Dimerization of tris(o-ureidobenzyl)amines: A novel class of aggregates

Article abstract of DOI:10.1039/b007955n

Dimeric aggregates are formed by the assembly of two tripodal moieties which are held together, both in solution and in the solid state, by a belt of 6 hydrogen-bonded urea functions.

Full text of DOI:10.1039/b007955n

Dimerization of tris(o-ureidobenzyl)amines: a novel class of aggregates†
Mateo Alajarín,*a Antonia López-Lázaro,a Aurelia Pastor,a Paul D. Prince,b Jonathan W. Steed*b and Ryuichi
Arakawac
a Departamento de Química Orgánica, Facultad de Química, Campus de Espinardo, Universidad de Murcia,
E-30100 Murcia, Spain. E-mail: alajarin@um.es
b Department of Chemistry, King’s College London, Strand, London, UK WC2R2LS. E-mail: jon.steed@kcl.ac.uk
c
Department of Applied Chemistry, Kansai University, Suita, 564-8680 Osaka, Japan.
E-mail: arak@ipcku.kansai-u.ac.jp
Received (in Cambridge, UK) 2nd October 2000, Accepted 11th December 2000
First published as an Advance Article on the web 4th January 2001
Dimeric aggregates are formed by the assembly of two
tripodal moieties which are held together, both in solution
and in the solid state, by a belt of 6 hydrogen-bonded urea
functions.
corresponding to equilibrium mixtures of both compounds (Fig.
1b).
The dimeric species featured two well separated doublets
assigned to the diastereotopic methylenic protons of the
(ArCH2)3N fragment (Jgem = 14.5–15.7 Hz), instead of the
singlet observed for the same nuclei in DMSO-d6. In the dimers
emerging from 2 and 3 the ABX systems formed by the three
protons of the –CH2NH– fragments were clearly evident. The
signals assigned to the NH protons of the dimers (near 6.0 and
7.6 ppm, in 2·2 and 3·3) appeared significantly sharp and shifted
to lower field when compared to those attributed to the
monomers (near 5.2 and 6.3 ppm). The involvement of the urea
carbonyl groups as hydrogen bonding acceptors is supported by
the d value of their carbon atoms in the 13C NMR spectra, which
were shifted to downfield in CDCl3 (Dd = 2.8–3.2 ppm). FT-IR
of CHCl3 solutions of 1 (13.7 mM) and 2 (16.4 mM) revealed
typical hydrogen-bonded NH-stretching bands9 at 3317–3327
When two or more identical subunits are geometrically and
functionally complementary, they may self-assemble to form a
super molecule.1 Urea or thiourea functionalities are excellent
candidates to construct molecules that self-assemble by hydro-
gen-bonding not only in the solid state but are able to persist in
solution.2 Rebek3 and Böhmer4 have independently established
that calix[4]arenes containing four urea functions at the upper
rim form dimers by interdigitation of the all eight ureas in a
head-to-tail directional array of 16 hydrogen bonds. Mendoza
and coworkers have described dimeric capsules derived from
tris(ureido)calix[6]arenes.5 Herein we report a novel type of
self-assembled dimeric aggregate derived from tris(o-ureido-
benzyl)amines which resemble the structure of ureidocalixar-
enes.
cm21
.
All those data revealed that the dimers 1·1, 2·2 and 3·3 should
possess a highly ordered, hydrogen-bonded structure. Further
indication of the existence of 1·1 and 3·3 in solution came from
ESI-MS experiments. This technique was used in virtue of its
gentle ionization and has been reported to reflect, at least
qualitatively, solution phenomena.10 The spectra in CHCl3
showed the molecular ions of the protonated dimers 1·1 (1463)
and 3·3 (1547).
The tris(ureas) 1–36 shown in Scheme 1, easily available7
from previously reported tris(o-azidobenzyl)amines,8 showed
dramatic differences in their 1H NMR spectra when recorded in
CDCl3 or DMSO-d6. While the spectra of 1–3 in DMSO-d6
displayed the expected patterns consistent with averaged C3v
symmetries (Fig. 1a), by changing the solvent to CDCl3 a new
set of signals corresponding to a dimer (see below) emerged in
each case. The ratio in which both species, monomer and dimer,
were present in CDCl3 depended on the substituent R2 to a great
extent. Thus, while for the tris(urea) 1 (R2 = p-tolyl) only the
signals attributed to the dimer were apparent, for the tris(ureas)
Thus, monomers and their dimeric aggregates coexist in
equilibrium in CDCl3. Preliminary calculations of the dimeriza-
tion constant of 1 by 1H NMR experiments at three concentra-
tions (in the range 1–10 mM in CDCl3) following known
2 and 3 (R2
=
Bn) their spectra were interpreted as
equations11 showed values (82518, 83832 and 84755 M21
)
which are comparable within the experimental error margin.
Scheme 1
Fig. 1 (a) 1H NMR spectrum (300 MHz) of the tris(urea) 2 in DMSO-d6 (the
singlet at 3.39 ppm is H2O from the solvent), (b) 1H NMR spectrum
measured in CDCl3 showing a mixture of 2 and 2·2.
† Electronic supplementary information (ESI) available: 1H NMR spectra.
See http://www.rsc.org/suppdata/cc/b0/b007955n/
DOI: 10.1039/b007955n
Chem. Commun., 2001, 169–170
This journal is © The Royal Society of Chemistry 2001
169

Fig. 2 A perspective view of the molecular structure 2·2, as projected along
the pseudothreefold axis containing the two pivotal nitrogen atoms.
Since DMSO-d6 is able to disrupt the intermolecular hydrogen
bonds, only the monomeric species could be observed in this
solvent. The thermodynamic stability of the dimeric aggregate
1·1 proved to be higher than 2·2 and 3·3. The dimer 1·1 is
virtually the only species observed (!98%) in a 30 mM CDCl3
solution of 1. In contrast, the 1H NMR spectra of 2·2 and 3·3 in
CDCl3 solutions of the same concentration displayed consider-
able amounts of their respective monomers (15–20%). These
dimerization equilibria were concentration dependent, and
could be shifted toward the monomer by decreasing the
concentration. These equilibria could be also totally shifted to
the monomeric tris(urea) by adding DMSO-d6 (40%) to the
CDCl3 solution. Finally, the composition of a mixture of 2 and
2·2 was found to be temperature dependent; an increase in the
temperature shifted the equilibrium toward the monomer. Thus,
the 85+15 ratio of 2·2 to 2 measured at 296 K decreased to
72+28 at 323 K (38 mM in CDCl3).
1
Fig. 3 Partial H NMR spectra (300 MHz, CDCl3) showing the NH-aryl
region: (a) 2·2; (b) 3·3 (the doublet at 7.53 ppm was assigned to the
monomer 3); (c) mixture of equimolecular quantities of 2·2 and 3·3.
for
a
Marie Curie fellowship (contract HPMF-CT-
1999-00126).
Notes and references
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Pochini, P. Prados and J. de Mendoza, Chem. Eur. J., 2000, 6, 73.
6 All the tris(ureas) 1–3 were characterized on the basis of their IR, 1H and
13C NMR spectra and CHN-analyses.
7 Sequential treatment of the corresponding tris(azide) with LiAlH4
(64–68% yield) and p-tolyl or benzyl isocyanate, led to the tris(ureas)
1–3 in good yields (61–99%).
8 M. Alajarín, P. Molina, A. López-Lázaro and C. Foces-Foces, Angew.
Chem., Int. Ed. Engl., 1997, 36, 67; M. Alajarín, A. López-Lázaro, A.
Vidal and J. Berná, Chem. Eur. J., 1998, 4, 2558.
9 For IR studies of hydrogen bonds, see: I. M. Klotz and J. S. Franzen,
J. Am. Chem. Soc., 1962, 84, 3461; G. P. Dado and S. H. Gellman, J. Am.
Chem. Soc., 1994, 116, 1054.
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A single crystal X-ray structure12 of 2·2 confirmed unambi-
guously the existence of the hydrogen-bonded dimers in the
solid state, and provided an exact description of their geometry
(Fig. 2). The dimer is composed of two enantiomeric units
entangled via their urea residues, which form a belt of 12
hydrogen bonds with N…O distances ranging from 2.897(4) to
3.024(4) Å. The dimeric core is of approximate S6 symmetry,
although this is broken by the pendant phenyl substituents. The
centre of the capsule is empty and is too small to contain any
guest species, however extensive disordered solvent exists in
external pockets formed by the aryl groups of the dimer. On the
basis of the NMR data (CDCl3) we believe that the conforma-
tion shown by the solid state structure of 2·2 is retained in
solution.
The formation of heterodimers by the combination of two
homodimeric species is a well-known phenomenon in ur-
eidocalixarenes.3,4 In our case, a mixture of equimolecular
amounts of the dimers 1·1 and 2·2 in CDCl3 did not show the
formation of heterodimers. However, the 1H NMR spectrum of
an equimolecular mixture of 2·2 and 3·3 revealed the appear-
ance of signals attributable to the heterodimer 2·3, besides those
of homodimers 2·2 and 3·3 and monomers 2 and 3. In this
experiment the region of the aryl-NH protons (7.45–7.80 ppm)
was especially informative (Fig. 3). Thus, four NH singlets
appeared (Fig. 3c), two of them due to the homodimers 2·2 (d =
7.63 ppm) and 3·3 (d = 7.61 ppm), and the other two to both
aryl-NH protons of the heterodimer 2·3 (d = 7.51 ppm and d =
7.73 ppm). The integration revealed a nearly statistical mixture
of the three dimers.
In summary, we have shown that tris(o-ureidobenzyl)amines
1–3 self assemble to form dimeric aggregates in which six urea
groups constitute a cyclic array involving a closed network of
12 hydrogen bonds.
This work was supported by DGES (Project PB95-1019) and
Fundación Séneca-CARM (Project PB/2/F5/99). J. W. S. thanks
the EPSRC and King’s College London for the funding of the
diffractometer system. A. P. thanks the European Commission
11 D. J. Cram, H. J. Choi, J. A. Bryant and C. B. Knobler, J. Am. Chem.
Soc., 1992, 114, 7748.
12 Crystallographic data for 2·2: Formula: C50H51Cl2N7O3, triclinic
¯
crystal, space group P1, a = 13.936(3), b = 13.985(3), c = 14.350(3)
Å, a = 117.719(3), b = 94.551(3), g = 108.840(3)°. T = 100(2) K, U
= 2253.4(8) Å3, Dc 1.281 mg m23, 7864 independent reflections used
in refinement, 498 parameters, R1 (I > 2s(I)) = 0.0805, wR2 (all data)
= 0.2211. CCDC 182/1878.
170
Chem. Commun., 2001, 169–170