Inclusion and gelation properties of novel tetra- and hexasalicylide derivatives

Article abstract of DOI:10.1021/ol8004485

(Chemical Equation Presented) Some novel tetra- and hexasalicylide derivatives were synthesized. The tetrasalicylides having a 5-substituted halogen atom on the aromatic ring form organogels with several kinds of organic solvents, whereas the parent compound does not. In contrast, hexasalicylides form stable inclusion crystals with several organic guest molecules.

Full text of DOI:10.1021/ol8004485

ORGANIC
LETTERS
2008
Vol. 10, No. 11
2119-2122
Inclusion and Gelation Properties of
Novel Tetra- and Hexasalicylide
Derivatives
Koichi Tanaka,*,† Satoshi Hayashi,† and Mino R. Caira*,‡
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials
and Bioengineering & High Technology Research Center, Kansai UniVersity, Suita,
Osaka 564-8680, Japan, Department of Chemistry, UniVersity of Cape Town,
Rondebosch 7701, South Africa
ktanaka@ipcku.kansai-u.ac.jp
Received February 28, 2008
ABSTRACT
Some novel tetra- and hexasalicylide derivatives were synthesized. The tetrasalicylides having a 5-substituted halogen atom on the aromatic
ring form organogels with several kinds of organic solvents, whereas the parent compound does not. In contrast, hexasalicylides form stable
inclusion crystals with several organic guest molecules.
There has been increasing interest in host-guest inclusion
compounds because of their potential applications such as
separation of isomeric compounds, optical resolution of
enantiomers, reaction medium of included molecules, and
sensor materials.1 Tri-o-thymotide 1 is one of the well-studied
clathrate host compounds that form inclusion crystals with
a wide variety of guest molecules.1 The propeller-shaped tri-
o-thymotide molecule 1 has the specific property of undergo-
ing spontaneous resolution on crystallization, and many
applications such as optical resolution of guest molecules,
asymmetric reactions of included guests, separation of
specific molecules from complex mixtures, determination of
guest configuration, matrix isolation of labile molecules, and
nonlinear optical properties have been studied.2 However,
inclusion properties of higher homologues of 1 have not been
investigated so far. Herein, we report the synthesis, crystal
structure, and inclusion properties of some novel tetra- and
hexasalicylide derivatives (2, 3). Upon exploring the inclu-
(2) (a) Facey, G.; Ripmeester, J. A. Chem. Commun. 1990, 1585, 1587.
(b) Bonner, W. A. Origins Life EVol. Biosphere 1990, 29, 317–328. (c)
Xu, L.; Keehn, P. M.; Gnaim, J. M.; Green, B. S. J. Org. Chem. 1992, 57,
3208–3213. (d) Facey, G. A.; Ratcliffe, C. I.; Hynes, R.; Ripmeester, J. A.
J. Phys. Org. Chem. 1992, 5, 670–682. (e) Aliev, A. E.; Harris, K. D. M.;
Mahdyarfar, A. J. Chem. Soc., Faraday Trans. 1995, 91, 2017–2026. (f)
Gnaim, J. M.; Schurig, V.; Grosenick, H.; Green, B. S. Tetrahedron:
Asymmetry 1995, 6, 1499–1502. (g) Pang, L.; Brisse, F. J. Chem. Cryst.
1996, 26, 461–465. (h) S.-Gonzalez, H.; Harris, K. D. M. J. Solid State
Chem. 1999, 148, 63–74. (i) Gerdil, R.; Liu, H.; Bernardinelli, G. HelV.
Chem. Acta 1999, 82, 418–434. (j) S.-Gonzalez, H.; Harris, K. M; D, J.
Mol. Struct. 2000, 519, 41–54. (k) Gerdil, R.; Barchietto, G. HelV. Chim.
Acta 2004, 77, 691–708. (l) Gupta, V. K.; Jain, A. K.; Kumar, P.; Agawal,
S.; Maheshwari, G. Sensors Actuators, B 2006, 113, 182–186.
† Kansai University.
‡ University of Cape Town.
(1) (a) ComprehensiVe Supramolecular Chemistry; Atwood, J. L.,
Davies, J. E. D., MacNicol, D. D., Eds.; Pergamon: Oxford, 1996; Vols.
1-11. (b) Encyclopedia of Supramolecular Chemistry; Atwood, J. L., Steed,
J. W., Eds.; Marcel Dekker: New York, 2004; Vols. 1 and 2. (c) Crystalline
Molecular Complexes and Compounds; Herbstein, F. H., Ed.; Oxford
Science Publications: Oxford, 2005; Vols. 1 and 2.
10.1021/ol8004485 CCC: $40.75
Published on Web 04/25/2008
2008 American Chemical Society

sion properties of these compounds, we found unexpected
organogelation abilities of tetrasalicylides (2b-e) with a wide
variety of organic solvents. In contrast, hexasalicylides (3a,
3b) were found to form stable inclusion crystals with several
organic solvents. The crystal structures of some tetra- and
hexasalicylides were also studied.
Table 1. Gelation Properties of Tetrasalicylide Derivatives 2a-f
solvent
2a
2b
2c
2d
2e
CHCl3
THF
dioxane
cyclopentanone
cyclohexanone
DMSO
Ca
PG (5)c
G (10)
G (5)
G (5)
G (5)
G (5)b
G (10)
G (10)
G (10)
G (10)
G (5)
C
DMF
benzene
toluene
chlorobenzene
aniline
G (10)
G (5)
G (2)
G (2)
G (10)
G (5)
G (5)
G (5)
G (2)
G (5)
G (10)
PG (5)
PG (5)
G (10)
G (5)
G (5)
G (5)
pyridine
a C: 1:2 inclusion complex. b G: gel; values in parentheses refer to
minimum concentration necessary for gelation (mg/mL). c PG: partial gel.
A mixture of 2-hydroxybenzoic acid and POCl3 was heated
in toluene solution under reflux for 6 h. After the reaction
mixture was cooled, the crystals deposited were separated
by filtration and washed with toluene and MeOH. The
crystalline solid was collected and extracted with hot
chloroform using Soxhlet apparatus, and the extract was
concentrated to give the tetrasalicylide. In the case of the
reactions of 5-fluoro- and 5-iodosalicylic acids, a mixture
of tetrasalicylide (2) and hexasalicylide (3) was formed, and
the components were separated by recycling HPLC to give
pure tetrasalicylide (2) and hexasalicylide (3), respectively
(Scheme 1).
To obtain visual insight into the molecular aggregate, we
prepared dry gels for scanning electron microscopy (SEM).
Figure 1 (right) shows a typical result obtained from dried
gels. The SEM photograph shows the three-dimensional
network formed by entanglement of self-assembled nanofi-
bers. It has been well recognized that anisotropic interactions
through hydrogen bonding, CH/π, and π/π stacking are
responsible for the linear aggregation of low molecular
weight organic gelators, allowing the gel formation.3
Scheme 1. Synthesis of Tetra- and Hexasalicylides
Figure 1. Photographs of typical toluene gels (left) and SEM image
of dried gels (right).
Hexasalicylide derivatives (3a and 3b) incorporate several
kinds of organic guest molecules into stable inclusion
complexes in the ratios indicated in Table 2. The host/guest
stoichiometric ratios of 1:3 and 1:5 are exceptionally large,
which indicates the high efficiency of guest accommodation
(3) (a) Terech, P.; Weiss, R. G. Chem. ReV. 1997, 97, 3133. (b) Van
Esch, J; De Feyter, S.; Kellog, R. M.; De Schryver, F.; Feringa, B. L. Chem.
Eur. J. 1997, 3, 1238. (c) Van Esch, J; Schoonbeek, F.; De Loos, M.;
Kooijman, H.; Spek, A. L.; Kellog, R. M.; Feringa, B. L. Chem. Eur. J.
1999, 5, 937. (d) Gronwald, O.; Shinkai, S. Chem. Eur. J. 2001, 7, 4328.
(e) George, M.; Tan, G.; Jhon, V. T.; Weiss, R. G. Chem. Eur. J. 2005, 11,
3243. (f) Hoeben, F.J. M.; Jonkheijim, P.; Meijer, E. W.; Schenning,
A. P. H. J. Chem. ReV. 2005, 105, 1491. (g) George, M.; Weiss, R. G. Acc.
Chem. Res. 2006, 39, 489–497. (h) Ghosh, R.; Chakraborty, A.; Maiti, D. K.;
Puranik, V. G. Org. Lett. 2006, 8, 1061–1064. (i) Langford, S. J.; Latter,
M. J.; Lau, V. L.; Martin, L. L.; Mechler, A. Org. Lett. 2006, 8, 1371–
1373. (j) Adarsh, N. N.; Kumar, D. K.; Dastidar, P. Tetrahedron 2007, 63,
7386–7396. (k) Baddeley, C.; Yan, Z.; King, G.; Woodward, P. M.; Badjic,
J. D. J. Org. Chem. 2007, 72, 7270–7278.
Upon crystallization from the solvents listed in Table 1,
2a formed inclusion crystals with CHCl3 and DMSO in 1:2
ratios. In contrast, tetrasalicylides (2b-e) having halogen
atoms on the aromatic ring formed organogels (Figure 1,
left). Among 2b-e, 2c showed excellent organogelation
abilities for several organic solvents listed in Table 1.
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Org. Lett., Vol. 10, No. 11, 2008

Table 2. Inclusion Properties of Hexasalicylide Derivatives
3a,ba
guest
3a
3b
CHCl3
cyclohexanone
DMSO
DMF
pyridine
1:1 (147)
1:3 (171)
1:3 (115)
1:5 (142)
1:5 (101)
1:3 (159)
1:2 (125)
a Host-guest ratios were determined by TG and 1H NMR; values in
parentheses refer to guest release temperature (°C).
of these host compounds (Figure 2). It is also remarkable
that these hosts form stable inclusion crystals and the guest
molecules are liberated at much higher temperatures than
their guest boiling points. For example, the 1:1 inclusion
crystal of 3b with chloroform decomposed when the inclu-
sion crystal was heated above 147 °C, although the boiling
point of chloroform is only 61 °C.
Figure 3. ORTEP diagram of the molecule of 2c with thermal
ellipsoids drawn at the 50% probability level.
C4-O8-C9-C5i ) 180° (i ) y, 3/2-x, 1/2-z)). Evi-
dence of internal steric strain is the short intramolecular
j
distance between a central oxygen atom (O8) and its 4-
related neighbor, where O· · ·O is 2.663(2) Å. These central
oxygen atoms are more evident in Figure 4, the crystal
Figure 2. TG trace of 1:3 inclusion crystals of 3b and cyclohex-
anone.
The observation that host 2c displayed exceptional organ-
ogelation ability when interacting with solvents, whereas the
parent host 2a was found to form only inclusion compounds,
prompted a comparative study of their crystal structures. The
X-ray structure of the new host 2c was therefore determined in
this study4 and compared with the published structure of 2a.5
Figure 3 shows the structure of 2c.
j
The molecule is located on a special site of 4 symmetry
with the orientations of the four arylcarboxylate units
alternating up and down. These four units are held together
by trans ester linkages (representative dihedral angle
Figure 4. [001] projection of the crystal structure of 2c.
(4) Crystal data for 2c: C28H12Cl4O8, M ) 618.18, tetragonal, space
group P42/n (No. 86), a ) b ) 13.2927(3) Å, c ) 7.3547(2) Å, V )
1299.55(5) Å3, Z ) 2, Dc ) 1.580 g/cm3, F000 ) 624, Mo KR radiation, λ
) 0.71073 Å, T ) 113(2) K, 2θmax ) 50.6°, 17580 reflections collected,
1184 unique (Rint ) 0.0646). Final GooF ) 1.098, R1 ) 0.0332, wR2 )
0.0831, R indices based on 943 reflections with I >2σ(I) (refinement on
F2), 92 parameters, 0 restraints. Lp and absorption corrections applied, µ
) 0.508 mm-1.
packing diagram. The projected square arrays of Cl atoms
(arranged around a 42-axis) are also a notable feature.
Close contacts of 3.520(2) Å occur between the diagonally
related Cl atoms, linking molecules in chains along the
crystallographic a- and b-directions. There are two unique
intermolecular hydrogen bonds of type C-H· · ·O:
(5) Du, D.-M.; Chen, X.; Hua, W.-T.; Jin, X.-L. Jiegou Huaxue. 2003,
22, 512–516.
Org. Lett., Vol. 10, No. 11, 2008
2121

C2-H2· · ·O10ii (ii ) 1-x, 1-y, 1-z) and C6-H6· · ·O10iii
(iii ) 1/2+y, 1-x, 1/2+z), with C· · ·O 3.372(2) and
3.398(2) Å, respectively. When the full symmetry of
molecule 2c is applied, a complex network involving a
total of 16 C-H· · ·O hydrogen bonds per molecule arises.
It is noteworthy that these H-bonds involve the two H
atoms ortho to the Cl atom and the carbonyl oxygen atom
O10 as acceptor exclusively. Close stacking of molecules in
the z-direction is achieved by interlocking of the V-shaped
grooves formed by diad-related arylcarboxylate planes.
Figure 6 illustrates the inclusion of two DMF molecules
within a cavity created by two host molecules in the
compound 3a·(DMF)2. Each DMF molecule inserts into the
The parent compound 2a (monoclinic, P21/n) crystallizes
with two independent molecules in the asymmetric unit.5
j
These have pseudo-4 symmetries and conformations very
Figure 6. Inclusion of DMF molecules by host 3a.
similar to one another and to that of the chlorinated analogue
2c. However, in its own crystal, 2a displays minimal
C-H· · ·O hydrogen bonding,5 and the enhanced ability of
host 2c to form hydrogen bonds may be related to its
tendency to form gels. The crystal packing of 2a also differs
from that of 2c. In 2a, close packing is achieved by insertion
of a phenyl ring of one molecule within the V-groove of a
neighboring molecule. The result is extensive molecular
overlap when the crystal structure is viewed down the
bowl-like cavity generated by three alternate arylcarboxylate
units, the whole assembly shown having a center of inversion.
Inspection of the crystal packing shows that guest molecules
are fully surrounded by host molecules. Only one weak
host-guest hydrogen bond was detected: C13-H13· · ·O31ii
with C· · ·O 3.353(2) Å (ii ) 2-x, 1-y, 1-z, atom O31 being
that of the DMF molecule).
H-bonding between host molecules is minimal; only one
bond with C· · ·O < 3.4 Å was found, namely C4-H4· · ·O19ii
(ii ) x, 1+y, z) with C· · ·O ) 3.143(2) Å. In contrast to 2c,
where Cl-induced acidity in flanking C-H groups appears
to promote C-H· · ·O hydrogen bonding, the F atoms
surprisingly do not appear to manifest analogous effects in
the crystal of inclusion compound 3a·(DMF)2.
j
common direction of the host pseudo-4 axes (Figure 5).
While the factors favoring organogelation are not fully
understood, self-assembly via noncovalent interactions,
including H-bonding, have been indicated as playing a role.7
For the novel host compounds reported here, the small
sample of crystal structures gives some indications of
H-bonding potential in the solid state. Possible structural
differences in crystals of the gelator 2c and the nongelator
2a that may account for their different behaviors include the
presence of numerous intermolecular C-H· · ·O hydrogen
bonds and close Cl· · ·Cl contacts for the former compound
versus only relatively few C-H· · ·O hydrogen bonds for the
latter. Further X-ray studies and investigation of the nature
of molecular association in the gels are necessary to develop
a possible mechanism for organogelation and to understand
the different behaviors of the two series of host compounds.
Figure 5. Crystal packing in 2a viewed approximately parallel to
the [101] direction.
The novel hexasalicylide host 3a is located on a center of
inversion.6 Aryl carboxylate units are linked by trans ester
linkages (C-C-O-C range -176.1(2) to +176.7(2)°) and
alternate in orientation. Space-filling models show that in
this conformation the central region of the host is blocked
by oxygen atoms of the ester groups with O· · ·O distances
of 2.806(2) and 3.157(2) Å. The molecule therefore presents
two bowl-shaped cavities to potential guest molecules, above
and below the belt of constricting oxygen atoms.
Acknowledgment. This work was supported by the “High-
Tech Research Center” Project for Private Universities:
mating fund subsidy from MEXT (Ministry of Education,
Culture, Sports, Science and Technology), 2005-2009.
M.R.C. acknowledges research support from the University
of Cape Town and the NRF (Pretoria).
Supporting Information Available: Synthetic procedure,
spectroscopic characterization, and CIF files for compounds
2c and 3a·(DMF)2. This material is available free of charge
via the Internet at http://pubs.acs.org.
(6) Crystal data for 3a·(DMF)2: empirical formula C24H16F3NO7, M )
487.38, triclinic, space group P-1 (No. 2), a ) 9.5721(7) Å, b ) 10.0848(7)
Å, c ) 12.5819(6) Å, R ) 69.849(4)°, ꢀ ) 73.108(4)°, γ ) 75.513(4)°, V
) 1075.7(1) Å3, Z ) 2, Dc ) 1.505 g/cm3, F000 ) 500, Mo KR radiation,
λ ) 0.71073 Å, T ) 213(2)K, 2θmax ) 52.8°, 7836 reflections collected,
4386 unique (Rint ) 0.0490). Final GooF ) 1.031, R1 ) 0.0371, wR2 )
0.0885, R indices based on 3333 reflections with I >2σ(I) (refinement on
F2), 319 parameters, 0 restraints. Lp corrections applied, µ ) 0.128 mm-1.
OL8004485
(7) Pal, A.; Ghosh, Y. K.; Bhattacharya, S. Tetrahedron 2007, 63, 7334–
7348.
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Org. Lett., Vol. 10, No. 11, 2008