Macrocyclic aromatic polysulfones and sulfide-sulfones: Synthesis and structural characterisation of molecular pentagons and rectangles

Article abstract of DOI:10.1039/b912193e

Cyclo-condensation of arylenedithiols with bis(4-chlorophenylenesulfone)s under pseudo-high-dilution conditions affords macrocyclic aromatic sulfide-sulfones which are readily oxidised to all-sulfone-linked macrocycles. The cyclic pentamer of poly(1,4-phe

Full text of DOI:10.1039/b912193e

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Macrocyclic aromatic polysulfones and sulfide-sulfones: synthesis and
structural characterisation of molecular pentagons and rectangles†
Abderrazak Ben-Haida,a Howard M. Colquhoun,*b Philip Hodge,*a James Raftery,a Andrew J. P. Whitec and
David J. Williams*c
Received 22nd June 2009, Accepted 10th September 2009
First published as an Advance Article on the web 19th October 2009
DOI: 10.1039/b912193e
Cyclo-condensation of arylenedithiols with bis(4-chlorophenylenesulfone)s under pseudo-high-dilution
conditions affords macrocyclic aromatic sulfide-sulfones which are readily oxidised to all-sulfone-linked
macrocycles. The cyclic pentamer of poly(1,4-phenylenesulfone) and cyclic dimer of
poly(1,4-phenylenesulfonyl-4,4¢-biphenylenesulfone) have been isolated and characterised.
Introduction
Macrocyclic compounds are of considerable interest for the
construction of molecular-recognition and ion-binding systems.1
Well known examples include crown ethers,2 cyclodextrins,3
resorcinarenes,4 cucurbiturils,5 macrocyclic bipyridinium ions,6
aromatic diimides,7 and diimide-sulfones.8
Crystallographic studies have shown that the diaryl sulfone
moiety tends to adopt a preferred conformation in which the
planes of the aryl rings lie approximately orthogonal to the
C-S-C plane: the so-called “open book” conformation.9 It has
been suggested that this conformation may be stabilised by the
overlap of filled aromatic-carbon p-orbitals with a vacant d-p
hybrid orbital on sulfur10 [though intramolecular dipolar interac-
+
tions between the aromatic ortho-hydrogens (d ) and the sulfone
oxygens (d-) would also tend to stabilise the same conformation].
Thus, it might be expected that macrocyclic aromatic sulfones
based on 1,4-linkages would adopt “box-like” conformations in
which the planes of the aromatic rings lie perpendicular to the
plane of the sulfur atoms. The strongly electron-withdrawing and
rather rigid nature of the diaryl-sulfone unit suggest that such
macrocycles have the potential to behave as p-electron-deficient
molecular receptors. Unlike analogous systems based on the
cationic 4,4¢-bipyridinium unit,11 they would have no requirement
for counterions and would, in addition, afford a high degree of pre-
organisation in any non-covalent complexation process. We have
previously reported the synthesis and structure of a small, highly
strained macrocyclic tetrasulfone (1, Fig. 1),12 but the extreme
insolubility of this rigid macrocycle has so far made complexation
studies impracticable.
aDepartment of Chemistry, University of Manchester, Oxford Road,
, Manchester M13 9P, UK. E-mail: philip.hodge@man.ac.uk
bDepartment of Chemistry, University of Reading, Whiteknights, Reading,
RG6 6AD, UK. E-mail: h.m.colquhoun@rdg.ac.uk
cDepartment of Chemistry, Imperial College, London, SW7 2AY, UK.
E-mail: d.williams01@imperial.ac.uk
† Electronic supplementary information (ESI) available: Details of crystal-
lographic data collection, structure solution and refinement, including the
Fig. 1 X-Ray structure of the macrocyclic tetrasulfone 1 (from ref. 12).
resolution of disorder in the structure of macrocycle 6. CCDC reference
numbers 737298–737302. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/b912193e
In the present paper we report the syntheses of two
somewhat larger box-type sulfone macrocycles, via nucleophilic
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cyclo-condensation of arylene dithiols with bis(4-chloroarylene-
sulfone)s and peroxide-oxidation of the intermediate macrocyclic
sulfide-sulfones. One final product is the pentagonal pentasulfone
2 and the other is the rectangular tetrasulfone 3—geometrically
an analogue of Stoddart’s bipyridinium-based “blue box” 4.
These results confirm that the diarylene-sulfone moiety can be a
useful motif for the construction of box-like molecular structures,
though their relative insolubility still remains an issue for binding
studies.‡
Trisulfide-disulfone macrocycle 5. A solution of 4,4¢-bis(4-
chlorobenzoyl)diphenylsulfide (5.16 g, 15.0 mmol) and 1,4-ben-
zenedithiol (2.13 g, 15.0 mmol) in N,N -dimethylacetamide
(DMAc, 100 mL) was added from a syringe-pump over 24 h to
a vigorously stirred suspension of potassium carbonate (1.17 g,
8.50 mmol) in a refluxing mixture of DMAc (170 mL) and toluene
(30 mL), under nitrogen, with continuous removal of water via a
Dean–Stark trap. The mixture was then cooled, filtered, acidified
with dilute HCl to pH 3, and poured onto ice. The precipitate
was filtered off and extracted with boiling water and methanol,
affording a crude product of which 2.0 g was subjected to gradient
elution chromatography with dichloromethane/ethyl acetate on
silica gel. Macrocycle 5 was obtained as a colourless crystalline
solid, m.p. 354 ◦C (0.56 g, 28% yield). 1H-NMR (CDCl3, 300 MHz)
d 7.87 (d, J = 8.4 Hz, 4H), 7.79 (d, J = 8.4 Hz, 4H), 7.60 (d, J =
8.4 Hz, 4H), 7.57 (d, J = 8.4 Hz, 4H), 7.01 (s, 4H); m/z (EI) 604
(100%, M+). Anal. calcd. for C30H20O4S5: C, 59.60; H, 3.31; S,
26.49. Found: C, 59.73; H, 3.40; S, 26.52%.
Experimental
Starting materials (ex Aldrich) were standard reagent grade and
were used without further purification. Benzene-1,4-dithiol,13 9,9-
dimethylfluorene,14 4,4¢-bis(4-chlorobenzene-sulfonyl)biphenyl,15
and 4,4¢-biphenyldithiol16 were prepared according to the liter-
R
ature. Thin layer chromatography was carried out on Polygramꢀ
SIL-G/UV254 plates. Compounds were visualised under UV light.
Column chromatography was conducted on Aldrich silica gel,
Cyclopenta(1,4-phenylenesulfone) 2. To a stirred suspension of
macrocycle 5 (0.25 g, 0.41 mmol) in a mixture of chloroform
(7 mL) and trifluoroacetic acid (12 mL) at 50 ◦C was added 30%
(v/v) hydrogen peroxide (10 mL) dropwise over 15 min, and the
temperature was then raised to 60 ◦C. A clear solution formed
initially, but then a white precipitate developed and after 3 h the
solid was filtered off, washed successively with water and with
methanol, and dried to give the all-sulfone macrocycle 2 (0.27 g,
95%) This compound showed no melting point up to 500 ◦C. 1H-
NMR (CDCl3/CF3COOD, 2:1 v/v, 300 MHz) d 7.30 (s, 20H); m/z
(FAB) 700 (100%, M+). Anal. calcd. for C30H20O10S5: C, 51.42; H,
2.85; S, 22.85. Found: C, 51.48; H, 2.90; S, 22.90%.
˚
230-400 mesh, 60A. Proton NMR spectra were recorded on a
Varian Unity Inova-300 spectrometer. Conventional mass spectra
(EI/CI/FAB) were run on a Kratos Concept spectrometer, and
MALDI-TOF MS analyses were obtained on Kratos Kompact
and Micromass Tofspec instruments. Elemental analyses were pro-
vided by the analytical service of Manchester University. Melting
points were determined by DSC under nitrogen using a Mettler-
DSC20 system. Single crystal X-ray data for macrocycles 2, 3, 6
and 7 were obtained at Imperial College on a Siemens P4/RA
diffractometer with graphite-monochromated Cu-Ka radiation,
and X-ray data for 5 were collected at Manchester using a Bruker
SMART CCD diffractometer with graphite-monochromated
Mo-Ka radiation.
Cyclobis(1,4-phenylenesulfonyl-4,4¢-biphenylenesulfone) (3)
Cyclopenta(1,4-phenylenesulfone) (2)
Disulfide-disulfone macrocycle 6. A solution of 4,4¢-bis(4-
chlorobenzenesulfonyl)biphenyl (5.03 g, 10.0 mmol) and 4,4¢-
biphenyldithiol (2.18 g, 10.0 mmol) in N,N -dimethylacetamide
(DMAc, 100 mL) was added from a syringe-pump over 8 h to
a vigorously stirred suspension of potassium carbonate (2.75 g,
20.0 mmol) in a refluxing mixture of DMAc (200 mL) and toluene
(40 mL). The mixture was refluxed for a further 12 h and was
then cooled, filtered, concentrated to ca. half volume, and added
slowly with stirring to water (300 mL) containing concentrated
hydrochloric acid (10 mL). The precipitated solid was filtered
off and extracted successively with boiling water and boiling
methanol, affording a crude product of which 2.0 g was subjected
to gradient elution chromatography with dichloromethane/ethyl
acetate on silica gel. Macrocycle 6 was obtained as a colourless
crystalline solid, m.p. 466 ◦C (0.35 g, 18% yield). 1H-NMR
(CDCl3, 300 MHz) d 7.94 (d, J = 8.4 Hz, 4H), 7.75 (d, J =
8.4 Hz, 4H), 7.67 (d, J = 8.3 Hz, 4H), 7.53 (d, J = 8.4 Hz, 4H),
7.42 (d, J = 8.4 Hz, 4H), 7.34 (d, J = 8.3 Hz, 4H); m/z (FAB) 649
(100%, [M+H]+). Anal. calcd. for C30H20O4S5: C, 66.64; H, 3.72;
S, 19.76. Found: C, 66.11; H, 3.48; S, 20.00%.
4,4¢-Bis(4-chlorobenzenesulfonyl)diphenylsulfide.
A
mixture
of diphenyl sulfide (12.10 g, 0.065 mmol) and 4-chloro-
benzenesulfonyl chloride (33.70 g, 0.180 mmol) in 1,2,4-
trichlorobenzene (6 mL) was heated under nitrogen with stirring
◦
to 120 C. Anhydrous iron(III) chloride (0.100 g) was added and
the temperature was raised to 150 ◦C. When evolution of HCl had
ceased, the solution was cooled and added to vigorously stirred
acetone (150 mL) to give a solid which was recovered by filtration,
washed with acetone, dried, and finally recrystallised from toluene
(200 mL, containing 5 mL of acetylacetone to sequester residual
iron) to g◦ive colourless 4,4¢-bis(4-chlorobenzoyl)diphenylsulfide,
1
m.p. 236 C (27.8 g, 80% yield). H-NMR (CDCl3, 300 MHz)
d 7.91 (d, J = 8.4 Hz, 4H), 7.88 (d, J = 8.5 Hz, 4H), 7.53
(d, J = 8.4 Hz, 4H), 7.45 (d, J = 8.5 Hz, 4H); m/z (EI) 535
(100%, M+). Anal. calcd. for C24H16O4Cl2S3: C, 53.03; H, 2.99;
Cl, 13.29; S, 17.97. Found: C, 53.10; H, 3.05; Cl, 13.30; S,
17.96%.
Tetrasulfone macrocycle 3. Macrocycle 6 (0.12 g, 0.18 mmol)
was oxidised as described for the synthesis of macrocycle 2, giving
an essentially quantitative yield of 3. This compound showed
no melting point up to 550 C. H-NMR (CDCl3/CF3COOD,
2:1 v/v, 300 MHz) d 8.04 (s, 8H), 7.95 (d, J = 8.6 Hz, 8H), 7.73 (d,
‡ It was anticipated that the larger macrocyclic sulfones reported in the
present paper, with their greater degrees of conformational freedom,
would have higher entropies of dissolution and therefore higher solublities
than macrocycle 1. In practice however, the rigidity of the diarylene-
sulfone linkages still proved sufficient to limit drastically the solubility
of macrocycles 2 and 3.
◦
1
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J = 8.6 Hz, 8H); m/z (FAB) 713 (100%, [M+H]+). Anal. calcd. for
C36H24O8S4: C, 60.65; H, 3.39; S, 17.98. Found: C, 60.45; H, 3.42;
S, 17.71%.
6. C36H24O4S4.CH2Cl2, M = 733.72, monoclinic, P21/n
˚
(no. 14), a = 14.5898(11), b = 23.7421(19), c = 20.4841(7) A,
◦
3
˚
a = 93.522(5) , V = 7082.1(8) A , Z = 8 [3 independent
complexes, 2 with Ci symmetry], Dc = 1.376 g cm-3, m(Cu-
Ka) = 4.170 mm-1, T = 293 K, Siemens P4 diffractometer; 10688
independent measured reflections (Rint = 0.0352), F2 refinement,
R1(obs) = 0.070, wR2(all) = 0.218, 6098 independent observed
absorption-corrected reflections [|Fo| > 4s(|Fo|), 2qmax = 124◦],
848 parameters. CCDC 737301.
Fluorene-based disulfide-disulfone macrocycle (7)
2,7-Bis(4-chlorobenzenesulfonyl)-9,9-dimethylfluorene. This
compound was obtained by reaction of 9,9-dimethylfluorene
(12.61 g, 0.065 mol) with 4-chlorobenzenesulfonyl chloride
(33.70 g, 0.180 mol) under the conditions described above for
the synthesis of 4,4¢-bis(4-chlorobenzoyl)diphenylsulfide. The title
compound was obtained as a white crystalline solid (27.53 g,
7. C39H28O4S4.CH2Cl2, M = 773.78, monoclinic, P21/c
˚
(no. 14), a = 10.0673(10), b = 17.1131(16), c = 21.5403(16) A, a =
1
◦
3
-3
˚
78% yield). H NMR (CDCl3, 300 MHz) d 8.08 (s, 2H), 7.95-
96.428(7) , V = 3687.7(6) A , Z = 4, Dc = 1.394 g cm , m(Cu-
Ka) = 4.034 mm-1, T = 293 K, Siemens P4 diffractometer; 5229
independent measured reflections (Rint = 0.0461), F2 refinement,
R1(obs) = 0.061, wR2(all) = 0.169, 3419 independent observed
absorption-corrected reflections [|Fo| > 4s(|Fo|), 2qmax = 120◦],
424 parameters. CCDC 737302.
7.88 (m, 8H); 7.54 (d, J = 8.6 Hz, 4H), 1.32 (s, 6H); m/z (EI) 543
(100%, M+). Anal. calculated for C27H20Cl2O4S2: C, 59.66; H, 3.71;
Cl 13.04; S 11.79. Found: C, 59.70; H, 3.74; Cl, 13.03; S, 11.80%.
Disulfide-disulfone macrocycle 7. This compound was ob-
tained by reaction of 2,7-bis(4-chlorobenzenesulfonyl)-9,9-
dimethylfluorene (8.15 g, 15.0 mmol) with 4,4¢-biphenyldithiol
(3.27 g, 15.0 mmol) under the conditions described above
for the synthesis of macrocycle 5. Macrocycle 7 was ob-
tained as a colourless crystalline solid (0.28 g, 14% yield) by
column chromatography of 2.0 g of the crude product with
Results and discussion
Synthesis of a pentagonal macrocyclic pentasulfone (2)
The C-S-C b◦ond angle in an unstrained diarylsulfone is generally
close to 105 .17 This suggests that macrocycle 2, if it could be
obtained, should be a near-regular pentagon (internal bond angle
108◦) with only a small degree of ring strain.
1
trichloroethene/dichloromethane/ethyl acetate on silica gel. H
NMR (CDCl3/CF3COOD, 2:1 v/v, 300 MHz) d (ppm) 8.05 (d,
2H), 7.90 (d, 2H), 7.78 (s, 2H), 7.66 (d, 4Hd), 7.54 (d, 4H), 7.43
(d, 4H), 7.32 (d, 4H) and 1.36 (s, 6H). m/z (EI) 689 (100%, M+).
Anal. calculated for C39H28O4S4: C, 77.99; H, 4.10; S 18.61. Found
C, 77.98; H, 4.08; S, 18.60%.
Moreover, as noted above, the diarylene sulfone units would
tend to adopt “open book” conformations with the result that
the molecule would be predicted to form a box-type structure.
The macrocyclic pentasulfone 2 was obtained in a three-step
synthesis (Scheme 1), via (i) bis-sulfonylation of diphenylsulfide
with 4-chlorobenzenesulfonyl chloride, (ii) nucleophilic cyclo-
condensation of the product with 1,4-benzenedithiol to give
an intermediate trisulfide-disulfone macrocycle (5), and finally
(iii) oxidation of 5 to pentasulfone 2 with hydrogen peroxide in
trifluoroacetic acid.18 Single crystal X-ray analyses (Fig. 2, 3 and
4) confirmed the proposed formulations of both macrocycles.
Crystal data
2. C30H20O10S5.3.75C4H9NO,
M
=
1027.47, monoclinic,
˚
P21/m (no. 11), a = 11.0349(4), b = 20.6530(5), c = 11.1727(5) A,
◦
3
˚
a = 110.111(2) , V = 2391.05(15) A , Z = 2 (Cs symmetry), Dc =
1.427 g cm-3, m(Cu-Ka) = 2.824 mm-1, T = 183 K, Bruker P4/RA
diffractometer; 3663 independent measured reflections (Rint
=
0.0245), F2 refinement, R1(obs) = 0.046, wR2(all) = 0.130, 2905
independent observed absorption-corrected reflections [|Fo| >
4s(|Fo|), 2qmax = 120◦], 209 parameters. CCDC 737298.
3. C36H24O8S4.COCl2.2CHCl3, M = 1050.44, monoclinic,
˚
P21/n (no. 14), a = 9.8261(19), b = 10.809(2), c = 20.350(4) A,
◦
3
˚
a = 93.555(16) , V = 2157.2(7) A , Z = 2 [Ci symmetry], Dc =
1.617 g cm-3, m(Cu-Ka) = 7.052 mm-1, T = 173 K, colour-
less prisms, Bruker P4/RA diffractometer; 3397 independent
measured reflections (Rint = 0.0459), F2 refinement, R1(obs) =
0.054, wR2(all) = 0.151, 2739 independent observed absorption-
corrected reflections [|Fo| > 4s(|Fo|), 2qmax = 124◦], 218
parameters. CCDC 737299.
5. C30H20O4S5.CH3OH, M = 636.80, monoclinic, P21/c, a =
◦
˚
18.8662(12), b = 12.4037(8), c = 11.9873(8) A, a = 97.805(1) , V =
3
-3
-1
˚
2779.2(3) A , Z = 4, Dc = 1.522 g cm , m(Mo-Ka) = 0.460 mm ,
T = 100 K, Bruker SMART CCD diffractometer; 6643 in-
dependent measured reflections (Rint = 0.0471), F2 refinement,
R1(obs) = 0.057, wR2(all) = 0.189, 5005 independent observed
absorption-corrected reflections [|Fo| > 4s(|Fo|), 2qmax = 58◦],
362 parameters. CCDC 737300.
Scheme 1 Synthesis of macrocycles 2 and 5.
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In the crystal, one molecule of methanol is neatly encapsulated
at the centre of macrocycle 5, as shown in Fig. 2. The trisulfide-
disulfone 5 has a rather irregular conformation in the solid state
(Fig. 3), the tendency for diarylsulfone units to adopt open-book
geometry (where C-C-S-C torsion angles = 90◦) conflicting with
the preferred symmetrically-skewed conformation (∠ C-C-C-S =
30◦) of the diarylsulfide linkage. In this molecule, the torsion
angles at sulfone are 75/83 and 60/70◦, and at sulfide they are
33/33, 42/65 and 14/72◦. Bond angles (C-S-C) at sulfone are
103 and 104◦ and at sulfide are 102, 102, and 105◦. There are no
perceptible distortions of the S-Ar-S units in 5, in contrast to the
geometry of the strained tetrasulfone 1, and its disulfide-disulfone
precursor, in which the S-Ar-S groups are bowed outwards from
collinearity by ca. 9◦. Macrocycle 5 is thus, as predicted, essentially
unstrained.
Fig. 4 Molecular structure of the macrocyclic pentasulfone 2.
sulfur atoms are essentially coplanar, with no one sulfur lying
˚
more than 0.07 A from their mean plane. Oxidation of the sulfide
linkages to sulfone has clearly caused their attached aromatic rings
to re-orient themselves into near-fivefold equivalence, though in
the solid state the molecule has only twofold, mirror, symmetry.
In Fig. 4, the crystallographic mirror plane would be vertical.
Slight deviations from fivefold symmetry are represented by
independent C-C-S-C torsion angles of 89, 85, 80, 78 and 69◦,
and C-S-C bond angles at 104.4, 104.6 and 105.9◦. The true
molecular symmetry of 2 is however demonstrated by its 1H NMR
spectrum (CF3CO2D/CDCl3), which shows just a single resonance
at 7.30 ppm, reflecting the equivalence of all 20 protons in the
molecule.
Synthesis of a rectangular macrocyclic tetrasulfone (3)
The synthesis of the rectangular macrocyclic tetrasulfone 3 via its
precursor disulfide-disulfone 6 is outlined in Scheme 2.
Fig. 2 Crystal structure of macrocycle 5 (methanol solvate) showing Van
der Waals surfaces at 2.4 ¥ CPK atomic radii.
Scheme 2 Synthesis of the rectangular macrocycles 3 and 6.
Fig. 3 Molecular structure of the trisulfide-disulfone macrocycle 5.
The oxidation step proceeded in essentially quantitative yield
and afforded the rather insoluble macrocycle 3 in high purity.
Single crystal X-ray structures for 6 and 3 are shown in Fig. 5
and 6 respectively. Solution of the structure of 6 was complicated
by orientational disordering of the three crystallographically
The macrocyclic pentasulfone 2 adopts a very much more
symmetrical structure than 5 in the crystal (Fig. 4), with all five
diarylenesulfone moieties oriented approximately perpendicular
to the mean (transannular) plane of the macrocycle. The five
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The two independent C-S-C bond angles are 101.7 and 101.8◦,
again reflecting a significant degree of ring-strain. The degree of
outward bowing of biphenylene and phenylene units is very similar
to that observed in the precursor-molecule 6, and the C-C-S-C
torsion angles lie in the range 75-85◦. Crystals of macrocycle 3
were grown by vapour diffusion of diethyl ether into a solution
in chloroform-trifluoroacetic acid, and although the crystal lattice
contains chloroform of solvation, the centre of the macrocycle
is occupied by a molecule of phosgene, which is (necessarily)
disordered about the inversion centre. This unexpected guest
presumably arises from the well-known oxidation of chloroform in
air, and is trapped in the macrocyclic cavity during crystallisation
as a result of its complementary shape.
It is instructive to compare the geometry of the phosgene
“complex” of macrocycle 3 with that of Stoddart’s tetracationic
4,4¢-bipyridinium-based macrocycle 4 in the form of its complex
with tetrathiafulvalene.19 Both supramolecules are shown in
Fig. 7, drawn at the same scale. The close geometric analogy
between the two systems, and the p-electron-deficient character
of the macrocyclic tetrasulfone (arising from the presence of
four strongly electron-withdrawing sulfone substituents) suggest
that 3 could have significant potential as a complexing agent
for electron-rich p-systems. However, in practice, its extreme
Fig. 5 Molecular structure of the macrocyclic disulfide-disulfone 6.
◦
intractability (m.p. >500 C, soluble only in strong-acid solvent
mixtures such as trifluoroacetic acid/chloroform) greatly limited
the scope of complexation experiments, and a potentially more
soluble, fluorene-based analogue (8) was therefore designed and
its synthesis targeted (Scheme 3).
Fig. 6 Molecular structure of the macrocyclic tetrasulfone 3.
independent molecules in the cell, resulting in apparent super-
position of the sulfone and sulfide linkages. Ultimately this was
resolved in terms of ca. 80/20 occupancy of the two orientations
for one molecule and 50/50 occupancy for the other two molecules.
Rotational disorder within the 4,4¢-biphenylene units was also
resolved. See ESI.†
The extensive disordering in the crystal structure of 6 reflects a
marked similarity of conformation at the sulfone and sulfide units.
The various C-C-S-C torsion angles thus lie in the narrow range
83-88◦, indicating that here the “open book” conformation is
adopted at both types of sulfur linkages, in contrast to the situation
for macrocycle 5. Bond angles (C-S-C) are markedly compressed
(100.6-102.1◦, c.f. 104.4-105.9◦) in 5, indicating significant ring-
strain. This strain is also reflected in a substantial outward bowing
of the biphenylene and phenylene units, the centroids of which lie
˚
0.47 and 0.13 A respectively outside the (almost perfect) rectangle
Fig. 7 Visual comparison of the structures of the tetrasulfone macrocycle
3 (encapsulating phosgene) and the bis-bipyridinium macrocycle 4 (as its
tetrathiafulvalene complex). Van der Waals surfaces are shown at 2.4 ¥
CPK atomic radii.
defined by the four sulfur atoms.
The X-ray structure of tetrasulfone 3 shows a highly symmetri-
cal macrocycle with an inversion centre at the centre of the cavity.
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Conclusions
Two new, all-para, macrocyclic aromatic sulfones, 2 and 3, have
been successfully synthesised, with pentagonal and rectangular ge-
ometries respectively. Full characterisation data, including single-
crystal X-ray structures, have been obtained for these compounds
and their macrocyclic sulfide-sulfone precursors. Their box-like
geometries and electron-deficient aromatic character suggest the
possibility of their being able to act as receptors for electron-rich
guest molecules. In practice however, their extreme insolubility
limits the scope of binding studies to strong-acid solvents in
which potential guests may be unstable. An attempt to en-
hance the solubility of macrocyclic sulfones by introducing the
dimethylfluorenylene residue lead only to degradation during the
oxidation stage (sulfide to sulfone) of the synthesis. It should
be noted that the structural concepts developed in this work
have also been applied to the design of unsymmetrical diimide-
disulfone macrocycles. A number of these latter compounds show
moderate (though still not good) solubility in organic solvents,
and significant binding capabilities for molecules such as pyrene
and perylene which have electron-rich, aromatic p-systems (e.g.
Fig. 9).20
Scheme 3 Attempted synthesis of a the dimethyl-fluorene-derived macro-
cyclic tetrasulfone 8. The final oxidation step led only to the formation of
unidentified degradation products.
The initial sulfonylation and cyclisation steps proceeded in
reasonable yield, with macrocycle 7 (the cyclic “monomer”) being
isolated from a mixture containing a series of higher macrocyclic
oligomers. These were identified by MALDI-TOF MS up to the
cyclic trimer, and the monomer, dimer and trimer were quantified
by GPC as being formed in 24, 17, and 14% yields respectively.
The molecular structure of 7 was confirmed by single crystal
X-ray analysis (Fig. 8), which showed one of the two methyl
groups oriented towards the centre of the macrocycle (and thus
lying within the ring-current shielding zones of several aromatic
1
rings) and the other directed outwards. The H NMR spectrum
of 7 however showed only a single methyl resonance, indicating
rapid exchange of the two methyl environments (presumably by
flipping about the C-S bonds) at ambient temperature. Attempted
oxidation of 7 with hydrogen peroxide in trifluoroacetic acid, as
carried out successfully with the all-aromatic disulfide-disulfone
6, failed to yield the target tetrasulfone 8. It is possible that acid-
promoted ring-opening at the isopropylidene bridge under these
conditions could lead to degradation of the aliphatic groups, and
hence to more generalised decomposition of macrocycle 7.
Fig. 9 Formation and X-ray structure of the complex between a
macrocyclic diimide-disulfone and perylene.8a Van der Waals surfaces are
shown at 2.4 ¥ CPK atomic radii.
Notes and references
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2 Crown Ethers and Analogs, S. Patai and Z. Rappoport, Eds., Wiley,
Fig. 8 X-Ray structure of the dimethylfluorene-based macrocycle 7.
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