Synthesis and diatropicity of trans-2′,5′,10b,10c-tetramethylfurano[3,4-e]-10b,10c-dihydropyrene. A valence isomerization to form a novel isoannulenofuran at the expense of two benzene and one furan rings

Article abstract of DOI:10.1021/jo951586o

The 1,4-dicarbonyl compound 22 was prepared by an oxidative coupling of the benzyl methyl ketone 19. Dehydration of 22 gave the 3,4-diarylfuran 16 which upon functional group transformations and a subsequent intramolecular cyclization afforded only the anti isomer of the furanothiacyclophane 27. Ring contraction following a Wittig rearrangement - Hofmann elimination sequence led to the isolation of anti furanocyclophanene 15b. Valence isomerization of 15b to the isoannulenofuran 14b could be achieved either photochemically or thermally with 15b as the thermodynamically more stable isomer. Compound 14b was found to exhibit only a very small ring current. The diatropicity of 14b is clearly affected by a weak participation of the oxygen in π-electron delocalization and a steric effect of its external methyl groups resulting in a deviation from planarity of its molecular periphery. The thermal conversion of 15b to 14b was determined to have a high activation energy of 114 kJ mol^-1. This thermal process, in addition to involving the disruption of π-electron delocalization in two benzene and one furan rings, is another example of an unsual concerted, symmetry-forbidden reaction.

Full text of DOI:10.1021/jo951586o

J . Org. Chem. 1996, 61, 935-940
935
Syn th esis a n d Dia tr op icity of
tr a n s-2′,5′,10b,10c-Tetr a m eth ylfu r a n o[3,4-e]-10b,10c-d ih yd r op yr en e.
A Va len ce Isom er iza tion To F or m a Novel Isoa n n u len ofu r a n a t th e
Exp en se of Tw o Ben zen e a n d On e F u r a n Rin gs
Yee-Hing Lai* and Pu Chen
Department of Chemistry, National University of Singapore, Kent Ridge, Republic of Singapore
Received August 30, 1995X
The 1,4-dicarbonyl compound 22 was prepared by an oxidative coupling of the benzyl methyl ketone
19. Dehydration of 22 gave the 3,4-diarylfuran 16 which upon functional group transformations
and a subsequent intramolecular cyclization afforded only the anti isomer of the furanothiacyclo-
phane 27. Ring contraction following a Wittig rearrangement-Hofmann elimination sequence led
to the isolation of anti furanocyclophanene 15b. Valence isomerization of 15b to the isoannule-
nofuran 14b could be achieved either photochemically or thermally with 15b as the thermodynami-
cally more stable isomer. Compound 14b was found to exhibit only a very small ring current. The
diatropicity of 14b is clearly affected by a weak participation of the oxygen in π-electron
delocalization and a steric effect of its external methyl groups resulting in a deviation from planarity
of its molecular periphery. The thermal conversion of 15b to 14b was determined to have a high
activation energy of 114 kJ mol-1. This thermal process, in addition to involving the disruption of
π-electron delocalization in two benzene and one furan rings, is another example of an unsual
concerted, symmetry-forbidden reaction.
The aromaticity of the heterocycles pyrrole (1), furan
(2), and thiophene (3) has been well studied in terms of
both chemical and physical properties.1,2 The general
conclusion has always been that furan (2) is the least
aromatic. The fusion of these heterocycles at the 3,4-
positions to unsaturated carbocycles, i.e., isoannelation,
has also been examined. Results from the calculations3
of the topological resonance energy per π-electron for the
series of isoannelated compounds 4-6 again indicate that
5 is the least aromatic. The participation of oxygen in
nondiatropic, while there is a significant decrease in
diatropicity in compound 8 (|δHi - δHo| ≈ 3)7 relative to
that of the benzo[14]annulene 9 (|δHi - δHo| ≈ 8).8
Compound 8 is not very stable, and its aromatic protons
are likely to be affected by local anisotropic effects.9 The
[a]-ring furano-annelated dihydropyrene 10 (δCH3
)
0.13, 0.15)10 has also qualitatively been found to exhibit
only about 16% of the ring current of the parent com-
pound 11 (δCH3 ) -4.25).11 The cyclophanediene 12 was
the aromaticity of the resulting isoannelated macroring
thus seems to be the least effective of the selected
heteroatoms. Deshielded signals (δ 7.8-8.4)4 experimen-
1
tally observed for the furanoid protons in the H NMR
spectrum of 5 (n ) 0), however, suggests the presence of
a strong ring current and somewhat contradicts the data
obtained from theoretical calculations.
Among the few reported isoannulenofurans5 (oxa[17]-
annulenes), compound 7 (|δHi - δHo| ≈ 0)6 is essentially
X Abstract published in Advance ACS Abstracts, J anuary 1, 1996.
(1) Comprehensive Heterocyclic Chemistry; Bird, C. W., Cheeseman,
G. W. H., Eds.; Pergamon Press: New York, 1984; Vol. 4.
(2) Balaban, A. T.; Banciu, M.; Ciorba, V. Annulene, Benzo-, Hetero-,
Homo-Derivatives and Their Valence Isomers; CRC Press: Boca Raton,
FL, 1987; Vol. 3.
(3) J uric´, A.; Sabljic´, A.; Trinajstic´, N. J . Heterocycl. Chem. 1984,
21, 273.
(4) (a) Warrener, R. N. J . Am. Chem. Soc. 1971, 93, 2346. (b) Wege,
D. Tetrahedron Lett. 1971, 2337. (c) Wiersum, U. E.; Mijs, W. J . J .
Chem. Soc., Chem. Commun. 1972, 347.
(5) This term is derived qualitatively from isobenzofuran.
(6) (a) Beeby, P. J .; Weavers, R. T.; Sondheimer, F. Angew. Chem.,
Int. Ed. Engl. 1974, 13, 138. (b) Weavers, R. T.; Sondheimer, F. Angew.
Chem., Int. Ed. Engl. 1974, 13, 141.
(7) (a) Ebe, H.; Nakagawa, T.; Iyoda, M.; Nagakawa, M. Tetrahedron
Lett. 1981, 22, 4441. (b) Iyoda, M.; Nakagawa, T.; Ebe, H.; Oda, M.;
Nakagawa, M.; Yamamoto, K.; Higuchi, H.; Ojima, J . Bull. Chem. Soc.
J pn. 1994, 67, 778.
(8) Yasuhara, A.; Satake, T.; Iyoda, M.; Nakagawa, M. Tetrahedron
Lett. 1975, 895.
0022-3263/96/1961-0935$12.00/0 © 1996 American Chemical Society

936 J . Org. Chem., Vol. 61, No. 3, 1996
Lai and Chen
reported to undergo valence isomerization12 readily to
give the [e]-ring annelated benzo[14]annulene 13 (δCH3
) -1.85)san example of interrupting the delocalization
of π-electrons in three benzene rings to form a benzan-
nelated dihydropyrene. Many other benzannelated de-
rivatives of 11 were found to behave similarly.13 The high
diatropicity (aromaticity) achieved in the dihydropyrene
moiety is believed to be one of the main driving forces
for such a conversion. Given the fact that isoannelation
would only lead to a significantly less diatropic (aromatic)
macroring, it would thus be doubtful whether an isoan-
nulenofuran such as 14a could be obtained from the
valence isomerization of 15a at the expense of two
benzene and one furan rings. We wish to report the
the aldehyde 20, was obtained from this reaction, and
its yield increased with reaction time. This, we believe,
was due to further oxidation of 19 at the benzylic position
followed by oxidative cleavage. Alternatively, the ketone
19 could be synthesized by the treatment of the mono-
Grignard prepared from 2,6-dichlorotoluene with 3-bromo-
2-methoxy-1-propene18 to give the intermediate 21 fol-
lowed by an acid hydrolysis of the latter.
The 1,4-dicarbonyl compound 22 was then prepared via
an oxidative coupling of 19 with activated manganese
dioxide in acetic acid.19 This reaction in fact afforded a
mixture of the diketone 22 and the diarylfuran 16 in 18%
and 9% yield, respectively. These two compounds could
be separated readily by column chromatography. The
latter was clearly formed by the acid-catalyzed dehydra-
tion of the former. In fact, dehydration20 of 22 with
phosphorus pentoxide in a mixture of THF and ethanol
gave the desired 3,4-diarylfuran 16 in good yield. Steri-
cally, the anti conformation 22a is expected to be the
synthesis of cyclophanene 15b and its physical and
chemical properties.
Resu lts a n d Discu ssion
(a ) Syn th esis. The synthesis of [e]-ring annelated
derivatives of 11 commonly involves, as a precursor, a
suitably substituted tert-aryl derived from an o-dibromo
aromatic compound or an o-quinone.10b,12-14 These ap-
proaches are, however, inappropriate for the synthesis
of a 3,4-diarylfuran. In order to minimize any complica-
tion from addition and/or substitution reactions at the
2,5-positions of a furan ring, we have selected the 3,4-
diarylfuran 16 as a synthetic precursor for 15b.
1
most stable. In the H NMR spectrum of 22, however,
the aryl methyl protons appeared at δ 1.84ssignificantly
shielded compared to the methyl protons of toluene (δ
2.35).21 This shielding is consistent with an anti-stepped
conformation with a hydrogen bond between the two
acetyl groups as shown in 22b. For the diarylfuran 16,
1
its H NMR spectrum showed two singlets at δ 2.16 and
2.15 (1:1) which correspond to the methyl groups on the
benzene rings. Their resolution indicates the presence
of anti and syn conformers 16a and 16b, respectively,
similar to that observed in other tert-aryl systems.22,23
The methyl groups on the furan ring were, however,
unresolved and appeared as a singlet at δ 2.09.
Treatment of the mono-Grignard15 prepared from 2,6-
dichlorotoluene with 3-bromopropene gave compound
17. Conversion of 17 to the alcohol 18 was achieved by
an oxymercuration/demercuration16 sequence in quanti-
tative yield. The oxidation of 18 with J ones’ reagent17
in acetone afforded the desired ketone 19. A side product,
(9) Mitchell, R. H.; Williams, R. V.; Mahadevan, R.; Lai, Y.-H.;
Dingle, T. W. J . Am. Chem. Soc. 1982, 104, 2571.
(10) (a) Mitchell, R. H.; Zhou, P. Tetrahedron Lett. 1991, 32, 6319.
(b) Mitchell, R. H.; Iyer, V. S.; Khalifa, N.; Mahadevan, R.; Venugo-
palan, S.; Weerawarna, S. A.; Zhou, P. J . Am. Chem. Soc. 1995, 117,
1514.
(11) Mitchell, R. H.; Boekelheide, V. J . Am. Chem. Soc. 1974, 96,
1547.
(12) Mitchell, R. H.; Yan, J . S. H.; Dingle, T. W. J . Am. Chem. Soc.
1982, 104, 2551.
(13) Mitchell, R. H. Adv. Theor. Interesting Mol. 1989, 1, 135.
(14) Lai, Y.-H. J . Am. Chem. Soc. 1985, 107, 6678.
(15) Mitchell, R. H.; Lai, Y.-H. J . Org. Chem. 1984, 49, 2534.
(16) Brown, H. C.; Geoghegan, P. J ., J r. J . Org. Chem. 1970, 35,
1844.
(17) Bowers, A.; Halsall, T. G.; J ones, E. R. H.; Lemin, A. J . J . Chem.
Soc. 1953, 2548.

Formation of a Novel Isoannulenofuran
J . Org. Chem., Vol. 61, No. 3, 1996 937
Conversion of 16 to 26 was achieved with minor
modifications via a similar sequence of reactions reported
for the syntheses of the corresponding 1,2-diaryl-
benzenes10b,12,22 and 9,10-diarylphenanthrenes.14 The
optimized overall yield of dibromide 26 was about 58%.
The existence of anti and syn conformers in this series
of compounds is evident by the resolution of the corre-
sponding pairs of methyl groups on the furan and/or
benzene ring. The chemical shift difference of each pair
is, however, very small and considered unreliable to serve
as a probe for dynamic 1H NMR studies for the estimation
of the conformational energy barrier.24
THF at room temperature led to the isolation of colorless
crystals of the anti cyclophanene 15b in 96% yield. Due
to a gradual thermal conversion to 14b (see later discus-
sion) the melting point of 15b could only be estimated to
be 135-137 °C. Retention of the anti stereochemistry
in 15b is supported by its shielded internal methyl
protons at δ 1.38 comparable to that observed for anti
31 (δ 1.41).12
An intramolecular coupling of the dibromide 26 with
sodium sulfide under high dilution conditions25 afforded
the thiacyclophane 27. Only its anti isomer 27a , mp
208-211 °C, was isolated. There was no detectable
quantity of the corresponding syn isomer 27b. The anti
stereochemistry of 27a was confirmed by its significantly
shielded internal methyl protons at δ 0.87 similar to that
reported for anti 28 (δ 0.94).12 The bridging methylene
protons of 27a appeared as an AB quartet at δ 3.79 and
3.67.
(b) Va len ce Isom er iza tion a n d Dia tr op icity. The
reversible photochemical valence isomerization29 between
dimethyldihydropyrene 11 and cyclophanediene 32 is a
unique and interesting physical property of 11. This
phenomenon was also observed in most derivatives of
11.13,29 The conversion of 11 to 32 could be achieved by
irradiation with visible light, and the reversed process
was favored by irradiation with UV light.
A general synthetic approach to the parent dimeth-
yldihydropyrene 1111 and its derivatives involving ring
contraction reactions of thiacyclophanenes or dithiacy-
clophanes has been well documented.10b,13,26 Thus, a
Wittig rearrangement27 of 27a with n-butyllithium fol-
lowed by methyl iodide quench gave only the anti
metacyclophane 29. Its internal methyl protons are
unresolved and appear as a sharp singlet at δ 0.54sshifted
further upfield due to a closer stacking of the opposite
benzene rings when one of the bridges is shortened going
from 27a to 29. The above observation suggests that the
SCH3 group in 29 occupies a pseudoaxial position pro-
jecting away from the adjacent methyl group, thus
resulting in no significant deshielding effect by the sulfur
atom. Remethylation of 29 with dimethoxycarbonium
fluoroborate28 gave the intermediate sulfonium salt 30,
which upon treatment with potassium tert-butoxide in
A pale yellowish solution of 15b in thoroughly degassed
benzene, when irradiated with UV light at 254 nm for
20 min, resulted in a dark purple solution containing a
mixture of 15b and its valence isomer, trans-14b. The
presence of the latter was evident by the appearance of
two new singlets at δ 0.63 and 2.38 in a 1:1 ratio in the
1H NMR spectrum. A similar spectrum could also be
obtained thermally by warming a solution of 15b. It is
clear that the oxa[17]annulene 14b sustains a weak
diamagnetic ring current resulting in only a small
shielding of the internal methyl protons compared with
those in a nonaromatic reference 33 (δCH3 ) 0.97).30
Complete conversion of 15b to 14b , however, was not
possible either thermally or photochemically, and pro-
longed reaction times seemed to result in decomposition
of the product(s). The formation of 14b was, however,
confirmed by its reversed isomerization to 15b when the
solution was irradiated with visible light.
(18) J acobson, R. M.; Raths, R. A.; McDonald, J . H. J . Org. Chem.
1977, 42, 2545.
(19) Vinogradov, M. G.; Direi, P. A.; Nikishin, G. I. J . Org. Chem.
USSR (Engl. Transl.) 1978, 14, 1894.
(20) (a) Mukaiyama, T.; Hata, T. Bull. Chem. Soc. J pn. 1961, 43,
99. (b) Nozaki, H.; Koyama, T.; Mori, T. Tetrahedron 1969, 25, 5357.
(21) The Aldrich Library of NMR Spectra, 2nd ed.; Aldrich Chemical
Co.: Milwaukee, 1983; Vol. 1, p 733B.
(22) Mitchell, R. H.; Yan, J . S. H. Can. J . Chem. 1980, 58, 2584.
(23) (a) Lai, Y.-H. J . Chem. Soc., Perkin Trans. 2 1986, 1667. (b)
Lai, Y.-H.; Chen, P. J . Chem. Soc., Perkin Trans. 2 1989, 1665.
(24) (a) Calder, I. C.; Garratt, P. J . J . Chem. Soc. B 1967, 660. (b)
Dixon, K. R.; Mitchell, R. H. Can. J . Chem. 1983, 61, 1598. (c) Gygax,
R.; Wirz, J .; Sprague, J . T.; Allinger, N. L. Helv. Chim. Acta 1977, 60,
2522. (d) Oki, M. Applications of Dynamic NMR Spectroscopy to
Organic Chemistry; VCH Publishers: Deerfield Beach, FL, 1985.
(25) (a) Rossa, L.; Vo¨gtle, F. Top. Curr. Chem. 1983, 113, 1. (b)
Knops, P.; Sendhoff, N.; Mekelburger, H.-B.; Vo¨gtle, F. Top. Curr.
Chem. 1991, 161, 1. (c) Ostrowicki, A.; Koepp, E.; Vo¨gtle, F. Top. Curr.
Chem. 1991, 161, 37.
Only a single maximum was observed at 230 nm in
the UV/vis spectrum of 15b. The spectrum for a mixture
of 14b and 15b (Figure 1) clearly shows new bands of
14b in the range of 250-600 nm similar to those of the
parent 1131 and benzannelated derivative 13.12 The
maxima of 14b in the range of 280-380 nm are, however,
significantly blue shifted.
(29) (a) Blattmann, H. R.; Schmidt, W. Tetrahedron 1970, 26, 5885.
(b) Blattman, H. R.; Meuche, D.; Heilbronner, E.; Molyneux, R. J .;
Boekelheide, V. J . Am. Chem. Soc. 1965, 87, 130. (c) Schmidt, W. Helv.
Chim. Acta 1971, 54, 862. (d) Schmidt, W. Tetrahedron Lett. 1972, 13,
581.
(26) Lai, Y.-H.; Chen, P.; Peck, T. G. Pure Appl. Chem. 1993, 65,
81.
(27) Mitchell, R. H.; Otsubo, T.; Boekelheide, V. Tetrahedron Lett.
1975, 219.
(28) Borch, R. F. J . Org. Chem. 1969, 34, 627.
(30) Boekelheide, V.; Phillips, J . B. J . Am. Chem. Soc. 1967, 89,
1695.
(31) Mitchell, R. H.; Boekelheide, V. J . Chem. Soc. D 1970, 1555.

938 J . Org. Chem., Vol. 61, No. 3, 1996
Lai and Chen
F igu r e 1. UV/vis absorption spectrum of a mixture of 14b
and 15b taken in cyclohexane.
F igu r e 2. Plot of log [Ao]/[A] against time for valence
isomerization of 15b to 14b: 0, 39 °C; b, 49 °C; O, 59 °C.
An interesting observation was that when no precau-
tion was taken to exclude air thoroughly decomposition
of 14b was more apparent during the photochemical
experiments. Irradiation of 1,3-diphenylisobenzofuran
(34) in the presence of oxygen was reported32 to give an
ozonide 35 followed by formation of the diketone 36.
(aromaticity) of the isoannelated compound 14b (internal
methyl protons at δ 0.63). Assuming that proton shield-
ing is proportional to ring current,33 14b exhibits only
<7% of the ring current of 11 (δCH3 ) -4.25)sa value
about 10% lower than that of the [a]-ring annelated
system 10 (δCH3 ) 0.13, 0.15). This we believe is
associated with the steric interactions derived from the
external methyl groups in 14b resulting in a deviation
from planarity of its molecular periphery. “Bay-area”
steric interactions in 39 were also reported to be respon-
sible for a preference to cyclophanediene 40 in their
valence isomerization processes.14
The activation energy for the conversion of 32 f 11
was determined by UV spectroscopy29 due to fast reaction
rates. 1H NMR spectroscopy is, however, a more suitable
method to measure the activation energy for the rela-
tively slower conversion of 12 f 1312 or 40 f 39.14 The
When a solution of 15b was irradiated with light at 254
nm for a longer reaction time (2.5 h) with no precaution
to exclude air, a dark violet solution was obtained with
significant decomposition as evident by formation of
1
insoluble solids. The H NMR spectrum of the product
mixture showed a strongly shielded singlet at δ -3.97
and a deshielded singlet at δ 2.77 in a 1:1 ratio. The
above observation suggests the formation of 37 followed
by that of 38. The internal methyl protons (δ -3.97) of
38 are expected to be shielded similarly as those (δ -4.25)
in the parent 11; the external methyl protons of 38
observed at δ 2.77 are typical of conjugated acetyl groups.
The presence of 38 was further supported by a peak,
albeit weak, at m/ z 316 in the mass spectrum of the
product mixture. All attempts to isolate 38, however,
failed. Chromatography of the product mixture, directly
or after irradiation with visible light, always recovered
only the cyclophanene 15b in varied yields. Apparently
the dihydropyrene 38, due to unknown reasons, was too
unstable to be isolated.
slow thermal conversion of 15b f 14b was thus exam-
ined by H NMR spectroscopy. From a plot of log[Ao]/
1
[A] against time (Figure 2), where [Ao] is the initial
concentration of 15b and [A] the concentration of 15b at
time t, the rate constants, k, at 39, 49, and 59 °C,
respectively, were determined to be 8.32 × 10-7, 2.81 ×
10-6, and 1.30 × 10-5 s-1
.
The rate constants for
conversions of 32 f 1129 and 12 f 1312 were found to be
1.67 × 10-5 and 0.73 × 10-5 s-1 at 30 and 32 °C,
respectively, thus supporting qualitatively a significantly
slower conversion rate for 15b f 14b. From a plot of
-log k against 1/T (Figure 3), the energy of activation,
E
act, for 15b f 14b was estimated to be 114 kJ mol-1
compared to values of 97 and 105 kJ mol-1, respectively,
for 32 f 1129 and 12 f 13.12
The dihydropyrene 11 and its derivatives are usually
the thermodynamically more stable isomers relative to
their corresponding cyclophanedienes. The photochemi-
cal or thermal conversion of 15b to 14b could, however,
be driven only up to an optimum buildup concentration
of about 50% of 14b. This process is thus significantly
less favorable than that of 32 f 1129 or 12 f 13.12 An
obvious explanation is a significantly lower diatropicity
Con clu sion
Isoannelation and a poor participation of oxygen in
sustaining a ring current in an oxa[17]annulene clearly
results in a drastic decrease in diatropicity going from
11 (100%) to 13 (54%) to 14b (<7%). This order is also
reflected in an increase in the energy of activation for
(32) Gollnick, K.; Griesbeck, A. Tetrahedron 1985, 41, 2057.
(33) Mitchell, R. H.; Yan, J . S. H. Can. J . Chem. 1977, 55, 3347.

Formation of a Novel Isoannulenofuran
J . Org. Chem., Vol. 61, No. 3, 1996 939
1-(3-Ch lor o-2-m et h ylp h en yl)p r op a n -2-ol (18). Com-
pound 17 (5.00 g, 30 mmol) was added to a solution of mercuric
acetate in water (30 mL) and THF (30 mL). The reaction
mixture was stirred at room temperature for 30 min. Aqueous
NaOH (3.0M, 30 mL) was added to the mixture followed by a
solution of 0.5 M sodium borohydride in 3.0 M NaOH (30 mL).
After the mercury had settled, the reaction mixture was
extracted with dichloromethane, washed, dried, and evapo-
rated to give a quantitative yield of the alcohol 18 isolated as
a colorless oil: 5.51 g (100%); 1H NMR δ 7.1-7.4 (m, 3 H),
3.90-4.12 (m, 1 H), 2.81 (d, 2 H, J ) 6.3 Hz), 1.64 (s, 1 H),
1.38 (s, 3 H), 1.26 (d, 3 H, J ) 6.3 Hz); IR (neat) 3380 (OH),
2960, 2920, 1560, 1370, 1110, 1080, 1000, 930, 910, 770, 710
cm-1; MS m/ z 184 (M+, 17), 140 (87), 105 (100), 91 (6); Mr
calcd for C10H13ClO 184.0655, found (MS) 184.0642.
1-(3-Ch lor o-2-m eth ylp h en yl)p r op a n on e (19). (a) J ones’
reagent17 (4.1 mL) was added dropwise to a solution of the
alcohol 18 (2.00 g, 10.8 mmol) in acetone (50 mL) cooled in an
ice bath. The reaction mixture was stirred for 2 min at room
temperature and diluted with water (50 mL). The mixture
was then extracted with ether. The organic layer was washed
with water, dried, and evaporated. The crude product was
chromatographed on silica gel using dichloromethane/hexane
(1:1) as eluent to give the ketone 19 isolated as a pale yellow
F igu r e 3. Plot of -log k against reciprocal absolute temper-
ature for the valence isomerization of 15b to 14b.
the valence isomerization of 32 f 11 (97 kJ mol-1), 12
f 13 (105 kJ mol-1), and 15b f 14b (114 kJ mol-1). An
interesting result is obviously the fact that cyclophanene
15b is the thermodynamically more stable isomer in
contrast to the parent 11 and most of its derivatives.
Despite all the unfavorable thermodynamic factors, it
was rather surprising to observe thermally the formation
of isoannulenofuran 14b at the expense of interrupting
the π-electron delocalization in two benzene and one
furan rings in 15b. This is especially novel since the
general thermal valence isomerization of 32 f 11 rep-
resents one of those unusual concerted, symmetry-
forbidden reactions.29 Another favorable driving force for
such a conversion is believed to derive from the excep-
tional symmetrical and rigid molecular structure of the
10b,10c-dihydropyrene system.
1
liquid: 1.20 g (60%); H NMR δ 7.0-7.3 (m, 3 H), 3.75 (s, 2
H), 2.26 (s, 3 H), 2.15 (s, 3 H); IR (neat) 1715 (CdO), 1565,
1440, 1410, 1350, 1320, 1220, 1155, 1140, 1080, 1015, 790, 770,
735, 710 cm-1
; MS m/ z 182 (M+, 2), 147 (38), 141 (16), 139
(42), 105 (12), 103 (15), 77 (17); Mr calcd for C10H11ClO
182.0498, found (MS) 182.0493.
(b) A solution of 3-bromo-2-methoxypropene (12.6 g, 83.1
mmol) in benzene was added to a solution of the mono-
Grignard reagent15 prepared from 2,6-dichlorotoluene (23.8 g,
148 mmol) in dry THF at 0 °C. The reaction mixture was then
stirred at room temperature for 18 h. The mixture was then
hydrolyzed with H2SO4/H2O (1:1) until all solids dissolved. It
was then extracted with dichloromethane. The organic layer
was washed, dried, and evaporated to give the intermediate
product 21. This was hydrolyzed by stirring in 1 N HCl for 1
h. The reaction mixture was then extracted with dichlo-
romethane, washed, dried, and evaporated. The crude product
was chromatographed on silica gel using dichloromethane/
hexane (1:1) as eluent to give the ketone 19: 8.8 g (58%),
identical (1H NMR, IR, MS) to the previously obtained sample.
3,4-Bis(3-ch lor o-2-m eth ylph en yl)h exan e-2,5-dion e (22).
Activated MnO2 (0.85 g, 9.78 mmol) was added to a solution
of 19 (3.00 g, 16.4 mmol) in acetic acid (10 mL). The reaction
mixture was heated at 120 °C for 5 h and then treated with
water and extracted with dichloromethane. The organic layer
was washed, dried, and evaporated. The residue was chro-
matographed on silica gel using dichloromethane/hexane (1:
1) as eluent. Eluted first was the diketone 22: 0.53 g (18%).
Recrystallization from benzene and hexane gave colorless
Exp er im en ta l Section
All melting points were determined with a Sybron-Ther-
molyne MP-12615 melting point apparatus and are uncor-
rected. 1H NMR spectra were determined in CDCl3 on a J EOL
FX90Q (90 MHz) or a Bruker ACF300 (300 MHz) spectrom-
eter. All proton chemical shifts are reported in ppm downfield
from TMS, which was used as an internal standard. IR
spectra were recorded on a Perkin-Elmer 1310 spectrometer.
UV/vis spectra were determined in cyclohexane on a Shimadzu
UV240 Graphicord spectrometer. EIMS was determined on
a VG Micromass 7035 mass spectrometer at 70 eV. Relative
intensities are given in parentheses. Only the molecular ion
containing 35Cl and/or 79Br is given for any compound contain-
ing chlorine and/or bromine; the correct isotope pattern was
obtained in each case. Microanalyses were performed by the
Microanalytical Laboratory of the Department of Chemistry,
National University of Singapore. All evaporations were
carried out under reduced pressure on a rotary evaporator at
about 40 °C, and all organic layers were washed with water,
unless otherwise stated, and dried with anhydrous magnesium
sulfate.
1
crystals of 22: mp 246-248 °C; H NMR δ 7.1-7.4 (m, 6 H),
4.95 (s, 2 H), 2.76 (s, 6 H), 1.84 (s, 6 H); IR (KBr) 3060, 2990,
2905, 1700 (CdO), 1560, 1460, 1350, 1290, 1260, 1200, 1170,
1140, 1120, 1000, 950, 845, 770, 710, 660, 625 cm-1; MS m/ z
362 (M+, 8), 342 (20), 318 (57), 301 (85), 276 (67), 266 (28),
180 (47), 138 (49), 114 (20). Anal. Calcd for C20H20Cl2O2: C,
66.13; H, 5.55. Found: C, 66.15; H, 5.55.
Eluted next was colorless crystals of the furan 16: 0.25 g
(9%); mp 54-56 °C; 1H NMR δ 6.8-7.3 (m, 6 H), 2.16 (s, 3 H),
2.15 (s, 3 H), 2.09 (s, 6 H); IR (KBr) 3060, 2950, 2920, 2850,
1600, 1555, 1455, 1430, 1375, 1255, 1215, 1180, 1140, 1125,
1070, 985, 850, 780, 755, 720, 690 cm-1; MS m/ z 344 (M+, 100),
329 (14), 310 (12), 215 (19), 125 (15); Mr calcd for C20H18Cl2O
344.0735, found (MS) 344.0735.
3,4-Bis(3-ch lor o-2-m et h ylp h en yl)-2,5-d im et h ylfu r a n
(16). A solution of the diketone 22 (7.00 g, 19.3 mmol) in dry
THF (100 mL) and ethanol (12 mL) was added dropwise to
phosphorus pentoxide (32.9 g, 232 mmol) and cooled in an ice
bath. After the addition, the reaction mixture was brought
to reflux, heated for 1 h, and filtered. The residue was
thoroughly washed with dichloromethane. The organic frac-
tions were combined, washed, dried, and evaporated. The
crude product was chromatographed on silica gel using dichlo-
3-(3-Ch lor o-2-m eth ylp h en yl)p r op en e (17). To a solution
of the mono-Grignard reagent prepared15 from 2,6-dichloro-
toluene (48.3 g, 0.30 mol) in dry THF cooled in an ice bath
was added 1-bromo-3-propene (36.3 g, 0.30 mol). The reaction
mixture was allowed to warm to room temperature, stirred
for 15 h, cooled in an ice bath, and hydrolyzed with H2SO4/
H2O (1:1) until all solids dissolved. The mixture was extracted
with ether, washed, dried, and evaporated. The product 17
was collected as a colorless liquid at 212-214 °C upon
1
distillation at 760 mmHg: 39.5 g (79%); H NMR δ 7.0-7.3
(m, 3 H), 5.70-6.14 (m, 1 H), 4.82-5.23 (m, 2 H), 3.37 (d, 2 H,
J ) 5.9 Hz), 2.31 (s, 3 H); IR (neat) 3080, 1640, 1570, 1440,
1405, 1310, 1200, 1165, 1135, 1010, 990, 840, 780, 720, 670
cm-1; MS m/ z 166 (M+, 40), 151 (10), 131 (100), 116 (23), 115
(20), 91 (21). Anal. Calcd for C10H11Cl: C, 72.07; H, 6.65.
Found: C, 72.00; H, 6.48.

940 J . Org. Chem., Vol. 61, No. 3, 1996
Lai and Chen
romethane/hexane (1:3) as eluent to afford 16: 4.80 g (72%),
identical (1H NMR, IR, MS) to the previously obtained sample.
3,4-Bis(3-cya n o-2-m et h ylp h en yl)-2,5-d im et h ylfu r a n
(23).34 This was obtained, after recrystallization from benzene
(24), 285 (12), 283 (12), 255 (22), 241 (13), 240 (10). Anal. Calcd
for C22H22OS: C, 79.00; H, 6.63. Found: C, 79.10; H, 6.48.
a n t i-8,16,2′,5′-Te t r a m e t h yl-1-(m e t h ylsu lfa n yl)[2.2]-
m eta cyclo[9,10-c]fu r a n (29). A solution of n-butyllithium
in hexane (0.90 mmol) was added dropwise to a solution of
the thiacyclophane 27a (0.15 g, 0.45 mmol) in dry THF (30
mL) under nitrogen at 0 °C for 20 min. Methyl iodide (1.5
mmol in 1 mL of THF) was added, until the purple color was
discharged. Water and dichloromethane were added and the
organic layer was washed, dried, and evaporated. The crude
product was chromatographed on silica gel using dichlo-
romethane/hexane (1:2) as eluent to yield colorless crystals of
1
and hexane, as colorless crystals (74%): mp 118-120 °C; H
NMR δ 7.1-7.6 (m, 6 H), 2.21 (s, 6 H), 2.11(s, 6 H); IR (KBr)
2940, 2905, 2840, 2205 (CtN), 1600, 1460, 1430, 1370, 1260,
1210, 985, 920, 810, 795, 740 cm-1; MS m/ z 326 (M+, 100),
311 (18), 283 (20); Mr calcd for C2H18N2O 326.1419, found (MS)
326.1425.
3,4-Bis(3-for m yl-2-m et h ylp h en yl)-2,5-d im et h ylfu r a n
(24).34 This was obtained, after recrystallization from benzene
1
and hexane, as colorless crystals (96%): mp 140-142 °C; H
1
29: 0.15 g, (96%); mp 196-198 °C; H NMR δ 7.0-7.8 (m, 6
NMR δ 10.22 (s, 2 H), 7.2-7.7 (m, 6 H), 2.39 (s, 6 H), 2.18 (s,
3 H), 2.17 (s, 3 H); IR (KBr) 3240, 3180, 3120, 3080, 2950,
2910, 2850, 2750, 1675 (CdO), 1575, 1460, 1440, 1400, 1375,
1320, 1280, 1260, 1240, 1180, 1110, 1045, 990, 790, 715, 675
cm-1; MS m/ z 332 (M+, 100), 317 (18), 289 (14), 202 (8). Anal.
Calcd for C22H20O3: C, 79.50; H, 6.06. Found: C, 79.18; H,
5.93.
H), 3.80 (dd, 1 H, J ) 2.9, 3.2 Hz), 3.14 (t,, 1 H, J ) 2.9 Hz),
2.58 (dd, 1 H, J ) 2.9, 3.2 Hz), 2.51 (s, 6 H), 2.14 (s, 3 H), 0.54
(s, 6 H); IR (KBr) 2907, 1600, 1420, 1375, 1250, 1205, 995,
925, 795, 750, 710 cm-1; MS m/ z 348 (M+, 70), 333 (15), 301
(30), 286 (38), 285 (100), 271 (29), 226 (14); Mr calcd for C23H24
-
SO 348.1547, found (MS) 348.1541.
a n ti-8,16,2′,5′-Tetr a m eth yl[2.2]m eta cyclo[9,10-c]fu r a n -
1-en e (15b). A solution of 29 (0.15 g, 0.43 mmol) in dichlo-
romethane (5 mL) was added to a stirred suspension of
dimethoxycarbonium fluoroborate (0.14 g, 0.86 mmol) in
dichloromethane (5 mL) at -30 °C under nitrogen. After the
addition, the reaction mixture was stirred without cooling for
2 h. Ethyl acetate (10 mL) was then added and the mixture
stirred for another 30 min. The crystals formed were filtered
to yield the salt 30: 0.10 g (64%); mp > 300 °C.
Potassium tert-butoxide (60 mg, 0.53 mmol) was added to a
suspension of the salt 30 (100 mg, 0.27 mmol) in dry THF (10
mL) at room temperature. The reaction mixture was stirred
for 20 min and then decomposed with water and extracted with
ether. The organic layer was washed, dried, and evaporated.
The crude product was chromatographed on silica gel using
cyclohexane as eluent to give colorless crystals of 15b: 79 mg
(96%); mp 135-137 °C; 1H NMR δ 6.62-8.5 (m, 6 H), 6.16 (s,
2 H), 2.30 (s, 6 H), 1.38 (s, 6 H); IR (KBr) 3000, 2940, 2905,
1600, 1443, 1370, 1245, 1200, 1068, 978, 920, 885, 820, 788,
743, 726, 665, 625 cm-1; MS m/ z 300 (M+, 14), 285 (100), 270
(75), 226 (32). Anal. Calcd for C22H20O: C, 87.96; H, 6.71.
Found: C, 87.70; H, 6.70.
3,4-Bis[3-(h yd r oxym et h yl)-2-m et h yp h en yl]-2,5-d im e-
th ylfu r a n (25).34 This was obtained, after recrystallization
from benzene, as colorless crystals (90%): mp 178-180 °C;
1H NMR δ 7.0-7.4 (m, 6 H), 4.58, 4.55 (s, 1.2:1.0 total 4 H),
2.16, 2.17 (s, ratio 1.2:1.0, total 6 H), 1.95, 2.04 (s, ratio 1.2:1,
total 6 H), 1.64 (br s, 2 H); IR (KBr) 3360 (OH), 3075, 2920,
2875, 1600, 1440, 1375, 1260, 1218, 1170, 1090, 795, 760, 730,
650 cm-1; MS m/ z 336 (M+, 100), 321 (7), 303 (8), 275 (14),
245 (14), 215 (13); Mr calcd for C22H24O3 336.1725, found (MS)
336.1739.
3,4-Bis[3-(br om om eth yl)-2-m eth ylp h en yl]-2,5-d im eth -
ylfu r a n (26).34 This was obtained, after chromatography, as
1
colorless crystals (91%): mp 156-158 °C; H NMR δ 6.9-7.3
(m, 6 H), 4.42, 4.44 (s, ratio 1.2:1, total 4 H), 2.18 (s, 6 H),
2.02, 2.11 (s, ratio 1.2:1.0, total 6 H); IR (KBr) 2910, 1597,
1430, 1370, 1250, 1203, 980, 923, 790, 720 cm-1; MS m/ z 463
(M+, 52), 462 (100), 460 (50), 383 (84), 381 (80), 259 (41), 229
(31), 151 (49). Anal. Calcd for C22H22Br2O: C, 57.17; H, 4.80.
Found: C, 57.21; H, 4.80.
a n ti-8,16,2′,5′-Tet r a m et h yl-1-t h ia [3.2]m et a cyclo[9,10-
c]fu r a n (27a ). A solution of 26 (1.05 g, 2.27 mmol) in benzene
(200 mL) and a solution of 95% sodium sulfide nonahydrate
(0.57 g, 2.27 mmol) in 95% ethanol/water (9:1; 200 mL) were
added, in separate rotaflow dropping funnels, dropwise at the
same rate into vigorously stirred 95% ethanol (1000 mL) under
nitrogen over a period of 6 h. After the addition, the mixture
was stirred for another 15 h, and the bulk of the solvent was
then removed under reduced pressure. The residue was
extracted with dichloromethane. The organic layer was
washed, dried, and evaporated. The crude product was
chromatographed on silica gel using dichloromethane/hexane
(1:2) as eluent to give 27a : 0.50 g (66%). Recrystallization
from benzene and hexane gave colorless crystals of 27a : mp
P h otoch em ica l Va len ce Isom er iza tion of 15b To Give
14b. A solution of 15b in benzene (5 mL) in a quartz cell was
irradiated with UV light at 254 nm for 20 min. A dark purple
solution was obtained. The solvent was rapidly removed, and
the sample contained a mixture of 14b and 15b: 1H NMR δ
6.2-8.5 (m, 6 H), 6.16 (s, 2 H), 2.30, 2.38 (s, ratio 2.0:1.0, total
6 H), 1.38, 0.30 (s, ratio 2.0:1.0, total 6 H); UV/vis (cyclohexane)
λmax 218 (sh), 230, 278, 291, 318, 353, 370, 540, 586 nm.
Ack n ow led gm en t . This work was supported
(RP860606) by the National University of Singapore
(NUS). P.C. thanks the NUS for the Research Student-
ship (1988-91). Assistance from the technical staff of
the Department of Chemistry, NUS, is gratefully
acknowledged.
1
234-236 °C; H NMR δ 7.0-7.4 (m, 6 H), 3.79, 3.67 (AB q, 4
H, J ) 12.9 Hz), 2.47 (s, 6 H), 0.67 (s, 6 H); IR (KBr) 2980,
2905, 1600, 1460, 1430, 1370, 1250, 1200, 1155, 1083, 988, 977,
920, 860, 780, 760, 720, 635 cm-1; MS m/ z 332 (M+, 100), 299
(34) For the general conditions of the series of reactions involving
Cl f CN f CHO f CH2OH f CH2Br, refer to refs 14 and 22.
J O951586O