Calix[n]bispyrrolylbenzenes: Synthesis, characterization, and preliminary anion binding studies

Article abstract of DOI:10.1002/chem.200400894

A series of novel calixpyrrole-like macrocycles, calix[n]bis(pyrrol-2-yl) benzene (calix[n]BPBs, n = 2-4) 9a-11a, have been synthesized by means of the TFA-catalyzed condensation reaction of bis(pyrrol-2-yl)benzene 8 a with acetone. Calix[2]BPB 9a represe

Full text of DOI:10.1002/chem.200400894

FULL PAPER
Calix[n]bispyrrolylbenzenes: Synthesis, Characterization, and Preliminary
Anion Binding Studies
Jonathan L. Sessler,*[a] Deqiang An,[a] Won-Seob Cho,[a] Vincent Lynch,[a] and
Manuel Marquez[b]
Abstract: A series of novel calixpyr-
role-like macrocycles, calix[n]bis(pyr-
rol-2-yl)benzene (calix[n]BPBs, n=2–
4) 9a–11a, have been synthesized by
means of the TFA-catalyzed condensa-
tion reaction of bis(pyrrol-2-yl)benzene
8a with acetone. Calix[2]BPB 9a rep-
resents an expanded version of calix[4]-
pyrrole in which two of the four meso
bridges are replaced by benzene rings.
By contrast, systems 10a and 11a,
which bear great considerable to calix-
bipyrroles 2 and 3, represent higher ho-
mologues of the basic calix[n]BPB
motif. Solution-phase anion binding
studies, carried out by means of
1H NMR spectroscopic titrations in
[D2]dichloromethane and isothermal ti-
tration calorimetry (ITC) in 1,2-di-
chloroethane, reveal that 9a binds typi-
cal small anions with substantially
higher affinities than 1, even though
the same number of hydrogen bonding
donor groups are found in both com-
pounds. The basic building block for
9a, benzene dipyrrole 8a, also displays
a higher affinity for anions than the
building block for 1, dimethyldipyrro-
methane 16. Structural studies, carried
out by single-crystal X-ray diffraction
analyses, are consistent with the so-
lution-phase results and reveal that 9a
is able to stabilize complexes with chlo-
ride and nitrate in the solid state.
Structures of the PF6 and NO3 com-
plexes of 10a were also solved as were
those of the acetone adduct of 9a and
the ethyl acetate adduct of 11a.
À
À
Keywords: anions
·
hydrogen
bonds · macrocycles · molecular
recognition · receptors
Introduction
design specificity and which might offer advantages, on a
pure cost of good basis, when used in various “real world”
applications.[1–6] Among the more attractive of the easy-to-
prepare anion-binding systems is calix[4]pyrrole.[1] Assem-
bled in one high-yielding step from commercially available
starting materials, calix[4]pyrroles (e.g., 1) have been found
to bind small anions, such as fluoride and chloride, with
good affinity in aprotic solvents. Such findings, in turn, have
inspired efforts aimed at extending the chemistry of calix[4]-
pyrroles. To date, this has been done through the prepara-
tion of larger calix[n]pyrrole systems (n>4)[7–10] and through
the formal replacement of one or more of the pyrrole rings
by some other aromatic subunit, for example, pyridine,[11]
benzene,[12] furan, or thiophene.[13] We have also recently
found that bipyrrole may be used as a “building block” and
In recent years, considerable effort has been focused on the
generalized problem of anion recognition. This has led,
among other things, to the design and synthesis of a number
of highly sophisticated receptor systems, including ones that
display very specific anion-binding selectivities. It has also
spawned efforts to produce simpler systems whose ease of
synthesis might serve to overcome any lack of inherent
[a] Prof. J. L. Sessler, D. An, W.-S. Cho, V. Lynch
Department of Chemistry and Biochemistry
Institute of Cellular and Molecular Biology
The University of Texas at Austin
1 University Station-A5300, Austin, TX 78712-1167 (USA)
Fax : (+1)512-471-7550
E-mail: sessler@mail.utexas.edu
[b] Dr. M. Marquez
Chemical Science and Technology Division
Los Alamos National Laboratory
Los Alamos, NM 87545 (USA)
and
IꢀNEST Group, New Technology Research Department, PMUSA
Richmond, VA 23298 (USA)
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2005, 11, 2001 – 2011
DOI: 10.1002/chem.200400894
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2001

have reported the synthesis of calix[n]bipyrroles 2 and 3
(n=3, 4)[14] and calix[2]bipyrrole[2]furan and calix[2]bipyr-
role[2]thiophene systems (e.g., 4 and 5).[15] In independent
Results and Discussion
Synthesis and crystal structures: The synthesis of target mole-
cules 9–11 is shown in Scheme 1. Here, the key 1,3-bis(pyr-
rol-2-yl)benzene precursors, 8a–c, were synthesized by using
a modification of a literature method used to prepare 1,4-
bis(pyrrol-2-yl)benzene.[17] Intermediates 12a,b were then
obtained from the reaction of the corresponding isophthalo-
yl chlorides, 13 and 14, with allylamine and triethylamine in
dichloromethane. The ether-functionalized system 12c was
obtained by the aminolysis of dimethyl-5-hexyloxyisophtha-
late 15 in the presence of allylamine. Reaction of 12a–c
with phosgene (to give the presumed imino chloride deriva-
tives), followed by immediate reaction with potassium tert-
butoxide in THF afforded 8a–c in yields of 29%, 43%, and
96%, respectively. The electron-donating groups at the 5-po-
sition of the benzene rings are expected to stabilize the in-
termediate carbocations formed during the reaction, thus ac-
counting for the increased yields observed on passing from
8a to 8c. Stirring intermediates 8a–c in acetone overnight
in the presence of one equivalent of trifluoroacetic acid af-
forded products 9a–c, 10a–c, and 11a–c. All new com-
pounds were characterized by standard spectroscopic tech-
work, Leeꢀs group has also reported the synthesis of a mac-
rocycle, 6, that is based on pyrrole and bithiophene.[16] The
finding that systems 2, 4, and 5, in particular, act as highly
effective anion-binding agents[14,15] led us to consider the
next logical step, namely the use of terpyrrole (7) as the key
pyrrole-containing building block. Unfortunately, to date we
have been unable to isolate any stable products from con-
densation reactions involving terpyrrole 7 and various ke-
tones (e.g., acetone). However, we have now found that an
alternative precursor, namely 1,3-bis(pyrrol-2-yl)benzene
(BPB, 8), shows considerable promise as a building block
and wish to report here the synthesis and characterization of
the calix[n]1,3-bis(pyrrol-2-yl)benzenes 9–11; these large cy-
clophane-like systems differ in terms of the size of the calix
core (n=2, 3, and 4) and the nature of 5-substituent on the
benzene rings (series a, b, and c). We also wish to report the
results of preliminary anion binding studies carried out with
8a–11a. One of these receptors, system 9a, in spite of con-
taining the same number of pyrrole NH hydrogen-bond
donor groups (four), displays an affinity for many anions, in-
cluding perchlorate, that is enhanced relative to that of
calix[4]pyrrole 1.
1
niques, including H and 13C NMR spectroscopy, and high-
resolution mass spectrometry (HRMS). Compounds 9a,
10a, 11a, and 8a were also characterized by X-ray diffrac-
tion analysis.
An X-ray structural analysis of 8a revealed that the mole-
cule adopts a “cis-” conformation in solid state and contains
an internal symmetry plane. Both pyrrole NH donor groups
point in towards the center of the resulting cleft (Figure 1
top), but are twisted out of the plane defined by the ben-
zene ring with N1-C4-C5-C6 torsion angles of 23.488 (c.f.,
Figure 1 middle). No evidence of p stacking is observed in
the packing diagram. However, the possibility of intermolec-
ular hydrogen-bonding interactions of the NH–p type in-
volving the pyrrole-NH protons of one molecule and the
benzene p-electrons of another can be inferred from this
same packing profile (Figure 1 bottom).
Diffraction grade crystals of 9a·2(CH3)2CO were obtained
by slow evaporation of a solution of 9a in dichloromethane
and acetone. X-ray analysis revealed that the molecule
adopts a 1,2-alternate (C2h) conformation (Figure 2). The
two benzene rings, although on opposite sides of the mole-
cule, are nearly coplanar. By contrast, the pyrrolic subunits
connected to each of the two meso-carbon atoms are tilted
out of the plane defined by the benzene rings. Each of the
two pyrrole units around the bridging meso-carbon atoms is
hydrogen bonded (NH···O) to one acetone molecule and
À
each pair points to a different side of the plane. The N O
distances are in the range of 3.033(3)–3.122(3) ꢂ, the NH
À
H O distances are in the range of 2.12(3)–2.16(3) ꢂ, and
the N-H-O angles are in the range of 167(2)–177(3)8. The
X-ray analysis also revealed that the host molecule uses the
two sets of pyrrole units bound to the two meso-carbon
atoms, or more precisely, their NH donor subunits, to inter-
act with the bound acetone molecules, rather than the alter-
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Calix[n]bispyrrolylbenzenes
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counterion); it revealed that 9a
adopts a cone-shaped (or V-
shaped, C2v) conformation in
the solid state, with four pyrrole
NH protons involved in hydro-
gen-bonding interactions to the
chloride anion (Figure 3). The
À
N Cl distances are in the range
of 3.306(3)–3.401(3) ꢂ, while
À
the corresponding NH H Cl
distances range between 2.37(3)
and 2.58(2) ꢂ. The chloride ion
resides 1.377(4) ꢂ above the N4
root-mean-square plane of the
core of 9a. The N-H-Cl angles
Scheme 1. Synthesis of 9a–c, 10a–c, and 11a–c.
Figure 1. X-ray crystal structure of 8a (ORTEP, displacement ellipsoids
scaled to the 50% probability level). Top: top view; middle: side view;
bottom: unit-cell packing diagram.
Figure 2. X-ray crystal structure of 9a·2(CH3)2CO (ORTEP, displacement
ellipsoids scaled to the 50% probability level; some hydrogen atoms
have been removed for clarity). Top: top view; bottom: side view.
native pairing of the pyrrole subunits attached to the two
benzene rings.
À
Dashed lines are indicative of N H···O hydrogen bonds.
The hydrogen-bonding interactions seen between macro-
cycle 9a and acetone in the solid state led to the considera-
tion that 9a might also act as a receptor for anions of appro-
priate size and shape. Preliminary support for this notion
came from a single-crystal X-ray structural analysis of the
chloride anion complex of 9a (tetrabutylammonium, TBA,
are in the range of 169–1778. The distances between the CH
protons (2-position of BPB benzene ring) and the bound
chloride anion are 2.588 ꢂ and 2.721 ꢂ, respectively, while
the corresponding C-H-Cl angles are 157.88 and 162.608.
These parameters are within the range expected for hydro-
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J. L. Sessler et al.
Figure 3. X-ray crystal structure of 9a·ClÀ (ORTEP, displacement ellip-
soids scaled to the 50% probability level; some hydrogen atoms have
been removed for clarity). Top: top view; bottom: side view. Dashed
lines are indicative of N H···ClÀ hydrogen bonds.
À
À
Figure 4. X-ray crystal structure of 9a·NO3 (ORTEP, displacement ellip-
soids scaled to the 50% probability level; some hydrogen atoms have
been removed for clarity). Top: top view; bottom: side view. Dashed
À
lines are indicative of N H···O hydrogen bonds.
gen-bonding interactions, leading to the consideration that
these CH protons may also be acting to stabilize the bound
chloride anion.
À
Diffraction-grade crystals of 9a·NO3 were also obtained
by using conditions analogous to those used to obtain crys-
tals of 9a·ClÀ. X-ray structural analysis shows that, as is true
for 9a·ClÀ, the macrocycle adopts a cone-like conformation
in the solid state and interacts with the bound nitrate anion
through four NH···O hydrogen bonds (Figure 4). However,
in contrast to what was found for 9a·ClÀ, in which each of
that might be endowed with a degree of inherent selectivity
based on, for example, an ability of certain substrates, sol-
vents, and so forth to modulate their conformational flexibil-
ity.
In the case of 10a, diffraction grade crystals were ob-
À
tained for the hexafluorophosphate complex, 10a·PF6
the four pyrrolic NH protons is hydrogen bonded to the
(TBA counterion). The corresponding X-ray analysis re-
vealed a structure without any evident symmetry (Figure 5).
However, it also revealed that the PF6À ion is bound through
five well-defined hydrogen bonds involving five out of the
six possible pyrrole NH donor groups. The associated NH
À
single chloride anion, in the crystal structure of 9a·NO3
,
the four pyrrolic NH protons are involved in hydrogen-
bonding interactions with only two out of the three nitrate
oxygen atoms. In particular, it is seen that one oxygen atom
(O2a) is bound to three NH protons (N1H, N2H, and
N4H), while another oxygen atom (O1a) is bound to one
À
H F distances are in the range of 2.38–2.63 ꢂ, and the N-H-
F bond angles are in the range of 165.5–173.88. Other possi-
À
NH proton (N3H). The N O distances are in the range of
ble hydrogen bonds are also seen involving N6H···F6 and
À
2.956(2)–3.405(3) ꢂ, the NH proton–oxygen distances are in
the range of 2.09(3)–2.56(3) ꢂ, and the N-H-O bond angles
are in the range of 159(2)–175(2)8.
N4H···F1. In this case, the N F bond lengths, 3.049(12) and
3.318(11) ꢂ, respectively, were found to be within the range
expected for these kinds of hydrogen-bonding interactions.
However, the corresponding bond angles of 116.78 and
138.18, respectively, are less than ideal. When the structure
A separate important feature of this structure is that it re-
veals, in conjunction with those for 9a·2(CH3)2CO and
9a·ClÀ, that macrocycle 9a may adopt different conforma-
tions in the solid state and display different binding modes
when interacting with different substrates. This leads us to
suggest that 9a and its congeners could be versatile hosts
À
is viewed from the perspective of the bound PF6 ion, it is
seen that four out of the six possible fluorine atoms also par-
ticipate in binding interactions, as determined from their hy-
À
drogen binding parameters. In particular, these latter N F
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Calix[n]bispyrrolylbenzenes
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À
Figure 6. X-ray crystal structure of 10a·NO3 (ORTEP, displacement el-
lipsoids scaled to the 50% probability level; some hydrogen atoms have
been removed for clarity). Top: top view; bottom: side view. Dashed
À
Figure 5. X-ray crystal structure of 10a·PF6 (ORTEP, displacement ellip-
soids scaled to the 50% probability level; some hydrogen atoms have
been removed for clarity). Top: top view; bottom: side view. Dashed
À
lines are indicative of N H···O hydrogen bonds.
À
lines are indicative of N H···F hydrogen bonds.
Further comparison of the solid-state molecular structure
À
À
of 10a·NO3 with that of 10a·PF6 reveals that, in both
cases, not all the pyrrole units are involved in hydrogen-
bonding interactions with the bound anions. As with the so-
lution phase Ka data given in Table 1, these solid-state struc-
tural features are thought to reflect a cavity in 10a that is
less optimized, in terms of size, shape, and perhaps inherent
flexibility, for small-anion binding than that present in 9a.
An X-ray structural analysis of 11a, studied as
11a·4C4H8O2, revealed that this larger macrocycle adopts a
square-shaped conformation (Figure 7). In contrast to the
distances are in the range of 3.263(12)–3.523(12) ꢂ. In con-
trast to what is seen in the structure of 9a·2(CH3)2CO, in
the case of 10a·PF6À, the two fluoride atoms participating in
the hydrogen bonding interact pairwise with the pyrrole
groups attached to the two benzene rings, as opposed to
those attached to the bridging, meso-like carbon atoms.
À
Diffraction-grade crystals of 10a·NO3 were obtained by
using conditions analogous to those used to obtain crystals
of 9a·NO3À. The resulting structure is shown in Figure 6.
Here, it is seen that the macrocycle adopts a V-shaped con-
formation (Cs), with four out of its six pyrrole NH protons
bound to a nitrate anion through four NH···O hydrogen
bonds. In contrast to what is seen in the case of 9a·NO3À, all
Table 1. Anion-binding constants [mÀ1
] determined in [D2]dichloro-
1
methane by means of H NMR spectroscopic titrations.[a]
9a
10a
11a
1
8a
16
À
three oxygen atoms of the nitrate anion in 10a·NO3 are in-
FÀ
>10000[b]
>10000
>10000
>10000
>10000
6300
>10000[b]
3100
390
n.d. 17000[c] 2300[b] 2100
volved in hydrogen-bonding interactions with the receptor
in the solid state. Specifically, these hydrogen bonds include
ClÀ
BrÀ
IÀ
>10000
>10000
n.d.
n.d.
n.d.
>10000
110
350[c] 4300
10[c] 1100
110
19
<10
<10
310
11
<10[c]
<10[c]
190
290
À
À
À
À
150
850
1700
5100
30
N1 H···O3b, N3 H···O1b, N4 H···O1b, and N6 H···O2b.
The two remaining pyrrole units (those containing the N5
and N2 atoms) are not involved in any hydrogen-bonding in-
À
HSO4
H2PO4
NO3
ClO4
À
97[c] 1300
À
>10000
7900
<10
n.d.
280
32
À
À
teractions with the bound anion. The N O distances are in
<10
the range of 3.107(4)–3.304(3) ꢂ, the NH proton–oxygen
distances are in the range of 2.32(3)–2.51(2) ꢂ, and the N-
H-O bond angles are in the range of 167(3)–172(3)8.
[a] Anion used in the assay were in the form of their tetrabutylammoni-
um salts; n.d. not determinable. [b] Tetrabutylammonium fluoride trihy-
drate was used as the anion source. [c] From reference [1].
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J. L. Sessler et al.
conformation of BPB seen in the solid state (cf. Figure 1), in
11a each BPB unit adopts a trans conformation with both
pyrrole units pointing away from the center. The four ethyl
acetate molecule interacts with the macrocycle through
NH···O (carbonyl) hydrogen bonds. Interestingly, the two
pyrrole units attached to the meso-carbon C15 (and C15a)
À
are bound to one ethyl acetate molecule through two NH
O hydrogen bonds, while each of the pyrrole units attached
to the meso-carbon C30 (and C30a) form hydrogen bonds to
one ethyl acetate molecule. This last species is also bound to
a second pyrrole from another macrocycle. As the result of
these interactions, the unit cell packing diagram reveals a
columnlike assembly, as can be seen from an inspection of
Figure 7 (bottom).
Anion-binding studies: Due to the poor solubility of com-
pound 9a in acetonitrile and DMSO, preliminary anion-
binding studies of compounds 9a–11a were carried out in
[D2]dichloromethane by using standard 1H NMR spectro-
scopic titration methods. Analogous titrations involving
compounds 8a, 1, and dimethyldipyrromethane 16 (consid-
ered here as the building block for calix[4]pyrrole 1 and
thus used for comparison with building block 8a) were also
carried out.
In the case of 9a, the pyrrole NH signals were initially
found to broaden beyond the point of clear identification
upon the addition of the various halide anions and dihydro-
gen phosphate anion (these and other anions studied as
their TBA salts) before again becoming sharp in the pres-
ence of excess anion. Such broadening was also observed for
the BPB 2-CH signal in the case of the halides. It was not
observed for either signal in the case of HSO4À, NO3À, and
ClO4À. Rather, clear shifts in these signals were seen. How-
ever, in all cases, substantial shifts for the BPB 2-CH signal
in 9a were seen over the full course of the titration, with
downfield shifts ranging between 0.52 and 2.05 ppm, de-
pending on the choice of anion.
In light of the above observations, the change in chemical
shift of the pyrrolic NH resonance as a function of anion
concentration was used to determine the Ka in the case of
HSO4À, NO3À, and ClO4À. By contrast, the changes in either
the b-pyrrolic CH or benzene 2-CH resonances were used
to follow the binding process in the case of the halides and
dihydrogen phosphate, respectively. In all cases, curve fitting
was carried out by using standard methods (i.e., as described
by Wilcox[18] or Connor;[19] see the Supporting Information).
The anion-binding constants determined in this way for
macrocycle 9a and open-chain control 8a are given in
Table 1, along with those recorded for 1 and 16. As might
be inferred from the broadening of the NH peaks seen in
Figure 7. X-ray crystal structure of 11a·(C4H8O2)4 (ORTEP, displacement
ellipsoids scaled to the 30% probability level; some hydrogen atoms
omitted for clarity). Top: top view; middle: side view; bottom: unit-cell
À
packing diagram. Dashed lines are indicative of N H···O hydrogen
bonds. The ethyl acetate molecules with atoms O1b, O1ba are hydrogen
bonded to a second macrocycle related by a b axis translation.
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Calix[n]bispyrrolylbenzenes
FULL PAPER
Table 2. Anion-binding constants measured by ITC titration method in
1,2-dichloroethane.[a]
many of the NMR spectroscopic titrations, compound 9a
was found to be a very effective anion receptor. In fact, with
the exception of dihydrogen phosphate and perchlorate, for
which Ka values of 6300 and 8400mÀ1, respectively, were re-
corded, in all cases the anion affinities proved too large to
measure accurately by standard 1H NMR spectroscopic titra-
tion methods. This stands in marked contrast to what is seen
in the case of 1, for which strong binding is seen only in the
case of fluoride anion and no appreciable binding is seen in
the case of perchlorate. Interestingly, the open-chain control
system 8a was also found to be a more effective anion re-
ceptor than 16, and even macrocycle 1 in some cases, al-
though it was found to be a far less selective receptor than
these last two species.
9a
5600000
21000000
1200000
2500000
10a
11a
1
8a
ClÀ
82000
5600
11000
3800
240000
44000
76000
220000
18000
n.d.
6800
3300
n.d.
BrÀ
À
HSO4
NO3
n.d.
n.d.
À
n.d.
[a] Anion used in the assay were in the form of their tetrabutylammoni-
um salts; n.d. not determinable.
that 9a binds chloride anion with a 1:1 affinity constant, Ka,
of 5.6ꢃ106 mÀ1, or roughly 300 times as well as 1 under anal-
ogous conditions (Ka =1.8ꢃ104 mÀ1). In contrast to what
might be inferred from the NMR studies carried out in di-
chloromethane, analogous ITC studies involving 8a revealed
that this open-chain control system binds chloride anion less
effectively than 1 in 1,2-dichloroethane (DCE) (Ka =6.8ꢃ
103 vs. 1.8ꢃ104 mÀ1 for 8a and 1, respectively). Surprisingly,
9a binds the bromide anion even more strongly than the
chloride anion, a phenomenon that is rarely seen in the
calixpyrrole-type anion receptors. This enhanced affinity for
BrÀ over ClÀ displayed by 9a, we think, is a direct reflection
of the fact that the receptor cavity present in 9a provides a
better size match for this larger halide anion and that this
compatibility is sufficient to overcome any inherent binding
differences due to charge density or purely electrostatic ef-
fects.
Table 1 also shows that compared to 9a, the larger macro-
cyclic receptor 10a is a less effective anion receptor for
almost all anions of interest. This is thought to reflect the
destabilizing effects of its large cavity size and relatively
rigid structure. Not only is the large cavity size present in
10a incompatible with the size of most anions of interest,
the rather rigid nature of the receptor (close to triangular
shape) limits its ability to adopt different conformations
suitable for coordinating anions with different sizes and ge-
ometries. However, 10a does show a high affinity for the ni-
trate anion, traditionally a weak hydrogen-bonding acceptor.
This selectivity, we think, reflects the relatively good size
and geometry matching between this particular triangular
anion and the central core defined by the receptor.
Compound 10a displays selectivity for ClÀ over BrÀ,
À
1H NMR spectroscopic titration studies involving com-
pound 11a failed to provide reliable binding constants for
FÀ, IÀ, HSO4À, and H2PO4À, due either to loss in the chemi-
cal shifts used to follow the anion-binding process (FÀ,
HSO4À, and NO3 as determined by ITC in dichloroethane.
This stands in contrast to what is inferred from 1H NMR
spectroscopic titrations carried out in dichloromethane, in
À
which selectivity towards NO3 was observed. The differ-
À
HSO4À, and H2PO4 ) or difficulties in fitting the binding
ence between what is seen by ITC in dichloroethane and by
1H NMR spectroscopic titration in dichloromethane pro-
vides a cogent reminder of the fact that the anion-binding
properties (absolute affinities; relative selectivities) of an
anion receptor can be substantially different in different sol-
vent media.[1,20] There are a number of factors that could ac-
count for this, including differences in ion pairing in both
the product and the initial anion–cation salt, as well as the
fact that these two methods probe different chemistries
(e.g., interactions with pyrrolic NH protons vs. overall
system thermodynamics). Such concerns aside, it is impor-
tant to appreciate that the basic conclusion, namely that 10a
is a less effect anion receptor than 9a, still stands.
profile curve (IÀ) using standard curve fitting methods.
However, with the exception of ClO4À, for the other anions
À
of interest (ClÀ, BrÀ, and NO3 ) 11a shows higher binding
affinities than 10a. Compound 11a has larger apparent core
size than either 10a or 9a, a feature that should make it
even less compatible with most anions, than either 10a or
9a. However, macrocycle 11a is more flexible than either
macrocycle 10a or 9a; this flexibility may allow it to “mold
itself” to various anions. To the extent this occurs, higher,
rather than lower, anion affinities would be in fact expected.
Because of the limitations inherent in NMR-spectroscopy-
based titrations, efforts were made to determine the anion
affinities of these compounds by means of other, more sensi-
tive methods. Unfortunately, the lack of a spectroscopic
“handle” in 9a–11a meant that no useful binding informa-
tion could be obtained from UV-visible or fluorescence ti-
tration experiments. On the other hand, it was found that
reliable isothermal titration calorimetry (ITC) measure-
ments could be carried out in 1,2-dichloroethane.
Compound 11a also displays higher anion affinities than
10a. However, it binds most test anions more weakly than
9a. Compounds 9a–11a all display stronger anion-binding
affinities than 1, and their building block 8a. Compound 8a
also displayed a greater propensity to bind anions than 16, a
species that displayed no evidence of anion binding under
the conditions of the present ITC studies. These findings are
1
Table 2 shows the binding constants for compounds 8a–
consistent with the results from H NMR titration studies.
À
11a, and 1 with ClÀ, BrÀ, HSO4À, and NO3 ions. Com-
The ITC studies serve to highlight further the fact that,
under identical conditions of measurement, macrocycle 9a is
a far more effective anion receptor than calix[4]pyrrole 1.
This difference is notable, since they both possess the same
pound 9a has the highest anion affinities for all four anions
relative to the other anion receptors. However, it lacks good
selectivity. For example, in the case of chloride, it is seen
Chem. Eur. J. 2005, 11, 2001 – 2011
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ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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J. L. Sessler et al.
number of potential NH hydrogen-bond donor groups (four
in both cases). One potential explanation lies in the fact that
the basic subunit present in 9a, namely 1,3-bis(pyrrol-2-yl)-
benzene (8a), displays a higher inherent anion affinity than
the corresponding “building block” present in calix[4]pyr-
role 1, namely dimethyldipyrromethane (16). For example,
this latter species fails to show evidence of anion binding by
ITC and gives rise to only a modest Ka (ca. 110mÀ1) for
chloride in [D2]dichloromethane, as determined from stan-
dard 1H NMR titration methods. It is thus clearly a very
weak stand-alone anion receptor. By contrast, compound 8a
displays a high affinity not only for chloride, but also dem-
onstrates some degree of affinity for most of the anions
tested by 1H NMR titration (cf. Table 1).
Presumably, the large disparity in chloride anion affinity
observed for these two bis-pyrrole fragments reflects the
fact that the bite angle present in 8a provides a better struc-
tural match to chloride (and likely most other anions) than
does dimethyldipyrromethane. However, electronic effects
could also contribute, due to the presence of the benzene
ring and the CH–anion interaction involving the 2-position
of this bridging group.
Many of these same effects are expected to be important
in the case of the macrocyclic system 9a, with the impor-
tance of the CH–anion hydrogen-bonding interactions being
specifically inferred from both the solid-state structural anal-
ysis of 9a·ClÀ (Figure 3) and the changes in the chemical
shifts seen in the NMR titrations (vide supra). However, in
the case of the macrocycle, conformational effects are also
likely to play a greater role than in the case of the corre-
sponding open-chain systems. Here, it is specifically pro-
posed that the larger nature of the BPB fragment present in
9a and the presence of two bridging phenyl groups that can
rotate rather freely allows it to adopt more readily confor-
mations favorable to the complexation of most anions, in-
cluding specifically the chloride anion.
Experimental Section
Tetrabutylammonium chloride was dried under vacuum at 408C for 24 h
before use. Dichloromethane was dried by distillation under argon over
calcium hydride. Tetrahydrofuran (THF) was dried by passage through
two columns of activated alumina. [D2]Dichloromethane was purchased
in individual ampoules from Cambridge Isotope Inc. and used without
further purification or drying. All other reagents were obtained from
commercial sources and used as received. Melting points were measured
on a Mel-Temp II device and not corrected. 1H and 13C NMR spectra
used in the characterization of product and titration studies were record-
ed on Varian Unity 400 MHz spectrometers. Low-resolution FAB and CI
mass spectra were obtained on a Finningan MAT TSQ 70 mass spectrom-
eter. High-resolution FAB and CI mass spectra were obtained on a VG
ZAB2-E mass spectrometer.
N,N’-Diallylisophthaldiamide (12a): Allylamine (12.56 g, 0.22 mol) and
triethylamine (30.36 g, 0.3 mol) were dissolved in dichloromethane
(100 mL) in a 500 mL round-bottomed flask equipped with a 250 mL ad-
dition funnel and cooled with an ice–water bath. Isophthaloyl chloride
(13; 20.30 g, 0.1 mol) dissolved in dichloromethane (100 mL) was then
added dropwise through an addition funnel to the amine solution. Once
the addition was complete, the cooling bath was removed and the reac-
tion was stirred at room temperature overnight. The reaction mixture
was washed with water (3ꢃ100 mL) and brine (100 mL), and dried with
sodium sulfate. The volatile components were removed using a rotary
evaporator and the residue was dried under vacuum. The resulting pale
yellow solid (23.15 g, 95%) was used for the next step without further pu-
rification. M.p. 1158C; 1H NMR (400 MHz, [D1]chloroform, 258C): d=
4.08 (m, 4H; NHCH2), 5.19 (dd, J=1.2, 10 Hz, 2H; C=CHH cis), 5.26
(dd, J=1.2, 17.2 Hz, 2H; C=CHH trans), 5.92 (m, 2H; CH=CH2), 6.47
(s, 2H; NH), 7.51 (t, J=8 Hz, 1H; benzene CH), 7.94 (dd, J=2, 8 Hz,
2H; benzene CH), 8.22 ppm (t, J=2 Hz, 1H; benzene CH); 13C NMR
(100 MHz, [D1]chloroform, 258C): d=42.53, 116.92, 125.33, 128.95,
130.02, 133.74, 134.65, 166.50 ppm; HRMS (CI+): m/z calcd for
C14H17N2O2 [M+H]+: 245.1290; found: 245.1292.
N,N’-Diallyl-5-(tert-butyl)isophthaldiamide (12b): A mixture of 5-(tert-
butyl)isophthalic acid (11.10 g, 50 mmol), thionyl chloride (150 mL), and
ten drops of DMF was heated under refulx for 5 h. Excess thionyl chlo-
ride was removed under vacuum to give 5-(tert-butyl)isophthaloyl chlo-
ride (14), which was used directly in the next step without purification.
Allylamine (6.28 g, 0.11 mol) and triethylamine (12.12 g, 0.12 mol) were
dissolved in dichloromethane (100 mL) in a 500 mL round-bottomed
flask equipped with a 250 mL addition funnel and cooled with ice–water
bath. 5-(tert-Butyl)isophthaloyl dichloride (excess) dissolved in dichloro-
methane (100 mL) was then added dropwise through the funnel to the
amine solution. Once the addition was complete, the cooling bath was re-
moved and the reaction was stirred at room temperature overnight. The
reaction mixture was washed with water (3ꢃ100 mL) and brine
(100 mL), and dried with sodium sulfate. The volatile components were
removed using a rotary evaporator, and the residue was dried under
vacuum. The resulting pale yellow solid (15 g, quantitative) was used for
the next step without further purification. M.p. 1398C; 1H NMR
(400 MHz, [D1]chloroform, 258C): d=1.31 (s, 9H; CH3), 4.04 (m, 4H;
NHCH2), 5.14 (dd, J=1.2, 10 Hz, 2H; C=CHH cis), 5.22 (dd, J=1.2,
16.8 Hz, 2H; C=CHH trans), 5.88 (m, 2H; CH=CH2), 6.54 (s, 2H; NH),
7.94 (d, J=1.6 Hz, 2H; benzene CH), 7.92 ppm (t, J=1.6, 2H; benzene
CH); 13C NMR (100 MHz, [D1]chloroform, 258C): d=31.16, 35.05, 42.57,
116.92, 122.21, 127.29, 133.87, 134.50, 152.58, 167.00 ppm; HRMS (CI+):
m/z calcd for C18H25N2O2 [M+H]+: 301.1916; found: 301.1920.
Conclusion
In conclusion, we have synthesized three new calixpyrrole-
like macrocycles, namely 9–11, from an easy-to-synthesize
building block, BPB 8, which serves as a structural surrogate
for terpyrrole. Anion-binding studies carried out in dichloro-
methane and dichloroethane confirm that compound 9a is a
versatile anion receptor, binding most anions, including
chloride, with affinities that are greatly enhanced relative to
those of 1. Such observations are rationalized in terms of
the presence of a “building block”, BPB 8a, which displays
a higher inherent affinity for anions than does dimethyldi-
pyrromethane 16, the analogous core subunit present in
calix[4]pyrrole 1. The ability to more readily adopt confor-
mations that are suitable for anion binding is also consid-
ered important, especially in the case of the larger system
11a. Current work is focused on preparing new systems that
will allow the interplay of these various influencing factors
to be better understood.
N,N’-Diallyl-5-hexyloxyisophthaldiamide (12c): Dimethyl-5-hexyloxy-
isophthalate (15; 8.82 g, 30 mmol) was dissolved in allylamine (90 mL),
and the mixture was stirred at RT for 4 days. The excess solvent was re-
moved under reduced pressure. Column chromatographic purification
(silica gel, 1% CH3OH in dichloromethane, eluent) of the residue afford-
ed 12c in the form of a brown oil (9 g, 75%). 1H NMR (400 MHz,
[D1]chloroform, 258C): d=0.91 (t, J=7.2 Hz, 3H; CH3), 1.33 (m, 4H;
CH2), 1.45 (m, 2H; CH2), 1.78 (m, 2H; CH2), 4.01 (t, J=6.4 Hz, 2H;
OCH2), 4.06 (m, 4H; NHCH2), 5.18 (dd, J=1.2, 10 Hz, 2H; C=CHH
2008
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Chem. Eur. J. 2005, 11, 2001 – 2011

Calix[n]bispyrrolylbenzenes
FULL PAPER
cis), 5.25 (dd, J=1.2, 16.8 Hz, 2H; C=CHH trans), 5.91 (m, 2H; CH=
CH2), 6.46 (s, 2H; NH), 7.45 (d, J=2.0 Hz, 2H; benzene CH), 7.73 ppm
(t, J=1.2 Hz, 2H; benzene CH); 13C NMR (100 MHz, [D1]chloroform,
258C): d=14.00, 22.55, 26.00, 29.03, 31.47, 42.55, 68.57, 116.12, 116.89,
116.99, 133.73, 136.01, 159.57, 166.38 ppm; HRMS (CI+): m/z calcd for
C20H29N2O3 [M+H]+: 345.2178; found: 345.2181.
HRMS (CI+): m/z calcd for C34H33N4 [M+H]+: 497.2705; found:
497.2700.
Compound 10a: White solid (82 mg, 17%); m.p. >1408C (decomp);
1H NMR (400 MHz, [D1]chloroform, 258C): d=1.72 (s, 18H; CH3), 6.20
(t, J=2.8 Hz, 6H; b-pyrrole CH), 6.40 (t, J=2.8 Hz, 6H; b-pyrrole CH),
7.15–7.24 (m, 12H; benzene CH), 7.96 ppm (s, 6H; pyrrole NH);
13C NMR (100 MHz, [D1]chloroform, 258C): d=29.29, 35.73, 105.80,
105.89, 118.51, 121.55, 129.21, 131.53, 132.96, 140.08 ppm; HRMS (CI+):
m/z calcd for C51H49N6 [M+H]+: 745.4019; found: 745.4028.
1,3-Bis(pyrrol-2-yl)benzene (8a): A mixture of 12a (2.44 g, 10 mmol),
phosgene (20% solution in toluene, 40 mL), and DMF (4 drops) was
stirred for 15 h at room temperature under Ar. The resulting mixture was
then heated at 40–458C for 2 h, after which the solvent was removed in
vacuo (caution: phosgene is highly toxic and must be handled with ap-
propriate care. Two cold traps immersed in liquid N2 were used to receive
the solvent and phosgene). The residue was dissolved in THF (60 mL)
and added dropwise with stirring to a solution of potassium tert-butoxide
(5.89 g, 52 mmol) in THF (60 mL) at 5–108C under Ar. After stirring for
1 h at this temperature, the reaction mixture was poured into ice water
and extracted with chloroform (3ꢃ100 mL). The organic phase was dried
(Na2SO4) and evaporated to dryness. The residue was subjected to
column chromatography (silica gel, dichloromethane, eluent) to give
crude product, which upon recrystallization from dichloromethane/hex-
anes afforded 8a in the form of a white solid (0.6 g, 29%). M.p. 1638C;
1H NMR (400 MHz, [D1]chloroform, 258C): d=6.32 (q, J=2.8 Hz, 2H;
pyrrole CH), 6.56 (m, 2H; pyrrole CH), 6.89 (m, 2H; pyrrole CH), 7.30–
7.39 (m, 3H; benzene CH), 7.58 (t, J=1.6 Hz, 1H; benzene CH),
8.47 ppm (brs, 2H; pyrrole NH); 13C NMR (100 MHz, [D1]chloroform,
258C): d=100.18, 110.16, 118.98, 119.62, 121.77, 129.40, 131.95,
133.36 ppm; HRMS (CI+): m/z calcd for C14H13N2 [M+H]+: 209.1079;
found: 209.1079.
Compound 11a: White solid (64 mg, 13%); m.p. >1408C (decomp.);
1H NMR (400 MHz, [D1]chloroform, 258C): d=1.70 (s, 24H; CH3), 6.17
(t, J=2.8 Hz, 8H; b-pyrrole CH), 6.41 (t, J=2.8 Hz, 8H; b-pyrrole CH),
7.15–7.23 (m, 12H; benzene CH), 7.33 (t, J=1.2 Hz, 4H; benzene CH),
8.03 ppm (m, 8H; pyrrole NH); 13C NMR (100 MHz, [D1]chloroform,
258C): d=29.26, 35.70, 105.83, 105.88, 118.97, 121.45, 129.19, 131.43,
133.05, 140.06 ppm; HRMS (CI+): m/z calcd for C68H65N8 [M+H]+:
993.5332; found: 993.5304.
Calix[n]5-(tert-butyl)-1,3-bis(pyrrol-2-yl)benzene (9b–11b): This set of
compounds was prepared from 8b (0.26 g, 1 mmol) in a manner analo-
gous to that used to prepare 9a–11a. Column chromatography (silica gel,
gradient of hexanes to hexanes/ethyl acetate 1:9 as eluent) afforded 9b–
11b:
Compound 9b: White solid (50 mg, 16%); m.p. >2008C (decomp);
1H NMR (400 MHz, [D1]chloroform, 258C): d=1.34 (s, 18H; benzene
CH3), 1.72 (s, 12H; meso CH3), 6.17 (t, J=2.8 Hz, 4H; b-pyrrole CH),
6.37 (t, J=2.8 Hz, 4H; b-pyrrole CH), 7.03 (t, J=1.6 Hz, 2H; benzene
CH), 7.40 (d, J=1.6 Hz, 4H; benzene CH), 8.08 ppm (s, 4H; pyrrole
NH); 13C NMR (100 MHz, [D1]chloroform, 258C): d=30.34, 31.24, 34.77,
35.87, 105.96, 106.86, 118.15, 122.54, 132.02, 133.84, 134.00, 152.56 ppm;
HRMS (CI+): m/z calcd for C42H49N4 [M+H]+: 609.3957; found:
609.3966.
5-(tert-Butyl)-1,3-bis(pyrrol-2-yl)benzene (8b): Compound 8b was pre-
pared from 12b (3 g, 10 mmol) in the same manner as 8a. After column
chromatography (silica gel, dichloromethane/hexanes 4:1, eluent), the
crude product was recrystalized from benzene/hexanes to afford 8b in
the form of a pale yellow solid (1.13 g, 43%). M.p. 1638C; 1H NMR
(400 MHz, [D1]chloroform, 258C): d=1.37 (s, 9H; CH3), 6.32 (m, 2H;
pyrrole CH), 6.54 (m, 2H; pyrrole CH), 6.88 (m, 2H; pyrrole CH), 7.4
(d, J=1.2 Hz, 2H; benzene CH), 7.38 (t, J=1.2 Hz, 1H; benzene CH),
8.47 ppm (brs, 2H; pyrrole NH); 13C NMR (100 MHz, [D1]chloroform,
258C): d=31.33, 34.81, 106.03, 110.06, 117.44, 118.73, 119.40, 132.50,
133.14, 152.30 ppm; HRMS (CI+): m/z calcd for C18H21N2 [M+H]+:
265.1705; found: 265.1700.
Compound 10b: White solid (66 mg, 22%); m.p. 1948C (decomp);
1H NMR (400 MHz, [D1]chloroform, 258C): d=1.30 (s, 27H; benzene
CH3), 1.73 (s, 18H; meso CH3), 6.20 (t, J=2.8 Hz, 6H; b-pyrrole CH),
6.39 (t, J=2.8 Hz, 6H; b-pyrrole CH), 7.07 (t, J=1.2 Hz, 3H; benzene
CH), 7.21 (d, J=1.2 Hz, 6H; benzene CH), 8.03 ppm (s, 6H; pyrrole
NH); 13C NMR (100 MHz, [D1]chloroform, 258C): d=29.43, 31.26, 34.71,
35.75, 105.68, 105.80, 116.37, 119.17, 131.99, 132.72, 139.89, 152.11 ppm;
HRMS (CI+): m/z calcd for C63H73N6 [M+H]+: 913.5897; found:
913.5912.
Compound 11b: White solid (34 mg, 11%); m.p. >1808C; 1H NMR
(400 MHz, [D1]chloroform, 258C): d=1.29 (s, 36H; benzene CH3), 1.70
(s, 24H; meso CH3), 6.15 (t, J=2.8 Hz, 8H; b-pyrrole CH), 6.38 (t, J=
2.8 Hz, 8H; b-pyrrole CH), 7.11 (t, J=1.2 Hz, 4H; benzene CH), 7.19 (d,
J=1.2 Hz, 8H; benzene CH), 8.04 ppm (s, 8H; pyrrole NH); 13C NMR
(100 MHz, [D1]chloroform, 258C): d=29.30, 31.26, 34.70, 35.70, 105.76,
116.78, 119.35, 131.98, 132.91, 139.90, 152.10 ppm; HRMS (CI+): m/z
calcd for C84H97N8 [M+H]+: 1217.7836; found: 1217.7833.
5-Hexyloxy-1,3-bis(pyrrol-2-yl)benzene (8c): This compound was pre-
pared from 12c (5 g, 14.5 mmol) in the same manner as 8a. Column chro-
matography (silica gel, dichloromethane/hexanes 1:1, eluent) afforded 8c
in the form of a pale yellow solid (3.30 g, 96%). M.p. 668C; 1H NMR
(400 MHz, [D1]chloroform, 258C): d=0.91 (t, J=6.8 Hz, 3H; CH3), 1.36
(m, 4H; CH2), 1.49 (m, 2H; CH2), 1.81 (m, 2H; CH2), 4.02 (t, J=6.4 Hz,
2H; OCH2), 6.31 (m, 2H; pyrrole CH), 6.54 (m, 2H; pyrrole CH), 6.85
(d, J=1.2 Hz, 2H; benzene CH), 6.87 (m, 2H; pyrrole CH), 7.16 (t, J=
1.2 Hz, 1H; benzene CH), 8.45 ppm (brs, 2H; pyrrole NH); 13C NMR
(100 MHz, [D1]chloroform, 258C): d=14.03, 22.60, 25.73, 29.27, 31.57,
68.11, 106.31, 108.16, 110.07, 112.33, 118.91, 131.96, 134.55, 160.01 ppm;
HRMS (CI+): m/z calcd for C20H25N2O [M+H]+: 309.1967; found:
309.1967.
Calix[n][5-hexyloxy-1,3-bis(pyrrol-2-yl)benzene] (9c–11c): This set of
compounds was prepared from 7c (0.46 g, 1.5 mmol) by using the same
procedure as used to prepare 9a–11a. Column chromatography (silica
gel, gradient of hexanes to hexanes/ethyl acetate 1:19 as eleuent) afford-
ed 9c–11c:
Compound 9c: White solid (58 mg, 11%); m.p. 1728C; 1H NMR
(400 MHz, [D1]chloroform, 258C): d=0.90 (t, J=6.8 Hz, 6H; CH2CH3),
1.34 (m, 8H; CH2), 1.46 (m, 4H; CH2), 1.72 (s, 12H; meso CH3), 1.79 (m,
4H; CH2), 3.99 (t, J=6.8 Hz, 4H; OCH2), 6.16 (t, J=2.8 Hz, 4H; b-pyr-
role CH), 6.36 (t, J=2.8 Hz, 4H; b-pyrrole CH), 6.80 (t, J=1.2 Hz, 2H;
benzene CH), 6.90 (d, J=1.2 Hz, 4H; benzene CH), 8.10 ppm (s, 4H;
pyrrole NH); 13C NMR (100 MHz, [D1]chloroform, 258C): d=14.03,
22.60, 25.70, 29.20, 30.17, 31.56, 35.80, 68.10, 106.07, 107.28, 111.01,
112.72, 131.60, 135.28, 140.14, 159.93 ppm; HRMS (CI+): m/z calcd for
C46H57N4O2 [M+H]+: 697.4482; found: 697.4482.
Calix[n]1,3-bis(pyrrol-2-yl)benzenes 9a–11a: Compound 8a (0.42 g,
2 mmol) was dissolved in acetone (40 mL) and the mixture was degassed
by bubbling with Ar for ten minutes. Trifluoroacetic acid (0.23 g, 2 mmol)
was added, and the resulting mixture was stirred at room temperature for
12 h. Triethylamine was added to quench the reaction, and the solvent
was evaporated in vacuo. Column chromatography (silica gel, gradient of
hexanes to hexanes/ethyl acetate 1:9 as eluents) afforded the title com-
pounds 9a–11a:
Compound 9a: White solid (68 mg, 14%); m.p. >1808C (decomp);
1H NMR (400 MHz, [D1]chloroform, 258C): d=1.74 (s, 12H; CH3), 6.17
(t, J=2.8 Hz, 4H; b-pyrrole CH), 6.37 (t, J=2.8 Hz, 4H; b-pyrrole CH),
7.20 (s, 2H; benzene CH), 7.35 (s, 6H; benzene CH), 8.09 ppm (s, 4H;
pyrrole NH); 13C NMR (100 MHz, [D1]chloroform, 258C): d=30.13,
35.81, 106.14, 107.32, 120.14, 124.88, 129.56, 131.54, 134.02, 140.27 ppm;
Compound 10c: White solid (104 mg, 20%); m.p. >808C (no clear
m.p.); 1H NMR (400 MHz, [D1]chloroform, 258C): d=0.89 (t, J=6.8 Hz,
9H; CH2CH3), 1.31 (m, 12H; CH2), 1.44 (m, 6H; CH2), 1.71 (s, 18H;
meso CH3), 1.75 (m, 6H; CH2), 3.95 (t, J=6.4 Hz, 6H; OCH2), 6.18 (t,
Chem. Eur. J. 2005, 11, 2001 – 2011
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ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2009

J. L. Sessler et al.
J=2.8 Hz, 6H; b-pyrrole CH), 6.38 (t, J=2.8 Hz, 6H; b-pyrrole CH),
6.69 (d, J=1.6 Hz, 6H; benzene CH), 6.83 (t, J=1.6 Hz, 3H; benzene
CH), 7.93 ppm (s, 6H; pyrrole NH); 13C NMR (100 MHz,
[D1]chloroform, 258C): d=14.03, 22.57, 25.70, 29.26, 29.29, 31.56, 35.71,
68.01, 105.86, 105.96, 107.77, 111.44, 131.54, 134.19, 140.00, 159.80 ppm;
HRMS (FAB+): m/z calcd for C69H84N6O3 [M]+: 1044.6605, found:
1044.6631.
anes. The data crystal was cut from a large cluster of crystals and had ap-
proximate dimensions 0.51ꢃ0.16ꢃ0.08 mm: orthorhombic, space group
Pbcn, a=40.79880(10), b=12.5954(2), c=17.7740(6) ꢂ, a=b=g=908,
V=9133.7(3) ꢂ3, Z=8, 1calcd =1.165 gcmÀ3
, , F(000)=
m=0.073 mmÀ1
3472. A total of 494 frames of data were collected using w-scans with a
scan range of 0.78 and a counting time of 108 seconds per frame. A total
of 18428 reflections were measured, 10412 of which were unique (Rint
=
0.1244). The structure was refined on F2 to 0.126, with R(F) equal to
0.0676 and a goodness of fit S=1.21.
Compound 11c: White solid (34 mg, 11%); m.p. >1208C (no clear
m.p.); 1H NMR (400 MHz, [D1]chloroform, 258C): d=0.89 (t, J=6.8 Hz,
12H; CH2CH3), 1.32 (m, 16H; CH2), 1.43 (m, 8H; CH2), 1.69 (s, 24H;
meso CH3), 1.75 (m, 8H; CH2), 3.94 (t, J=6.4 Hz, 8H; OCH2), 6.13 (t,
J=2.8 Hz, 8H; b-pyrrole CH), 6.38 (t, J=2.8 Hz, 4H; b-pyrrole CH),
6.69 (d, J=1.2 Hz, 8H; benzene CH), 6.90 (s, 4H; benzene CH),
8.02 ppm (s, 8H; pyrrole NH); 13C NMR (100 MHz, [D1]chloroform,
258C): d=14.03, 22.57, 25.71, 29.26, 31.57, 35.67, 68.03, 105.83, 106.10,
107.87, 111.80, 131.44, 1354.35, 139.99, 159.82 ppm; HRMS (FAB+): m/z
calcd for C92H112N8O4 [M]+: 1392.8807; found: 1392.8788.
Compound 10a·C16H36NPF6·3CH2Cl2: C70H86Cl6F6N7P; crystals grew as
colorless lathes by slow evaporation of a solution of 10a and tetrabu-
tylammonium hexafluorophosphate (1:1) dissolved in dichloromethane in
an atmosphere saturated with hexanes. The data crystal was a long lathe
that had approximate dimensions; 0.56ꢃ0.24ꢃ0.07 mm: monoclinic,
space group P21/c, a=19.570(2), b=17.228(2), c=21.934(3) ꢂ, a=g=
908, b=104.622(4)8, V=7155.6(15) ꢂ3, Z=4, 1calcd =1.228 gcmÀ3
, m=
0.323 mmÀ1, F(000)=2920. A total of 300 frames of data were collected
using w-scans with a scan range of 18 and a counting time of 169 seconds
per frame. A total of 12703 reflections were measured, 7963 of which
were unique (Rint =0.1369). The structure was refined on F2 to 0.199, with
R(F) equal to 0.154 and a goodness of fit S=1.61.
X-ray structure determinations: The data were collected on a Nonius
Kappa CCD diffractometer using a graphite monochromator with MoKa
radiation (l=0.71073 ꢂ). The data were collected at 153 K by using an
Oxford Cryostream low-temperature device. Data reduction were per-
formed using DENZO-SMN.[21] The structures were solved by direct
methods using SIR92[22] or SIR97,[23] and refined by full-matrix least-
squares on F2 with anisotropic displacement parameters for the non-H
atoms by using SHELXL-97.[24] The hydrogen atoms on carbon were cal-
culated in ideal positions with isotropic displacement parameters set to
1.2Ueq of the attached atom (1.5Ueq for methyl hydrogen atoms). Neutral
atom scattering factors and values used to calculate the linear absorption
coefficient are from the International Tables for X-ray Crystallography
(1992).[25]
Compound 10a·C16H36NNO3·3CH2Cl2: C70H90Cl6N8O3; crystals grew as
pale yellow plates by slow evaporation of a solution of 10a and tetrabu-
tylammonium nitrate (1:1) dissolved in dichloromethane in an atmos-
phere saturated with hexanes. The data crystal was cut from a cluster of
crystals and had approximate dimensions; 0.30ꢃ0.24ꢃ0.17 mm: mono-
clinic, space group P21/c, a=18.6292(3), b=16.9861(3), c=22.4638(4) ꢂ,
a=g=908, b=102.662(1)8, V=6935.5(2) ꢂ3, Z=4, 1calcd =1.249 gcmÀ3
,
m=0.299 mmÀ1, F(000)=2768. A total of 304 frames of data were collect-
ed using w-scans with a scan range of 18 and a counting time of
217 seconds per frame. A total of 27570 reflections were measured,
15772 of which were unique (Rint =0.0710). The structure was refined on
F2 to 0.201, with R(F) equal to 0.116 and a goodness of fit S=2.39.
Compound 8a: C14H12N2; crystals grew as large thin plates with a slight
violet tinge by slow evaporation of a solution of 8a dissolved in dichloro-
methane in an atmosphere saturated with hexanes. The data crystal was
cut from a larger crystal and had approximate dimensions; 0.27ꢃ0.17ꢃ
0.09 mm: orthorhombic, space group Pnma, a=6.4010(2), b=23.0270(6),
Compound 11a·4C4H8O2: C42H48lN4O4; crystals grew as long colorless
needle and lathes on the wall of a test tube right after the column chro-
matography (silica gel, ethyl acetate/hexanes 1:9). The data crystal was
cut from a large cluster of crystals and had approximate dimensions
0.48ꢃ0.22ꢃ0.11 mm: monoclinic, space group P21/n, a=20.1548(6), b=
6.5134(2), c=28.2362(10) ꢂ, a=g=908, b=91.508(2)8, V=3705.5(2) ꢂ3,
Z=4, 1calcd =1.206 gcmÀ3, m=0.078 mmÀ1, F(000)=1440. A total of 476
frames of data were collected using w-scans with a scan range of 0.88 and
a counting time of 145 seconds per frame. A total of 11762 reflections
were measured, 11762 of which were unique. The structure was refined
on F2 to 0.189, with R(F) equal to 0.106 and a goodness of fit S=1.94.
c=7.2189(2) ꢂ, a=b=g=908, V=1064.04(5) ꢂ3, Z=4, 1calcd
=
1.300 gcmÀ3, m=0.078 mmÀ1, F(000)=440. A total of 412 frames of data
were collected using w-scans with a scan range of 18 and a counting time
of 129 seconds per frame. A total of 2206 reflections were measured,
1250 of which were unique (Rint =0.0410). The structure was refined on
F2 to 0.129, with R(F) equal to 0.0550 and a goodness of fit S=1.14.
Compound 9a·2C3H6O: C40H44N4O2; crystals grew as colorless lathes by
slow evaporation of a solution of 9a dissolved in dichloromethane and
acetone in an atmosphere saturated with hexanes. The data crystal was
cut from a larger crystal and had approximate dimensions; 0.20ꢃ0.20ꢃ
0.08 mm: orthorhombic, space group P212121, a=7.25800(10), b=
21.3115(4), c=21.5388(4) ꢂ, a=b=g=908, V=3331.60(10) ꢂ3, Z=4,
1calcd =1.222 gcmÀ3, m=0.076 mmÀ1, F(000)=1312. A total of 280 frames
of data were collected using w-scans with a scan range of 18 and a count-
ing time of 190 seconds per frame. A total of 7584 reflections were mea-
sured, 4315 of which were unique (Rint =0.0672). The structure was re-
fined on F2 to 0.0924, with R(F) equal to 0.0455 and a goodness of fit S=
1.00.
CCDC-248670 (9a·2C3H6O), CCDC-248671 (9a·C16H36NNO3), CCDC-
248672 (9a·C16H36NCl), CCDC-248673 (10a·C16H36NNO3·3CH2Cl2),
CCDC-248674 (10a·C16H36NPF6·3CH2Cl2), CCDC-248675 (8a), and
CCDC-248676 (11a·4C4H8O2) contain the supplementary crystollographic
data for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
Compound 9a·C16H36NCl: C50H68ClN5; crystals grew as pale brown or
very light tan plates by slow evaporation of a solution of 9a and tetrabu-
tylammonium chloride (1:1) dissolved in dichloromethane in an atmo-
sphere saturated with hexanes. The data crystal was cut from a large clus-
ter of crystals and had approximate dimensions 0.43ꢃ0.21ꢃ0.12 mm: or-
thorhombic, space group Pbcn, a=41.0311(5), b=12.6474(1), c=
Acknowledgement
This work was supported by the National Institute of Health (Grant No.
GM 58907 to J.L.S.) and Kraft Foods.
17.3594(2) ꢂ,
a=b=g=908,
V=9008.43(17) ꢂ3,
Z=8,
1calcd =
1.142 gcmÀ3, m=0.124 mmÀ1, F(000)=3360. A total of 913 frames of data
were collected using w-scans with a scan range of 0.68 and a counting
time of 78 seconds per frame. A total of 18826 reflections were measured,
10137 of which were unique (Rint =0.1062). The structure was refined on
F2 to 0.154, with R(F) equal to 0.0607 and a goodness of fit S=1.06.
[1] P. A. Gale, J. L. Sessler, V. Kral, V. Lynch, J. Am. Chem. Soc. 1996,
118, 5140–5141.
[2] K. Kavallieratos, C. M. Bertao, R. H. Crabtree, J. Org. Chem. 1999,
64, 1675–1683.
[3] P. A. Gale, S. Camiolo, G. J. Tizzard, C. P. Chapman, M. E. Light,
S. J. Coles, M. B. Hursthouse, J. Org. Chem. 2001, 66, 7849–7853.
[4] K. Sato, S. Arai, T. Yamagishi, Tetrahedron Lett. 1999, 40, 5219–
5222.
Compound 9a·C16H36NNO3: C50H68N6O5; crystals grew as colorless plates
by slow evaporation of a solution of 9a and tetrabutylammonium nitrate
(1:1) dissolved in dichloromethane in an atmosphere saturated with hex-
2010
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 2001 – 2011

Calix[n]bispyrrolylbenzenes
FULL PAPER
[5] A. Szumna, J. Jurczak, Eur. J. Org. Chem. 2001, 4031–4039.
[6] K. Choi, A. D. Hamilton, Coord. Chem. Rev. 2003, 240, 101–110.
[7] a) B. Turner, M. Botoshansky, Y. Eichen, Angew. Chem. 1998, 110,
2633–2637; Angew. Chem. Int. Ed. 1998, 37, 2475–2478; b) B.
Turner, A. Shterenberg, M. Kapon, K. Suwinska, Y. Eichen, Chem.
Commun. 2001, 13–14; c) B. Turner, A. Shterenberg, M. Kapon, K.
Suwinska, Y. Eichen, Chem. Commun. 2002, 404–405; d) B. Turner,
A. Shterenberg, M. Kapon, K. Suwinska, Y. Eichen, Chem.
Commun. 2002, 726–727.
[8] a) G. Cafeo, F. H. Kohnke, G. L. La Torre, A. J. P. White, D. J. Wil-
liams, Angew. Chem. 2000, 112, 1561–1563; Angew. Chem. Int. Ed.
2000, 39, 1496–1498; b) G. Cafeo, F. H. Kohnke, G. L. La Torre,
A. J. P. White, D. J. Williams, Chem. Commun. 2000, 1207–1208;
c) G. Cafeo, F. H. Kohnke, G. L. La Torre, M. F. Parisi, R. P. Nas-
cone, A. J. P. White, D. J. Williams, Chem. Eur. J. 2002, 8, 3148–
3156; d) G. Cafeo, F. H. Kohnke, M. F. Parisi, R. P. Nascone, G. L.
La Torre, D. J. Williams, Org. Lett. 2002, 4, 2695–2697.
[9] J. L. Sessler, P. Anzenbacher, Jr., J. A. Shriver, K. Jurisꢄkovꢅ, H.
Miyaji, V. Lynch, M. Marquez, J. Am. Chem. Soc. 2000, 122, 12061–
12062.
[14] J. L. Sessler, D. An, W.-S. Cho, V. Lynch, Angew. Chem. 2003, 115,
2380–2383; Angew. Chem. Int. Ed. 2003, 42, 2278–2281.
[15] J. L. Sessler, D. An, W.-S. Cho, V. Lynch, J. Am. Chem. Soc. 2003,
125, 13646–13647.
[16] E.-C. Lee, Y.-K. Park, J.-H. Kim, H. Hwang, Y.-R. Kim, C.-H. Lee,
Tetrahedron Lett. 2002, 43, 9493–9495.
[17] G. A. Sotzing, J. R. Reynolds, A. R. Katritzky, J. Soloducho, S. Be-
lyakov, R. Musgrave, Macromolecules 1996, 29, 1679–1684.
[18] C. S. Wilcox in Frontiers in Supramolecular Organic Chemistry and
Photochemistry (Eds.: H.-J. Schneider, H. Dꢆrr), VCH, Weinheim,
1991, pp. 123–143.
[19] K. A. Connors, Binding Constants, John Wiley, New York, 1987.
[20] F. P. Schmidtchen, Org. Lett. 2002, 4, 431–434.
[21] Z. Otwinowski, W. Minor, Methods Enzymol. 1997, 276, 307–326.
[22] “SIR92: A program for crystal structure solution”: A. Altomare, G.
Cascarano, C. Giacovazzo, A. Guagliardi, J. Appl. Crystallogr. 1993,
26, 343–350.
[23] “SIR97: A program for crystal structure solution”: A. Altomare,
M. C. Burla, M. Camalli, G. L. Cascarano, C. Giacovazzo, A. Gua-
gliardi, A. G. G. Moliterni, G. Polidori, R. Spagna, J. Appl. Crystal-
logr. 1999, 32, 115–119.
[24] G. M. Sheldrick, SHELXL97. Program for the Refinement of Crys-
tal Structures, 1997, University of Gçttingen, Gçttingen (Germany).
[25] International Tables for X-ray Crystallography Vol. C (Ed.: A. J. C.
Wilson), Kluwer Academic Press, Boston, 1992, Tables 4.2.6.8 and
6.1.1.4.
[10] J. A. Shriver, Ph.D. Dissertation, The University of Texas at Austin
(USA), 2002.
[11] V. Krꢅl, P. A. Gale, P. Anzenbacher Jr., K. Jursꢄkovꢅ, V. Lynch, J. L.
Sessler, Chem. Commun. 1998, 9–10.
[12] J. L. Sessler, W.-S. Cho, V. Lynch, V. Krꢅl, Chem. Eur. J. 2002, 8,
1134–1143.
[13] a)Y.-S. Jang, H.-J. Kim, P.-H. Lee, C.-H. Lee, Tetrahedron Lett. 2000,
41, 2919–2923; b) N. Arumugam, Y.-S. Jang, C.-H. Lee, Org. Lett.
2000, 2, 3115–3117; c) A. Nagarajan, J.-W. Ka, C.-H. Lee, Tetrahe-
dron 2001, 57, 7323–7330.
Received: August 31, 2004
Published online: December 29, 2004
Chem. Eur. J. 2005, 11, 2001 – 2011
www.chemeurj.org
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2011