Giant cyclophanes built from polyphenyl aromatic substructures

Article abstract of DOI:10.1021/jo000236l

Two very large cyclophanes (3, C₁₃₂H₉₂O₈S₄; 4, C₁₇₂H₁₂₀O₈S₄) were prepared by means of short syntheses (~5 steps) from commercial starting materials. In each of these cyclophanes, two octaphenylnaphthalene subunits or two 1,3-bis(pentaphenylphenyl)benzene subunits were tethered to form the final macrocycle. X-ray analysis of 3 shows it to have a collapsed conformation, but molecules of 4 have large central cavities which are aligned in the crystal to form wide, solvent-containing channels.

Full text of DOI:10.1021/jo000236l

VOLUME 65, NUMBER 23
NOVEMBER 17, 2000
© Copyright 2000 by the American Chemical Society
Articles
Gia n t Cyclop h a n es Bu ilt fr om P olyp h en yl Ar om a tic Su bstr u ctu r es
Robert A. Pascal, J r.,* Lisa Barnett, Xiaoxin Qiao, and Douglas M. Ho
Department of Chemistry, Princeton University, Princeton, New J ersey 08544
Received February 22, 2000
Two very large cyclophanes (3, C132H92O8S4; 4, C172H120O8S4) were prepared by means of short
syntheses (∼5 steps) from commercial starting materials. In each of these cyclophanes, two
octaphenylnaphthalene subunits or two 1,3-bis(pentaphenylphenyl)benzene subunits were tethered
to form the final macrocycle. X-ray analysis of 3 shows it to have a collapsed conformation, but
molecules of 4 have large central cavities which are aligned in the crystal to form wide, solvent-
containing channels.
Polyphenyl aromatic compounds are excellent building
blocks from which to construct robust nanostructures
with well-defined conformations, often by means of short
syntheses. A very recent review of such “polyphenylene
nanostructures” shows a remarkable diversity of sizes
and shapes.1 In general, such polyphenyl aromatics are
more densely substituted, and possibly have greater
rigidity, than the majority of dendrimers,2 catenanes,3
or other deviously connected4 molecules featuring aro-
matic substructures. Our own recent work with poly-
phenyl aromatic compounds has focused on the prepara-
tion and structural characterization of twisted polycyclic
aromatic ribbons5,6 and large molecular clefts.7,8 In the
latter case, where the principle substructures are deriva-
tives of hexaphenylbenzene or octaphenylnaphthalene,
the syntheses are very short and the overall yields can
be quite good, and these features encouraged us to
employ these polyphenyl aromatics for the construction
of a new class of cyclophanes with large central cavities.
In the present work we describe the synthesis and
crystallographic characterization of two giant cyclo-
phanes (3 and 4, Scheme 1) formed from easily prepared
derivatives of octaphenylnaphthalene (1) and 1,3-bis-
(pentaphenylphenyl)benzene (2).
(1) Berresheim, A. J .; Mu¨ller, M.; Mu¨llen, K. Chem. Rev. 1999, 99,
1747-1785.
(2) (a) Bosman, A. W.; J anssen, H. M.; Meijer, E. W. Chem. Rev.
1999, 99, 1665-1688. (b) Newkome, G. R.; He, E.; Moorefield, C. N.
Chem. Rev. 1999, 99, 1689-1746.
(3) Raymo, F. M.; Stoddart, J . F. Chem. Rev. 1999, 99, 1643-1663.
(4) Sritana-Anant, Y.; Seiders, T. J .; Siegel, J . S. Top. Curr. Chem.
1998, 196, 1-43.
Resu lts
(5) Qiao, X.; Padula, M. A.; Ho, D. M.; Vogelaar, N. J .; Schutt, C.
E.; Pascal, R. A., J r. J . Am. Chem. Soc. 1996, 118, 741-745.
(6) Qiao, X.; Ho, D. M.; Pascal, R. A., J r. Angew. Chem., Int. Ed.
Engl. 1997, 36, 1531-1532.
Oct a p h en yln a p h t h a len e-Ba sed Cyclop h a n es. A
cyclophane containing face-to-face octaphenylnaphtha-
(7) Tong, L.; Ho, D. M.; Vogelaar, N. J .; Schutt, C. E.; Pascal, R. A.,
J r. Tetrahedron Lett. 1997, 38, 7-10.
(8) Tong, L.; Ho, D. M.; Vogelaar, N. J .; Schutt, C. E.; Pascal, R. A.,
J r. J . Am. Chem. Soc. 1997, 119, 7291-7302.
10.1021/jo000236l CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/16/2000

7712 J . Org. Chem., Vol. 65, No. 23, 2000
Pascal et al.
Sch em e 1
lenes was our first target. Preliminary molecular me-
chanics calculations suggested that two seven-atom links
between the para positions of the C(1) and C(4) phenyl
groups in two molecules of 1 would permit those mol-
ecules to nestle comfortably so that the naphthalene faces
and phenyl edges would define a central cavity. More
importantly, such links would be too short to permit the
two naphthalenes to swing away from each other. Methyl
derivatives of 1 are easy to prepare,9 so the dimethylated
octaphenylnaphthalene 6 (Scheme 1) was chosen as the
key substructure for preparation of this cyclophane.
Compound 6 was prepared in one step from the known
cyclopentadienone 510 and 3,4,5,6-tetraphenylanthranilic
acid5 (via the aryne) in 83% yield, and NBS bromination
gave the corresponding bis(bromomethyl) 7 in 73% yield.
The synthesis of the cyclophane 8 was achieved easily,
if in low yield (3.5%), by condensation of 7 with 1,3-
benzenedithiol at high dilution in the presence of cesium
carbonate. A trace of a trimeric cyclophane was also
isolated, but it was characterized only by FAB MS.
Finally, peracid oxidation of 8 gave the more highly
crystalline tetrasulfone 3.
the crystals effloresced (decomposed by loss of solvent of
crystallization) very rapidly upon removal from the
mother liquor, and it was necessary to use a glass
capillary mount for the X-ray data collection. The struc-
ture was solved without difficulty in the monoclinic space
group C2/c, with Z ) 4; that is, the cyclophane lies on a
special position, in this case a crystallographic C2 axis.
The refinement was aided by the extra symmetry, but it
was complicated by the presence of disordered chloroform
molecules in the lattice (five CHCl3 molecules per asym-
metric unit). Indeed, the disordered solvent occupies 43%
of the unit cell volume. Ultimately the SQUEEZE/
BYPASS procedure11 was employed to account for the
solvent electron density, and subsequent refinement gave
a satisfactory structure.
The molecular structure of cyclophane 3 is illustrated
in Figure 1. The two naphthalene rings are slightly
twisted (end-to-end twist 23.7°) and their mean planes
are nearly parallel to one another (dihedral angle 7.0°).
However, the naphthalenes are not directly on top of one
another, but significantly slipped so that the edge-on
phenyl substituents of one naphthalene partly fill the
space above the opposite naphthalene, essentially elimi-
nating any central cavity. The closest such contacts are
between H(37) of the C(6) phenyl group and C(8A) and
C(9A) of the opposite (symmetry-related) naphthalene
(3.25 and 3.28 Å, respectively; the crystallographic
numbering has been used). There is not sufficient space
between the naphthalenes to accommodate even a single
But does the cyclophane contain a cavity? Molecular
modeling can provide pleasing pictures of large macro-
cycles, and can serve as a useful guide to research, but
compounds as large as 3 contain so many conformational
degrees of freedom that X-ray structures are a virtual
requirement for their reliable characterization. Cyclo-
phane 3 crystallized easily from chloroform solution, but
(9) Qiao, X.; Pelczer, I.; Pascal, R. A., J r. Chirality 1998, 10, 154-
158.
(10) Mehr, L.; Becker, E. I.; Spoerri, P. E. J . Am. Chem. Soc. 1955,
77, 984-989.
(11) Van der Sluis, P.; Spek, A. L. Acta Crystallogr., Sect. A 1990,
46, 194-201.

Cyclophanes Built from Polyphenyl Substructures
J . Org. Chem., Vol. 65, No. 23, 2000 7713
F igu r e 2. Molecular structure of cyclophane 4. The crystal-
lographically independent half-molecule is drawn with 50%
probability thermal ellipsoids (top), and a ball-and-stick draw-
ing of the full cyclophane is illustrated at the bottom.
F igu r e 1. Molecular structure of cyclophane 3. The crystal-
lographically independent half-molecule is drawn with 50%
probability thermal ellipsoids (top), and a ball-and-stick draw-
ing of the full cyclophane is illustrated at the bottom.
11 was followed immediately by condensation with 1,3-
benzenedithiol to give cyclophane 13 in 4.5% yield. Once
again, this material was oxidized with MCPBA to give a
more highly crystalline tetrasulfone (4).
molecule of solvent; all of the solvent included in the
crystal lies outside the cyclophanes.
Bis(p en t a p h en ylp h en yl)b en zen e-Ba sed Cyclo-
p h a n es. The easy synthesis of 3 suggested that even
larger cyclophanes might be prepared, but its X-ray
structure emphasized the need to design a noncollapsible
cavity. A good way to prepare such a cavity is to join two
rigid molecular clefts. Large polyphenyl aromatics are
ideal for this purpose, and 1,3-bis(pentaphenylphenyl)-
benzene (2) seemed to be an especially good candidate.
Two simple syntheses of 2 have been reported,8,12 and
its crystal structure shows it to possess a shallow cleft
between the pentaphenylphenyl groups.12 Molecular
mechanics calculations indicated that a small spacer
could be used to connect two molecules of 2 to form a
relatively rigid, parallelogram-shaped molecule with a
substantial central cavity. It was simplest to employ the
same linking group that was used in the preparation of
3, and thus a dimethyl derivative of 2 (compound 11,
Scheme 1) was chosen as our key substructure. The
introduction of methyl groups at the desired positions in
2 was less efficient than with 1, but the synthesis of 11
was still very simple. Diketone 9 was formed in a Claisen
condensation of commercial starting materials in one step
but in only 16% yield. Double aldol condensation with
benzil gave the biscyclopentadienone 10 (42%), and a
double Diels-Alder reaction with diphenylacetylene gave
the desired hydrocarbon 11 (53%). NBS bromination of
Compound 4 deposited single crystals from DMSO-
ether. These crystals, like those of 3, contained substan-
tial solvent of crystallization, but they only slowly
effloresced upon removal from the mother liquor. As with
3, compound 4 crystallized in the monoclinic space group
C2/c, with Z ) 4, but in this case the molecule lies on a
crystallographic center of inversion. Both DMSO and
ether molecules are present in the crystal, badly disor-
dered, and occupying 36% of the unit cell volume. Once
again, the SQUEEZE/BYPASS procedure was used to
account for the solvent electron density to obtain a
satisfactory refinement.
The molecular structure of cyclophane 4 is shown in
Figure 2. The clefts of the two bis(pentaphenylphenyl)-
benzene substructures face each other to form a large
central cavity, with “corner-to-corner” distances across
the interior, C(2)‚‚‚C(2A) and C(85)‚‚‚C(85A), of 12.5 and
17.5 Å, respectively. These distances are quite similar
to those found in the MMFF-optimized13,14 Ci-symmetric
structure for compound 4s13.5 and 17.2 Å, respectivelys
and and these two structures differ little in energy. For
example, MMFF calculations indicate that compression
of the C(2)‚‚‚C(2A) distance from the “ideal” 13.5 Å to
the crystallographically observed 12.5 Å requires only 0.8
(13) Halgren, T. A. J . Comput. Chem. 1996, 17, 490-519.
(14) All molecular mechanics calculations were performed by using
SPARTAN Version 5.0, Wavefunction, Inc., Irvine, CA.
(12) Mu¨ller, M.; Iyer, V. S.; Ku¨bel, C.; Enkelmann, V.; Mu¨llen, K.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1607-1610.

7714 J . Org. Chem., Vol. 65, No. 23, 2000
Pascal et al.
F igu r e 3. Unit cell and packing of cyclophane 4 viewed down the crystallographic b axis.
kcal/mol. However, to reduce substantially the size of
the internal cavity by closing the C(2)‚‚‚C(2A) distance
to 10.0 Å requires 7.4 kcal/mol. It is for this reason that
the cavity is effectively noncollapsible.
Compounds 3 (C132H92O8S4) and 4 (C172H120O8S4) are
among the largest crystallographically characterized
cyclophanes. A search of the Cambridge Structural
Database15 found 23 different cyclophanes having more
than 130 carbon atoms (transition metal complexes
were excluded from the search). Twenty of these are
carcerands from Cram’s research group16 or closely
The symmetry-related hexaphenylbenzene subunits on
opposite sides of the macrocycle are parallel to each other,
and the mean planes of their central rings are 13.4 Å
[C(7)-C(12) and C(7A)-C(12A)] and 9.2 Å [C(13)-C(18)
and C(13A)-C(18A)] apart. These cavities are large
enough to accommodate several solvent molecules, and
in the crystal they are occupied by disordered ethers
(not shown). Interestingly, the macrocycles pack to max-
imize contacts between hexaphenylbenzene subunits on
adjacent molecules, with the result that the molecules
stack with their cavities perfectly aligned to form infinite
channels along the b axis of the crystals (Figure 3).
(15) Allen, F. H.; Kennard, O.; Taylor, R. Acc. Chem. Res. 1983, 16,
146-153.
(16) The formulas of the cyclophanes described in each paper are
given after the reference. (a) Tanner, M. E.; Knobler, C. B.; Cram, D.
J . J . Am. Chem. Soc. 1990, 112, 1659-1660 [C131H112O22]. (b) Sherman,
J . C.; Knobler, C. B.; Cram, D. J . J . Am. Chem. Soc. 1991, 113, 2194-
2204 [C132H112O24]. (c) Helgeson, R. C.; Paek, K.; Knobler, C. B.;
Maverick, E. F.; Cram, D. J . J . Am. Chem. Soc. 1996, 118, 5590-5604
[C140H128O24]. (d) Helgeson, R. C.; Knobler, C. B.; Cram, D. J . J . Am.
Chem. Soc. 1997, 119, 3229-3244 [C140H160O24, C144H168O24, C148H176O24].
(e) Eid, C. N., J r.; Knobler, C. B.; Gronbeck, D. A.; Cram, D. J . J . Am.
Chem. Soc. 1994, 116, 8506-8515 [C144H120O24, C144H128O24]. (f)
Robbins, T. A.; Knobler, C. B.; Bellew, D. R.; Cram, D. J . J . Am. Chem.
Soc. 1994, 116, 111-122 [C144H136O24]. (g) Byun, Y.-S.; Vadhat, O.;
Blanda, M. T.; Knobler, C. B.; Cram, D. J . Chem. Commun. 1995,
1825-1827 [C144H136O28]. (h) Yoon, J .; Sheu, C.; Houk, K. N.; Knobler,
Discu ssion
As is usually the case with large polyphenyl polycyclic
aromatic compounds, all of the large cyclophanes (3, 4,
8, and 13), as well as their precursors, are quite soluble
and easily handled. Although the overall synthetic yields
of these molecules suffer in the macrocyclization steps,
the synthesis of 8 (which contains 132 carbons) was
achieved in only three steps from two known compounds
(each of which was prepared in two steps from com-
mercial starting materials), and the preparation of 13
(172 carbons) required only a five-step, linear synthesis.
Oxidation of the thioethers (8 and 13) to the correspond-
ing sulfones (3 and 4) was essentially quantitative.
C. B.; Cram, D. J . J . Org. Chem. 1996, 61, 9323-9339 [C145H138O24
,
C148H136O24]. (i) Yoon, J .; Knobler, C. B.; Maverick, E. F.; Cram,
D. J . Chem. Commun. 1997, 1303-1304 [C148H136O24]. (j) Byun,
Y.-S.; Robbins, T. A.; Knobler, C. B.; Cram, D. J . Chem. Commun. 1995,
1947-1948 [C148H144O24]. (k) Park, B. S.; Knobler, C. B.; Eid, C. N.,
J r.; Warmuth, R.; Cram, D. J . Chem. Commun. 1998, 55-56
[C156H152O32]. (l) Cram, D. J .; Blanda, M. T.; Paek, K.; Knobler,
C. B. J . Am. Chem. Soc. 1992, 114, 7765-7773 [C160H136O24].
(m) Choi, H.-J .; Buhring, D.; Quan, M. L. C.; Knobler, C. B.; Cram,
D. J . Chem. Commun. 1992, 1733-1735 [C160H128N8O24]. (n) Quan,
M. L. C.; Knobler, C. B.; Cram, D. J . Chem. Commun. 1991, 660-
662 [C160H120O32]. (o) Von dem Bussche-Hunnefeld, C.; Buhring, D.;
Knobler, C. B.; Cram, D. J . Chem. Commun. 1995, 1085-1087
[C208H168O24].

Cyclophanes Built from Polyphenyl Substructures
J . Org. Chem., Vol. 65, No. 23, 2000 7715
related compounds,17 two are large hydrocarbons based
on fluorene subunits,18 and one is a tetrameric tetra-
pyrrole.19 Compound 4 is larger than all but three of these
compounds,16m-o and the use of polyphenyl aromatics as
key substructures is unique to 3 and 4.
83%): mp 289-291 °C; 1H NMR (CDCl3, 270 MHz) δ 2.01
(s, 6 H), 6.37 and 6.42 (AA′BB′ system, 8 H), 6.64 (m, 30
H); 13C NMR (CDCl3, 75 MHz) δ 20.9, 124.2, 124.7, 125.8,
126.0, 126.1, 126.8, 128.3, 131.2, 131.86, 131.93, 133.5,
133.7, 138.2, 138.3, 139.0, 139.66, 139.74, 140.7, 140.8,
142.2 (21 of 22 expected resonances observed); MS m/z
764 (M+, 100), 687 (M - C6H5, 33), 673 (M - CH3C6H4,
14); exact mass 764.3428, calcd for C60H44 764.3443.
1,4-Bis[p-(br om om eth yl)p h en yl]-2,3,5,6,7,8-h exa -
p h en yln a p h th a len e (7). Compound 6 (1.44 g, 1.88
mmol), NBS (0.67 g, 3.8 mmol), and a few bits of AIBN
were heated to reflux in CCl4 (30 mL) under a tungsten
lamp for 8 h. The hot reaction mixture was filtered and
rinsed with CCl4. CH2Cl2 was added, and the solution
was washed with saturated NaHCO3, dried over Na2SO4,
and concentrated to dryness. The residue was chromato-
graphed on silica gel (1:1 CHCl3-hexanes). The appropri-
ate fractions were combined and concentrated, and the
resulting solid was recrystallized twice from CH2Cl2-
methanol to yield 7 as colorless needles (1.26 g, 1.37
mmol, 73%): mp 272-274 °C; 1H NMR (CDCl3, 270 MHz)
δ 4.22 (s, 4 H), 6.51-6.75 (m, 38 H); 13C NMR (CDCl3,
68 MHz) δ 34.3, 124.9, 126.1, 126.2, 126.3, 126.4, 126.9,
131.0, 131.9, 132.1, 133.1, 133.3, 137.7, 138.2, 139.6,
139.9, 140.2, 140.3, 141.7, 142.3 (20 of 22 expected
resonances observed); FAB MS m/z 923 (M[79Br81Br] +
H, 100), 844 (M + H - Br, 44).
Our intent was to design molecules with large cavities.
Compound 3 retained sufficient conformational freedom
to permit the cavity to collapse, but in 4 the relatively
rigid, cleft-containing substructures force the macrocycle
to remain open. Moreover, the central cavity in 4 is large
enough to hold two or three small molecules side by side.
It was also our hope that such cyclophanes would stack
in the solid state so that their central cavities would form
continuous channels through the crystal. It is extremely
difficult to design the packing of molecular crystals, but
in the case of 4, this goal was met, whether by design or
chance. The four slab-like, hydrophobic, polyphenyl
aromatic sides of 4 favor the packing of these sides
against each other, and as a consequence, the macro-
cycles’ cavities are perfectly aligned to form channels in
the crystal. These channels are wide enough that small
molecules could pass each other within them, and thus
the channel contents might be exchanged in the crystal
if the crystals were sufficiently stable. If such a structure
were very robust, then one would have the equivalent of
a zeolite with a completely hydrophobic interior.
Unfortunately, crystals of 4 do decompose upon loss
of solvent. We suspect that it is the loss of solvent outside
the channels that compromises the structural integrity,
not the loss of ether in the “noncollapsible” channels. We
have previously reported one example of an extremely
stable, channel-containing crystal of a polyphenyl poly-
cyclic aromatic compoundsdecaphenylanthracene5s
where the crystals melt above 400 °C, and for which NMR
and X-ray studies show the channels to be incompletely
filled with solvent. Unfortunately, the channels in deca-
phenylanthracene are too narrow to permit solvent
exchange. Perhaps in the future it will be possible to
modify the exterior surface of 4 so that it packs in the
crystal without any interstitial solvent molecules to form
an extremely stable structure with large zeolite-like
channels.
Cyclop h a n e 8. Two solutions were prepared: (1)
compound 7 (0.55 g, 0.60 mmol) and 1,3-benzenedithiol
(0.085 g, 0.60 mmol) were dissolved in 150 mL of benzene,
and (2) Cs2CO3 (0.78 g, 2.4 mmol) was dissolved in
ethanol (100 mL). Solutions 1 and 2 were separately and
simultaneously added to a refluxing solution of benzene
(150 mL) and ethanol (50 mL) over 2 h under argon. After
being heated for 1.5 days, the mixture was cooled and
the solvent was removed under reduced pressure. CHCl3
(500 mL) was added, and the resulting mixture was
heated at reflux for 2.5 h and then filtered while hot.
After concentration, the residue was chromatographed
on silica gel (2:1 CHCl3-hexanes). The fractions contain-
ing the desired cyclophane 8 were combined and concen-
trated. Further purification of this material by prepara-
tive TLC (silica gel GF; solvent 2:1 CHCl3-cyclohexane)
gave 8 as a colorless solid (19 mg, 11 µmol, 3.5%): mp
Exp er im en ta l Section
1
230 °C dec; H NMR (CDCl3, 500 MHz) δ 3.69 (s, 8 H),
1,4-Di(p -t olyl)-2,3,5,6,7,8-h e xa p h e n yln a p h t h a -
len e (6). A solution of 2,5-di(p-tolyl)-3,4-diphenylcyclo-
pentadienone10 (5; 1.22 g, 2.96 mmol) in 1,2-dichloro-
ethane (40 mL) was heated to reflux under argon. A
solution of isoamyl nitrite (1.5 mL) in dichloroethane (80
mL) was added, followed by the dropwise addition of a
solution of tetraphenylanthranilic acid5 (1.73 g, 4.10
mmol) in dichloroethane (140 mL) over 1.5 h. After the
resulting solution was heated for 1 h more, the reaction
was terminated by addition of ethanol (55 mL) and 1%
aqueous KOH (160 mL). CHCl3 was added; then the
organic layer was separated, washed with aqueous
NaHCO3, dried over MgSO4, and concentrated to dryness.
The residue was recrystallized twice from benzene-
ethanol to yield 6 as off-white crystals (1.88 g, 2.46 mmol,
6.26 and 6.38 (AA′BB′ system, 16 H), 6.46 (t, J ) 8 Hz,
8 H), 6.51 (m, 16 H), 6.56 (m, 14 H), 6.61 (dd, J ) 8 Hz,
2 Hz, 4 H), 6.70 (m, 20 H), 6.81 (td, J ) 8 Hz, 2 Hz, 4 H),
7.42 (t, J ) 2 Hz, 2 H); 13C NMR (CDCl3, 125 MHz) δ
39.6, 124.5, 124.76, 124.80, 126.0, 126.1, 126.4, 126.7,
128.4, 131.0, 131.1, 131.6, 131.9, 132.0, 133.0, 134.0,
135.3, 135.6, 138.1, 138.4, 140.1, 140.39, 140.45, 140.49,
140.9, 141.9 (26 of 26 expected resonances observed); FAB
MS m/z 1806 (M[13C1] + H, 100), 1665 (M - C6H4S2, 41).
A trace of a trimeric cyclophane was also isolated, but
it was characterized only by its FAB MS: m/z 2710
(M[13C3] + H, 30), 764 (100).
Cyclop h a n e 3. A solution of cyclophane 8 (7.2 mg, 4.0
µmol) in CH2Cl2 (0.5 mL) was placed in an ice bath.
Freshly purified MCPBA (5.4 mg) in CH2Cl2 (0.5 mL) was
added dropwise. After the ice bath was removed, the flask
was placed under an argon atmosphere and stirred at
room temperature for 48 h. Some crystalline material was
deposited during this time. CHCl3 (20 mL) was added,
dissolving everything. The solution was washed with
dilute Na2S2O3 and saturated Na2CO3, and it was dried
(17) Ungaro, R.; Pochini, A.; Andreetti, G. D.; Ugozzoli, F. J .
Inclusion Phenom. 1985, 3, 409-420 [C144H224O16].
(18) Ipaktschi, J .; Hosseinzadeh, R.; Schlaf, P.; Dreiseidler, E.;
Goddard, R. Helv. Chim. Acta 1998, 81, 1821-1834 [C144H112, C160H144].
(19) Khoury, R. G.; J aquinod, L.; Nurco, D. J .; Pandey, R. K.; Senge,
M. O.; Smith, K. M. Angew. Chem., Int. Ed. Engl. 1996, 35, 2496-
2499 [C140H136O28].

7716 J . Org. Chem., Vol. 65, No. 23, 2000
Pascal et al.
Ta ble 1. Cr ysta llogr a p h ic Da ta for Com p ou n d s 3 a n d 4
over MgSO4. Concentration yielded cyclophane 3 as a
colorless solid (8 mg) which exhibited a single component
upon TLC analysis (CHCl3, Rf 0.05). Crystals of the
tetrasulfone 3 suitable for X-ray analysis were obtained
from CHCl3: mp > 350 °C (darkens gradually above
3
4
chemical formula
C
132H92O8S4‚
C172H120O8S4‚2C2H6OS‚
10CHCl3
7C4H10
3118.02
O
fw
3127.98
1
200 °C); H NMR (CDCl3, 500 MHz) δ 3.95 (d, J ) 15
cryst size (mm)
space group
a, Å
b, Å
c, Å
R, deg
â, deg
γ, deg
V, Å3
0.42 × 0.38 × 0.12 0.38 × 0.12 × 0.10
C2/c (no. 15)
28.7412(8)
15.4254(5)
38.3795(11)
90
C2/c (no. 15)
49.754(7)
11.6954(11)
39.053(6)
90
Hz, 4 H), 4.16 (d, J ) 15 Hz, 4 H), 5.33 (d, J ) 7 Hz, 4
H), 6.14-7.00 (m, 78 H), 8.38 (s, 2 H); FAB MS m/z 1934
(M[13C1] + H, 80), 1729 (M - C6H4S2O4, 31), 460 (100).
1,3-Bis[3-(p-tolyl)-2-oxop r op yl]ben zen e (9). Ether
(50 mL) and n-butyllithium (2.5 M in hexanes, 8.8 mL,
22.0 mmol) were stirred under argon in a two-necked
flask cooled in an ice bath. Diisopropylamine (2.1 mL,
15 mmol) was added, and after the resulting solution was
stirred for 30 min, methyl (p-tolyl)acetate (3.1 g, 18.9
mmol) was added dropwise. The resulting solution was
stirred for 15 min. Dimethyl 1,3-benzenediacetate (2.0
g, 9.0 mmol) was then added dropwise, the ice bath was
removed, and the mixture was stirred overnight at room
temperature. The reaction mixture was poured into 1 N
HCl, and the layers were separated. The aqueous layer
was extracted twice with ether, and the combined ether
extracts were washed with water and dried over Na2SO4.
The solvent was removed under reduced pressure, and
the residue was heated with 6 N HCl (20 mL) and acetic
acid (150 mL) for 7 h. After cooling and removal of the
solvent, the residue was extracted with ether. The extract
was washed with aqueous NaHCO3 and dried over
Na2SO4. After concentration, the residue was chro-
matographed on silica gel (4:1 hexanes-ethyl acetate).
The fractions containing the desired product (Rf 0.51)
were combined and concentrated to afford white solid
111.3650(10)
90
129.320(3)
90
15846.0(8)
4
17580(4)
4
Z
F
calcd, g/cm3
1.311
1.178
µ, mm-1
T, K
0.62
0.14
298(2)
28.3
170(2)
22.5
θmax, deg
no. of reflections
total
unique
36730
17119
4785
85211
11364
4484
0.0595
0.1342
1.203
0.1572
0.1611
0.858
obsd [I > 2σ(I)]
R(F) (obsd data)a
0.0791
Rw(F2) (obsd data)a 0.1643
S (obs. data)a
R(F) (all data)a
wR(F2) (all data)a
S (all data)a
1.265
0.2296
0.2092
0.823
R(F) ) ∑||Fo| - |Fc||/∑|Fo|; Rw(F2) ) [∑w(Fo2 - Fc2)2/∑w(Fo2)2]1/2
;
a
S ) goodness-of-fit on F2 ) [∑w(Fo - Fc2)2/(n - p)]1/2, where n is
the number of reflections and p is the number of parameters
refined.
2
screw-capped Pyrex tube for 3.5 h at 300 °C. The tube
was cooled to room temperature, and acetone (∼1.5 mL)
was added to precipitate the product. The off-white
precipitate was collected by suction filtration. TLC
analysis (9:1 hexanes-ethyl acetate) showed one major
component (Rf 0.64). The product 11 was dried under
vacuum overnight (151 mg, 0.148 mmol, 53%): mp >
1
9 (530 mg, 1.43 mmol, 16%): mp 77-78 °C; H NMR
(CDCl3, 270 MHz) δ 2.32 (s, 6 H), 3.66 (s, 4 H), 3.67 (s, 4
H), 6.90 (br s, 1 H), 7.03 and 7.11 (AA′BB′ system, 8 H),
7.02 (m, 2 H), 7.25 (t, J ) 8 Hz, 1 H); MS m/z 370 (M+,
19), 105 (M - C8H9, 100); exact mass 370.1912, calcd for
C26H26O2 370.1933.
1
350 °C; H NMR (CDCl3, 500 MHz) δ 2.06 (s, 6 H), 6.20
1,3-Bis[2-oxo-3-(p -t olyl)-4,5-d ip h en ylcyclop en t a -
1,4-d ien yl]ben zen e (10). Compound 9 (400 mg, 1.1
mmol) and benzil (454.4 mg, 2.16 mmol) were dissolved
in ethanol (12 mL). In a separate test tube, KOH (256
mg, 4.56 mmol) was dissolved in water (0.25 mL), and
ethanol (2 mL) was added. Half of this KOH solution
was added dropwise to the solution of diketone 9 and
benzil at room temperature. The reaction flask was then
immersed in a water bath at 85 °C, and the other portion
of the KOH solution was added dropwise. The resulting
solution was heated with gentle swirling for 15 min. A
purple precipitate formed, and after it was cooled to room
temperature and subsequent refrigeration, the product
was collected by suction filtration and washed with cold
ethanol. TLC analysis (4:1 hexanes-ethyl acetate) showed
one major spot at Rf 0.66. Recrystallization of this
material from ethanol afforded deep purple crystals of
10 (323 mg, 0.450 mmol, 42%): mp 290-292 °C; 1H NMR
(CDCl3, 270 MHz) δ 2.38 (s, 6 H), 7.13 (m, 32 H); 13C NMR
(CDCl3, 125 MHz) δ 22.0, 125.8, 125.9, 128.3, 128.5,
128.6, 128.9, 129.1, 129.5, 129.9, 130.0, 130.7, 131.5,
132.7, 133.7, 134.1, 138.0, 154.2, 155.4, 201.0 (20 of
22 expected peaks observed); MS m/z 718 (M+, 100), 690
(M - CO, 10); exact mass 718.2890, calcd for C54H38O2
718.2872.
(m, 6 H), 6.75 (m, 46 H); 13C NMR (CDCl3, 125 MHz) δ
21.2, 125.0, 125.2, 126.5, 127.1, 127.4, 129.1, 131.3, 131.5,
131.6, 131.7, 134.5, 136.1, 137.8, 139.0, 139.1, 140.1,
140.4, 140.8, 141.0, 141.2 (21 of 21 expected peaks
observed); FAB MS m/z 1019 (M + H, 100).
Cyclop h a n e 13. Compound 11 (250 mg, 0.25 mmol)
and NBS (44.5 mg, 0.25 mmol) were heated to reflux in
CCl4 (35 mL), and heating was continued under a
tungsten lamp for 4 h. The resulting brown mixture was
cooled to room temperature and filtered. After concentra-
tion of the filtrate on a rotary evaporator, the residue
was chromatographed on silica gel (9:1 hexanes-ethyl
acetate) to yield a roughly 2:1 mixture of the desired
dibromide 12 and starting material 11 (202 mg total) as
judged by 1H NMR analysis. This material was used
without further purification. Two solutions were then
prepared: (1) 1,3-benzenedithiol (24.2 mg, 0.170 mmol)
and crude compound 12 (200 mg, nominally 0.17 mmol)
were dissolved in benzene (30 mL), and (2) KOH (28.7
mg, 0.435 mmol) was dissolved in ethanol (30 mL).
Solutions 1 and 2 were then separately and simulta-
neously added dropwise over 2 h to a refluxing mixture
of ethanol (80 mL) and benzene (20 mL) under argon.
The resulting mixture was heated at reflux overnight.
After cooling, the solvent was removed under reduced
pressure, and the residue was fractionated by preparative
TLC (silica gel GF; solvent 2:1 CH2Cl2-hexanes). The
1,3-Bis[4-(p-tolyl)-2,3,5,6-tetr a p h en ylp h en yl]ben -
zen e (11). Compound 10 (200 mg, 0.28 mmol) and
diphenylacetylene (200 mg, 1.1 mmol) were heated in a

Cyclophanes Built from Polyphenyl Substructures
J . Org. Chem., Vol. 65, No. 23, 2000 7717
material with Rf 0.25 was collected and shown by MS
and 1H NMR analysis to be crude cyclophane 13. A
second purification by preparative TLC yielded 13 as a
white solid (13 mg, 5.6 µmol, 4.5% from 11): 1H NMR
(CDCl3, 270 MHz) δ 3.65 (s, 8 H), 6.80 (m, 112 H); FAB
MS m/z 2315 (M[13C2] + H, 48), 2175 (M - C6H4S2, 22),
1048 (C80H56S+, 100).
Cyclop h a n e 4. A solution of cyclophane 13 (7.0 mg,
3.0 µmol) in CH2Cl2 (0.5 mL) was placed in an ice bath.
Freshly purified MCPBA (4.0 mg) in CH2Cl2 (0.5 mL) was
added dropwise. After the ice bath was removed, the flask
was placed under an argon atmosphere and stirred at
room temperature for 48 h. CHCl3 was added to the
mixture, and it was washed with saturated Na2CO3 and
dried over MgSO4. After removal of the solvent, a white
solid was obtained (10 mg). Crystals of the tetrasulfone
4 suitable for X-ray analysis were grown from a DMSO-
ether solution of the crude solid: mp > 350 °C (darkens
slowly above 200 °C); 1H NMR (CDCl3, 500 MHz) δ 4.00
(s, 8 H), 6.09-6.27 (m, 20 H), 6.62-7.00 (m, 142 H), 8.30
(s, 2 H); FAB MS m/z 2443 (M[13C2] + H, 50), 1017
(C80H57+, 35), 363 (100).
were solved by using Siemens SHELXTL,21 and both were
refined by full-matrix least-squares on F2 using
SHELXTL or SHELXTL-93.22 All non-hydrogenatoms
were refined anisotropically, and hydrogens were in-
cluded with a riding model. Due to the very large number
of disordered solvent molecules present in each crystal,
the SQUEEZE/BYPASS procedure11 implemented in
PLATON-9623 was employed to account for disordered
solvent electron density. Specific crystal, reflection, and
refinement data are contained in Table 1, and full details
are provided in the Supporting Information.
Ack n ow led gm en t. This work was supported by
Grant No. 32370-AC4 from the Petroleum Research
Fund, administered by the American Chemical Society,
and by Grant No. CHE-9707958 from the National
Science Foundation, both of which are gratefully ac-
knowledged. We thank C. F. Campana for the X-ray
data collection for compound 3.
Su p p or tin g In for m a tion Ava ila ble: Crystal structure
reports for 3 and 4 (including full experimental details, tables,
and figures), and 1H NMR spectra and selected 13C NMR
spectra of compounds 3, 4, 6-11, and 13. This material is
available free of charge via the Internet at http://pubs.acs.org.
Gen er a l X-r a y Cr ysta llogr a p h ic P r oced u r es. X-
ray data were collected by using graphite-monochromated
Mo KR radiation (0.710 73 Å) on either a Siemens
SMART CCD diffractometer (compound 3) or a Nonius
KappaCCD diffractometer (4). The diffraction data were
processed by using Siemens SAINT for the former
structure, and by using DENZO20 for the latter. Both
J O000236L
(21) Sheldrick, G. M. SHELXTL Version 5, Siemens Analytical X-ray
Instruments, Madison, Wisconsin, 1996.
(22) Sheldrick, G. M. SHELXL-93. Program for the Refinement of
Crystal Structures. University of Gottingen, Germany, 1993.
(23) Spek, A. L. Acta Crystallogr., Sect. A 1990, 46, C34.
(20) Otwinowski, Z.; Minor, W. Methods Enzymol. 1997, 276, 307-
326.