Bernier et al.
CHART 1. Structure of the Macrobicycle DBF-bz
achieved by cooperative effects of geometric fit and strong
interactions between partners.
2
c,5g
Macrobicycles (also named cryptands) are particularly inter-
esting artificial receptors, which offer a wide range of potential
useful molecular recognition properties for anions, cations, or
2,5g,7
both.
ments, one of them designed for the appropriate bind of an anion
in general formed by N-H fragments from amine, amide, or
These systems may consist of two different compart-
(
urea groups) and the other one for the binding of a cation (in
general containing a crown ether moiety). For instance, Esteban-
8
G o´ mez et al. studied macrobicyclic receptors exhibiting high
-
binding selectivity to Cl over the other halides and sulfate over
+
-
the presence of K , the receptor affinity toward Cl was 13-
fold enhanced, due to a cooperative electrostatic effect.
nitrate. Moreover, the three-dimensional preorganized structure
of macrobicycles may offer the possibility of mutual location
of an ion pair into the two compartments of the receptor
producing, in certain cases, a positive cooperative effect leading
to an increase in the binding affinity. For instance, the
macrobicycle containing oxa-crown and amide binding sites
In spite of some attractive examples in the literature, the
recognition phenomena based on macrobicyclic receptors remain
a research area to explore. In this context, we report here the
design and the synthesis of a macrobicycle, DBF-bz (Chart 1),
formed by an isophthalamide bridge linked through two
ethylenic chains to a tetraoxadiaza macrocycle. The macrocyclic
moiety, mainly composed by a rigid dibenzofuran unit and a
flexible trioxa fragment, is expected to present enough space
for inclusion of cationic species such as alkali cations or
9
presented by Smith et al. is capable to accommodate both the
cation (e.g., K ) and the anion (e.g., Cl ) in close contact: in
+
-
(
2) For recent reviews, see: (a) Gale, P. A.; Garc ´ı a-Garrido, S. E.; Garric, J.
Chem. Soc. ReV. 2008, 37, 151–190. (b) Amendola, V.; Bonizzoni, M.; Esteban-
G o´ mez, D.; Davis, A. P. Coord. Chem. ReV. 2006, 250, 2939–2951. (c) Kang,
S. O.; Hossain, M. A.; Bowman-James, K. Coord. Chem. ReV. 2006, 250,
10
ammonium substrates. On the other hand, the isophthalamide
unit can strongly interact with anionic substrates such as
6d,e
6a,b
3
0383052. (d) Garc ´ı a-Espa n˜ a, E.; D ´ı az, P.; Llinares, M. J.; Bianchi, A. Coord.
chloride or carboxylate. Thus, the recognition phenomena
between BDF-bz and different substrates was studied in the
present work in order to obtain information on the binding
process. Results will be discussed in terms of binding strength
and geometrical requirements.
Chem. ReV. 2006, 250, 2952–2986.
(
3) For recent reviews, see: (a) Nguyen, B. T.; Anslyn, E. V. Coord. Chem.
ReV. 2006, 250, 3118–3127. (b) Fabbrizzi, L.; Licchelli, M.; Sancen o´ n, F.;
Taglietti, A. Coord. Chem. ReV. 2006, 250, 1451–1470. (c) Gunnlaugsson, T.;
Glynn, M.; Tocci, G. M.; Kruger, P. E.; Pfeffer, F. M. Coord. Chem. ReV. 2006,
2
50, 3094–3117.
(
(
4) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486–516.
5) (a) Carvalho, S.; Delgado, R.; Drew, M. G. B.; Calisto, V.; F e´ lix, V.
Results and Discussion
Tetrahedron 2008, 64, 5392–5403. (b) Cruz, C.; Calisto, V.; Delgado, R.; F e´ lix,
V. Chem.sEur. J. 2009, 15, 3277–3289. (c) Delepine, A.-S.; Tripier, R.; Handel,
H. Org. Biomol. Chem. 2008, 6, 1743–1750. (d) Gonz a´ lez-Alvarez, A.; Alfonso,
I.; D ´ı as, A. R.; Garc ´ı a-Espa n˜ a, E.; Gotor-Fern a´ ndez, V.; Gotor, V. J. Org. Chem.
Synthesis and Characterization of the Macrobicyclic
Compound. The synthetic approach (Chart 2) is modular
allowing the two building blocks of the molecule, the isoph-
thalamide head unit and the tetraoxadiaza macrocycle, to be
modified leading to a wide variety of receptors. The target
compound, DBF-bz, was prepared by reaction of the N,N′-bis(2-
aminoethyl) derivative of the macrocycle [22](DBF)N
m-xylyldicarbonyl dichloride in high dilution at 0 °C, with Et
as base and in dry CH Cl /THF mixture of solvents. The
2
008, 73, 374–382. (e) Korendovych, I. V.; Cho, M.; Makhlynets, O. L.; Butler,
P. L.; Staples, R. J.; Rybak-Akimova, E. V. J. Org. Chem. 2008, 73, 4771–
782. (f) Fonari, M. S.; Ganin, E. V.; Gelmboldt, V. O.; Basok, S. S.; Luisi,
4
B. S.; Moulton, B. Inorg. Chem. Commun. 2008, 11, 497–501. (g) Lakshmi-
narayanan, P. S.; Ravikumar, I.; Suresh, E.; Ghosh, P. Inorg. Chem. 2007, 46,
4
769–4771. (h) Llinares, J. M.; Powell, D.; Bowman-James, K. Coord. Chem.
ReV. 2003, 240, 57–75.
6) (a) Ghosh, K.; Saha, I. Tetrahedron Lett. 2008, 49, 4591–4595. (b) Brooks,
S. J.; Caltagirone, C.; Cossins, A. J.; Gale, P. A.; Light, M. Supramol. Chem.
008, 20, 349–355. (c) Ros-Lis, J. V.; Mart ´ı nez-M a´ nˇ ez, R.; Sancen o´ n, F.; Soto,
10
O
2 3
with
(
3
N
2
2
2
J.; Rurack, K.; Weiꢀhoff, H. Eur. J. Org. Chem. 2007, 2449–2458. (d) Santacroce,
P. V.; Davis, J. T.; Light, M. E.; Gale, P. A.; Iglesias-S a´ nchez, J. C.; Prados, P.;
Quesada, R. J. Am. Chem. Soc. 2007, 129, 1886–1887. (e) Lin, C.; Simov, V.;
Drueckhammer, D. G. J. Org. Chem. 2007, 72, 1742–1746. (f) Lakshminaray-
anan, P. S.; Ravikumar, I.; Suresh, E.; Ghosh, P. Chem. Commun. 2007, 5214–
compound was obtained as a crystalline powder upon silica gel
column chromatography purification in 37% yield. Single
crystals suitable for X-ray diffraction determination were grown
from slow evaporation of CH
2 2 3
Cl /CH OH solution of the
5
216. (g) Kang, S.-O.; Powell, D.; Day, V. W.; Bowman-James, K. Angew.
compound at low temperature; see below.
Chem., Int. Ed. 2006, 45, 1921–1925. (h) Chmielewski, M. J.; Jurczak, J.
Chem.sEur. J. 2005, 11, 6080–6094.
1
13
H and C NMR spectra of the macrobicycle are consistent
(7) (a) Ravikumar, I.; Lakshminarayanan, P. S.; Suresh, E.; Ghosh, P. Inorg.
with a symmetric species, and cross-peak correlations of COSY,
Chem. 2008, 47, 7992–7999. (b) Esteban-G o´ mez, D.; Platas-Iglesias, C.; Avecilla,
F.; de Blas, A.; Rodr ´ı guez-Blas, T. Eur. J. Inorg. Chem. 2007, 1635–1643. (c)
Chae, M. K.; Lee, J.-I.; Kim, N.-K.; Jeong, K.-S. Tetrahedron Lett. 2007, 48,
HMQC and HMBC spectra provided the complete assignment
1
of all magnetically different nuclei. The H spectrum, in CDCl
3
6
2
1
624–6627. (d) Hisaki, I.; Sasaki, S.-I.; Hirose, K.; Tobe, Y. Eur. J. Org. Chem.
007, 607–615. (e) Das, M. C.; Bharadwaj, P. K. Eur. J. Inorg. Chem. 2007,
229–1232. (f) Ambrosi, G.; Dapporto, P.; Formica, M.; Fusi, V.; Giorgi, C.;
solution, shows the H
.66/3.37 ppm (Jii′ ) 12.2 Hz), and the two triplet resonances
of H and H protons as two AA′BB′ systems; see Chart 1 for
labeling. One of these systems involves the H /H at 2.13/2.98
ppm (J ) 12.0 Hz) and the other H /H at 2.83/3.27 ppm (J )
2.5 Hz). The H , H , and H protons are thus diastereotopic in
pairs, attesting the rigidity of the molecule around the tertiary
i
proton resonances as an AB system at
4
Guerri, A.; Micheloni, M.; Paoli, P.; Pontellini, R.; Rossi, P. Inorg. Chem. 2006,
5, 304–314. (g) Mahoney, J. M.; Nawaratna, G. U.; Beatty, A. M.; Duggan,
e
j
4
k
e
P. J.; Smith, B. D. Inorg. Chem. 2004, 43, 5902–5907. (h) Bonizzoni, M.;
Fabbrizzi, L.; Piovani, G.; Taglietti, A. Tetrahedron 2004, 60, 11159–11162.
j
d
(
i) Mahoney, J. M.; Shukla, R.; Marshall, R. A.; Beatty, A. M.; Zajicek, J.;
Smith, B. D. J. Org. Chem. 2002, 67, 1436–1440.
8) Esteban-G o´ mez, D.; Platas-Iglesias, C.; de Blas, A.; Fabbrizzi, L.;
Rodriguez-Blas, T. Chem.sEur. J. 2008, 14, 5829–5838.
9) (a) Mahoney, J. M.; Beatty, A. M.; Smith, B. D. J. Am. Chem. Soc. 2001,
23, 5847–5848. (b) Mahoney, J. M.; Davis, J. P.; Beatty, A. M.; Smith, B. D.
1
i
e
j
(
amines. In contrast, the DBF protons (H
as those of the isophthalamide group (H
f
, H
, H
g
, and H ) as well
c
, and H ) and the
h
(
a
b
1
J. Org. Chem. 2003, 68, 9819–9820. (c) Mahoney, J. M.; Beatty, A. M.; Smith,
B. D. Inorg. Chem. 2004, 43, 7617–7621. (d) Mahoney, J. M.; Stucker, K. A.;
Jiang, H.; Carmichael, I.; Brinkmann, N. R.; Beatty, A. M.; Noll, B. C.; Smith,
B. D. J. Am. Chem. Soc. 2005, 127, 2922–2928.
(10) (a) Li, F.; Delgado, R.; Drew, M. G. B.; F e´ lix, V. Tetrahedron 2006,
62, 8550–8558. (b) Li, F.; Li, L.; Delgado, R.; Drew, M. G. B.; F e´ lix, V. Dalton
Trans. 2007, 1316–1324.
4
820 J. Org. Chem. Vol. 74, No. 13, 2009