Synthesis, structural characterization and complexation properties of the first "crowned" dipyrrolylquinoxalines

Article abstract of DOI:10.1002/1099-0690(200211)2002:22<3768::AID-EJOC3768>3.0.CO;2-R

The synthesis of four crown-substituted dipyrrolylquinoxalines 1-4 is reported. The key step in the synthesis is reaction of a 1,2-diaminobenzocrown with 1,2-bis(1H-pyrrol-2-yl)ethanedione (20). A single crystal X-ray diffraction analysis of the 18-crown-6-dipyrrolylquinoxaline 1 revealed that this molecule forms a tetramer centered around a single molecule of water, with no fewer than 10 hydrogen bonds holding the supramolecular structure together. In the case of the 15crown-5-dipyrrolylquinoxaline 2, however, X-ray diffraction analysis revealed that this species exists as a dimeric pair in the solid state, with the NH protons of one pyrrole lying within hydrogen-bonding distance of two oxygen atoms on an adjacent crown ether. A second single crystal structure of 2 was solved; it demonstrated that this system is able to coordinate a potassium cation, thereby forming an intermolecular sandwich complex, at least in the solid state. In [D₆]acetone solution receptor 2 and congeners 1, 3 and 4 were also found to complex sodium and potassium cations within the crown diethyl ether binding sites, in a 1:1 manner as judged by ¹H NMR spectroscopic analyses. Although systems 1-4 appear to bind fluoride anion as well as cations, the inability to obtain quantitative binding affinities of 1-4 with fluoride anion rendered the evaluation of the systems for cooperative binding impossible. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).

Full text of DOI:10.1002/1099-0690(200211)2002:22<3768::AID-EJOC3768>3.0.CO;2-R

FULL PAPER
Synthesis, Structural Characterization and Complexation Properties of the
First ‘‘Crowned’’ Dipyrrolylquinoxalines
Gregory J. Kirkovits,[a] Rebecca S. Zimmerman,[a] Michael T. Huggins,[a]
Vincent M. Lynch,[a] and Jonathan L. Sessler*[a]
Keywords: Host-guest chemistry / Crown compounds / Hydrogen bonds / Supramolecular chemistry
The synthesis of four crown-substituted dipyrrolylquinoxal- of 2 was solved; it demonstrated that this system is able to
ines 1−4 is reported. The key step in the synthesis is reaction
coordinate a potassium cation, thereby forming an inter-
of a 1,2-diaminobenzocrown with 1,2-bis(1H-pyrrol-2-yl)e- molecular sandwich complex, at least in the solid state. In
thanedione (20). A single crystal X-ray diffraction analysis [D6]acetone solution receptor 2 and congeners 1, 3 and 4
of the 18-crown-6-dipyrrolylquinoxaline 1 revealed that this
molecule forms a tetramer centered around a single molecule
of water, with no fewer than 10 hydrogen bonds holding the
supramolecular structure together. In the case of the 15-
crown-5-dipyrrolylquinoxaline 2, however, X-ray diffraction
analysis revealed that this species exists as a dimeric pair in
the solid state, with the NH protons of one pyrrole lying
within hydrogen-bonding distance of two oxygen atoms on
an adjacent crown ether. A second single crystal structure
were also found to complex sodium and potassium cations
within the crown diethyl ether binding sites, in a 1:1 manner
as judged by H NMR spectroscopic analyses. Although sys-
tems 1−4 appear to bind fluoride anion as well as cations, the
inability to obtain quantitative binding affinities of 1−4 with
fluoride anion rendered the evaluation of the systems for
cooperative binding impossible.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
1
Introduction
observed,[6dϪ6f,6hϪ6j,7jϪ7l] and in a limited number of cases
membrane transport has also been demonstrated.[3d,6b,6g]
Recently, dipyrrolylquinoxalines have emerged as a new
class of neutral anion receptor, that demonstrate high se-
lectivity towards fluoride anion.[8] In view of this and their
recognized ease of construction, we felt that covalent con-
jugates, wherein a dipyrrolylquinoxaline moiety is linked to
a cation selective crown diethyl ether would result in new
ditopic receptors capable of effecting complementary anion
and cation recognition. In this work we report the synthesis
of four new ‘‘crowned’’ dipyrrolylquinoxalines namely, 1Ϫ4
as well as the control dimethoxy-dipyrrolylquinoxaline 21.
The solid-state structures of the free receptors 1, 2, and 21
and the potassium complex of 2 are also reported as are
For over thirty years now, supramolecular chemists have
worked to develop abiotic receptors capable of binding pos-
itively or negatively charged species with ever-improving se-
lectivities.[1] As a result, there is now an abundant literature
regarding the design, synthesis and study of such receptors.
In spite of the progress this literature represents, significant
challenges remain in the area. One of these involves the
construction of so-called ditopic receptor species, that can
complex cation and anion pairs concurrently within a single
molecular system.[2] Incentives to prepare such systems in-
clude their capacity to coordinate zwitterionic amino ac-
ids[3] and peptides,[4] and their potential applicability as
toxic material extractants[5] and through-membrane trans-
port agents.[3d,6b,6g] To date, ditopic receptors reported in
the literature have typically combined Lewis acid centers,
positively charged groups, pyrroles, and amide or (thio)urea
groups for anion recognition, with calixarene[6] and
crown diethyl ether subunits[7] for cation complexation.
In certain instances, allosteric effects have been
1
the results of H NMR titration experiments. These latter
findings support the conclusion that these systems are cap-
able of complexing both alkali metal cations and fluoride
anions in [D6]acetone solution. However, these same studies
also reveal no evidence of cooperative anion and cation
binding.
Results and Discussion
[a]
Department of Chemistry and Biochemistry and Institute for
Cellular and Molecular Biology, University of Texas at Austin,
Austin, Texas 78712-1167, USA
Synthesis
Fax: (internat.) ϩ 1-512/471-7550
E-mail: sessler@mail.utexas.edu
Supporting information for this article is available on the
WWW under http://www.ejoc.com or from the author.
The choice of 18-crown-6 and 15-crown-5 scaffold was
obvious; simply put, the alkali metal cation complexation
chemistry of these systems has been thoroughly investig-
3768
 2002 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/02/1122Ϫ3768 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2002, 3768Ϫ3778

“Crowned” Dipyrrolylquinoxalines
FULL PAPER
Scheme 1
ated.[9] Inclusion of the nitrogen atom in receptors 3 and 4 amine 16؊19 in an approximately 1:1 mixture of EtOH and
was done to highlight the versatility of this synthetic ap- acetic acid, under reflux conditions. This produced the
proach with regard to potential future functionalizations. ‘‘crowned’’ dipyrrolylquinoxalines 1Ϫ4 in moderate to
Such considerations then led to the identification of crown quantitative yields (49Ϫ100%) (Scheme 2). Gratifyingly, the
diethyl ethers 8؊11 as key precursors. While 8 and 9 are all-oxygen analogues 1 and 2 were isolated in analytically
commercially available, benzoaza crowns 10 and 11 had to pure form without the need for column chromatography.
be synthesized. They were obtained by adapting the proced- Crystals suitable for X-ray diffraction analysis were then
ure of Okahara and co-workers that was developed to pre- obtained by recrystallization from acetone. Compounds 3
pare mono-azacrown diethyl ethers (Scheme 1).[10] Specific- and 4 were purified by column chromatography (neutral
ally, 1,2-bis[2-(p-tosyloxy)ethoxy]benzene (5)[11] was reacted alumina; 1.5% MeOH/CH2Cl2, eluent).
with azadiol 6 or diethanolamine 7 in a tert-butyl alcohol/
In a manner similar to that outline above, the control
dioxane mixture in the presence of potassium tert-butoxide dimethoxydipyrrolylquinoxaline 21 was prepared by reac-
to give benzo-aza-18-crown-6 10 (26%) and benzo-15- tion of air-sensitive 1,2-dimethoxy-4,5-diaminobenzene[3d]
crown-5 11 (16%), respectively.[12] To the best of our know- with 1,2-bis(1H-pyrrol-2-yl)ethanedione (20) (Scheme 3).
ledge, this is the first time that the synthesis and full charac- The synthesis of 2,3-bis(1H-pyrrol-2-yl)quinoxaline (22) is
terization of 10 has been described.
reported elsewhere.[8a]
Nitration of benzocrowns 8؊11 was then carried out and
produced the dinitro intermediates 12؊15 in moderate to
high yields (44Ϫ88%). Reduction of the dinitro functionali-
Solid-State Structure of 1
Crystals of 1 suitable for X-ray structural analysis were
ties afforded the corresponding air-sensitive diamines grown by dissolving the receptor in boiling acetone, then
(16؊19), which were used directly in the final quinoxaline- the solution was cooled and left standing overnight. A top
producing step. This step involved reaction of 1,2-bis(1H- face view of the basic unit of the solid-state structure of
pyrrol-2-yl)ethanedione (20)[8a] with the appropriate di- 18-crown-6-dipyrrolylquinoxaline 1 shows a tetramer held
Scheme 2
Eur. J. Org. Chem. 2002, 3768Ϫ3778
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G. J. Kirkovits, R. S. Zimmerman, M. T. Huggins, V. M. Lynch, J. L. Sessler
FULL PAPER
Scheme 3
Figure 1. Ortep view of the supramolecular tetramer that exists as a repeating motif in crystals of 1. Also shown is the heteroatom
labeling scheme. Nonessential hydrogens have been omitted for clarity. Hydrogen bonding interactions are indicated by dashed lines.
Thermal ellipsoids are scaled to the 50% probability level.
together by no fewer than ten hydrogen bonding interac- noxaline unit, one of which is perpendicularly directed, and
tions (Figure 1). In this arrangement, one pyrrole NH and the other of which is directed in a parallel fashion from this
one pyrazine nitrogen from each quinoxaline point inward plane. To exemplify, the set of nearly perpendicular quinox-
into a water-filled pore. Additionally, the four crown diethyl alines are oriented at a 103° angle to one another; this ar-
ether moieties of each quinoxaline form the corners of a rangement is facilitated by hydrogen bonding interactions
square.
between the inward-facing pyrazine nitrogen on each qui-
When looking at the crystal lattice from the top face (Fig- noxaline and a bound water molecule. The set of nearly
ure 2), the result of this conformation is the formation of parallel interactions involves one of the molecules from the
five infinite sets of similarly oriented channels, four of first set and a molecule directly above or below it at a dis-
˚
˚
which are formed by the ‘‘corner’’ crown diethyl ethers, and tance ranging from 4.16 A to 5.70 A across the face of the
one in the center framed by a network of inward-pointing two planes formed by the quinoxaline units.
pyrrole and pyrazine nitrogens. The side view (Figure 3)
The supramolecular motif highlighted in Figure 2 and 3
shows that the tetramer is comprised of two sets of two is reinforced by numerous hydrogen bonds, all of which oc-
intermolecular interactions relative to the plane of each qui- cur in a regular pattern. For instance, when looking at the
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“Crowned” Dipyrrolylquinoxalines
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Figure 2. Ortep view of the top face of the crystal lattice of 1. Encapsulated water molecules are repeated twice within each unit cell.
Nonessential hydrogens have been omitted for clarity. Thermal ellipsoids are scaled to the 50% probability level.
top face of the tetramer unit (Figure 1), it can be seen that as a hydrogen-bound dimer in the solid state, stabilized by
there are two molecules on opposite corners of the ‘‘square’’ two sets of identical intermolecular bifurcated hydrogen
˚
˚
that have their quinoxaline unit overlaying the quinoxaline bonds from N2···O4Ј (2.90 A) and N2···O5Ј (3.36 A). In
unit on the molecule adjacent to it. Only the inward facing this antiparallel arrangement, the quinoxaline groups ap-
pyrrole NH atoms (N1A and N1B) of the two overlaying pear to be stacking, with atom-to-atom distances ranging
˚
molecules participate in hydrogen bonding to the encapsul- from 4.15 to 4.28 A. However, this distance is greater, by a
˚
˚
ated water molecule (NH···Ow of 2.13 A). Likewise, it is considerable margin, than the approximately 3.3 to 3.6 A
also only the overlaying, inward facing pyrazine nitrogens separations typically seen for stacked systems.[13] The fused
(N3A and N3B) that participate in hydrogen bonding to aromatic rings are not completely planar, but are twisted
˚
this same molecule of water (N···HϪOw of 2.08 A). Intra- slightly in opposite directions. This would appear to be the
molecular hydrogen bonding interactions are present between result of an intramolecular hydrogen bonding involving the
the inward-pointing pyrazine nitrogen atoms of all four qui- second out-of-plane pyrrole NH proton (N1) and the pyra-
˚
noxalines in the tetramer and the inward pointing pyrrole zine nitrogen atom N3 (N1···N3 ϭ 2.77 A).
NH atoms, specifically N3A to N1A, N3B to N1B, N3C to
Crystals of the potassium complex of 2 suitable for X-
˚
N1C, and N3D to N1D; N···HN of 2.49 A. Curiously, the
ray structural analysis were grown by vapor diffusion of
only direct interactions between the two ‘‘layers’’ seen in
diethyl ether into an acetonitrile solution containing the li-
this view are hydrogen bonds between one of the methoxy-
gand and potassium trifluoromethanesulfonate. The side
like oxygens in the phenolic position of the overlaying qui-
view of the complex is shown in Figure 5. As anticipated,
the receptor forms a 2:1, ligand:Kϩ intermolecular complex
with the benzo-15-crown-5 unit from each dipyrrolylquin-
oxaline sandwiching the potassium cation. The K···O dis-
noxaline and the NH of the outward-facing pyrrole of the
corresponding underlying unit (O1A to N2C and O1B to
˚
N2D; NH···O of 2.20 A). This extraordinary ensemble is
thus stabilized by ten hydrogen bonds: two NH···Ow, two
N···HϪOw, four N···HN, and two NH···O interactions.
˚
tances range from 2.795(2) to 2.995(2) A. The formation of
such a sandwich complex is not uncommon, and the dis-
tances are well within the normal limits for such con-
tacts.[14] As a result of these interactions, the two sets of
bifurcated hydrogen bonds between N2···O4Ј and N2···O5Ј
Solid-State Structure of 2 and its KCF3SO3
Complex [2·K؉]
Crystallization of 2, also from acetone, yielded the struc- seen in Figure 4 for the free receptor are no longer present.
ture shown in Figure 4. This side view shows that 2 exists Presumably as a consequence, molecules of the ‘‘crowned’’
Eur. J. Org. Chem. 2002, 3768Ϫ3778
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G. J. Kirkovits, R. S. Zimmerman, M. T. Huggins, V. M. Lynch, J. L. Sessler
FULL PAPER
Figure 3. Ortep view of the side face of the unit cell of 1. Nonessential hydrogens have been omitted for clarity. Thermal ellipsoids are
scaled to the 50% probability level.
Figure 4. Ortep view of the hydrogen bonded dimer seen in crystals of 2. Also shown is the heteroatom labeling scheme. Non-essential
hydrogens have been omitted for clarity. Hydrogen bonding interactions are indicated as dashed lines. Thermal ellipsoids are scaled to
the 50% probability level.
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“Crowned” Dipyrrolylquinoxalines
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Figure 5. Ortep view of (18-crown-6-quinoxaline)2·K·CF3SO3·2H2O·CH3CN showing the heteroatom labeling scheme. Nonessential hy-
Ϫ
drogens, the CF3SO3 counter anion, and a CH3CN solvent molecule have been omitted for clarity. Hydrogen bonding interactions are
indicated as dashed lines. Thermal ellipsoids are scaled to the 50% probability level.
quinoxaline are offset from one another, giving what is pre- Solid-State Structure of 21
sumably the lowest energy, least sterically hindered struc-
ture.
Crystallization of 21, from acetone, yielded the structure
In the above structure, examination of the pyrrole groups shown in Figure 6. This side view shows that 21 exists, like
reveals that each is tilted out of the plane defined by the the 15-crown-5 derivative, as an antiparallel hydrogen-
ten atom quinoxaline rings. Interestingly, two water molec- bound dimer, also stabilized by two sets of identical inter-
˚
ules are present, but are hydrogen-bound to only one of molecular hydrogen bonds from N4···O1Ј (3.06 A) and
the quinoxaline groups present in the Kϩ-bridged dimer via N4···O2Ј (3.29 A). Interestingly, the two quinoxaline groups
˚
˚
pyrrole NH···O interactions, with distances of 1.980 A are offset from one another and hence ‘‘slipped’’ relative to
˚
(H1A···O1w) and 1.984 A (H2A···O2w). Also present is an what is seen for the 15-crown-5 analog (2) (Figure 4). The
˚
intramolecular hydrogen bond of 2.70 A length between two fused benzene rings present in 21 appear to stack but
˚
N1B and N3B. This interaction is presumed to play an im- the atom-to-atom distances of approximately 4 A, although
portant role in defining the dihedral angle between the qui- shorter than those observed for 2, are greater than those
noxaline core and this particular pyrrole. The counter tri- expected for systems linked by strong π-π stacking interac-
fluoromethanesulfonate anion and a molecule of acetonitr- tions. In the unit cell, each dimer is further hydrogen-bound
ile are present in the crystal lattice but only as spectator spe- to an adjacent dimer, via a set of two pyrazine-N···pyrrole-
˚
cies.
NH interactions of 2.247 A.
Figure 6. Ortep view of 21 showing the heteroatom labeling scheme. Nonessential hydrogens have been omitted for clarity. Hydrogen
bonding interactions are indicated as dashed lines. Thermal ellipsoids are scaled to the 50% probability level.
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Cation and Anion Binding Studies
tial studies were conducted using tert-butylammonium flu-
oride trihydrate leading to inconclusive results. This could
1
Solution state H NMR spectroscopic titrations of the
four crown-substituted dipyrrolylquinoxalines 1؊4 were
undertaken. [D6]acetone was chosen as the solvent due to
its ability to solubilize all of the species being studied, as
well as to minimize potential ion pairing. Initially, the bind-
ing of the alkali metal cation (as the trifluoromethanesul-
fonate salt) to each receptor was performed in order to ob-
tain a ‘‘baseline’’ of sorts against which evidence of cooper-
ativity in mixed studies could be judged. These results,
which show a number of patterns, are summarized in
Table 1.
potentially be explained by the inherent instability of tetra-
n-alkylammonium fluorides,[16] coupled with the recent ob-
servations of Schmidtchen[17] that quaternary ammonium
cations are less innocent as spectator species than previ-
ously thought. As a result we considered an alternative
source of fluoride anion, the potassium cryptand[2,2,2] flu-
1
oride salt (see Exp. Sect. for preparation) for H NMR and
UV/Vis spectroscopic titrations. Unfortunately, the inability
of the cryptand[2,2,2] to solubilize KF in the presence of
18-crown-6 1 in acetone, dimethyl sulfoxide, and methanol
precluded quantitative analysis of fluoride anion binding or
evaluation of systems 1؊4 as ditopic receptors.
During the course of these investigations it was thought
that the propensity of ‘‘crowned’’ dipyrrolylquinoxalines to
engage in cooperative anion and cation recognition could
be increased by reducing the large distance between the cat-
ion and anion binding sites. In a number of known ditopic
receptors, the simultaneous binding of the cation and anion
Table 1. Binding constants (Ka) measured in Ϫ1 for compounds
1Ϫ4
Compound[a]
1
2
3
4
Naϩ [b]
Kϩ [b]
57500[c]
86900[c]
1200[d]
11400[c]
13100[c]
200[d]
[e]
[e]
[a]
Titrations were performed in [D6]acetone. All errors are Յ 20% takes place over a shorter distance. The benefits of this ap-
in goodness of fit. [b] Used as trifluoromethansulfonate salts. [c] De-
proach are particularly well exemplified by the diazacrown-
[d]
termination of 1:1 binding stoichiometry by mole ratio method.
based receptor prepared by Smith and co-workers[7n] that
[e]
Unable to determine stoichiometry.
Not measured due to the
binds alkali halides within contact ion pairing distance.
Such systems take advantage of the driving force for the
formation of the ion contact pair while concurrently hydro-
apparent formation of 2:1 complexes.[14]
The cation binding behavior of receptors 1؊4, studied in gen bonding each ion to the corresponding portion of the
[D6]acetone, follows two distinct patterns for both Naϩ and receptor. It is of particular interest to note that Nishizawa
Kϩ. First, the 18-crown-6 1 (Ka ϭ 57500 Ϯ 7820 Ϫ1) and et al.[7k] successfully demonstrated the ditopic binding
the aza-18-crown-6 3 (Ka ϭ 11400 Ϯ 1140 Ϫ1) showed properties of a thiourea-functionalized benzo-15-crown-5,
higher binding for Naϩ than their smaller 15-crown-5 coun- similar to our current design, but which has an inherently
terparts 2 and 4 (Ka ϭ 1230 Ϯ 22 Ϫ1 and 195 Ϯ 6 Ϫ1
,
shorter distance between the cation and anion binding sites.
respectively), a finding that is consistent with the crown di- The present results suggest that the generation of bona fide
ethyl ether binding literature.[9] A similar comparison could ditopic anionϪcation receptors wherein such conditions are
not be made for Kϩ since clean 1:1 binding was not ob- met remains a substantial challenge.
served in the case of 2 and 4. This is fully consistent with
the extensive literature precedence that details the forma-
tion of 2:1 complexes of Kϩ with the benzo-15-crown-5
Conclusions
unit.[14] It is also in agreement with our own observation
that 2 forms a 2:1 Kϩ complex in the solid state (Figure 5).
The four new ‘‘crowned’’ dipyrrolylquinoxalines reported
Additionally, the all-oxygen receptors 1 and 2 exhibited here have been shown to bind alkali-metal cations effec-
stronger binding for Naϩ cation than the corresponding tively, with binding constants in good agreement with those
aza-analogs 3 and 4, respectively. Likewise, 1 demonstrated for analogous pure crown diethyl ether systems. Although
enhanced binding for Kϩ cation compared to its aza-analog compounds 1Ϫ4 act as effective receptors for alkali metal
3. This occurrence can be explained by classic crown diethyl cations, their affinity for fluoride anion and subsequent
ether coordination chemistry; the softer nitrogen donors in ability to behave as ditopic receptors in [D6]acetone was
the aza analogs 3 and 4 do not bind alkali metals as unable to be evaluated. We are currently pursuing the pos-
strongly as their harder oxygen counterparts.[15]
Mole ratio plots were also used to confirm classical cation and anion binding sites.
sibilities of reducing the separation distance between the
crownϪdiethyl ether type 1:1 binding stoichiometries for
Separate from their properties as receptors, the solid state
the 18-crown-6 1 with both Naϩ and Kϩ, as well as for the structure of 1 deserves comment. Unlike 15-crown-5-di-
aza-18-crown-6 3 with Naϩ and Kϩ. The binding of the 15- pyrrolylquinoxaline 2 and dimethoxydipyrrolylquinoxaline
crown-5 2 and the aza-15-crown-5 4 with Naϩ was too 21 which both form intermolecular dimers in the solid state,
weak to be determined by the mole ratio method; however, the ‘‘crowned’’ system 1 is found to form a tetramer in the
there is ample precedence to suggest a 1:1 binding solid state that is characterized by five infinite channels. The
mode.[9,15]
key feature of this unique structure is the finding that one
Next, our attention turned to the investigation of fluoride pyrrole NH and one pyrazine nitrogen from each quinoxa-
anion binding by the crowned dipyrrolylquinoxalines. Ini- line point inward into a water-filled pore. The elegance of
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“Crowned” Dipyrrolylquinoxalines
FULL PAPER
eluent) gave a pale orange oil which solidified on standing. Recrys-
this structure coupled with the current interest in nanotube
technology, particularly artificial ion channels, leads us to
suggest that supramolecular assemblies of this type could
have a role to play as mimics of the biologically significant
aquaporin water channels,[18] or anion-conducting channels,
of which there is currently only one example in the literat-
ure.[19]
tallization from hexanes afforded 10 as a white crystalline solid
1
(3.96 g, 26%). H NMR (250 MHz, CDCl3): δ ϭ 2.21 (br. s, 1 H,
NH), 2.77Ϫ2.83 (m, 4 H, CH2N), 3.60Ϫ3.74 (m, 8 H, CH2O),
3.80Ϫ3.84 (m, 2 H, CH2O), 3.88Ϫ3.92 (m, 2 H, CH2O), 4.12Ϫ4.19
(m, 4 H, PhOCH2), 6.88 (pseudo-s, 4 H, Ph-H) ppm. 13C NMR
(62 MHz, CDCl3): δ ϭ 49.3, 68.6, 68.8, 69.4, 69.8, 70.3, 70.7, 113.9,
114.6, 121.3, 121.4, 149.0, 149.06 ppm. HRMS (CIϩ): calcd. for
C16H26N1O5 [M
ϩ
H]ϩ 312.1811; found m/z: 312.1812.
C16H25N1O5: calcd. C 61.72, H 8.09, N 4.50; found C 61.73, H
8.13, N 4.44.
Experimental Section
Benzoaza-15-crown-5 (11): This compound was prepared in agree-
ment with the procedure used for 10 but starting from dieth-
anolamine (7) (10.38 g, 0.10 mol) and potassium metal (4.63 g, 0.12
mol) in tert-butyl alcohol (160 mL), and 5 (25.00 g, 0.05 mol) in
dioxane (140 mL). Purification by column chromatography (neutral
alumina, 1.5% MeOH/CH2Cl2 eluent) gave the product as a white
solid. Recrystallization from n-heptane afforded 11 as a white crys-
General: Proton and 13C NMR spectra were obtained on a Bruker
AC250 spectrometer. All high-resolution (HR) chemical ionization
(CI) mass spectra were performed on a VG ZAB-2E instrument.
Elemental analyses were performed by Atlantic Microlabs, Inc., At-
lanta, GA, and are reported as percentages. All reactions were con-
ducted under dry Ar unless otherwise stated. All solvents were of
reagent grade quality and purchased commercially. All starting
materials, except for 1,2-dimethoxy-4,5-dinitrobenzene (from Lanc-
aster) were purchased from Aldrich Chemical Co. and used without
further purification. The trifluoromethanesulfonate sodium and
potassium salts, cryptand[2,2,2] and KF (99.99%) were obtained
from Aldrich. All NMR spectroscopic solvents were purchased
from Cambridge Isotope Laboratories. Merck type 60 (230Ϫ400
mesh) silica gel and Brockmann I activated neutral alumina (150
mesh) were used for column chromatography. Thin-layer chromato-
graphy (TLC) analyses were performed on silica gel 60 F254
(200 µm thickness) or aluminum oxide 60 F254 (200 µm thickness)
as appropriate, with 5% MeOH in CH2Cl2 as the eluent. 1,2-Bis[2-
(p-tosyloxy)ethoxy]benzene (5),[11] 1,2-bis(1H-pyrrol-2-yl)ethane-
dione (20),[8a] and 2,3-bis(1H-pyrrol-2-yl)quinoxaline (22)[8a] were
prepared as previously reported.
1
talline solid (2.12 g, 16%). H NMR (250 MHz, CDCl3): δ ϭ 2.60
(br. s, 1 H, NH), 2.80Ϫ2.84 (m, 4 H, CH2N), 3.71Ϫ3.75 (m, 4 H,
CH2O), 3.85Ϫ3.88 (m, 4 H, CH2O), 4.09Ϫ4.12 (m, 4 H, CH2O),
6.80Ϫ6.89 (m, 4 H, Ph-H) ppm. 13C NMR (62 MHz, CDCl3): δ ϭ
49.1, 67.6, 68.9, 70.2, 112.4, 120.8, 148.7 ppm. HRMS (CIϩ): calcd.
for C14H21NO4 [M
ϩ
H]ϩ 268.1549; found m/z: 268.1558.
C14H21N1O4: calcd. C 62.90, H 7.92, N 5.24; found C 63.12, H
7.89, N 5.03.
General Procedure. Synthesis of Dinitro-3n-benzo-n-crowns 12؊14:
To a stirred solution of the appropriate benzo-3n-crown-n (8؊11)
(4.6Ϫ20.8 mmol) in glacial acetic acid (7Ϫ30 mL) cooled to less
than 15 °C, was added conc. nitric acid (70%, 5Ϫ20 mL) dropwise
over 15 min. After the addition the solution was stirred at ambient
temperature for 15 min. The reaction mixture was allowed to warm
to room temp. and stirred overnight. The solution was again cooled
to less than 15 °C and fuming nitric acid (90%, 11Ϫ50 mL) was
added dropwise over a period of 30 min. The orange solution was
poured into water (100 mL) and extracted with CH2Cl2 (3 ϫ
100 mL). The combined organic extracts were dried (MgSO4) and
concentrated in vacuo.
3-Aza-6-oxaoctane-1,8-diol (6): This compound was prepared in
agreement with the procedure used to synthesize 6-aza-3,9-di-
oxaundecane-1,11-diol.[20] 2-Chloroethanol (38.29 g, 0.48 mol) in
toluene (120 mL) was added to a mixture of 2-(2-aminoethoxy)-
ethanol (200.0 g, 1.90 mol) and Na2CO3 (55.44 g, 0.52 mol) heated
at reflux in toluene (1.2 L). The resulting mixture was stirred at
reflux for a further 2 days using a condenser equipped with a
DeanϪStark adaptor. The reaction mixture was allowed to cool,
filtered and concentrated in vacuo. The remaining residue was puri-
fied by fractional distillation to give 6 as a pale yellow oil (28.68 g,
40%). The physical properties of this material agree with those pre-
viously reported.[10]
Dinitrobenzo-18-crown-6 (12): 12 was synthesized from benzo-18-
crown-6 (8) (6.5 g, 20.8 mmol). Product 12 was obtained as a yellow
1
solid after recrystallization from acetone (7.34 g, 88%). H NMR
(250 MHz, CDCl3): δ ϭ 3.64 (pseudo-s, 4 H, CH2O), 3.66Ϫ3.70
(m, 4 H, CH2O), 3.73Ϫ3.76 (m, 4 H, CH2O), 3.93Ϫ3.96 (m, 4 H,
CH2O), 4.26Ϫ4.30 (m, 4 H, PhOCH2), 7.34 (pseudo-s, 2 H, Ph-H)
ppm. 13C NMR (62 MHz, CDCl3): δ ϭ 68.8, 69.8, 70.4, 70.7, 71.0,
108.3, 133.3, 151.6 ppm. HRMS (CIϩ): calcd. for C16H23N2O10 [M
ϩ H]ϩ: 403.1353; found m/z: 403.1345. C16H22N2O10: calcd. C
47.76, H 5.51, N 6.96; found C 47.80, H 5.53, N 6.98.
Benzoaza-18-crown-6 (10): 3-Aza-5-oxaoctane-1,8-diol (6) (18.41 g,
0.123 mol) and potassium metal (5.79 g, 0.118 mol) were dissolved
in tert-butyl alcohol (160 mL), with stirring at 40 °C. 1,2-Bis[2-(p-
tosyloxy)ethoxy]benzene (5) (25.00 g, 0.049 mol) dissolved in di-
oxane (140 mL) was added dropwise over 90 min. After the addi-
tion was complete, heating and stirring was continued for a further
2 h. The reaction mixture was then allowed to cool, upon which
point it was passed through a sintered funnel. The resulting precip-
itate was washed with CH2Cl2 and the combined filtrates were con-
centrated in vacuo. The residue obtained in this way was redis-
solved in water (30 mL), washed with hexanes (40 mL), and then
extracted with CH2Cl2 (3 ϫ 50 mL). The combined CH2Cl2 ex-
tracts were concentrated to ca. 50 mL, and extracted with 1  HCl
(50 mL). The aqueous layer was adjusted to pH 10Ϫ11 using
Na2CO3, and extracted with CH2Cl2 (2 ϫ 100 mL) and the com-
bined organic extracts were concentrated in vacuo. Purification by
column chromatography (neutral alumina, 2.5% MeOH/CH2Cl2
Dinitrobenzo-15-crown-5 (13): 13 was synthesized from benzo-15-
crown-5 (9) (2.50 g, 9.3 mmol). Product 13 was obtained as a yellow
1
solid after recrystallization from acetone (2.78 g, 84%). H NMR
(250 MHz, CDCl3): δ ϭ 3.70Ϫ3.77 (m, 8 H, CH2O), 3.91Ϫ3.95 (m,
4 H, CH2O), 4.23Ϫ4.26 (m, 4 H, PhOCH2), 7.31 (s, 2 H, Ph-H)
ppm. 13C NMR (62 MHz, CDCl3): δ ϭ 68.7, 69.7, 70.1, 71.1, 108.5,
136.8, 151.9 ppm. HRMS (CIϩ): calcd. for C14H19N2O9 [M ϩ H]ϩ
359.1091; found m/z: 359.1082. C14H18N2O9: calcd. C 46.93, H
5.06, N 7.82; found C 47.02, H 5.04, N 7.88.
Dinitrobenzoaza-18-crown-6 (14): 14 was synthesized from
benzoaza-18-crown-6 (10) (3.6 g, 11.6 mmol). However, the workup
was modified in the following manner: The orange solution was
poured into water (150 mL), and washed with CH2Cl2 (3 ϫ
Eur. J. Org. Chem. 2002, 3768Ϫ3778
3775

G. J. Kirkovits, R. S. Zimmerman, M. T. Huggins, V. M. Lynch, J. L. Sessler
150 mL). The aqueous layer was adjusted to pH 10Ϫ11 using 15-Crown-5-dipyrrolylquinoxaline (2): The intermediate diamine 17
FULL PAPER
Na2CO3 and extracted with CH2Cl2 (3 ϫ 150 mL). The combined
was synthesized from 13 (2.50 g, 6.98 mmol) according to the gen-
eral procedure given above. This was then treated with 20 (0.60 g,
organic extracts were dried (MgSO4) and concentrated in vacuo to
afford 14 as a yellow solid (3.61 g, 78%). 1H NMR (250 MHz, 3.2 mmol). Product 2 was obtained, pure, as a fine brown powder
CDCl3): δ ϭ 2.33 (br. s, 1 H, NH), 2.76Ϫ2.82 (m, 4 H, CH2N), (1.44 g, 100%). 1H NMR (250 MHz, CDCl3): δ ϭ 3.78Ϫ3.85 (m,
3.59Ϫ3.72 (m, 8 H, CH2O), 3.84Ϫ3.92 (m, 4 H, CH2O), 4.24Ϫ4.29
12 H, CH2O), 4.06Ϫ4.09 (m, 4 H, PhOCH2), 6.26 (m, 2 H, pyr-
(m, 4 H, PhOCH2), 7.30 (s, 1 H, Ph-H), 7.31 (s, 1 H, Ph-H) ppm. H), 6.54 (m, 2 H, pyr-H), 6.93 (s, 2 H, Ph-H), 6.98 (m, 2 H, pyr-
13C NMR (62 MHz, CDCl3): δ ϭ 49.4, 68.3, 68.7, 69.3, 69.6, 70.1,
H), 9.62 (br. s, 2 H, pyr-NH) ppm. 13C NMR (62 MHz, CDCl3):
δ ϭ 68.2, 69.1, 70.3, 71.3, 106.9, 109.8, 111.2, 120.9, 129.3, 136.8,
70.6, 70.7, 107.8, 108.1, 136.5, 151.5, 151.6 ppm. HRMS (CIϩ):
calcd. for C16H24N3O9 [M ϩ H]ϩ 402.1513; found m/z: 402.1510. 141.9, 151.5 ppm. HRMS (CIϩ): calcd. for C24H27N4O5 [M ϩ H]ϩ:
C16H23N3O9: calcd. C 47.88, H 5.78, N 10.47; found C 47.94, H
5.87, N 10.37.
451.1981; found m/z: 451.1964. C24H26N4O5: calcd. C 63.99, H
5.82, N 12.44; found C 63.73, H 5.72, N 12.22. UV/Vis: λmax
(CH3CN, ε/Ϫ1 cmϪ1) ϭ 269 (27,800), 402 (17,700) nm.
Dinitrobenzoaza-15-crown-5 (15): 15 was synthesized from
benzoaza-15-crown-5 (11) (1.24 g, 4.6 mmol). Workup in the man-
ner described for 14, afforded 15 as a yellow solid (1.15 g, 44%).
1H NMR (250 MHz, CDCl3): δ ϭ 2.50 (br. s, 1 H, NH), 2.79Ϫ2.83
(m, 4 H, CH2N), 3.73Ϫ3.76 (m, 4 H, CH2O), 3.88Ϫ3.92 (m, 4 H,
CH2O), 4.20Ϫ4.23 (m, 4 H, PhOCH2), 7.27 (s, 2 H, Ph-H) ppm.
13C NMR (62 MHz, CDCl3): δ ϭ 49.2, 68.1, 68.8, 70.5, 107.5,
136.7, 151.6 ppm. HRMS (CIϩ): calcd. for C14H19N3O8 [M ϩ H]ϩ
358.1250; found m/z: 358.1252. C14H19N3O8: calcd. C 47.06, H
5.36, N 11.76; found C 47.02, H 5.35, N 11.73.
Crystallization of 2 and its KCF3SO3 Complex: Receptor 2 was dis-
solved in boiling acetone and then allowed to cool to room temp.
Pale yellow crystals of 2, suitable for X-ray diffraction analysis,
were obtained by letting stand overnight. The complex was ob-
tained by dissolving 2 and excess KCF3SO3 in MeCN at ambient
temperature, and allowing vapor diffusion of Et2O in a screw-
capped vial. In this manner, amber crystals, suitable for X-ray dif-
fraction analysis, were obtained after several days.
General Procedure. Synthesis of 3n-Crown-n-dipyrrolylquinoxalines
1؊4 and 6,7-Dimethoxy-2,3-bis(1H-pyrrol-2-yl)quinoxaline (21):
Aza-18-crown-6-dipyrrolylquinoxaline (3): The intermediate di-
amine 18 was synthesized from 14 (2.01 g, 5.0 mmol) according to
the general procedure given above. This was then treated with 20
(0.43 g, 2.3 mmol) to yield the crude product as the acetate salt.
Therefore, the workup was modified in the following manner: The
reaction mixture was redissolved in a mixture of CH2Cl2 (100 mL)
and a 20% w/v aqueous Na2CO3 solution (100 mL). The aqueous
solution was further extracted with CH2Cl2 (2 ϫ 100 mL). The
combined organic extracts were washed sequentially with saturated
NaHCO3 solution (100 mL), water (100 mL), and brine (100 mL),
before being dried (MgSO4) and concentrated in vacuo. Purifica-
tion by column chromatography (neutral alumina, 1.5% MeOH/
CH2Cl2 eluent) afforded 3 as a fine brown powder (0.697 g, 62%).
1H NMR (250 MHz, CDCl3): δ ϭ 2.84Ϫ2.87 (m, 4 H, CH2N),
3.64Ϫ3.81 (m, 12 H, CH2O), 4.10Ϫ4.14 (m, 4 H, PhOCH2), 6.25
(m, 2 H, pyr-H), 6.55 (m, 2 H, pyr-H), 6.94 (s, 1 H, Ph-H), 6.97 (s,
1 H, Ph-H), 6.99 (2 H, pyr-H), 9.64 (br. s, 2 H, pyr-NH) ppm. 13C
NMR (62 MHz, CDCl3): δ ϭ 49.2, 49.3, 68.3, 68.4, 68.6, 69.0,
70.0, 70.1, 71.2, 70.7, 106.7, 106.8, 109.8, 111.2, 120.1, 129.3, 136.7,
142.0, 151.3 ppm. HRMS (CIϩ) calcd. for C26H32N5O5 [M ϩ H]ϩ:
494.2403; found m/z: 494.2408. UV/Vis: λmax (CH3CN, ε/Ϫ1
cmϪ1) ϭ 270 (25700), 405 (20900) nm.
The
appropriate
dinitro-3n-benzo-n-crown
(12؊15)
(2.35Ϫ7.0 mmol) or 1,2-dimethoxy-4,5-dinitrobenzene (3.58 g,
15.70 mmol), and 10% Pd/C (170Ϫ500 mg) were suspended in eth-
anol (33Ϫ135 mL) and glacial acetic acid (2Ϫ7 mL) and shaken in
a Parr hydrogenation apparatus at 50 psi H2 pressure and ambient
temperature for 44 h. The resultant diamine was assumed to form
in quantitative yield and was used immediately in the subsequent
reaction. The reaction mixture was filtered through a pad of Celite
into the next reaction vessel and washed with ethanol (50 mL). 1,2-
Bis(1H-pyrrol-2-yl)ethanedione (20) (1.1Ϫ7.24 mmol) dissolved in
glacial acetic acid (80Ϫ180 mL) was added to the solution and the
resultant mixture was heated at reflux for 24 h. The reaction mix-
ture was allowed to cool, and then concentrated in vacuo. The re-
maining residue was redissolved in a mixture of CH2Cl2 (75 mL)
and water (75 mL). The aqueous layer was further extracted with
CH2Cl2 (3 ϫ 75 mL). The combined organic extracts were washed
sequentially with saturated NaHCO3 solution (100 mL), water
(100 mL), and brine (100 mL), before being dried (MgSO4) and
concentrated in vacuo.
18-Crown-6-dipyrrolylquinoxaline (1): The intermediate diamine 16
was synthesized from 12 (2.82 g, 7.0 mmol) according to the gen-
eral procedure given above. This was then treated with 20 (0.60 g,
3.2 mmol). Product 1 was obtained in pure form as a fine brown
Aza-15-crown-5-dipyrrolylquinoxaline (4): The intermediate di-
amine 19 was synthesized from 15 (0.84 g, 2.35 mmol) according
to the general procedure given above. This was then treated with
20 (0.20 g, 1.1 mmol) to yield the crude product as the acetate salt.
Workup was effected in the manner described for 3. Purification by
column chromatography (neutral alumina, 1.5% MeOH/CH2Cl2,
eluent) then afforded 4 as a fine red-brown powder (0.234 g, 49%).
1H NMR (250 MHz, CDCl3): δ ϭ 2.98Ϫ3.01 (m, 4 H, CH2N),
3.84Ϫ3.88 (m, 4 H, CH2O), 3.97Ϫ4.01 (m, 4 H, CH2O), 4.22Ϫ4.26
(m, 4 H, PhOCH2), 6.27 (m, 2 H, pyr-H), 6.72 (m, 2 H, pyr-H),
6.97 (m, 2 H, pyr-H), 7.13 (s, 2 H, Ph-H), 9.49 (br. s, 2 H, pyr-
NH) ppm. 13C NMR (62 MHz, CDCl3): δ ϭ 49.0, 67.5, 68.7, 69.3,
106.6, 109.8, 111.3, 120.1, 129.3, 136.8, 141.8, 151.5 ppm. HRMS
powder (1.58 g, 100%). 1H NMR (250 MHz, CDCl3):
δ ϭ
3.68Ϫ3.84 (m, 16 H, CH2O), 4.10Ϫ4.13 (m, 4 H, PhOCH2), 6.26
(m, 2 H, pyr-H), 6.55 (m, 2 H, pyr-H), 6.96 (s, 2 H, Ph-H), 6.99
(m, 2 H, pyr-H), 9.64 (br. s, 2 H, pyr-NH) ppm. 13C NMR
(62 MHz, CDCl3): δ ϭ 68.8, 69.0, 70.4, 70.9, 71.1, 106.9, 109.8,
111.2, 120.2, 120.2, 129.3, 136.7, 141.9, 151.5 ppm. HRMS (CIϩ):
calcd. for C26H31N4O6 [M ϩ H]ϩ 495.2244; found m/z: 495.2235.
C26H30N4O6·H2O: calcd. C 60.93, H 6.29, N 10.93; found C 60.97,
H 6.16, N 10.51. UV/Vis: λmax (CH3CN, ε/Ϫ1 cmϪ1) ϭ 271
(28900), 407 (23300) nm.
Crystallization of 1: Receptor 1 was dissolved in boiling acetone
and then allowed to cool to room temp. Yellow-green crystals of 1, (CIϩ) calcd. for C24H28N5O4 [M ϩ H]ϩ 450.2141; found m/z:
suitable for X-ray diffraction analysis, were obtained by letting the
solution stand overnight.
450.2142. UV/Vis: λmax (CH3CN, ε/Ϫ1 cmϪ1) ϭ 270 (24800), 404
(13300) nm.
3776
Eur. J. Org. Chem. 2002, 3768Ϫ3778

“Crowned” Dipyrrolylquinoxalines
FULL PAPER
Table 2. X-ray Crystallographic and experimental data for receptors 1, 2, 21 and 2·K؉.
Receptor
1
2
21
2·Kϩ
Formula
C53.5H65N8O13.5
1036.14
Pccn
17.5406(2)
32.6958(4)
9.3167(1)
90
90
90
4
5343.17(11)
1.288
153(2)
0.71073
0.094
0.142
0.0532
1.357
C24H26N4O5
450.49
P21/n
9.7020(1)
15.1942(2)
14.7039(2)
90
101.686(1)
90
4
2122.63(5)
1.410
153(2)
0.71073
0.100
0.1024
0.0440
1.02
C18H16N4O2
320.35
C2/c
23.9261(7)
7.6176(2)
17.0385(5)
90
101.385
90
8
3044.32(15)
1.398
153(2)
0.71073
0.095
0.0979
0.0492
1.030s
C51H59F3KN9O15S
1166.23
P21/c
10.0780(1)
21.1467(2)
25.4861(3)
90
92.829(1)
90
4
5424.89(10)
1.428
153(2)
0.71073
0.223
0.168
Formula mass (g molϪ1
Space group
)
˚
a (A)
˚
b (A)
˚
c (A)
α (deg)
β (deg)
γ (deg)
Z
3
˚
V (A )
ρcalcd. (Mg mϪ3
T (K)
)
˚
λ (A)
µ (mmϪ1
)
Rw(F2)
R(F) [I Ͼ 2σ(I)]
0.0648
1.247
Goodness-of-fit on F2
6,7-Dimethoxy-2,3-bis(1H-pyrrol-2-yl)quinoxaline (21): The requis-
ite intermediate, 1,2-diamino-4,5-dimethoxybenzene was synthe-
sized from 1,2-dimethoxy-4,5-dinitrobenzene (3.58 g, 15.70 mmol).
This was then treated with 20 (1.36 g, 7.24 mmol) in agreement
with the standard procedures described above. This gave product
21 as a yellow powder (2.05 g, 89%) after purification by column
chromatography (silica, 2% MeOH/CH2Cl2, eluent). 1H NMR
(250 MHz, CDCl3): δ ϭ 4.04 (s, 6 H, OCH3), 6.28 (m, 2 H, pyr-
H), 6.77 (m, 2 H, pyr-H), 6.97 (m, 2 H, pyr-H), 7.24 (s, 2 H, Ph-
H), 9.48 (br. s, 2 H, pyr-NH) ppm. 13C NMR (62 MHz, CDCl3):
δ ϭ 56.2, 106.1, 109.9, 111.5, 120.2, 129.3, 136.8, 141.7, 152.2 ppm.
HRMS (CIϩ) calcd. for C18H17N4O2 [M ϩ H]ϩ 321.1352; found
m/z: 321.1352. C18H16N4O2·0.25 H2O: calcd. C 66.55, H 5.12, N
17.25; found C 66.55, H 5.08, N 17.11.
X-ray Crystallographic Study
Single crystal X-ray diffraction data were collected for free receptors
1, 2, 21 and the potassium complex of 2 ([2·K؉]). For each structure
the data were collected on a NoniusϪKappa CCD diffractometer at
153(2) K by using a graphite monochromator with Mo-Kα radiation
˚
(λ ϭ 0.71073 A). Crystal and refinement data are listed in Table 2.
CCDC-183336 to -183339 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: (internat.) ϩ 44-1223/336Ϫ033; E-mail:
deposit@ccdc.cam.ac.uk].
Crystallization of 21: Receptor 21 was dissolved in boiling acetone
and then allowed to cool to room temp. Yellow crystals of 21, suit-
able for X-ray diffraction analysis, were obtained by letting stand
overnight.
Acknowledgments
This work was supported by NIH (NIH Grant GM58907). We
would also like to thank Mr. G. Dan Pantos for helpful discussions.
1H NMR and UV/Vis Titration Studies
1H NMR titration studies were carried out with either a Varian
300-MHz or Bruker 250-MHz NMR spectrometer. All samples
were prepared in [D6]acetone, dried over activated 4-A molecular
[1] [1a]
J.-M. Lehn, Supramolecular Chemistry, VCH Verlagsge-
[1b]
sellschaft, Weinheim, 1995.
J. W. Steed, J. L. Atwood, Sup-
˚
ramolecular Chemistry, Wiley, Chichester, 2000.
[2]
For reviews, see: [2a] M. T. Reetz in Comprehensive Supramolec-
ular Chemistry, Vol. 2 (Eds.: J. L. Atwood, J. E. D. Davies, D.
D. MacNicol, F. Vögtle, G. W. Gokel), Pergamon, Oxford,
sieves. The trifluoromethanesulfonate salts (sodium and potas-
sium), Kryptofix 222 and KF were dried under vacuum at 40 °C
for 12 h prior to use. The preparation of the potassium
cryptand[2,2,2] fluoride salt was attempted by stirring a 1:1 mixture
of the Kryptofix 222 and KF in a known concentration of
crowned dipyrrolylquinoxaline host for 12 hours. The cationic gu-
est in question was dissolved in a solution of the receptor at the
initial concentration of the receptor to account for dilution effects.
The guest was added in aliquots to provide increasing concentra-
tions of the guest in the initial receptor solution until saturation of
the signal was observed. For the cation binding studies, the shift of
the benzyl hydrogen on the quinoxaline unit was followed. The data
were fit to a 1:1 binding profile using the Wilcox equation.[21] Job
plots and mole ratio plots were used to determine binding stoichi-
ometry when possible.[22] Fits of the titration profiles for 1؊4 and
1996, pp. 553Ϫ562. [2b] M. M. G. Antoinisse, D. N. Reinhoudt,
Chem. Commun. 1998, 443Ϫ448.
[2c]
P. D. Beer, P. A. Gale,
Angew. Chem. 2001, 113, 502Ϫ532; Angew. Chem. Int. Ed.
2001, 40, 486Ϫ516. [2d] G. J. Kirkovits, J. A. Shriver, P. A. Gale,
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41, 69Ϫ75.
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[3b]
1119Ϫ1120.
org. Chem. 1998, 37, 5042Ϫ5043.
D. T. Rosa, V. G. Young, D. Coucouvanis, In-
[3c]
H. Tsukabe, M. Wada, S.
[3d]
Shinoda, H. Tamiaki, Chem. Commun. 1999, 1007Ϫ1108.
J. D. Pike, D. T. Rosa, D. Coucouvanis, Eur. J. Inorg. Chem.
2001, 761Ϫ777 and references cited therein.
[4] [4a]
M. A. Hossain, H.-J. Schneider, J. Am. Chem. Soc. 1998,
120, 11208Ϫ11209. [4b] M. Sirish, H.-J. Schneider, Chem. Com-
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1
21 from H NMR titration experiments, and stoichiometric deter-
[5]
minations can be found in the Supporting Information.
[5a] P. D. Beer, P. K. Hopkins, J. D. McKinney, Chem. Commun.
Eur. J. Org. Chem. 2002, 3768Ϫ3778
3777

G. J. Kirkovits, R. S. Zimmerman, M. T. Huggins, V. M. Lynch, J. L. Sessler
FULL PAPER
[5b]
[8] [8a]
1999, 1253Ϫ1254.
D. J. White, N. Laing, H. Miller, S. Par-
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[6]
[6a]
´
For calixarene based ditopic receptors see:
D. M. Rudkev-
zenbacher, Jr., A. C. Try, H. Miyaji, K. Jusikova, V. M. Lynch,
ich, W. Verboom, D. N. Reinhoudt, J. Org. Chem. 1994, 59,
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[6b]
[8c]
3683Ϫ3686.
J. D. Rudkevich, J. D. Mercer-Chalmers, W.
10268Ϫ10272.
T. Mizuno, W.-H. Wei, L. R. Eller, J. L.
[8d]
Verboom, R. Ungaro, F. de Jong, D. N. Reinhoudt, J. Am.
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J. L.
Sessler, H. Maeda, T. Mizuno, V. M. Lynch, H. Furuta, Chem.
Commun. 2002, 862Ϫ863.
[9]
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R. M. Izatt, K. Pawlak, J. S. Bradshaw, R. L. Bruening, Chem.
Rev. 1991, 91, 1721Ϫ1785 and references cited therein.
H. Maeda, S. Furuyoshi, Y. Nakatsuji, M. Okahara, Bull.
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[6d]
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