl4.
The reaction mixture was heated with a 200-W lamp at solvent refluxing
temperature for 2 h. After filtration, the filtrate was washed with water,
dried, and evaporated. The residue was chromatographed on silica gel
with hexane as eluant to give the dibromide 8a (37%) as colorless
crystals: mp 108-109 °C. 1H NMR δ 7.85-7.97 (m, 4H), 7.38-7.57
(m, 6H), 4.26, 4.21 (ABq, J ) 10.0 Hz, 4H). MS m/z 388 (10, M+),
229 (100). Anal. Calcd for C18H14Br2: C, 55.42; H, 3.62. Found: C,
55.61; H, 3.54.
1,3-Bis(bromomethyl)-2-(1-naphthyl)benzene, 8b. This was pre-
pared by a procedure similar to that described for 8a. Compound 8b
The difference in relative stability between 6A and 6E was
estimated to be 16.4 kJ mol-1, and on this basis alone an
interconversion between them might seem possible. It is,
however, considered unlikely having to go through a transition
1
was isolated as colorless crystals (40%): mp 72-73 °C. H NMR δ
7.94 (t, J ) 7.9 Hz, 2H), 7.2-7.6 (m, 8H), 4.18. 3.94 (ABq, J ) 10.1
Hz, 4H). MS m/z 388 (10, M+), 299 (100). Anal. Calcd for C18H14Br2:
C, 55.42; H, 3.62. Found: C, 55.51; H, 3.61.
state 6C′ with an energy barrier estimated to be 42.7 kJ mol-1
.
1,3-Bis(mercaptomethyl)-2-(2-naphthyl)benzene, 9a. A solution
of dibromide 8a (1.20 g, 3.07 mmol) and thiourea (0.47 g, 6.15 mmol)
in THF (40 mL) was heated at reflux for 5 h. After removal of THF
under reduced pressure, the residue was treated with 0.36 M KOH
solution (50 mL), and the mixture was heated at reflux for 5 h. The
solution was acidified with dilute HCl at 0-5 °C and then extracted
with CH2Cl2 (150 mL). The organic layer was washed with water, dried,
and evaporated. The residue was chromatographed on silica gel to give
Thus, we believe that 6 adopts a rigid conformation 6A or 6E
at room temperature. Restricted rotation of the naphthyl ring
and a preference for 6A was indicated by results from a series
of NOE experiments. Irradiation of the H8′ signal of 6 showed
only selective enhancement of H6-8, unlike the comprehensive
enhancement observed for H1-10 in similar experiments of 5
described earlier. This is the first example of confirmed restricted
rotation of an internal substituent within the π-cloud of the
10b,10c-dihydropyrene system. Molecular rigidity in 6 was
1
the dithiol 9a (95%) as yellow oil. H NMR δ 7.94 (d, J ) 8.4 Hz,
1H), 7.85-7.91 (m, 2H), 7.78 (s, 1H), 7.52-7.65 (m, 2H), 742 (dd, J
) 1.7 Hz, J ) 8.4 Hz, 1H), 7.36 (br s, 3H), 3.48, 3.40 (dq, J ) 7.6 Hz,
J ) 13.2 Hz, 4H), 1.60 (t, J ) 7.6 Hz, 2H). MS m/z 296 (30, M+), 229
(100). Anal. Calcd for C18H16S2: C, 72.93; H, 5.44. Found: C, 73.11;
H, 5.64.
1
further supported by a dynamic H NMR study. The results
showed only a small change (0.25 ppm) in the chemical shift
of H2′ in the temperature range of -90 to 90 °C. Chemical
shifts of all other protons remained almost invariant.
1,3-Bis(mercaptomethyl)-2-(2-naphthyl)benzene, 9b. This was
prepared by a procedure similar to that described for 9a. Compound
1
9b was isolated as yellow oil (90%). H NMR δ 7.93 (d, J ) 8.3 Hz,
Experimental Section
2H), 7.2-7.6 (m, 8H), 3.38, 3.18 (dq, J ) 7.9 Hz, J ) 13.5 Hz, 4H),
1.49 (t, J ) 7.6 Hz, 2H). MS m/z 296 (40, M+), 229 (100). Mr Calcd
for C18H16S2: 296.0693; found (MS) 296.0691. This was used for the
subsequent reaction without further purification.
General Procedures. All reactions were carried out under nitrogen.
Commercially available reagents and solvents were used without further
purification. 1H NMR spectra were obtained at 300 MHz using CDCl3
9
J. AM. CHEM. SOC. VOL. 126, NO. 3, 2004 913

A R T I C L E S
Ting and Lai
anti- and syn-2,11-Dithia-18-methyl-9-(2-naphthyl)[3.3]metacyclo-
phanes, 10a. A solution of KOH (0.94 g, 16.8 mmol) in 95% EtOH (1
L) was heated to gentle reflux. A solution of 2,6-bis(bromomethyl)-
toluene (1.46 g, 5.25 mmol) and dithiol 9a (1.56 g, 5.25 mmol) in
benzene (200 mL) was added dropwise over a period of 6 h to the
warm KOH solution. After the addition, the mixture was stirred for 15
h while maintaining at near solvent refluxing temperatures. The solution
was then cooled and the bulk of the solvent removed under reduced
pressure. The residue was extracted with CH2Cl2. The organic layer
was dried, concentrated, and chromatographed on silica gel using a
1:1 mixture of CH2Cl2/hexane as eluant. A mixture of anti- and syn
10a in a 3:1 ratio was isolated (68%). Recrystallization from EtOH/
Wittig Rearrangement of 10b To Give 11b. This was prepared
by a procedure similar to that described for 11a. A mixture of the
isomers of 11b was isolated as yellow oil (90%). 1H NMR δ 6.6-8.1
(m), 4.0-4.3 (m), 2.6-3.2 (m), 2.0-2.2 (m), 0.8-0.9 (m). MS m/z
440 (<10, M+), 275 (70), 165 (100). Mr Calcd for C29H28S2: 440.1632;
found (MS) 440.1637. This was used for the subsequent reaction without
further purification.
trans-10b-Methyl-10c-(2-naphthyl)-10b,10c-dihydropyrene, 5. To
a solution of an isomeric mixture of 11a (g, 0.81 mmol) in CH2Cl2 (10
mL) was added (CH3)3CHBF4 (0.48 g, 3.23 mmol) at -30 °C. The
mixture was stirred at this temperature for 0.5 h and then at room
temperature for 5 h. Ethyl acetate (15 mL) was added, and the mixture
was stirred until fine precipitate was obtained. After removal of the
clear supernatant liquor, the residual solid was washed with ethyl acetate
and dried under vacuum to give the salt 12a. This was treated with
t-BuOK (2.0 mmol) in refluxing THF for 0.5 h. After removal of THF
under reduced pressure, the residue was extracted with cyclohexane.
The organic layer was washed with water, dried, and evaporated. The
dark-blue residue was chromatographed on silica gel using hexane as
eluant to give 5 (18%). Careful recrystallization from hexane/EtOH
gave dark-green crystals of 5: mp 160-161 °C. 1H NMR δ 8.81 (d, J
) 7.8 Hz, 2H), 8.75 (d, J ) 7.8 Hz, 2H), 8.67 (d, J ) 7.7 Hz, 2H),
8.52 (d, J ) 7.7 Hz, 2H), 8.40 (t, J ) 7.8 Hz, 1H), 8.21 (t, J ) 7.8 Hz,
1H), 7.06-7.24 (m, 1H), 6.89-6.97 (m, 2H), 6.57-6.60 (m, 1H), 6.50
(d, J ) 8.8 Hz, 1H), 3.62 (dd, J ) 2.0 Hz, J ) 8.8 Hz, 1H), 2.47 (d,
J ) 2.0 Hz, 1H), -4.24 (s, 3H). MS m/z 344 (28, M+), 329 (100), 202
(74). UV-vis λmax (cyclohexane) 232 (ꢀ 84 060), 272 (11 800), 282
(10 670), 344 (57 720), 362 (23 970), 386 (43 590), 484 (8570) nm.
Anal. Calcd for C27H20: C, 94.14; H, 5.86. Found: C, 94.24; H, 5.76.
trans-10b-Methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene, 6. This
was prepared by a procedure similar to that described for 5. Careful
recrystallization of from hexane/EtOH gave dark-blue crystals of 6:
1
CH2Cl2 gave colorless crystals of 10a: mp 162-165 °C. H NMR δ
6.8-7.8 (m), 4.25 (d, J ) 15.2 Hz, syn), 4.01 (d, J ) 14.3 Hz, syn),
3.82, 3.69 (AB, J ) 14.3 Hz, anti), 3.76 (d, J ) 15.2 Hz, syn), 3.74,
3.59 (AB, J ) 13.7 Hz, anti), 3.69 (d, J ) 14.3 Hz, syn), 2.52 (s, syn),
1.59 (s, anti). MS m/z 412 (40, M+), 262 (75), 229 (100). Anal. Calcd
for C27H24S2: C, 78.59; H, 5.86; S, 15.54. Found: C, 78.43; H, 5.83;
S, 15.74.
anti- and syn-2,11-Dithia-18-methyl-9-(1-naphthyl)[3.3]metacyclo-
phanes, 10b. A solution of 2,6-bis(bromomethyl)toluene (0.90 g, 3.2
mmol) and dithiol 9b (0.95 g, 3.2 mmol) in DMF (400 mL) was added
dropwise to stirred suspension of Cs(CO3)2 (3.13 g, 9.6 mmol) in DMF
(1 L) maintained at 60-70 °C over a period of 12 h. After the addition,
the reaction mixture was stirred at this temperature range for an
additional 12 h. After removal of DMF under vacuum, the resulting
residue was dissolved in CH2Cl2, washed with water, dried, and
evaporated. The crude mixture was chromatographed on silica gel using
CH2Cl2/hexane (1:1) as eluant to give 10b (8%) as a mixture of anti
and syn isomers in a 5:1 ratio. Recrystallization from EtOH/CH2Cl2
1
gave colorless crystals of 10b: mp 174-178 °C. H NMR δ 8.48 (d,
J ) 8.4 Hz, syn), 6.9-7.9 (m), 6.52 (d, J ) 8.5 Hz, anti), 6.26 (dd, J
) 1.0 Hz, J ) 7.2 Hz, anti), 4.22 (d, J ) 15.2 Hz, syn), 3.84, 3.68
(AB, J ) 14.3 Hz, anti), 3.78 (d, J ) 15.2 Hz, syn), 3.57, 3.53 (AB,
J ) 11.4 Hz, syn), 3.52, 3.23 (AB, J ) 13.6 Hz, anti), 2.62 (s, syn),
1.61 (s, anti). MS m/z 412 (40, M+), 262 (55), 229 (100). Anal. Calcd
for C27H24S2: C, 78.59; H, 5.86; S, 15.54. Found: C, 78.65; H, 5.79;
S, 15.57.
Wittig Rearrangement of 10a to Give 11a. To a solution of 10a
(0.11 g, 0.27 mmol) in THF (15 mL) maintained at 0-5 °C was added
n-BuLi (0.27 mmol). The dark-brown solution was kept at this
temperature for 20 min. CH3I (0.5 mL) was added and the mixture
stirred for 1 h. The mixture was then extracted with CH2Cl2 (100 mL).
The organic layer was washed with water, dried, and evaporated. The
residue was chromatographed on silica gel using CH2Cl2 as eluant to
give a mixture of isomers of 11a as yellow oil (91%). 1H NMR δ 6.9-
8.0 (m), 3.9-4.3 (m), 2.3-3.3 (m), 2.1-2.2 (m), 0.8-0.9 (m). MS
m/z 440 (<10, M+), 275 (70), 165 (100). Mr Calcd for C29H28S2:
440.1632; found (MS) 440.1639. This was used for the subsequent
reaction without further purification.
1
mp 154-156 °C. H NMR δ 8.81 (d, J ) 7.8 Hz, 2H), 8.62 (d, J )
7.8 Hz, 2H), 8.60 (d, J ) 7.8 Hz, 2H), 8.34 (d, J ) 7.8 Hz, 2H), 8.28
(t, J ) 7.8 Hz, 1H), 7.86 (t, J ) 7.8 Hz, 1H), 7.13-7.16 (m, 1H),
6.98-7.02 (m, 2H), 6.82 (d, J ) 8.0 Hz, 1H), 5.80 (t, J ) 8.0 Hz,
1H), 5.62-5.65 (m, 1H), 1.42 (br d, J ) 8.0 Hz, 1H), -4.32 (s, 3H).
MS m/z 344 (14, M+), 329 (60), 217 (65), 202 (100). UV-vis λmax
(cyclohexane) 224 (ꢀ 58 200), 274 (10 000), 332 (21 260), 356 (22 140),
372 (22 000), 394 (30 650), 480 (4360), 504 (3750) nm. Anal. Calcd
for C27H20: C, 94.14; H, 5.86. Found: C, 93.78; H, 6.16.
Acknowledgment. Financial support for the work was
provided by the National University of Singapore (NUS). We
thank Dr. G. Philip Kiruba Sebastina Mary for assisting us in
the theoretical calculations, and the staff of the Chemical and
Molecular Analysis Centre, Department of Chemistry, NUS, for
their technical assistance.
JA038380M
9
914 J. AM. CHEM. SOC. VOL. 126, NO. 3, 2004