Three-dimensional four-connecting organic scaffolds with a twist: Synthesis and self-assembly

Article abstract of DOI:10.1021/jo051205z

We have synthesized a novel class of four-connecting three-dimensional molecular scaffolds 2-5 based on biaryls for supramolecular self-assembly. The X-ray crystal structure analysis of 2 with ethanol reveals a novel O-H...O hydrogen-bonded helical self-a

Full text of DOI:10.1021/jo051205z

the fact that the chirality can be readily introduced at a
molecular level, there is a growing interest in developing
molecular networks that functionally mimic the proper-
ties of inorganic zeolites.7 A prudent approach to the
development of porous organic materials constitutes
molecular tectonics,6e an art of building solids based on
molecules with predesigned topologies and properties,
which hinges on two key aspects, viz., the geometrical
features of the building block and location as well as
choice of functional groups that lend themselves to
reliable, repetitive, and robust association motifs/syn-
thons. We have recently conceived of a unique four-
connecting three-dimensional module (1, Scheme 1) based
on bimesityl core for supramolecular self-assembly, and
demonstrated its utility in the self-assembly of three-
dimensional discrete8a as well as polymeric coordination
architectures.8b We reasoned that installation of func-
tional groups such as hydroxyl and carboxyl at the para
positions of 3,3′,5,5′-tetraphenylbimesityl (2 and 3, Scheme
1) could yield hydrogen-bonded networks with voids for
guest inclusion.9 Indeed, it was readily surmised that
linear linkage, for example, of the tetraacid 3 via the
dimeric motif of the carboxyl group, should afford the
polymeric (10,3)-b net10 as shown in Figure 1, in which
the channels run in a perpendicular direction. We have
thus synthesized the unique three-dimensional modules
2-5 based on bimesityl core and explored their self-
assembly based on O-H‚‚‚O hydrogen bonding. A further
advantage with bimesityl core unit could be gauged from
the feasibility for facile structural expansion as can be
seen, for example, with the expanded derivatives 4 and
5 (Scheme 1). Herein, we report the facile synthesis of
structurally novel tetrarylbimesityls 2-5 based on a
4-fold Suzuki coupling protocol and novel self-assembly
Three-Dimensional Four-Connecting
Organic Scaffolds with a Twist: Synthesis
and Self-Assembly
Jarugu Narasimha Moorthy,*,†
Ramalingam Natarajan,† and Paloth Venugopalan‡
Department of Chemistry, Indian Institute of Technology,
Kanpur - 208 016, India, and Department of Chemistry,
Panjab University, Chandigarh - 160 014, India
moorthy@iitk.ac.in
Received June 14, 2005
We have synthesized a novel class of four-connecting three-
dimensional molecular scaffolds 2-5 based on biaryls for
supramolecular self-assembly. The X-ray crystal structure
analysis of 2 with ethanol reveals a novel O-H‚‚‚O hydrogen-
bonded helical self-assembly in three dimensions leading to
the generation of channels in the crystal lattice. The tet-
raacid 3 also forms analogous channels in which the solvent
molecules, viz., DMSO and H2O, reside. The structures of 2
and 3 amply illustrate the potential of three-dimensional
four-connecting biaryls in developing functional mimics of
inorganic zeolites.
(6) Our thorough literature search has revealed only a limited
number of three-dimensional molecular systems, which have been
exploited for crystal packing in three dimensions; see: (a) Ermer, O.
J. Am. Chem. Soc. 1988, 110, 3747. (b) Boldog, I.; Rusanov, E. B.; Sieler,
J.; Blaurock, S.; Domasevitch, K. V. Chem. Commun. 2003, 740. (c)
Holy, P.; Zavada, J.; Cisarova, I.; Podlaha, J. Angew. Chem., Int. Ed.
1999, 38, 381. (d) Holy, P.; Zavada, J.; Cisarova, I.; Podlaha, J.
Tetrahedron Asymmetry 2001, 12, 3035. (e) Wang, X.; Simard, M.;
Wuest, J. D. J. Am. Chem. Soc. 1994, 116, 12119. (f) Reddy, D. S.;
Craig, D. C.; Desiraju, G. R. J. Am. Chem. Soc. 1996, 118, 4090. (g)
Brunet, P.; Simard, M.; Wuest, J. D. J. Am. Chem. Soc. 1997, 119,
2737. (h) Reddy, D. S.; Dewa, T.; Endo, K.; Aoyama, Y. Angew. Chem.,
Int. Ed. 2000, 39, 4266. (i) Thaimattam, R.; Sharma, C. V. K.;
Clearfield, A.; Desiraju, G. R. Cryst. Growth Des. 2001, 1, 103. (j)
Fournier, J.-H.; Maris, T.; Wuest, J. D.; Guo, W.; Galoppini, E. J. Am.
Chem. Soc. 2003, 125, 1002. (k) Fournier, J.-H.; Maris, T.; Simard,
M.; Wuest, J. D. Cryst. Growth Des. 2003, 3, 535. (l) Boldog, I.;
Rusanov, E. B.; Chernega, A. N.; Sieler, J.; Domasevitch, K. V. Angew.
Chem., Int. Ed. 2001, 40, 3435. (m) Sauriat-Dorizon, H.; Maris, T.;
Wuest, J. D. J. Org. Chem. 2003, 68, 240. (n) Laliberte, D.; Maris, T.;
Wuest, J. D. J. Org. Chem. 2004, 69, 1776.
(7) (a) Janiak, C. Angew. Chem., Int. Ed. Engl. 1997, 36, 1431. (b)
Seo, J. S.; Whang, D.; Lee, H.; Jun, S. I.; Oh, J.; Jeon, Y. J.; Kim, K.
Nature 2000, 404, 982. (c) Wu, C.-D.; Hu, A.; Zhang, L.; Lin, W. J.
Am. Chem. Soc. 2005, 127, 8940. (d) Fang, Q.; Zhu, G.; Xue, M.; Sun,
J.; Wei, Y.; Qiu, S.; Xu, R. Angew. Chem., Int. Ed. 2005, 44, 3845.
(8) (a) Natarajan, R.; Savitha, G.; Moorthy, J. N. Cryst. Growth Des.
2005, 5, 69. (b) Natarajan, R.; Savitha, G.; Dominiak, P.; Wozniak,
K.; Moorthy, J. N. Angew. Chem., Int. Ed. 2005, 44, 2115.
(9) For remarkably porous networks based on anthracene-bisresor-
cinol by Aoyama and co-workers, see: (a) Endo, K.; Ezuhara, T.;
Koyanagi, M.; Masuda, H.; Aoyama, Y. J. Am. Chem. Soc. 1997, 119,
499. (b) Dewa, K.; Endo, K.; Aoyama, Y. J. Am. Chem. Soc. 1998, 120,
8933.
(10) Wells, A. F. Three-Dimensionanl Nets and Polyhedra; Wiley-
Interscience: New York, 1977.
Control of molecular organization is pivotal for the
development of organic solids with predefined functional
properties.1 Whereas the recent literature in supramo-
lecular chemistry is replete with examples of control of
molecular organization in one and two dimensions,2,3 that
in the third dimension continues to be a challenging
proposition;4 one of the reasons for this may be traced to
a limited number of three-dimensional molecular scaf-
folds that could be exploited for self-assembly in three
dimensions by installing functional groups responsible
for reliable synthons5 at strategic locations.6 Control of
molecular ordering in three dimensions is particularly
relevant to developing porous organic solids. In view of
† Indian Institute of Technology.
‡ Panjab University.
(1) (a) Desiraju, G. R. Crystal Engineering. The Design of Organic
Solids; Elsevier: Amsterdam, The Netherlands, 1989. (b) Langley, P.
J.; Hulliger, J. Chem. Soc. Rev. 1999, 28, 279. (b) Hollingsworth, M.
D. Science 2002, 295, 2410.
(2) (a) MacDonald, J. C.; Whitesides, G. M. Chem. Rev. 1994, 94,
2383. (b) Lawrence, D. S.; Jiang, T.; Levett, M. Chem. Rev. 1995, 95,
2229.
(3) (a) Melendez, R. E.; Hamilton, A. D. Top. Curr. Chem. 1998, 198,
97. (b) Tanaka, T.; Tasaki, T.; Aoyama, Y. J. Am. Chem. Soc. 2002,
124, 12453.
(4) (a) Gong, B.; Zheng, C.; Skrzypczak-Jankun, E.; Yan, Y.; Zhang,
J. J. Am. Chem. Soc. 1998, 120, 11194. (b) Sharma, C. V. K.; Clearfield,
A. J. Am. Chem. Soc. 2000, 122, 4394. (c) Malek, N.; Maris, T.; Perron,
M.-E.; Wuest, J. D. Angew. Chem., Int. Ed. 2005, 44, 4021.
(5) Desiraju, G. R. Angew. Chem., Int. Ed. Engl. 1995, 34, 2311.
10.1021/jo051205z CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/21/2005
8568
J. Org. Chem. 2005, 70, 8568-8571

SCHEME 1. Synthesis of Bimesityls 1-5
of tetraphenol 2 and tetraacid 3 into channel-type inclu-
dimeric motif of the carboxyl groups located at para
positions of the phenyl rings as in 2 and 3 was, in
principle, expected to yield a porous (10,3)-b net as shown
in Figure 1. Expectedly, the tetraphenols 2 and 4 were
found to exhibit ready guest inclusion as revealed by the
1H NMR analyses of the crystals grown from different
solvents. Whereas 2 was found to incorporate in its lattice
the guest molecules such as ethanol, ethyl formate, and
ethyl acetate, the expanded analogue 4 was found to
include larger molecules such as p-xylene (1H:3G), mesi-
tylene (1:1G), and anisole (1H:2G); see the Supporting
Information. While good single crystals suitable for X-ray
analysis could be grown readily for 2 from ethanol with
the stoichiometry 2•2 EtOH (vide infra), our attempts to
obtain the inclusion compounds of 2 with other guest
molecules were in vain. Figure 2 shows the crystal-
packing diagram of the tetraphenol 2. The core mesityl-
ene rings are almost orthogonal with the molecule sitting
on the 2-fold c-axis (orthorhombic, P21212). The p-
hydroxyphenyl rings are also almost orthogonal (83.3 and
94.3°) to each of the mesitylene rings of the bimesityl
skeleton. The remarkable crystal packing, which results
in the formation of voids for guest incorporation, may be
described as follows. Each of the hydroxyl groups is a
sion host compounds.11
The synthesis of tetraaryl derivatives of bimesityl was
accomplished by Suzuki coupling12 between arylboronic
acids and 3,3′,5,5′-tetraiodobimesityl; the latter was
synthesized by subjecting the readily prepared bimesityl13
to tetraiodination with I2 in acetic acid containing a mix-
ture of Conc H2SO4-HNO3. Thus, the coupling of tetra-
iodobimesityl with p-methoxyphenylboronic acid and 4′-
methoxybiphenyl-4-boronic acid14 followed by demethyl-
ation with BBr3 yielded tetrakis(4-hydroxyphenyl)bimesi-
tyl 2 and tetrakis(4-hydroxybiphenyl)bimesityl 4, respec-
tively (Scheme 1). The coupling of tetraiodobimesityl with
formyl-substituted boronic acids in a similar way led to
the isolation of formyl derivatives, which were oxidized
with oxone (KHSO5) to the corresponding acids 3 and 5.15
The phenolic OH groups exhibit a varied array of
packing motifs of which the helical motif is the most
frequently observed one, while the dimeric one is the least
encountered.16 In contrast, the carboxyl groups predomi-
nantly adopt the dimeric/catemeric motif,17 although
other modes of association are known with a low statisti-
cal probability.18 Given that the tetrarylbimesityls are
rigid architectures, the least encountered linear self-
assembly of the hydroxyl and most frequently observed
(11) Bishop, R. Chem. Soc. Rev. 1996, 25, 311.
(12) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M.
Chem. Rev. 2002, 102, 1359.
(13) Cahiez, G.; Chaboche, C.; Mahuteau-Betzer, F.; Ahr, M. Org.
Lett. 2005, 7, 1943.
(14) Virgil, P.; Peihwei, C.; Masaya, K. Macromolecules 1994, 27,
4441.
(15) Travis, B. R.; Sivakumar, M.; Hollist, G. O.; Borhan, B. Org.
Lett. 2003, 5, 1031.
(16) (a) Brock, C. P.; Duncan, L. L.; Chem. Mater. 1994, 6, 1307. (b)
Thallapally, P. K.; Katz, A. K.; Carrel, H. L.; Desiraju, G. R. Chem.
Commun. 2002, 344.
(17) (a) Kolotuchin, S. V.; Fenlon, E. E.; Wilson, S. R.; Loweth, C.
J.; Zimmerman, S. C. Angew. Chem., Int. Ed. 1995, 34, 2654. (b)
Almarsson, O¨ .; Zaworotko, M. J. Chem. Commun. 2004, 1889.
(18) For example, for unique helical self-assembly of aromatic
carboxylic acids, see: Moorthy, J. N.; Natarajan, R.; Mal, P.; Venugo-
palan, P. J. Am. Chem. Soc. 2002, 124, 6530.
FIGURE 1. Packing type anticipated for three-dimensional
modules 2-5.
J. Org. Chem, Vol. 70, No. 21, 2005 8569

FIGURE 4. Formation of a porous channel from two parallel
helices generated each by the self-assembly of 2 via O-H‚‚‚O
hydrogen bonds. Note that only two p-hydroxyphenyl groups
are involved in the assembly.
tion results in the generation of parallel channels down
b-axis in which the guest molecules reside.19 Indeed, each
channel may be described as arising from two parallel
helices constructed via hydrogen bonding between the
tetraphenols 2 by utilizing only two of the four p-
hydroxyphenyl rings (pattern II) as shown in Figures 2
and 4. Thus, the crystal packing of 2 is mediated entirely
by O-H‚‚‚O hydrogen bonded helices in all three dimen-
sions.20
As mentioned earlier, the expanded analogue 4 yielded
only needles with various aromatic guest molecules,
which were unsuitable for X-ray work. We believe that
hydrogen bonding between the phenolic OH groups, as
observed in the case of 2, control the crystal packing in
the complexes of 4 as well. The crystallization of tetraacid
3 from solvents such as methanol, ethanol, ethyl acetate,
acetone, etc. was unsuccessful despite innumerable crys-
tallization experiments. However, crystallization in DMSO/
toluene yielded seemingly excellent crystals, which dif-
fracted only poorly. The reason for the latter was traced
subsequently to the severely disordered solvent mol-
ecules, vide infra. The crystals were found to lose crys-
tallinity once they were removed from the mother liquor.
The crystal structure analysis shows that the tetraacid
3 crystallizes in the space group Pbca with each of the
carboxyl hydrogens bonded to DMSO/H2O via a hydrogen
bond (Figure 5). From the difference Fourier analysis,
we succeeded in locating five DMSO and two H2O
molecules. The overall crystal packing of 3 is as follows.
The glide-related acid molecules 3 along the a-axis
associate via aryl-aryl edge-to-face21 (C-H‚‚‚π) stacking
interactions, cf. Supporting Information; it should be
noted that one of the hydrogens of the p-carboxyphenyl
rings points toward the e-rich mesitylene core. This mode
of association leads to the formation of strands running
along a-axis, within which occur the channels in which
the solvent molecules reside, cf. the Supporting Informa-
FIGURE 2. Crystal packing of tetraphenol 2. The bottom
space-filling diagram reveals the voids (guest EtOH molecules
are shown with a ball-and-stick model) resulting from the self-
assembly of 2 via O-H‚‚‚O hydrogen bonds.
FIGURE 3. Helical self-assembly of the hydroxy groups of
four symmetry-related molecules (I). Also shown is how the
helical propagation of 2 occurs along the Z-axis via O-H‚‚‚O
hydrogen bonds between two of the hydroxyphenyl rings of
the tetraphenol 2.
donor as well as an acceptor. The hydroxyl groups of four
distinct translation- and 21-screw-related molecules self-
assemble to produce a hydrogen-bonded “psuedo helical
spine” along the b-axis as shown by the pattern I in
Figures 2 and 3; the geometrical parameters for the two
O-H‚‚‚O hydrogen bonds are as follows: dO-H‚‚‚O ) 1.863-
(4) Å, DO‚‚‚O ) 2.663(5) Å, and θO-H‚‚‚O ) 164.8°; dO-H‚‚‚O
) 1.993(4) Å, DO‚‚‚O ) 2.788(6) Å, and θO-H‚‚‚O ) 163.3°.
The unique hydrogen-bonding ensures helical self-as-
sembly along both a- and c-axes as well (see patterns II
and III); the propagation along the latter is typically
shown in Figure 3. Remarkably, the helical spine forma-
(19) For hydrogen-bonded helical (31-screw) assembly of aliphatic
cyclic diols into inclusion host systems, see: Kim, S.; Bishop, R.; Craig,
D. C.; Dance, I. G.; Scudder, M. L. J. Org. Chem. 2002, 67, 3221 and
references therein.
(20) An altogether different mode of packing has been reported for
the analogous tetraphenols based on spirobifluorene and tetraphenyl-
methanes, which presumably is due to various ways in which the
phenolic hydroxyl groups self-assemble, see: (a) Fournier, J.-H.; Maris,
T.; Wuest, J. D. J. Org. Chem. 2004, 69, 1762. (b) Fournier, J.-H.;
Maris, T.; Simard, M.; Wuest, J. D. Cryst. Growth Des. 2003, 3, 535.
(21) (a) Jennings, W. B.; Farrell, B. M.; Malone, J. F.; Acc. Chem.
Res. 2001, 34, 885. (b) Meyer, E. A.; Castellano, R. K.; Diedrich, F.
Angew. Chem., Int. Ed. 2003, 42, 1210. (c) Aravinda, S.; Shamala, N.;
Das, C.; Sriranjini, A.; Karle, I. L.; Balaram. P. J. Am. Chem. Soc.
2003, 125, 5308.
8570 J. Org. Chem., Vol. 70, No. 21, 2005

In summary, we have accomplished the synthesis (4-
fold Suzuki coupling) of a novel class of three-dimensional
four-connecting molecular scaffolds based on biaryls and
explored their hydrogen-bonded self-assembly. The tet-
raphenol 2 is found to include in its crystal lattice the
guest molecules such as ethyl formate, ethyl acetate,
ethanol, etc. The X-ray crystal structure analysis of the
inclusion compound with ethanol reveals a novel helical
self-assembly based on O-H‚‚‚O hydrogen bonds in all
of the three dimensions, which results in the creation of
channels in the lattice. The biphenyl-expanded tetraphen-
ol 4 is found to include larger guest molecules such
1
p-xylene, anisole, mesitylene, etc., as revealed from H
NMR spectroscopic analysis of the solid inclusion crys-
tals. That the tetraacid 3 also forms analogous channels
in which the solvent molecules, viz., DMSO and H2O, are
found to reside is revealed by the single-crystal X-ray
structural analysis. While the expected dimer motif is
not observed due to competitive hydrogen bonding of
DMSO/H2O with the carboxylic acid hydrogens, the
formation of channels in the crystal lattice amply il-
lustrates the potential of three-dimensional modules
based on biaryls in the development of functional mimics
of inorganic zeolites. As simple desymmetrization of the
bimesityl core may lead to chiral atropisomers, whose
resolution chemistry is well founded, these scaffolds may
offer a facile entry into chiral porous materials, particu-
larly with tetrapyridyl derivatives. We are presently
exploring the utility of these unique scaffolds in the
development of porous and chiral organic and metal-
organic frameworks.
FIGURE 5. Ball-and-stick representation of acid 3, which is
hydrogen bonded directly and via H2O to four DMSO mol-
ecules; for the sake of clarity, only major positions of DMSO
are shown.
Experimental Section
The synthetic procedures and characterization data for the
tetraarylbimesityls 2-5 are described in the Supporting Infor-
mation.
X-ray Crystal Structure Determination of 2 and 3. The
tetraphenol 2 was crystallized by slow evaporation of the solution
of 2 in ethanol over 4-5 days, and the tetraacid 3 was
crystallized by slow diffusion of toluene into a solution of 3 in
DMSO. The X-ray intensity data were collected for 2 on an
Enraf-Nonius CAD4 and for 3 on a Bruker SMART APEX CCD
diffractometer. For both 2 and 3, a graphite-monochromated
MoKR (λ ) 0.71073 Å) radiation was employed at 293(2) and
100(2) K, respectively. Both of the structures were solved by
direct methods using SHLEXS-97 and refined by full-matrix
least-squares method based on F2 using SHLEXL-97.
Crystal data for 2: molecular formula C42H38O4‚C2H6O;
orthorhombic, P21212 (No. 18), a ) 25.418(5) Å, b ) 6.2412(12)
Å, c ) 12.466(3) Å, V ) 1977.6(1) Å3, Z ) 4, 3047 reflections
collected of which 893 are unique, GOOF ) 0.974, R1 ) 0.0580;
wR2 ) 0.0785, for [I > 2σ(I)].
FIGURE 6. Crystal packing of acid 3 viewed down the a-axis.
Notice the formation of channels.
tion. Presumably, these solvent molecules act as an
adhesive to hold the strands together. The formation of
channels between the strands is shown in Figure 6.
Due to weak diffraction of the crystals caused by severe
disorder of the solvent molecules in the channels, which
leads to a structure with poor figures of merit (R1
)
0.174), we have not attempted to analyze various interac-
tions involved in the overall crystal packing. Otherwise,
the ability of the three-dimensional D2d-symmetric tet-
raacid 3 to exhibit inclusion properties is amply revealed
from the X-ray crystal structure analysis, although the
expected dimer motif of the carboxyl groups is not ob-
served due to competitive hydrogen bonding by DMSO/
H2O with the acid hydrogens. Our attempts to obtain
inclusion crystals of the expanded acid 5 have heretofore
been unsuccessful. Given the various possible ways in
which both acids as well as phenols may self-assemble,
tetraphenol 2 and the tetracid 3 may in principle crystal-
lize out in different polymorphic forms depending on the
conditions of crystalllization. We have, however, not been
successful in identifying polymorphic growth of 2 and 3
thus far.
Crystal data for 3: molecular formula C56H42O15S5; orthor-
hombic, Pbca (No. 61), a ) 13.5422 (14) Å, b ) 28.132(3) Å, c )
1 31.458(3) Å, V ) 11985(2) Å3, Z ) 8, 9369 reflections collected
of which 4103 are unique, GOOF ) 1.755, R1 ) 0.1746; wR2 )
0.3086, for [I > 2σ(I)].
Acknowledgment. We are thankful to the Depart-
ment of Science and Technology (DST, India) for gener-
ous financial support.
Supporting Information Available: The details of syn-
thesis of bimesityls 2-5, 1H and 13C NMR spectra of 2-5, and
packing diagrams of 5. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO051205Z
J. Org. Chem, Vol. 70, No. 21, 2005 8571