Molecular and supramolecular diversity displayed by dienone-ether macrocycles

Article abstract of DOI:10.1021/cg100235x

Dienone-ether macrocycles (DEMs) represent a new class of supramolecular building blocks for the preparation of crystalline materials with potentially diverse applications. A modular, building block approach to the synthesis employs a range of linked aryl

Full text of DOI:10.1021/cg100235x

DOI: 10.1021/cg100235x
Molecular and Supramolecular Diversity Displayed by
Dienone-Ether Macrocycles
2010, Vol. 10
2409–2420
Luke T. Higham,† Janet L. Scott,*,† and Christopher R. Strauss*,‡
†School of Chemistry and Centre for Green Chemistry, Monash University, Wellington Road, Clayton,
Victoria 3800, Australia, and ‡QUILL Centre, The Queen’s University of Belfast, David Keir Building,
Stranmillis Road, Belfast BT9 5AG, Northern Ireland, U.K.
Received February 19, 2010; Revised Manuscript Received March 30, 2010
ABSTRACT: Dienone-ether macrocycles (DEMs) represent a new class of supramolecular building blocks for the preparation
of crystalline materials with potentially diverse applications. A modular, building block approach to the synthesis employs a
range of linked aryl aldehydes and cyclic ketones. Consequently, the structures of DEMs can be tuned with regard to size and
shape and the incorporation of functional elements for specific purposes. Fourteen examples are presented, illustrating the
diversity of DEMs accessible by this approach. The effect of molecular structure on conformation, supramolecular inclusion,
and crystal packing is discussed.
Introduction
be altered, for example, by changing the polarity of the solvent
and in other cases by exposure to light.12
Calixarenes,1 resorcinarenes,2 cyclotriveratrylenes,3 cucur-
biturils,4 and crown ethers5 exemplify families of macrocyclic
compounds that have found extensive use in supramolecular
chemistry. Key features suchasfacialcurvature and the ability
to include or coordinate metal ions have given rise to many
and varied applications of such compounds. Recent examples
include bowl-shaped cyclotriguaiacylene capsules,6 resorci-
narene cocrystals,7 calixarene/drug8 and calixarene/quinoline9
inclusion complexes, calixarene/metal self-inclusion polymers,10
and macrocycles bearing crown ether-like moieties.11
The building block approach13 employing aryl aldehydes
and cyclic ketones delivered a family of molecules referred to
herein as dienone-ether macrocycles (DEMs).14 Such com-
pounds could be transformed in one step to flexible Horning-
crowns, for example, a family of macrocycles with structures
that are hybrids of calixarenes and crown ethers.15
Strategic selection of appropriate salicylaldehyde, dibromo
linking units and cycloalkanone reactants enables the size and
shape of a DEM to be predetermined and specific functional
groups to be inserted (Scheme 1).
Such molecules typically are produced from single repeat-
ing units. Accordingly, the synthetic strategies in effect afford
macrocyclic oligomers. An unfortunate consequence is that
they limit the scope for incorporation of structural diversity. If
mixtures of starting units were to be employed instead of
single components, complex mixtures of essentially randomly
generated products could be expected. Pure products could
prove difficult to produce in satisfactory yields and to isolate.
Consequently, if synthetic modifications were required in
order to obtain specific macrocyclic molecules having requi-
site shape, size, charge distribution, or functional group
arrays, the chemistry usually would need to be performed
after formation of the macrocyclic ring. In many cases, the
identical nature of the various repeated individual units
making up the macrocycle would hamper exclusive reaction
at a predetermined position on a specific moiety.
We have attempted to avoid these circumstances by devel-
oping a versatile array of novel, highly functionalized macro-
cycles that could be assembled readily from individual
building blocks. Efforts have been made to incorporate into
the design various means of switching the shape of these
molecules to enable them to capture and release specific
substrates efficiently and economically. Molecular shape can
Rectangular or parallelogram-shaped (as viewed from
above) macrocycles are formed by four sequential Claisen-
Schmidt condensation reactions involving two identical lin-
kers. Linkers of differing chain lengths may be inserted by
application of the multitasking solvent and catalyst, DIM-
CARB, as disclosed previously (Scheme 1).13,16,17 To convey
the building block approach and to outline its flexibility, we
have used a plumbing analogy. Building blocks bearing
activated, nucleophilic methylene groups have been desig-
nated as male, and those bearing electrophilic, nonenolizable
aldehydic functionalities, as female.18 In DEM syntheses, they
correspond to cycloalkanone rigid male linkers II and salicyl-
aldehyde-based flexible female unions IV, as illustrated in
Figure 1. Compounds III, prepared by DIMCARB mediated
condensation, are thus flexible male unions. A vast range of
salicylaldehyde and cycloalkanone derived components is
available commercially, and dibrominated linkers are readily
prepared. Hence, a multitude of DEMs can be produced, and
molecular diversity can be readily generated without the need
for complex synthetic strategies.
Herein we illustrate both the ease with which these
macrocycles may be synthesized and the diversity of shapes
and sizes that are accessible. The crystal structures of a
range of DEMs are compared to illustrate the effects on the
size and shape of variations in structure as well as the
impact of structural modification on solid-state packing
motifs and intermolecular interactions. The broad scope of
molecular and supramolecular structures accessible suggests
*To whom correspondence should be addressed. Current addresses:
J.L.S.: Centre for Sustainable Chemical Technologies, University of Bath,
Bath BA2 7AY, U.K.; e-mail, j.l.scott@bath.ac.uk; telephone, þ44 1225
386073. C.R.S.: Strauss Consulting Ltd, P.O. Box 1065, Kunyung LPO, Mt
Eliza, Victoria 3930, Australia.
r
2010 American Chemical Society
Published on Web 04/20/2010
pubs.acs.org/crystal

2410 Crystal Growth & Design, Vol. 10, No. 5, 2010
Higham et al.
Figure 1. Schematic of construction of (a) a “symmetrical” DEM with identical flexible linkers from two flexible female unions and two rigid
male unions, and (b) an “unsymmetrical” DEM with different flexible linkers prepared by sequential assembly of a flexible male union from a
flexible female union and two rigid male unions, followed by reaction with a second (different) flexible female union.
Scheme 1. Synthetic Route to DEMsa
a Aryldialdehyde flexible female unions I are prepared from salicylaldehydes and dibromo linkers by microwave-assisted Williamson etherification in
EtOH; reaction with a cycloalkanone II in DIMCARB yields a flexible male union III, which may in turn be reacted with a second flexible female union
IV in a Claisen-Schmidt condensation to afford the DEM V. If R4 = R5, direct reaction of flexible female union I with the cycloalkanone in a
Claisen-Schmidt condensation reaction provides access to a “symmetrical” DEM.
Table 1. DEMs Reported in This Work
no.
R1
R2
R3
R4
(CH2)2
R5
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)3
(CH2)2O(CH2)2
(CH2)2O(CH2)2
(CH2)2
X
n
yielda/%
crystal structure
CH2Cl2 solvate
CH2Cl2 solvate
1
2
3
4
5
6
7
8
H
H
H
H
H
H
Me
t-Bu
Ph
H
H
H
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
0
0
0
1
1
1
1
1
1
1
1
1
1
1
39
32
OMe
OEt
H
H
H
OMe
OEt
H
H
H
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2O(CH2)2
(CH2)2
(CH2)4
21
3414
39
CH2Cl2/CH3CN solvate14
(s,s)-isomer chlorobenzene solvate
(s,s)-isomer p-xylene solvate
31
28
25
H
H
OMe
OEt
H
H
H
OMe
OEt
H
H
H
CH2Cl2 solvate
nonsolvated
9
21
10
11
12
13
14
2413
2213
2514
31
CHCl3/H2O solvate13
p-xylene/water solvate
H
H
Me
H
H
H
H
H
CH2Cl2/toluene solvate
(CH2)4
CH
18
a Yields are for recrystallized material, with typically narrow melting point ranges (NMR spectra are provided in the Supporting Information) and are
based on dialdehyde I.
that the potential applications of DEMs (and the rela-
ted Horning-crowns that may be derived therefrom15) may
become as wide as those of calixarenes, resorcinarenes, or
crown ethers, particularly for the preparation of crystalline
materials.
Results and Discussion
The DEMs prepared and described herein are summarized
in Table 1. They include examples with linkers of various
lengths and composition, para-substituted cycloalkanone

Article
Crystal Growth & Design, Vol. 10, No. 5, 2010 2411
Figure 2. Compounds VI and VII.
Figure 3. Side views of macrocycles showing the shape adopted in each of the crystal structures. Crystal structures of 4 and 10, previously
published,13,14 are included for comparison. In all cases the view is oriented such that the CdO group labeled O1 or O10 is to the left and oxygen
and nitrogen atoms are represented as spheres with all other atoms rendered in stick mode. (The second disorder component in 11 is depicted
with dashed bonds; in all other cases only the major components are shown.)
moieties, and aryl corners bearing differing substituents. An
example of a heteroatom-containing cycloalkanone moiety is
also provided.
diversity rather than optimization of a specific synthesis,
and accordingly, the simplicity and flexibility of the synthe-
tic route makes it amenable to parallel synthesis of libraries
of DEMs, useful for screening of specific applications as
materials.
Although yields were not high, all synthetic steps were
executed without protection/deprotection or preactivation
strategies, and tandem or cascade-type processes were em-
ployed where possible to minimize sequences (Scheme 1).
Dilute conditions afforded the DEM as the major product.
In general, cyclopentanone reacted more rapidly than did
cyclohexanone in the condensations performed, and product
DEMs tended to precipitate from solution. 1H NMR spectra
of DEMs derived from 4-substituted cyclohexanones exhibi-
ted signals due to two distinct species, designated “(s,s)” or
“(s,r)” with respect to the orientation of the para substituents
of the cyclohexanone moiety. Also, 1H and 13C NMR spectra
of DEMs were sometimes complicated by additional signals
attributable to conformers arising from E/Z photoisomerism
of double bonds. The thermodynamically preferred E,E,E,E
conformers are formed exclusively in Claisen condensations
and could be isolated in all cases. Mixed E,Z conformers may
be formed subsequently. They were isolated by selective
crystallization, and the photoisomerism of these macrocycles
will be reported elsewhere. Byproducts, including “deletion
products”, i.e. those lacking one cycloalkanone male union,
such as VI (see Figure 2), or short oligomers, such as VII,
could be difficult to separate from the desired DEM. This
resulted in product losses during purification by recrystalliza-
tion. The primary focus of this work concerns structural
Indeed, even a relatively small library of <20 DEMs has
allowed us to demonstrate that subtle changes in the DEM
molecularstructures cansignificantlyinfluence physicochemi-
cal properties. For example, addition of alkoxy groups to the
salicylyl corner groups as in 2, 3, 8, and 9 yielded DEMs with
significantly greater solubility than that of the unsubstituted
parent macrocycles 1 and 4 in a range of common solvents.
The ease with which specific functional units may be incorpo-
rated by choice of building block suggests potential for
applications where specific functionality is required either
for direct activity or after further structural elaboration.
To examine the effect of variation of molecular structure on
the solid-state structures and conformational arrangements of
the DEMs, crystal structures of a range of solvates and
nonsolvated forms were examined. For comparison, struc-
tures reported previously13,14;the dichloromethane/aceto-
nitrile solvate of rectangular DEM 414 and the water/
dichloromethane solvate of trapezoidal DEM 1013;are also
discussed. ORTEP diagrams with full molecular numbering
are provided in the Supporting Information.
In projection, the DEMs approximate a rectangular or
trapezoidal shape, but when viewed from side-on, they resem-
ble two semirigid “leaves” linked by flexible ether “hinges.”

2412 Crystal Growth & Design, Vol. 10, No. 5, 2010
Higham et al.
Figure 4. Simplified cartoon depiction of the macrocycle shapes: speckled rectangles represent aryl corner groups (salicylyl moieties), thin lines
represent flexible linkers, and arrows represent cyclopentyl or cyclohexyl moieties (with the tail indicating the orientation of the out-of-plane
CH2 group in the envelope conformers of cyclohexyl moieties).
Figure 5. Molecular shape as defined by the Hirshfeld surfaces19 for the DEMs in (a) 4; (b) (s,s)-5; (c) 11 (the hydrogen bonded water molecule
is depicted in stick mode); and (d) 9. All molecules are orientated with bis(benzylidene)cyclohexanone leaves forming the sides, viewed in the
hollow of the V (where appropriate) with CdO groups pointing inward.
This conformation allows the bis(benzylidene)cyclohexanone
systems to fold relative to each other. Side views of the DEMs
show the range of folded structures adopted (Figures 3 and 4).
Clearly, even chemically identical macrocycles may adopt
various folded or stepped conformations, as occurs in the
dichloromethane solvate of 2.
where the promolecule electron density contributes more than
half of the total procrystal electron density”,19 provides a
visual comparison (Figure 5). Conformer type F, represented
by 4, has an open channel through the center of the macro-
cycle into which solvent molecules pack (Figure 5a), while
conformer type A, represented by (s,s)-5, has no channel.
Extension of the length of the flexible linker(s) allows an
opening in the center of the DEM, even when the A type
conformer is adopted, as is illustrated for 11 in Figure 5c. As a
water molecule is hydrogen-bonded across the two CdO
groups in 11 in a bridging fashion, the annulus is effectively
propped open and this may point to opportunities for inclu-
sion of other hydrogen bond donors into the cavity. The
parallel offset conformer D, represented by 9, exhibits a small
hole through the center of the DEM (Figure 5c), which is now
flat and extended in length due to the addition of bulky
ethoxyl groups to the corner salicylyl moieties (Figure 5d).
DEM 9 is the only nonsolvated form, and here the central hole
is filled by the ethoxyl group of a neighboring DEM.
In the schematic of the DEM conformers provided in
Figure 4, we have depicted aryl groups as parallel with each
other and the planar C-C-C(O)-C-C part of the cycloalk-
anone moiety as flat and uniformly twisted with respect to the
aryl groups. The implication is that the “leaves” of the
conjugated Ar;CdC;C(O);CdC;Ar bis(benzylidene)-
cyclohexanone system seldom adopt a flat conformation and,
in these structures, may be bowed or twisted (orboth). Indeed,
only one (of four in each structure) of the leaves of macro-
cycles 1 and 2 and one (of two) of the leaves of 13 adopt a
largely coplanar arrangement, as is discernible by close ex-
amination of Figure 3. Out-of-plane twists of the approxi-
mately planar C-C-C(O)-C-C system of cyclopentyl or
cyclohexyl groups appear common, and aryl rings of a bis-
(benzylidene)cyclohexanone system may be twisted with re-
spect to each other. To describe these twists and bows, the
planes and lines depicted in Figure 6 are used to effect
measurement of the dihedral angles between aryl rings and
anadjacent C-C(O)-C group, —1 and —2, and between aryl
groups of the same leaf, —3 (Table 2). The angle between lines
The relative orientations of the aryl and cycloalkanone
moieties may be divided into six types, as depicted in Figure 4.
These are characterized, at the extremes, by carbonyl groups
swung into the V shape of the folded DEM (form A) and two
carbonyl groups reversed out of the cavity (form F). In
between these extremes are the following: B, one carbonyl
approximately coplanar with the aryl groups; C, both carbo-
nyl groups in-plane with the aryl groups of their respective
benzylidene systems; D, carbonyl groups twisted with respect
to the approximately coplanar aryl groups but parallel with
each other, with aryl groups offset and parallel to each other;
and E, as per C, but with approximately coplanar aryl groups
(Figure 4). Clearly, these types represent points on a con-
tinuum and some macrocycles adopt conformations that are
part-way between two types. Thus, type A is found in 5, 6, 10,
and 11; type B in 13; type C in 1 and 10 (albeit distorted); type
D in 9; type E in 8 and 80; type E in 2 (but not 20); and type F in
the previously reported 4 only. (Macrocycle 20 exhibits a
remarkably twisted and distorted shape, and we return to
discussion of this later.) Clearly, certain types will follow from
specificcrystallographicsymmetry elements; thus, A, C, and F
may result when a macrocycle is situated across a mirror plane
or centered on a 2-fold axis; D and E may correspond to a
center of inversion in the center of the annulus, and B requires
that the ASU contains an entire crystallographically unique
macrocycle.
The effect of rotation of the carbonyl group out of the
hollow of the V of the folded DEM, as in 4, into the hollow, as
in (s,s)-5, (s,s)-6, 10, and 11, or partially into the hollow, as
in 13, has a dramatic effect on the size of the annulus and the
shape of the DEM. Consideration of the shape of the DEMs
as their Hirshfeld surfaces, thus illustrating the shape of the
molecule in the crystal as defined by the “portion of space

Article
Crystal Growth & Design, Vol. 10, No. 5, 2010 2413
coincident with CdO groups of opposite leaves is used to
define the pitch of the V.
3 Structures dominated by CH OdC interactions.
3 3 3
4 Nonsolvated structures in which self-inclusion of a
neighboring DEM replaces solvent inclusion.
One bis(benzylidene)cyclohexanone leaf of 1 approaches
planarity, as does one leaf of 13 and both leaves of 2 (second
generated by symmetry). At the opposite end of the spectrum,
both leaves of 20 are highly twisted, and thus, the independent
DEMs in the crystal structure have very different shapes, as
is illustrated by comparison of their Hirshfeld surfaces
(Figure 7).
To discern whether certain DEM molecular conformations
lead to specific solid state packing and/or intermolecular inter-
actions (or vice versa), the crystal structures were compared
and grouped. Analysis of the extended packing motifs of the
different macrocycles reveals four main types of structure:
1 Overlapped ππ stacked DEM systems.
Classifying the structures in this manner leads to an inter-
esting correlation between conformer type and extended
packing motif, illustrated in Table 3. It appears that certain
conformer types are correlated with particular extended
packing motifs. Conformer types C and B are similar, differ-
ing by rotation of one C-C(O)-C group into the V. Thus,
both ππ stacked systems adopt similar B and C conformers
and two of the three channel type systems adopt the E
Table 3. Classification of Structures into Extended Structure Types and
DEM Conformer Types
2 Structures containing channels in which solvent is
accommodated.
Figure 6. Planes and lines defined to describe the twist and bow of
bis(benzylidene)cyclohexanone leaves and the dihedral angle be-
tween CdO groups of opposite leaves of the DEMs. Planes i and iii
are the aromatic rings and ii the C-C(O)-C system, while line iv
defines the CdO group.
Table 2. Molecular Geometry Defined by Relative Angles between Planes and Lines of the Bis(benzylidene)cyclohexanone
Moieties and across the Macrocycle
DEM
conformer type
C
—1/deg (plane i - ii)
—2/deg (plane ii - iii)
—3/deg (plane i - iii)
—4/deg (line iv - iv)
1
4.1(2)
7.4(2)
11.0(3)
8.8(3)
4.3(4)
9.0(2)
43.3(2)
36.9(3)
31.9(2)
14.6(3)
69.6(2)
42.6(2)
62.3(1)
60.0(1)
73.7(1)
68.8(2)
40.9(1)
38.5(1)
53.9(1)
56.3(1)
59.3(1)
70.5(1)
49.3(1)
34.7(2)
17.5(2)
9.9(2)
35.9(2)
30.4(3)
33.6(1)
10.3(3)
74.5(2)
15.1(2)
33.2(1)
17.4(1)
39.5(1)
34.3(2)
13.0(2)
11.7(2)
23.2(1)
26.8(1)
38.7(1)
42.7(1)
30.1(2)
14.2(2)
11.6(1)
87.6(2)
10
C
80.4(2)
a
a
2
20
4
5
E
b
5.0(2)
F
A
42.1(2)
55.6(1)
43.1(1)
57.4(1)
61.3(2)
36.9(1)
36.6(1)
47.2(1)
49.5(1)
46.2(1)
49.7(1)
45.8(1)
31.3(2)
6.8(2)
36.9(1)c
43.6(1)
6
A
49.2(2)
a
a
a
8
E
E
D
A
80
9
10
44.0(1)
30.3(2)
38.5(1)
11
13
A
B
a These planes are parallel because the second CdO group is generated by a center of symmetry from half a macrocycle of the ASU. b Twisted
conformation not categorized. c Symmetry transformation operation used to define the opposite cycloalkanone C-C(O)-C motif: 1 - x, y, 1/2 - z.
Figure 7. Hirshfeld surfaces of (a) 2 and (b) 20. Single leaves viewed down the line OC of the CdO group (c) 2 is almost planar, and (d) 20 shows
the large out of plane twist and bend of one aryl group.

2414 Crystal Growth & Design, Vol. 10, No. 5, 2010
Higham et al.
Figure 8. “Face to face” ππ overlap in (a) DEM 1 and (b) DEM 10 in the 1 2CH2Cl2 solvate structure with symmetry generated macrocycles
depicted in dark gray and oxygen atoms as spheres. Both DEMs are in the C type conformation, but the rings of each leaf are not entirely
3
coplanar. Instead, the overlapped parts tend to adopt a planar arrangement, while the nonoverlapped aryl ring is slightly twisted out of the
plane.
Figure 9. Intermolecular interactions in 1 2CH2Cl2 (a) illustrated in stick mode with close contacts indicated by dotted lines (10 DEM,
3
generated by the symmetry operator x - 1, 1 þ y, z - 1, is depicted in dark gray) and (b) in space fill mode with arrows indicating the ππ overlap.
These are: (a) back to back ππ overlap of 10, (b) face to face ππ overlap of 1 (as depicted in Figure 8a), (c) face to face ππ overlap of 10 (as depicted
in Figure 8b), and (d) back to back ππ overlap of 1.
Table 4. Summary of CH O Interactions in 1 and 13
3 3 3
C-H Oa
d(H A)/A d(D A)/A —DHA/deg
˚
˚
3 3 3
3 3 3
3 3 3
4.28(1)
3.97(1)
1
1 C3G1-H3G1a O20
3.44
3.02
2.49
2.52
2.41
2.52
2.56
2.29
2.39
2.73
2.95
2.53
3.68
2.79
2.47
2.86
145
162
133
126
153
138
142
154
126
130
146
150
126
130
109
100
3 3 3
2 C3G1-H3G1a O30
3 3 3
3 C3G1-H3G2a O10
3.245(6)
3.206(6)
3.317(5)
3.320(5)
3.389(5)
3.213(5)
3.078(5)
3.451(5)
3.809(5)
3.425(5)
4.337(4)
3.512(4)
2.947(4)
3.192(4)
3 3 3
4 C3G1-H3G2a O40
3 303
5 C6-H6Ab O1
3 3 3
6 C7-H7Ab O40
3 3c3
7 C180-H18D
O1
O4
c 3 3 3
3 3 3
8 C170-H17D
9 C4G-H4G2 O1
3 3 3
10 C4G-H4G2 O4
3 3 3
11 C4G-H4G1 O6
3 3 3
12 C4G-H4G1 O5
3 3 3
13 1 C8G-H8G2 O5
3 3 3
2 C8G-H8G2 O6
3 3 3
3 C8G-H8G1 O4
3 3 3
4 C8G-H8G1 O1
3 3 3
a Symmetry operations used to define atoms: (a) x - 1, y, z; (b) x,
y - 1, 1 þ z; (c) x, 1 þ y, z - 1.
Figure 10. DEM intermolecular interactions in the 13 CH2Cl2
toluene solvate structure. Oxygen, nitrogen, and chlorine atoms
are depicted as spheres and CH O interactions as dotted lines.
Unusually, ππ overlap is not offset and closest distances between
planes are atom/atom distances. This “in registration” configura-
tion is usually considered to be energetically unfavorable and one
must consider it possible that this is a weakly repulsive interaction
imposed by packing rather than a weakly attractive interaction
leading to specific arrangements of molecules.
3
3
3 3 3
conformer. All structures characterized by the CH OdC inter-
3 3 3
actions have DEMs in the A conformer, which decreases the
size of the annulus in the DEM, and the nonsolvate is the only
structure wherein the DEM adopts the D conformer. The
previously described solvate, 4 3/4CH2Cl2 1/2CH3CN, also
3
3
proves to be an odd structure out, but this will be discussed
under the section on channel type structures.
As illustrated in Figure 9, two included CH2Cl2 solvent
molecules exhibit close contacts with the oxygen atoms of the
DEM and the solvent molecule is fitted into a cavity on the
apex of the V of the DEMs to one side of the CdO groups.
The corresponding cavity on the other side is filled by the side
chain of the second DEM with corresponding close contacts
between methylene hydrogen atoms and carbonyl oxygen
atoms (Table 4). The pairs of DEMs so formed then pack in
the extended structure such that partial overlap of π systems
ππ Stacked Systems. In the absence of strong intermole-
cular interactions, such as hydrogen bonds, a number of
weaker interactions may be discerned in a study of close
contacts. Thus, in 1 2CH2Cl2 a series of ππ stacking inter-
3
actions were noted between DEMs (Figure 8). The “face to
face” ππ overlapped systems all adopt a flat or nearly flat
conformation, while nonoverlapped aryl groups may be
twisted well out of the plane.

Article
Crystal Growth & Design, Vol. 10, No. 5, 2010 2415
of adjacent pairs occurs, in either a back-to-back or face-to-
face manner (Figure 9).
rotated out of the hollow of the V shaped DEM. In both
cases, however, a central cavity is opened up and solvent
molecules may be accommodated in this space. Packing
diagrams of both E type conformer structures are presented
in Figure 11.
In 13, similar insertion of the CH2Cl2 solvent into the apex
of the V and face to face ππ overlap occurs (Figure 10), but
the CH O interactions of one ethereal linker of one DEM
3 3 3
with the carbonyl groups of its neighbor (that resulted in
a “clipping together” of the DEMs) are lacking, as are back
The packing diagram of 2 CH2Cl2 (Figure 11a) is parti-
3
cularly revealing, as it becomes clear that the previously
nonclassifiable, twisted conformer 20 is not part of the
channel forming structure but serves to fill space, separating
sheets of parallel channels and propping the almost flat
DEMs 2 apart to accommodate the solvent molecules. The
two independent DEMs 8 and 80 (two and a half DEMs in the
to back ππ interactions. CH O distances (summarized
3 3 3
in Table 4) are longer and an unusual “in registration”
arrangement of the overlapped unsaturated systems occurs
(Figure 10).
The extra solvent molecules, 2CH2Cl2 and toluene, in 1
and 13, respectively, appear to fill cavities in the structure,
and an isomorphous solvate structure of 13 CH2Cl2
ASU) both adopt the open annulus shape in the 8 2CH2Cl2
3
3
3
Table 5. Summary of CH O Interactions in 2 and 8
3 3 3
EtOAc, where a molecule of ethyl acetate adopts the position
of toluene, has also been isolated (not reported here).
Channels. The two conformational types leading to chan-
nel type structures are quite different: E results from parallel
offset CdO groups, while F results from CdO groups
˚
˚
C-H
O
d(H A)/A d(D A)/A —DHA/deg
3 3 3
3 3 3
3 3 3
2
8
1
1
2
C1G-H1GB O1
2.65
2.29
2.30
3.513(7)
3.125(4)
3.124(4)
146
142
141
3 3 3
O1
C1G-H1G0
3 3 3
C2G-H2G O10
3 3 3
Figure 11. Packing diagrams of (a) 2 CH2Cl2 and (b) 8 2CH2Cl2, both viewed down [1 0 0]. In part a, channels formed by 2 and
3
3
accommodating CH2Cl2 molecules are clearly visible, while 20, depicted in dark gray, does not participate in channel formation. In part b,
both DEMs (two and a half DEMs in the ASU) form channels. Close CH O contacts between CH2Cl2 molecules and CdO groups are shown
in the insets.
3 3 3
Figure 12. (a) Overlapping DEMs in (s,s)-6 11/2p-xylene. One DEM is illustrated with CPK coloring, while the second symmetry generated
DEM is depicted in dark gray. CH O close contacts are indicated with dotted lines, and all disordered groups are shown. Note that flexible
3
3 3 3
linker disorder results in alternate C-H O interactions between CH2 and CdO groups. (b) Overlapping DEMs with one molecule depicted
as its Hirshfeld surface. The bulge due to flexible linker puckering fits into the cavity of the neighboring macrocycle. (c) Pairs of DEMs
3 3 3
overlapped as illustrated in parts a and b exhibit ππ stacking with neighboring pairs.

2416 Crystal Growth & Design, Vol. 10, No. 5, 2010
Higham et al.
Figure 13. Packing diagrams of (a) (s,s)-5 C6H5Cl viewed down [0 1 -1] (top) and rotated; (b) (s,s)-6 11/2p-xylene viewed down [1 1 0] and
3
3
rotated; (c) 10 1/2CHCl3 H2O viewed down [0 0 -1] and rotated; (d) 11 p-xylene 11/2H2O viewed down [0 0 1] and rotated. In all cases
3
3
3
3
included, solvent molecules have been removed for clarity (except the strongly hydrogen bonded water molecules in parts c and d), and one or
two pairs of DEMs are depicted in space filling mode with an arrow to indicate the direction of view of the rotated layer below each packing
diagram. The DEMs depicted in parts b, c, and d tend to form puckered sheets, and only one sheet is depicted in each case;the subsequent layer
is offset such that hollows and humps are suitably aligned. Conversely, (s,s)-5 (in the structure of the chlorobenzene solvate) (a) does not form
puckered sheetlike structures of similarly orientated DEMs but has alternating rows of pairs forming sheets of variable thickness. Solvent
molecules fill spaces left by imperfect packing or even fill cavities in sheets, as in part b, where the hatched circle demarcates a solvent position.
solvate (Figure 11b). Describing these as channel forming
may be a little misleading, as the channel walls result from
intercalation of side chains (8 2CH2Cl2) or rings and side
occurs. The constricted channels of 8 are reflected in a
relatively high guest loss temperature, as measured by ther-
mogravimetric analysis, where DCM solvent is lost in the
range 80-120 ꢀC. This is reflected in the stability of this
3
chains (2 CH2Cl2), and the open annulus forming conforma-
3
tion of the DEM. In common with other CH2Cl2 solvates,
close contacts between solvent hydrogen atoms and DEM
oxygen atoms are noted, as depicted in the inset close-ups in
Figure 11 and listed in Table 5.
complex, with single crystals of 8 2CH2Cl2 showing no loss
3
of crystallinity when exposed to the atmosphere for a lengthy
period.
CH OdC interactions. The most commonly encoun-
3 3 3
These two conformer type E channel structures differ from
that of 4 in the F conformer previously published,14 where
the channel walls are largely due to the truncated conelike
shape of the DEM resulting from twisting of the CdO
groups out of the hollow of the V and true cavity inclusion
tered conformer type in these DEM solvate crystals is the A
type, where both carbonyl groups are rotated into the hollow
of the V of the folded DEM. In all cases, these DEMs pack
together in pairs with a side chain of one protruding into the
hollow of its neighbor, as is illustrated for the (s,s)-isomer of

Article
Crystal Growth & Design, Vol. 10, No. 5, 2010 2417
6 in the p-xylene solvate (Figure 12). This results in hydrogen
atoms of flexible linker methylene groups coming into
relatively close contact with DEM carbonyl group oxygen
atoms.
possible importance of this relatively weakly attractive inter-
action in the absence of other stronger interactions, such as
traditional hydrogen bonds. The C-H OdC supramole-
3 3 3
cular synthon may reflect either classical, weak CH
hydrogen bonding or the less oft discussed electrostatic
O
3 3 3
This motif of overlapped complementarily shaped DEMs
in the A type conformer with CH OdC close contacts is
interaction between somewhat acidic protons and π systems,
3 3 3
repeated in (s,s)-5 C6H5Cl, 10 1/2CHCl3 H2O, and 11
i.e. C-H π(OdC).20 We have tended to focus on the
3
3
3
3
3 3 3
p-xylene 11/2H2O, but the interactions and relative orienta-
tions of neighboring pairs of DEMs differ markedly from
structure to structure, as is illustrated in the partial packing
diagrams (Figure 13). A summary of CH O close contacts
is provided in Table 6. Clearly, the differing shapes of the
DEMs provide (or frustrate) opportunities for a series of
CH O interactions both with oxygen atoms of the carbo-
nyl groups (used to categorize this group of structures) and of
the ethereal flexible linkers. In some cases, packing of
neighboring sheets or pairs of DEMs is such that further
former as a defining interaction in this group of structures,
but it is certain that there is also an element of the latter in
many cases.
3
It is notable that the hydrate forms, 10 1/2CHCl3 H2O
3 3 3
3
3
and 11 p-xylene 11/2H2O, both adopt the A conformer,
form dimers with CH OdC close contacts, and pack in
3
3
3 3 3
puckered sheetlike structures. In the solid state, the bridging
water molecule serves to lock the DEM into the A conformer
and one might expect some evidence of dimerization in
solutions containing small quantities of water, similar to
that detected in the Horning-crown macrocycles derived
from these DEMs.21 In this regard, it is noteworthy that
the “(s,s)” and “(s,r)” forms are readily distinguishable by
3 3 3
CH O close contacts are possible (Table 6), indicating the
3 3 3
Table 6. Summary of CH O Interactions in (s,s)-5, (s,s)-6, 10, and 11
3 3 3
1
analysis of H NMR spectra, which may be indicative that
solid state conformers are propagated in solution.
C-H Oa
d(H A)/A d(D A)/A —DHA/deg
˚
˚
3 3 3
3 3 3
3 3 3
5
C18-H18Ba O4
2.43
2.64
2.66
2.34
2.58
2.75
2.71
2.52
2.55
2.65
2.80
2.68
2.44
2.65
2.84
2.60
2.36
2.78
2.66
2.64
2.31
2.63
3.253(3)
3.253(3)
3.574(3)
3.236(3)
3.380(6)
3.632(7)
3.589(5)
3.403(5)
3.440(3)
3.465(3)
3.700(4)
3.672(3)
3.281(3)
3.426(3)
3.764(3)
3.465(5)
3.251(5)
3.581(5)
3.402(5)
3.47(1)
140
142
163
158
138
149
154
154
150
140
152
178
147
140
165
146
150
138
132
142
164
136
Self-inclusion. The “odd one out” in this collection of
structurally diverse, yet related, DEM structures is that of
the nonsolvated 9. Not only is solvent not trapped in the
structure, but the DEM adopts a conformation not seen in
any of the other examples, that of the parallel offset CdO
groups and parallel offset aryl rings, type D.
The extended, flexible ethoxyl substituents of the DEM
corner groups become self-included into the annulus of a
neighboring macrocycle, thus forming interlocking sheets of
DEMs that pack together efficiently without inclusion of
space filling solvent molecules (Figure 14).
3 3 3
C18-H18Aa O6
3 3 3
C40-H40a O2
3 3 3
C29-H29b O1
3 3 3
6
C7-H7Ac O1
3 3 3
C7-H7Bc O3
3 3 3
C29-H29c O5
3 3 3
C30-H30c O6
3 3 3
10
C6-H6Ad O4
3 3 3
C7-H7Ad O1
3 3 3
C18-H18B O7
3 3 3
C19-H19Be O1
3 3 3
C27-H27f O7
3 3 3
C31-H31d O6
3 3 3
C43-H43e O4
3 3 3
11
C6-H6Bg O2
3 3 3
Conclusions
C6-H6Ag O4
3 3 3
C6-H6Ag O1W
3 3 3
The modular building-block approach to the synthesis of
dienone-ether macrocycles provides simple, direct synthetic
access to a range of macrocyclic structures. The ease with
which components may be altered to provide materials bear-
ing substituents on any of the ringcomponents or withvarious
linker lengths makes the task of designing a DEM for a
particular application a simple task. In addition, numerous
commercially available starting materials are available for this
C7-H7Ag O1
3 3 3
C17-H6Ch O6
3 3 3
C18-H18Dh O5
3.27(1)
3.382(5)
3 3 3
C30-H30g O5
3 3 3
a Symmetry operations used to define atoms: (a) -x, 1 - y, 1 - z;
(b) x, 1/2 - y, z - 1/2; (c) 1 - x, 1 - y, -z; (d) 2 - x, -y, -z; (e) 21/2 - x,
y - 1/2, 1/2 - z; (f) 21/2 - x, 1/2 þ y, 1/2 - z; (g) 1 - x, 3 - y, -z - 1; (h) -x,
3 - y, -z - 1.
Figure 14. Packing diagrams of 9 viewed down [1 0 0] (left) and [0 1 0] (right). Only one layer is shown at left, but at right, the stacking of layers is
depicted. For clarity, alternate DEMs are picked out in darker shades, but note that all molecules are symmetry related and that the ASU
contains half a DEM only.

2418 Crystal Growth & Design, Vol. 10, No. 5, 2010
Higham et al.
synthetic protocol, allowing tuning of the molecular structure
or exploration of molecular space by combinatorial array
techniques.
5: (14S,29S)/(14S,29R) Isomeric Mixture of (1E,11E,16E,26E)-
3,4:9,10:18,19:24,25-Tetrabenzo-14,29-dimethyl-5,8,20,23-tetraoxa-
tricyclo[25.3.1.112,16]dotriaconta-1,3,9,11,16,18,24,26-octaene-31,32-
dione. Orange solid; mp 295-296 ꢀC; νmax/cm-1 (neat) 1665w (CdO),
1596m (olefinic CdC); δH (400 MHz; CF3COOD) 9.10 and 9.04
(1.00:0.16; 4H, s, CH), 7.71-7.60 (16 H, m, Ar), 7.25-7.18 (16 H,
m, Ar), 4.74 (16 H, m, OCH2), 3.31-3.25 (8 H, m, CH2), 2.70-2.56
(8 H, m, CH2), 2.17-1.98 (4 H, m, CH), 1.24-1.20 (12 H, m, CH3); δC
(100 MHz; CF3COOD) 198.1, 197.3, 160.3, 160.1, 146.9, 146.6, 136.5,
136.3, 136.1, 136.0, 133.7 (2C), 127.0, 126.9, 124.0, 123.9, 115.3, 115.0,
68.9, 68.5, 37.9, 37.1, 31.8, 31.0, 21.8, 21.4; m/z (ESI) 715.3025 (M þ
Naþ, 100%; C46H44NaO6þ requires 715.3036).
The supramolecular versatility of these materials has also
been demonstrated, and this, combined with the relative
simplicity and potential greenness of the synthetic method,
renders these DEMs appropriate starting materials for the
supramolecular, “bottom-up” approach to the development
of new crystalline materials. The terms “design” or “designer”
have been widely applied to describe macrocycles with vari-
able shapes, sizes, or functional groups that are readily altered
either during synthesis or by post synthetic modification. This
work indicates that DEMs are equally, if not more, amenable
to genuine design for function. Significantly, these macro-
cycles are complementary to the well-known calixarene,
resorcinarene, and crown ether groups that have been
investigated actively for decades in that regard.
6: (14S,29S)/(14S,29R) Isomeric Mixture of (1E,11E,16E,26E)-
3,4:9,10:18,19:24,25-Tetrabenzo-14,29-di-tert-butyl-5,8,20,23-tetra-
oxatricyclo[25.3.1.112,16]dotriaconta-1,3,9,11,16,18,24,26-octaene-31,
32-dione. Yellow solid; mp 297-298 ꢀC; νmax/cm-1 (neat) 1670w
(CdO), 1596s (olefinic CdC); δH (400 MHz; CF3COOD) 8.94
(8.86) (4 H, s, CH), 7.66-7.53 (16 H, m, Ar), 7.20-7.11 (16 H, m,
Ar), 4.64 (16 H, m, OCH2), 3.30-3.23 (8 H, m, CH2), 2.53-2.44 (8
H, m, CH2), 1.59-1.52 (4 H, m, CH), 0.94-0.93 (18 H, m, CH3); δC
(100 MHz; CF3COOD) 198.8, 197.6, 160.6, 160.4, 146.5 (2C), 146.5,
137.2, 137.0, 136.8, 136.6, 133.8, 133.7, 127.2, 127.1, 124.3, 124.2,
115.7, 115.5, 69.4, 68.9, 34.1, 34.0, 31.2, 31.1, 28.4, 28.2, 28.0, 27.6;
m/z (ESI) 799.3959 (M þ Naþ; C52H56NaO6þ requires 799.3975).
7: (14S,29S)/(14S,29R) Isomeric Mixture of (1E,11E,16E,26E)-
3,4:9,10:18,19:24,25-Tetrabenzo-14,29-diphenyl-5,8,20,23-tetraoxa-
tricyclo[25.3.1.112,16]dotriaconta-1,3,9,11,16,18,24,26-octaene-31,32-
dione. Yellow powder; mp 278-279 ꢀC; νmax/cm-1 (neat) 1660w
(CdO), 1595s (olefinic CdC); δH (300 MHz; CF3COOD) 9.22 and
9.12 (1.00:0.20; 4H, s, CH), 7.66 (8 H, m, Ar), 7.36 (12 H, m, Ar),
7.21 (8 H, m, Ar), 4.78 and 4.73 (8H, s, CH2), 3.52 and 3.50 (4H, s,
CH), 3.19 and 3.17 (8H, s, CH2); δC (75 MHz; CF3COOD) 185.9,
184.8, 148.7, 148.4, 135.5, 135.2, 133.6, 133.3, 125.0, 124.7, 124.1,
124.0, 122.1 (2C), 119.0 (2C), 117.4, 117.3, 116.7, 116.6, 115.1 (2C),
112.4, 112.2, 103.7, 103.4, 57.3, 56.8, 31.2, 30.1, 25.6, 24.7; m/z (ESI)
817.3522 (M þ Hþ; C56H49O6þ requires 817.3580).
In addition, as we have described previously,15 all of these
DEMs are readily converted into Horning-crowns: flexible,
phenol-ether macrocycles with demonstrated flexibility and
switchability, so extending the range of supramolecular build-
ing blocks or ligands available for the preparation of crystal-
line materials.
Experimental Section
Synthesis. The syntheses of DEMs 4, 10, 11, and 12 have been
previously reported, and full characterization data are contained in
refs 12 and 13. Synthesis of macrocycle 2 is provided as a repre-
sentative example of all DEM syntheses; detailed syntheses of other
DEMs can be found in the Supporting Information. Characteriza-
tion data of all new DEMs is reported below.
2: (1E,11E,15E,25E)-3,4:9,10:17,18:23,24-Tetra(6-methoxybenzo)-
5,8,19,22-tetraoxatricyclo[24.2.1.112,15]triaconta-1,3,9,11,15,17,23,
25-octaene-29,30-dione. A mixture of 2,20-(ethane-1,2-diylbis(oxy))-
bis(3-methoxybenzaldehyde) (0.782 g, 2.37 mmol) and cyclopenta-
none (0.299 g, 3.55 mmol) in 96% EtOH (120 mL) and 20% w/v aq
NaOH (3.6 mL, 18 mmol) was stirred at rt for 3 days. The orange
solid that had precipitated was collected by vacuum filtration,
washed with 1.0 M HCl (2 ꢀ 5 mL), water (2 ꢀ 5 mL) and 96%
EtOH (2 ꢀ 5 mL), and dried under vacuum (0.728 g). The solid was
recrystallized from CH2Cl2 (40 mL) to give the dienone macrocycle
2 (0.283 g, 0.374 mmol, 32%) as a yellow solid; mp 296-298 ꢀC.
Anal. Found: C, 72.7; H, 5.7. Calcd for C46H44O10: C, 73.0; H, 5.9.
8: (1E,11E,16E,26E)-3,4:9,10:18,19:24,25-Tetra(6-methoxybenzo)-
5,8,20,23-tetraoxatricyclo[25.3.1.112,16]dotriaconta-1,3,9,11,16,18,24,-
26-octaene-31,32-dione. Yellow solid; mp 243-244 ꢀC; νmax/cm-1
(neat) 1666w (CdO), 1573m (olefinic CdC); δH (300 MHz; CDCl3)
7.95 (4H, s, CH), 7.04 (4H, dd, J 8.1 and 7.9, Ar), 6.92 (4H, dd, J 7.9
and 1.4, Ar), 6.90 (4H, dd, J 8.1 and 1.4, Ar), 4.31 (8H, s, OCH2),
3.88 (12H, s, OCH3), 2.82 (8H, m, CH2), 1.77 (4H, m, CH2); δC (75
MHz, CDCl3) 189.9, 153.0, 148.1, 137.7, 132.6, 131.0, 123.5, 122.6,
113.1, 72.6, 56.2, 29.2, 23.6; m/z (ESI) 785.3323 (M þ Hþ, 100%;
C
48H49O10þ requires 785.3320).
9: (1E,11E,16E,26E)-3,4:9,10:18,19:24,25-Tetra(6-ethoxybenzo)-
5,8,20,23-tetraoxatricyclo[25.3.1.112,16]dotriaconta-1,3,9,11,16,18,-
24,26-octaene-31,32-dione. Yellow solid, mp 262-265 ꢀC; found: C,
74.2; H, 6.5. C52H56O10 requires C, 74.3; H, 6.7%; νmax/cm-1 (neat)
1665w (CdO), 1572s (olefinic CdC); δH (300 MHz; CDCl3) 7.94
(4 H, s, CH), 7.00 (4 H, dd, J 8.0 and 7.8, Ar), 6.91 (4 H, dd, J 7.8 and
1.4, Ar), 6.88 (4 H, dd, J 8.0 and 1.4, Ar), 4.33 (s, 8 H, OCH2), 4.07
(8 H, q, J 7.0, OCH2CH3), 2.80 (8 H, m, CH2), 1.76 (4 H, m, CH2),
1.43 (12 H, t, J 7.0, CH3); δC (100 MHz; CDCl3) 189.8, 152.1, 148.2,
137.7, 132.6, 131.2, 123.3, 122.6, 114.3, 72.4, 64.7, 29.2, 23.5, 15.1;
m/z (ESI) 841.5 (M þ Hþ, 79%).
δ
H (300 MHz; CDCl3) 7.87 (4 H, s, CH), 7.14 (4 H, dd, J 7.9 and 1.4,
Ar), 7.06 (4 H, dd, J 8.1 and 7.9, Ar), 6.92 (4 H, dd, J 8.1 and 1.4, Ar),
4.31 (8 H, s, OCH2), 3.88 (12 H, s, OCH3), 2.99 (8 H, s, CCH2); δC
(100 MHz; CDCl3) 195.7, 153.0, 148.4, 139.5, 131.0, 128.2, 123.8,
122.2, 113.5, 72.6, 52.2, 26.9; m/z (ESI) 779.4 (M þ Naþ, 100%),
757.5 (M þ Hþ, 93).
1: (1E,11E,15E,25E)-3,4:9,10:17,18:23,24-Tetrabenzo-5,8,19,22-
tetraoxatricyclo[24.2.1.112,15]triaconta-1,3,9,11,15,17,23,25-octaene-
29,30-dione. Yellow solid; mp (dec.) 230 ꢀC; νmax/cm-1 (neat) 1687w
(CdO), 1617m (olefinic CdC); δH (300 MHz; CDCl3) 7.88 (4 H,
s, CH), 7.51-7.47 (4 H, m, Ar), 7.34-7.24 (4 H, m, Ar), 7.01-6.89
(4 H, m, Ar), 4.45 (8 H, s, OCH2), 2.95 (8 H, s, CCH2); δC (75 MHz;
CF3COOD) 200.7, 161.9, 142.9, 138.2, 137.9, 133.9, 126.9, 124.5,
115.3, 69.1, 29.5; m/z (ESI) 659.3 (M þ Naþ, 100%); m/z (ESI)
659.2415 (M þ Naþ, 100%; C42H36NaO6þ requires 659.2398).
3: (1E,11E,15E,25E)-3,4:9,10:17,18:23,24-Tetra(6-ethoxybenzo)-
5,8,19,22-tetraoxatricyclo[24.2.1.112,15]triaconta-1,3,9,11,15,17,23,25-
octaene-29,30-dione. Yellow solid; mp 257-258 ꢀC; νmax/cm-1 (neat)
1692w (CdO), 1608m (olefinic CdC); δH (300 MHz; CDCl3) 7.91
(4 H, s, CH), 7.15 (4 H, dd, J 7.9 and 1.4, Ar), 7.04 (4 H, dd, J 8.1 and
7.9, Ar), 6.90 (4 H, dd, J 8.1 and 1.4, Ar), 4.35 (8 H, s, OCH2), 4.08
(8 H, q, J 7.0, OCH2CH3), 3.01 (8 H, s, CCH2), 1.47 (12 H, t, J 7.0,
CH3); δC (100 MHz; CF3COOD) 195.0, 145.7, 144.4, 133.7 (2C),
131.9, 123.1, 119.4, 117.0, 70.1, 59.6, 21.2, 7.6; m/z (ESI) 835.3 (M þ
13: (1E,11E,16E,26E)-3,4:9,10:18,19:24,25-Tetrabenzo-14,29-di-
methyl-5,8,20,23-tetraoxa-14,29-diazatricyclo[25.3.1.112,16]dotriaconta-
1,3,9,11,16,18,24,26-octaene-31,32-dione. Yellow solid, mp (dec.)
245 ꢀC; νmax/cm-1 (neat) 2772w (N;Me), 1668w (CdO), 1596m
(olefinic CdC); δH (300 MHz; CDCl3) 8.13 (4 H, s, CH), 7.32-7.27
(4 H, m, Ar), 7.21-7.18 (4 H, m, Ar), 6.99-6.94 (4 H, m, Ar),
6.91-6.88 (4 H, m, Ar), 4.46 (8 H, s, OCH2), 3.71 (8 H, s, CCH2),
2.36 (6 H, s, CH3); δC (75 MHz; CF3COOD) 188.2, 187.8, 159.4,
159.3, 145.7, 145.3, 136.1 (2C), 136.1, 132.9, 132.8, 126.9, 126.6,
124.5 (2C), 124.0 (2C), 115.2 (2C), 68.6, 68.3, 57.9, 57.7, 45.1, 44.9;
m/z (ESI) 717.4 (M þ Naþ, 100%), 1411.5 (2 M þ Naþ, 87). m/z
(ESI) 695.3133 (M þ Hþ, 100%; C44H43N2O6þ requires 695.3116).
14: (1E,13E,18E,30E)-3,4:8,9:20,21:28,29-Tetrabenzo-5,10,22,27-
tetraoxatricyclo[29.3.1.114,18]hexatriaconta-1,3,11,13,18,20,28,30-
octaene-35,36-dione. Yellow solid; mp 246-247 ꢀC; νmax/cm-1
(neat) 1662w (CdO), 1596s (olefinic CdC); δH (400 MHz; CDCl3)
Naþ, 100%); m/z (ESI) 813.3624 (M þ Hþ, 100%; C50H53O10
þ
requires 813.3679).

Article
Crystal Growth & Design, Vol. 10, No. 5, 2010 2419
Crystal Data for 13 CH2Cl2 Toluene. CCDC deposition number
8.03 (4 H, s, CH), 7.34-7.31 (4 H, m, Ar), 7.29-7.25 (4 H, m, Ar),
6.95-6.92 (4 H, m, Ar), 6.90-6.87 (4 H, m, Ar), 4.08 (8 H, t, J 6.2,
OCH2), 2.87 (8 H, m, CCH2), 2.06 (8 H, t, J 6.0, OCH2CH2), 1.77 (4
H, m, CH2); δC (100 MHz; CDCl3) 190.1, 158.1, 136.3, 132.7, 130.7,
130.0, 125.8, 120.1, 111.9, 68.2, 29.4, 25.9, 23.8; m/z (ESI) 743.3351
(M þ Naþ, 100%; C48H48NaO6þ requires 743.3349).
3
3
757274, C44H42O6N2 CH2Cl2 C6H5CH3, Mr = 871.86, triclinic,
3
3
˚
˚
˚
space group P1, a=10.816(2) A, b=13.601(3) A, c=15.868(3) A,
3
˚
R=102.67(3)ꢀ, β=90.47(3)ꢀ, γ=102.84(3)ꢀ, V=2217(1) A , Z=2,
D
calc=1.306 g cm-3, μ(Mo KR)=0.200 mm-1. Of 10598 unique
3
reflections measured, 4923 had I > 2σ(I), R indices [I > 2σ(I)] R1=
0.0661, wR2=0.1691, GoF on F2=0.988 for 560 refined parameters
and six restraints.
Crystallography. Crystals suitable for single crystal X-ray dif-
fraction experiments were grown by slow cooling or slow evapora-
tion of solutions of the DEM. Data were collected on a Bruker
Kappa Apex CCD diffractometer at 123 K using graphite mono-
1 2CH2Cl2. DEM 1 crystallizes from dichloromethane solution
3
as a 1:2 solvate in the triclinic crystal system and space group P1.
There are two complete DEMs and four solvent molecules in the
ASU. One DEM exhibits disorder of the corner aromatic moiety
and associated ether flexible linker and is modeled over two posi-
tions with site occupancy factors (sof’s) of 0.6 and 0.4 for major and
minor components. Atoms of both aryl ring components and the
minor component of the flexible ether side chain are modeled
isotropically, while all other DEM non-hydrogen atoms are allowed
to refine anisotropically. Two CH2Cl2 solvent molecules are also
modeled as disordered: one with three possible positions for the Cl
atoms (0.4, 0.3, and 0.3 sof) but a common CH2 position, and a
second over three possible positions (0.5, 0.25, and 0.25) with a
common Cl atom position for the 0.25 occupancy components.
Temperature factors of disordered non-hydrogen atoms are refined
isotropically. Appropriate DFIX restraints are applied to C-C and
C-Cl bond lengths of disordered aryl groups and solvent molecules.
˚
chromated Mo KR radiation (λ=0.71073 A, 0.5ꢀ or 1ꢀ j and ω scans
as appropriate). Structures were solved by direct methods using the
program SHELXS-97and refined by full matrix least-squares re-
finement on F2 using the programs SHELXS-97 and SHELXL-9722
with gui X-Seed.23 Generally, non-hydrogen atoms of the hosts were
refined anisotropically and hydrogen atoms inserted in geometri-
cally determined positions with temperature factors fixed at 1.2
times that of the parent atom. Hydrogen atoms of the hydroxyl
groups were located from electron density difference maps and
refined. Specific details pertaining to each crystal structure solution
and refinement are summarized below.
Crystal Data for 1 2CH2Cl2. CCDC deposition number 757267,
3
(C42H36O6)2 (CH2Cl2)4, Mr=1613.12, triclinic, space group P1, a=
3
˚
˚
˚
14.4827(4) A, b=16.0400(4) A, c=19.258(1) A, R=68.049(1)ꢀ,
3
˚
β=87.473(1)ꢀ, γ=68.047(2)ꢀ, V=3824.6(2) A , Z=2, Dcalc=1.401 g
3
cm-3, μ(Mo KR) = 0.360 mm-1. Of 14274 unique reflections
measured, 7160 had I > 2σ(I), R indices [I > 2σ(I)], R1=0.0719,
wR2=0.1383, GoF on F2=1.017 for 994 refined parameters and 10
restraints.
2 CH2Cl2. DEM 2 crystallizes from dichloromethane solution as
3
a 1:1 solvate in the triclinic crystal system and space group P1. There
are two and a half DEMs and one complete solvent molecule in the
ASU. All non-hydrogen atoms are refined anisotropically.
Crystal Data for 2 CH2Cl2. CCDC deposition number 757268,
C46H44O10 CH2Cl2, Mr = 841.74, triclinic, space group P1, a =
8.8260(5) A, b= 13.737(1) A, c= 18.333(2) A, R= 69.160(7)ꢀ, β=
(s,s)-5 C6H5Cl. The (s,s) (with respect to the Me groups of the
3
3
cyclohexanone moiety) form of DEM 5 crystallizes from chloro-
benzene solution as a 1:1 solvate in the monoclinic crystal system
and space group P21/c. There is one complete DEM and one
complete (disordered) solvent molecule in the ASU. One DEM
methyl group is disordered and modeled over two positions with
sof’s 0.6 and 0.4. These disordered carbon atoms are refined
isotropically as are all carbon atoms of the disordered chloroben-
zene solvent, which is rotationally disordered and modeled over
three positions, with three orientations for the Cl atom and asso-
ciated in-plane displacement of the aryl rings. Sof’s are fixed at 0.5,
0.3, and 0.2 for the different positions and the aryl rings restrained to
be regular hexagons.
3
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˚
˚
3
80.028(4)ꢀ, γ=89.354(2)ꢀ, V=2042.8(3) A , Z=2, Dcalc=1.368 g cm-3
,
˚
3
μ(Mo KR)=0.220 mm-1. Of 9297 unique reflections measured, 2702
had I > 2σ(I), R indices [I > 2σ(I)], R1=0.0854, wR2=0.1487, GoF on
F2=0.966 for 536 refined parameters and 0 restraints.
Crystal Data for (s,s)-5 C6H5Cl. CCDC deposition number
3
757269, C46H44O6 C6H5Cl, Mr=805.36, monoclinic, space group
˚
3
˚
˚
P21/c, a = 16.4092(3) A, b = 16.9899(3) A, c = 17.0534(4) A, β =
116.98(3)ꢀ, V=4237.0(2) A , Z=4, Dcalc=1.263 g cm-3, μ(Mo KR)=
3
˚
3
0.142 mm-1. Of 10313 unique reflections measured, 5258 had I >
2σ(I), R indices [I > 2σ(I)], R1=0.0631, wR2=0.1157, GoF on F2=
1.015 for 545 refined parameters and 0 restraints.
(s,s)-6 11/2p-Xylene. The (s,s) (with respect to the t-Bu groups
3
Crystal Data for (s,s)-6 11/2p-Xylene. CCDC deposition num-
of the cyclohexanone moiety) form of DEM 6 crystallizes from
p-xylene solution as a 1:1.5 solvate in the triclinic crystal system and
space group P1. There is one complete DEM and one and a half
xylene molecules in the ASU, with the half xylene molecule centered
3
ber 757270, C52H56O6 (C8H10)3/2, Mr = 936.21, triclinic, space
˚
group P1, a=12.4050(4) A, b=13.7850(4) A, c=16.6000(4) A,
3
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˚
3
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R=78.930(2)ꢀ, β=71.360(2)ꢀ, γ=80.000(2)ꢀ, V=2620.4(1) A , Z=2,
1
D
calc=1.187 g cm-3, μ(Mo KR)=0.074 mm-1. Of 12581 unique
on special position 0, 0, /2. Both t-Bu-cyclohexyl moieties of the
3
reflections measured, 5356 had I > 2σ(I), R indices [I > 2σ(I)], R1=
0.0902, wR2=0.2149, GoF on F2=1.044 for 632 refined parameters
and 45 restraints.
DEM are disordered over two positions, with sof’s of 0.7 and 0.3
resulting from rotation of the t-Bu group and displacement of
carbon atoms 3 and 4 of the cyclohexyl ring. The disorder does
not reflect inclusion of (s,r)-6 but instead results from a lesser
component of “reverse folded” (s,s)-6, i.e. with the out-of-plane
carbon atoms of the envelope conformer of the t-Bu-cyclohexyl
group pointing downward with respect to the V of the folded DEM
and the t-Bu groups pointing upward. The large bulk of the t-Bu
group means that the space occupied by these two conformers is
similar.
Crystal Data for 8 2CH2Cl2. CCDC deposition number 757271,
48H48O10 (CH2Cl2)2, Mr=954.72, monoclinic, space group P21/n,
3
C
3
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˚
˚
a=7.8629(3) A, b=19.818(1) A, c=29.592(1) A, β=92.019(3)ꢀ, V=
3
4608.4(3) A , Z=4, Dcalc=1.376 g cm-3, μ(Mo KR)=0.316 mm-1
.
˚
3
Of 9432 unique reflections measured, 4889 had I > 2σ(I), R indices
[I > 2σ(I)], R1=0.0615, wR2=0.1086, GoF on F2=1.016 for 581
refined parameters and 0 restraints.
Crystal Data for 9. CCDC deposition number 757272,
(C52H56O10)1/2, Mr=420.48, orthorhombic, space group Pbca, a=
8 2CH2Cl2. DEM 8 crystallizes from dichloromethane solution as
3
a 1:2 solvate in the monoclinic crystal system and space group P21/n.
There are two and a half DEMs and two complete solvent molecules
in the ASU. All non-hydrogen atoms are refined anisotropically.
9. DEM 9 crystallizes nonsolvated from toluene solution in
the orthorhombic crystal system and space group Pbca. There is a
half DEM in the ASU, and all non-hydrogen atoms are refined
anisotropically.
3
16.9103(5) A, b=14.9230(4) A, c=17.4123(6) A, V=4394.0(2) A ,
˚
˚
˚
˚
Z=8, Dcalc =1.271 g cm-3, μ(Mo KR)=0.087 mm-1. Of 5097
3
unique reflections measured, 2256 had I > 2σ(I), R indices [I > 2σ(I)],
R1 = 0.0488, wR2 = 0.0974, GoF on F2 = 0.881 for 282 refined
parameters and 0 restraints.
Crystal Data for 11 1/2p-Xylene 11/2H2O. = CCDC deposition
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number 757273, C46H44O7 (C8H10)1/2
monoclinic, space group P21/c, a= 15.7880(3) A, b= 15.1484(3)
(H2O)3/2, Mr = 788.92,
˚
11 p-Xylene 11/2H2O. DEM 11 crystallizes as a mixed solvate
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3
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from wet p-xylene solutions in the monoclinic crystal system and
space group P21/c. There is one complete DEM, one and a half
water molecules, and two and a half p-xylene molecules in the ASU.
The p-xylene solvent is disordered and two and a half molecules are
modeled with aryl rings approximately centered on the spe-
cial position 0, 0, 1/2, resulting in two overlapping positions for
3
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˚
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A, c=17.6179(6) A, β=98.792(1)ꢀ, V=4164.0(2) A , Z=4, Dcalc
=
1.258 g cm-3, μ(Mo KR)=0.085 mm-1. Of 10142 unique reflections
3
measured, 4331 had I > 2σ(I), R indices [I > 2σ(I)], R1=0.0896,
wR2=0.2048, GoF on F2=1.031 for 532 refined parameters and 16
restraints.

2420 Crystal Growth & Design, Vol. 10, No. 5, 2010
Higham et al.
the p-xylene solvent. The longer of the flexible ether linkers is
disordered in one -CH2CH2- group, with two equally occupied
positions modeled. A water molecule, present at 0.5 occupancy, is
associated with one of these positions and is within hydrogen
bonding distance of the water molecule that forms a hydrogen bond
bridge between the two CdO groups. All disordered atoms are
refined isotropically while all other non-hydrogen atoms are refined
anisotropically. Bond length restraints are applied by use of appro-
priate DFIX cards to disordered moieties.
Springer-Verlag: Berlin, Heidelberg, New York, 2004; Vol. 111,
pp 139-174.
(4) First prepared in 1905: Behrend, R.; Meyer, E.; Rusche, F. Justus
Liebigs Ann. Chem. 1905, 339, 1. and named after their pumpkin
shape: Mock, W. L. Top. Curr. Chem. 1995, 175, 1. Cucurbiturils have
been recently reviewed: Lagona, J.; Mukhopadhyay, P.; Chakrabarti,
S.; Isaacs, L. Angew. Chem., Int. Ed. 2005, 44, 4844. These molecules
often require functionalization: Lee, J. W.; Samal, S.; Sawapalam, N.;
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(5) Crown ethers were first synthesized by Pedersen in the 1960s:
Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 2495. and by Pedersen,
C. J. J. Am. Chem. Soc. 1967, 89, 7017. And they have been widely
used as metal complexing agents and supramolecular tectons ever since.
Diverse recent applications include components of supramolecular
daisy chains: Cantrill, S. J.; Youn, G. J.; Stoddart, J. F.; Williams,
D. J. J. Org. Chem. 2001, 66, 6857. and “molecular meccano”:
Cantrill, S. J.; Fulton, D. A.; Heiss, A. M.; Pease, A. R.; Stoddart,
J. F.; White, A. J. P.; Williams, D. J. Chem.;Eur. J. 2000, 6, 2274.
while metal complexation by crown ether moieties enables the con-
struction of electroactive polymers: Fabre, B.; Simonet, J. Coord.
Chem. Rev. 1998, 178, 1211. and organic/inorganic hybrid materials:
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13 CH2Cl2 Toluene. DEM 13 crystallizes as a mixed solvate
3
3
from dichloromethane/toluene solutions in the triclinic crystal
system and space group P1. There is one complete DEM, one
toluene, and one CH2Cl2 molecule in the ASU, no disorder is noted,
and all non-hydrogen atoms are refined anisotropically.
Acknowledgment. We acknowledge funding from the
Australian Research Council (ARC).
Supporting Information Available: Experimental details and
characterization data (including NMR spectra and ORTEP dia-
grams) for all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
(6) Ronson, T. K.; Hardie, M. J. CrystEngComm 2008, 10, 1731.
€
(7) Busi, S.; Saxell, H.; Frohlich, R.; Rissanen, K. CrystEngComm
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