Helix versus zig-zag: Control of supramolecular topology via carboxylic acid conformations in ortho-substituted phenyl amines

Article abstract of DOI:10.1039/b110049a

ortho-Substituted phenyl amines form supramolecular helices or zig-zag structures, depending on the conformation of the carboxylic acid substituents - which can be controlled by an intramolecular hydrogen-bonding interaction.

Full text of DOI:10.1039/b110049a

Helix versus zig-zag: control of supramolecular topology via carboxylic
acid conformations in ortho-substituted phenyl amines
Jason E. Field and D. Venkataraman*
Department of Chemistry, University of Massachusetts, Amherst, Massachusetts, USA 01003.
E-mail: dv@chem.umass.edu; Fax: +1-413-545-4490; Tel: +1-413-545-2028
Received (in Columbia, MO, USA) 5th November 2001, Accepted 2nd January 2001
First published as an Advance Article on the web 17th January 2002
ortho-Substituted phenyl amines form supramolecular heli-
ces or zig-zag structures, depending on the conformation of
the carboxylic acid substituents — which can be controlled
by an intramolecular hydrogen-bonding interaction.
motifs I or II due to the allowed intermolecular hydrogen
bonding. In contrast, the asymmetric conformation, with the
carbonyls both pointing in the same direction, can potentially
pack in any of the three motifs. We set out to synthesize a series
of bis(benzoic acids) with bridging groups that can form
intramolecular hydrogen-bonds with the carboxylic acid
groups, thereby controlling their conformations and thus the
overall supramolecular motif.
Molecule 1 (Fig. 2) was synthesized through a novel copper-
catalyzed coupling of methyl anthranilate and methyl-2-iodo-
benzoate which was developed by our group.8 Subsequent base
hydrolysis and recrystallization from ethanol gave 1† as large
yellow crystals. The resulting solid-state structure was obtained
from single crystal X-ray diffraction and is shown in Fig. 3a.
This structure shows that the intramolecular hydrogen-bonding
of the secondary amine to the acid carbonyls serves to fix the
conformation of the intermolecular hydrogen-bonds, which in
turn gives rise to an overall zig-zag motif (I). It is important to
note that this is not a helical structure, as the hydrogen-bonds
are bisected by an imaginary central axis rather than coiled
around it. We hypothesize that motif II is less favoured than
motif I due to inefficient packing between stacks.
Of all of nature’s structures, there is arguably none more
beautiful or widely scrutinized than the helix. Chemists have
been attempting to mimic the helical motif in supramolecular
assemblies in order to achieve functional materials.1,2 With the
development of crystal engineering,3 chemists have identified a
large number of intermolecular interactions to assemble
targeted supramolecular motifs. Hydrogen-bonding is often
applied in this regard due to the strength, directionality, and
specificity of the interaction,4 as well as its ubiquitous presence
in naturally occurring assemblies. The major challenge that
chemists face in creating predictable supramolecular assemblies
from small molecules is to decipher nature’s hierarchy of
molecular interactions. It was our goal to manipulate an
intramolecular interaction in order to control the conformation
of an intermolecular interaction and thus provide a route to a
predictable solid-state motif.5 In this paper, we report an ortho-
substituted phenyl amine that can form a hydrogen-bonded,
crystalline, supramolecular helix. Furthermore, the conforma-
tion of the intermolecular hydrogen-bonds, and thus the overall
structure, can be controlled through an intramolecular hydro-
gen-bond interaction.
There is some precedence to using the directionality of
hydrogen-bonds to control supermolecular structure. For exam-
ple, Wuest and co-workers have utilized symmetric and
asymmetric dipyridones to control dimerization versus ex-
tended structure formation.6 Our goal was to takes this idea one
step further by controlling the conformation of a carboxylic acid
hydrogen-bond synthon using an intramolecular interaction.7
Fig. 1 shows three possible packing motifs of a bis(benzoic
acid) system. Motif I is composed of two atropisomers and
results in a zig-zag structure. Motifs II and III contain only a
single atropisomer assembled as a trigonal coil and a circular
helix respectively. The packing motifs available to this system
are further limited by the three possible conformations of the
carboxylic acids. The two symmetric conformations, with the
carbonyls pointing in opposing directions, can only pack in
Fig. 2 The control of carboxylic acid conformations of 1, 2, and 3 (R =
Phenyl) by internal hydrogen-bonding (green dashed). Intermolecular
hydrogen-bond donors (blue) and acceptors (red); disordered hydrogen
(magenta).
Fig. 3 The supramolecular structures of a) 1, b) 2, and c) 3 from single
crystal X-ray diffraction. Carboxylic hydrogen bonds are connected for
clarity. Internal hydrogen bonds (yellow dashed lines); oxygen (red),
carbonyl oxygen (purple), nitrogen (blue), carbon (grey), hydrogen (white),
imaginary axis (light blue) parallel to the specified crystallographic axis.
Fig. 1 The three possible packing motifs of a bridged bis(benzoic acid)
system. X = bridging group. Motif I is racemic, motif II and III are
composed of a single atropisomer.
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CHEM. COMMUN., 2002, 306–307
This journal is © The Royal Society of Chemistry 2002

0.1305 (all data). Carbonyl groups assigned by C–O bond lengths. CCDC
173736. See http://www.rsc.org/suppdata/cc/b1/b110049a/ for crystallo-
graphic files in .cif or other format.
‡ Crystal data for 2: C14H10NO5, M = 258.23, monoclinic, space group C2/
c (no. 15), a = 13.5889 (5), b = 6.6994 (3), c = 13.5648 (6) Å, V =
1217.39 (9) Å3, T = 298 K, Z = 4, m = 0.11 mm21, 1972 reflections
To test our ability to control the carboxylic acid conforma-
tion, we synthesized 2 using a copper-catalyzed ether coupling
of o-methylphenol and o-iodotoluene, previously reported by
our group,9 followed by oxidation with KMnO4.10 We
hypothesized that the ether linkage would hydrogen-bond with
one of the acidic hydrogens, resulting in the asymmetric
conformation. Unfortunately, single crystal X-ray diffraction of
2‡ (Fig. 3b) reveals that both carbonyls are facing in the same
direction, resulting in a similar zig-zag structure as seen in 1,
except the conformation of the carboxylic acids are completely
reversed. We hypothesize that the carboxyl hydrogens are
slightly disordered such that one occupies the three-oxygen
cavity for some percentage of time in the solid-state (Fig. 2),11
thus providing stabilization for this conformation.
In order to achieve the desired assymmetric conformation, we
synthesized 3 through an Ullmann coupling,§ followed by
simple base hydrolysis and recrystallization from a water–
acetone mixture. Single crystal X-ray diffraction shows that 3¶
obtains an asymmetric conformation except the intermolecular
hydrogen bonds are not dimeric. This is due to the internal
hydrogen-bonds between the two carboxylic acids as well as the
tertiary amine (Fig. 2). Moreover, 3 is observed to self-assemble
into a supramolecular helix (Fig. 3c) as predicted by packing
motif III. It should be noted that both the right-handed and left-
handed helices are present in the unit cell. It is also important to
note that solvent water does not interfere in the assembly of this
helical structure, a common problem in supramolecular chem-
istry due to competition by the protic solvent for hydrogen
bonds.12
As discussed previously, motif II is less favoured due to
inefficient inter-stack packing, but it also forms a more rigid and
a less efficient coil (more residues per length) than motif III.
More difficult to explain is the absence of the zig-zag motif (I),
which facilitates packing between stacks. The angle between
the planes of the two benzoic acid rings are approximately 44°,
66°, and 81° corresponding to compounds 1, 2, and 3,
respectively. The more open angle of 3, combined with its
bonding conformation, may give rise to the helical assembly
over the zig-zag structure. It is also possible that the bulk of the
additional phenyl group in 3 is better accommodated by the
helical motif in this case.
measured, 1057 unique (Rint = 0.031), R1 = 0.0632 (all data)], wR2
=
0.1455 (all data). Carbonyl groups assigned by C–O bond lengths. CCDC
173737.
§ Aniline (2.28 mL, 25 mmol), methyl-2-iodobenzoate (11.18 mL, 52.5
mmol), K2CO3 (7.26 g, 52.5 mmol), Cu (0.33 g, 5.2 mmol), and CuI (0.22,
1.2 mmol) combined in 20 mL di-n-butyl ether and refluxed under argon for
48 h. Column chromatography (4+1, hexane–ethyl acetate) followed by
recrystallization from ethanol gave the coupled product in 81% yield. Base
hydrolysis with NaOH in EtOH–H2O (1+1) gave 3 in 99% conversion.
Crystals were obtained from slow evaporation of an acetone–water solution
of 3.
¶ Crystal data for 3: C20H15NO4, M = 333.34, monoclinic, space group
P21/c (no. 14), a = 9.2755 (2), b = 10.7912 (4), c = 16.7186 (4) Å, V =
1658.61 (8) Å3, T = 298 K, Z = 4, m = 0.09 mm21, 5471 reflections
measured, 2901 unique (Rint = 0.034), R1 = 0.0539 (all data), wR2
=
0.1138 (all data). Carbonyl groups assigned by C–O bond lengths. CCDC
173738.
1 For general reviews see: (a) A. E. Rowan and R. J. M. Nolte, Angew.
Chem., Int. Ed., 1998, 37, 63; (b) D. S. Lawrence, T. Jiang and M.
Levett, Chem. Rev., 1995, 95, 2229; (c) A. P. Alivisatos, P. F. Barbara,
A. W. Castleman, J. Chang, D. A. Dixon, M. L. Klein, G. L. McLendon,
J. S. Miller, M. A. Ratner, P. J. Rossky, S. I. Stupp and M. E. Thompson,
Adv. Mater., 1998, 10, 1297.
2 For specific examples of helical architectures see: (a) C. Nuckolls, T. J.
Katz, G. Katz, P. J. Collings and L. Castellanos, J. Am. Chem. Soc.,
1999, 121, 79; (b) T. B. Norsten, R. McDonald and N. R. Branda, Chem.
Commun., 1999, 8, 719; (c) P. Gangopadhyay and T. P. Radhakrishnan,
Angew. Chem., Int. Ed., 2001, 40, 2451; (d) S. J. Geib, G. Vicent, E. Fan
and A. D. Hamilton, Angew. Chem., Int. Ed., 1993, 32, 119; (e) M. J.
Marsella, I. T. Kim and F. Tham, J. Am. Chem. Soc., 2000, 122, 974; (f)
K. Hanabusa, M. Yamada, M. Kimura and H. Shirai, Angew. Chem., Int.
Ed., 1996, 35, 1949; (g) S. Hanessian, M. Simard and S. Roelens, J. Am.
Chem. Soc., 1995, 117, 7630; (h) O.-S. Jung, Y. J. Kim, Y.-A. Lee, J. K.
Park and H. K. Chae, J. Am. Chem. Soc., 2000, 122, 9921.
3 G. R. Desiraju, Angew. Chem., Int. Ed., 1995, 34, 2311.
4 L. Leiserowitz, Acta Cryst. Sec. B, 1976, 32, 775.
5 C. Bilton, F. H. Allen, G. P. Shields and J. A. K. Howard, Acta Cryst.
Sec. B, 2000, 56, 849.
In summary, we have reported a novel molecular system in
which the conformation of the intermolecular hydrogen-
bonding, and thus the supramolecular structure, can be
controlled through an internal hydrogen-bond. This work is an
example of a rational design approach for assembling predict-
able molecular architectures that may potentially lead to
functional materials with interesting solid-state properties.13
The triphenylamine moiety may also assist in the development
of such materials.14 Studies are under way to determine if these
molecules aggregate in the solution phase.
6 (a) Y. Ducharme and J. D. Wuest, J. Org. Chem., 1988, 53, 5789; (b) E.
Boucher, M. Simard and J. D. Wuest, J. Org. Chem., 1995, 60, 1408; (c)
L. Vaillancourt, M. Simard and J. D. Wuest, J. Org. Chem., 1998, 63,
9746.
7 Intramolecular hydrogen bonds have been used to control helical
conformations in oligomers. See (a) J. Zhu, R. D. Parra, H. Zeng, E.
Skrzypczak-Jankun, X. C. Zeng and B. Gong, J. Am. Chem. Soc., 2000,
122, 4219; (b) Y. Hamuro, S. J. Geib and A. D. Hamilton, J. Am. Chem.
Soc., 1997, 119, 10587.
8 R. Gujadhur, D. Venkataraman and J. T. Kintigh, Tetrahedron Lett.,
2001, 42, 4791.
Financial support for this research was provided by the
University of Massachusetts, Amherst start-up funds. We thank
the X-ray Structural Characterization Laboratory supported by
National Science Foundation grant CHE-9974648 for collecting
single crystal data for 1, 2 and 3. DV gratefully acknowledges
the Camille and Henry Dreyfus New Faculty Award.
9 R. Gujadhur and D. Venkataraman, Synth. Commun., 2001, 31, 2865.
10 R. Shapiro and D. Slobodin, J. Org. Chem., 1969, 34, 1165.
11 Although not conclusive, X-ray diffraction shows some residual
electron density where the disordered proton is expected.
12 (a) G. M. Whitesides, J. P. Mathias and C. T. Seto, Science, 1991, 254,
1312; (b) G. R. Desiraju, J. Chem. Soc., Chem. Commun., 1991, 426; (c)
J. H. K. Ky Hirschberg, L. Brunsveld, A. Ramzi, J. A. J. M. Vekemans,
R. P. Sejbesma and E. W. Meijer, Nature, 2000, 407, 167.
13 Helical systems are candidates for circularly polarized light emitters.
See M. Grell and D. C. D. Bradley, Adv. Mater., 1999, 11, 895.
14 Triphenylamines are widely exploited as materials for display applica-
tions. See E. Bellmann, S. E. Shaheen, S. Thayumanavan, S. Barlow, R.
H. Grubbs, S. R. Marder, B. Kippelen and N. Peyghambarian, Chem.
Mater., 1998, 10, 1668 and references contained therein.
Notes and references
† Crystal data for 1: C14H11NO4, M = 251.27, monoclinic, space group C2/
c (No. 15), a = 13.1691 (7), b = 8.3651 (5), c = 11.7215 (5) Å, V =
1208.38 (11) Å3, T = 298 K, Z = 4, m = 0.11 mm21, 2456 reflections
measured, 1387 unique (Rint = 0.027), R1 = 0.0582 (all data), wR2
=
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307