Clare et al.
JOCArticle
the quest for increased affinity and selectivity has led to
the development of elaborate organic frameworks possessing
well-defined binding cavities of multiple chelating hydr-
ogen bond donor moieties.8 Sessler and co-workers’ classic
calix-4-pyrrole framework led to the recent publication of
novel receptors strapped with chromogenic dipyrrolylqui-
noxalines that exhibit selectivity for fluoride, dihydrogen
phosphate, and acetate anions.9 Other elaborate frameworks
have yielded receptors that also show remarkably high
selectivities.10
Hayashita and co-workers,11 as well as Fabbrizzi and co-
workers,12 have recently shown that “trivial” anion receptors
based on phenylurea have much to offer our understanding
of anion recognition; both groups have shown that this motif
is capable of strong binding (∼106 M-1) in polar solvents
such as acetonitrile and that affinity increases in the same
order as the anion basicity. Further, Gale and co-workers
studied the anion binding properties of 1,3-diphenylurea
itself and demonstrated that despite the absence of elec-
tron-withdrawing functionalities, this simple receptor is
capable of effectively binding anions in DMSO, a competi-
tive polar solvent.4 Gunnlaugsson and co-workers recently
employed an amide-functionalized variant of the same
diarylurea motif in a receptor capable of binding two anions
in a cooperative “allosteric” fashion.13
FIGURE 1. Receptors studied in this work.
event. The basic template of these responsive receptors
consists of a recognition site coupled to a subunit that
undergoes a measurable change in one or more physical
properties, such as color, fluorescence, or shifts in redox
potential upon binding.14,15 In particular, redox-active anion
and cation receptors based on ferrocene16 and tetrathiaful-
valene17 have received much attention. Redox-active cation
receptors that employ a functional equivalent of Wurster’s
reagent, N,N0-tetramethyl-p-phenylenediamine (p-TMPD),
as a signaling subunit, are also well-studied, but those for
anions are unknown.18 Here we report the synthesis, char-
acterization, anion affinities and electrochemistry of Wur-
ster-type ureas, new anion receptors that incorporate
p-phenylenediamine within the urea framework.
There is considerable interest in the design of receptors
that are further functionalized to record or signal a binding
ꢀ
(6) (a) Perez-Casas, C.; Yatsimirsky, A. K. J. Org. Chem. 2008, 73, 2275–
We studied 1-4 (Figure 1), simple N,N0-diphenylurea
derivatives functionalized to mimic the electrochemical
properties of p-TMPD. Incorporating the hydrogen bond
donor(s) in the redox center facilitates possible anion-depend-
ent electrochemical changes, and the optical properties of the
chromogenic centers may change on interaction with anions.
Symmetric receptor 1 was first synthesized in 1941 by
Gerchuk for the treatment of blood parasites,19 and more
recently, Nangia and co-workers synthesized receptor 3 for
the study of hydrogen-bond-directed homomolecular crystal
formation.20 Neither 1 nor 3 has been studied in the context
of anion recognition. Receptors 2 and 4 are acetonitrile-
soluble analogues of 1 and 3, respectively.
2284. (b) Formica, M.; Fusi, V.; Macedi, E.; Paoli, P.; Piersanti, G.; Rossi, P.;
Zappia, G.; Orlando, P. New J. Chem. 2008, 32, 1204–1214. (c) Ali, H. D. P.;
Kruger, P. E.; Gunnlaugsson, T. New J. Chem. 2008, 32, 1153–1161.
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Chem., Int. Ed. 2006, 45, 1921–1925. (b) Beer, P. D.; Sambrook, M. R.;
Curiel, D. Chem. Commun. 2006, 2105–2117. (c) Bondy, C. R.; Loeb, S. J.
Coord. Chem. Rev. 2003, 240, 77–99.
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(8) (a) Davis, A. P. Molecules 2007, 12, 2106–2122. (b) Lhotak, P. Anion
Receptors Based on Calixarenes; Springer: Berlin/Heidelberg, 2005. (c) Sessler,
J. L.; Camiolo, S.; Gale, P. A. Coord. Chem. Rev. 2003, 240, 17–55. (d)
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Results and Discussion
ꢀ
(12) Boiocchi, M.; Del Boca, L.; Gomez, D. E.; Fabbrizzi, L.; Licchelli,
Receptor Design and Synthesis. As has been previously
shown for cationic receptors, replacement of a donor atom
functionality with a redox-active phenylenediamine unit
adds redox activity (in some cases, reversible) without com-
promising the ability of the host to form complexes.18 For
example, it was shown that replacement of a single O atom in
18-crown-6withanN,N-dimethylamino-p-phenylenediamino
M.; Mozani, E. J. Am. Chem. Soc. 2004, 126, 16507–16514.
(13) dos Santos, C. M. G.; McCabe, T.; Watson, G. W.; Kruber, P. E.;
Gunnlaugsson, T. J. Org. Chem. 2008, 73, 9235–9244.
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6638 J. Org. Chem. Vol. 74, No. 17, 2009