Wurster's crownophanes: An alternate topology for para-phenylenediamine- based macrocycles

Article abstract of DOI:10.1016/j.tet.2005.09.091

Six redox-active cyclophane/crown hybrid molecules (crownophanes) were prepared via cyclization reactions involving N,N′-dimethyl-p- phenylenediamine and tosylated oligoethylene glycols of varying length. These new host molecules differ from other phenyle

Full text of DOI:10.1016/j.tet.2005.09.091

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Tetrahedron 61 (2005) 12350–12357
Wurster’s crownophanes: an alternate topology for
para-phenylenediamine-based macrocycles
a
b,
c
John W. Sibert,a, Greg R. Hundt, Andrew L. Sargent and Vincent Lynch
*
*
aDepartment of Chemistry, The University of Texas at Dallas, PO Box 830688, Richardson, TX 75083-0688, USA
bDepartment of Chemistry, East Carolina University, Greenville, NC 27858, USA
cDepartment of Chemistry, The University of Texas at Austin, Austin, TX 78712, USA
Received 15 July 2005; revised 20 September 2005; accepted 21 September 2005
Available online 14 October 2005
Abstract—Six redox-active cyclophane/crown hybrid molecules (crownophanes) were prepared via cyclization reactions involving N,N0-
dimethyl-p-phenylenediamine and tosylated oligoethylene glycols of varying length. These new host molecules differ from other
phenylenediamine-containing crown ethers in that the electron-rich p face is designed to be part of the ligating group. Their electrochemical
properties were determined by cyclic voltammetry with a correlation found between macrocyclic architecture and ease of oxidation. The
affinity of the smaller crownophanes for cations was studied by cyclic voltammetry with the result that these hosts show no electrochemical
response to alkali metal cations, but, dependent on macrocycle size, modest selectivity for alkaline earth metal cations. This stands in contrast
to previously reported phenylenediamine-containing crown ethers in which the redox centers are linked to guest ions through a macrocyclic
amino group.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
the macrocycle framework. Such structures preserve the
rich electrochemical properties of the phenylenediamine
subunit, thereby allowing for the sensing of bound metal
ions via the accompanying change in ligand oxidation
potential upon coordination.
Macrocycles containing electrochemically active subunits
are of interest because of their ability both to sense bound
guest species and control the coordination environment of
the host.1 We2 and others3 have previously prepared a series
of redox-active ligands centered around the electrochemi-
cally active phenylenediamine structure. The ligands
reported to date have been referred to as ‘Wurster’s crowns’
(see Fig. 1) because they are formally derived from the
famed Wurster’s reagent (N,N,N0,N0-tetramethyl-p-phenyl-
enediamine or TMPD).4 In all reported examples, the
phenylenediamine moiety has been attached to a crown
ether by a single phenylenediamine nitrogen atom within
Motivated by the efficient metal binding properties of the
Wurster’s crowns, we became interested in an alternate
structural motif for incorporating the electrochemically
active phenylenediamine unit into the body of a crown. In
these macrocycles, both N atoms of the phenylenediamine
moiety are now contained within the macrocyclic frame-
work to produce hybrid crown/cyclophane5 structures called
‘Wurster’s crownophanes’ (see Fig. 1). Similar to previously
Figure 1. Representative macrocycles derived from Wurster’s reagent (N,N,N0,N0-tetramethyl-p-phenylenediamine or TMPD).
Keywords: Cyclophane; Crown; Crownophane; Wurster; Redox.
*
Corresponding author. Tel.: C1 972 883 2918; fax: C1 972 883 2925.; e-mail: sibertj@utdallas.edu
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.091

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12351
reported redox-active crown ethers, these hosts are designed
to be electrochemically responsive to cations. However, the
mode of communication between the redox center and guest
ions in presumed endocyclic complexes should prove quite
distinct, occurring through the electron-rich p face of the
phenylenediamine moiety and not the amino group. In
addition to potential utility in electrochemical sensing
and/or switching applications, these compounds may prove
useful in probing hard cation-p interactions, a topic of
considerable recent interest due to an established signifi-
cance in controlling protein folding and enzyme-substrate
recognition.6
and 3 was accomplished using a general method that can be
extended by choice of electrophile to produce a range of
redox-active crownophanes. Specifically, N,N0-dimethyl-p-
phenylenediamine dihydrobromide, an oligoethylene glycol
ditosylate of appropriate length (tetraethylene glycol for 1,
pentaethylene glycol for 2, hexaethylene glycol for 3), and
carbonate base were refluxed for 3 days in acetonitrile to
yield the desired ligands. Following radial chromatography
on alumina, the crownophanes were isolated in approxi-
mately 20–25% yield as light brown oils. Shorter reaction
times revealed the presence of significant amounts of
starting materials as monitored by thin layer chromato-
graphy (TLC) while longer reaction times gave no
improvement in cyclization yields. Further, the reaction
yields were largely insensitive to the choice of alkali metal
carbonate used as base. While the yields are modest, the
products can be quickly and definitively identified by TLC
analysis. N-peralkylated p-phenylenediamines, like TMPD,
oxidize upon exposure to UV light resulting in the
characteristic blue color of the radical cation. As such,
TLC analysis of successful crude reaction mixtures show
the presence of a ‘Wurster’s blue’ spot that can be attributed
to the formation of the target Wurster’s crownophane.
However, during the preparation of the anticipated products
1, 2 and 3, additional products were formed as evidenced by
the presence of a second ‘Wurster’s blue’ spot on the TLC
of each crude reaction mixture. These minor products
proved to be the larger ‘2C2’ cyclization crownophanes 4,
5, and 6, isolated from the reaction mixtures in approxi-
mately 3–5% yield. These larger macrocycles are currently
being studied for their utility in the assembly of more
intricate supramolecular structures (e.g., rotaxanes and
catenanes).
Related crownophanes containing the electron-rich p
systems 1,4-dialkoxybenzene7 and tetrathiafulvalene
(TTF)8 have been previously reported. In the latter case,
the reversible electrochemistry of TTF has led to their study
as electrochemical sensors for metal cations. It is worth
noting that these ligands are typically synthesized as
mixtures of Z and E isomers. Further investigation by
mass spectrometry has indicated that the Z isomer alone
participates in binding allowing for the TTF moiety to
potentially interact either through the p system, hetero-
cyclic S atoms or through distortions of the p system caused
by complex formation.
Both Staab, et al.9 and, more recently, Takemura, et al.10
have reported on the redox properties and charge transfer
complexes of Wurster-type cyclophanes containing phenyl-
enediamine subunits. In both studies, the cyclophanes
contain alkyl linkages between two p-phenylenediamine
subunits and were, therefore, not designed nor studied for
metal chelation. Interestingly, however, the length of the
alkyl spacers and their respective points of attachment on
the phenylenediamine subunits gave clear differences in the
resulting electrochemical properties of the cyclophanes with
shorter linkages giving rise to cooperative effects between
the two redox centers.
2.2. Crystallographic study of 4
Unlike the smaller crowns 1, 2 and 3, which were isolated as
thick oils, macrocycle 4 is a crystalline solid. In fact, the
crude reaction mixtures containing 1 and 4 can be separated
by recrystallization from methanol with 4 forming crystals
and 1 remaining in solution. As shown in Figure 2, 4
In this report, we describe the synthesis and properties of
Wurster’s crownophanes along with unanticipated larger
macrocyclic byproducts and explore their ability to complex
hard cations.
˚
contains a large cavity with dimensions of 6.4 A (from the
˚
centroid of one aromatic ring to the other) by 14.4 A. The
two methyl groups are positioned ‘trans’ with respect to the
phenyl moiety. Individual molecules of 4 are stacked in
the crystal lattice to give long channels throughout the
structure (Fig. 3). The closest p–p distance between
neighboring molecules (6.6 A) rules out the possibility of
intermolecular p–p stacking.
2. Results and discussion
2.1. Ligand synthesis
˚
As shown in Scheme 1, the synthesis of macrocycles 1, 2
Scheme 1.

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J. W. Sibert et al. / Tetrahedron 61 (2005) 12350–12357
Table 1. Half-wave potentials (vs Ag/AgCl, 0.1 M TEABF4, CH3CN,
100 mV/s) of TMPD and Wurster’s crownophanes 1–6
Compound
E1/2 (mV)
E1/2 (mV)
TMPD
124
64
70
93
132
131
128
708
677
697
709
743
753
734
1
2
3
4
5
6
potentials similar to that of TMPD, the facile oxidation of 1,
2 and 3 must be associated with their common intra-
molecular arrangement of a polyether fragment directly
across from the redox center. That 1 exhibits the most facile
oxidation (60 mV easier to oxidize than TMPD) indicates
that its smaller ring size positions the polyether subunit
closest to the phenyl ring and, thus, best able to stabilize the
radical cation formed upon oxidation. An alternate
explanation is that compound 1 has the most electronic
strain between the dipoles created by the ether groups and
the electron rich p system. This strain is relieved by
oxidation which allows for a favorable electrostatic
interaction between the polyether and radical cationic
phenylenediamine subunits (vide infra).
Figure 2. X-ray crystal structure of 4 showing the atom labeling scheme.
Displacement ellipsoids are scaled to the 50% probability level with H
atoms omitted for clarity.
Cyclic voltammetry was also used to probe the electro-
chemical responses of 1, 2, and 3 to various hard cations.
Indeed, both aniline-11 and phenylenediamine-containing
crown ethers2a,2b,3c respond to the coordination of cations
through anodic shifts in their oxidation potentials. For the
alkali metal cations, the magnitude of the response
correlates well to complex stabilities. The electrochemical
responses of the Wurster’s crownophanes (as measured by a
shift in the first oxidation potential of the phenylenediamine
unit) after addition of 1.2 equiv of metal or ammonium salts
were analyzed. Interestingly, and in contrast to redox-active
crown ethers, the Wurster’s crownophanes show no
evidence for the binding of alkali metal ions. However the
first oxidation potential of the largest crownophane, 3, shifts
anodically in the presence of alkaline earth metal ions and
the ammonium cation (DEpa: 21 mV for Ca2C, 27 mV for
Sr2C, 54 mV for Ba2C, 21 mV for NHC4 ). This is likely due
to a generally enhanced affinity of this host for cations
because of its greater number of donor atoms and, in the
former case, the larger charge density of alkaline earth metal
cations in comparison to the alkali metal cations. The
response of 3 to alkaline earth metal cations but not alkali
metal cations is notable and suggests potential application in
the selective sensing of the former. Crownophane 3 shows
the greatest electrochemical response to Ba2C with its first
oxidation potential anodically shifted 54 mV from that of
the free ligand (Fig. 4). Similar to 3, a TTF-containing
crownophane of comparable size displays a preference for
alkaline earth versus alkali metal cations.8a In this case, the
TTF host showed a 100 mV anodic shift in its first oxidation
potential in the presence of a stoichiometric amount of
Ba2C. Interestingly, however, an X-ray structure of the
TTF-crownophane complex with Ba2C shows only the
participation of the polyether subunit in coordination of
the metal cation.8a Perhaps, then, it is not surprising that
compound 3 is the only Wurster’s crownophane to
Figure 3. Unit cell packing diagram for 4. The view is approximately down
the a-axis. Crystallographic structures 1 are shown in ball-and-stick fashion
while crystallographic structures 2 are in wireframe display form.
2.3. Electrochemistry
Cyclic voltammetry was used to explore the relationship
between the electrochemical properties of 1–6 and ligand
architecture. All six compounds show two reversible one-
electron oxidations, like TMPD. For the larger cyclo-
phanes 4–6, the two phenylenediamine subunits behave as
independent redox centers as might be expected con-
sidering the long aliphatic linkages between them. In fact,
Takemura, et al. demonstrated that a five carbon chain
between two p-phenylenediamine units is sufficient for the
redox centers to behave as discrete electrochemical
entities.10 As shown in Table 1, the smaller Wurster’s
crownophanes oxidize more easily than TMPD with the
effect strongest for the smallest crownophane 1. Consider-
ing the three larger cyclophanes 4, 5 and 6 oxidize at

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2.4. Computational analysis
Proton NMR spectra of 1, 2 and 3 show a single aromatic
peak indicative of the equilibration of cis and trans
conformers in solution. Consistent with these results, gas-
phase B3LYP/6-31CG* calculations reveal that the cis and
trans conformers of 1 are very close in energy, with the
latter only 0.59 kcal/mol more stable than the former. An
analysis of each of these conformers supports the
electrochemical results that Wurster’s crownophanes should
indeed oxidize more easily than TMPD (Fig. 5) through the
intramolecular stabilization of the radical cationic form of
the phenylenediamine moiety by the polyether subunit. In
the neutral state, the dipole moment of each conformer is
oriented with the negative end directed toward the electron-
rich phenylenediamine moiety. Upon oxidation, the positive
charge of the radical cation is localized on the phenylene-
diamine portion of the Wurster’s crownophane. The calcu-
lated natural atomic charges, listed in Figure 5, become
considerably less negative, or more positive, on the phenyl-
enediamine heavy atoms (excluding the terminal methyl
groups) thereby corroborating this view. Not only does the
magnitude of the dipole moment significantly decrease
(2.532–1.131 D for the trans, 4.209 to 2.996 D for the cis),
but the direction of the dipole moment changes as well, with
the positive end residing near the phenylenediamine group.
Motivated by the ensuing stabilization of the radical cation
charge, the molecular geometry responds to this shift in the
charge distribution by decreasing the distance between the
Figure 4. Cyclic voltammograms (0.1 M TEABF4, CH3CN, 100 mV/s) of
Wurster’s crownophane 3 (&), and 3 in the presence of 1.2 equiv of
Ba(OTf)2 (:).
demonstrate an ability to form complexes with hard cations
among the three ligands studied. In complexes of 3, the
second oxidation potential is unshifted relative to that of the
free crownophane (see Fig. 4, for example) indicating that
the second oxidation in the cyclic voltammogram of each
complex is, in actuality, that of the free ligand. Therefore,
the dicationic form of 3 does not support complexation with
ejection of the ion from the macrocyclic cavity presumed
upon its formation.
Figure 5. B3LYP/6-31CG* and UB3LYP/6-31-G* optimized geometries of the neutral and radical cation states, respectively, of the cis and trans forms of
compound 1. Natural atomic charges are listed beside the symmetry unique heavy atoms.