Macrocyclic cyclophanes with two and three α,ω-dichalcogena-1, 4-diethynylaryl units: Syntheses and structural properties

Article abstract of DOI:10.1021/jo801378p

(Chemical Equation Presented) By means of four- and six-component cyclization reaction various cyclophanes were synthesized. The components were the di(lithium) salts of 1,4-di(ethynyl)benzene (11), 4,4′-di(ethynyl) biphenyl (13), 1,4-di(ethynyl)-2,5-di(n-hexyl)benzene (18), and 1,4-di(ethynyl)-2,5-di(n-propyl)benzene (19). These building blocks were reacted with α,ω-dithiocyanato-n-alkanes and α,ω- diselenocyanato-n-alkanes with n = 3-6. In the case of 10 also 1,1′-di(2-thiocyanatoethyl)cyclohexane (24) was reacted to afford a cyclophane comprising three subunits of 11. From most of the resulting macrocyclic cyclophanes (4(n) (n = 3, 5), 5, 6, 7(n), 8(n) (n = 3-6), 9(n) (n = 3, 5), and 10), we were able to grow single crystals. The X-ray analysis of 4(3), 7(3), 8(3), 8(4), 6, 7(5), and 8(5) revealed close contacts between the chalcogen atoms. These chalcogen-chalcogen interactions impose a ribbon-shape arrangement of molecules in 4(3) and a mutual crossing of two perdendicular planes built of 8(4) molecules. For 4(3) we found a close contact (3.28 A) between the π planes of two neighboring C₆H₄ rings of different molecules, whereas in 8(4) such a close contact (3.74 A) was due to an intermolecular interaction. Tubular stacking of the macrocyclic rings was found for 7(5) and 8(5) caused by a ladder-type intermolecular chalcogen-chalcogen interaction.

Full text of DOI:10.1021/jo801378p

Macrocyclic Cyclophanes with Two and Three
r,ω-Dichalcogena-1,4-diethynylaryl Units: Syntheses and Structural
Properties
Daniel B. Werz,† Felix R. Fischer, Stefan C. Kornmayer, Frank Rominger, and
Rolf Gleiter*
Organisch-Chemisches Institut der UniVersita¨t Heidelberg, Im Neuenheimer Feld 270,
D-69120 Heidelberg, Germany
rolf.gleiter@oci.uni-heidelberg.de
ReceiVed June 24, 2008
By means of four- and six-component cyclization reaction various cyclophanes were synthesized. The
components were the di(lithium) salts of 1,4-di(ethynyl)benzene (11), 4,4′-di(ethynyl)biphenyl (13), 1,4-
di(ethynyl)-2,5-di(n-hexyl)benzene (18), and 1,4-di(ethynyl)-2,5-di(n-propyl)benzene (19). These building
blocks were reacted with R,ω-dithiocyanato-n-alkanes and R,ω-diselenocyanato-n-alkanes with n ) 3-6.
In the case of 10 also 1,1′-di(2-thiocyanatoethyl)cyclohexane (24) was reacted to afford a cyclophane
comprising three subunits of 11. From most of the resulting macrocyclic cyclophanes (4(n) (n ) 3, 5),
5, 6, 7(n), 8(n) (n ) 3-6), 9(n) (n ) 3, 5), and 10), we were able to grow single crystals. The X-ray
analysis of 4(3), 7(3), 8(3), 8(4), 6, 7(5), and 8(5) revealed close contacts between the chalcogen atoms.
These chalcogen-chalcogen interactions impose a ribbon-shape arrangement of molecules in 4(3) and a
mutual crossing of two perdendicular planes built of 8(4) molecules. For 4(3) we found a close contact
(3.28 Å) between the π planes of two neighboring C6H4 rings of different molecules, whereas in 8(4)
such a close contact (3.74 Å) was due to an intermolecular interaction. Tubular stacking of the macrocyclic
rings was found for 7(5) and 8(5) caused by a ladder-type intermolecular chalcogen-chalcogen interaction.
Introduction
These properties are usually related to the π systems of
cyclophanes, which act as electron donors or form weak
hydrogen bonds with the guest molecules. Incidently, the
chemical behavior of the bridges has not been studied to the
same extent as the aromatic building blocks. Here donor atoms
such as nitrogen or chalcogen centers support the complexing
properties of the cavity.2
Cyclophanes (e.g., compounds of type 1) are composed of
planar aromatic rings which are tethered by aliphatic chains.1
Thus the cyclophane ring system reveals the typical properties
of both building units. Especially the topology of larger
cyclophane rings provides a cavity prone to complex metal
atoms and metal ions, respectively, or to host neutral molecules.
† Present address: Institut fu¨r Organische and Biomolekulare Chemie der
Georg-August-Universita¨t Go¨ttingen, Tammannstr. 2, D-37077 Go¨ttingen,
Germany.
(1) Reviews: (a) Modern Cyclophane Chemistry; Gleiter, R., Hopf, H., Eds.;
Wiley-VCH: Weinheim, 2004. (b) Vo¨gtle, F. Cyclophane Chemistry; Wiley-
VCH: Chichester, 1993. (c) Diederich, F. Cyclophanes; Royal Society of
Chemistry: Cambridge, 1991. (d) Kuhn, P. M.; Rosenfeld, S. M. Cyclophanes;
Academic Press: New York, 1983; Vols. I and II.
(2) Reviews: (a) Gleiter, R.; Rausch, B. J.; Schaller, R. J. In Modern
Cyclophane Chemistry; Gleiter, R.; Hopf, H., Eds., Wiley-VCH: Weinheim, 2004,
159-188. (b) Schulz, J.; Vo¨gtle, F. Top. Curr. Chem. 1994, 172, 41–86. (c)
Mascal, M.; Kerdelhue´, J. L.; Blake, A. J.; Cooke, P. A. Angew. Chem. 1999,
111, 2094–2096; Angew. Chem., Int. Ed. 1999, 38, 1968-1971. (d) Kunze, A.;
Balalaie, S.; Gleiter, R.; Rominger, F. Eur. J. Org. Chem. 2006, 2942–2955. (e)
Kunze, A.; Gleiter, R.; Bethke, S.; Rominger, F. Organometallics 2006, 25, 4787–
4791.
10.1021/jo801378p CCC: $40.75
Published on Web 09/17/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 8021–8029 8021

Werz et al.
employed. In earlier days a donor-acceptor model was used,11
which was refined on the basis of a one-electron model invoking
the interaction of an occupied n(p)-type lone pair of a donor
center and an empty σ* orbital of a chalcogen-carbon bond.12
In the case of three chalcogen atoms in close contact, their
interaction was described as an electron-rich three-center
bond.10,13 With the advent of more sophisticated quantum
chemical methods these interactions have been modeled on the
basis of semiempirical,14 HF-SCF,15 and DFT16 theory. How-
ever, recent studies have shown that for a quantitative description
methods including electron correlation effects are necessary.17,18
To find out if further highly ordered structures in the solid state
arise when the alkyne units are separated by aryl units we
synthesized 4-10 and studied their structural properties.
The rather poor solubility of 4(3), 4(5), and 5 (Chart 2) in
common organic solvents imposed difficulties regarding their
purification. In an effort to overcome this problem we synthe-
sized 6, 7(3)-7(6), and 8(3)-8(6) together with the side
products 9(3) and 9(5) bearing alkyl substituents on the aromatic
rings prone to increase the solubility. In the case of 10 we
present an example where the alkyl groups were tethered to the
bridge.
CHART 1
Recently, we have studied a number of monocyclic systems
mirroring cyclophane topologies: rigid rods of two electron-
rich alkyne units, placed opposite to each other, are tethered
with two hydrocarbon chains of equal or nearly equal chain
length (e.g., 2).3 If the alkyne units were terminated with divalent
chalcogen centers the cyclic systems formed tubular structures
in the solid state. A closer investigation revealed that the
tubes were formed by stacking of rings on top of each other.4
This high order in the solid state was caused by van der Waals
forces between the chalcogen centers4 of various stacks as shown
in 3 (Chart 1). Similar close contacts between two or more
chalcogen atoms have been known for many years5-10 and have
been identified by means of X-ray diffraction studies on single
crystals or by solution NMR studies of carefully designed
molecules. To interpret the short chalcogen-chalcogen dis-
tances, bonding models of different levels of sophistication were
Results and Discussion
Syntheses. To derive the systems 4(3) and 4(5) we employed
a four-component cyclization reaction of the di(lithium) salt of
1,4-di(ethynyl)benzene (11) and the corresponding R,ω-dithio-
cyanatoalkanes 12(n) (n ) 3, 5) following previously published
procedures.3a,b,19 The dithiocyanatoalkanes used in this paper
have been described in the literature.20 The reaction was carried
out in anhydrous THF under argon atmosphere at -40 °C. The
yields of the macrocyclization products were low and amounted
to 7% for 4(3) and 11% for 4(5) (Scheme 1).
In analogy to 4(n) the macrocycle 5 was obtained from 4,4′-
di(ethynyl)biphenyl (13) and 1,5-dithiocyanatopentane (12(5)).20
The yield of 5 was only 3%, and moreover the resulting
cyclophane was nearly insoluble in any of the common solvents.
NMR investigations had to be performed in hot toluene.
In an effort to increase the solubility of larger rings we
attached alkyl groups to the aromatic moieties as depicted in
6-8 (Chart 2). As a starting material for 6 we first prepared
1,4-di(ethynyl)-2,5-di(n-hexyl)benzene (18) (Scheme 2).
(3) (a) Benisch, C.; Bethke, S.; Gleiter, R.; Oeser, T.; Pritzkow, H.; Rominger,
F. Eur. J. Org. Chem. 2000, 2479–2488. (b) Rausch, B. J.; Werz, D. B.; Rittinger,
S.; Gleiter, R.; Oeser, T.; Rominger, F. J. Chem. Soc., Perkin Trans. 2 2002,
72–76. (c) Werz, D. B.; Gleiter, R.; Rominger, F. J. Org. Chem. 2002, 67, 4290–
4297.
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F.; Gleiter, R. Org. Lett. 2002, 4, 339–342. (b) Werz, D. B.; Gleiter, R.;
Rominger, F. J. Am. Chem. Soc. 2002, 124, 10638–10639. (c) Gleiter, R.;
Werz, D. B.; Rausch, B. J. Chem. Eur. J. 2003, 9, 2676–2683. (d) Werz,
D. B.; Rausch, B. J.; Gleiter, R. Tetrahedron Lett. 2002, 43, 5767–5769. (e)
Schulte, J. H.; Werz, D. B.; Rominger, F.; Gleiter, R. Org. Biomol. Chem.
2003, 1, 2788–2794. (f) Werz, D. B.; Gleiter, R.; Rominger, F. Organome-
tallics 2003, 22, 843–849. (g) Werz, D. B.; Gleiter, R.; Rominger, F. J. Org.
Chem. 2004, 69, 2945–2952. (h) Werz, D. B.; Gleiter, R. J. Org. Chem. 2003,
68, 9400–9405. (i) Benisch, C.; Werz, D. B.; Gleiter, R.; Rominger, F.; Oeser,
T. Eur. J. Inorg. Chem. 2003, 1099–1112. (j) Gleiter, R.; Werz, D. B. Chem.
Lett. 2005, 34, 126–131.
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3559.
8022 J. Org. Chem. Vol. 73, No. 20, 2008

Macrocyclic Cyclophanes
CHART 2
Our synthesis of 18 commenced with 1,4-dichlorobenzene
(14), which was reacted with 2 equiv of n-hexylbromide
according to Kumada and Corriu21 to afford 1,4-di(n-hexyl)-
benzene (15).22 To introduce the alkyne groups we first carried
out an iodination23 in the ortho positions of 15 to give 16.
Subsequent Sonogashira-Hagihara coupling24 with trimethyl-
silylethyne (TMSA) provided 17. The deprotection of 17 with
diluted NaOH yielded the unprotected aromatic diyne 18. With
18 at hand we performed a four-component cyclization reaction
using 2 equiv of 1,5-dithiocyanatopentane (12(5)) and 2 equiv
of 18 analogous to the synthesis of 4(5) (Scheme 1). The yield
of the desired macrocycle 6 amounted to 8%.
The preparations of 7(n) and 8(n) were carried out in
accordance to that of 6. The starting materials were 1,4-
di(ethynyl)-2,5-di(n-propyl)benzene (19) and the R,ω-dithio-
cyanatoalkanes 12(3)-12(6)20 as well as the R,ω-diselenocy-
anatoalkanes 20(3)-20(6).25 The yields of the cyclophanes 7(n)
(n ) 3-6) and 8(n) (n ) 3-6) varied between 3% (8(4)) and
17% (7(3)). During the preparation of 7(3) and 7(5) we also
isolated the corresponding hexathiamacrocycles 9(3) and 9(5)
as colorless oils in low yields (Scheme 3).
The investigations of the molecular structures of 6-8 revealed
that the alkyl groups attached to the aromatic rings prevent the
inclusions of solvent molecules in the interior of the cyclophanes
due to the tilt of the benzene rings around the S · · ·S axis (see
below). Therefore we looked for simple ways of attaching
solubilizing functional groups to the alkyl bridges of the
cyclophanes. In a first attempt we replaced the central CH2 group
of a pentamethylene chain by a 1,1-diethylcyclohexane moiety.
The starting material 3,3-pentamethyleneglutaric acid (21)
(Scheme 4) is commercially available. Scheme 4 summarizes a
straightforward protocol to synthesize the 1,1-di(2-chalcogeno-
cyanatoethyl)cyclohexanes 24 and 25. The diacid 21 was
reduced using LiAlH4 to afford the 1,5-diol 22.30 The latter was
converted to 24 and 25 via the 1,1′-di(2-methane-sulfonyloxy-
ethyl)cyclohexane (23) in an overall yield of ca. 60%.
The reaction of the di(lithium) salt of 11 with 24 afforded
the cyclophane 10 in only <1% yield (Scheme 5). The expected
(21) (a) Tamao, K.; Sumitani, S.; Kumada, M. J. Am. Chem. Soc. 1972, 94,
4374–4376. (b) Corriu, R. J. P.; Masse, J. P. J. Chem. Soc., Chem. Commun.
1972, 144.
(22) Rehahn, H.; Schlu¨ter, A.-D.; Feast, W. J. Synthesis 1988, 386–388.
(23) Kukula, H.; Veit, S.; Godt, A. Eur. J. Org. Chem. 1999, 277–286.
(24) Takahashi, S.; Kuroyama, Y.; Sonogashira, K.; Hagihara, N. Synthesis
1980, 627–630.
(25) (a) Goodall, D. C. J. Inorg. Nucl. Chem. 1968, 30, 1269–1270. (b)
Clarembeau, M.; Cravador, A.; Dumont, W.; Hevesi, L.; Krief, A.; Lucchetti,
J.; van Ende, D. Tetrahedron 1985, 41, 4793–4812. (c) Krief, A.; Delmotte, C.;
Dumont, W. Tetrahedron 1997, 53, 12147–12158.
J. Org. Chem. Vol. 73, No. 20, 2008 8023

Werz et al.
SCHEME 1
SCHEME 3
SCHEME 4
SCHEME 5
SCHEME 2
product resulting from a four-component cyclization of 2 equiv
of 11 and 24 could not be detected. We attribute this observation
to the fact that the sterically demanding six-membered ring in
the center of the pentano chains in 10 is only able to adopt the
exo-position if the pentano chain chooses a gauche-gauche
(g,g)( conformation instead of the anti,anti (a,a) conformation
depicted in Scheme 6.26 The assumption of a gauche-gauche
(g,g)( conformation of the pentano chains in 10 is supported
by the molecular structures of 24 and 25 (Figure 1).
Structural Investigations. We were able to grow single
crystals of 4(3), 4(5), 6, 7(3)-7(5), and 8(3)-8(6), which were
suited for X-ray diffraction experiments. We have subdivided
8024 J. Org. Chem. Vol. 73, No. 20, 2008

Macrocyclic Cyclophanes
SCHEME 6
the structures with respect to the chain lengths which connect
the R,ω-dichalcogena(1,4-diethynylbenzene) units.
Rings with Propylene Bridges. The only structure in all
measured species without any crystallographically imposed
symmetry is that of 4(3). One propylene chain adopts a zigzag
conformation including the terminal sulfur atoms, the other
shows a gauche conformation at the end with the sulfur center
S3 (Figure 2). The sulfur centers are involved in single (S2,
S3) or double (S4) close S· · ·S contacts (3.336 and 3.907 Å
that combine four cyclophanes into one unit. As a result a ribbon
of molecules is created (Figure 2). Within this assembly we
encounter for each pair of molecules two parallel phenyl rings
FIGURE 3. Chalcogen-chalcogen network between S1 and S2 centers
of 7(3). Hydrogen atoms are omitted for the sake of clarity.
with a very close π-π distance of 3.28 Å. (In Figure 2 this
overlap is indicated by a gray arrow.)
This distance is shorter than the interlayer spacing in graphite
(3.345 Å)27 or the interplanar distance of 2,7-dimethylpyrene
(3.45 Å).28 The π-π interaction in 4(3) is facilitated by a
rotation of one aromatic ring of each cyclophane by 55.8° with
respect to the ring plane defined by the intramolecular vector
between the centers of the aromatic units. The related thia- and
selenamacrocycles bearing propyl substituents on the aromatic
rings (7(3), 8(3)) show different features. Although both
structures are alike but not isomorphic they reveal very similar
crystal structures. The molecules adopt a conformation with
inversion symmetry in the crystal. The propylene chains show
a gauche conformation at the S1 end. The chalcogen atoms
among neighboring molecules show close contacts between
S1· · ·S2· · ·S2· · ·S1 (Se1 · · ·Se2· · ·Se2· · ·Se1, respectively) cen-
ters (Figure 3) providing for a two-dimensional chalcogen
network between layers of cycles. The distances between the
proximal chalcogen centers are in the case of the sulfur congener
3.575, 3.624, and 3.575 Å and in the case of the selenium
congener 3.693, 3.583, and 3.693 Å.
FIGURE 1. ORTEP plot (50% ellipsoid probability) of the molecular
structure of 24. Hydrogen atoms of the cyclohexyl part are omitted for
the sake of clarity.
Rings with Butylene Bridges. The molecular structure of
7(4) is based on an inversion symmetry with gauche conforma-
tions of both sulfur atoms at the end of the butylene chains. In
the crystal packing no stacking or close S· · ·S contacts were
found. For 8(4) we observed a rather complex structure in the
solid state which will be described in a stepwise fashion. As
previously mentioned in the case of 7(4) the butylene chains in
8(4) adopt a gauche conformation at the selenium ends. In
contrast to all other ring systems in the series with inversion
symmetry, the conformation of the molecule comprises a 2-fold
symmetry axis (Figure 4a). This leads to a close (3.74 Å),
eclipsed stacking of the two aromatic rings, with a cross-over
of the rigid alkyne units. Via short Se · · ·Se contacts (3.697 Å)
the molecules are connected to sets of parallel grid-like planes,
as shown in Figure 4b. This figure also depicts the eclipsed
stacking with complete overlap of the benzene rings. The
structure of 8(4) in the solid state can be described as two
perpendicular oriented equivalent planes (Figure 4c). The mutual
crossing of the two planes occurs through the meshes of the
grid without building contacts between the perpendicular sets
of planes.
Rings with Pentylene Bridges. This group of molecules
comprises the macrocycles 4(5), 6, 7(5), and 8(5). The unsub-
stituted cyclophane 4(5) reveals a centrosymmetric structure with
FIGURE 2. Structure of 4(3) in the solid state oriented into a ribbon
via short S· · ·S interactions. Hydrogen atoms are omitted for the sake
of clarity.
J. Org. Chem. Vol. 73, No. 20, 2008 8025

Werz et al.
TABLE 1. List of Adopted Conformations and Torsion Angles
[deg] of 4(3), 7(3), 8(3), 7(4), 8(4), 4(5), 6, 7(5), 8(5), and 8(6)a
spacer torsion
torsion
length compound chalcogen angle R conformationc angle ꢀ
3
4(3)b
S
24.0
9.3
a
a
g
a
g
a
g
a
g
g
g
g
a
a
g
a
g
g
g
g
a
a
1.3
55.8
41.2
44.2
57.7
86.8
64.9
31.5
60.3
59.9
11.5
59.2
19.0
19.4
32.4
3.4
7(3)
8(3)
7(4)
8(4)
4(5)
6
S
Se
S
47.3
27.7
26.6
13.1
10.1
85.6
39.3
29.6
24.5
21.6
37.9
21.5
39.8
5.5
4
5
Se
S
S
7(5)
8(5)
8(6)
S
Se
Se
6
1.3
a For the definition of R and ꢀ see Figure 7. b Two independent
molecules exist in the unit cell. c a ) anti; g ) gauche.
only slightly longer than the sum of the van der Waals radii of
benzene and sulfur (3.55 Å).29
The congener with two hexyl substituents at the aromatic rings
(6) is centrosymmetric as is 4(5), yet it shows one sulfur atom
(S1) per chain with gauche conformation with respect to the
pentylene spacer (Figure 5, left). The crystal packing of 6 is
dominated by the parallel orientation of the dihexyl substituted
aromatic rings. It provides for only one S · · ·S contact (S1 · · ·S1
) 3.669 Å). In Figure 5, left, we have compared the molecular
structures of 4(5) (open bonds) with no gauche conformation
with that of 6 (black solid bonds) with one gauche conformation.
The transformation of the skeleton of 4(5) into that of 6 is
indicated by the gray arrows.
With propyl substituents at the aromatic rings we encounter
two isomorphous crystallizing sulfur-, 7(5), and selenium-
containing, 8(5), compounds. In both molecules the two
chalcogen atoms of each chain adopt a gauche conformation
with respect to the pentamethylene spacers.
In Figure 5, right, we have compared 6 with one gauche
conformation (black solid bond) with 7(5) (black broken bonds).
The adaptation of the second gauche conformation in going from
6 to 7(5) is indicated by a gray arrow. It is interesting to note
that the switch from 6 to 7(5) hardly deforms the other parts of
the ring.
The two gauche conformations of the chalcogen atoms in
7(5) and 8(5) allow a rather weak interaction between the
chalcogen centers (S · · ·S ) 4.089 Å, Se · · ·Se ) 4.015 Å) giving
rise to a ladder-like motif3,4 with stacked molecules as shown
in Figure 6.
FIGURE 4. (a) ORTEP plot (50% ellipsoid probability) of the
molecular structure of 8(4) showing a π-π interaction between the
phenyl rings, which are stacked in an ecliptic conformation on top of
each other (see also panel b). Hydrogen atoms are omitted for the sake
of clarity. (b) One plane of 8(4) molecules in the solid state. The short
Se· · ·Se interactions are indicated by dots. Hydrogen atoms are omitted
for the sake of clarity. (c) Mutual intercrossing of two perpendicular
planes of 8(4) molecules in the solid state. Hydrogen atoms are omitted
for the sake of clarity.
(26) (a) Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of Organic
Compounds; J. Wiley & Sons: New York, 1994; p 603. (b) Dale, J. Stereo-
chemistry and Conformation Analysis; Verlag Chemie: New York, 1978.
(27) Franklin, R. E. Acta Crystallogr. 1951, 4, 253–261.
(28) Irngartinger, H.; Kirrstetter, R. G. H.; Krieger, C.; Rodewald, H.; Staab,
H. A. Tetrahedron Lett. 1977, 18, 1425–1428.
a clean zigzag conformation in both methylene chains, including
the terminal sulfur atoms. In the crystal neither stacking of the
molecules nor intermolecular S · · ·S contacts were observed. We
cannot rule out weak sulfur-π interactions between the S atoms
and the aromatic rings since the contact (3.688-3.709 Å) is
(29) Pauling, L. The Nature of the Chemical Bond, 3rd ed.; Cornell University
Press: Ithaca, NY, 1973.
8026 J. Org. Chem. Vol. 73, No. 20, 2008

Macrocyclic Cyclophanes
FIGURE 5. (Left) Comparison of the ring size of 4(5) without gauche conformation (open bonds) with 6 with one gauche conformation in each
bridge (solid bonds) demonstrating the ring size as a function of conformation. Hydrogen atoms are omitted for the sake of clarity. (Right) Comparison
of 6 and 7(5) with one and two gauche conformations, respectively, in the chains. The shape of 7(5) is indicated in black broken lines. Hydrogen
atoms are omitted for the sake of clarity.
TABLE 2. Recorded van der Waals Distances [Å] of Chalcogen
Centers X (X ) S or Se) in 4(3), 7(3), 8(3), 8(4), 6, 7(5), and 8(5)
compound
X · · ·X
Å
4(3)
S4· · ·S2
S4· · ·S3
S2· · ·S1
S2· · ·S2
Se2· · ·Se1
Se2· · ·Se2
3.336
3.907
3.575
3.624
3.693
3.583
7(3)
8(3)
8(4)
Se1· · ·Se1
3.697
6
7(5)
8(5)
S1· · ·S1
S1· · ·S2
Se1· · ·Se2
3.669
4.089
4.015
for an orientation of the aromatic rings in the plane of the
macrocycle. No stacking or short Se · · ·Se contacts were
observed.
A comparison of the structural parameters of 4(3), 7(3), 8(3),
7(4), 8(4), 4(5), 6, 7(5), 8(5), and 8(6) (Table 1) reveals very
similar bond distances in all rings. The average value for the
distance between the aromatic rings and the triple bonds amounts
to 1.44 Å, the length of the triple bonds was found to be 1.20
Å, and the average bond length between the triple bonds and
the sulfur (selenium) atoms amounts to 1.69 (1.83) Å. More
variation is found for the torsion angles R and ꢀ (see Figure 7).
The angle R is defined as the torsion of the S(e)-CH2 bond
with respect to the aromatic plane. The angle ꢀ measures the
rotation of the aromatic ring with respect to a line going through
centers 1 and 4 of each aromatic ring. No obvious and general
correlation between the different torsion angles and the con-
formation (anti or gauche) can be found. The distribution of R
shows a pattern with a maximum between 10° and 30° and a
minimum close to 90°. However, quantum chemical calculations
performed at the B3LYP/6-31G(d) level of theory did not reveal
any significantly favored conformation for the model system
PhCCXMe (X ) S, Se).
FIGURE 6. Stacking of the rings of 8(5) in the solid state. The
intermolecular ladder-type interaction between the chalcogen centers
is indicated by broken lines. Hydrogen atoms are omitted for the sake
of clarity.
FIGURE 7. Definition of the torsional angles R and ꢀ on hand of a
Newman projection of 4(3).
Rings with Hexylene Bridges. The largest spacers in this
series were employed in the synthesis of 8(6). Again the solid
state structure shows inversion symmetry. The zigzag conforma-
tion of the hexylene chains without any gauche conformation
of the terminal selenium atoms opens a very wide ring, providing
At several occasions we noticed short contacts between the
chalcogen centers. This is documented in Figures 2, 3, 4b, and
6. Table 2 summarizes the recorded values. It is found that the
J. Org. Chem. Vol. 73, No. 20, 2008 8027

Werz et al.
TABLE 3. Crystal Data and Details of the Refinement Procedure for 4(3), 4(5), 6, 7(3), 7(4), and 7(5)
4(3)
4(5)
6
7(3)
7(4)
7(5)
empirical formula
formula weight
crystal system
space group
a [Å]
C33H28S4
552.84
C30H28S4
516.80
monoclinic
P21/c
11.3467(3)
10.1243(3)
12.5302(3)
90
92.643(1)
90
C54H76S4
853.44
C38H44S4
628.97
monoclinic
P21/c
13.159(2)
9.170(1)
15.565(2)
90
114.261(3)
90
2
1712.3(4)
1.22
0.30
C40H48S4
657.02
monoclinic
P21/c
9.6400(2)
17.2157(1)
11.4959(2)
90
106.265(1)
90
2
1831.49(5)
1.19
0.29
C42H52S4
685.08
monoclinic
P21/n
5.9995(1)
20.0529(3)
16.1288(2)
90
95.919(1)
90
2
triclinic
triclinic
j
j
P1
P1
9.8227(2)
10.8655(2)
13.7005(2)
90.428(1)
96.336(1)
93.668(1)
2
659.01(3)
1.27
0.35
8.2206(3)
12.8156(4)
13.7297(5)
65.421(1)
86.628(2)
75.320(1)
1
1270.66(8)
1.12
0.22
b [Å]
c [Å]
R [deg]
ꢀ [deg]
γ [deg]
Z
2
V [Å3]
1437.91(7)
1.19
0.35
1930.07(5)
1.18
0.27
Dcalc [g/cm3]
µ [mm-1
]
max/min transm
θ range (deg)
reflections collected
0.97/0.87
1.50 - 27.47
14927
0.96/0.72
1.80 - 27.46
14384
0.97/0.91
1.63 - 27.50
13289
0.97/0.93
2.6 - 28.3
17081
0.94/0.88
2.2 - 26.4
15793
0.96/0.90
1.6 - 26.4
17828
independent/(Rint
)
6594 (0.029)
4671
1.01
0.037
0.085
3286 (0.035)
2534
1.03
0.041
0.103
5785 (0.048)
2827
0.98
0.055
0.130
4212 (0.036)
3819
1.21
0.049
0.115
3732 (0.029)
2836
1.05
0.037
0.089
3958 (0.036)
3033
1.04
0.035
0.078
observed (I > 2σ(I))
goodness-of-fit on F2
R(F)
Rω(F2)
∆F max/min (eÅ-3
)
0.35/-0.27
0.47/-0.38
0.32/-0.23
0.52/-0.25
0.24/-0.21
0.24/-0.30
TABLE 4. Crystal Data and Details of the Refinement Procedure for 8(3), 8(4), 8(5), 8(6), 24, and 25
8(3)
8(4)
8(5)
8(6)
24
25
empirical formula
formula weight
crystal system
space group
a [Å]
C38H44Se4
816.57
monoclinic
P21/c
12.5412(3)
8.8176(2)
16.9559(4)
90
110.527(1)
90
2
1755.99(7)
1.54
4.20
C46H54Se4
922.73
C42H52Se4
872.68
monoclinic
P21/n
5.9637(6)
19.835(2)
16.5139(17)
90
95.294(2)
90
2
1945.1(3)
1.49
3.80
C44H56Se4
900.73
monoclinic
P21/c
12.646(1)
10.267(1)
17.521(2)
90
106.627(3)
90
2
2179.7(4)
1.37
3.39
C12H18N2S2
254.40
monoclinic
P21/c
11.6618(4)
10.3412(4)
11.5186(4)
90
107.935(1)
90
C12H18N2Se2
348.20
monoclinic
P21/c
11.646(1)
10.434(1)
11.443(1)
90
106.003(2)
90
tetragonal
j
P421c
17.2898(3)
17.2898(3)
14.4921(4)
90
90
90
b [Å]
c [Å]
R [deg]
ꢀ [deg]
γ [deg]
Z
4
4
4
V [Å3]
4332.23(16)
1.41
3.42
1321.61(8)
1.28
0.38
1336.8(2)
1.73
5.51
Dcalc [g/cm3]
µ [mm-1
]
max/min transm
θ range (deg)
reflections collected
independent/Rint
observed (I > 2σ(I))
goodness-of-fit on F2
R(F)
0.46/0.28
1.7 - 27.5
17656
4006/0.028
3258
1.06
0.025
0.057
0.48/-0.62
0.82/0.55
1.7 - 27.8
44476
5082/0.144
2611
1.01
0.041
0.066
0.43/-0.67
0.68/0.64
2.40 - 28.32
19785
4801/0.036
4103
1.05
0.027
0.057
0.59/-0.28
0.69/0.20
2.33 - 20.81
11141
2251/0.043
1895
1.03
0.031
0.074
0.45/-0.43
0.96/0.91
1.84 - 27.48
13354
3022/0.032
2470
1.04
0.032
0.075
0.26/-0.25
0.73/0.56
1.82 - 28.31
13812
3322/0.021
2991
1.07
0.040
0.093
1.18/-0.26
Rω(F2)
∆F max/min (eÅ-3
)
distances recorded for the S · · ·S contacts are slightly below or
close to the sum of the van der Waals radii (3.70 Å).29 The
same holds true for the Se· · ·Se distances where the sum of the
van der Waals radii is 4.00 Å.29 The anticipated tubular
structures were only found in the cases of 7(5) and 8(5) (c.f.
Figure 6).
blocks. Initial problems caused by the low solubility of the
macrocycles 4 and 5 were overcome by the introduction of
solubilizing alkyl chains on the aromatic rings of macrocycles
6-8. X-ray crystal structure analysis revealed the formation
of tubular structures in the case of the cyclophanes 7(5) and
8(5). The study of chalcogen-chalcogen interactions led to
the identification of particularly well-defined solid-state
architectures: 4(3) crystallizes in a ribbon structure compris-
ing close π-π interactions between neighboring aromatic
rings. In the case of 8(4) we identified ecliptic intramolecular
aromatic π-π stacking interactions. The short intermolecular
Se · · · Se interaction in 8(4) gave rise to two-dimensional
sheets crossing each other mutually in a perpendicular way.
Despite the very similar scaffolds of 4(n)-7(n) we observe
a great variety of their solid state structures. This observation
was traced back to a subtle interplay between weak forces
among the chalcogen centers and π-π interactions of the
Conclusion
In the past years we prepared and investigated macrocyclic
rings composed of two or three rigid units and two or three
flexible bridges comprising four to six chalcogen atoms at
the termini of the rigid subunits (e.g., 2, Chart 1). Intermo-
lecular van der Waals forces between chalcogen centers gave
rise to tubular structures (e.g., 3, Chart 1). Herein we describe
the synthesis and the structural variations induced by using
R,ω-dichalcogena(1,4-diethynylbenzene) units (4) and R,ω-
dichalcogena(1,4-diethynylbiphenyl) units (5) as building
8028 J. Org. Chem. Vol. 73, No. 20, 2008

Macrocyclic Cyclophanes
7(5), 8(3), 8(4), and 24, and a Bruker APEX diffractometer for
7(3), 8(5), 8(6), and 25, both equipped with a sealed tube Mo KR
radiation source and a graphite monochromator (λ ) 0.71073 Å).
The data sets were collected at a temperature of 200 K for most of
the structures; in the cases of 7(3), 8(5), and 25 the temperature
was 100 K. Omega-scans of 0.3° were taken, covering a whole
sphere in reciprocal space in each case. All intensities were
corrected for Lorentz and polarization effects, and absorption
corrections were applied using SADABS31 based on the Laue
symmetry of the reciprocal space. The structures were solved by
direct methods, the structural parameters of the non-hydrogen atoms
were refined anisotropically according to a full-matrix least-squares
technique against F2. Hydrogen atoms were treated by appropriate
riding models, except for 8(5) and 25 where they were refined
isotropically and 8(6) where they were treated in a mixed manner.
Structure solution and refinement were carried out with the
SHELXTL (5.10) software package.32 Crystallographic data and
details of the data collection and the refinement procedure are given
in Tables 3 and 4. CCDC-691838 (4(3)), -691839 (4(5)), -691840
(6), -691841 (7(3)), -691842 (7(4)), -691843 (7(5)), -691844 (8(3)),
-691845 (8(4)), -691846 (8(5)), -691847 (8(6)), -691848 (24), and
-691849 (25) contain the supplementary crystallographic data for
this paper. Copies of the data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html or on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, U.K. [Fax: (int) +
44-1223/336-033, E-mail: data_request@ccdc.cam.ac.uk], on
quoting the deposition numbers. ORTEP drawings were obtained
by Ortep-3 for Windows by Farrugia.32
aromatic units on one side and steric effects within and
between alkyl chains and groups, respectively, on the other.
Experimental Section
General Procedure for the Preparation of Tetrathia- and
Tetraselenamacrocycles 4(n), 5, 6, 7(n), and 8(n). A flame-dried
250-mL Schlenk tube was charged under argon with 1.0 equiv of
1,4-di(ethynyl)-2,5-di(n-propyl)benzene in 200 mL of anhydrous
THF and cooled to -40 °C. Then, 2.0 equiv of n-butyllithium
(nBuli) or lithium hexamethyldisilazide (LiHMDS) in THF was
slowly added, and the resulting suspension was vigorously stirred
for 15 min at -40 °C. A flame-dried 2000-mL round-bottom flask
with two 250-mL addition funnels was charged under argon with
750 mL of anhydrous THF and cooled to -50 °C. The above
prepared solution of the lithium salt was transferred into the first
funnel and diluted with dry THF to a total volume of 250 mL. The
second funnel was charged with 1.0 equiv of R,ω-dithiocyanatoal-
kane or R,ω-diselenocyanatoalkane in 250 mL of anhydrous THF.
Both solutions were added simultaneously at -50 °C over a period
of 4-5 h. The resulting solution was stirred for 12 h at 24 °C, and
the solvent was concentrated by rotary evaporation. The residue
was filtered through a plug of silica (SiO2; 3% NEt3, toluene).
Column chromatography (SiO2; 3% NEt3, hexane/toluene) of the
crude product yielded the macrocycles as colorless solids. Repre-
sentative analytical data are given below.
4,8,14,18-Tetrathia-12,15,112,115-tetra(n-propyl)-1(1,4),11(1,4)-
dibenzenacycloeicosa-2,9,12,19-tetraynophane (7(3)). Starting
materials: 1,4-di(ethynyl)-2,5-di(n-propyl)benzene (19, 2.08 g, 9.9
mmol), LiHMDS (1.06 M in THF, 19.0 mL, 20.1 mmol), 1,3-
dithiocyanatopropane (12(3), 1.57 g, 9.9 mmol). Column chroma-
tography (SiO2; 3% NEt3, hexane/toluene, 3:1). Yield: 534 mg
(17%) of 7(3) as a colorless solid. Rf (SiO2, hexane/toluene, 3:1)
Acknowledgment. We are grateful to the Deutsche Fors-
chungsgemeinschaft (DFG) and the Fonds der Chemischen
Industrie for financial support. D.B.W. thanks the Studienstiftung
des deutschen Volkes for a graduate fellowship. We thank Mrs.
P. Kra¨mer for typing the manuscript and A. Flatow for setting
up the Supporting Information.
1
0.26; mp 158 °C; H NMR (500 MHz, CD2Cl2) δ 6.89 (s, 4 H),
2.82 (t, 3J ) 7.4 Hz, 8 H), 2.44 (quint., 3J ) 7.3 Hz, 4 H), 2.35 (t,
3
3J ) 7.6 Hz, 8 H), 1.50-1.40 (m, 8 H), 0.87 (t, J ) 7.4 Hz, 12
H); 13C NMR (125 MHz, CD2Cl2) δ 141.9, 131.8, 122.3, 92.8, 82.2,
35.9, 33.6, 29.6, 23.4, 13.9; IR (KBr) ν˜ ) 2954, 2926, 2867, 2153
cm-1; UV-vis (0.056 mg/mL in CH2Cl2) λmax (log ε) ) 336 (4.47),
286 (4.45) nm; FAB-MS m/z 628.2 (100, M+); HRMS(FAB) calcd
for [C38H44S4+] 628.2326, found 628.2341. C38H44S4 (628.23) calcd:
C, 72.56; H, 7.05; S, 20.39. Found: C, 72.64; H, 7.10; S, 19.93.
X-ray Structure Analyses. The reflections were collected with
a Bruker Smart CCD diffractometer at 200 K for 4(3), 4(5), 6, 7(4),
Supporting Information Available: Protocols for the prepa-
ration of diyne 19 and compounds 4-10 and 23-25, as well
as analytical data thereof. Crystal data (CIF files) for 4(3), 4(5),
6, 7(3)-7(5), 8(3)-8(6), 24, and 25. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO801378P
(31) Sheldrick, G. M. SADABS; Bruker Analytical X-ray Division: Madison,
WI, 1997.
(32) Sheldrick, G. M. Acta Crystallogr. A 2008, 64, 112–122.
(30) Eilbracht, P.; Acker, M.; Trotzauer, W. Chem. Ber. 1983, 116, 238–
242.
J. Org. Chem. Vol. 73, No. 20, 2008 8029