Nature of urea-fluoride interaction: Incipient and definitive proton transfer

Article abstract of DOI:10.1021/ja045936c

1,3-bis(4-nitrophenyl)urea (1) interacts through hydrogen bonding with a variety of oxoanions in an MeCN solution to give bright yellow 1:1 complexes, whose stability decreases with the decreasing basicity of the anion (CH ₃COO^- > C₆H₅COO^- > H₂PO₄^- > NO₂^- > HSO₄^- > NO₃^-). The [Bu ₄N][1·CH₃COO] complex salt has been isolated as a crystalline solid and its molecular structure determined, showing the formation of a discrete adduct held together by two N-H...O hydrogen bonds of moderate strength. On the other hand, the F^- ion first establishes a hydrogen-bonding interaction with 1 to give the most stable 1:1 complex, and then on addition of a second equivalent, induces urea deprotonation, due to the formation of HF₂^-. The orange-red deprotonated urea solution uptakes carbon dioxide from air to give the tetrabutylammonium salt of the hydrogencarbonate H-bond complex, [Bu₄N][1·HCO ₃], whose crystal and molecular structures have been determined.

Full text of DOI:10.1021/ja045936c

Published on Web 11/24/2004
Nature of Urea-Fluoride Interaction: Incipient and Definitive
Proton Transfer
Massimo Boiocchi,‡ Laura Del Boca,† David Esteban Go´mez,† Luigi Fabbrizzi,*,†
Maurizio Licchelli,† and Enrico Monzani†
Contribution from the Dipartimento di Chimica Generale, UniVersita` di PaVia,
Via Taramelli 12, 27100 PaVia, Italy, and Centro Grandi Strumenti, UniVersita` di PaVia,
Via Bassi 10, 27100 PaVia, Italy
Received July 7, 2004; E-mail: luigi.fabbrizzi@unipv.it
Abstract: 1,3-bis(4-nitrophenyl)urea (1) interacts through hydrogen bonding with a variety of oxoanions in
an MeCN solution to give bright yellow 1:1 complexes, whose stability decreases with the decreasing basicity
of the anion (CH3COO- > C6H5COO- > H2PO4 > NO2 > HSO4 > NO3-). The [Bu4N][1‚CH3COO]
complex salt has been isolated as a crystalline solid and its molecular structure determined, showing the
formation of a discrete adduct held together by two N-H‚‚‚O hydrogen bonds of moderate strength. On
the other hand, the F- ion first establishes a hydrogen-bonding interaction with 1 to give the most stable
1:1 complex, and then on addition of a second equivalent, induces urea deprotonation, due to the formation
of HF2-. The orange-red deprotonated urea solution uptakes carbon dioxide from air to give the
tetrabutylammonium salt of the hydrogencarbonate H-bond complex, [Bu4N][1‚HCO3], whose crystal and
molecular structures have been determined.
-
-
-
Introduction
feature which allows the design of receptors capable of
differentiating between anions with different geometries and
The design of artificial receptors capable of selective interac-
tions with electrically charged substrates stays at the basis of
many important subdisciplines of supramolecular chemistry,
which investigate a variety of functions, including recognition,
sensing, catalysis, and carrier-mediated transport across mem-
branes.1 In a historical prospect, supramolecular chemistry
developed with the synthesis of neutral receptors (cyclic and
polycyclic poly-ethers)2,3 suitable for the selective interaction
with alkali metal cations. Reversibility of the cation-donor atom
interaction is an essential requirement for the above-mentioned
functions to take place. In a broad sense, these studies
represented an extension to s-block metals of the concepts and
principles of classical coordination chemistry, which had
developed much earlier from the study of the interactions of
d-block cations with neutral receptors (ligands) containing amine
groups (even if the metal-amine interaction may be irrevers-
ible). A coordination chemistry of anions has developed more
recently based on electrostatic and dipolar interactions between
the receptor and the substrate.4,5 In particular, neutral receptors
exist also for anions; most of them contain -NH fragments
which act as hydrogen bond donors for the anion.6 In contrast
to merely electrostatic interactions, H-bonds are directional, a
hydrogen-bonding requirements. As an example, seminal papers
by Wilcox and Hamilton showed that urea is a good H-bond
donor and an excellent receptor for Y-shaped anions, such as
carboxylates, through the formation of two hydrogen bonds.7,8
A variety of receptors containing one or more urea subunits
have been designed and tested for anion recognition and sensing
over the past years.9 Moreover, selectivity is also related to the
energy of the receptor-anion interaction; in this sense, strong
H-bond interactions are established with anions containing the
most electronegative atoms: F (fluoride) and O (carboxylates,
inorganic oxoanions). According to a recent view, “all hydrogen
bonds can be considered as incipient proton-transfer reactions,
and for strong hydrogen bonds, this reaction can be in a very
advanced state”.10 Thus, for a given -NH-containing receptor
(the acid), selectivity should be mainly related to the basicity
of the A- anion (i.e., to the pKa value of the conjugated acid
HA); the higher anion basicity, the stronger the hydrogen-
bonding interaction. Solvent cannot be water or any other
hydrogen bond-forming medium (e.g., alcohols) since they
would compete successfully with the receptor for the anion.
Thus, aprotic solvents of varying polarity are currently employed
in anion recognition studies based on H-bonds (e.g., CHCl3,
MeCN, and DMSO).
† Dipartimento di Chimica Generale.
‡ Centro Grandi Strumenti.
(1) Lehn, J.-M. Supramolecular Chemistry, Concepts and PerspectiVes;
VCH: Weinheim, Germany, 1995.
(2) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017-7036.
(3) Dietrich, B.; Lehn, J.-M.; Sauvage, J.-P. Tetrahedron Lett. 1969, 34, 2885-
2888.
(4) Supramolecular Chemistry of Anions; Bianchi, A., Bowman-James, K.,
Garc´ıa-Espan˜a, E., Eds.; Wiley-VCH: New York, 1997.
(5) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486-516.
(6) Gale, P. A. Coord. Chem. ReV. 2003, 240, 1-226.
9
10.1021/ja045936c CCC: $27.50 © 2004 American Chemical Society
J. AM. CHEM. SOC. 2004, 126, 16507-16514
16507

A R T I C L E S
Boiocchi et al.
Table 1. Crystal Data for the Complex Salts, [Bu4N][1‚CH3COO]
and [Bu4N][1‚HCO3]‚2H2O
In this context, we were interested in investigating in detail
the nature of the interaction of the urea subunit with anions. In
particular, we chose the derivative 1, 1,3-bis(4-nitrophenyl)-
urea. 4-Nitrophenyl substituents were appended to the urea
moiety for two main reasons. (i) Presence of -NO2 electron-
withdrawing substituents is expected to enhance the acidity and,
as a consequence, the H-bond donor properties of the receptor.
(ii) The optical properties of the chromogenic nitrophenyl
fragment may be altered following receptor-anion interaction,
thus providing colorimetric and spectral sensing of the recogni-
tion event. Indeed, it has been shown that even simple
chromophores, containing hydrogen-bonding donor groups, can
operate as efficient colorimetric sensors for the naked-eye
detection of anions.11
[Bu4N][1
‚
CH3COO]
[Bu4N][1‚HCO3]‚2H2O
formula
M
C31H49N5O7
603.75
C30H51N5O10
641.76
color
deep yellow
0.70 × 0.50 × 0.35
monoclinic
P21/c (no. 14)
10.0827(17)
20.4341(23)
17.2817(48)
106.067(22)
3421.5(12)
4
1.172
0.083
ω - 2θ scans
2-26
7094
deep yellow
dimension (mm)
crystal system
space group
a [Å]
b [Å]
c [Å]
0.70 × 0.50 × 0.35
monoclinic
P21/c (no. 14)
9.6592(25)
18.2763(14)
19.8024(27)
91.517(10)
3494.4(12)
4
1.220
0.092
ω - 2θ scans
2-26
14221
â [deg]
V [Å3]
Z
F
calcd [g cm-3
]
µ Mo KR [mm-1
scan type
]
Experimental Section
θ range [deg]
measured reflns
unique reflns
General Procedures and Materials. All reagents for the syntheses
were purchased by Aldrich/Fluka and used without further purification.
UV-vis spectra were recorded on a Varian CARY 100 spectropho-
tometer, with a quartz cuvette (path length ) 1 cm), and on a Hewlett-
Packard 8452A spectrophotometer, with a quartz cuvette (path length
) 10 cm). The cell holder was thermostated at 25.0 °C, through
circulating water. 1H NMR spectra were obtained on a Bruker
AVANCE 400 spectrometer (400 MHz), operating at 9.37 T. Spec-
trophotometric titrations were performed on 2-5 × 10-5 and 1.0 ×
10-6 M solutions of 1 and in MeCN (polarographic grade). Typically,
6700
0.0331
6859
0.0735
a
Rint
strong data [IO > 2σ(IO)]
R1, wR2 (strong data)b
R1, wR2 (all data)b
GOFc
2198
2429
0.0757, 0.1254
0.2425, 0.1794
0.980
0.0600, 0.1102
0.1995, 0.1524
0.946
refined parameters
395
0.15/-0.14
431
0.19/-0.15
max/min residuals [e Å-3
]
2
2
a Rint ) ∑|Fo2 - Fo (mean)|/∑ Fo . b R1 ) ∑ ||Fo| - |Fc||/∑ |Fo|, wR2
) [∑ [w(Fo - Fc )2]/[∑w(Fo )2]]1/2, where w ) 1/[σ2Fo + (aP)2 + bP]
2
2
2
2
and P ) [(max (Fo ,0) + 2Fc ]/3. c GOF ) {∑[w(Fo2 - Fc )2]/(n - p)}1/2
,
2
2
2
aliquots of a fresh alkylammonium salt standard solution of the
where n is the number of reflections and p the total number of refined
envisaged anion (CH3COO-, C6H5COO-, H2PO4-, NO2-, HSO4
,
-
parameters.
NO3-, F-, or Cl-) were added, and the UV-vis spectra of the samples
were recorded. All spectrophotometric titration curves were fitted with
the HYPERQUAD program.12 Care was taken that in each titration,
the p parameter (p ) [concentration of complex]/[maximum possible
concentration of complex]) was lower than 0.8, a condition required
for the safe determination of a reliable equilibrium constant.13 1H NMR
titrations were carried out on DMSO-d6 solution, at a higher concentra-
tion of 1 (5 × 10-3 M).
age.14 Absorption effects were evaluated with the psi-scan method,15
and absorption correction was applied to the data (min/max transmission
factors for the crystals were 0.922/0.968 and 0.910/0.971). Crystal
structures were solved by direct methods (SIR 97)16 and refined by
full-matrix least-squares procedures on F2 using all reflections (SHELXL
97).17 Anisotropic displacement parameters were refined for all non-
hydrogen atoms. Hydrogens bonded to carbon atoms were placed at
calculated positions with the appropriate AFIX instructions and refined
using a riding model; hydrogens bonded to the N(1) and N(3) amines,
as well as those belonging to water molecules and the hydrogencar-
bonate anion, were located in the ∆F map and refined by restraining
the X-H distance to be 0.89 ( 0.02 Å.
Synthesis of 1,3-Bis(4-nitrophenyl)urea (1). 4-Nitrophenylisocy-
anate (0.027 g, 0.163 mmol) was added to a solution of 4-nitroaniline
(0.022 g, 0.163 mmol) in dry dioxane (10 mL), in a round flask filled
with argon. The mixture was heated at 100 °C under magnetic stirring
for 24 h. During the reaction, a yellow precipitate formed, which was
collected by filtration, washed with water, and dried in vacuo. The
yellow solid (0.044 g, 89%) is air stable, soluble in DMSO, partially
soluble in acetonitrile, and insoluble in all other common solvents: 1H
NMR (DMSO-d6) δH 8.22 (d, 2H, Hâ), 7.73 (d, 2H, HR), 9.70 (s, 2H,
Results and Discussion
The interaction of receptor 1 with the Y-shaped anion
CH3COO- was investigated in an MeCN solution through
spectrophotometric titration experiments. In particular, a standard
solution of [Bu4N]CH3COO was added stepwise to a 4 × 10-5
M solution of 1 at 25 °C. Upon acetate addition, the pale yellow
solution of 1 took a bright yellow color, as shown in the picture
in Figure 1.
Figure 2 shows the family of spectra taken in the course of
the titration. Upon addition of CH3COO-, the band at 345 nm
progressively decreases, while a new band at 370 nm forms
and develops. Presence of two sharp isosbestic points at 262
and 354 nm indicates that only two species coexist at the
equilibrium. The profile of the intensities of the bands at 345
NH), coupling constants determined for an AA′MM′ system JHR,Hâ
)
JHâ,HR ) 8 Hz; IR (Nujol, cm-1) ν 1741 (CdO), 1577 ν(N-O), 1461
νas(NO2), 1301 νs(NO2), 3365, 3339 νas,νs(N-H), 1498, 1249 δas,δs-
(N-H).
X-ray Crystallographic Studies. Diffraction data were collected
at room temperature by means of an Enraf-Nonius CAD4 four-circle
diffractometer, working with graphite-monochromatized Mo KR X-
radiation (λ ) 0.71073 Å). Crystal data for the [Bu4N][1‚CH3COO]
and [Bu4N][1‚HCO3]‚2H2O complex salts are reported in Table 1.
Data reductions (including intensity integration, background, Lorentz,
and polarization corrections) were performed with the WinGX pack-
(7) Smith, P. J.; Reddington, M. V.; Wilcox, C. S. Tetrahedron Lett. 1992,
41, 6085-6088.
(8) Fan, E.; van Arman, S. A.; Kincaid, S.; Hamilton, A. D. J. Am. Chem.
Soc. 1993, 115, 369-370.
(14) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837-838.
(15) North, A. C. T.; Phillips, D. C.; Mathews, F. S. Acta Crystallogr. 1968,
A24, 351-359.
(9) Fitzmaurice, R. J.; Kyne, G. M.; Douheret, D.; Kilburn, J. D. J. Chem.
Soc., Perkin Trans. 1 2002, 841-864.
(10) Steiner, T. Angew. Chem., Int. Ed. 2002, 41, 48-76.
(11) Miyaji, H.; Sessler, J. L. Angew. Chem., Int. Ed. 2001, 40, 154-157.
(12) Gans, P.; Sabatini, A.; Vacca, A. Talanta 1996, 43, 1739-1753.
(13) Wilcox, C. S. Frontiers in Supramolecular Chemistry and Photochemistry;
VCH: Weinheim, Germany, 1991; pp 123-143.
(16) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo,
C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna, R. J. Appl.
Crystallogr. 1999, 32, 115-119.
(17) Sheldrick, G. M. SHELX97: Programs for Crystal Structure Analysis;
University of Go¨ttingen: Go¨ttingen, Germany, 1997.
9
16508 J. AM. CHEM. SOC. VOL. 126, NO. 50, 2004

Nature of the Urea−Fluoride Interaction
A R T I C L E S
Figure 1. Color changes observed with the addition of anions to an MeCN
solution of 1.
Figure 3. Titration of a 5 × 10-3 M solution of 1 in DMSO-d6 with (a)
CH3COO- and (b) F-.
higher solubility. However, apart from the different resolution,
spectra recorded in CD3CN and in DMSO-d6 exhibited similar
patterns. In particular, a 5 × 10-3 M DMSO-d6 solution in 1
was titrated with CH3COO-, which was added stepwise up to
5 equiv. Figure 3a shows the NMR spectra obtained in the
course of the titration and illustrates the spectral shifts of the
aromatic protons of the phenyl rings linked to the urea moiety,
HR and Hâ, with the addition of acetate. Spectra indicate the
formation of a discrete H-bond complex. In fact, two effects
are expected to derive from the hydrogen bond formation
between the urea subunit and the anion. (i) The increase of
electron density in the phenyl rings, with a through-bond
propagation; this causes a shielding effect and should promote
an upfield shift. (ii) The polarization of the C-H bonds, induced
by a through-space effect, electrostatic in origin; in particular,
the partial positive charge created onto the proton causes a
deshielding effect and promotes a downfield shift. The latter
effect is expected to vanish at higher distances and should
therefore operate only on the C-HR bond. In fact, in the case
of C-HR proton, the electrostatic effect dominates, and a
progressive downfield shift is observed, which stops after a 1
equiv addition. On the other hand, C-Hâ protons feel neither
the anion-induced electrostatic effect nor the C-HR polarization
effect, thus being affected only by the through-bond effect,
which induces a moderate upfield shift. Also in this case, shift
stops after a 1 equiv addition of acetate.
The above evidence points toward the formation of a
[1‚CH3COO]- H-bond complex. The nature of such a complex
was definitively demonstrated through X-ray diffraction studies.
In particular, on slow evaporation of an MeCN solution
containing equimolar amounts of 1 and [Bu4N]CH3COO,
crystals of a salt of formula [Bu4N][1‚CH3COO], suitable for
crystallographic studies, were obtained. The ORTEP diagram
of the complex salt is shown in Figure 4.
It is observed that the acetate ion establishes two directional
H-bonds with the two -NH fragments of the urea subunit. To
our knowledge, this is the first crystallographic report in which
a distinct urea subunit interacts with an acetate ion, in a discrete
Figure 2. (a) Family of spectra taken in the course of the titration of a 2.6
× 10-5 M solution in 1 with a standard solution of [Bu4N]CH3COO at 25
°C. (b) Titration profile for the 2.6 × 10-5 M MeCN solution ×in 1, which
indicates the formation of a 1:1 adduct [1‚CH3COO]. (c) Titration profile
for a 1.0 × 10-6 M solution in 1, from which the association constant was
determined, log K ) 6.61 ( 0.09.
(decreasing) and 370 nm (increasing), shown in Figure 2a,
indicates a 1:1 stoichiometry for the receptor-acetate interac-
tion. Data can be interpreted on the basis of the following
equilibrium: 1 + CH3COO- / [1‚CH3COO]-, in which
[1‚CH3COO]- represents the receptor-anion complex. How-
ever, the curvature in the titration profile reported in graph a is
too steep to allow a safe determination of the binding constant.
In particular, the p parameter (p ) [concentration of complex]/
[maximum possible concentration of complex]) was found
higher than 0.8, a condition which does not permit the
determination of a reliable equilibrium constant.13 Thus, titration
was carried out on a distinctly more diluted solution (1.0 ×
10-6 M; see the smoother titration profile in inset c). In these
conditions, the p parameter was lower than 0.8, and a reliable
value of the association constant could be determined through
nonlinear least-squares treatment of the titration profile: log K
) 6.61 ( 0.01.
The interaction of receptor 1 with acetate (used as tetrabu-
tylammonium salt) was investigated by 1H NMR spectroscopy.
However, the limited solubility of 1 prevented the recording of
well-resolved spectra in CD3CN. Thus, 1H NMR titration
experiments were carried out in DMSO-d6, where 1 presents a
9
J. AM. CHEM. SOC. VOL. 126, NO. 50, 2004 16509

A R T I C L E S
Boiocchi et al.
Figure 4. ORTEP view of the [1‚CH3COO]- complex (thermal ellipsoids
are drawn at the 30% probability level; only H atoms involved in
intermolecular hydrogen bonds are drawn). Tetrabutylammonium ion has
been omitted for clarity. Dashed lines indicate the hydrogen-bond interac-
tions.
Figure 5. Family of spectra taken in the course of the titration of a 1 ×
10-6 M MeCN solution in 1 with a standard solution of [Bu4N]H2PO4 at
25 °C. Titration profiles (inset) indicate the formation of a 1:1 complex,
[1‚H2PO4], to which a binding constant, log K ) 5.37 ( 0.01, corresponds.
Table 2. Geometrical Features of the NH‚‚‚O Interactions with the
Y-Shaped Anions in [1‚CH3COO]- and [1‚HCO3]-‚H2Oa
Table 3. Constants of the Complex Formation Equilibriuma
D
‚‚‚
A
H
‚‚‚
A
D
−
H
‚‚‚
A
acceptor
atom
donor group
anion
(Å)
(Å)
(deg)
1
anion
log Kb
ꢀ
(M-1 cm-
)
N(1)-H(1N)
CH3COO- 2.693(5) 1.797(28) 170.9(26)
CH3COO-
C5H6COO-
6.61 (1)
6.42 (1)
5.37 (1)
log K1) 7.38 (9)
log K2) 6.37 (12)
4.33 (1)
4.26 (1)
3.65 (5)
42172 (370 nm)
38249 (370 nm)
39406 (370 nm)
20712 (370 nm)
19324 (470 nm)
27200 (370 nm)
28600 (370 nm)
23300 (370 nm)
28700 (370 nm)
-
HCO3
2.811(4) 1.929(23) 166.8(21) O(6)
N(3)-H(3N)
CH3COO- 2.770(5) 1.852(30) 174.4(27)
-
H2PO4
-
HCO3-
HCO3-
HCO3-
HCO3-
2.790(4) 1.897(23) 169.7(20) O(7)
F-c
O(8)-H(80)
O(9)-H(90A)
O(9)-H(90B)
2.617(4) 1.681(22) 171.5(21) O(7)′
2.982(4) 2.113(36) 162.1(26) O(1)′′
2.908(4) 2.043(33) 160.2(29) O(6)
2.767(4) 1.863(26) 172.5(19) O(9)
3.069(4) 2.238(32) 152.9(25) O(3)′′′
-
NO2
-
HSO4
O(10)-H(91A) HCO3-
-
NO3
O(10)-H(91B) HCO3
Cl-
4.55 (1)
a Features of the O-H‚‚‚O interactions involving OH groups in
[1‚HCO3]-‚H2O are also reported. Symmetry codes: (′) ) -x + 1, -y +
1, -z; (′′) ) x + 1, y, z; (′′′) ) -x + 1, -y + 1, -z + 1.
°
a In an MeCN solution at 25 C: 1 + anion- / [1‚anion]-, and molar
absorbances (ꢀ) of the [1‚anion]- H-bond complexes. b The value in
parentheses is the uncertainty of the last figure. c The value of log K1 refers
to the H-bond complex formation; log K2 refers to the receptor’s deproto-
nation equilibrium: [LH‚F]- + F- / L- + [HF2]-.
1:1 anionic complex. A report was given in which a urea
fragment belonging to a metal-bound multidentate ligand
interacted with acetate anions.18 The N(urea)-O(acetate) dis-
tances in the [1‚CH3COO]- complex (2.69 and 2.77 Å) situate
the interaction among “moderate” hydrogen bonds, whose nature
is mainly electrostatic, according to Jeffrey’s classification.19
Significant bond distances and angles for the hydrogen-bonding
interactions in the [1‚CH3COO]- complex are reported in Table
2. In the table, relevant data for the hydrogencarbonate complex
of 1, [1‚HCO3]-‚H2O, are also reported and to be discussed
later.
Notice that the distances between the ortho protons nearest
to the carbonyl oxygen [2.217(4) and 2.207(4) Å] are among
the shortest observed for diarylureas.20 These features suggest
the presence of weak symmetrical CH‚‚‚O interactions, satisfy-
ing the hydrogen bond acceptor ability of the carbonyl oxygen.
Moreover, it has to be noted that the nitrophenyl substituents
are not perfectly coplanar with the urea subunit: the two dihedral
angles of the N-CO-N group are 7.4(2) and 11.2(3)°. Such a
nonplanarity can be ascribed to crystal packing effects associated
with the asymmetrical position of the tetrabutylammonium
cation.
The electronic rearrangement of receptor 1 following interac-
tion with acetate is demonstrated also by IR spectra. In
particular, the CdO stretching band of the urea fragment of 1
moves from 1742 to 1720 cm-1 in the [1‚CH3COO]- complex,
indicating definite bond weakening. This reflects the acetate-
induced increase of the electron density, which goes in part to
populate the π* orbital of the CdO fragment, reducing bond
order.
Analogous investigations were carried out with a variety of
oxoanions (H2PO4-, NO3-, NO2-, HSO4-, and C6H5COO-).
In particular, an MeCN solution of 1 was titrated with a standard
solution of the tetrabutylammonium salt of the chosen anion.
In all cases, a new absorption band at ∼370 nm developed on
titration, and sharp isosbestic points were observed in the
recorded family of spectra. As an example, Figure 5 displays
the spectra obtained on titration with [Bu4N]H2PO4. Spectral
features are the same as those observed for CH3COO-. Simply,
the titration profile (inset) shows a smoother curvature, to which
a smaller value of the binding constant corresponds (log K )
5.37 ( 0.01). Log K values and pertinent spectroscopic
parameters for all investigated oxoanions are reported in Table
3.
(18) Carcelli, M.; Ianelli, S.; Pelagatti, P.; Pelizzi, G. Inorg. Chim. Acta 1999,
292, 121-126.
(19) Jeffrey, G. A. An Introduction to Hydrogen Bonding; Oxford University
Press: Oxford, 1997.
(20) Etter, M. C.; Urban˜czyk-Lipkowska, Z.; Zia-Ebrahimi, M.; Panunto, T.
W. J. Am. Chem. Soc. 1990, 112, 8415-8426.
1H NMR titration experiments with oxoanions showed similar
patterns as those observed with CH3COO-. The above evidence
points toward the formation of a 1:1 adduct held together by
two hydrogen bonds, each one involving an -NH fragment of
9
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Nature of the Urea−Fluoride Interaction
A R T I C L E S
relationship points toward the electrostatic nature of the recep-
tor-oxoanion interaction and rules out any geometrical effect
on the binding (e.g., matching of the distance of the N atoms
of the urea subunit and the distance of the O atoms of the
oxoanion).
Fluoride displays a more intricate behavior. Figure 7a shows
the complete family of spectra obtained during the titration of
a 1.0 × 10-6 M solution of 1 in MeCN with [Bu4N]F; it is
seen that the band at 345 nm decreased, while a band at 370
nm formed and developed, as previously noticed for oxoanions.
In particular, the band at 370 nm reached its limiting value after
the addition of 1 equiv of F-. This behavior is illustrated in
Figure 7c. However, when approaching 1 equiv of F-, a new
band began to form at 475 nm. The band at 475 nm reached a
limiting value after the addition of 2 equiv of F- (see Figure
7d), while the solution took an orange-red color (see Figure 1).
The titration profiles, shown in insets c and d of Figure 7, clearly
indicate the presence of two distinct steps.
Figure 6. Linear relationship between the log K value of the complexation
equilibrium (1 + X- / [1‚X]-) in MeCN and the average negative charge
on the oxygen atom of the oxoanion, X-. Partial charges were calculated
through an ab initio method.
In fact, best fitting of the overall titration data was obtained
by assuming the existence of two stepwise equilibria, in which
(i) 1 interacts with F- to give [1‚F]- and (ii) the [1‚F]- complex
interacts with another F- ion. Constants for the two stepwise
equilibria, as calculated through nonlinear least-squares treat-
ment of spectrophotometric titration data, were log K1 ) 7.38
( 0.09 (1 + F-) and log K2 ) 6.37 ( 0.12 ([1‚F]- + F-). The
distribution diagram of the three species present at the equilib-
rium in the course of the titration with F-, calculated by the
1 and an oxygen atom of the oxoanion. The sequence of the
log K values (CH3COO- > C6H5COO- > H2PO4- > NO2
>
-
HSO4- > NO3-) should reflect the decreasing intrinsic basicity
of the anion. In particular, a reasonably linear correlation was
observed between log K and the average negative charge on
the oxygen atoms of each oxoanion, as calculated through an
ab initio method (see Figure 6).
The higher the negative charge, the higher the H-bond
acceptor tendencies of the anion. The existence of such a
Figure 7. (a) Family of spectra taken in the course of the titration of a 1.0 × 10-6 M MeCN solution ×in 1 with a standard solution of [Bu4N]F at 25 °C.
(b) Distribution diagram of the species present at the equilibrium, which has been calculated for a 1.0 × 10-6 M solution of 1 in MeCN titrated with
[Bu4N]F. The solid line refers to the uncomplexed ligand 1, the dashed line to the H-bond complex [1‚F]-, and the dotted line to the deprotonated form of
1. (c) Addition of up to 1.0 equiv of F-. (d) Addition of 1.0-5 equiv of F-. Insets: titration profiles of the band at 345 nm, which corresponds to the H-bond
adduct [1‚F]- (c), and of the band at 475 nm, which corresponds to the deprotonated form of 1 (d).
9
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A R T I C L E S
Boiocchi et al.
Scheme 1. Charge Transfer Transition Occurring in the
Deprotonated Form of 1
HYPERQUAD software package12 from pertinent log K values
for a 1.0 × 10-6 M solution of 1, is shown in Figure 7b. The
three species are (i) the receptor 1, (ii) the product of the first
equilibrium, presumably the [1‚F]- H-bond complex, which
reaches its maximum concentration (∼60%) with addition of 1
equiv of F-, and (iii) the product of the second equilibrium,
whose nature has to be ascertained and whose concentration
tends to 100%, with the addition of excess F-.
A DMSO-d6 solution of 1 was titrated with [Bu4N]F, and
corresponding 1H NMR spectra are shown in Figure 3b.
Different patterns are observed in the titration ranges of 0-1
and 1-2 equiv. In fact, C-Hâ protons undergo upfield shift in
both the 0-1 and 1-2 equiv ranges, while C-HR protons are
insensitive to the first equivalent addition but undergo upfield
shift with the addition of the second equivalent of fluoride. In
any case, the shift is stopped after addition of the second
equivalent. This state of affairs can be accounted for by
hypothesizing that the first added F- establishes H-bond
interaction with the urea subunit of 1. On addition of the second
fluoride ion, deprotonation of one -NH fragment takes place,
which brings electron density onto the phenyl rings according
to a through-bond mechanism, thus increasing the shielding of
HR nuclei and inducing upfield shift. Notice also that, in the
deprotonated form, the polarization effect is no longer present
since the anion does not remain in proximity to the receptor.
Thus, it is suggested that the first added F- interacts with 1
through hydrogen bonding, while the second F- induces the
deprotonation of one -NH fragment of the urea subunit, with
formation of the [HF2]- ion, as illustrated by the equation below
(LH ) 1):
Figure 8. Linear correlation between the binding constants and the limiting
absorbance at 370 nm for the [1‚anion]- adducts in MeCN solution.
Thus, it appears that urea deprotonation is signaled by the
appearance of a new absorption band at a long wavelength and
takes place only in the case of fluoride. The F- ion first
establishes the strongest H-bond interaction with the receptor,
as indicated by the highest value of log K. This is an expected
behavior, in view of the high electronegativity of fluorine.
Hydrogen-bonding interaction has been defined as an incipient
proton-transfer process from the receptor to the anion.10 F-,
among the investigated anions, induces the most pronounced
“frozen” proton transfer from the urea subunit when added in
a subequivalent amount. Indeed, a neat proton transfer takes
place in the presence of a second equivalent of F-. This is due
to the particular stability of the [HF2]- dimer, for which the
highest hydrogen bond energy in the gas phase has been
calculated (39 kcal mol-1).21 Thus, if one F- ion is a fairly
strong base in an MeCN solution, as documented by its ability
to establish intense H-bond interactions with 1 and by the highest
value of log K1, two F- ions represent a very strong base,
capable of abstracting a proton from the urea subunit. It has to
be noticed that the acidity of the urea moiety has been enhanced
and its deprotonation favored due to the presence of two
electron-withdrawing nitro substituents on the covalently linked
phenyl rings.
With regard to the H-bond complexes between 1 and the
oxoanions, a roughly linear relationship exists between log K
and the limiting molar absorbance ꢀ, as shown in Figure 8. The
higher the energy of the H-bond interaction (expressed by log
K), the higher the value of the molar absorbance of the complex.
To explain such an empirical relationship, one should consider
that, on H-bond interaction with the anion, electron density is
increased on each -NH fragment, thus strengthening the
electrical dipole on each aromatic subunit of 1. Thus, the band
at 370 nm, resulting from the charge-transfer transition from
the -NH fragment to the -NO2 group, on each side of the
chromophore, moves up with anion addition. The probability
of the transition is related to the intensity of the dipole; the
higher the dipole intensity (which is related to the H-bond
interaction energy and to log K), the higher the probability of
the transition and the value of the molar absorbance. Thus, the
molar absorbance of the band at 370 nm gives a rather rough
estimate of the intensity of the hydrogen-bonding interaction
[LH‚F]- + F- / L- + [HF2]-
(1)
The deprotonated species (L-) is a push-pull chromophore,
which undergoes an optical charge-transfer transition, as il-
lustrated in Scheme 1. This low-energy transition is responsible
for the appearance of the band at 475 nm and for the
development of the orange-red color.
Due to the rather large log K2 value, which characterizes the
proton transfer equilibrium (eq 1), the deprotonated form of the
receptor forms quite early in the titration with fluoride. This
accounts for the formation of the band at 475 nm even before
the addition of 1 equiv of F-. In particular, with the addition of
1 equiv, 20% of the deprotonated form of 1 is present, which
substantiates the detectable appearance of the band at 475 nm
(see Figure 7c) and the orange nuance of the solution (see Figure
1).
Titration was carried out also with [Bu4N]Cl, which induced
the development of the band at 370 nm, as observed for
previously mentioned oxoanions. No band development at
higher wavelengths was detected also with the addition of a
large excess of chloride. It is suggested that a hydrogen-bonding
adduct, [1‚Cl]-, is formed, whose binding constant was calcu-
lated from the titration profile, log K ) 4.55 ( 0.01.
(21) Gronert, S. J. Am. Chem. Soc. 1993, 115, 10258-10266.
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16512 J. AM. CHEM. SOC. VOL. 126, NO. 50, 2004

Nature of the Urea−Fluoride Interaction
A R T I C L E S
Figure 9. ORTEP view of the [1‚HCO3]-‚H2O complex (thermal ellipsoids
are drawn at the 30% probability level; only H atoms involved in
intermolecular hydrogen bonds are drawn). Tetrabutylammonium ion has
been omitted for clarity. Dashed lines indicate the hydrogen-bond interac-
tions in the asymmetric unit and between symmetrically equivalent atoms.
Symmetry codes: (′) ) -x + 1, -y + 1, -z; (′′) ) x + 1, y, z; (′′′) ) -x
+ 1, -y + 1, -z + 1.
Figure 10. H-bond motif in the {[1‚HCO3]-}2 dimer. H-bonds have been
drawn in light blue.
the deprotonated form of 1 (L-) with carbon dioxide, in the
presence of water, as illustrated by eq 2:
and accounts for the approximately linear correlation between
log K and ꢀ. At this point, one could wonder about the behavior
of the [1‚F]- complex, which exhibits the highest log K value
(log K1 ) 7.38 ( 0.09), but whose absorbance is about one-
half of that observed for acetate and dihydrogen phosphate
complexes. We can tentatively suggest the following explana-
tion: each investigated oxoanion (CH3COO-, C6H5COO-,
H2PO4-, NO2-, HSO4-, and NO3-) forms with the urea subunit
two N-H‚‚‚O hydrogen bonds, from which two dipoles and
two possible optical transitions originate. On the other hand, it
is suggested that the small F- ion specifically interacts with
only one -NH fragment, thus strengthening only a single dipole,
which justifies a reduced value of the molar absorbance. In
contrast, chloride is well-behaving with respect to the ꢀ/log K
linear correlation, which suggests that the larger Cl- anion
establishes a bifurcated hydrogen-bonding interaction with the
urea subunit of 1, thus making the [1‚Cl]- complex subject to
two possible charge-transfer transitions. Unfortunately, we were
not able to obtain crystals of [1‚Cl]- to support this hypothesis
on the basis of X-ray diffraction study. However, the crystal
structure of the analogous complex, [L‚Cl]- (L ) 1,3-bis(4-
chlorophenyl)urea), indicates bifurcated interaction of the
chloride ion.22
Attempts were made to obtain crystals of the tetrabutylam-
monium salt of the deprotonated form of 1 with slow diffusion
of diethyl ether into an MeCN solution containing the receptor
and an excess of [Bu4N]F. However, only a red oil separated.
The red oil was redissolved in THF, and the solution was left
to evaporate in open air. In a few days, yellow crystals of the
salt, [Bu4N][1‚HCO3]‚2H2O, were obtained, suitable for X-ray
diffraction studies. Figure 9 shows the ORTEP diagram il-
lustrating the molecular structure of the salt, which consists of
a tetrabutylammonium cation, and of the anionic complex
between 1 and HCO3-, with two molecules of water of
crystallization. Apparently, the complex formed by reaction of
L- + H2O + CO2 f [LH‚HCO3]-
(2)
It is seen that the 1,3-bis(4-nitrophenyl)urea framework is
not perfectly planar, with dihedral angles between the N-CO-N
group and the two phenyl rings of 3.5(1) and 7.8(1)°. Such a
deviation, which is less pronounced than that observed in the
[1‚CH3COO]- adduct, may also be ascribed to crystal packing
effects, related to the presence of asymmetrically located water
molecules.
More interestingly, the urea subunit of 1 gives a definite
hydrogen-bonding complex with an HCO3- ion, with formation
of two NH‚‚‚O bonds. Moreover, each urea-bound HCO3- ion
donates and accepts a hydrogen bond to/from another urea-
-
bound HCO3 ion, giving rise to a dimer. A sketch of the
H-bond dimer is shown in Figure 10. In particular, the O(7)
atom, already involved in the interaction with the -NH fragment
of the urea subunit, is also a proton acceptor for the OH‚‚‚O
interaction that occurs with the OH donor group of an adjacent
HCO3-; thus, the two N-CO-N groups are linked via two
hydrogencarbonate ions. This situation is common when urea
and HCO3- are present; in particular, it occurs with very similar
features in urea-hydrogencarbonate complexes, containing
tetraethyl- or tetrabutylammonium as cations.21 Relevant geo-
metrical parameters related to the hydrogen-bonding interactions
in the crystalline complex salt, [Bu4N][1‚HCO3]‚2H2O, are
shown in Table 2.
It has to be noted that NH‚‚‚O interactions are weaker than
those observed with the CH3COO- anion, as judging from the
higher N‚‚‚ O distance. This may be due to the fact that the
-
acetate ion is solely involved in two H-bonds, while HCO3
further interacts with another HCO3-. Moreover, further H-
bonds result from the presence of the water molecules in the
crystal. The O(9) atom of the first water molecule is a proton
donor for the O(6) atom of a hydrogencarbonate ion and for
the O(1) carbonyl oxygen of an N-CO-N group, and then an
-
HCO3 ion and a water molecule connect the donor -NH
fragments and the acceptor carbonyl oxygen of two urea groups.
(22) Wamhoff, H.; Bamberg, C.; Herrmann, S.; Nieger, M. J. Org. Chem. 1994,
59, 3985-3993.
9
J. AM. CHEM. SOC. VOL. 126, NO. 50, 2004 16513

A R T I C L E S
Boiocchi et al.
Finally, the O(10) of the second water molecule acts as a proton
donor of OH‚‚‚O interactions, with the O(9) atom of the first
water molecule and with the O(3) atom of a nitro group.
Noticeably, it has been recently reported that in a 4-amino-
1,8-naphthalimide-based receptor, the addition of excess F-
induced the deprotonation of the amino group, and that following
fixation of atmospheric CO2, an H-bond complex formed
between the neutral receptor and HCO3-, according to an
analogous mechanism.23
charge. Thus, among anions, F- establishes the strongest H-bond
interaction with an -NH fragment of the urea subunit. In
particular, the interaction should correspond to an advanced
stage of the proton transfer.10 Indeed, proton transfer takes place
-
in the presence of a second F- ion, with formation of HF2
,
the most-stable H-bond complex that fluoride can form. Just in
view of the unique stability of HF2-, excess addition of fluoride
should induce deprotonation of most urea derivatives, with the
process being signaled by the appearance of a charge-transfer
absorption band in the visible region and by a drastic color
change. Despite the visual evidence, this feature has been missed
in a recent report.24
Conclusions
This investigation may represent a case study for the
interaction of ureas with anions. Urea is an appropriate receptor
for oxoanions because it can form two N-H‚‚‚O bonds with
two consecutive oxygen atoms of the anion. The interaction is
essentially electrostatic, and its energy is related to the intrinsic
basicity of the anion, whose magnitude can be evaluated, for
instance, from the partial negative charge located on each
Acknowledgment. The financial support of the European
Union (RTN Contract HPRN-CT-2000-00029) and the Italian
Ministry of University and Research (PRIN, Dispositivi Su-
pramolecolari; FIRB, Project RBNE019H9K) is gratefully
acknowledged.
oxygen atom of the anion. Thus, the sequence of log K values
found in this work (CH3COO- > C6H5COO- > H2PO4
>
-
Supporting Information Available: Crystallographic infor-
mation (CIF) on the complex salts, [Bu4N][1‚CH3COO] and
[Bu4N][1‚HCO3]‚2H2O. This material is available free of charge
via the Internet at http://pubs.acs.org.
NO2- > HSO4- > NO3-) corresponds to the natural order, to
be observed in any urea-containing receptor in the absence of
severe steric constraints, and ultimately determines the selectivity
of anion recognition. Fluoride is a particular case as it has a
size comparable to that of oxygen but holds an integral negative
JA045936C
(23) Gunnlaugsson, T.; Kruger, P. E.; Jensen, P.; Pfeffer, F. M.; Hussey, G. M.
(24) Kwon, J. Y.; Yun Jung Jang, Y. J.; Kim, S. K.; Lee, K.-H.; Kim, J. S.;
Tetrahedron Lett. 2003, 49, 8909-8913.
Yoon, J. J. Org. Chem. 2004, 69, 5155-5157.
9
16514 J. AM. CHEM. SOC. VOL. 126, NO. 50, 2004