The squaramide versus urea contest for anion recognition

Article abstract of DOI:10.1002/chem.200903190

The interaction of a neutral squaramide-based receptor, equipped with two 4-nitrophenyl substituents (R_sq), with halides and oxoanions has been studied in MeCN. UV/Vis and ¹H NMR spectroscopy titration experiments clearly indicated the formation of 1:1 hydrogen bonding [R _sq...X]+ complexes with all the investigated anions. X-ray diffraction studies on the chloride and bromide complex salts confirmed the 1:1 stoichiometry and indicated the establishment of bifurcated hydrogen-bond interactions between the squaramide-based receptor and the halide anion that involved both 1) amide N-H and 2) aryl proximate C-H fragments, for a total of four bonds. Probably due to the contribution of C-H fragments, complexes of R_sq with halides are 1 to 2 orders of magnitude more stable than the corresponding ones with the analogous ureabased receptor that contains two 4-nitrophenyl substituents (R_ur). In the case of oxoanions, R _sq forms complexes, the stability of which decreases with the decreasing basicity of the anion (H₂PO₄- > NO ₂- ≈ HSO₄- > NO₃-), and is comparable to that of complexes of the urea-based receptor R_ur. Such a behaviour is ascribed to the predominance of different contributions: electrostatic interaction for halides, acid-to-base 'frozen' proton trans-fer for oxoanions. Finally, with the strongly basic anions F- and CH₃COO-, R _sq first gives genuine hydrogen-bond complexes of 1:1 stoichiometry; then, upon addition of a second anion equivalent, it undergoes deprotonation of one N-H fragment, with the simultaneous formation of the dianion hydrogen-bond complexes, [HF₂]- and [CH₃COOH-CH₃COO]-, respectively. In the case of the ureabased derivative R_ur, deprotonation takes place with fluoride but not with acetate. The apparently higher Bronsted acidity of R_sq with respect to R_ur reflects the capability of the squaramide receptor to delocalise the negative charge formed on N-H deprotonation over the cyclobutene-1,2-dione ring and the entire molecular framework.

Full text of DOI:10.1002/chem.200903190

DOI: 10.1002/chem.200903190
The Squaramide versus Urea Contest for Anion Recognition
Valeria Amendola,[a] Greta Bergamaschi,[a] Massimo Boiocchi,[b] Luigi Fabbrizzi,*[a] and
Michele Milani[a]
Abstract: The interaction of a neutral
squaramide-based receptor, equipped
with two 4-nitrophenyl substituents
(Rsq), with halides and oxoanions has
been studied in MeCN. UV/Vis and
1H NMR spectroscopy titration experi-
ments clearly indicated the formation
of 1:1 hydrogen bonding [Rsq···X]+
complexes with all the investigated
anions. X-ray diffraction studies on the
chloride and bromide complex salts
confirmed the 1:1 stoichiometry and in-
dicated the establishment of bifurcated
hydrogen-bond interactions between
the squaramide-based receptor and the
halide anion that involved both
Rsq with halides are 1 to 2 orders of
magnitude more stable than the corre-
sponding ones with the analogous urea-
based receptor that contains two 4-ni-
trophenyl substituents (Rur). In the
case of oxoanions, Rsq forms com-
plexes, the stability of which decreases
fer for oxoanions. Finally, with the
strongly
basic
anions
Fꢀ and
CH3COOꢀ, Rsq first gives genuine hy-
drogen-bond complexes of 1:1 stoichi-
ometry; then, upon addition of
a
second anion equivalent, it undergoes
ꢀ
deprotonation of one N H fragment,
with the decreasing basicity of the
with the simultaneous formation of the
dianion hydrogen-bond complexes,
[HF2]ꢀ and [CH3COOH···CH3COO]ꢀ,
respectively. In the case of the urea-
based derivative Rur, deprotonation
takes place with fluoride but not with
acetate. The apparently higher Brønst-
ed acidity of Rsq with respect to Rur re-
flects the capability of the squaramide
receptor to delocalise the negative
ꢀ
anion
(H2PO4ꢀ >NO2ꢀ ꢁHSO4
>
ꢀ
NO3 ), and is comparable to that of
complexes of the urea-based receptor
Rur. Such a behaviour is ascribed to the
predominance of different contribu-
tions: electrostatic interaction for hal-
ides, acid-to-base ꢁfrozenꢀ proton trans-
ꢀ
1) amide N H and 2) aryl proximate
Keywords: acid–base equilibria
·
ꢀ
ꢀ
C H fragments, for a total of four
charge formed on N H deprotonation
anions · charge transfer · hydrogen
bonds · pi interactions
bonds. Probably due to the contribu-
over the cyclobutene-1,2-dione ring
and the entire molecular framework.
ꢀ
tion of C H fragments, complexes of
Introduction
building block for designing anion receptors because it pos-
ꢀ
sesses two N H fragments, which can bind 1) a single ac-
Anion recognition by artificial host molecules (receptors) is
an important topic of supramolecular chemistry.[1] Receptors
can be neutral or positively charged. Most neutral artificial
ceptor atom (e.g., that of a halide ion), thus forming a six-
membered chelate ring, or 2) two adjacent oxygen atoms of
an oxoanion, to give an eight-membered chelate ring. A va-
riety of receptors that contain two or more urea moieties
have been synthesised. Examples include cyclic and acyclic
systems of varying complexity, arranged for multipoint rec-
ognition of anionic guests.[5] Moreover, Hay et al. used the
urea subunit as a building block for the computer-aided
design of sophisticated receptors for targeted anions of vary-
ing geometrical features.[6] It has been recently demonstrat-
ed that synthons that contain covalently linked bipyridine
and urea fragments, which profit from the template effect of
four NiII ions, self-assemble to encapsulate a sulfate ion in
water, thereby forming a complex of unprecedented stabili-
ty.[7]
receptors establish hydrogen-bonding interactions with the
[2]
ꢀ
anion by means of N H fragments from amides, urea/thio-
urea[3] and pyrroles.[4] Urea in particular is an attractive
[a] Dr. V. Amendola, Dr. G. Bergamaschi, Prof. L. Fabbrizzi,
Dr. M. Milani
Dipartimento di Chimica Generale, Universitꢂ di Pavia
via Taramelli 12, 27100 Pavia (Italy)
Fax : (+39)0382-528544
E-mail: luigi.fabbrizzi@unipv.it
[b] Dr. M. Boiocchi
Centro Grandi Strumenti, Universitꢂ di Pavia
via Bassi, 27100 Pavia (Italy)
More recently, thanks to the pioneering work of Costaꢀs
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200903190.
group,[8] another neutral subunit capable of establishing, like
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Chem. Eur. J. 2010, 16, 4368 – 4380

FULL PAPER
urea, a bifurcated hydrogen-bond interaction has been con-
sidered in the design of anion receptors: squaramide. Theo-
retical studies have shown the superiority of squaramide
over urea as a hydrogen-bonding donor,[9] a feature that has
been essentially ascribed to the increase of the aromatic
character of the squaramide ring upon anion complexa-
tion.[10] A further contribution in the field involved the
design of a macrotricyclic CuII cryptate that contained two
squaramide moieties capable of including halide ions.[11] Re-
cently, a squaramide-based chloride ion receptor, the anion
binding cavity of which can be opened and closed by using
carbonyl groups as valves, has been described.[12]
In this context, we intend to investigate in detail anion-
recognition tendencies of the squaramide subunit, to be
compared with those of the urea subunit. Anion binding of
the urea derivative, equipped with the most powerful elec-
tron-withdrawing substituent (1,3-bis(4-nitrophenyl)-urea,
1), towards anions in acetonitrile has been previously inves-
Figure 1. An ORTEP view of the two symmetrically independent mole-
cules of the [2···Cl]ꢀ receptor–anion complex that constitute the crystal.
(Thermal ellipsoids are drawn at the 30% probability level. Only hydro-
gen atoms involved in hydrogen bonds are shown. Hydrogen bonds have
been drawn as dashed lines.) Atoms of the two non-equivalent receptor–
anion complexes were named by adding a final “a” and “b” suffix to the
same atom-naming scheme.
are reported in Table 1, together with those observed for the
analogous [2···Br]ꢀ complex (vide infra). The donor–accept-
or distances (N···Cl) fall in the range 3.10–3.14 ꢄ, which cor-
responds to the formation of “moderate” hydrogen bonds,
mainly electrostatic in nature, according to Jeffreyꢀs classifi-
cation.[14]
Table 1. Structural features of the hydrogen-bond interactions in [2···Cl]ꢀ
and [2···Br]ꢀ receptor–anion complexes.
tigated by this group.[13] We report here the synthesis and
the anion-binding properties of the squaramide analogue 2,
which has been investigated in MeCN through spectroscopic
titration experiments. Moreover, the crystal structure of the
hydrogen-bond complexes of 2 with chloride and bromide
ions will be discussed. It is anticipated that, judging from
the association constants with a variety of anions, squara-
mide is a better receptor than urea, with a special reference
to halide ions. Such superiority can be accounted for by con-
sidering the structural features of the receptor–halide com-
plexes.
ꢀ
Donor group
D···A [ꢄ] H···A [ꢄ] D H···A [8] Acceptor atom
ꢀ
N(1a) H
N
2.21(4)
2.31(3)
2.33(3)
2.25(4)
2.53(4)
2.44(3)
177.3(31)
170.4(32)
172.5(32)
174.3(30)
169.5(31)
173.7(32)
Cl(1a)
Cl(1a)
Cl(1b)
Cl(1b)
Br(1)
ꢀ
N(2a) H
ꢀ
N(1b) H
ꢀ
N(2b) H
ꢀ
N(1) H(N1)
ꢀ
N(2) H(N2)
Br(1)
One of the two independent receptor moieties (a, with
atom names reporting the “a” suffix) exhibits an almost co-
planar molecular geometry: the deviations for C, N and O
atoms that constitute the squaramide ring from their best
plane are less than 0.01(1) ꢄ, and the dihedral angles be-
tween the two phenyl rings and the squaramide unit are
0.2(1) and 3.4(1)8. The second receptor moiety, b, shows a
slightly distorted squaramide unit, as the deviations of C, N
and O atoms from the best plane fall in the range ꢀ0.11(1)–
0.10(1) ꢄ. Also, the dihedral angles between the two aro-
matic rings and the squaramide group (6.1(1) and 9.1(1)8)
are appreciably greater than observed for the other com-
plex.
Results and Discussion
The crystal and molecular structures of the chloride and
bromide complexes: The tendency of 2 to form 1:1 com-
plexes with anions in the solid state was revealed by X-ray
studies. In particular, on slow evaporation of a solution of
equimolar amounts of 2 and [BnEt3N]Cl in MeCN, crystals
of a salt of formula [BnEt3N]ACTHNUTRGNE[NUG 2···Cl] suitable for crystallo-
graphic studies were obtained. The ORTEP diagram of the
complex is shown in Figure 1.
In particular, the crystal contains two asymmetrically
equivalent [2···Cl]ꢀ hydrogen-bond complexes and the corre-
sponding two [BnEt3N]+ counterions (not shown in
Figure 1, but shown in Figure S7 of the Supporting Informa-
tion). Each receptor establishes a bifurcated hydrogen-bond
Interestingly, the planarity of the moieties of the receptor
allows the formation of face-to-face p-stacking interactions
among all the phenyl rings of adjacent nitrophenyl arms. In
particular, the crystal contains couples of centrosymmetri-
cally related molecules formed by atoms carrying the “a”
suffix, which are superimposed onto couples of centrosym-
metrically related molecules, the atoms of which are labelled
ꢀ
interaction with the chloride ion through the amide N H
ꢀ
fragments. Geometrical features of the N H···Cl interactions
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4369

L. Fabbrizzi et al.
with the “b” suffix. Each “a” and “b” centrosymmetrically
related pair is characterised by two face-to-face p-stacked
phenyl rings that show the same value of the centroid–cent-
roid distance: 3.70(1) ꢄ for the “a” molecular couple and
3.72(1) ꢄ for the “b” molecular couple. Likewise, the two
superimposed phenyl rings exhibit the same value for the
closest C···C contact: 3.41(1) ꢄ for the “a” molecular couple
and 3.43(1) ꢄ for the “b” molecular couple.
Analogous face-to-face p-stacking interactions are estab-
lished between the phenyl rings of adjacent “a” and “b” re-
ceptor couples: the two centroid–centroid distances between
the two adjacent phenyl rings are 3.61(1) and 3.94(1) ꢄ,
whereas the corresponding closest C···C contacts are 3.40(1)
and 3.41(1) ꢄ. These features favour the assembling of su-
perimposed molecular receptors to form 1D molecular rows
of face-to-face p-stacked molecules. The molecular rows
extend along the a crystallographic axis of the crystal, as
sketched in Figure 2.
However, each chloride ion ends up sandwiched between
two cyclobutene rings of the two receptor molecules placed
above and below any molecular receptor. Such a geometri-
cal arrangement could favour the formation of anion–p in-
teractions, as observed between anions and a variety of elec-
tron-poor six-membered aromatic rings.[15] In particular, in
the present case, the anion–centroid distances are 3.62 and
3.64 ꢄ for Cl(1a), and 3.46 and 3.67 ꢄ for Cl(1b), respec-
tively, whereas the shorter Cl···C contacts are: Cl(1a)···C(3b)
3.51(1), Cl(1a)···C(2a) 3.52(1), Cl(1b)···C(4b) 3.52(1) and
Cl(1b)···C(1b) 3.54(1) ꢄ. These distances are distinctly
smaller than the sum of the van der Waals radii of the
carbon atom, 1.70 ꢄ,[16] and of the chloride ion, 2.47 ꢄ,[17]
that is, 4.17 ꢄ, thereby indicating the occurrence of signifi-
cant anion–p interactions. Recently, the crystal structure of
the chloride complex of a squaramide derivative with an ap-
pended alkylammonium side chain has been reported.[18] In
particular, the chloride ion establishes a definite p interac-
tion with the cyclobutene-1,2-dione subunit, located over
the ring plane at 3.55 ꢄ.[18]
The cyclobutene ring of any single receptor molecule
points in the opposite direction with respect to the two clos-
est receptors, thus preventing the formation of face-to-face
p-stacking interactions between adjacent cyclobutene rings.
Crystals suitable for X-ray diffraction analyses were ob-
tained also for the 1:1 complex with a bromide ion. The
crystal and molecular structure of the [Bu4N]ACTHUNRTGNEUNG[2···Br] com-
plex salt, shown in Figure 3, indicates that receptor 2 estab-
lishes a bifurcated hydrogen-bonding interaction with the
bromide ion, in the same way as observed for chloride.
Donor–acceptor distances (Table 1) are appreciably larger
than for the chloride ions, a behaviour that reflects the
greater ionic radius of bromide.
Figure 3. An ORTEP view of the [2···Br]ꢀ receptor–anion complex.
(Thermal ellipsoids are drawn at the 30% probability level. Only hydro-
gen atoms involved in hydrogen bonds are shown. Hydrogen bonds have
been drawn as dashed lines.) The tetrabutylammonium ion in not shown
in this figure, but is shown in Figure S8 of the Supporting Information.
The [Bu4N]ACTHNUGRTNEUNG[2···Br] complex salt also contains an almost
coplanar 2 receptor: the mean deviation of C, N and O
atoms that constitute the squaramide ring from their best
plane is 0.03(1) ꢄ, whereas the dihedral angles between the
two phenyl rings and the squaramide unit are 6.6(1) and
9.2(1)8. As observed for the chloride analogue, in the crystal
of the bromide complex two equivalent molecules of 2, re-
lated to each other by an inversion centre, form couples
Figure 2. A simplified sketch of face-to-face p-stacked 2 receptor mole-
cules that assemble to form infinite 1D molecular rows in the [BnEt3N]-
ACHTUNGTRENNUNG[2···Cl] crystal; the letters “a” and “b” identify the symmetrically equiva-
lent molecules formed by atoms that carry the “a” or “b” suffix in the
atom names. The Clꢀ anions (large spheres) are bonded to receptors
through hydrogen bonds (dashed lines) and are sandwiched between two
cyclobutene rings, thereby establishing anion–p interactions.
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Squaramide versus Urea
FULL PAPER
with extensive face-to-face p-stacking interactions among
the phenyl rings of adjacent nitrophenyl arms. The centroid–
centroid distance (3.65(1) ꢄ), as well as the closest C···C
contact for both adjacent phenyl rings (3.33(1) ꢄ), are simi-
lar to those observed in the chloride complex. Moreover, in
the present case, too, cyclobutene rings of adjacent mole-
cules have opposite orientations and are excluded from
face-to-face p-stacking interactions.
However, in contrast to what was observed for the chlo-
ride analogue, no extensive p-stacking interactions exist be-
tween adjacent couples in the crystal of the [2···Br]ꢀ com-
plex, because only one of the two nitrophenyl groups ends
up superimposed among adjacent molecular couples. The
centroid–centroid distance between the superimposed
phenyl rings of adjacent couples is 3.64(1) ꢄ, whereas the
closest C···C contact is 3.37(1) ꢄ. These features favour the
assembly of superimposed receptor couples according to a
1D zigzag-folded stacking, as illustrated in Figure 4.
of the carbon atom (1.70 ꢄ)[16] and of the bromide ion
(2.58 ꢄ),[17] that is, 4.28 ꢄ, thereby indicating the establish-
ment of some anion–p interactions. It is therefore concluded
that the overall stabilisation of the 3D packing in the crystal
structure of both chloride and bromide complexes results
from the dipolar character of both the nitrophenyl and
squaramide rings, from the formation of p–p interactions
between facing receptor molecules and, to some extent,
from a p interaction between the anion and the cyclobutene
subunit.
Moreover, it is worth noting here that receptor 2, when
interacting with chloride and bromide, exhibits an overall
planar geometry. The planarity not only promotes the for-
mation of face-to-face p-stacking interactions, but also fa-
ꢀ
vours the placement of the protons of the Ca H fragments
of the two phenyl substituents on positions suitable for the
ꢀ
ꢀ
establishment of further Ca H···[X] interactions. In fact,
the Ha protons lie on the plane defined by the bifurcated
N H···[X] interaction. This favourable spatial arrangement
plays a crucial role in determining the unusually high stabili-
ꢀ
ꢀ
ty of halide complexes of 2 (vide infra).
The interaction of receptor 2 with anions in MeCN, studied
by spectrophotometry: The interaction of receptor 2 with
anions was investigated as a solution in MeCN through
spectrophotometric titration experiments. In a typical ex-
periment, a solution of 2 in MeCN was titrated with a stan-
dard solution of the tetraalkylammonium salt of the chosen
anion. The occurrence of the receptor–anion interaction was
documented by distinctive changes of the absorbance of the
receptor in the UV/Vis region. Figure 5a and b show the
spectrum of a solution of 2 in MeCN (solid line).
The spectrum displays two bands: one, centred at 272 nm
(*1), ascribed to the highest-energy charge-transfer transi-
tion illustrated in Scheme 1, which results in the zwitterion
with the negative charge being placed on one of the oxygen
atoms of the carbonyl fragments and with the positive
charge centred on one of the amide nitrogen atoms; the
other, centred at 395 nm (*2) and corresponding to the
lowest-energy transition, is responsible for the formation of
the zwitterionic excited state in which the negative charge is
located on one of the oxygen atoms of the nitro groups.
Quite interestingly, semiempirical studies using the ZINDO/
S method showed that moving from the HOMO to LUMO
level induces a displacement of charge density on the nitro
groups of the phenyl substituents, transition *2 ; whereas, in
the higher energy molecular orbital, the electron density in
essentially localised over the squaramide subunit (transition
*1, see Figure S1 of the Supporting Information).
Figure 4. A simplified sketch of face-to-face p-stacked molecules of 2, as-
sembled to give a 1D zigzag-folded molecular chain in the crystal of the
[Bu4N]ACHTUNGTRENNUNG[2···Br] complex salt. Each bromide anion (large spheres) is bound
to the receptor through hydrogen bonds (dashed lines) and is close to
only one cyclobutene ring, placed according to a weak unidirectional
anion–p interaction.
It is expected that the interaction of an anion at the
ꢀ
amide N H fragments stabilises both excited states, which
retain a positive charge on one nitrogen atom, thus reducing
the energy of the optical transition. This should induce a
redshift of the two absorption bands. Indeed, upon anion ad-
dition, both charge-transfer bands undergo a definite red-
shift, as illustrated by representative examples in Figure 5,
with chloride (a) and dihydrogenphosphate (b).
Notice that bromide ions are not sandwiched between
two cyclobutene rings, but each Brꢀ ion is placed above one
cyclobutene rings. The anion–centroid seems quite large
(4.10(1) ꢄ). In any case, the Br···C (Br(1)···C(3) 3.87(1) ꢄ)
contacts are shorter than the sum of the van der Waals radii
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L. Fabbrizzi et al.
Figure 5. Solid lines: spectrum of a solution of receptor 2 in MeCN.
Dashed lines: a) spectrum obtained after excess addition of [Et3Bn]Cl;
b) spectrum obtained after excess addition of [Bu4N]H2PO4.
Figure 6. a) Family of spectra taken over the course of the titration of a
1ꢅ10ꢀ4 m solution of 2 (=LH) with a standard solution of [Bu4N]Br in
MeCN. Dashed line: spectrum of receptor 2 prior to bromide addition.
b) Lines: percent concentration of the species present at the equilibrium
over the course of the titration with bromide (left axis). Triangles: ab-
sorbance at 410 nm, which monitors the formation of the [LH···Br]ꢀ com-
plex (right axis).
the course of the titration of a 1ꢅ10ꢀ4 m of 2 with a standard
solution of [Bu4N]Br, at 258C.
Upon bromide addition, the charge-transfer band of the
receptor centred at 395 nm (ascribed to transition *2) is sig-
nificantly redshifted, whereas the displacement to higher
wavelengths of the band centred at 272 nm (assigned to
transition *1) is much less pronounced. The presence of defi-
nite isosbestic points (at 310 and 392 nm) indicates that only
two species coexist at the equilibrium. The profile of the
molar absorbance at 410 nm versus equivalents of bromide
(the triangles in Figure 6b) suggests the formation of a re-
ceptor/anion complex of 1:1 stoichiometry, the structure of
which should be the same as that observed in the solid state
and illustrated in Figure 3. Results can thus be interpreted
on the basis of the following equilibrium [Eq. (1); LH=2,
X=Br]:
Scheme 1. The hypothesised charge-transfer transitions in receptor 2.
The interaction of 2 with halides and oxoanions: Spectro-
photometric titration experiments were carried out with hal-
ꢀ
ꢀ
ꢀ
ides and some selected oxoanions (H2PO4 , NO3 , HSO4 ,
CH3COOꢀ). The stoichiometry and the binding constants of
the species present at the equilibrium were determined by
treatment of spectrophotometric titration data by a non-
linear least-squares procedure, using HyperQuad.[19] As an
example, Figure 6a shows the family of spectra taken over
LHþXꢀ Ð ½LH ꢂ ꢂ ꢂ Xꢃꢀ
ð1Þ
in which [LH···X]ꢀ represents the receptor–anion hydrogen-
bond complex. Through the non-linear least-squares treat-
ment of the titration profiles over the 350–450 nm interval,
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Squaramide versus Urea
FULL PAPER
the association constant of Equation (1) (X=Br) was deter-
mined (logK=4.70ꢄ0.01). From the logK value, the per-
cent concentration of the species present at the equilibrium
(abundance) over the course of the titration could be calcu-
lated (lines in Figure 6b). It is observed that the absorbance
of the band of the association complex superimposes well
on the concentration profile of [LH···Br]ꢀ, thus corroborat-
ing the integrity of the model.
Analogous titration experiments were performed with
other anions. In all cases, with the notable exception of Fꢀ
and CH3COOꢀ, the formation of a receptor/anion complex
of 1:1 stoichiometry was ascertained, even in the presence
of a large anion excess. Pertinent logK values for equilibria
of the type shown in Equation (1) are reported in Table 2.
The interaction of 2 with fluoride and acetate—the occur-
ꢀ
rence of N H deprotonation: The more basic anions
CH3COOꢀ and Fꢀ displayed a more complex behaviour.
Figure 7a shows the family of spectra taken over the course
of the titration of a 2ꢅ10ꢀ5 m solution of 2 (LH) with a 2ꢅ
10ꢀ3 m solution of [Bu4N]F.
It appears that the interaction of the fluoride ion with re-
ceptor 2 takes place according to two well-defined steps. In
particular, upon addition of the first equivalent of Fꢀ, a dis-
tinct redshift of the charge-transfer bands of the receptor is
observed, which is ascribed to the formation of the hydro-
gen-bond complex [LH···F]ꢀ, according to Equation (2):
Figure 7. a) Family of spectra taken over the course of the titration of a
2ꢅ10ꢀ5 m solution of 2 (=LH) with a 2ꢅ10ꢀ3 m solution of [Bu4N]F in
MeCN. b) Lines: percent concentration of the species present at the equi-
librium over the course of the titration (left axis). Open triangles: absorb-
ance at 427 nm, which monitors the formation of the [LH···F]ꢀ complex
(right axis). Grey triangles: absorbance at 540 nm, which monitors the
formation of the deprotonated receptor Lꢀ (far-right axis).
LHþFꢀ Ð ½LH ꢂ ꢂ ꢂ Fꢃꢀ
ð2Þ
The 1:1 stoichiometry of the complex is confirmed by the ti-
tration profile shown in Figure 7b. In particular, the absorb-
ance at 427 nm (open triangles), pertinent to the band asso-
ciated to the [LH···F]ꢀ complex, increases up to the addition
of 1 equiv of Fꢀ, then abruptly decreases. It is anticipated
that the absence of a smooth curvature in the profile pre-
cludes any safe determination of K1, the constant for Equa-
tion (2). Then, upon addition of the second equivalent of Fꢀ,
the intensity of the band centred at 425 nm rapidly decreas-
es, and a new band forms and develops at 500 nm. Appear-
ance of a band at high wavelengths upon addition of excess
fluoride has been previously observed with urea[13] and thio-
urea derivatives[20] equipped with electron-withdrawing sub-
stituents, and it has been associated with the occurrence of
an equilibrium of the following type [Eq. (3)]:
½LH ꢂ ꢂ ꢂ FꢃꢀþFꢀ Ð Lꢀþ½HF2ꢃꢀ
ð3Þ
Table 2. Constants of the complex formation equilibria that involve a solution of receptors 2 and 1 (=LH) in MeCN at 258C. The standard deviations
are given in parentheses.
Anion: Xꢀ
logK1
LH+XꢀQ[LH···X]ꢀ
1[b]
logK2
Dl [nm][a]
(395 nm)
Dl [nm][a]
ACHTUNGTRENNUNG(272 nm)
G
E
N
2
2
1[b]
Fꢀ
8.0(2)
7.4(1)
4.55(1)
3.22(3)
6.0(2)
–
–
–
–
–
–
–
6.4(1)
27
16
13
6
8
13
9
11
4
2
0
2
4
3
6
10
Clꢀ
Brꢀ
Iꢀ
6.05(2)
4.70(1)
3.51(2)
3.68(1)
4.75(2)
4.02(3)
5.42(7)
6.5(2)
–
–
–
–
–
–
–
–
<2
ꢀ
NO3ꢀ
3.65(5)
4.33(1)
4.26(1)
5.37(1)
6.61(1)
NO2
ꢀ
HSO4
ꢀ
H2PO4
26
23
CH3COOꢀ
3.1(2)
[a] The variable Dl [nm] refers to the extent of the redshift of the pertinent charge-transfer absorption band after the addition of excess anion.
[b] Values from ref. [13].
Chem. Eur. J. 2010, 16, 4368 – 4380
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4373

L. Fabbrizzi et al.
ꢀ
in which an N H fragment of the receptor is deprotonated
tration) on symbols (absorbance) was obtained by assuming
logK1 =8.0ꢄ0.2 and logK2 =6.0ꢄ0.2. Uncertainties were
estimated by considering that a variation of 0.2log units of
logK values caused a visually detectable deviation from best
fitting. It has to be noted that concentration curves may sub-
stantially deviate from titration profiles over the course of
the titration, for instance, the concentration of the [LH···F]ꢀ
complex (dashed line) from the titration profile at 427 nm
(open triangles) after the addition of 2 equiv of Fꢀ (see Fig-
ure 7b). Deviations have to be ascribed to the fact that
chosen absorbances do not pertain to a single species but
rather result from the contribution of the different species
present at equilibrium, sometimes in comparable amounts.
It had been observed with the analogous urea-based re-
while the [HF2]ꢀ hydrogen-bond self-complex forms. Thus, it
ꢀ
is suggested that N H deprotonation takes place also with
the squaramide-based receptor 2. In particular, the absorb-
ance at 540 nm has been considered to monitor the deproto-
nation process of the receptor (grey triangles in Figure 8b):
it is observed that a limiting value of absorbance is achieved
upon addition of 4 equiv or more of Fꢀ. It has been men-
tioned that K1 has too high a value for being determined
through a least-squares curve-fitting procedure (e.g., using
the HyperQuad package).[19] However, we could obtain ap-
proximate values of K1 and K2 by doing tentative fitting of
the two titration profiles shown in Figure 7b. In particular,
several couples of K1 and K2 were chosen, and pertinent per-
cent concentration curves of the species present at the equi-
librium were calculated and were ꢁvisuallyꢀ fitted on the ti-
tration profiles. The best superimposition of lines (concen-
ꢀ
ceptor 1 that N H deprotonation occurred only on titration
with Fꢀ, a circumstance attributed to the especially high sta-
bility of the hydrogen-bond self-complex [HF2]ꢀ. Other
basic Xꢀ anions, including CH3COOꢀ, formed only the
[LH···X]ꢀ complex, even in the presence of a large excess of
Xꢀ.
Figure 8a shows the family of spectra taken over the
course of the titration of a 2ꢅ10ꢀ4 m solution of 2 with a
standard solution of [Bu4N]CH3COO in MeCN. It is ob-
served that, upon addition of the first equivalent of acetate,
the amide-to-nitrophenyl charge-transfer band undergoes
the typical redshift that corresponds to the formation of the
1:1 hydrogen-bonding complex. However, upon further
anion addition, the band associated with the hydrogen-bond
complex, centred at 435 nm, decreases in intensity, and a
new band develops at 500 nm. The appearance of this band
ꢀ
clearly indicates the occurrence of the N H deprotonation,
according to an equilibrium of the type shown in Equa-
tion (3).
In
particular,
the
formation
of
a
[CH3COOH···CH3COO]ꢀ hydrogen-bond self-complex has
to be hypothesised. Indeed, the [CH3COOH···CH3COO]ꢀ
species has been previously isolated as a solid and its struc-
ture had been elucidated through a neutron-diffraction ex-
periment.[21] A sketch based on deposited crystallographic
coordinates is shown in Figure 9.
Figure 9. The molecular structure of the [CH3COOH···CH3COO]ꢀ hydro-
gen-bond self-complex; the sodium counterion has been omitted for clari-
ty. A proton is shared by the oxygen atoms of two equivalent acetate sub-
units, as inferred from neutron diffraction studies.[21] Structure redrawn
from data deposited at the Cambridge Crystallographic Data Centre.
Figure 8. a) Family of spectra taken over the course of the titration of a
2ꢅ10ꢀ4
m
solution of
2
(=LH) with
a
standard solution of
[Bu4N]CH3COO in MeCN. Solid line: spectrum of receptor 2 prior to ad-
dition of acetate. Short dashed line: spectrum taken after the addition of
1 anion equivalent. Dash-dot line: spectrum taken after the addition of
four equivalents. b) Lines: percent concentration (abundance) of the spe-
cies present at the equilibrium over the course of the titration with ace-
tate (left axis). Solid line: uncomplexed receptor 2 (L). Short-dashed
line: hydrogen-bond complex [LH···CH3COO]ꢀ. Long-dashed line: de-
protonated receptor Lꢀ. Open symbols: absorbance at 435 nm, which
monitors the formation of the [LH···CH3COO]ꢀ complex (right axis).
Filled symbols: absorbance at 500 nm, which monitors the formation of
the deprotonated form of the receptor, Lꢀ (far-right axis).
In the present case, too, the titration profile based on ab-
sorbances pertinent to the [LH···CH3COO]ꢀ complex
(dashed line) does not show a smooth curvature. Thus, logK
values were tentatively determined through visual fitting of
abundance curves and titration profiles, as shown in Fig-
4374
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Chem. Eur. J. 2010, 16, 4368 – 4380

Squaramide versus Urea
FULL PAPER
ure 9b: logK1 =6.5ꢄ0.2; logK2 =3.2ꢄ0.2. Notice that the
logK2 value is approximately three orders of magnitude
lower than that observed for the corresponding reaction
with fluoride. This may reflect the lower stability of the
[CH3COOH···CH3COO]ꢀ self-complex with respect to
[HF2]ꢀ. In fact, even upon excess addition of CH3COOꢀ
(4 equiv), only 40% of the deprotonated receptor Lꢀ has
been spectrophotometrically detected.
2 in [D6]DMSO. DMSO was chosen as a solvent to afford a
concentration suitable for 1H NMR spectroscopic studies
(5ꢅ10ꢀ3 m). It is observed that Ha and Hb protons undergo
an upfield shift upon addition of acetate. Upfield shift of
both Ha and Hb protons of the nitrophenyl substituents had
been observed in the titration of 1 with fluoride, thereby in-
[13]
ꢀ
dicating deprotonation of one of the urea N H fragments.
The fact that the upfield shift is observed also upon addi-
tion of 0.25 equiv of CH3COOꢀ may indicate that in the
present experiment deprotonation of the receptor begins to
occur well before one equivalent. This may be due 1) to the
distinctly polar nature of the used solvent (DMSO), which
favours the formation of charged species and the occurrence
of the acid–base neutralisation process, and 2) to the fact
that titration has been carried out at a concentration 25-fold
higher than the spectrophotometric one. It has to be noted
that upfield shift results from a through-bond mechanism,
which brings electron density to the phenyl substituents and
causes a shielding effect. Upon addition of the first aliquots
Figure 10 shows the 1H NMR spectra taken over the
course of the titration with acetate of a 5ꢅ10ꢀ3 m solution of
ꢀ
of acetate, such an upfield shift is significant for the C Hb
ꢀ
signal and moderate for the C Ha signal. In fact, in the
[LH···CH3COO]ꢀ complex, the C Ha fragment is polarised
by the close anion, thus inducing a deshielding effect, which
partially reduces the upfield shift originated by the through-
bond mechanism.
ꢀ
Looking at correlations between thermodynamic and spec-
tral data: The logK values are related to the free-energy
change, DG8, which in turn results from the combination of
two distinct contributions: 1) the enthalpy term, DH8, which
comprises all binding energies, including receptor–anion hy-
drogen-bond interactions, and 2) the entropy term, TDS8,
which mainly refers to changes in the solvation of reagents
and products and to solvent reorganisation during the com-
plexation process.[22] However, in the absence of calorimetric
data, it is assumed that in a homogeneous class of anions
the entropy change does not vary too much, so that the
trends of logK values are interpreted in terms of bonding
energy. In this sense, anion recognition is currently being ac-
counted for on a molecular basis. On the other hand, spec-
tral data may give direct information about the intensity of
bonding interactions within the complex. In particular, the
redshift (Dl in nm) of the charge-transfer bands is related to
the energy of the interaction between the anion and the re-
ceptor in its excited state.
Figure 11a discloses the existence of a reasonable linear
correlation between logK and the redshift of the band at
395 nm, which refers to the charge-transfer transition *2 in
Scheme 1, and holds for both halides and oxoanions. Fig-
ure 11b pertains to the band at 272 nm (transition *1 in
Scheme 1). Although a general increase in logK with Dl is
observed, it appears that halides and oxoanions display dis-
tinctly different behaviours, since corresponding points lie
on two different, nearly parallel straight lines. In particular,
halides seem to be able to induce the formation of negative
charge onto squaramide carbonyl oxygen atoms to a greater
extent than oxoanions. The origin of this effect is not clear.
Figure 10. 1H NMR spectra taken over the course of the titration of a 5ꢅ
10ꢀ3 m solution of 2 in [D6]DMSO with a standard solution of acetate.
The spectra are taken in the absence of a) anion and after the addition of
b) 0.25, c) 0.5, d) 0.75 and e) 1.25 equiv of acetate.
Chem. Eur. J. 2010, 16, 4368 – 4380
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4375

L. Fabbrizzi et al.
Figure 12. Plot of logK1 versus halide ionic radius, which illustrates the
electrostatic nature of the receptor–halide interaction within the hydro-
gen-bond complex [LH···X]ꢀ.
holds for both receptors 1 and 2 and points towards a pre-
dominantly electrostatic nature of the receptor–halide inter-
action (the higher the charge density—electric charge over
ionic radius—of the anion, the stronger the interaction es-
tablished). In particular, the squaramide derivative 2 seems
capable of more-intense electrostatic interactions with hal-
ides than the urea derivative 1. Such different behaviour can
be accounted for through an inspection of available structur-
al data.
Figure 13a displays the molecular structure of the
[LH···Cl]ꢀ complex (LH=2), the ORTEP view of which is
shown in Figure 3, whereas Figure 13b shows the structure
of the chloride complex of the urea derivative N,N’-di-4-
chlorophenylurea (3),[23] the only chloride complex of a di-
arylurea-based receptor for which structural data are avail-
able. In Table 3, distances relevant to the hydrogen-bond in-
Figure 11. a) Plot of logK versus the redshift of the band of receptor 2
centred at 395 nm (charge-transfer transition *2 in Scheme 1); b) plot of
logK versus the redshift of the band of receptor 2 centred at 272 nm
(charge-transfer transition *1 in Scheme 1).
However, it may be in some way related to the relatively
higher stability of halide complexes of 2 with respect to
those of oxoanions, as compared to corresponding ones of
the urea-based receptor 1 (vide infra).
A comparison of the anion-binding tendencies of squara-
mide- and urea-based receptors: The logK values for the
anion-binding equilibria of 2 are compared in Table 2 to
those of the analogous urea-based receptor 1.[13] It is ob-
served that 1) for both receptors, halide complex stability
decreases along the series Fꢀ >Clꢀ >Brꢀ >Iꢀ, but for a
given anion, 2 forms a complex 1 to 2 orders of magnitude
more stable than 1; 2) in the case of oxoanions, both recep-
tors form with a given anion complexes of the same stability,
which decreases according to the sequence CH3COOꢀ >
ꢀ
H2PO4ꢀ >NO2ꢀ >HSO4ꢀ >NO3 .
Figure 13. Structures of the [LH···Cl]ꢀ complexes with squaramide- and
urea-based receptors; a) LH=2, this work; b) LH=3.[23] Structure re-
drawn from data deposited at the Cambridge Crystallographic Data
Centre.
As far as the interaction with halide ions is concerned,
Figure 12 reveals the existence of a linear correlation be-
tween logK1 values and anion radius. Such a relationship
4376
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Chem. Eur. J. 2010, 16, 4368 – 4380

Squaramide versus Urea
FULL PAPER
ꢀ
ꢀ
ꢀ
ꢀ
Table 3. N H and Ca H contact distances for bifurcated interactions in [L H···Cl] complexes with squara-
mide- and urea-based receptors.
Ca···Br distances are 3.87 and
3.93 ꢄ (to be compared with
the average value of (3.94ꢄ
[a]
Ca···Cl [ꢄ][b]
Ref.
ꢀ
ꢀ
Receptor
N H···Cl [ꢄ]
N–-Cl [ꢄ]
Ca H···Cl [ꢄ]
2
3
2.21, 2.33
2.24, 2.40
3.10, 3.14
3.14, 3.33
3.06, 3.14
3.34, 4.15
3.78, 3.86
4.03, 4.64
this work 0.16) ꢄ).[24]
[23]
Quite surprisingly, such an
additional contribution from
[a] Average value from 288 observed distances is (3.07ꢄ0.15) ꢄ.[24] [b] Average value from 288 observed dis-
tances is (3.82ꢄ0.15) ꢄ.[24]
ꢀ
convergent Ca
H
fragments
teractions are given. It can be seen that, as far as interac-
tions of Clꢀ with N H fragments are concerned, H···Cl and
ꢀ
N···Cl distances exhibit comparable values, which indicate a
similar contribution to the binding energy and to the magni-
tude of logK values.
However, significant differences are observed in the con-
ꢀ
tact distances between chloride and the Ca H fragments of
the phenyl substituents. The occurrence of hydrogen-bond
ꢀ
interactions between anions and aromatic C H groups has
been observed in a large variety of examples and it has been
critically reviewed in a recent paper.[24] It is observed that in
ꢀ
the squaramide complex Ca H···Cl and Ca···Cl distances fall
in the range expected for the establishment of a definite in-
teraction (see values in Table 3). On the other hand, in the
case of the urea-based receptor 3, pertinent distances are
distinctly beyond the range of interaction. Thus, the extra
energy observed in the interaction with chloride of 2 with
respect to 1 (DlogK=1.5, DDG8=~8.6 kJmolꢀ1) seems to
Figure 14. a) 1H NMR spectra taken over the course of the titration of a
5ꢅ10ꢀ3 m solution of 1 in [D6]DMSO in the absence and in the presence
of a fourfold excess of chloride; b) 1H NMR spectra taken over the
course of the titration of a 5ꢅ10ꢀ3 m solution of 2 in [D6]DMSO in the
absence and in the presence of a fivefold excess of chloride.
be ascribed to the contribution of the additional hydrogen-
ꢀ
bond bifurcated interaction with the two aryl Ca H frag-
ments. This should depend upon the higher convergence of
these fragments, which are therefore placed closer and
better oriented with respect to the anion.
The different nature of the interaction of the Clꢀ ion with
receptors 1 and 2 has been documented also by 1H NMR
spectroscopic studies. Figure 14a shows the spectra taken for
a 5ꢅ10ꢀ3 m solution in 1 in [D6]DMSO, in the absence and
in the presence of a fourfold excess of chloride. Anion addi-
does not seem to operate in the case of oxoanions, which
form complexes of similar stability with both 1 and 2. This
ꢀ
may suggest that the interactions of the N H fragments of 1
and 2, whether with halides or with oxoanions, have a differ-
ꢀ
ꢀ
tion induces a downfield shift of d=1.32 ppm of the N H
ent nature. Indeed, each N H fragment of ureas and squara-
signal, thereby indicating the establishment of a hydrogen-
bond interaction. On the other hand, a fivefold excess addi-
tion of chloride to a 5ꢅ10ꢀ3 m solution of 2 in [D6]DMSO
(see spectra in Figure 14b) induces: 1) a downfield shift of
mides establishes an individual hydrogen-bond interaction
with an oxygen atom of the oxoanion, according to a paral-
lel mode, as sketched in Scheme 2.
In particular, it has been pointed out that hydrogen bond-
ing should be considered as a ꢁfrozenꢀ proton transfer from
the hydrogen-bond donor atom to the hydrogen-bond ac-
ꢀ
the N H signal (d=1.35 ppm), thereby indicating a hydro-
gen-bonding interaction of comparable intensity with re-
spect to urea derivative 1, and 2) a highly detectable down-
ꢀ
ꢀ
field shift of the Ca H signal, whereas the Cb H signal does
not experience any measurable shift. This indicates the exis-
tence of a definite hydrogen-bond interaction between the
ꢀ
two Ca H groups and the chloride ion. Such an interaction
is not established with receptor 1, as demonstrated by the
ꢀ
insensitivity of the Ca H signal to anion addition (see Fig-
ACHTUNGTRENNUNGure 14a).
Scheme 2. The hydrogen-bond interaction with oxoanions of urea-based
(I) and squaramide-based (II) receptors. Urea forms an eight-membered
chelate ring with the oxoanion, squaramide a nine-membered one. The
formation of the latter geometrical arrangement has been observed
(through X-ray diffraction studies) in the nitrate complex of the squara-
mide-based receptor 4-bis[2-(2-pyridyl)ethylamino]-3-cyclobutene-1,2-
dione.[25]
ꢀ
H
This additional hydrogen-bond contribution from Ca
fragments seems to be present also in the bromide complex.
In fact, in the solid complex, Ca H···Br distances are 3.11
ꢀ
and 3.18 ꢄ (to be compared with the average value of
(3.19ꢄ0.17) ꢄ, based on 180 observed distances),[24] whereas
Chem. Eur. J. 2010, 16, 4368 – 4380
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4377

L. Fabbrizzi et al.
ceptor atom;[26] in the present case, this is from the amide
nitrogen atom to the oxygen atom of the oxoanion. The
more acidic the donor and the more basic the acceptor, the
more advanced the proton transfer. From this perspective, it
would seem that the two hydrogen-bond donors 1 and 2
give rise with a chosen oxoanion to proton-transfer process-
es at the same state of advancement. This would imply that
Experimental Section
General procedures and materials: All reagents for syntheses were pur-
chased form Aldrich/Fluka and used without further purification. Mass
spectra were acquired using a Thermo-Finnigan ion trap LCQ Advantage
Max instrument equipped with an ESI source. 1H NMR spectra were
taken using a Bruker ADVANCE 400.
Instruments: UV/Vis spectra were run using a Varian Cary 100 SCAN
spectrophotometer. All titrations were performed at (25.0ꢄ0.1)8C. Titra-
tion data were processed with the Hyperquad package[19] to determine
the equilibrium constants (reported in Table 2). Abundance profiles of
the species at the equilibrium were drawn by using the program HySS.[27]
ꢀ
the polarisation of the N H fragments is essentially dictated
by the nitrophenyl electron-withdrawing substituents, where-
as the carbonyl group(s) play a minor role. Such a hypothe-
sis might contrast with the observation that 2 is deprotonat-
ed in the presence of CH3COOꢀ, and 1 is not. However, it
must be considered that deprotonation of 2 is favoured by
the great stabilisation experienced by the Lꢀ ion, due to the
negative charge delocalisation extended to the entire molec-
ular framework and that may involve two carbonyl groups,
as illustrated by the resonance formulae in Scheme 3. This
term is less favourable for 1 in view of 1) the smaller molec-
ular framework and 2) the presence of a single C=O group.
In any case, the sequence of logK1 values (CH3COOꢀ >
Synthesis of 2: Squaric acid chloride (0.15 g) was added to a suspension
of 1-amino-4-nitrobenzene (0.41 g) in toluene. The mixture was heated at
reflux for 24 h; the obtained red precipitate was filtered, washed with
methanol and dried under vacuum. After recrystallisation, a pure product
was obtained (0.21 g, 60%). 1H NMR ([D6]DMSO): d=10.7 (s, 2H), 8.3
(d, 2H), 8.2 (d, 2H), 7.95 (s, 1H), 7.85 (d, 2H), 7.7 ppm (d, 2H); MS
(ESI; MeOH): m/z: 353 [Mꢀ1]ꢀ, 354 [M+1]+, 399 [M+HCOOH]+.
X-ray crystallographic studies: Diffraction data for a yellow crystal (di-
mensions of about 0.50ꢅ0.43ꢅ0.32 mm) of the [Bu4N]ACTHNUTRGNE[NUG 2···Br] molecular
complex were collected at ambient temperature by means of an Enraf–
Nonius CAD4 four-circle diffractometer equipped with a punctual detec-
tor (scintillation counter). The [BnEt3N]ACHTNUTGRNEUNG[2···Cl] complex salt forms only
ꢀ
H2PO4ꢀ >NO2ꢀ >HSO4ꢀ >NO3 ) parallels the intrinsic ba-
sicity of oxoanions, thus confirming the acid–base nature of
the receptor–anion interaction.
small single crystals and diffraction data for an orange crystal (dimen-
sions of about 0.08ꢅ0.06ꢅ0.04 mm) have been collected by means of a
Bruker-Axs CCD-based diffractometer. Both diffractometers work with
graphite-monochromatised MoKa X-radiation (l=0.71073 ꢄ). Crystal
data for the two molecular complexes are shown in Table 4.
Data reductions (including intensity integration, background, Lorentz
and polarisation corrections) for intensities collected using the conven-
tional diffractometer were performed with the WinGX package;[28] ab-
sorption effects were evaluated with the psi-scan method,[29] and absorp-
tion correction was applied to the data (min/max transmission factors
were 0.592/0.673). Frames collected using the CCD-based diffractometer
were processed with the SAINT software,[30] and intensities were correct-
ed for Lorentz and polarisation effects; absorption effects were empiri-
Scheme 3. Resonance formulae of the deprotonated forms of a urea-
based (1a and 1b) and of a squaramide-based (2a and 2b) receptor.
Table 4. Crystal data for the investigated complex salts.
Conclusion
[Bu4N]
E
ACHUTGTNRNE[NUG BnEt3N]ACHTUNGTRENNUNG[2···Cl]
formula
Mr
crystal system
space group
a [ꢄ]
b [ꢄ]
c [ꢄ]
a [8]
b [8]
C32H46Br N5O6
676.64
C58H64Cl2N10O12
1164.10
Urea is currently being employed as a versatile subunit in
the synthesis of anion receptors of increasing complexity.[5]
Theoretical efforts have been made for the computer-aided
design of neutral receptors that contain urea moieties for
targeting anions of varying geometrical features.[6] This work
has demonstrated that the squaramide subunit can rightfully
challenge urea as a building block in the synthesis of neutral
receptors for anions. In fact, if it establishes with oxoanions
hydrogen-bonding interactions of an energy comparable to
those observed with urea derivatives, with halides it gives
complexes of definitely higher stability, thanks to the pres-
triclinic
triclinic
¯
¯
P1 (no. 2)
P1 (no. 2)
12.033(5)
12.118(2)
13.697(3)
87.04(2)
64.29(2)
76.20(2)
1744.5(9)
2
1.288
1.226
w scans
2–28
8841
8362
0.040
3613
403
0.0562, 0.1685
0.1048, 0.1370
1.004
0.34/ꢀ0.38
14.225(1)
14.734(1)
15.865(1)
86.84(1)
64.44(1)
74.89(1)
2889.6(3)
2
1.338
0.183
w scans
2–25
31276
10238
0.049
5944
751
0.0612, 0.1130
0.1597, 0.1934
1.021
0.30/ꢀ0.25
g [8]
V [ꢄ3]
Z
1calcd [gcmꢀ3
]
m (MoKa) [mmꢀ1
scan type
]
ꢀ
ence of convergent aryl Ca H fragments that act as addi-
tional hydrogen-bond donors. In conclusion, squaramide-
based receptors are expected to donate four hydrogen
bonds to monoatomic anions such as halides, which makes
them superior to their urea-based counterparts, which are
capable of donating only two hydrogen bonds. Chemical sta-
bility of the squaramide framework and ready availability of
intermediates provide additional benefits, which may en-
courage synthetic chemists toward the design of neutral mul-
tisite receptors based on the squaramide subunit.
q range [8]
measured reflns
unique reflns
Rint
strong data (I>2s(I))
refined parameters
R1, wR2 (strong data)
R1, wR2 (all data)
GOF
max/min residuals [eꢄꢀ3
]
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Chem. Eur. J. 2010, 16, 4368 – 4380

Squaramide versus Urea
FULL PAPER
cally evaluated by the SADABS software,[31] and absorption correction
was applied to the data (min/max transmission factors were 0.891/0.992).
R. Ungaro, Org. Biomol. Chem. 2003, 1, 1802–1809; T. Gunnlaugs-
son, A. P. Davis, G. M. Hussey, J. Tierney, M. Glynn, Org. Biomol.
Chem. 2004, 2, 1856–1863; V. Amendola, M. Boiocchi, D. Esteban-
Gꢇmez, L. Fabbrizzi, E. Monzani, Org. Biomol. Chem. 2005, 3,
2632–2639; A. L. Sisson, J. P. Clare, A. P. Davis, Chem. Commun.
2005, 5263–5265; D. R. Turner, M. J. Paterson, J. W. Steed, J. Org.
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Both crystal structures were solved by direct methods (SIR 97)[32] and re-
fined by full-matrix least-squares procedures on F2 using all reflections
(SHELXL 97).[33] Anisotropic displacement parameters were refined for
all non-hydrogen atoms. Hydrogen atoms bonded to C atoms were
placed at calculated positions with the appropriate AFIX instructions
and refined using a riding model; hydrogen atoms bonded to N atoms
ꢀ
and defining the N H···ACTHNUTRGNE[UNG halogen] interactions were located in the final
DF maps; their positions were successively refined during the final least-
squares procedures without restraints on the atom coordinates.
CCDC-754724 ([Bu4N]ACHTUNGTRENNUNG[2···Br]) and 754725 ([BnEt3N]ACHTUNGTERN[NUGN 2···Cl) contain the
supplementary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
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Received: November 20, 2009
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