10a-(4-Biphenyl)-10b-methyl-10a,10b-dihydropyrene: a conformational study and ring current effect

Article abstract of DOI:10.1016/j.tetlet.2008.04.137

A dithiacyclophane was employed as a precursor to the title compound. A conformational study of the dithiacyclophane revealed a unique phenomenon in its terphenyl unit: one ring is rigidly held, the other terminal ring undergoes free rotation and the central ring exhibits restricted mobility. The aromatic protons of the biphenyl unit are all shielded by the dihydropyrene unit and well resolved in the ¹H NMR spectrum, consistent with a ring current effect extended to eight conjugated carbon atoms away from the molecular plane of dihydropyrene.

Full text of DOI:10.1016/j.tetlet.2008.04.137

Tetrahedron Letters 49 (2008) 4282–4285
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Tetrahedron Letters
journal homepage: http://www.elsevier.com/locate/tetlet
10a-(4-Biphenyl)-10b-methyl-10a,10b-dihydropyrene: a conformational
study and ring current effect
*
Sook-Yee Yoon, Yee-Hing Lai
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
A dithiacyclophane was employed as a precursor to the title compound. A conformational study of the
dithiacyclophane revealed a unique phenomenon in its terphenyl unit: one ring is rigidly held, the other
terminal ring undergoes free rotation and the central ring exhibits restricted mobility. The aromatic
protons of the biphenyl unit are all shielded by the dihydropyrene unit and well resolved in the 1H
NMR spectrum, consistent with a ring current effect extended to eight conjugated carbon atoms away
from the molecular plane of dihydropyrene.
Received 17 March 2008
Revised 14 April 2008
Accepted 24 April 2008
Available online 27 April 2008
Keywords:
Dihydropyrene
Ó 2008 Elsevier Ltd. All rights reserved.
Dithiacyclophane
Conformational mobility
Ring current effect
The first examples of doping poly(p-phenylene) (PPP) to estab-
lish its conducting properties were reported some 30 years ago.1
Many PPP derivatives of type 1 copolymers have since been pre-
pared for various applications based on their electrical, electronic,
and/or optical properties.2 They are collectively among the most
comprehensively studied organic polymers today. The properties
of copolymers 1 depend significantly on the linear conjugation in
the polymer backbone. A series of copolymers 2 incorporating
paracyclophanes into the polymer backbone showed that transan-
nular p–p interactions could affect the optical properties of poly-
mers significantly.3 Thus an interesting area is to investigate
whether homo-conjugation could also be employed to tune the
properties of polymers. Compound 34 is the only example where
a carbocylic non-benzenoid has been introduced into a polymer
backbone. It is a low molecular weight polymer, which shows
interesting photochromic properties. A designer copolymer could
be 4 where propagation of the properties of the polymer depends
on homo-conjugation between the biphenyl and dihydropyrene
segments. While relatively inconclusive in the study of 5a,5
homo-conjugation was evident in its naphthalene derivatives6
and compound 6.7
In this Letter, dihydropyrene 5b was used as a model for 4 to
investigate the conformational mobility of the biphenyl segment.
Another interesting aspect is to examine whether adjacent
dihydroypyrenes in 4 would be in sufficient proximity to interact.
A study of 78 showed that its ring current effect reached the pro-
tons on the C8 carbons but its methylene chain could be folded.
Monitoring the proton at C400 (Scheme 1) in the rigid biphenyl unit
in 5b should provide a better indication of the extent of the ring
current effect of the dihydropyrene.
The synthetic route to 5b is summarized in Scheme 1. A Ni(II)-
catalyzed9 coupling reaction between the Grignard reagent pre-
pared from 4-bromobiphenyl and 1-bromo-2,6-dimethylbenzene
* Corresponding author. Tel.: +65 6516 2914; fax: +65 6779 1691.
E-mail address: chmlaiyh@nus.edu.sg (Y.-H. Lai).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.137

S.-Y. Yoon, Y.-H. Lai / Tetrahedron Letters 49 (2008) 4282–4285
4283
8 afforded the terphenyl 9.10 Free radical benzylic bromination11 of
9 gave the desired dibromide which was converted to the dithiol
10.12 A cyclization reaction between 10 and the dibromide 1113
gave a mixture of anti-dithiacyclophane 12 and its syn isomer in
an approximately 9:1 ratio based on 1H NMR estimation.14 The anti
stereochemistry of 12 was clearly evident from a significantly
shielded methyl signal at d 1.55. Compound 12 was obtained in
42% yield after repeated recrystallizations. Its syn isomer, however,
could not be isolated in pure form. A Witting rearrangement15
–
Hofmann elimination16 sequence13 on 12 afforded a 44% yield of
the desired trans-dihydropyrene 5b isolated as dark green crystals
after chromatography and recrystallization. The trans stereochem-
istry was evident from a strongly shielded methyl signal at d ꢀ4.28
in its 1H NMR spectrum. In fact, a spectrum of the product mixture
immediately after reaction indicated about 10% of the cis-isomer
(dCH3 = ꢀ2.64). This compound could not, however, be isolated
due to its decomposition on chromatography.
The conformational behavior of p-terphenyl,17 methyl-substi-
tuted p-terphenyls,18 and oligo(p-phenylene)s19 has been studied.
p-Terphenyl was shown to exist as two stable rotational isomers
around the inter-ring C–C bonds in solution.17 In the terphenyl unit
in 12, ring C is conformationally rigid, it would be interesting to
examine whether rings A and B would exhibit unrestricted rotation
about the two C–C bonds independently. The 1H NMR spectrum of
dithiacyclophane 12 at or near room temperature (Fig. 1) showed
well-resolved signals that could be assigned, through homo-decou-
pling and NOE experiments, to all the aromatic protons except
those in ring A (Scheme 1). In fact the resolution of these signals
remained relatively unchanged apart from marginal shifts when
the sample was cooled from 308 to 213 K. This is a clear indication
that there was unrestricted rotation about the bond joining ring A
and ring B even at the low temperature limit. The aromatic protons
at C2, C3, C5, and C6 in ring A were not observed at or below room
temperature suggesting that there was a separate slow exchange
process. At 213 K, these protons (H20, H30, H50, and H60) were
observed as four separate sets of well-resolved double doublets
(Fig. 1). This is a clear indication that there was restricted rotation
about the C–C bond between ring A and ring C. Wobbling behavior,
as shown in Figure 2, is believed to occur as was evident by the
presence of only two well-resolved AB systems for the four pairs
of bridging methylene protons.14 As the temperature was raised,
Figure 1. 1H NMR spectra (500 MHz, CDCl3) of the aromatic protons in dithia-
cyclophane 12 at different temperatures [proton numbering as in Scheme 1].
in addition to signal broadening, there were significant shifts of
the four double doublets resulting in the appearance of only two
singlets at the higher temperature limit (Fig. 1) consistent with a
fast exchange process (unrestricted rotation of ring A). The two
singlets [d 7.48 (sharp, H20,60); d 6.82 (broad, H30,50)], however,
did not appear at the approximate centers of the corresponding
pairs of double doublets [d 7.61 (H20), 7.47 (H60); d 7.29 (H30),
6.71 (H50)]. The significant signal shifts could be a result of the
varying angle a (Fig. 2) at different temperatures (thus varying
averaged chemical shifts) before free rotation occurred after a
certain temperature.
Scheme 1. Synthetic route to dihydropyrene 5b. Reagents and conditions: (i) 4-
bromobiphenyl/Mg, THF, reflux, 3 h; (ii) Ni(acac)2, THF, ꢀ78 °C, 5 min; reflux, 15 h;
(iii) NBS, CCl4, hm, reflux, 3 h; (iv) (NH2)2CS, 95% EtOH, reflux, 1 h; KOH, H2O, reflux,
15 h; (v) KOH, 95% EtOH/benzene (4:1), 65 °C, 23 h; (vi) LDA, THF, rt, 10 min; MeI,
THF, rt, 30 min; (vii) (CH3O)2CHBF4, CH2Cl2, ꢀ30 °C, 15 min; rt, 20 h; (viii) t-BuOK,
THF, reflux, 1 h.

4284
S.-Y. Yoon, Y.-H. Lai / Tetrahedron Letters 49 (2008) 4282–4285
Acknowledgment
This work was supported by the Singapore Ministry of Educa-
tion through AcRF Tier 1 Grant R-143-000-169-112. The authors
thank the staff at the Chemical, Molecular and Materials Analysis
Center, Department of Chemistry, National University of Singapore,
for technical assistance.
Figure 2. The wobbling process in dithiacyclophane 12 at low temperatures (j:
Ring C; : Ring A).
References and notes
Employing the coalescence temperature method20 to estimate
1. (a) Shacklette, L. W.; Chance, R. R.; Ivory, D. M.; Miller, G. G.; Baughman, R. H.
Synth. Met. 1979, 1, 307; (b) Ivory, D. M.; Miller, G. G.; Sowa, J. M.; Shacklette, L.
W.; Chance, R. R.; Baughman, R. H. J. Chem. Phys. 1979, 71, 1506; (c) Shacklette,
L. W.; Elsenbaumer, R. L.; Chance, R. R.; Sowa, J. M.; Ivory, D. M.; Miller, G. G.;
Baughman, R. H. Chem. Commun. 1982, 361–362.
2. Kaeriyama, K. In Photonic Polymer Systems: Fundamentals, Methods, and
Applications; Wise, D. L., Wnek, G. E., Trantolo, D. J., Cooper, T. M., Gresser, J.
D., Eds.; Marcel Dekker: New York, 1998; pp 33–60.
3. (a) Wang, W.-L.; Xu, J.-W.; Lai, Y.-H.; Wang, F.-K. Macromolecules 2004, 37,
3546–3553; (b) Wang, W.-L.; Xu, J.-W.; Zhe Sun, Z.; Xinhai Zhang, X.; Lu, Y.; Lai,
Y.-H. Macromolecules 2006, 39, 7277–7285; (c) Wang, W.-L.; Xu, J.-W.; Lai, Y.-H.
J. Polym. Sci., Part A: Polym. Chem. 2006, 44, 4154–4164.
4. Marsella, M. J.; Wang, Z.-Q.; Mitchell, R. H. Org. Lett. 2000, 2, 2979–2982.
5. Mitchell, R. H.; Anker, W. Tetrahedron Lett. 1981, 22, 5139–5140.
6. Ting, Y.; Lai, Y.-H. J. Am. Chem. Soc. 2004, 126, 909–914.
the
free
energy
of
activation
ðDGz ¼ 4:57 Tc½9:97þ
c
log10ðTc=DtÞꢁ),21 there are two sets of data available for compari-
son. The coalescence temperatures (Tc) for the two pairs of double
doublets (Dt = 74 and 287 Hz) could be estimated at 270 and 283 K,
respectively (Fig. 1). These correspond to DGzc values of 54.4 and
53.9 kJ molꢀ1. It was surprising to note that this conformational
barrier of about 54 kJ molꢀ1 observed for 12 was essentially iden-
tical to that estimated for its phenyl (in place of biphenyl) analog.22
Clearly ring B in 12 does not inflict any undesirable buttressing/
steric effect on ring A in hindering its rotation about the C–C bond
between ring A and ring C.
7. Jiang, J.; Lai, Y.-H. J. Am. Chem. Soc. 2003, 125, 14296–14297.
All the aromatic protons of dihydropyrene 5b were resolved in
its 1H NMR spectrum (Fig. 3). The spectrum remained essentially
unchanged with only marginal broadening and shifts when a sam-
ple was cooled from 298 to 213 K. It is evident that the biphenyl
unit in 5b enjoyed unrestricted free rotation even at the low tem-
perature limit. Protons H30, 50 were strongly shielded at d 2.89.
Although the shielding effect declined quickly for H20, 60 and H200,
600 (Fig. 3), H300, 500 and H400 appeared at d 7.10 and d 7.05, respec-
tively. These are, however, still at relatively higher field than the
corresponding protons (d 7.3–7.6) in 4-t-butylbiphenyl23 as a refer-
ence. It is apparent that the ring current effect of the dihydro-
pyrene extends to even H400—eight conjugated carbon atoms
away from the molecular plane of the dihydropyrene within 5b.
This supports an empirical correlation established in the study of
7 where the proton shielding was also extended to C8 of the
methylene chain.8 An interesting observation was that H400 is
slightly less shielded than H300,500 in 5b. These three protons are
near the limit of the ring current effect and thus in addition to
the distance from the center of the dihydropyrene molecular plane,
their actual coordinates may result in the marginal difference in
their chemical shifts.
In conclusion, free rotation of the aromatic rings in 5b, and 12
at above room temperature, suggests that free rotation of the
biphenyl spacer in polymer 4 is expected to allow conformational
flexibility in their alignment for optimal homoconjugation with
the dihydropyrenes. Secondly, a ring current study may suggest
that the adjacent dihydropyrenes in 4 could be held by the
rigid spacer in sufficient proximity to interact magnetically or
electronically to propagate their properties along the polymer
backbone.
8. Lai, Y.-H.; Zhou, Z.-L. J. Org. Chem. 1997, 62, 925–931.
9. Mitchell, R. H.; Yan, J. S. H. Can. J. Chem 1980, 58, 2584–2587.
10. 4-Bromobiphenyl (0.98 g, 4.2 mmol) in dry THF (20 ml) was added dropwise to
Mg (11 mg, 4.5 mmol) in gently refluxing dry THF under Ar for 3 h. The
resulting Grignard reagent was cooled to ꢀ78 °C, and 1-bromo-2,6-
dimethylbenzene (0.77 g, 4.2 mmol) in dry THF (15 ml) was added dropwise
(5 min) followed by Ni(acac)2 (12 mg, 0.3 mmol). The mixture was warmed to
rt and further maintained at refluxing temperature for 15 h. Water was added
and the product was extracted into CH2Cl2, washed with 10% aqueous HCl and
water, and dried. Chromatography on silica gel using hexane as eluent followed
by recrystallization from cyclohexane gave 9 as a white solid (0.58 g, 70%),
mp = 94–96 °C. 1H NMR (300 MHz, CDCl3) d 7.66 (dd, J = 8.0, 1.7 Hz, 4H), 7.46
(t, J = 7.5 Hz, 2H), 7.35 (t, J = 7.4 Hz, 1H), 7.11–7.25 (m, 5H), 2.08 (s, 6H). EIMS
m/z 258 (M+, 100), 243 (30), 181 (26). CHN Calcd for C20H18: C, 92.98; H, 7.02.
Found: C, 92.63; H, 7.36.
11. NBS (0.78 g, 4.4 mmol) and 9 (0.53 g, 2 mmol) in CCl4 (200 ml) were heated at
refluxing temperature by irradiation with visible light. When all the NBS had
reacted (ca. 3 h), the mixture was cooled and filtered. The filtrate was washed
with water and dried. Recrystallization from cyclohexane gave 2,6-bis-
(bromomethyl)terphenyl as a white solid (0.82 g, 76%), mp = 146–147 °C. 1H
NMR (300 MHz, CDCl3) d 7.68–7.73 (m, 4H), 7.36–7.51 (m, 8H), 4.27 (s, 4H).
EIMS m/z 414 (M+, 16; correct isotope pattern for Br2), 255 (100). CHN Calcd for
C
20H16Br2: C, 57.72; H, 3.88. Found: C, 57.58; H, 4.12.
12. 2,6-Bis(bromomethyl)terphenyl (0.473 g, 1.1 mmol) and thiourea (0.258 g,
3.3 mmol) in 95% EtOH were heated at refluxing temperature for 1 h. The
resulting bis(thiouronium) salt precipitate was filtered and added to an
aqueous solution of KOH (0.94 mg, 20 mmol). The mixture was heated at
refluxing temperature for 15 h, cooled and acidified with 1 M aqueous HCl. The
product was extracted into ether and dried. Chromatography of the product
mixture on silica gel using hexane/CH2Cl2 (3:2) as eluent gave 10 (0.311 g, 88%)
as a thick oil. Slow evaporation of a solution of 10 in cyclohexane kept at 0 °C
gave pure 10, mp = 62–65 °C. 1H NMR (300 MHz, CDCl3) d 7.67–7.72 (m, 4H),
7.49 (br t, J = 7.6 Hz, 2H), 7.35–7.41 (m, 6H), 3.50 (d, J = 7.7 Hz, 4H), 1.64 (t,
J = 7.7 Hz, 2H). EIMS m/z 322 (M+, 69), 255 (100). CHN Calcd for C20H18S2: C,
74.49; H, 5.63. Found: C, 74.85; H, 5.66.
13. Mitchell, R. H.; Boekelheide, V. J. Am. Chem. Soc 1974, 96, 1547–1557.
14. A solution of 10 (0.259 g, 0.8 mmol) and 11 (0.222 g, 0.8 mmol) in benzene
(150 ml) was added dropwise with vigorous stirring over 8 h to KOH (0.75 g,
16 mmol) in 95% EtOH/benzene (4:1, 600 ml) at ca. 65 °C. The mixture was
stirred at ca. 65 °C for another 15 h. The bulk of the solvent was removed under
reduced pressure and the product was extracted into CH2Cl2 (150 ml). The 1H
NMR spectrum of the product mixture indicated
a 9:1 ratio of anti
(dCH3 = 1.56): syn (dCH3 = 2.35) isomers. Chromatography on silica gel using
hexane/CH2Cl2 (1:1) as eluent followed by repeated recrystallizations from
cyclohexane gave colorless crystals of 12 (0.148 g, 42%), mp = 180–181 °C. 1H
NMR (500 MHz, CD2Cl2, ꢀ60 °C) d 7.67 (d, J = 7.4 Hz, 2H), 7.61 (dd, J = 8.1,
1.8 Hz, 1H), 7.54 (d, J = 7.6 Hz, 2H), 7.51 (t, J = 7.6 Hz, 2H), d 7.47 (dd, J = 8.0,
1.9 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.38 (t, J = 7.5 Hz, 1H), 7.29 (dd, J = 8.1,
1.6 Hz, 1H), 7.25 (d, J = 7.6 Hz, 2H), 7.03 (t, J = 7.5 Hz, 1H), 6.71 (dd, J = 8.0,
1.7 Hz, 1H), 3.86 (d, J = 13.6 Hz, 2H),
d 3.81 (d, J = 14.3 Hz, 2H), 3.72 (d,
J = 14.3 Hz, 2H), 3.49 (d, J = 13.6 Hz, 2H), 1.55 (s, 3H). EIMS m/z 438 (M+, 62),
287 (30), 255 (100), 253 (46). Calcd for C29H26S2: C, 79.41; H, 5.97. Found: C,
79.08; H, 6.11.
15. LDA prepared from n-BuLi (1.6 M in hexane; 0.4 ml) and diisopropylamine
(61 mg, 0.6 mmol) in dry THF (5 ml) was added dropwise to 12 (109 mg,
0.25 mmol) in dry THF (10 ml) under N2 at rt. After 10 min, excess MeI
1
Figure 3. H NMR spectrum (MH2, CD2Cl2) of aromatic protons (excluding H30, 50 at
d 2.89) in dihydropyrene 5b.

S.-Y. Yoon, Y.-H. Lai / Tetrahedron Letters 49 (2008) 4282–4285
4285
(284 mg, 2 mmol) was added and the mixture stirred at rt for 30 min. Water
and CH2Cl2 were then added, and the organic phase was separated and dried.
Chromatography on silica gel using hexane/CH2Cl2 (3:1) gave a mixture of 13
as a white solid (86 mg, 74%): 1H NMR (500 MHz, CDCl3) d 8.02 (d, J = 6.2 Hz),
7.78 (d, J = 6.4 Hz), 7.5–7.7 (m), 7.53 (d, J = 7.1 Hz), 7.4–7.5 (m), 7.41 (t,
J = 7.7 Hz), 7.2–7.3 (m), 7.15 (t, J = 7.4 Hz), 6.7–7.0 (m), 6.50 (d, J = 8.4 Hz), 4.28
(dd, J = 11.4, 7.1 Hz), 4.15–4.20 (m), 3.97 (dd, J = 11.3, 4.2 Hz), 2.65–2.95
(several sets of multiplets), 2.15, 2.19, 2.25 (s), 0.83, 0.85, 0.87 (s). EIMS m/z
466 (M+, 21), 403 (29), 370 (24), 301 (100), 255 (65). Calcd for C31H30S2 (MS):
466.6999. Found: 466.6986. This was used directly for subsequent reaction.
44%), mp = 143–145 °C. 1H NMR (500 MHz, CDCl3) d 8.79 (d, J = 7.8 Hz, 2H),
8.72 (d, J = 7.7 Hz, 2H), 8.70 (d, J = 7.7 Hz, 2H), 8.46 (d, J = 7.7 Hz, 2H), 8.34 (t,
J = 7.7 Hz, 1H), 8.18 (d, J = 7.8 Hz, 1H), 7.10 (t, J = 7.2 Hz, 2H), 7.05 (t, J = 7.0 Hz,
1H), 6.94 (dd, J = 7.7, 1.6 Hz, 2H), 6.11 (d, J = 8.6 Hz, 2H), 2.89 (d, J = 8.6 Hz,
2H), ꢀ4.28 (s, 3H). EIMS m/z 370 (M+, 26), 355 (43), 217 (36), 202 (100). Calcd
for C29H22: C, 94.01; H, 5.99. Found: C, 93.82; H, 6.17.
17. (a) Honda, K.; Furukawa, Y. J. Mol. Struct. 2005, 735,736, 11–19; (b) Zhuravlev,
K. K.; McCluskey, M. D. J. Chem. Phys. 2004, 120, 1841–1845; (c) Johnston, M. B.;
Herz, L. M.; Khan, A. L. T.; Köhler, A.; Davies, A. G.; Linfield, E. H. Chem. Phys.
Lett. 2003, 377, 256–262; (d) Kato, M.; Taniguchi, Y. J. Chem. Phys. 1990, 92,
887–890.
16.
A mixture of 13 (0.140 g, 0.3 mmol) in CH2Cl2 (5 ml) was added to
(MeO)2CHBF4 (162 mg, 1 mmol) suspended in CH2Cl2 (5 ml) at ꢀ30 °C under
N2. The mixture was then stirred at rt for 5 h. EtOAc (4 ml) was added and the
mixture stirred for 15 h. The resulting bis(sulfonium) salt was filtered and
18. (a) Delmond, S.; Létard, J.-F.; Lapouyade, R.; Rettig, W. J. Photochem. Photobiol.,
A. 1997, 105, 135–148; (b) Menzel, R.; Lueck, H. Chem. Phys. 1988, 124, 417–
424.
dried. t-BuOK (103 mg, 1 mmol) was added to
a
suspension of the
19. Heimel, G.; Somitsch, D.; Knoll, P.; Zojer, E. J. Chem. Phys. 2002, 116, 10921–
10931.
20. Oki, M. Applications of Dynamic NMR Spectroscopy to Organic Chemistry; VPH:
bis(sulfonium) salt in dry THF (15 ml) at rt under N2. The mixture was
heated at refluxing temperature for 1 h, cooled, and extracted with CH2Cl2. The
organic layer was washed with water and dried. The 1H NMR spectrum of the
¯
Deerfield Beach, 1985.
product mixture indicated a 10:1 ratio of trans (dCH3 = ꢀ4.28): cis (dCH3
=
21. Gutowsky, H. S.; Holm, C. H. J. Chem. Phys. 1956, 25, 1228–1234.
22. Mitchell, R. H.; Anker, W. Tetrahedron Lett. 1981, 22, 5135–5138.
23. Mino, T.; Shirae, Y.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2005, 70, 2191–2194.
ꢀ2.64) isomers. Chromatography on silica gel using hexane as eluent followed
by recrystallization from cyclohexane gave green crystals of trans-5b (49 mg,